FUNDACION BDV

DOCUMENTA

H u m a n Genome
Project:
Ethics
 OBJECTIVE

It has b e c o m e i n c r e a s i n g l y i m p o r t a n t t o i m p r o v e
i n t e r n a t i o n a l a g r e e m e n t s . A l t h o u g h in Science t h e r e has
t r a d i t i o n a l l y b e e n i n f o r m a l c o o p e r a t i o n , i t has b e e n
c a r r i e d o u t b y a f e w o r b y small g r o u p s o f s c i e n t i s t s
i n t e r e s t e d in specific p r o b l e m s . O n l y m o r e r e c e n t l y
s o m e l a r g e r g r o u p s have b e e n o r g a n i z e d a n d s u p p o r t e d
b y a n u m b e r o f n a t i o n s ; h o p e f u l l y t h e r e w i l l b e m o r e in
t h e f u t u r e . T h e n e w p r o m i n e n t r o l e o f b i o l o g y in m a n y
c o u n t r i e s w i t h its b e n e f l t s , especially m e d i c a l a n d
technological, requires generous and efficient
m e c h a n i s m s t o b e n e f i t o t h e r less s c i e n t i f i c a l l y
p r o m i n e n t c o u n t r i e s as w e l l as s u p p o r t f r o m p r í v a t e
and g o v e r n m e n t a l sources f o r p r o j e c t s w h i c h because
of cost and/or w o r l d w i d e interest make cooperation
d e s i r a b l e if n o t e s s e n t i a l . T h e r e c e n t i n t e r e s t a n d
d e b a t e r e g a r d i n g t h e G e n o m e P r o j e c t , especially as i t
applies t o h u m a n s , i n d í c a t e t h e n e c e s s i t y f o r
i n t e r n a t i o n a l p r o g r a m s . T h i s w o r k s h o p h a d as its m a i n
a i m t o s t i m u l a t e i n t e r n a t i o n a l c o o p e r a t i o n in t h e e t h i c a l
aspects o f t h e H u m a n G e n o m e P r o j e c t . W e thankthe
many participants w h o c o n t r i b u t e d t h e i r t i m e and
t a l e n t in t h e r e a l i z a t i o n o f t h i s a i m .
 FUNDACION BBV

DOCUMENTA

Human Genome
Pro/ect;
Ethics
T h i s v o l u m e c o n t a i n s t h e p a p e r s o f f e r e d a t t h e II W o r k s h o p on
International Co-operation for the Human Genome Project,
o r g a n i z e d a n d s p o n s o r e d by t h e B a n c o B i l b a o V i z c a y a F o u n d a t i o n
in c o l l a b o r a t i o n w i t h t h e V a i e n c i a n F o u n d a t i o n f o r Advanced
Studies.

© C o p y r i g h t Foundation BBV
Plaza de San Nicolás, 4 - 48005 Bilbao

Translated by
María José Velasco

C o v e r designed by
Alberto Corazón

Registered n u m b e r : M.9.860-1992
ISBN 84-604-2244-5

Printed by Alfil A r t e s Gráficas, S. A .

Embajadores, 262 - 28045 M a d r i d
 FUNDACION BDV
DOCUMENTA

Human Genome
Project:
Ethics
PRESENTATION
It is t o d a y p o s s i b l e t o t r a c e o u t a g e n e t i c m a p , t o o f f e r a d e s c r i p -
t i o n o f a c o m p l e t e biological b o o k o f t h e human being. Y e t this
scientific k n o w l e d g e can b e u s e d in d i v e r s e w a y s .

Responsible p r o c e d u r e demands t h a t t h e scientist should foresee

as f a r as p o s s i b l e t h e c o n s e q u e n c e s t o b e d e r i v e d f r o m t h e a p p l i -
c a t i o n s o f t h e s e a d v a n c e s in t h e u n d e r s t a n d i n g o f living m a t t e r .
P r o f o u n d ethical dilemmas are posed by t h e n e w possibilities
o p e n t o us.

T h e B B V F o u n d a t i o n , in its c o n c e r n t o c r é a t e spaces f o r t h o u g h t
t h a t help t o p o i n t t o ways o f solving these p r o b l e m s , takes u p o n
itself t h e t a s k o f p r o v i d i n g t h e m e a n s t o d o j u s t t h i s .

Reflecting c o m p e t e n t l y and a u t h o r i t a t i v e l y o n t h e ethical implica-

t i o n s o f t h e h u m a n g e n o m e w i l l p e r h a p s n o t lead t o an e l i m i n a -
r o n of the uncertainties which the Human G e n o m e Project will
b r i n g m a n k i n d o v e r t h e n e x t f e w y e a r s . H o w e v e r , i t w i l l e n a b l e us
t o prepare advantageously f o r c o n f r o n t a r o n w i t h these uncer-
t a i n t i e s as t o t h e c o n d i t i o n s in w h i c h o u r b e h a v i o u r e v o l v e s in
n e w e n v i r o n m e n t s against n e w o p t i o n s a n d a l t e r n a t i v e s .

O u r F o u n d a t i o n is p r o u d t o have s p o n s o r e d a n d c o l l a b o r a t e d in
t h e o r g a n i z a t i o n o f t h i s i m p o r t a n t w o r k s h o p , in w h i c h s o m e o f
t h e g r e a t e s t w o r l d e x p e r t s have had t h e o c c a s i o n t o i n f o r m us
and m a t c h t h e i r o w n conclusions w i t h t h o s e o f t h e i r colleagues. I
s h o u l d h e r e l i k e t o e x p r e s s m y s i n c e r e t h a n k s t o all o f t h e m a n d
p a r t i c u l a r l y t o Prof. Santiago G r i s o l í a .

W e h o p e t h a t t h i s p u b l i c a t i o n , w h i c h o f f e r s in s u f f i c i e n t d e t a l l t h e
i n t e r v e n t i o n s o f t h e 3 6 e x p e r t s w h o p a r t i c i p a t e d in t h e II W o r k -
shop on International C o - O p e r a t i o n for the Human Genome
P r o j e c t : Ethics, in t h e c i t y o f V a l e n c i a , m a y t h u s b e c o m e a useful
r e f e r e n c e g u i d e b o t h f o r s c h o l a r s a n d specialists in t h i s f i e l d a n d
f o r t h o s e w h o in s o m e w a y a r e r e s p o n s i b l e f o r m a n a g i n g a n d
o r i e n t i n g t h e activities and patterns o f behaviour o f t h e i r fellows.

josé Angel Sánchez Asiaín

President of t h e Banco Bilbao Vizcaya Foundation.

INTRODUCTION

Santiago Grisolía

I n s t i t u t e o f C y t o l o g i c a l R e s e a r c h , V a l e n c i a (Spain)
Since t h i s c o n f e r e n c e is c o n c e r n e d w i t h i n t e r n a t i o n a l aspects o f | 3
c o o p e r a t i o n o n e t h i c a l issues in H u m a n G e n o m e r e s e a r c h , I
s h o u l d like t o begin b y p o i n t i n g o u t t h a t i t is g e n e r a l l y a c c e p t e d
that t h e H u m a n G e n o m e Project and p r o g r a m m e s associated
w i t h it are likely t o p r e s e n t society w i t h a n u m b e r o f i m p o r t a n t
e t h i c a l a n d social p r o b l e m s , as w e l l as t h e b e n e f i t s , in t h e d e c a d e s
t o c o m e . Scientists t h u s have a r e s p o n s i b i l i t y t o i n f o r m other
s e c t o r s o f t h e c o m m u n i t y , a n d t h e d e c i s i ó n m a k e r s in p a r t i c u l a r ,
o f t h e i r advances and t h e n e w dilemmas. T h e 1988 workshop
h e l d in V a l e n c i a , t o w h i c h I shall r e f e r l a t e r o n , m a r k e d an i m p o r -
t a n t f i r s t s t e p in t h e i n t e r d i s c i p l i n a r y d e b a t e s t h a t w i l l be n e e d e d .

I p r o p o s e d t h e r e f o r e t o D r . José A . S á n c h e z - A s i a í n , p r e s i d e n t o f
t h e Banco Bilbao-Vizcaya Foundation (FBBV), a p p r o x i m a t e l y o n e
y e a r ago, t h a t a m e e t i n g b e h e l d f o c u s e d t h e e t h i c a l aspects o f
t h e H u m a n G e n o m e P r o j e c t . I w o u l d like h e r e t o t h a n k D r . Sán-
c h e z - A s i a í n , a n d t h e b o a r d o f t h e FBBV, f o r a c c e p t i n g t h a t p r o -
posal a n d f o r s p o n s o r i n g t h i s m e e t i n g , w h i c h , w i t h o u t d o u b t , has
b e e n v e r y successful.

T h e s e w o r d s have t o be c o n s i d e r e d as a s i m p l e i n t r o d u c t i o n t o t h i s
m o n o g r a p h w h i c h contains many of the excellent contributions o f
t h e participants in t h i s m e e t i n g w h i c h s h o u l d i n t e r e s t many.

A m o s t i m p o r t a n t g o a l o f s c i e n c e , o r b e t t e r said, f o r t h e scien
t i s t , is t o m a k e p u b l i c his d i s c o v e r i e s a n d t h u s share his k n o w l e d g e
b u t w i t h o u t t h e o p p o r t u n i t y t o claim p r i o r i t y , scientists would
l o s e w h a t is p r o b a b l y t h e m o s t a t t r a c t i v e i n c e n t i v e f o r their
w o r k ; t h a t is, t h e a d m i r a t i o n a n d / o r e n v y o f t h e i r c o l l e a g u e s , as
w e l l as d e m o n s t r a t i n g t h e i m p o r t a n c e o f t h e i r w o r k t o t h e s o -
c i e t y w h i c h s u p p o r t s t h e m . T h i s is n o w m o r e i m p o r t a n t than
e v e r since n o t o n l y t h e G e n o m e P r o j e c t b u t m u c h o f modern
science requires e v e r m o r e and g r e a t e r r e s o u r c e s and s u p p o r t
f r o m t h e society.

T o w h o m d o s c i e n t i f i c d i s c o v e r i e s belong? In e a r l i e r t i m e s , w h e "
scientists r e c e i v e d help and subsidies f r o m prívate p a t r o n s or
f o u n d a t i o n s , t h e i r p r o p r i e t a r y i n t e r e s t c o u l d be d e f e n d e d . In b i o -
logy m a j o r d i s c o v e r i e s have o f t e n b e e n m a d e w i t h o u t a s k i n g f o r
financial b e n e f i t s . W e have t h e e x a m p l e s o f t h e p e n i c i l l i n d i s c o -
v e r y f r o m w h i c h n e i t h e r F l e m i n g , F l o r e y ñ o r C h a i n d e r i v e d any
fiscal b e n e f i t s , o r m o r e r e c e n t l y t h e d i s c o v e r y o f m o n o c l o n a l a n -
t i b o d i e s by K o h l e r a n d M i l s t e i n . T h i n g s have c h a n g e d d r a m a t i c a l l y
in r e c e n t t i m e s , h o w e v e r w i t h t h e massive s u p p o r t t h a t s c i e n c e
needs and receives f r o m society. Thus, and although up t o now
t h e a m e r i c a n as w e l l as o t h e r G o v e r n m e n t s have b e e n lenient
a n d have in f a c t e n c o u r a g e d t h e f r e e p a t e n t i n g o f n e w b i o l o g i c a l
d i s c o v e r i e s a n d e v e n species, w e m u s t c o m e t o a c l e a r d e c i s i ó n
f o r t h e inmediate f u t u r e regarding t h e H u m a n G e n o m e initiative.

If w e a c c e p t t h a t t h e H u m a n G e n o m e is a p a t r i m o n y o f m a n k i n d ,
t h e s i t u a t i o n a n d t h e a n s w e r is clear. T h e r e s h o u l d b e a c o m p l e t e ,
14 rapid and f r a n k disclosure. H o w e v e r , t h e scientist o f t h e present
g e n e r a t i o n , a n d I d a r e s a y o f all, have m a d e a f e t i s h , as I have a i -
r e a d / indicated, of claiming p r i o r i t y . Thus t h e situation becomes
m o r e c o m p l i c a t e d and difficult.

T h i s w o r k s h o p has b e e n v e r y i m p o r t a n t because u n d e r t h e p r e -
s e n t s t r u c t u r e s a n d c u s t o m s , I see n o easy w a y w h e r e b y t o t a l
s h a r l n g o f t h e p r o j e c t can b e r e a c h e d o n a w i d e s p r e a d , If n o t
c o m p l e t e l y I n t e r n a t i o n a l l e v e l , un/ess we insist a n d w o r k very h a r d
t o change habits and suspiclons o n t h e c r e a t i o n and sharlng o f
k n o w l e d g e . T h l s s h a r l n g m a y b e r e a c h e d m a l n l y in t h e e t h l c a l a n d
social a s p e c t s . R e m e m b e r , h o w e v e r , t h a t e t h l c s as s u c h Is n o t an
o b j e c t l v e d i s c i p l i n e . R a t h e r It t e n d s m o r e t o e m p l o y principies
that vary w i t h t i m e and people.

A s w e p o i n t e d o u t by R o b e r t C o o k - D e e g a n , w h o w o r k e d t i r e -
lessly o n a n d d u r i n g t h e p r o g r a m m e , t h e s e c o n d w o r k s h o p t r l e d
t o c l e a r l y analyze a n d i n t é g r a t e t h e social i m p l i c a t l o n s o f w o r k o n
t h e G e n o m e as i t r e l a t e s t o r e s e a r c h a n d t h e I n v e s t i g a t o r s in t h i s
área.

W i t h o u t g o l n g I n t o d e t a l l , as a l r e a d y m e n t i o n e d , e t h l c s repre-
sents a n d r e f l e c t s t h e c u s t o m s a c c e p t e d b y a s o c l e t y . N o w the
a l m o s t e x p o n e n t i a l d e v e l o p m e n t o f s c i e n c e a n d its i m p a c t o n s o -
clety modifies and w i l l , w i t h o u t d o u b t , c o n t i n u é t o m o d i f y ethlcal
c o n c e p t s , as w a s p o i n t e d o u t In t h e f i r s t w o r k s h o p h e l d in 1988.
A f t e r t h a t w o r k s h o p t h e urgent need t o devote t i m e t o t h e ethl-
cal a s p e c t s o f t h e p r o j e c t t h r o u g h an i n t e r d i s c i p l i n a r y meeting
b e c a m e e v e n m o r e a p p a r e n t , since m a n is able t o , a n d m u s t , a n t i -
c í p a t e e v e n t s a n d p o s s i b l e c o n s e q u e n c e s o f his acts.

A s t r o n g i n f l u e n c e leading t o t h e e s t a b l i s h m e n t o f t h i s i n t e r d i s c i -
plinary m e e t i n g was t h e c o n c e r n expressed by many t h a t b i o m e -
dical i n v e s t i g a t o r s m i g h t e n c o u n t e r t h e s a m e p r o b l e m s suffered
by n u c l e a r physicists a f t e r W o r l d W a r II. M a n y i n v e s t i g a t o r s w h o
w o r k e d o n nuclear fission, and t h e r e f o r e w i t h t h e a t o m i c b o m b ,
manifested a f t e r w a r d s t h e i r r e g r e t at having p a r t i c i p a t e d and,
a b o v e all, r e s e n t e d t h e i m p o s e d c o m m i t m e n t t o s e c r e c y w h i c h
denied t h e m f r a n k and o p e n discussion o f t h e i r w o r k . Another
i m p o r t a n t reason f o r t h e w o r k s h o p was t h e historical fact t h a t
t h e r e w e r e s o m e s c i e n t i s t s in t h e past w h o d e v e l o p e d a n d c o n -
d u c t e d p r o g r a m m e s in e u g e n i c s . T h i s has d a r k e n e d g e n e t i c re-
s e a r c h a n d is a f a c t o r leading s o m e c o u n t r i e s a n d c e r t a i n g r o u p s
t o fear genetic research.

C e r t a i n l y t h e r e a r e s e r i o u s d o u b t s a b o u t leaving h u m a n g e n e t i c s
in t h e hands o f a s c i e n t i f i c é l i t e . Such f e a r s a r e s especially s t r o n g
in G e r m a n y , as has b e e n s t a t e d b y m a n y , a l t h o u g h m a n y m o r e
have a c t u a l l y h a d i t in m i n d . S o m e o n e has said - I b e l i e v e i t w a s
t h e a s t r o n o m e r H o y l e , a n d I h o p e he w a s j o k i n g - t h a t in a f e w
y e a r s w e w i l l see t h e n u c l e a r physicists f r e e a n d t h e g e n e t i c i n -
vestigators behind bars.
T h e last d e c a d e has b e e n especially n o t a b l e in t h e d e v e l o p m e n t | 5
o f t e c h n i q u e s a n d a d v a n c e s in m o l e c u l a r b i o l o g y a n d g e n e t i c s ,
c u l m i n a t i n g d u r i n g t h e last five y e a r s In t h e p r o p o s a l o f t h e feasi-
b i l l t y o f t h e p r o j e c t k n o w n as t h e H u m a n G e n o m e P r o j e c t . T h e
¡dea, w h i c h w a s p r o p o s e d i n d e p e n d e n t l y a n d a l m o s t simulta-
n e o u s l y by s e v e r a l US s c i e n t i s t , d e v e l o p e d I n t o n a t i o n a l r e s e a r c h
p r o g r a m m e s in m a n y c o u n t r i e s besides t h e U S A , s u c h as Italy,
t h e U K , t h e USSR, Japan, a n d F r a n c e . W i t h o u t d o u b t , o t h e r na-
t i o n s w i l l j o i n a n d also c r é a t e t h e i r o w n n a t i o n a l p r o g r a m m e s .

I w o u l d like t o stress w h a t t h e c u r r e n t m i n i s t e r o f e d u c a t i o n , Javier

Solana, t o l d m e s o m e t i m e ago, t h a t Spain s h o u l d p a r t i c í p a t e in t h e
G e n o m e P r o j e c t , a l t h o u g h l i t t l e has b e e n d o n e t h u s f a r t o d e v e l o p
it. U n t i l n o w , t h e m i n i s t r y in Spain w h i c h has s h o w n m o r e i n t e r e s t
is t h a t o f health a n d its c o m p e t e n t m i n i s t e r , Julián García-Vargas,
w h o aided a n d a t t e n d e d also t h e f i r s t w o r k s h o p a n d t h e n k i n d l y
a r r a n g e d f o r m e t o p a r t i c í p a t e w i t h h i m in a l o n g i n t e r v i e w w i t h
t h e p r e s i d e n t o f t h e g o v e r n m e n t , Felipe G o n z á l e z . T h e p r e s i d e n t
s h o w e d a r e s o l u t e i n t e r e s t in t h e active p a r t i c i p a t i o n o f Spain in i n -
t e r n a t i o n a l c o l l a b o r a t i o n a n d in t h e feasibility o f d e v e l o p i n g a na-
tional programme. Mr. González showed a broad knowledge of
t h e social a n d ethical p r o b l e m s e n t a i l e d as a r e s u l t o f t h e advances
in t h e H u m a n G e n o m e P r o j e c t . T h i s is w h y I a m t r y i n g t o a s c e r t a i n
t h e p o t e n t i a l a n d n u m b e r o f y o u n g spanish i n v e s t i g a t o r s w h o a r e
i n t e r e s t e d a n d m a y be able t o d e v e l o p a p r o g r a m m e s i m i l a r t o
t h o s e o f o t h e r countries and perhaps o n e o r t w o centres d e v o t e d
t o t h e H u m a n G e n o m e P r o j e c t . W i t h t h i s a i m , w e w i l l in t h e
c o u r s e o f 1 9 9 ! assemble t h o s e spanish scientists w h o w o u l d like
t o p a r t i c í p a t e , t o s t u d y t h e feasibility a n d t h e n m a k e r e c o m m e n d a -
t i o n s f o r t h e d e v e l o p m e n t o f a m o b i l i z i n g p r o g r a m m e . It is also
h o p e d t h a t t h e e x a m p l e o f Spain w i l l stimulate o t h e r s and give r e c o g -
n i t i o n t o t h e f a c t t h a t c e r t a i n I n t e r n a t i o n a l o r g a n i z a t i o n s , especially
U N E S C O , a r e giving t h e i r m o r a l a n d as m u c h m a t e r i a l s u p p o r t as
possible t o advance t h e still u n e x p l o r e d g e n e t i c f r o n t i e r s , w i t h t h e
h o p e s , first o f being able t o c o m b a t diseases m o r e efficiently t h a n
in t h e past, a n d s e c o n d o f k n o w i n g each o t h e r b e t t e r .

T h e r e is n o d o u b t t h a t p u b l i c e n t h u s i a s m is g r e a t , b u t , as a l r e a d y
m e n t i o n e d , i t is t i n g e d w i t h t h e f e a r o f h o w t h e n e w k n o w l e d g e
will be used. T h e discussions a b o u t h o w n e w genetic k n o w l e d g e
is g o i n g t o c o n c e r n us all w i l l i n c r e a s e in t h e c o m i n g y e a r s . P r i n c i -
pies o f b i o e t h i c s e l a b o r a t e d r e c e n t l y in r e l a t i o n t o p e o p l e , b e n e -
fits, a u t o n o m y a n d j u s t i c e , m u s t be i n c l u d e in legal p r o t e c t i o n o f
t h e p e o p l e as w e l l as o f s o c i e t y . T h e s e p r i n c i p i e s , a m o n g w h i c h
t h e D e c l a r a t i o n o f Valencia m u s t be c o n s i d e r e d pioneering, w i l l
no be adequate t o solve m a n y o f t h e c o m p l e x questions and c o n -
t r o v e r s i e s r e s u l t i n g f r o m t h i s s t e p f o r w a r d in g e n e t i c s . C e r t a i n l y ,
ethical dilemmas will arise because o f t h e conflicts between
collective and individual interests.

S o - c a l l e d e u g e n i c s a n d r a c i a l h y g i e n e w e r e b a s e d o n an e r r o -
n e o u s b e l i e f in t h e i m p r o v e m e n t o f t h e i n h e r i t a n c e p o o l , leading
| 6 t o n e g a t i o n o f i n d i v i d u a l d e c i s i o n s a b o u t having c h i l d r e n , c h o o s i n g
m a t e s , a n d , u n d e r nazi g e n o c i d e , t h e r i g h t t o life. E u g e n i c s in
t e r m s o f c o e r c i v e social p o l i t i c s has n o t d i s a p p e a r e d ; i t is alive in
s o m e c o u n t r i e s in w h i c h t h e r e a r e e v e n a t p r e s e n t s t e r i l i z a t i o n
c o d e s , a n d as i d e o l o g y i t is t a k e n i n t o c o n s i d e r a t i o n in s o m e
c o u n t r i e s a n d is t r y i n g t o a p p e a r in c e r t a i n g r o u p s , e.g. A m e r i c a n
right-wing extremists. Investigations related t o behavioral genet-
ics a n d t h e i r r e s u l t s a r e easily m i s u s e d , as w e have o f t e n seen in
t h e c o n t r o v e r s i e s a b o u t I Q tests, affective d i s o r d e r s and o t h e r
m e n t a l diseases.

T h e p r o b l e m s a n d d i l e m m a s r e l a t e d t o t h e use o f e u g e n i c I n f o r -
m a t i o n w i l l n o t n e e d special d r a c o n i a n m e a s u r e s , b u t w e m u s t be
r e a d y . A s w e have m e n t i o n e d b e f o r e , e m p l o y e r s , p e r s o n n e l d i r e c -
t o r s a n d I n s u r a n c e c o m p a n i e s c o u l d d i s c r i m í n a t e against t h o s e
w h o s e genetic characteristics make t h e m susceptible t o certain
diseases, p r e m a t u r e d e a t h o r disability. W i t h o u t d o u b t t h e r e is a
potential conflict a m o n g individual interests and t h o s e o f society.
H o w e v e r , w e s h o u l d r e m i n d t h e r e a d e r t h a t n o o n e c h o o s e s his
o r h e r g e n e s , a n d t h a t t h e I n f o r m a t i o n g i v e n by t h e m m u s t b e
c o n f i d e n t i a l . N o o n e s h o u l d be a n a l y z e d g e n e t i c a l l y w i t h o u t his
k n o w l e d g e , and t h e I n f o r m a t i o n o b t a i n e d m u s t n o t be released
w i t h o u t t h e c o n s e n t o f its o w n e r , unless i t is n e c e s s a r y t o a v o i d
d a m a g e t o o t h e r p e o p l e . A l l t h e s e aspects w e r e discussed d u r i n g
t h i s s e c o n d w o r k s h o p , w h i c h o r i g i n a t e d t h e II D e c l a r a t i o n o f V a -
lencia.

W e w e r e aware t h a t this w o r k s h o p could n o t solve many ethical

p r o b l e m s , because t h e y e n c o m p a s s m o r e t h a n t h e s c l e n t l f i c basis.
B u t investigators have a v e r y i m p o r t a n t r o l e , I daresay, t o d a y
m o r e t h a n ever; t h e y m u s t e x p r e s s and publicly discuss their
w o r k . F o r t u n a t e l y t h e y have b e e n t h e f i r s t in r e c o g n i z i n g t h e i m -
p o r t a n c e o f such q u e s t i o n s a n d a r e a w a r e t h a t t h e i r f i n d i n g s can
b e m i s u s e d . T h u s , t h e y a r e In a p e r h a p s less t h a n e n v i a b l e p o s i -
t i o n t o o r i g í n a t e p u b l i c d e b a t e a b o u t t h e s e n e w áreas. I have said
t h a t public p o w e r s and organizations c a n n o t ignore t h e m , b u t
t h e y m u s t be p r o m p t e d t o d e f e n d a n d m o d i f y t h e i r p r i o r i t i e s .

I r e p e a t , i t is n e c e s s a r y t o have c l e a r e x p l a n a t i o n s a n d e x t e n s i v e
d i s c u s s i o n s . T h e II w o r k s h o p o n i n t e r n a t i o n a l c o o p e r a t i o n for
t h e H u m a n G e n o m e P r o j e c t : Ethics, w a s a p i o n e e r i n g e v e n t in as-
s e m b l i n g an i n t e r d i s c i p l i n a r y g r o u p o f o u t s t a n d i n g l e a d e r s in g e -
netics, clinical r e s e a r c h , social sclence, t h e o l o g y , h u m a n l t y and
government.

I b e l i e v e i t w o u l d be a w a s t e n o t t o use as a basis f o r f u t u r e i m -
p l e m e n t a t i o n t h e r e s u m e o f Valencia, t h e conclusions o f w h i c h
w e r e reached after a s p i r i t e d discussion led by D r s . W y n g a a r d e n
a n d M c K u s i c k . It is n o t e w o r t h y t h a t a l t h o u g h t h e r e w a s a v i g -
o r o u s case m a d e f o r U N E S C O ' s c o o p e r a t i o n , t h e ñ a m e o f t h i s
a g e n c y d i d n o t a p p e a r in t h e D e g l a r a t i o n o f V a l e n c i a d u e t o t h e
larger influence and novelty I believe, of t h e t h e n n e w l y f o r m e d
Human Genome Organization ( H U G O ) . From my viewpoint, | 7
this was a s e h o u s mistake, p a r t i c u l a r / since U N E S C O has a
b r o a d n e t w o r k as w e l l as a d m i n i s t r a t i v e k n o w - h o w . In t h i s r e g a r d ,
a n d as I p o i n t e d o u t in a r e p o r t o f t h e H a s t i g n s C e n t e r ( J u l y / A u -
gust, 1989), a n u m b e r o f c o m m e n t s w e r e heard at t h e t i m e o f
t h e f i r s t m e e t i n g in V a l e n c i a s u g g e s t i n g t h a t if t h e t h e n newly
f o r m e d H U G O o r g a n i z a t i o n w e r e t o be e f f e c t i v e , each n a t i o n ,
i n c l u d i n g t h e s m a l l n a t i o n s , m u s t c o n t r i b u t e t o t h e f u n d i n g ac-
c o r d i n g t o t h e i r possibilities.

In r e s u m e , I suggest t h a t c o o p e r a t i o n a t an I n t e r n a t i o n a l level is
difficult b u t necessary and reachable w i t h different degrees of
e a r l y success d e p e n d i n g o n c o n t i n o u s a n d v i g o r o u s expositions
a n d d i s c u s s i o n s s u c h as t h e o n e s w h i c h w e r e d e v e l o p e d during
this w o r k s h o p .
WORKSHOP ON INTERNATIONAL 19
C O O P E R A T I O N F O R T H E HUMAN
C E N O M E P R O J E C T . Valencia Declaratíon
on the Human Genome Project

1. The members of the w o r k s h o p believe t h a t knowledge

g a i n e d f r o m m a p p i n g a n d s e q u e n c i n g t h e H u m a n G e n o m e can
have g r e a t b e n e f i t f o r h u m a n h e a l t h a n d w e l l b e i n g . T o w a r d s
these ends, participating scientists a c k n o w l e d g e t h e i r r e s p o n -
s i b i l i t y t o h e l p e n s u r e t h a t g e n e t i c i n f o r m a t i o n be u s e d o n l y
t o e n h a n c e t h e d i g n i t y o f t h e i n d i v i d u a l . T h e y also e n c o u r a g e
p u b l i c d e b a t e o n e t h i c a l , s o c i a l , legal, a n d c o m m e r c i a l i m p l i -
c a t i o n s o f t h e use o f g e n e t i c I n f o r m a t i o n .

2. T h e members endorse the concept of international collabo-

r a t i o n f o r t h e p r o j e c t and urge t h e w i d e s t possible participa-
tion of countries t h r o u g h o u t the w o r l d , within the resources
a n d i n t e r e s t s o f each c o u n t r y .

3. T h e participants s t r o n g l y encourage parallel studies o f ge-

n o m e s o f selected animal, plant and m i c r o - o r g a n i s m models
in o r d e r t o a c h i e v e a d e e p e r u n d e r s t a n d i n g o f t h e Human
Genome.

4. T h e w o r k s h o p urges c o o r d i n a t i o n o f research and i n f o r m a -

t i o n o n c o m p l e x genomes a m o n g nations and across disci-
plines a n d specíes.

5. T h e w o r k s h o p believes t h a t i n f o r m a t i o n r e s u l t i n g f r o m m a p -
p i n g a n d s e q u e n c i n g o f t h e H u m a n G e n o m e s h o u l d b e in t h e
p u b l i c d o m a i n a n d m a d e f r e e l y available t o s c i e n t i s t s o f all
countries.

6. T h e participants encourage continued effort t o develop c o m -

p a t i b l e g e n o m i c d a t a bases a n d n e t w o r k s a n d m e a s u r e s to
e n s u r e w o r l d - w i d e access t o t h e s e r e s o u r c e s .

7. T h e w o r k s h o p endorses The Human G e n o m e Organization

( H U G O ) as t h e lead b o d y , in c o l l a b o r a t i o n w i t h o t h e r n o n -
governmental and g o v e r n m e n t organizations, t o p r o m o t e t h e
goals a n d o b j e c t i v e s a d d r e s s e d in t h i s d e c l a r a t i o n .

O c t o b e r 2 4 - 2 6 , 1988
V a l e n c i a (Spain)
II W O R K S H O P O N I N T E R N A T I O N A L 21
C O O P E R A T I O N F O R T H E HUMAN
G E N O M E P R O J E C T : E T H I C S . Valencia
Deciaratíon on Ethics and the Human
Genome Project

1. W e , t h e p a r t i c i p a n t s in t h e V a l e n c i a W o r k s h o p , a f f l r m t h a t a
c i v i l i z e d s o c i e t y entails r e s p e c t f o r h u m a n d i v e r s i t y , i n c l u d i n g
genetic variations. W e acknowledge o u r responsibility to
h e l p e n s u r e t h a t g e n e t i c I n f o r m a t i o n is used t o e n h a n c e t h e
d i g n i t y o f t h e i n d i v i d u a l , t h a t all p e r s o n s in n e e d have access
t o genetic services, and t h a t genetics p r o g r a m s abide by t h e
ethical principies o f respect f o r persons, beneficence, and
justice.

2. We believe t h a t k n o w l e d g e gained f r o m mapping and se-

q u e n c i n g t h e H u m a n G e n o m e w i l l have g r e a t b e n e f i t f o r h u -
man health and wellbeing. W e e n d o r s e International collabo-
ration f o r g e n o m e research and urge t h e w i d e s t possible
participation of countries t h r o u g h o u t the w o r l d , within the
r e s o u r c e s a n d i n t e r e s t s o f each c o u n t r y .

3. W e u r g e c o o r d i n a t i o n a m o n g n a t i o n s a n d a c r o s s disciplines
in t h e c o n d u c t o f r e s e a r c h a n d t h e s h a r i n g o f Information
a n d m a t e r i a l s r e l a t i n g t o t h e g e n o m e s o f h u m a n beings a n d
o t h e r organisms.

4. C o n c e r n s a b o u t t h e use a n d m i s u s e o f n e w g e n e t i c know-
l e d g e h a v e p r o v o k e d d e b a t e in m a n y q u a r t e r s . In a d d i t i o n
t o d i s c u s s i o n s in p r o f e s s i o n a l c i r c l e s , f u r t h e r p u b l i c d e b a t e
o n t h e e t h i c a l , s o c i a l , a n d legal i m p l i c a t i o n s o f c l i n i c a l , c o m -
m e r c i a l , a n d o t h e r uses o f g e n e t i c I n f o r m a t i o n is u r g e n t l y
needed.

5. W e s u p p o r t e f f o r t s t o e d ú c a t e t h e p u b l i c , t h o u g h all m e a n s
i n c l u d i n g t h e press a n d t h e s c h o o l s , a b o u t g e n o m e m a p p i n g
a n d s e q u e n c i n g , g e n e t i c diseases, a n d g e n e t i c s e r v i c e s .

6. In l i g h t o f t h e g r e a t i n c r e a s e in p r o g n o s t i c a n d t h e r a p e u t i c I n -
f o r m a t i o n t h a t w i l l arise f r o m t h e g e n o m e p r o j e c t , w e u r g e
g r e a t e r s u p p o r t f o r training o f genetic counselors and ge-
netic e d u c a t i o n o f o t h e r health professionals.

7. A s a g e n e r a l p r i n c i p i e , g e n e t i c i n f o r m a t i o n a b o u t an i n d i v i -
dual s h o u l d b e a s c e r t a i n e d o r d i s c l o s e d o n l y w i t h a u t h o r i z a -
t i o n f r o m t h e i n d i v i d u a l o r his o r h e r legal r e p r e s e n t a t i v e .
A n y e x c e p t i o n s t o this principie r e q u i r e s t r o n g ethical and
legal j u s t i f i c a t i o n .
22 8- W e a g r e e t h a t s o m a t i c cell g e n e t h e r a p y m a y be u s e d f o r t h e
t r e a t m e n t o f specific h u m a n diseases. G e r m - l i n e g e n e t h e r -
a p y faces t e c h n i c a l o b s t a c l e s a n d d o e s n o t c o m m a n d e t h i c a l
consensus. W e e n d o r s e f u r t h e r discussion o f t h e technical,
m e d i c a l , a n d social issues o n t h i s t o p i c .

N o v e m b e r 14, 1990
V a l e n c i a (Spain)
G E N E R A L
REMARKS
 25

GENETIC POLYMORPHISM
AND THE SURROUNDING
ENVIRONMENT

Jomes Wotson

C o l d Spring H a r b o r Laboratory, N e w Y o r k (USA)

ABSTRACT

The genetic differences observed between people,

which are the basis o f h u m a n evolution, are both i m -
portant a n d frequent, a n d determine the existence
from serious illnesses to skiíls a n d aptitudes typicaí
o f m a n . However, it is very difíicuit to show h o w
much is genetic determinism a n d how much is envi-
ronmental inheritance.

It is equally difficult to find an answer to the question

o f how to dea! with this human genetic variability.
W e o w e a g r e a t deal o f g r a t i t u d e t o Santiago G r i s o l í a f o r b r i n g i n g 27
us t o g e t h e r t o discuss t h e e t h i c a l i m p l i c a t i o n s o f t h e H u m a n C e -
n ó m e P r o j e c t . T h e H u m a n G e n o m e P r o j e c t has an e x t r a o r d i n a r -
ily i m p o r t a n t o b j e c t i v e : t o w o r k o u t t h e c o m p l e t e s e t o f i n s t r u c -
t i o n s w h i c h m a k e us h u m a n , as d i s t i n c t f r o m say a m o n k e y . It is a
difficult question, h o w e v e r , t o p r o b é h o w m u c h w e are deter-
m i n e d b y o u r genes as o p p o s e d t o o u r e n v i r o n m e n t . Moreover,
even given t h e sum o f o u r genetic and e n v i r o n m e n t a l heritages, I
d o n ' t t h i n k t h e r e is a n y o n e h e r e in t h i s r o o m w h o feels t h a t in
s o m e s e n s e o r o t h e r h e o r she d o e s n ' t have f r e e w i l l . In a n y
case, w e g o a b o u t o u r lives a c t i n g as if w e a r e n o t c o n s t a n t l y h e l d
back by o u r genes.

T h a t w e all d o n o t have t h e s a m e s e t o f genes is o b v i o u s . G e n e t -

ic analysis o n l y can e x i s t if y o u o b s e r v e d i f f e r e n c e s b e t w e e n t w o
individuáis, and it was by observing t h e d i s t r i b u t i o n of traits
passed d o w n f r o m p a r e n t s t o p r o g e n y t h a t M e n d e l ' s laws w e r e
w o r k e d o u t . T h e question thus becomes, are these differences
in h u m a n s m a j o r o r m i n o r ? M a n y p e o p l e w o u l d l i k e t o wish
t h e s e d i f f e r e n c e s t o be m i n o r , a n d t h a t all h u m a n beings a r e b o r n
w i t h v i r t u a l l y equal chances t o s u c c e e d in t h e i r l a t e r lives. A s s c i -
entists, h o w e v e r , w e k n o w these l a t t e r longings d o n o t reflect
r e a l i t y . M a j o r g e n e t i c d i f f e r e n c e s a b o u n d a n d a r e s e e n in t h e i r
m o s t e x t r e m e f o r m s in i n d i v i d u á i s s u f f e r i n g f r o m h o r r i d g e n e t i c
diseases like m u s c u l a r d y s t r o p h y o r Tay-Sachs disease.

T h e s e all t o o m a n y s u c h f o r m s o f g e n e t i c i n j u s t i c e a r i s e t h r o u g h
t h r o w s o f the genetic dice that opérate w h e n o u r sperm and
egg a r e f o r m e d . T h i s g e n e t i c v a r i a b i l i t y b e t w e e n h u m a n s re-
f l e c t s t h e f a c t t h a t t h e g e n e d u p l i c a t i o n p r o c e s s is n o t p e r f e c t ,
a n d t h e n e w g e n e t i c m u t a t i o n s a r e c o n s t a n t l y a r i s i n g . T h e r e is
n o w a y t o s t o p t h i s p r o c e s s . M o r e o v e r , t h i s v a r i a t i o n has b e e n
t h e basis o f o u r e v o l u t i o n . W i t h o u t t h e d i f f e r e n t i a l s u r v i v a l o f
m o r e f i t v a r i a n t s , w e as h u m a n b e i n g s w o u l d n o t h a v e o u r h i g h
p o w e r e d b r a i n s t h a t h a v e l e t us d e v e l o p t h e l a n g u a g e s , both
spoken and w r i t t e n that underlie t h e c r e a t i o n o f o u r various ci-
vilizations.

T h e q u e s t i o n n o w faces us, as w e w o r k o u t t h e d e t a i l s o f t h e h u -
m a n g e n e t i c message, as t o h o w w e a r e g o i n g t o deal w i t h t h e s e
d i f f e r e n c e s b e t w e e n i n d i v i d u á i s . In t h e past, a t t h e t i m e o f t h e Eu-
genics m o v e m e n t in t h e U n i t e d States a n d in England, a n d d u r i n g
t h e r e i g n o f r a c i s t t h o u g h t s in N a z i G e r m a n y , t h e r e w a s v e r y l i t -
tle genetic k n o w l e d g e . M o s t decisions t h e n w e r e made w i t h o u t
solid genetic evidence. T h e r e w e r e many prejudices, b u t a l m o s t
n o r e a l h u m a n g e n e t i c s . N o w w e have t o face t h e f a c t t h a t w e
s o o n w i l l have r e a l facts, a n d h o w a r e w e g o i n g t o r e s p o n d t o
t h e m ? W h o is g o i n g t o t a k e c a r e o f t h o s e p e o p l e w h o a r e d i s -
a b l e d b y t h e genes t h e y h a v e i n h e r i t e d ? H o w can w e c o m p é n s a t e
t h e m f o r t h e f a c t t h a t m a n y individuáis a r e n o t as equal g e n e t -
ically as o t h e r people? I d o n ' t t h i n k w e k n o w t h e a n s w e r s , a n d
t h a t is w h y w e a r e h e r e f o r t h i s m e e t i n g .
 29

THE HUMAN CENOME PROJECT

AND PUBLIC OPINION

j a c k McConnell

H i l t o n H e a d Island, S.C. ( U S A )

ABSTRACT

Bearing in m i n d the rapid political-economic changes

t h a t have taken place on a world-wide scale over
the last decades, with g r o w i n g emergency o f the
subject, the author proposes that befare continuing
with the H u m a n Genome Project, a n d in order to
avoid future rejection o f the project by public opin-
ión, this programme should be presented to society,
including the ethical considerations it entails.
W e a r e g a t h e r e d h e r e t o begin t h r e e days o f i n t e n s e e x a m i n a t i o n
o f t h e e t h i c s issues o f t h e P r o g r a m t o M a p a n d S e q u e n c e t h e H u -
man G e n o m e . I wish it w e r e under different circumstances. I
w o u l d like t h e w o r l d t o b e less t u r b u l e n t , w o u l d be easier t o m e a s -
u r e t h e effects o n s o c i e t y o f o u r w o r k . B u t t h a t is n o t t h e case.
O u r p r o g r a m is j u s t g e t t i n g u n d e r w a y a t a t i m e w h e n t h e w o r l d
is in t h e m i d s t o f its g r e a t e s t p e r i o d o f t r a n s i t i o n in a c e n t u r y o r
m o r e . In s i m p l e r t i m e s changes o c c u r r e d b u t w e h a d t i m e t o r e -
f l e c t o n t h e changes a n d a d a p t t o t h e m . N o t s o n o w . T h e d o m i -
n a n t t h e m e o f t h e n e x t f e w d e c a d e s is t h e i n c r e a s i n g r a t e a n d
pace o f c h a n g e o c c u r r i n g . It is t r u e n o t o n l y in t h e scientific a r e n a
b u t in all s e c t o r s o f s o c i e t y .

N a t i o n a l b a r r i e r s , w h i c h have s t o o d d e f i a n t l y f o r d e c a d e s , have
c o m e t u r b l i n g d o w n in a m a t t e r o f m o n t h s . C o m m e r c i a l b a r r i e r s
have d i s a p p e a r e d a m o n g s o m e o f t h e w o r l d ' s g r e a t e c o n o m i e s ,
r e s u l t i n g in t h e d e v e l o p m e n t o f n e w m a r k e t s . I n t e r n a t i o n a l c o m p e -
t i t i o n is e m e r g i n g f r o m s o m e o f t h e m o s t u n e x p e c t e d places r e -
versing t h e roles o f suppliers and consumers. W o r l d powers,
w h o u n t i l r e c e n t l y f a c e d each o t h e r t h r o u g h g u n sights, n o w find
c o m m o n g r o u n d in t r y i n g t o r o l l back aggression o f o t h e r s . I
have listed o n l y a f e w o f t h e áreas a f f e c t e d b u t , in t r u t h , n o s e c t o r
is s p a r e d .

W h i l e t h e w o r l d is d o i n g it's o w n t o p s y t e r v y d a n c e , w e a r e e n -
gaged in t h e d e v e l o p m e n t o f t e c h n o l o g y w h i c h m a y , in t h e l o n g
r u n , c r é a t e m o r e change t h a n any o f t h e global events now
u n d e r w a y . T h e y shuffle m o n e y , p o w e r , m a r k e t s a n d p o l i t i c s . O u r
a c t i v i t y h o l d s t h e p o t e n t i a l t o c h a n g e m a n a t his m o s t f u n d a m e n -
t a l level. W i t h t h i s in m i n d i t is i m p e r a t i v e t h a t w e pause in o u r
p r o g r a m a n d c o m e t o g r i p e w i t h t h e e t h i c a l issues i n h e r e n t in
o u r efforts.

F o r c e n t u r i e s t h e s c i e n t i f i c c o m m u n i t y has b e e n a b l e t o opér-
a t e w i t h a high d e g r e e o f a u t o n o m y a n d i n d e p e n d e n c e . W e have
been able t o select and p u r s u e o u r o w n áreas o f i n t e r e s t , a n -
s w e r i n g t o v e r y f e w . W i t h t h e t r a n s i t i o n s o c c u r r i n g in s o c i e t y , has
c o m e a n e w awareness by t h e public t h a t t h e y w a n t t o be m o r e
i n v o l v e d in s c i e n t i f i c i n i t i a t i v e s . T h e y w a n t n o t o n l y t o b e i n -
f o r m e d o f t h e r e s u l t s o f o u r e f f o r t s b u t t o b e i n v o l v e d in t h e
p l a n n i g a n d e x e c u t i o n as w e l l . T h e y m a y n o t u n d e r s t a n d the
scientific t e r m s b u t t h e y have a solid intuitive feeling regarding
t h e e t h i c a l issues i n v o l v e d a n d h o w t h e y w i l l i m p a c t t h e m .

Unless and until w e are fully equipped and p r e p a r e d t o take i n t o

a c c o u n t t h e i r anxieties and c o n c e r n s and t o present o u r p r o g r a m
t o t h e m , i n c l u d i n g especial o u r v i e w s o f t h e e t h i c a l issues, t h e y
m a y delay o r cali a h a l t t o o u r e f f o r t s . It has h a p p e n e d b e f o r e a n d
c o u l d easily h a p p e n again.

T h e f o r m a t o f t h e c o n f e r e n c e has b e e n d e v e l o p e d t o p r o v i d e f o r
an i n t e n s e e x a m i n a t i o n o f t h e e t h i c a l issues, a n d w e h o p e t h a t
32 o c c u r s . W h e t h e r o r n o t t h e c o n f e r e n c e is a success d e p e n d s o n
y o u . Y o u r insights, v i s i ó n , i n p u t o f e n e r g y a n d y o u r w i l l can m a k e
this a great conference.

T h i s is as u n i q u e o p p o r t u n i t y f o r t h e p r o g r a m t o m a p a n d se-
q u e n c e t h e H u m a n G e n o m e , f o r t h e scientific c o m m u n i t y a n d f o r
s o c i e t y . W h e t h e r o r n o t t h e c o n f e r e n c e is a success d e p e n d s o n
y o u . T h e i n p u t o f y o u r v i s i ó n , e n e r g y , insights a n d w i l l can m a k e
this a great conference.

N o w l e t i t begin a n d w h e n w e finish m a y be able t o say w e have

s e r v e d w e l l . T h e P r o g r a m , t h e scientific c o m m u n i t y a n d s o c i e t y .
SCIENTIFIC REVISION
THE CURRENT STATE AND
FUTURE PROSPECTS OF THE
PHYSICAL MAPPING O F T H E
HUMAN CENOME

David Schlessinger

D e p a r t m e n t o f M o l e c u l a r M i c r o b l o l o g y and C e n t r e of
Genetics in M e d i c i n e , Faculty of Medicine of the
U n i v e r s i t y o f W a s h i n g t o n , St. L o u i s , M O ( U S A )

ABSTRACT

The construction o f a H u m a n Genetic m a p is a fea-

sible aim thanks to the avaiíability o f new technol-
ogies. In this sense, ¡arge-scale cloning m e t h o d s ,
amongst which the artificial methods produced by
yeasts (YAC) are the most highly developed, provide
intact genes which facilítate the integration o f broad
contiguous fragments. In this way, easy, rapid cover-
age o f ¡arge regions o f the genome is achieved. The
analysis o f the YACs, as likewise other alternative
techniques, shows the effort required to attain wide-
ranging mapping.
A t t h e t i m e w h e n t h e H u m a n G e n o m e Initiative s t i m u l a t e d discus- 37
sions o f o p t i m i s t i c 5 o r 10-year t a r g e t s f o r c o m p l e t e analysis o f
g e n o m e s , b o t h t h e physical m a p p i n g a n d s e q u e n c i n g t h a t w e r e
i m p l i e d a r o u s e d s k e p t i c i s m a m o n g m a n y w o r k e r s in t h e f i e l d . In
t h e i n t e r v e n i n g y e a r s , t h e m a p p i n g goals a n d e v e n s o m e o f t h e
s e q u e n c i n g goals have b e c o m e m u c h m o r e t r a c t a b l e . T h e r e a s o n
is clear: t h e availability o f n e w t e c h n o l o g y .

T h e n a t u r e o f t h e m a p r e m a i n s t h e s a m e in all f o r m u l a t i o n s .
Maps a r e c h a r a c t e r i z e d by a n u m b e r o f p r o p e r t i e s , t h e c h i e f o n e s
being c o n t i n u i t y and r e s o l u t i o n . For c o m p l e x genomes, t h e goal
is c l e a r l y t o o b t a i n l o n g - r a n g e c o n t i g u i t y o f D N A a n d , e v e n t u a l l y ,
t o e x t e n d analyses u n t i l t h e t o t a l s e q u e n c e o f t h e D N A is avail-
able. In o t h e r w o r d s , c o m p l e t e c o n t i n u i t y o f t h e m a p w o u l d be
a c h i e v e d w i t h m á x i m u m r e s o l u t i o n t o t h e n u c l e o t i d e level.

H e r e I w i l l c o n c é n t r a t e mainly o n t h e i m p a c t o f yeast artificial

c h r o m o s o m e s [and t o a lesser e x t e n t , o f p o l y m e r a s e chain r e a c t i o n
( P C R ) m e t h o d s ] o n large-scale c l o n i n g a n d D N A analysis f o r m a p
c o n s t r u c t i o n . I w i l l also discuss b r i e f l y t h e d e v e l o p m e n t o f a n u m -
ber of potentially s t r o n g m e t h o d s t o build contigs and t o ap-
p r o a c h c l o s u r e o f p a r t i a l l y - f o r m e d m a p s . T h i s leads t o s o m e final
c o m m e n t s a b o u t t h e progressively increasing complementaron
of technologies - b o t h f o r mapping and sequencing, and f o r genet-
ic a n d physical m a p p i n g - t h a t is m a k i n g a u n i f i e d m a p a feasible
goal.

Y A C s as a cloning vector of choice

R e g a r d i n g t h e o p t i m a l c l o n e d u n i t f o r m a p p i n g p u r p o s e s , i t is
n o w c l e a r t h a t large-scale c l o n i n g m e t h o d s - o f w h i c h y e a s t a r t i f i -
cial c h r o m o s o m e s 1 a r e t h e m o s t d e v e l o p e d - can p r o v i d e e v e n
q u i t e large g e n e s i n t a c t a n d in n o r m a l c o n t e x t f o r biochemical
a n d g e n e t i c s t u d i e s ; a n d t h a t s u c h c l o n e s c a n f a c i l í t a t e t h e as-
sembly o f large contigs2. A s a result, t h e unit o f c l o n e d DNA
used as a b u i l d i n g b l o c k in t h e a s s e m b l y o f c o n t i g s is c l e a r l y shift-
ing d e c i s i v e l y t o w a r d s a y e a s t a r t i f i c i a l c h r o m o s o m e . T h e r e a r e a
n u m b e r o f r e a s o n s f o r t h i s ; b u t t h e y i n c l u d e b o t h a prior/ c o n s i -
derations and practical limitations of o t h e r m e t h o d s .

Conventional cloning methods, f o r example, rarely exceed 40 kb

in i n s e r t l e n g t h . F u r t h e r m o r e , c o s m i d s , l a m b d a s , a n d o t h e r s t a n -
d a r d v e c t o r s have b e e n s h o w n t o c l o n e c o m p l e x g e n o m i c DNA
in a biased f a s h i o n , s o t h a t m o r e t h a n I04 h o l e s m i g h t be e x p e c t -
e d in a c o s m i d l i b r a r y o f H u m a n G e n o m i c DNA.

In c o n t r a s t , Y A C s c a n b e 2 0 - f o l d t h e size o f c o s m i d s . Their
l a r g e size m e a n s q u i c k e r a n d e a s i e r c o v e r a g e o f l a r g e g e n o m i c
regions. Also, w h e n the representation of genomic DNA in
Y A C s is t e s t e d , i t s e e m s t o i n c l u d e m u c h if n o t all D N A cloned
38 in m o r e - o r - l e s s r a n d o m f a s h i o n . D a t a w i t h Y A C c l o n i n g o f D.
me/onogoster a n d C. elegans D N A have g e n e r a l l y b e e n in a c c o r d
w i t h t h i s v i e w 3 , 4 . F o r h u m a n D N A , a c o m p a r a b l e i n f e r e n c e can
b e m a d e f r o m a t least t h r e e lines o f e v i d e n c e : f i r s t , Y A C c o n t i g s
o f 2 M b o r l a r g e r h a v e b e e n a s s e m b l e d f o r a n u m b e r o f sites in
t h e H u m a n G e n o m e (see, f o r e x a m p l e s , r e f s . 2, 5, 6, a n d 7 ) ; sec-
o n d , s c r e e n i n g o f a l i b r a r y o f t o t a l h u m a n D N A in Y A C s w i t h a
series of several h u n d r e d p r o b e s f o u n d cognate Y A C s for
n e a r l y all o f t h e p r o b e s t e s t e d ( r e f . 8 a n d B r o w n s t e i n e t al. u n -
published results); and t h i r d , t h e yield of numbers of cognate
Y A C s f r o m a library of f o u r genomic equlvalents of X q 2 4 - X q 2 8
Y A C s , in t h e s t u d i e s o f o u r l a b o r a t o r y w i t h t h a t o f M . D ' U r s o
(see b e l o w ) , has c o n s i s t e n t l y b e e n i n d i s t i n g u i s h a b l e f r o m t h e e x -
p e c t a t i o n by P o i s s o n s t a t i s t i c s - t h a t is, e v e r y s e g m e n t o f h u m a n
DNA seems t o have a c o m p a r a b l e chance t o be c l o n e d into
Y A C v e c t o r s 9. F i g u r e I e m p h a s i z e s t h e c o n t r a s t b e t w e e n Y A C
and conventional cloning systems schematically.

Y A C s a r e n o t an ideal c l o n i n g v e c t o r . F o r e x a m p l e , I % o f t h e m
are patently unstable, t h r o w i n g off deletion derivatives during
g r o w t h , a n d in c u r r e n t l i b r a r l e s , 10 t o 3 0 % o f t h e c l o n e s c o n t a i n
disparate segments of D N A artifactually cocloned f r o m different
p o r t i o n s o f t h e g e n o m e . H o w e v e r , t h e availability o f m a n y p r o b e s
a n d o f a n u m b e r o f Y A C s f r o m any p a r t i c u l a r l o c u s f a c i l i t a t e s t h e
i d e n t i f i c a t i o n a n d analysis o f t h e s e a r t i f a c t u a l c l o n e s - a n d once
again, t h e f r e q u e n c y o f s c r a m b l e d c l o n e s in n o g r e a t e r t h a n t h a t
o b s e r v e d in c o s m i d l i b r a r l e s . Y A C s t h u s have s o m e d e f i c i e n c i e s ,
b u t a r e t h e b e s t t h i n g available, a n d t h e y c o n t i n u é t o be i m p r o v e d .

T h e h a n d l i n g a n d analysis o f Y A C s - l i k e s o m a n y i n v e s t i g a t i o n s o f
DNA- is g r e a t l y f a c i l i t a t e d b y t h e p o l y m e r a s e c h a i n r e a c t i o n ,
w h i c h p e r m i t s t h e s e l e c t i v e a m p l i f i c a t i o n o f specific bits o f c l o n e d
D N A , facilitates t h e diagnosis a n d c o m p a r i s o n o f m u t a t e d c o m -
pared t o n o r m a l D N A w l t h o u t t h e need t o c l o n e any o f t h e
s e q u e n c e s , a n d a l s o p e r m i t s easy r e c o v e r y o f p r o b é a n d se-
q u e n c e I n f o r m a t i o n f r o m c l o n e d D N A s - s u c h as f r o m t h e e n d s
o f Y A C s l0' n - l 2 .

T h e p o w e r o f t h e c o m b i n e d use o f Y A C s a n d P C R has e n c o u r -
aged t h e d e v e l o p m e n t o f a f o r m a t f o r maps t h a t p r o v i d e s a
c o m m o n language f o r m a p s o f all t y p e s . It is based o n t h e use o f
"STS's" o r sequence-tagged sites, p r i m e r pairs t h a t define
c h a r a c t e r i s t i c P C R p r o d u c t s f o r c o r r e s p o n d i n g p o i n t s in t h e g e -
n o m e l3.

Approaches to contigs

C o m m i t m e n t t o Y A C s as t h e p r i m a r y c l o n i g t a c t i c d o e s not,
h o w e v e r , d e t e r m i n e t h e s e l e c t i o n o f a s t r a t e g y f o r m a p p i n g . In
p a r t i c u l a r , t h e r e a r e t w o c r i t e r i a t h a t a r e especially i m p o r t a n t :
 gcatítccaatgacíagclacgacat
gccaggittccagtaagggitattgc
gatcgtggaatcgatccctgaccclg
39
tgacgatgcgaggtcacatgaatgga
ttggaggatcccagtccatggg acct
ggtaccatgacagiigacggtaccgg
tgacgtaacgtgtgcgtgcaatgcgt
gg af catggacctga ccatgaccgat
tgacgaccgtggtaccagacctgcca
tacgagcvtgcattagccgaggtcca
tgacacctaggttcccacccatgggt
cagtcagtggticagtccgcataact
agtcaLgctggacgtccacgtttccag
gtacgtacggtcaggcaaacctggga
cag i cgat cgg tacg tccag t acg te

\
tgacacctaggttcccacccatgggt

Cosmids YAC

glacgtaTg^gtcaggcaaacctggga
caglcgatcgglacgtccagtacglc
tgacacctaggtlcccacccatgggt

Figure I. The putative advantage o f YACs and other large-fragment cloning methods.
T h e g e n o m e is s h o w n as a " b o o k " , w i t h an alphabet o f t h e f o u r different letters
s p e l l i n g o u t t h e l o n g g e n e t i c message o f 1 0 0 , 0 0 0 genes a r r a y e d in a t o t a l
3,000,000,000 nucleotides. W i t h conventional v e c t o r s , t h e g e n o m e is b r o k e n up
as if it had been s h r e d d e d , i n t o pieces t h e size o f a w o r d o r phrase. A l s o , a frac-
t i o n sufficient t o leave 10,000 holes in t h e t o t a l is unclonable and t h e r e f o r e lost
f r o m a t t e m p t s t o r e c o n s t r u c t t h e e n t i r e g e n o m e f r o m fragments. In c o n t r a s t ,
Y A C s are o f t h e size o f a paragraph o r halfpage, and can clone m o s t o r all o f t h e
g e n o m e , facilitating t h e assembly o f t h e e n t i r e g e n o m e in overlapping fragments
(contigs).

First, d o e s a m a p r e q u i r e t h a t c l o n e d D N A b e available a c r o s s its

b r e a d t h ? S o m e m a p p i n g m e t h o d s , as i n d i c a t e d b e l o w , d o not
c o m m i t t h e m s e l v e s t o t h e p r o v i s i ó n o f any s u b s t a n t i a l a m o u n t o f
cloned D N A . For medical and research purposes, h o w e v e r , it
s e e m s c e r t a i n t h a t w o r k e r s w i l l g e n e r a l l y w a n t t o have c l o n e d
D N A a t t h e i r d i s p o s i t i o n f o r f u r t h e r analysis.

S e c o n d , w h a t is t o b e t h e f o r m a t o f t h e map? T h e STS f o r m u l a -
t i o n is w i d e l y f a v o r e d b y i n v e s t i g a t o r s a n d b y t h e G e n o m e I n i t i a -
t i v e A d v i s o r y B o a r d in t h e U n i t e d States; b u t i t is b y n o m e a n s
a g r e e d t o b y all g r o u p s .

It m a y b e useful t o i n d í c a t e s o m e o f t h e a l t e r n a t i v e f o r m u l a t i o n s
a n d t e c h n o l o g i e s in t h e field a t p r e s e n t .

First, p u i s e d - f i e l d gel m a p p i n g . In t h i s m e t h o d , p r o b e s a r e s o u g h t
w h i c h w i l l h y b r i d i z e t o t h e s a m e large D N A f r a g m e n t in a g e l ,
40 p e r m i t t i n g t h e i n f e r e n c e t h a t t h e y can be n o f u r t h e r a p a r t t h a n
t h e e n d s o f t h a t f r a g m e n t . T h i s m e t h o d can a c h i e v e long-range
c o n t i n u i t y o f a m a p , b u t its r e s o l u t i o n is l o w ; it is d i f f i c u l t c a r r y
o u t (because o f t h e p r o b l e m s o f m e t h y l a t i o n o f h u m a n D N A ; va-
r i a b i l i t y in g e l m o b i l i t y , e t c . ) ; a n d i t p r o d u c e s n e i t h e r cloned
D N A ñ o r STS's as p a r t o f t h e p r o c e s s .

In a v a r i a n t o f p u l s e d - f i e l d gel m a p p i n g , " S T A R S " , r e g i o n s sur-

r o u n d i n g speclflc r a r e - c u t t e r r e s t r i c t l o n sites a r e s e q u e n c e d a n d
t u r n e d i n t o STS's, a n d t h e n l o c a l i z e d o n gel f r a g m e n t s l4. O n c e
again, a t t h e e n d o f t h e m a p p i n g p r o c e s s , h o w e v e r , n o cloned
D N A is available a p a r t f r o m t h e small bits t h a t d e f i n e t h e S T A R S .

S e c o n d , in situ h y b r i d i z a t i o n . M o d e r n m e t h o d s , u s i n g n o n r a d i o -
active labeling o f p r o b e s , can o r d e r Y A C s and c o s m i d s within
a b o u t 3 M b o n metaphase c h r o m o s o m e s , and w i t h i n a b o u t 600
k b using i n t e r p h a s e n u c l e i l5, l6. It has b e e n suggested t h a t t h e s e
m e t h o d s c a n b e u s e d t o align a n d e v e n o r i e n t Y A C s a l o n g a
c h r o m o s o m e ; b u t t h e m e t h o d d o e s n o t use o r p r o d u c e STS's
d u r i n g t h e m a p p i n g p r o c e s s , s o t h a t i t yields a m a p o f a v e r y dif-
ferent format.

T h i r d , r a d i a t i o n h y b r i d s can be used t o define t h e o r d e r of

cloned m a r k e r s along c h r o m o s o m e s ; b u t this approach m u s t be
s u p p l e m e n t e d b y o t h e r s in o r d e r t o a c h i e v e c o n t i n u i t y o r r e s o l u -
t i o n . In o n e f o r m u l a t i o n , a s e t o f r a d i a t i o n h y b r i d s a r e u s e d w i t h
auxiliary techniques t o define t h e o r d e r o f a n u m b e r o f p r o b e s ;
and t h e probes are t h e n used t o screen librarles f o r cognate
Y A C s l7; b u t i t is n o t c l e a r t h a t such m e t h o d s p e r m i t any r e a l
gain o v e r s t r a t e g i e s t h a t r e l y d i r e c t l y o n cycles o f s c r e e n i n g f o r
Y A C s w i t h random probes.

F o u r t h , I d e n t i f i c a t i o n o f o v e r l a p p i n g r e g i o n s by f l n g e r p r i n t i n g o f
c l o n e s , a t e c h n i q u e w h i c h has p e r m i t t e d t h e a s s e m b l y o f l a r g e
c o n t i g s f o r £. c o l i l 8 , S. cereWs/oe l9, a n d C. elegans 20, r e t a i n s c o n -
s i d e r a b l e p o w e r ; b u t i t is as y e t u n c l e a r w h e t h e r i t can m u s t e r
sufficient d i s c r i m i n a t i o n t o p e r m i t t h e a s s e m b l y o f c o n t i g s a c r o s s
t h e vast stretches o f m u c h m o r e c o m p l e x genomes; and o n c e
again, in its p u r é f o r m , i t n e i t h e r uses ñ o r g e n e r a t e s any STS's. A n
e l e g a n t f o r m u l a t i o n o f o n e v e r s i ó n o f f i n g e r p r i n t i n g has b e e n
presented by Lehrach, e m p l o y i n g t h e i n f o r m a t i o n derived by
hybridization o f a series o f o l i g o n u c l e o t i d e p r o b e s t o arrays o f
c l o n e s 21

T h e t a c t i c s e m p l o y e d b y d i f f e r e n t s t r a t e g i e s can also v a r y c o n -
s i d e r a b l y . F o r e x a m p l e , f i n g e r p r i n t i n g a n d in situ hybridization
generally depend c o m p l e t e l y o n hybridization m e t h o d s , w h e r e a s
o t h e r approaches e m p l o y m o r e PCR-based technology.

A t present, a healthy spirit o f c o m p e t i t i o n pervades t h e efforts at

long-range mapping, and it w i l l n o t be clear f o r s o m e t i m e w h i c h
m e t h o d s w i l l be m o s t e f f i c i e n t , i n e x p e n s i v e , a n d p o w e r f u l e n o u g h
t o achieve t h e status o f m e t h o d o f choice. F u r t h e r m o r e , c o m m i t - 41
m e n t t o o n e a p p r o a c h d o e s n o t p r e c l u d e t h e s u p p l e m e n t a r y use
of others - f o r example, fingerprinting methods may n o t t u r n o u t
t o be a m e t h o d o f c h o i c e t o g e n é r a t e c o n t i g s , b u t t h e y a r e o f
great valué t o verify contigs assembled by o t h e r m e t h o d s .

O u r o w n anecdotal e x p e r i e n c e may be relevant t o t h e discus-

s i o n . In o n e o f t h e l a r g e s t p i l o t t e s t s t o d a t e , o u r g r o u p a l o n g
w i t h D r . D ' U r s o ' s has b e e n m a p p p i n g 5 0 M b o f D N A a t t h e d i s -
t a l t i p o f t h e l o n g a r m o f t h e X c h r o m o s o m e . In t h a t p r o j e c t , a
t a r g e t t e d l i b r a r y o f Y A C s specific f o r X q 2 4 - X q 2 8 D N A has b e e n
d e r i v e d f r o m a h a m s t e r / h u m a n h y b r i d cell c o n t a i n i n g t h a t DNA
as its o n l y h u m a n c o n t e n t . T h e l i b r a r y c o n t a i n s e n o u g h c l o n e s t o
p r o v i d e l i k e l y c o v e r a g e o f m o s t o r all o f t h e r e g i ó n . A v a r i e t y o f
t e c h n o l o g i e s have t h e n b e e n e m p l o y e d t o a p p r o a c h long-range
c o n t i g u i t y w i t h o v e r l a p p i n g Y A C s 22.

In t w o a p p r o a c h e s t o g r o s s m a p p i n g w i t h i n c y t o g e n e t i c c o m p a r t -
m e n t s , p r o b e s p r e v i o u s l y assigned t o r e g i o n s have b e e n u s e d t o
f i n d c o r r e p o n d i g n Y A C s a n d large Y A C s have also b e e n p l a c e d
r o u g h l y a l o n g t h e c h r o m o s o m e b y in situ h y b r i d i z a t i o n . T h e s e a p -
p r o x i m a t e l o c a t i o n s have t h e n b e e n r e f i n e d a n d c o n t i g s a s s e m -
bled by fingerprinting m e t h o d s and by w a l k i n g p r o c e d u r e s . W a l k -
ing has b e e n d o n e , f o r e x a m p l e , b y t h e use o f e n d - c l o n e s f r o m
Y A C s , by t h e isolation of end-fragments o f Y A C inserts using
P C R - b a s e d m e t h o d s , a n d b y t h e use o f a r a d i o a c t i v e l y - l a b e l e d
Y A C as a p r o b é against t h e e n t i r e c o l l e c t i o n . In t h i s w a y , c o n t i g s
o f up t o 4 M b have b e e n d e r i v e d , a n d t h e r e s e e m s t o b e n o p r o -
f o u n d b a r r i e r t o t h e r e a s s e m b l y o f m u c h o f t h e r e g i ó n in o v e r -
lapping Y A C s .

T h e r e have b e e n t w o d e f i c i e n c i e s in t h i s w o r k t h a t have, h o w -
e v e r , i n c r e a s i n g l y c o n c e r n e d us. F i r s t , t h e w o r k p r o d u c e d no
STS's, s o t h a t l o n g - r a n g e c o n t i g u i t y w a s a c h i e v e d w i t h o u t t h e d e -
s i r e d m a p f o r m a t , r e q u i r i n g t h e a d d i t i o n o f STS's as a d e t a c h e d
exercise thereafter. Second, hybridization was used f o r t h e re-
c o g n i t i o n o f Y A C s , a n d has o f t e n p r o d u c e d false p o s i t i v e s , based
o n c r o s s - h y b r i d i z a t i o n , and false negatives, based o n poor
g r o w t h , w e a k signáis, e t c . W e have t h e r e f o r e t u r n e d in o u r o w n
case t o a d i f f e r e n t p a r a d i g m o f m a p f o r m a t i o n .

Overlapping Y A C / S T S content mapping

Philip C r e e n has s u g g e s t e d a p a r t i c u l a r l y p r o m i s i n g w a y t o as-

semble overlapping Y A C s and genérate a map w i t h t h e progres-
sive a c c u m u l a t i o n o f STS's, using a c o m b i n a t i o n o f t r a d i t i o n a l a n d
P C R - b a s e d m e t h o d s 23. W e have a d o p t e d his m e t h o d , STS c o n -
t e n t m a p p i n g , f o r o u r c u r r e n t w o r k . In t h i s a p p r o a c h , p r o b e s a n d
STS p r i m e r pairs a r e g e n e r a t e d i n d e p e n d e n t o f t h e c o l l e c t i o n o f
Y A C s . Each p r i m e r p a i r is t h e n u s e d t o f i n d c o g n a t e Y A C s , each
42 o í w h i c h is r e c o g n i z e d because i t p r o d u c e s t h e a p p r o p r i a t e P C R
p r o d u c t s t a r t i n g w i t h t h e p r i m e r s . T h u s , s c o r i n g is a b s o l u t e , a n d
p o s i t i v e s can be c l e a r l y d i s t i n g u i s h e d . F u r t h e r m o r e , t h e i r c o m -
m o n c o n t e n t o f STS's p r o g r e s s i v e l y a s s e m b l e s Y A C s i n t o c o n t i g s
o f o v e r l a p p i n g D N A , In t h i s w a y , t h e f o r m a t i o n o f t h e m a p a n d
t h e a c c u m u l a t i o n o f o v e r l a p p i n g Y A C s p r o c e e d s in p a r a l l e l , a n d
m a p c o n s t r u c t i o n m a k e s use o f t h e d i s c r i m i n a t i n g p o w e r o f P C R -
STS m e t h o d o l o g y . T h i s m e t h o d is n o w in a c t i v e use a t t h e C e n -
t e r f o r G e n e t i c s in M e d i c i n e a t o u r U n i v e r s i t y .

The problem of closure and the promise

of convergent technologies

" C l o s u r e " r e m a i n s a special, i m p o r t a n t , a n d still v e r y c h a l l e n g i n g

á r e a in m a p p í n g . It is still n o t c l e a r w h e t h e r Y A C c o n t i g s - w h i c h
a r e l i k e l y t o b e t h e m o s t e x t e n s i v e c o n t i g s available f o r t h e f o r e
seeable f u t u r e - can t r u l y be g e n é r a t e a t t h e M b level e v e r y w h e r e
a c r o s s c h r o m o s o m e s . E v e n if t h e y c a n , t h e y w i l l presumably
r e a c h a l i m i t size a t p o i n t s w h e r e D N A is e i t h e r u n c l o n a b l e or
u n s t a b l e in Y A C s . A n d o n c e c o n t i g s have r e a c h e d l i m i t size, t h e
problem of fitting t h e m together into a longer-range contiguous
m a p ( c l o s u r e ) r e m a i n s . F o r t u n a t e l y , h e r e as w e l l , a n u m b e r of
m e t h o d s can be r e v i e w e d w h i c h can o r d e r a n d o r i e n t c o n t i g s .
T h e y include b o t h genetic techniques (linkage mapping) and
p h y s i c a l m a p p i n g t e c h n i q u e s s u c h as in s i t u h y b r i d i z a t i o n l5' 16
j u m p i n g librarles 24, pulsed-field gel e l e c t r o p h o r e s i s 25, and r a d i a t i o n
h y b r i d m a p p i n g 26.

It is especially n o t a b l e in r e g a r d t o c l o s u r e t h a t i t is p o s s i b l e t o
d e v e l o p m a p p i n g s t r a t e g i e s t h a t d o d o u b l e d u t y . Just as o v e r l a p -
p i n g Y A C s can b e f o u n d a n d a m a p can b e s i m u l t a n e o u s l y f o r -
m a t t e d using STS's, s o t h e use o f STS's t h a t r e v e a ! p o l y m o r p h i s m
in t h e h u m a n p o p u l a t i o n p r o v i d e s a w a y t o r e f i n e t h e g e n e t i c
map, t o o r d e r contigs, and t o m e r g e t h e physical and genetic
m a p s . Such a p p r o a c h e s suggest t h a t o p t i m i s m a b o u t v e r y e x t e n -
sive l o n g - r a n g e m a p p i n g o f c o m p l e x g e n o m e s w i t h i n t h e d e c a d e
may n o t be misplaced.
 43

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B u r k e , D . T ; C a r i e , G . F . ; a n d O l s o n , M. V . Science 236: 806-812

(1987).

S c h l e s s i n g e r , D. Trends in Genet 6: August, 1990.

G a r z a , e t al. Science 246: 641-646 (1989).

C o u l s o n , A . e t al. Noíure 335: 184-186 (1988).

S i l v e r m a n e t a l . PNAS USA 86: 7485-7489 (1989).

B e n t l e y , D. e t a l . Absíract from the Cold Spring Harbor meeting on Ce-

nóme Mapping and Sequencing, p. 8 (1990).

G r e e n , E . D. e t a l . in press.

B r o w n s t e i n , B . H . e t a l . Science 244: 1348-135! (!989).

A b l d l , F . E . e t a l . Genomics 7: 363-376 ( ! 9 9 0 ) .

O c h m a n , H . e t a l . Genetics !20: 621-623 ( ! 9 8 9 ) .

T r i g l i a , T . e t a l . N u d . Adds Res. ! 6: 8186 (!988).

R i l e y , J . e t a l . N u d . Adds Res. ! 8 : 2887-2890 ( ! 9 9 0 ) .

O l s o n , M. V . e t a l . Sdence 245: ! 4 3 4 - ! 435 (1989).

S m i t h , C . L . Absíroct from the Cold Spring Harbor meeting on Cenóme

Mapping and Sequencing, p. 204 (! 990).

L í c h t e r , P. e t a l . Sdence 247: 64-69 ( ! 9 9 0 ) .

T r a s k , B . a n d G l t s c h i e r , J . Absíroct from the Cold Spring Harbor meeting

on Cenóme Mapping and Sequencing, p. 3 (!990).

M y e r s , R. a n d C o x , D., w o r k in progress.

K o h a r a , Y . e t a l . Ce// 50: 459-508 (! 987).

O l s o n , M. V . e t a l . PNAS USA 83: 7826-7830 ( ! 9 8 6 ) .

44 C o u l s o n , A . e t a l . PNAS USA 83: 7821 -7825 (1986)

D r m a n a c , S . e t a l . Genomics 4: I 14-128 (1989)

W a d a , e t a l . Am.J. Hum. Genet. 46: 95-106 (1990)

G r e e n , P. ms., in preparation (1990)

R o m m e n s , J . M. e t a l . Science 245: 1059-1065 (1989)

B a r l o w , D . P., a n d L e h r a c h , H . Trends in Genet 3: 167-17! (1987)

C o x , D.; P r í t c h a r d , C ; U g l u m , E . ; C a s h e r , D.; K o b o r í , J . ; a n d
M y e r s , R. Genomics 4: 397-407 (1989)
SEQUENCING THE
HUMAN CENOME.
CURRENT STATE

Wo/ter Gilbert

D e p t . o f Cellular and D e v e l o p m e n t a l Biology, H a r v a r d

University, T h e Biological L a b o r a t o r i e s .
C a m b r i d g e , Massachusetts (USA)

ABSTRACT

The H u m a n Genome Project really aims at identi-

fying the A D N o f organisms with genomes o f very
different dimensions. A t present, the sequencing o f
A D N enables us to attack h u m a n illnesses, to fight
ecological problems or study evolution. In future, m o -
lecular biology will be a theoretical biology a n d we
shall k n o w the genes we all have in common, as also
those which are different in each individual.
T h e D N A s e q u e n c e o f a g e n o m e gives us i n f o r m a t i o n a b o u t t h e 47
g e n e s o f t h e o r g a n i s m . T h e g o a l o f t h e g e n o m e p r o j e c t is t o
w o r k o u t all t h e genes o f t h e v e r y s i m p l e s t o r g a n i s m s , t h e m o r e
c o m p l i c a t e d o n e s t h a t w e s t u d y as m o d e l s , a n d t h e genes o f o u r
o w n bodies. T o d o that requires that w e w o r k o u t t h e D N A of
o r g a n i s m s w h o s e g e n o m e s r a n g e in size f r o m o n e megabase t o
3 , 0 0 0 megabases. T h e s m a l l e s t o f t h e s e o r g a n i s m s m a y have 5 0 0
g e n e s , a single e u k a r y o t i c cell l i k e y e a s t m a y have 5 , 0 0 0 , w h i l e w e
have s o m e t h i n g like 100,000 g e n e s .

T h e D N A c o n t e n t o f a h u m a n c e l l , w r i t t e n o u t in l e t t e r s , w o u l d
fill o n e t h o u s a n d 1,000-page t e l e p h o n e b o o k s . W e o f t e n s p e a k o f
t h a t D N A as c o n t a i n i n g o r e n c o d i n g 1 0 0 , 0 0 0 g e n e s . In s o m e
w a y s t h a t is a m i s s t a t e m e n t o f t h e c o m p l e x i t y , because w e k n o w
t h a t genes a r e c o m m o n l y r e l a t e d a n d fall i n t o families o r s u p e r -
f a m i l i e s , each h a v i n g o f t h e o r d e r o f 10 t o 100 m e m b e r s . T h e r e -
f o r e , t h i s c o m p l e x i t y is actually s o m e t h i n g o f t h e o r d e r o f 1,000 t o
a f e w t h o u s a n d d i f f e r e n t g e n e s t r u c t u r e s . B u t m a n y o f t h e genes
in o u r b o d i e s a r e a l t e r n a t i v e l y s p l i c e d . In t h e b r a i n t h e m o s t c o m -
p l i c a t e d p r o t e i n t h a t I k n o w , N - C A M , has a l r e a d y a t least 5 0 dif-
f e r e n t splicing p a t t e r n s . I t h i n k t h a t w h e n w e l o o k at t h e s t r u c -
t u r e o f o u r genes a n d ask w h a t i n d i v i d u a l s t r u c t u r e s w i l l d o w h a t
d i f f e r e n t t h i n g s , w e w i l l find a b o u t s e v e r a l m i l l i o n g e n e v a r i a n t s in
t h e b r a i n a n d o f t h e o r d e r o f 100,000 g e n e v a r i a n t s in t h e b o d y .
T h u s , t o u n d e r s t a n d t h e full c o m p l e x i t y o f t h e o r g a n i s m is g o i n g
t o b e v e r y d i f f i c u l t . H o w a r e w e g o i n g t o f i n d o u t t h e s e details o f
s t r u c t u r e , a n d specifically h o w t h e i n d i v i d u a l genes d e t e r m i n e t h e
i n d i v i d u a l p a r t s o f o u r bodies?

T h e a n s w e r is t h a t w e a r e g o i n g t o d o i t b y s e q u e n c i n g . A l t h o u g h
w e will identify a n u m b e r o f genes by mapping and o t h e r t e c h -
niques, ultimately w e are going t o p r e d i c t t h e m a j o r i t y o f gene
f o r m s f r o m their sequence.

I w o u l d l i k e t o say a w o r d a b o u t s e q u e n c i n g . A t t h e m o m e n t t h e
D N A s e q u e n c i n g t h a t w e d o in t h e l a b o r a t o r y is d o m i n a t e d b y
f o u r elements, o f a l m o s t equal difficulty. People o f t e n t h i n k t h a t
t h e e f f o r t o f s e q u e n c i n g is d o m i n a t e d b y r u n n i n g e l e c t r o p h o r e t i c
gels o r d o i n g c h e m i s t r i e s . In fact, m o s t o f t h e e f f o r t is s p e n t in
p r e p a r i n g t h e D N A , m u c h is s p e n t in r e a d i n g gels i n t o t h e c o m -
p u t e n a n d a g r e a t dea! o f e f f o r t is s p e n t in c o m p o s i n g t h e se-
q u e n c e in t h e c o m p u t e n T h e a u t o m a t i c m a c h i n e s a r e essentially
d e v i c e s f o r r e a d i n g t h e gels, a n d t o d a y t h e r e a r e a v a r i e t y of
c o m p u t e r a p p r o a c h e s t o s o l v e t h i s p r o b l e m . T h e a s s e m b l y o f se-
q u e n c e is b e c o m i n g w e l l - d e f i n e d . T h e p r o c e s s t o t h e gels f r o m
t h e c h e m i s t r i e s is s t r a i g h t f o r w a r d , a n d t h e m a j o r e f f o r t , I t h i n k ,
t h a t w i l l s i m p l i f y t h e b u l k s e q u e n c i n g , w i l l be in s o l v i n g t h e first
problem.

O v e r t h e n e x t f e w y e a r s t h e r e a r e g o i n g t o b e a series o f large
sequencing projects. W e are going t o do o n e on mycoplasma.
T h e r e a r e n o w t h r e e £ coli p r o j e c t s in t h e w o r l d . T h e r e is a C.
48 elegans p r o j e c t b e t w e e n England a n d A m e r i c a ; t h e r e is a y e a s t
p r o j e c t g o i n g o n in A m e r i c a a n d a y e a s t p r o j e c t g o i n g o n in E u -
r o p e . W i t h i n t h i s n e x t p e r i o d , t h e f i r s t large a m o u n t s o f c o h e r -
e n t D N A sequence will appear.

In A m e r i c a , t h e 1995 goals o f t h e g e n o m e p r o g r a m , s t a t e d in a
f i v e - y e a r plan, a r e t o have s e q u e n c e d 2 0 megabases o f DNA
f r o m m o d e l o r g a n i s m s a n d t o have s e q u e n c e d a p p r o x i m a t e l y 10
m e g a b a s e s o f h u m a n D N A , in l a r g e , c o h e r e n t r e g i o n s , a n d t o
have b r o u g h t t h e c o s t o f s e q u e n c i n g d o w n t o s o m e t h i n g like
$0.50 per finished basepair. It is g e n e r a l l y b e l i e v e d t h a t t h e c o s t
t o d a y o f s e q u e n c i n g is o f t h e o r d e r o f $ ! t o $ 2 p e r f i n i s h e d base-
pair, b a s e d o n e s t i m a t i n g w h a t t h e large, r e a s o n a b l y w e l l - t r a i n e d
l a b o r a t o r i e s s p e n d in t e r m s o f d o i n g s e q u e n c e .

M y o w n e x p e c t a t i o n , n o w t h a t I have given y o u t h e national

g o a l , is t h a t t h e w o r l d is g o i n g t o change m u c h m o r e r a p i d l y s o
t h a t b y 1995 t h e c o s t w i l l fall t o less t h a n $ 0 . 2 5 a base a n d t h e
f i r s t h u m a n c h r o m o s o m e w i l l have b e e n s e q u e n c e d . By t h e y e a r
2 0 0 0 t h e c o s t w i l l have fallen t o s o m e t h i n g like a p e n n y t o a, f e w
c e n t s a base, a n d all t h e h u m a n c h r o m o s o m e s w i l l have b e e n s e -
quenced.

H o w w i l l this happen? As t h e w o r l d starts large sequencing

p r o j e c t s in s e v e r a l l a b o r a t o r i e s , e a c h w i l l b e g i n t o d o d o w n t h e
e x p e r i e n c e c u r v e , t h e l e a r n i n g c u r v e , a n d w e w i l l d e v e l o p , as
h a p p e n s in e v e r y i n d u s t r i a l p r o d u c t i o n p r o j e c t , d e f i n e d , s i m -
p l e r , a n d c h e a p e r m e t h o d s . Each i n c r e m e n t in p r o d u c t i o n b y a
f a c t o r o f t e n g e n e r a l l y is a s s o c i a t e d w i t h a d r o p in c o s t b y a
f a c t o r o f t w o . T h e a m o u n t o f s e q u e n c e t o b e p r o d u c e d is s u c h
t h a t t h e c o s t s h o u l d d r o p o v e r t i m e t o t h e levéis t h a t I h a v e
just suggested.

F u r t h e r m o r e , s o m e t h i n g else is h a p p e n i n g in o u r s c i e n c e a t t h i s
t i m e t h a t is g e n e r a l l y u n r e a l i z e d . A t t h e s a m e m o m e n t t h a t m o -
lecular b i o l o g y has b e c o m e t h e u n d e r l y i n g science t h a t p e r v a d e s all
o f b i o l o g y , i t s e e m s t o be failing as a s c i e n c e ! T o d a y , n o t o n l y d o
w e a t t a c k p r o b l e m s o f h u m a n disease, as w e discussed t h i s m o r n -
ing, b y l o o k i n g a t genes a n d l o o k i n g ad D N A s e q u e n c e s , b u t w e
attack p r o b l e m s o f ecology by studying t h e D N A sequences o f
bacteria, w e study problems of evolution by c o m p a r i n g t h e DNA
s e q u e n c e s o f d i f f e r e n t o r g a n i s m s , w e s t u d y p r o b l e m s in s t r u c -
t u r a l cell b i o l o g y b y l o o k i n g a t t h e D N A sequences o f c o m p o n e n t s
o f t h e c e l l . M o l e c u l a r b i o l o g y , o v e r t h e last flve y e a r s , has p e n e -
t r a t e d all o f b i o l o g y b y using its a b i l i t y t o i s o l a t e g e n e s a n d w o r k
o n t h e i r s e q u e n c e s . Y e t a t t h e s a m e t i m e , as w e b e g i n t a l k i n g
a b o u t a h u m a n g e n o m e p r o j e c t , t h e n t r y i n g t o w o r k o u t all t h e
genes o f t h e o r g a n i s m s a r o u n d us in t h e w o r l d , p e o p l e a r e w o n -
d e r i n g , o r c o m p l a i n i n g , o r s u g g e s t i n g , t h a t s o m e t h i n g is w r o n g
w i t h b i o l o g y because e v e r y o n e s e e m s t o be s e q u e n c i n g , a n d w e
all k n o w t h a t s e q u e n c i n g is b o r i n g . I t h i n k w h a t is h a p p e n i n g .
w h a t w e d o n ' t realize, is t h a t w e a r e g o i n g t h r o u g h a p a r a d i g m 49
shift; o u r s c i e n c e is c h a n g i n g a r o u n d us.

T o d a y m o l e c u l a r b l o l o g y is d o m i n a t e d b y an e x p e r i m e n t a l a p -
proach: w e define a phenotype, w e find a gene, w e w o r k out
its s e q u e n c e , w e s t u d y a p r o t e l n . W e experiment first and
t h i n k later. T o m o r r o w t h a t w i H ' n o l o n g e r be t r u e . Molecular
b l o l o g y w i l l be d o m i n a t e d by t h e o r y : o n e w i l l t h i n k of the
p r o p e r t i e s o f a g e n e a n d t h e n g o t o d o e x p e r i m e n t s . T h a t is a
shocklng change.

T o d a y m o l e c u l a r b l o l o g y is d o m i n a t e d b y t e c h n i q u e s l i k e l i -
b r a r i e s , c l o n i n g , s e q u e n c i n g , P C R r e a c t i o n s , y e t all o f t h e s e a r e
b e c o m i n g m o r e a n d m o r e c o n v e n t i o n a l . T h e y can all b e l o o k e d
up in a b o o k , t h e Maniatis C o o k b o o k , o r p u r c h a s e d as kits, " f o l l o w
t h e p r o c e d u r e in t h e i n s e r t " .

All of these techniques will m o v e f r o m t h e laboratory into sup-

p o r t f a c i l i t i e s o v e r t h e n e x t f e w y e a r s . T h a t has h a p p e n e d b e -
fare in b i o l o g y . In t h e I 9 7 0 ' s , t h e r e s t r i c t i o n e n z y m e s w e n t f r o m
t h e f o r e f r o n t o f r e s e a r c h in t h e l a b o r a t o r y t o b e i n g p u r c h a s e d .
In 1 9 6 0 , o n e h a d t o s y n t h e s i z e r a d i o a c t i v e t r i p h o s p h a t e s in o r -
d e r t o w o r k o n t h e biosynthesis o f nucleic acids. S o o n after
t h a t t h e y c o u l d b e p u r c h a s e d . It c o n s t a n t l y h a p p e n s in s c i e n c e
t h a t n e w elements w h i c h had been b r e a k t h r o u g h s t h e n became
c o n v e n t i o n a l t h i n g s t h a t o n e has t e c h n i c i a n s w o r k o u t o r one
p u r c h a s e s f r o m t h e s t o c k r o o m . In t h e f u t u r e , t h e g e n o m e s e -
q u e n c e s w i l l b e p u t in a d a t á b a s e , a n d t h a t d a t á b a s e w i l l b e t h e
m a j o r research t o o l . F r o m t h o s e sequences w e will p r e d i c t first
gene p r o d u c t s , alternative splicing, and c o n t r o l sequences. T h e n
w e w i l l p r e d i c t t h e i n t e r a c t i o n s o f gene p r o d u c t s , and finally w e
w i l l p r e d i c t t h e w a y s in w h i c h t h e g e n e s f o r m t h e o r g a n i s m s .
T o d a y , if w e had t h e s e q u e n c e , w e c o u l d o b v i o u s l y predict
families o f genes, s t r u t u r e s o f r e c e p t o r s , t h e regulation o f t r a n -
scription. T o m o r r o w I promise you a theoretical biology in
w h i c h w e f i r s t p r e d i c t all a s p e c t s o f g e n e i n t e r a c t i o n a n d t h e n
go t o d o experiments.

I said t h i s p a r a d i g m s h i f t is a c t u a l l y h e r e . T o d a y t h e datábase is
large e n o u g h t o begin t o d o m í n a t e m o l e c u l a r b i o l o g y . T h e r e a s o n
f o r t h i s is t h a t t h e a m o u n t o f D N A s e q u e n c e in t h e datábase has
g o n e u p 6 0 % a y e a r f o r t h e p a s t 15 y e a r s . T h a t is a f a c t o r o f 10
e v e r y 5 y e a r s . T o d a y t h e r e a r e 5 0 megabases o f s e q u e n c e in t h e
datábase. ( T h e r e a r e a b o u t 10,000 l a b o r a t o r i e s a r o u n d t h e w o r l d
w o r k i n g o n s o m e a s p e c t o f s e q u e n c i n g g e n e s ) . Five y e a r s a g o
t h e r e w e r e o n l y five megabases o f D N A s e q u e n c e in t h e d a t a -
base, five y e a r s b e f a r e t h a t t h e r e w e r e o n l y 5 0 0 , 0 0 0 bases o f D N A
in t h e d a t á b a s e . T h i s is a d r a m a t i c change o v e r t i m e . If o n e w o r k s
o u t t h e s t r u c t u r e o f a g e n e t o d a y , o n e ' s f i r s t q u e s t i o n is t o g o t o
t h e c o m p u t e r t o see if s o m e b o d y has f o u n d s o m e t h i n g s i m i l a r .
A b o u t 7 0 % o f t h e t i m e , s o m e b o d y has, a n d if t h e y h a v e n ' t , y o u
had b e t t e r k e e p y o u r e y e o n t h e c o m p u t e r because a w e e k l a t e r
50 s o m e b o d y else w i l l have f o u n d s o m e g e n e t h a t is j u s t like t h e o n e
y o u have f o u n d .

W h a t c o n s e q u e n c e d o e s t h i s r a t e o f g r o w t h have f o r t h e f u t u r e ?
Five y e a r s f r o m n o w , if t h o s e r a t e s c o n t i n u é , w e w i l l have 5 0 0
megabases o f D N A in t h e d a t á b a s e , a n d b y t h e y e a r 2 0 0 0 f i v e
b i l l i o n bases o f D N A in t h e datábase. T h i s p r o j e c t e d r a t e o f i n -
crease is essentially a r e s t a t e m e n t o f t h e H u m a n G e n o m e p r o g r a m .
If c u r r e n t t r e n d s c o n t i n u é , f i v e y e a r s f r o m n o w o n e e x p e c t s t o
be d o i n g c h r o m o s o m e s a y e a r and by t h e end o f t h e century
g e n o m e s a year.

I t h i n k t h e w o r l d will g o even f u r t h e r than that. T e n years later,

b y 2 0 1 0 , I e x p e c t t h a t w e w i l l b e able t o s e q u e n c e a m i l l i o n bases
o f D N A f o r $ 3 0 0 . S e q u e n c i n g w h o l e genes w i l l b e c o m e a m e d i c a l
d i a g n o s t i c . Y o u w i l l b e able t o e x a m i n e a g e n e in y o u r b o d y c o m -
pletely. A f e w years after that, by 2020, I e x p e c t t h a t y o u w i l l be
able t o g o t o y o u r c ó r n e r d r u g s t o r e , a n d f o r $ 3 0 0 y o u w i l l b e
able t o leave a b l o o d s a m p l e a n d g e t a c o m p a c t disc. T h a t single
c o m p a c t disc w i l l c o n t a i n a H u m a n G e n o m e ; y o u r o w n . W h e n
w e d e s c r i b e t h e h u m a n g e n o m e as a s t r i n g o f l e t t e r s e x t e n d i n g
all a r o u n d t h e w o r l d if w r i t t e n o u t using o n e c e n t i m e t e r f o r each
base, i t s e e m s i m m e n s e . In t e r m s o f t h e c o m p u t e r potentiality
t h a t w e each have o n o u r d e s k s , t h e I n f o r m a t i o n in t h e g e n o m e
is n o t t h a t large.

I e x p e c t t h a t w e a r e g o i n g t o k n o w t h e genes t h a t w e all have in

c o m m o n , a b o u t 9 0 % o f o u r g e n e s , by t h e e n d o f t h e c e n t u r y , a n d
w e w i l l k n o w m o s t o f t h e v a r i a t i o n s , t h o s e 10,000 genes t h a t dif-
f e r a c r o s s h u m a n beings w i t h i n 10 t o 2 0 y e a r s a f t e r t h a t .

T h a t is t h e p r o b l e m t h a t faces us. I t is n o t r e a l l y t h a t w e a r e
doing a n e w p r o j e c t w h i c h will make this happen. W e are at a
p o i n t in o u r s c i e n c e w h e r e t h e m a r c h o f k n o w l e d g e is c a r r y i n g
us f o r w a r d t o t h e e n d t h a t w e w i l l b e a b l e t o e m b e d our-
s e l v e s , all o f o u r g e n e s , in t h e b a c k g r o u n d o f all l i v i n g s p e c i e s
in t h e w o r l d , a n d w e w i l l b e a b l e t o t r a c e t h e m o v e m e n t a n d
c r e a t i o n o f each o f o u r genes t h r o u g h o u t t h e e n t i r e c o u r s e o f
evolution.

T h e p u r p o s e o f t h i s w e e k is t o d i s c u s s s o m e o f t h e e f f e c t s o f
t h i s j u m p in k n o w l e d g e . O n e e f f e c t o f t h i s j u m p is a p h i l o s o p h -
ical o n e . T h e r e w i l l c o m e a m o m e n t , s o m e t i m e in t h e n e x t f i v e
o r t e n y e a r s , w h e n t h e w o r l d r e a l i z e s t h a t t h e r e is s o m e t r u t h
in t h e s t a t e m e n t t h a t w e c a n h a v e a h u m a n b e i n g o n a c o m p a c t
d i s c . T h a t is g o i n g t o b e a p h i l o s o p h i c a l s h o c k t o us a n d t o t h e
w o r l d b e c a u s e i t r e f l e c t s , in a h i g h d e g r e e , t h e e x t e n t t o w h i c h
b i o l o g i c a l s c i e n c e d e f i n e s , o f fails t o d e f i n e , a h u m a n b e i n g . H u -
m a n s o f t e n t h i n k o f t h e m s e l v e s t o d a y as h a v i n g a l m o s t i n f i n i t e
p o t e n t i a l . A s s c i e n t i s t s , o f c o u r s e , w e h a v e h a d t o l e a r n t o live
o v e r t h e y e a r s w i t h t h e f a c t t h a t o u r b o d i e s have a g e n e t i c d i c -
t a t i o n , t h a t m u c h o f o u r s t r u c t u r e a n d b e h a v i o r is t h e product
o f genes i n h e r i t e d f r o m o u r parents. T h e w o r l d does n o t y e t 5 I
live w i t h t h i s r e a l i z a t i o n . T h e w o r l d w i l l h a v e t o f i g h t o f f s u c -
c u m b i n g t o a s h a l l o w genetic d e t e r m i n i s m , " m y genes made m e
d o i t ! " a n d a l s o m u s t f i n d a b a l a n c e b e t w e e n g e n e s as s t r u c -
tural d e t e r m i n a n t s of t h e individual's b o d y and brain and our
ideas o f m i n d , l i b e r t y , s e l f - d e t e r m i n a t i o n , a n d i n d i v i d u a l w o r t h .
N A T I O N A L
POLICIES
 55

T H E HUMAN CENOME PROJECT.

THE FRENCH VIEW

Jeon Frangois Girará

D i r e c t i o n G é n é r a l e d e la S a n t é . M i n i s t é r e d e s A f f a i r e s
Sociales e t de la S o l i d a r l t é , París ( F r a n c e )

ABSTRACT

The French Government has undertaken a national

programme on the H u m a n Genome that covers as-
pects such as: coordination o f activities, sequendng
and A D N mapping, disagreement o f data-processing
systems a n d people's training a n d education, a n d
transferring o f information. As for the ethical impli-
cations aroused by genetic research, the French op-
tion considers that it is o f prime importance to set
up internal debates in which alí social sectors are rep-
resented. In this sense, the author points out that
French policy can fmd no current justification for ger-
m i n a l m o d i f i c a t i o n work, a n d will encourage the
principie o f genetic non-discrimination. At the same
time, it points to the need for a differential ethical
discussion on the possible solutions t h a t could be
suggested.
It is a g r e a t h o n o u r f o r m e t o have b e e n d e s i g n a t e d b y t h e P r e s - 57
idency o f t h e French Republic t o a t t e n d y o u r m e e t i n g and t o
p r e s e n t F r e n c h n a t i o n a l p o l i c y . It is a g r e a t h o n o u r , b u t i t is a l -
s o a g r e a t c h a l l e n g e t o h a v e t h e o p p o r t u n i t y t o s p e a k in f r o n t
o f f a m o u s s c i e n t i f i c w o r k e r s : b e c a u s e e v e n if I a m a p h y s i c i a n ,
f o r m e r l y a p r o f e s s o r o f m e d i c i n e , I a m n o t a t all a s p e c i a l i s t o f
e t h i c s . I a m n o t a t all a specialist o f H u m a n G e n o m e , o f g e n e t i c s ;
I m a y b e a s p e c i a l i s t o f n a t i o n a l p o l i c y , b e i n g in c h a r g e , in t h e
Ministry of Health, of the general policy f o r public and general
h e a l t h . If I c o m m e n t o n t h a t p o s i t i o n , i t is j u s t b e c a u s e ob-
v i o u s l y t h a t is r e l e v a n t f o r t h e m e a n i n g o f t h e c h o l e e French
a u t h o r i t i e s at t h e highest level had t o a t t e n d and c o n f r o n t in
that meeting.

M y f i r s t d u t y is o b v i o u s l y t o t h a n k t h e f o u n d a t i o n s w h o o r g a n -
ised t h e w o r k s h o p , a n d t h e o r g a n i s i n g c o m m i t t e e , f o r h a v i n g f o -
c u s e d t h i s s e c o n d w o r k s h o p o n e t h i c s , w h i c h is o b v i o u s l y o n e o f
t h e m a j o r issues. Ethics o f c o u r s e , a t least in F r a n c e , is o n e o f t h e
m o s t i m p o r t a n t tasks relevant t o t h e interface b e t w e e n science,
politics and d e m o c r a c y . T h e fight f o r human rights and dignity
w i l l be c o m p l e t e d , and w e d o k n o w risk c o m i n g f r o m several
sides - s o c i a l , e c o n o m i c , p o l i t i c a l s i d e s - a n d let's b e f r a n k ; s c i e n c e
c o u l d w e l l s u p p o r t a r i s k if w e a r e n o t c a u t i o u s .

O n t h e o t h e r h a n d - a n d t h i s is a s e c o n d r e a s o n t o p u t t h e e t h i c s
d e b a t e in t h e f r o n t s c e n e s - r e l a t i o n s b e t w e e n science a n d s o c i e t y
w e r e n o t a l w a y s easy, a n d n o t o n l y in t h e past. O n e o f t h e g o o d
r e a s o n s f o r d e v e l o p i n g e t h i c s is t h e g o o d o p p o r t u n i t y , a n d p r o b -
ably t h e b e s t , f o r scientific w o r k e r s t o c o m m u n i c a t e w i t h s o c i e t y .
And probably all t h e s e p r e l i m i n a r y remarks are of most
p o w e r f u l signifícation w h e n related t o t h e H u m a n G e n o m e .

T h e place o f e t h i c s f o r p o l i t i c s in France w a s i l l u s t r a t e d in t h e
v e r y early eighties, w h e n t h e French g o v e r n m e n t i m p l e m e n t e d a
n a t i o n a l c o m m i t t e e in 1983, w h i c h is a k i n d o f c o n s u l t a t i v e c o m -
m i t t e e - a n e t h i c s c o m m i t t e e - f o r life sciences a n d h e a l t h . T h i s
c o m m i t t e e e , c o m p o s e d o f 15 scientific w o r k e r s , 15 p e o p l e f r o m
society, and 5 representatives f r o m t h e m o s t c o m m o n religions
in F r a n c e , is, as I m e n t i o n e d a m i n u t e ago, a c o n s u l t a t i v e o n e . B u t
obviously, nearly 8 years later, it became a reference, w h i c h o f
c o u r s e w i l l n o t s u p p l e m e n t t h e P a r l i a m e n t , b u t w h i c h has o b -
v i o u s l y p e r m i t t e d , a n d e v e n i n d u c e , an i n t e r n a l d e b a t e , w h i c h f o r
us is m o s t i m p o r t a n t .

T h i s c o m m i t t e e has p o s i t i o n s a n d m a k e s s t a t e m e n t s o n g e n e r a l
m a t t e r s w h i c h a r i s e f r o m s c i e n t i f i c p r o g r e s s in t h e last y e a r s ,
such as p r e n a t a l diagnosis, g r a f t s , a n d n o n - p r o f i t f o r m t i s s u e a n d
cells a n d e v e r y t h i n g f r o m t h e h u m a n b o d y . T h e n a t i o n a l c o m m i t -
t e e also m a k e s s t a t e m e n t s o n e m b r y o r e s e a r c h a n d i t is in t h a t
g e n e r a l b a c k g r o u n d , t h a t t h e c o m m i t t e e is n o w f a c i n g w h a t is t o
be d i s c u s s e d f r o m t h e H u m a n G e n o m e a n d e t h i c s .
58 R e c e n t l y , in O c t o b e r 1990, t h e F r e n c h g o v e r n m e n t d e c i d e t o i m -
p l e m e n t a n a t i o n a l p r o g r a m m e f o r H u m a n G e n o m e , w h i c h is
mainly a p r o g r a m m e t o c o o r d í n a t e national activity and interna-
t i o n a l a c t i v i t y . O f c o u r s e s e v e r a l t e a m s have a l r e a d y b e e n w o r k -
ing f o r s e v e r a l y e a r s o n h u m a n g e n o m e a s p e c t s , a n d t h e p r o b l e m
o b v i o u s l y is t o c o o r d í n a t e t h i s a c t i v i t y , f i r s t insíde F r a n c e a n d
t h e n o u t s i d e . A n d m o n e y has b e e n p u t i n t o t h a t coordination
p r o g r a m m e , a m o u n t i n g t o 10 m i l l i o n d o l l a r s f o r 1991 a n d 2 0 m i l -
l i o n d o l l a r s f o r 1992.

A n o t h e r aspect o f t h e p r o g r a m m e besídes t h e c o o r d i n a t i o n I
m e n t i o n e d a m i n u t e ago, is s e q u e n c i n g o f D N A , t h a t is m a p p i n g
o f c o u r s e , a n d w e k n o w t h e r e l a t i o n t h e r e is a l r e a d y b e t w e e n Le
C e n t r e d ' E t u d e s d u P o l y m o r p h i s m e H u m a i n s , c h a i r e d b y Jean
D a u s s e t a n d t h e I m p e r i a l R e s e a r c h F u n d in t h e U K . T h i r d , a f t e r
s e q u e n c i n g a n d m a p p i n g , p r o c e s s i n g d a t a s y s t e m s w i l l have t o be
d e v e l o p p e d . B u t also t h e g e n o m e analysis o f small g e n o m e s w i l l
b e c a r r i e d o n a n d c o m p l e t e d in s o m e e x a m p l e s .

N e x t , t h e training and educatlon o f people and t r a n s f e r of In-

f o r m a t i o n , w h i c h so far seems t h e m o s t i m p o r t a n t task, t o per-
m i t and t o induce dicussion and general debate b e t w e e n scien-
tific w o r k e r s and the n a t i o n . O b v i o u s l y , as I h a v e already
m e n t i o n e d , t h e d e b a t e o n t h e H u m a n G e n o m e is p r o b a b l y o n e
o f t h e m o s t critical o n e s t o raise t h e q u e s t i o n o f ethics and
w h a t t h a t means...

W e have t h e o b l i g a t i o n t o o p e n t h e d i s c u s s i o n f a r a w a y , in l i t t l e
c i r c l e s - i m p o r t a n t o n e s b u t l i t t l e o n e s . If s c i e n t i f i c workers,
w i t h p h i l o s o p h e r s , w i t h judges and w i t h social w o r k e r s , are t h e
o n l y ones t o discuss t h e s e critical m a t t e r s , I t h i n k w e w i l l have
t r e m e n d o u s d i f f i c u l t y i n g o i n g t h r o u g h w h a t all t h e scientific
knowledge f r o m the Human G e n o m e could bring t o human so-
ciety.

I l i s t e n e d t o t h e r e m a r k o n t h e d i f f e r e n t a p p r o a c h if y o u c o m -
p a r e t h e U n i t e d States a n d E u r o p e . I d o n ' t believe w e can say t h a t
w e a r e c o n d u c t í n g e t h i c s a n d s c i e n c e in t h e s a m e w a y in E u r o p e ,
as in t h e U n i t e d S t a t e s w h e r e t h e y s t a r t e d o f f b u t i t doesn't
m a t t e r w h a t h a p p e n e d in p r e v i o u s y e a r s - f r o m n o w o n , w e really
have t o s h a r e b o t h p o i n t s o f v i e w . Y o u c l a i m t h a t scientific w o r k -
e r s a r e as a b l e as o t h e r s t o d i s c u s s t h e s e m a t t e r s , w e l l , not
q u i t e ; f o r scientific w o r k e r s a r e m a y be n o t q u i t e like o r d i n a r y c i t i -
zens w h e n it c o m e s t o discussing t h e m . W e bring something
w h i c h is, o f c o u r s e , u ñ a v o i d a b l e , t h a t is scientific k n o w l e d g e , b u t
a r e w e s u r e w e a r e q u i t e n e u t r a l , b e i n g scientifically i n v o l v e d in
these matters?

T h e s e a r e t h e d i s c u s s i o n s t h a t a r e r u n n i n g in F r a n c e a t t h e m o -
m e n t , a n d i t is m y t a s k t o m e n t i o n t h i s , m a y b e s o t h a t w e can
t a l k a b o u t i t l a t e r , a n d also t o b e a l i t t l e p r o v o c a t i v e w i t h scientif-
ic w o r k e r s . O b v i o u s l y , a t t h e m o m e n t , e v e n if w e h a v e s o m e
b a c k g r o u n d ¡n e t h i c a l d e b a t e in F r a n c e o n an official basis, t h o s e 59
questions c o n c e r n i n g human rights and dignity and concerning
h u m a n g e n o m e e t h i c s , a r e n o t q u i t e clear. T h e y a r e j u s t s t a r t i n g
t o be c l e a r ; t h e a n s w e r s , o f c o u r s e , a r e n o t . M a y b e t h e a n s w e r s
w h i c h a r e b e c o m i n g c l e a r a r e t h o s e w h i c h w e r e d e b a t e d in b o t h
France a n d t h e EEC, a n d in o n e w a y I r e g r e t t h a t t h e EEC ¡s n o t
itself r e p r e s e n t e d in t h i s w o r k g r o u p , t o give a t a l k o n w h a t w a s
d e c i d e d in Brussels s e v e r a l m o n t h s ago, w h e n t h e M i n i s t e r s o f
R e s e a r c h h a d a m e e t i n g in M a r c h 1990 t o discuss s u c h m a t t e r s .
But surely some people present could c o m m e n t on w h a t was
said a t t h i s m e e t i n g .

First, o b v i o u s l y , as s o m e b o d y m e n t i o n e d , g e n e t i c i n j u s t i c e d o e s
n o t mean and dos n o t justify genetic discrimination. T w o , t h e r e
is n o j u s t i f i c a t i o n a t t h e m o m e n t f o r w o r k i n g o n g e r m i n a l m o d i f i -
c a t i o n . T h r e e , t h e r e is, a t t h e m o m e n t , j u s t i f i c a t i o n f o r w o r k i n g
on somatic modification.

T h a t is f o r E u r o p e , a n d f o r F r a n c e i t w i l l p r o b a b l y be e n h a n c e d
w h e n t h e N a t i o n a l C o m m i t t e e f o r Ethics c o n v e n e s in D e c e m b e r
f o r t h e 1990 s e s s i o n .

B u t besides t h i s p r o b i e m , besides t h e s e aspects, w h i c h a r e a t t h e

c e n t r e o f French policy o n ethics and t h e human g e n o m e , o b -
viously s o m e o t h e r points have t o be discussed; I mean prenatal
diagnosis, w h i c h o b v i o u s l y has t h r e e d i f f e r e n t p a t t e r n s : p r e n a t a l
diagnosis f o r t h o s e h a r m f u l diseases w h i c h a r e p r e s e n t f r o m t h e
v e r y b e g i n n i n g o f life, o r e v e n in ú t e r o , t h a t is t h e f i r s t g r o u p .
T h e s e c o n d o n e , w h i c h a r o u s e s a d i f f e r e n t e t h i c a l d i s c u s s i o n , is
t h e diagnosis o f t h o s e diseases c o m i n g l a t e r o n his life, a t t h e age
o f 4 0 o r 5 0 . A n d t h e t h i r d g r o u p o f c o u r s e is t h e g r o u p o f diag-
nosis w h i c h w i l l f o c u s o n t h e p r o b a b i l i t y o f disease, a c c o r d i n g t o
some o t h e r factors linked t o these.

W e t h i n k w e must make a v e r y clear distinction b e t w e e n these

t h r e e g r o u p s o f s i t u a t i o n s , a n d w e h a v e t o g o f u r t h e r o n an
ethical basis t o k n o w w h e r e t o g o a n d w h e r e n o t t o g o . We
c a n ' t really discuss and d e b a t e ethics and t h e h u m a n genome
w i t h o u t p o i n t i n g o u t s o m e s e c o n d a r y a s p e c t s , as: I ) t h e r e l a -
t i o n b e t w e e n f o r e n s i c m e d i c i n e and genetic t r e a t m e n t , 2) t h e
confidentiality of I n f o r m a t i o n f r o m human g e n o m e and genetic
e q u i p m e n t , w h i c h in o u r v i e w s h o u l d b e p r o t e c t e d b y m e d i c a l
s e c r e c y j u s t as any o t h e r m e d i c a l I n f o r m a t i o n . W e can also h a v e
a discussion on economic and c o m m e r c i a l consequences of
these q u e s t i o n s , w i t h b u d g e t e r y consequences t o be c o m p a r e d
w i t h o t h e r p u r p o s e as e c h o g r a p h y o n a h u g e scale f o r d i a g n o s i s
of morphological abnormalities.

I t h i n k o f c o u r s e t h a t w e have n o c h o l e e ; w e have t o perform

b o t h things, and w e k n o w t h a t t h e k n o w l e d g e w h i c h w i l l arise
f r o m t h e H u m a n G e n o m e P r o j e c t , is o n e o f t h e m o s t t r i g g e r i n g
n e w f e a t u r e s in b i o l o g i c a l sciences, a n d f o r t h e h u m a n species.
60 I a p o l o g i s e s p e a k i n g a language w h i c h is n o t m y m o t h e r t o n g u e ,
o n s o m e t o p i c s r e q u i r i n g v e r y critical nuances, b u t t h e demo-
c r a t i c p o w e r o r o u r d e b a t e is s o m e t h i n g t o b e s h a r e d with
e v e r y b o d y - w i t h p o l i t i c i a n s , b u t also w i t h e v e r y o n e n e x t t o us;
t h a t is o n e o f t h e m a i n p o s s i t i o n s in F r a n c e . T h a n k y o u very
much.
A GERMAN POINT OF VIEW

Hans Martin Sass

D i r e c t o r o f t h e C e n t r e o f M e d i c a l Ethics in B o c h u m . D i r e c t o r o f
t h e E u r o p e a n P r o g r a m m e o f t h e K e n n e d y I n s t i t u t e o f Ethics,
W a s h i n g t o n , D C . President of the D e p a r t m e n t of Philosophy of
t h e University of the Ruhr, B o c h u m (Germany)

ABSTRACT

W i t h the histórica! antecedent o f Nazi-ism and un-

der pressure f r o m strong, so-cailed " a l t e r n a t i v e "
groups, Germán scientific policy thought that it was
important to come to public agreement on the legal
and ethical implications o f the application to people
o f genetic technology. To this end, different national
c o m m i t t e e s have d r a w n u p d i f f e r e n t r e p o r t s in
which, apart from acknowledging the advantages of-
f e r e d by g e n o m e analysis, g e n e r a l guidelines are
given which reject a predictive medicine with eugen-
esic aims a n d w h i c h f a v o u r specific vigilance in
precise áreas o f use a n d abuse such as pre-natal
diagnosis, diagnostic testing related to employment
a n d both civil a n d penal law-cases, protection o f da-
ta and privacy.
The scientific community, the author says, musí pro-
mote all types o f differential ethics. W i t h this aim in
mind, he ends with the presentation o f a methodo-
logical procedure, based on differentiation, assignation
and evaluation o f specific cases, which from the moral
a n d e t h i c a l p o i n t o f view facilitates d i s c e r n m e n t
between the benefits a n d risks o f genetic research.
In G e r m a n y , H u m a n G e n o m e P r o j e c t s have b e e n discussed u n d e r 63
t w o p e r s p e c t i v e s : t h e social a c c e p t a b i l i t y o f g e n e t e c h n o l o g y in
g e n e r a l a n d t h e e u g e n i c aspects in p a r t i c u l a r . G i v e n t h e h i s t o r i c a l
background o f Nazi e x p e r i m e n t a t i o n and t h e existence o f s t r o n g
so called ' a l t e r n a t i v e g r o u p s ' , w e l l c o n n e c t e d t o t h e m e d i a , p u b l i c
c o n c e r n has b e e n v o i c e d in r e g a r d t o m o r a l risks a s s o c i a t e d w i t h
t h e p r o j e c t s a n d d i s c u s s e d u n d e r ' w o r s t case s c e n a r i o ' p e r s p e c -
t i v e s . Even t h e use o f t h e t e r m ' g e n e ' , alike t h a t o f t h e t e r m ' r e -
p r o ' , w h i c h stands f o r r e p r o d u c t i v e m e d i c i n e , causes o v e r s e n s i t i -
v i t y a n d h i p e r i r r i t a b i l i t y in s o m e s e c t o r s o f s o c i e t y a n d t h e m e d i a .
A m i d a basic t e c h n o p h o b i c a t t i t u d e t o w a r d s n e w f o r m s o f high
t e c h , special fears have b e e n e x p r e s s e d in r e g a r d t o f u t u r e d i s -
c r i m i n a t i o n o f t h e r e t a r d e d a n d h a n d i c a p p e d , d i s c r i m i n a t i o n in t h e
w o r k place a n d in t h e h e a l t h c a r e a n d I n s u r a n c e s y s t e m s a n d an
i n c r e a s e in s e l e c t i v e a b o r t i o n s f o l l o w i n g p r e d i c t i v e prenatal
screening.

My presentation on the G e r m á n debate summarizes ( I ) the de-

v e l o p m e n t o f c o n s e n s u s f o r m a t i o n in p u b l i c p o l i c y , (2) t h e a l t e r -
n a t i v e g r o u p a r g u m e n t s against g e n o m e p r o j e c t a n d c o n s e n s u s
f o r m a t i o n , (3) professional and academic bioethical debates r e -
garding the H u m a n G e n o m e Project.

Germán science policy and

the Human Genome Project

Science p o l i c y in t h e F e d e r a l R e p u b l i c o f G e r m a n y , since d u r i n g
t h e last y e a r s has r e c o g n i z e d t h e i m p o r t a n c e o f a n t i c i p a t o r y m o r -
al d e b a t e a n d p u b l i c c o n s e n s u s f o r m a t i o n in r e g a r d t o t h e d e v e l -
o p m e n t a n d i n t r o d u c t i o n o f n e w t e c h n o l o g y . In 1983 t h e B M F T
(Federal M i n i s t r y f o r Research and D e v e l o p m e n t ) Minister Dr.
R i e s e n h u b e r i n v i t e d a d i v e r s e g r o u p o f e x p e r t s t o discuss e t h i c a l
a n d legal issues o f a p p l y i n g g e n e t e c h n o l o g y t o h u m a n s . S h o r t l y
t h e r e a f t e r an e n q u e t e c o m m i s s i o n o f t h e B u n d e s t a g w a s e s t a b -
lished a n d p u b l i s h e d its r e p o r t ' C h a n c e s a n d risks o f G e n e t e c h -
n o l o g y ' in 1987. T h e G e r m á n R e s e a r c h F o u n d a t i o n ( D F G ) a n d
t h e M a x Planck Society ( M P G ) i n t r o d u c e d p r o g r a m s f o r social
and m o r a l assessment o f research and s p o n s o r e d conferences
and publications. T h e n e w a p p r o a c h by Minister Riesenhuber in-
d i c a t e s t h a t t h e e x e c u t i v e b r a n c h as w e l l as t h e legislative, a n d
r e s e a r c h f u n d i n g i n s t i t u t i o n s in t h e F e d e r a l R e p u b l i c have l e a r n e d
f r o m p o l i t i c a l a n d m o r a l m i s m a n a g e m e n t o f t h e n u c l e a r d e b a t e in
G e r m a n y by encouraging public ethical debate p r i o r t o i n t r o d u c -
tion of new technology.

In 1987 an e n q u e t e c o m m i s s i o n o f t h e F e d e r a l P a r l i a m e n t issued
a r e p o r t o n ' C h a n c e s a n d Risks o f G e n e T e c h n o l o g y ' (Bunde-
stagsdrucksache 1 0 / 6 7 7 5 ) . T h e r e p o r t discussed d i f f e r e n t scena-
r i o s o f social a n d m o r a l a c c e p t a b i l i t y o f g e n e m a n i p u l a t i o n , i n -
cluding Human G e n o m e screening. The reports recognizes
64 d i a g n o s t i c benefits o f g e n o m e analysis a n d r e c o m m e n d s t o discuss
d i f f e r e n t s c e n a r i o s , p a r t i c u l a r l y t h o s e ¡n p r e n a t a l s c r e e n i n g a n d ¡n
t h e w o r k place, separately. R e c o m m e n d a t i o n s include n o n d i r e c t i v e
c o u n s e l i n g , n o n - e u g e n i c use o f n e w t e c h n o l o g y , c o o p e r a t i o n w l t h
t h e m e d i c a l p r o f e s s i o n t o d e v e l o p a c a t a l o g u e t r e a t a b l e diseases
f o r prenatal screening and f o r self-regulation t o disclose only
n o n - t r e a t a b l e s e v e r e a n o m a l l e s o r diseases p r i o r t o t h e 12th w e e k
o f p r e g n a n c y , t h e d e v e l o p m e n t o f b i n d i n g legal p a r a m e t e r s a n d
e m p l o y e r - e m p l o y e e c o o p e r a t i o n f o r g e n e t i c s c r e e n i n g in t h e
w o r k place (Sass, 1988).

A j o i n t Bund-Laender c o m m i s s i o n of sénior executives f r o m state

a n d f e d e r a l g o v e r n m e n t , in M a y o f 1990, i s s u e d g u i d e l i n e s re-
fusing general p r o h i b i t i o n o f genetic screening and favoring spe-
cific o v e r s i g h t in r e g a r d t o specific áreas o f possible use a n d abuse:
p r e n a t a l s c r e e n i n g , s c r e e n i n g in o c c u p a t i o n a l h e a l t h , a n d in civil
a n d penal c o u r t cases, p r o t e c t i o n o f data a n d p r i v a c y . F o r p r e n a t a l
s c r e e n i n g t h e legal a n d v o l u n t a r y access t o s c r e e n i n g , t h e t r i a s
c o u n s e l i n g - s c r e e n i n g - c o u n s e l i n g , n o s c r e e n i n g t o t o t i p o t e n t cells
a n d s c r e e n i n g o f n o n - t o t i p o t e n t t r o p h o b l a s t cells o n l y a f t e r c l i n -
ical s a f e t y s t a n d a r d s h a v e b e e n d e v e l o p e d , n o n - d i r e c t i v e and
n o n - a c u t e c o u n s e l i n g , special l i c e n s i n g f o r s c r e e n i n g p h y s i c i a n s ,
limited screening f o r severe and un-treatable anomalies and
diseases ( n o official list o f s u c h deseases shall be p r o v i d e d ) , c o s t s
paid b y s t a t u t o r y o r p r í v a t e I n s u r a n c e , r e s t r i c t e d I n f o r m a t i o n t o
p a r e n t s p r i o r t o t h e 12th. w e e k o f pregnancy, p a r t i c u l a r l y r e g a r d i n g
t h e s e x o f t h e f e t u s , n o o f f i c i a l l a r g e scale s c r e e n i n g f o r n o n -
t r e a t a b l e diseases. S c r e e n i n g in t h e w o r k place m a y n o t i n c l u d e
general D N A diagnosis ( c h r o m o s o m a l and p r o t e i n chemical
diagnosis o n l y f o r diseases o r risks r e l a t e d t o t h e p a r t i c u l a r w o r k
place), i n f o r m e d c o n s e n t o f t h e e m p l o y e e (illegal screening p r o g r a m s
a r e ¡ilegal e v e n w h e n c o n s e n t is o b t a i n e d ) , n o p r e v e n t i v e DNA
screening b u t specific c h r o m o s o m a l and p r o t e i n screening f o r
early d e t e c t i o n o f o c c u p a t i o n a l health risks. N o general screening
is a l l o w e d f o r t h o s e a p p l y i n g f o r h e a l t h c a r e o r Ufe i n s u r a n c e ,
specific s c r e e n i n g f o r d i a g n o s i n g v i s i b l e o r o t h e r w i s e diagnosed
risks m a y b e d o n e . T h e legal s y s t e m m a y n o t d o s c r e e n i n g f o r
c o d i n g a p e r s o n , o t h e r specific s c r e e n i n g f o r s e a r c h o r ¡n f o r e n -
sic m e d i c i n e ( D N A f i n g e r p r i n t i n g ) m a y b e d o n e .

T h e s e g u i d e l i n e s m a r k an i m p o r t a n t c o n s e n s u s in G e r m á n p u b l i c
policy and will d e t e r m i n e t h e f u t u r e course o f regulation, self-reg-
ulation, legisltion and e m p l o y e r - e m p l o y e e c o o p e r a t i o n (Buelow,
1990; Sass, 1 9 9 0 a ) . T h e y a r e s u p p o r t e d b y p o w e r f u l g r o u p s in
society and political parties, e x c e p t t h e G r e e n party. The
G r e e n ' s p o l i t i c s " i s d i r e c t e d against t h e c o n c e p t s o f b i o l o g y a n d
m e d i c i n e w h i c h a p p l y g e n e t i c e n g i n e e r i n g in a a t t e m p t t o m e r e l y
r e p a i r social a n d e n v i r o n m e n t a l p r o b l e m s . G e n e t i c engineering
t e c h n i q u e s a r e t h e p r o d u c t o f a r e l a t i o n s h i p t o N a t u r e w h i c h is
based o n e x p l o i t a t i o n a n d d o m i n a t i o n r a t h e r t h a n s u s t a i n a b i l i t y .
T h i s is t r u e n o t o n l y f o r a p p l i e d r e s e a r c h b u t f o r basic r e s e a r c h
as w e l l ; w i t h t h e a d v e n t o f g e n e t i c e n g i n e e r i n g , b o t h a r e b e -
c o m i n g increasingly d i r e c t e d by t h e objetives o f accelerating i n - 65
d u s t r i a l u t i l i z a t i o n o f N a t u r e . . . W e are d e m a n d i n g a n i m m e d i a t e
halt to o// genetic engineering research a n d to all related applications
a n d forms o f p r o d u c t i o n . " ( D i e G r u e n e n , 1986, p. 2 )

In July 1990, t h e G e r m á n G e n e t i c E n g i n e e r i n g L a w ( G e n g e s e t z )
i n c l u d i n g f i v e r e l a t e d r e g u l a t i o n s carne i n t o f o r c é a n d s u p p l e -
m e n t s t h e r e c o m m e n d a t i o n s o f t h e B u n d - L a e n d e r g r o u p in e n s u r -
ing p r o t e c t i o n against r i s k a n d d a n g e r s a r i s i n g f r o m recombinant
n u c l e i acids c o n s t r u c t e d in v i v o .

G e r m á n federal g o v e r n m e n t (Bundesregierung) and t h e federal

parliament (Bundestag) s u p p o r t t h e European G e n o m e Project.
T h e f i r s t d r a f t o f t h e EC P r e d i c t i v e M e d i c i n e P r o j e c t ( C O M ( 8 8 )
4 2 4 final - S Y N 146, July 2 0 , 1988), h o w e v e r , caused a s t o r m y d e -
b a t e in t h e f e d e r a l p a r l i a m e n t as all p o s i t i o n s , i n c l u d i n g t h e f e d e r -
al g o v e r n m e n t h a d p r o b l e m s w i t h t h e s e m a n t i c s o f t h e project
a n d its p o s s i b l e e u g e n i c c o n s e q u e n c e s . In p a r t i c u l a r , t h e w o r d i n g
" P r e d i c t i v e M e d i c i n e seeks t o p r o t e c t individuáis f r o m t h e k i n d s
o f Hiñeses t o w h i c h t h e y a r e g e n e t i c a l l y m o s t v u l n e r a b l e a n d ,
w h e r e appropiate, t o prevent the transmission of the genetic
susceptibilities t o t h e n e x t g e n e r a t i o n " (l.c, l . l ) was i n t e r p r e t e d
as i n t r o d u c i n g a e u g e n i c p u b l i c h e a l t h p o l i c y f o r e n t i r e E u r o p e .
W h i l e all p a r t i e s , e x c e p t t h e G r e e n s , a n d t h e g o v e r n m e n t , w e r e
in f a v o r o f p o s s i b l e d i a g n o s t i c b e n e f i t s , all p o s i t i o n s criticized
p o s s i b l e o r real e u g e n i c i d e o l o g y a n d i n t e n t i o n o f t h e p r o g r a m ,
t h e w o r d i n g a n d f o c u s o f w h i c h w a s s u b s e q u e n t l y c h a n g e d . It w a s
a s k e d w h e t h e r t h e p r o g r a m w o u l d l a t e r cali f o r a " e u g e n i c o r i -
e n t e d E u r o p e a n m e d i c a l a n d h e a l t h p o l i c y a n d mass screening,... a
E u r o p e a n a b o r t i o n p r o g r a m m o t i v a t e d b y e u g e n i c s " (Seesing), a l -
s o , w h e t h e r " w e G e r m a n s , in t h e l i g h t o f e x p e r i e n c e s d u r i n g t h e
years 1933 t h r o u g h , s h o u l d be s e n s i b l e , e v e n s u p e r s e n s i b l e " in
regard t o t h e p r o t e c t i o n o f human rights and human dignity
( C a t e n h u s e n ) ; M i n i s t e r Riesenhuber p o i n t e d o u t t h a t g e r m l i n e i n t e r -
v e n t i o n s h o u l d n o t be a c c e p t e d a n d g e n o m e analysis s h o u l d n o t
b e used f o r h e a l t h p o l i c y based o n eugenics, also, t h a t v o l u n t a r i -
ness a n d d a t a p r o t e c t i o n s h o u l d b e essential ( D e u t s c h e r B u n d e -
stag, P l e n a r p r o t o k o l l 1 1 / 1 2 2 , 8 9 3 8 - 8 9 4 3 , Jan 2 6 , 1989).

Alternatíve groups argumentation

against Human Genome Projects

T h e alternatíve scene, a s t r o n g p r o m o t o r o f anticapitalist ide-

ology, recognized t h e potentials of t h e eugenics debate when
t h e y p r e v e n t e d Peter Singer, t h e A u s t r a l i a n bioethicist, from
s p e a k i n g as an i n v i t e d g u e s t a t c o n f e r e n c e s in G e r m a n y in 1989.
Singer, in o n e o f his b o o k s , h a d discussed a c t i v e euthanasia o f se-
verely defected n e w b o r n s . These agitations t u r n e d t h e discussion
regarding selectively w i t h h o l d i n g t r e a t m e n t f r o m severely handi-
c a p p e d n e w b o r n s i n t o a d e b a t e o f f r e e s p e e c h . Singer, in a b i t t e r
66 a r t i c l e , d e s c r i b e s his e x p e r i e n c e s w i t h f r e e s p e e c h a n d a c a d e m i c
d i s c o u r s e in G e r m a n y in t h i s y e a r ' s f i r s t issue o f ' B i o e t h i c s ' ( B i o -
e t h i c s , 4 , 1990). T h e Singer d e b a t e r e s u l t e d in t h e development
of subcultural n e t w o r k s f r o m the e x t r e m e right t o t h e extreme
left, iniciating a c a m p a i g n 'gegen G e n u n d R e p r o ' , i. e. against g e n e
t e c h n o l o g y and r e p r o d u c t i v e t e c h n o l o g y . T h e annual m e e t i n g o f
t h e G e r m á n Society f o r A n t h r o p o l o g y and H u m a n Genetics was
c a n c e l e d in 1989 d u e t o t h r e a t s f r o m a l t e r n a t i v e g r o u p s a n d o t h -
er internal problems. The Bochum C e n t e r f o r Medical Ethics
l a t e r in 1 9 8 9 , n e v e r t h e l e s s , p r o c e e d e d w i t h an international
w o r k s h o p o n e t h i c a l issues r e g a r d i n g t h e H u m a n G e n o m e Pro-
j e c t a n d h u m a n s o m a t i c cell g e n e t h e r a p y . T h e local s t u d e n t o r -
g a n i z a r o n a n d g r o u p s a s s o c i a t e d w i t h t h e Evangelische S t u d e n -
t e n g e m e i n d e (local P r o t e s t a n t s t u d e n t unión) t h r e a t e n e d to
i n t r u d e a n d u p s e t t h e m e e t i n g , b u t finally a c c e p t e d t h e i n v i t a t i o n
t o a t t e n d a n d t o g e t i n v o l v e d in t h e d i s c u s s i o n . In t h e p r e t e x t o f
the meeting the students imputed that the conference's prime
a n d e x c l u s i v e g o a l w a s t o d e v e l o p an a c c e p t a n c e s t r a t e g y (Ak-
zeptanzstrategie) f o r undiscriminating human gemone manipula-
r o n , f o r d i s c r i m i n a t i o n in t h e w o r k place a n d f o r discriminating
against h a n d i c a p p e d a n d d i s a b l e c i t i z e n s . T h e y i m p u t e d t h a t all
discussion o n genes w o u l d necessarily be a discussion o n e u -
genics, i. e. a d v o c a t i n g a n d p r o m o t i n g eugenics.

In J u n e 1990 t h e E u r o p e a n S o c i e t y f o r P h i l o s o p h y o f Medicine
and Health C a r e (ESPMH), t h e professional organization o f E u r o -
pean b i o e t h i c i s t s , w a s s c h e d u l e d t o h o l d its 4 t h . A n n u a l Meeting
at t h e B o c h u m Z e n t r u m f u e r Medizinische Ethik focussing o n
' C o n s e n s u s F o r m a t i o n in M e d i c i n e a n d H e a l t h C a r e ' , a r a t h e r
non-controversial methodological theme. Nevertheless, the re-
g i o n a l a n d n a t i o n a l ' a l t e r n a t i v e s c e n e ' , i n c l u d i n g l e a d i n g left w i n g
journalists, decided t h a t these activities o f the B o c h u m center
a n d its p r o j e c t s in d i f f e r e n t i a l e t h i c s h a d t o be p u t t o an e n d .
T h e y s t a r t e d t h e d e f a m a t i o n c a m p a i g n against ' b i o e t h i c s ' in g e n -
e r a l a n d c a l l e d f o r p r e v e n t i n g t h e m e e t i n g t o t a k e p l a c e : " I t is
mandatory t o prevent, that under the cloak of tolerance, d e m o -
c r a c y , a n d l i b e r a l i s m , s t r a t e g i e s o f a n n i h i l a t i o n can be d i s c u s s e d .
T h i s is t h e r e a s o n , t h a t w e w i l l p r e v e n t t h e B o c h u m c o n g r e s s " .
(Sass, V i e f h u e s , 1990, p. 4 3 ) . A so called n a t i o n a l n e t w o r k , l e d b y
t h e G e n a r c h i v in Essen ( g e n e a r c h i v ) a n d an a d - h o c A n t i - E u t h a n a -
sia F o r u m R u h r g e b i e t (anti e u t h a n a s i a f o r u m r u h r área) o r g a n i z -
ed W i d e r s t a n d s t a g u n g e n (resistance meetings) and p r e p a r e d f o r
i n t e r r u p t i n g a n d harassing t h e m e e t i n g o f t h e E S P M H . T h e n a -
t i o n w i d e j o u r n a l ' K o n k r e t ' ( n o . 5, p. 2 2 ) e d i t e d in H a m b u r g , in its
June issue a n n o u n c e d a series o f a l t e r n a t i v e g r o u p a c t i v i t i e s : June
I -3 in C o l o g n e , ' C o n g r e s s o f t h e Radical L e f t ' ( K o n g r e - d e r r a d i -
kalen L i n k e n ) , a 2 1/2 day t e a c h - i n o n t o p i c s s u c h ' n e v e r a n e w
G e r m a n y again', ' a n t i c a p i t a l i s t i c e c o l o g y a n d p e r s p e c t i v e s o f resis-
t a n c e ' , ' e u g e n i c s ' , s p e a k e r s a n d panelists i n c l u d i n g f e m i n i s t s , l e f t -
radicals, k o m m u n i s t s , e x - a n d still G r e e n s ; a o n e day c o n f e r e n c e
June 9 in K u l t u r z e n t r u m B o c h u m L a n g e d r e e r o n ' D e a d l y E t h i c s '
(Tódliche Ethik), one of the topics was: h o w t o prevent the
E S P M H m e e t i n g . T h e E S P M H m e e t i n g s in B o c h u m w e r e m o v e d 67
f r o m B o c h u m t o M a a s t r i c h t . T h e b o a r d o f t h e E S P M H , in a l e t t e r
t o t h e ad h o c c o m m i t t e e o f e x p e r t s in b i o e t h i c s o f t h e E u r o p e a n
C o m m u n i t y ( C A H B I ) , June 18, 1990, called t h e e v e n t s " a v i o l a -
t i o n o f basic d e m o c r a t i c p r i n c i p i e s " , a n d c o m p l a i n e d a b o u t " t h e
s h a m e f u l fact... t h a t t h e basic d e m o c r a t i c p r i n c i p i e s o f f r e e d o m o f
a s s e m b l y a n d f r e e d o m o f s p e e c h c o u l d n o t be u p h e l d in a U n i -
v e r s i t y t o w n in t h e F e d e r a l R e p u b l i c o f G e r m a n y , a n d w e f e e l
t h a t t h e o c c u r r e n c e o f t h i s i n c i d e n t m u s t be m a d e publiciy
k n o w n . W e feel sure t h a t t h e vast m a j o r i t y o f t h e G e r m á n p e o -
pie w i l l a g r e e w i t h us t h a t i t is c o n t r a r y t o t h e i r i n t e r e s t s a n d t o
t h e i n t e r e s t s o f all E u r o p e a n s t h a t a c a d e m i c s o c i e t i e s s u c h as
o u r s a r e f o r c e d t o a v o i d h o l d i n g o u r c o n f e r e n c e s in t h e F e d e r a l
R e p u b l i c o f G e r m a n y " (Saas, V i e f h u e s , 1990, p. 2 9 f ) .

T h e " a l t e r n a t i v e " s t r a t e g y o f d i a l o g u e refusal is based o n m i s t r u s t

t o w a r d s t h e " e n t i r e e s t a b l i s h m e n t " , a s u s p i c i o n against a p r e s u m -
e d " c a r t e l o f o r g a n i z e d i n t e r e s t s " , i m p u t i n g class i n t e r e s t g u i d -
ing w i t h o u t e x e m p t i o n t h e p o s i t i o n s t a k e n b y all s p e a k e r s a n d
c o n f e r e n c e p a r t i c i p a n t s . A n a r t i c l e in t h e May/June issue o f ' B o -
riss', a B o c h u m s t u d e n t j o u r n a l , p u t s t h e t h e s i s , t h a t t h e m e t h o d
o f assessing a n d balancing g o o d s a n d m o r a l g o o d s ( G u e t e r a b w a e -
gung) sounds g o o d o n paper only, b u t will n o t w o r k w h e n it
c o m e s t o real-life issues, because p e r s o n a l a n d g r o u p i n t e r e s t s w i l l
p r e v a l í , s u c h as t h o s e against t h e b u r d e n s o f c a r i n g o f p a y i n g f o r
h a n d i c a p p e d a n d disable c i t i z e n s , a n d necessarily w i l l p r e p a r e t h e
r o a d f o r euthanasia. T h e r e f o r e t h e a u t h o r s u p p o r t s t h e " s u p r a r e -
gional coalition o f g r o u p s o f t h e r e t a r d e d and t h e crlppled, f e m i -
n i s t g r o u p s , e n e m i e s o f genes a n d r e p r o d u c t i o n " in its e f f o r t s t o
p r e v e n t t h e c o n f e r e n c e o f " p h i l o s o p h e r s calling t h e m s e l v e s b i o -
ethicists discussing euthanasia, m e t h o d s o f r e p r o d u c t i o n , and
d e a t h c r i t e r i a " (Sass, V i e f h u e s , 1990, p. 35f). B i o e t h i c s is d e f i n e d as
" e t h i c s o f t e c h n o c r a t s " , a n e w " f o r m o f r e s e a r c h in a c c e p t a b i -
lity", o r "services ethics", serving t o " p r o v i d e acceptance for
r i s k y t e c h n o l o g i e s , in o r d e r t o p r o m o t e easy i n t r o d u c t i o n o f a
health policy ready t o accept dead persons and t h e realization o f
c o s t - b e n e f i t based c a l c u l a t i o n s o f k i l l i n g u t o p i a s " (l.c. p. 3 6 ) .

T h e a u t h o r concludes, t h a t t h e ESPMH meeting scheduled for

B o c h u m " h a s t o be assessed as a c o n t r i b u t i o n t o f u r t h e r i n t r o d u c -
ing b i o e t h i c s i n t o E u r o p e a n d p a r t i c u l a r l y i n t o t h e F e d e r a l R e -
public", w i t h the intention " o r further suppression of critical
assessment o f gene- and r e p r o d u c t i v e technologies o r o f a health
policy exclusively o r i e n t e d along economic criteria".

I do n o t t h i n k that t h e 'alternative groups' represent a d o m i -

n a n t f o r c é in W e s t G e r m á n s o c i e t y , o n t h e c o n t r a r y . B u t in t h e
absence of a differentiating media debate and public discussion
o n issues o f m o r a l c o n c e r n in m e d i c i n e in p a r t i c u l a r a n d t e c h -
n o l o g y in g e n e r a l , t h e y a r e c a p a b l e t o o r g a n i z e i m p r e s s i v e s u p -
p o r t f o r ad h o c a c t i o n s . F o r t h o s e ad h o c a c t i o n s , t h e y e v e n -
tually m i g h t also get s u p p o r t o f a n a t i o n w i d e hard core of
68 violent anarchists, muffled r o w d i e s , t e r r o r i s t s , and toughs.
N e v e r t h e l e s s , t h e a r g u m e n t s v o i c e d by these g r o u p s reveal a
cultural and political attitude of a potentially g r o w i n g n u m b e r o f
so called a l t e r n a t i v e individuáis and t h e i r g r o u p s w h o have lost
t h e i r basic t r u s t in s o c i e t y a n d w h o h a v e b e c o m e suspicious
e v e n a g a i n s t t h o s e , w h o w o r k h a r d t o g i v e t h e i r b e s t in a n a l y z -
ing a n d assessing t h e w r o n g s a n d pitfalls o f m o d e r n medicine,
m o d e r n technology, of technocratism, e c o n o m i s m , and bureau-
c r a t i s m . T h e y d o n o t r e p r e s e n t , as t h e y c l a i m , an a l t e r n a t i v e t o
t h e e x i s t i n g s o c i e t y , r a t h e r t h e f a r o u t edges o f a s o c i e t y b a s e d
on a fabric o n c o o p e r a t i o n , mutual t r u s t , and solidarity, for
w h i c h d i a l o g u e a n d o p e n a n d f a i r d i s c o u r s e a r e e s s e n t i a i . In r e -
f u s i n g t h e d i s c u s s i o n a n d in t h r e a t e n i n g t o a c t i v e l y preventing
consensus o r i e n t e d discussions, t h e d e s t r o y t h e f u n d a m e n t of
societies based o n m u t u a l respect, discourse, and c o o p e r a t i o n .
In t a r g e t i n g t h e h u m a n g e n o m e p r o j e c t a n d o t h e r issues w h i c h
include m o r a l risks and dangers, t h e y are n o t d i r e c t l y i n t e r e s t -
e d in t h e issue itself, r a t h e r use i t t o p r e s e n t t h e i r p a r t i c u l a r v i -
s i ó n o f an a l t e r n a t i v e w o r i d , f o r a g i t a t i o n a n d n e t w o r k b u i l d i n g
a m o n g t h e dissatisfied and f r u s t r a t e d . Some o f these g r o u p s ,
s u c h as t h e G r e e n s , f o l l o w a d o u b l e s t r a t e g y o f i n v o l v e m e n t in
t h e societai n e t w o r k o f allocating and deciding o n t h e o n e side,
w h i l e o n t h e o t h e r hand criticizing and violently attacking t h e
'system' f r o m the outside.

Academíc and professíonal

bíoethical debates

i r r a t i o n a l a n d i d e o l o g i c a l o u t r i g h t a n d g e n e r a l refusai o f H u m a n
G e n o m e P r o j e c t s is a challenge n o t o n l y t o t h e f a b r i c o f a s o c i e t y
based o n c o m m u n i c a t i o n , d i a l o g u e a n d m u t u a l l y s h a r e d v a l ú e s ,
b u t aiso a challenge f o r t h e professíonal c o m m u n i t y o f scientists,
physicians a n d b i o e t h i c i s t s a n d t h e i r p r o f e s s í o n a l e t h o s . in a r g u i n g
w i t h t h e s e g r o u p s , m o r e is a t s t a k e t h a n a c a d e m i c f r e e d o m a n d
f r e e d o m of speech. W e need understanding, patience and e n d u r -
ance in n o t g i v i n g u p t o c o m m u n i c a t e w i t h t h o s e w h o d i s t r u s t ali
established f o r m s o f c o m m u n i c a t e and dialogue, w h o find secu-
r i t y in i n t e r n a l e m i g r a t i o n a n d in r e f u s i n g c o m m u n i c a t i o n , w h o
prefer violence o v e r dialogue, conflict o v e r c o m m u n i c a t i o n .

T h e a g i t a t i o n s , u n f o r t u n a t e as t h e y a r e , cali f o r an i n c r e a s e , n o t
an a b a n d o n m e n t , o f ali f o r m s o f d i f f e r e n t i a t i n g e t h i c s in p u b l i c
d i s c o u r s e , in e d u c a t i o n , a n d in t h e p r o f e s s í o n a l a n d p o l i t i c a l s e t -
tings. O n l y i n c r e a s e d c o m p e t e n c e in d i f f e r e n t i a l e t h i c s w i l l e n a b l e
individuáis, professions, and societies t o apply and d e v e l o p t e c h -
n o l o g y in a p r u d e n t , e t h i c a l , a n d socially r e s p o n s i b l e w a y . T h e r e -
fusai o f d i a l o g u e , t h e o p i n i o n a t e d , s t u b b o r n a n d d o g m a t i c refusai
o f c e r t a i n f o r m s o f t e c h n o l o g y a n d o f m o r a l t e c h n o l o g y assess-
m e n t w i l l o n l y d e s t r o y t h e s o c i a l , m o r a l , a n d finally p o l i t i c a l f a b r i c
o f p l u r a l i s t i c a n d t e c h n o l o g y based s o c i e t i e s .
Scientists a n d b i o e t h i c i s t have t o play an i m p o r t a n t r o l e in s u p - 69
p o r t i n g differentiating public debates and decisión making. A s ide-
o l o g i s t s t e n d t o a r g ü e v e r y g e n e r a l o n l y , i t is i m p o r t a n t t o be
v e r y specific in r e g a r d t o v e r y specific b e n e f i t s a n d h a r m s , t o d o
m o r a l s c e n a r i o a s s e s s m e n t case by case. A s w e d o n o t discuss
t h e m o r a l benefits o r harms o f electricity, w h i c h include light-
ening, e l e c t r i c m a c h i n e r y , e l e c t r o c u t i o n , e l e c t r i c t o r t u r e , a n d m a k e
m o r a l a s s e s s m e n t s p r o o r c o n t r a e l e c t r i c i t y based o n w o r s t case
s c e n a r i o v i s i ó n , w e m a y n o t discuss H u m a n G e n o m e Projects
in g e n e r a l u n d e r t h e aspects o f e u g e n i c abuse o r p e r s o n a l a n d
p r o f e s s i o n a l d i s c r i m i n a t i o n . R a t h e r , w e w a n t t o discuss p r o f e s -
sionally a n d p u b l i c l y its use f o r p r e v e n t i v e d e t e c t i o n o f v e r y s p e -
cific h e a l t h risks in v e r y specific w o r k places o r f o r p r e n a t a l d e -
t e c t i o n o f s e v e r e g e n e t i c c h r o m o s o m a l h e r i t a g e o f u n b o r n life a t
risk o r f o r D N A fingerprinting of crimináis. These scenarios offer
high m o r a l , m e d i c a l , a n d social benefits o v e r l o w risk and no
h a r m . O t h e r s c e n a r i o s , such as r o u t i n e g e n e r a l g e n e t i c s c r e e n i n g
o f e n t i r e p o p u l a t i o n s , c o d i n g specific individuáis w i t h l o n g t e r m
h e a l t h risks o r p r e n a t a l sex s e l e c t i o n p r e s e n t high m o r a l h a r m s
a n d risks a s s o c i a t e d w i t h m i n i m a l o r negligible m o r a l o r social
benefits. O p e n and pluralistic societies will agree o n many g o o d
s c e n a r i o s a n d o n m a n y u n w a n t e d a n d u n c a l l e d f o r ; t h e r e w i l l be
d i s a g r e e m e n t in r e g a r d t o s o m e s c e n a r i o s in t h e m i d d l e . B u t t h e
d i f f e r e n t i a t i o n b e t w e e n t y p i c a l s c e n a r i o s o f use a n d a b u s e w i l l
h e l p n o t o n l y r e s e a r c h e s , physicians, a n d p o l i t i c i a n s , b u t m o s t o f
all t h e e d u c a t e d i n d i v i d u a l c i t i z e n in assessing t h e b e n e f i t s a n d
l i m i t s o f any f o r m o f n e w t e c h n o l o g y , i n c l u d i n g t h e t e c h n o l o g i e s
w h i c h a l l o w us t o i d e n t i f y , d i a g n o s e , a n d e v e n t u a l l y heal a n d m a -
nipúlate t h e H u m a n G e n o m e heritage.

T h e B o c h u m C e n t e r f o r M e d i c a l Ethics has d e v e l o p e d a S c e n a r i o
D e v e l o p m e n t P r o c e d u r e f o r m o r a l assessment o f specific new
s c e n a r i o s d e f i n e d b y n e w use o f t e c h n o l o g y o r use o f n e w t e c h -
n o l o g y a n d c o m p l e x m o r a l c o n f l i c t s (Sass, 1 9 9 0 b ) . T h e m o r a l as-
s e s s m e n t p r o c e d u r e f o l l o w s p r o v e n m e t h o d s in t e c h n o l o g y as-
s e s s m e n t and r i s k analysis o r i g i n a l l y d e v e l o p e d in complex
technical o r e c o n o m i c situations f o r risk r e d u c t i o n and risk p r e -
v e n t i o n . T h e m o r a l s c e n a r i o a s s e s s m e n t m e t h o d a v o i d s basic i d e -
ological o r metaphysical weltanschauung discussion and c o n f r o n -
t a r o n . Its t w o f i r s t steps analyze a n d discuss m o r a l a n d t e c h n i c a l
p r i n c i p i e s a n d facts e s t a b l i s h i n g t h e f r a m e w o r k o f a specific s c e -
n a r i o . T h e n e x t t w o steps c o m p a r e a n d assess s c e n a r i o m o d i f i c a -
t i o n s p r o v i d i n g d i f f e r e n t m o r a l r i s k p a r a m e t e r s and d i f f e r e n t m o r -
al b e n e f i t - h a r m balances. T h e s c e n a r i o a s s e s s m e n t m e t h o d has
p r o v e n t o be a m o s t e f f e c t i v e f o r m s o f d e v e l o p i n g professional
e t h i c s e x p e r t i s e in s i m u l a t i n g a n d a n t i c i p a t i n g real-life challenges
t o e t h i c a l e x p e r t i s e in t h e w o r k place a n d in p e r s o n a l life. T h e
use o f m e t h o d o l o g i c a l l y r e f i n e d m o r a l s c e n a r i o a s s e s s m e n t p r o -
c e d u r e s is o f p a r t i c u l a r i m p o r t a n c e in p l u r a l i s t i c s o c i e t i e s f o r d e -
v e l o p i n g e x p e r t i s e in c o m p l e x a n d c o n s e n s u s o r i e n t e d v a l u é as-
s e s s m e n t in c o n c r e t e s i t u a t i o n s a n d f o r d e t e r m i n i n g t h e c o u r s e
o f a c t i o n in a p p l y i n g , d e v e l o p i n g a n d s t e w a r d i n g n e w t e c h n o l o g y .
70 including gene technologies. For a morally responsible, politically
p r u d e n t , and c u l t u r a l l y c o m f o r t a b l e a c c e p t a n c e o f H u m a n G e n o m e
P r o j e c t s d i f f e r e n t i a t i n g m o r a l s c e n a r i o p r o c e d u r e s m u s t be u s e d
in (a) c o n s u l t i n g o n p u b l i c p o l i c y o p t i o n s , (b) p r o f e s s i o n a l s c e n a r -
i o a s s e s s m e n t , (c) a n t i c i p a t o r y r i s k analysis, a n d ( d ) single case
evaluation.

M o s t a u t h o r s in t h e p u b l i c a t i o n w h i c h c a m e o u t o f t h e m e n t i o n -
e d B o c h u m m e e t i n g in 1989 (Saas, 1990), in assessing t h e p r o b -
able m o r a l a n d s o c i e t a l b e n e f i t s , h s k s a n d h a r m s o f H u m a n G e -
n o m e P r o j e c t s a n d h u m a n g e n e t h e r a p y , use t h e m e t h o d o l o g i c a l
a p p r o a c h o f d i f f e r e n t i a t i n g , allocating, and assessing m i d - l e v e l m o r -
al p r i n c i p i e s a n d t e c h n i c a l risks a n d u n c e r t a i n t i e s in c o n c r e t e sce-
n a r i o s in discussing t h e m o r a l b e n e f i t s a n d risks o f t h e Human
G e n o m e Project.
 71
SCENARIO DEVELOPMENT PROCEDURE

1. PROBLEM I D E N T I F I C A T I O N

a) C o l l e c t i n g technical data.
b) C o l l e c t i n g significant human data.
c) Identification o f valué elements.
d) Discuss relations b e t w e e n technical and human valúes.

2. DEVELOP A L T E R N A T I V E SCENARIOS FOR A C T I O N

a) Establish reasonable possibilities f o r each scenario.

b) Identify ethical principáis in each scenario.
c) D e t e r m i n e ethical costs and risks in each scenario.
d) Discuss ethical and technical cost-benefit assessments.

3. PRESENT A SET O F A L T E R N A T I V E S C E N A R I O S

a) Discuss uncertainty in each scenario prognosis.

b) Present technical cost-benefit-risk assessments.
c) Present ethical cost-benefit-risk assessments.
d) Discuss differences in benefit-cost-risk balances.

4. F O R M U L A T E A J U S T I F I C A T I O N FOR Y O U R S E L E C T I O N

a) Specify y o u r reasons f o r t h e selected c o u r s e o f action.

b) Clearly present t h e ethical basis f o r y o u r action.
c) U n d e r s t a n d ethical s h o r t c o m i n g s o f y o u r justification.
d) Anticípate and discuss objections t o y o u r selection.
 73

REFERENCES

B u n d e s a e r z t e k a m m e r ( 1 9 8 8 ) . Stellungnahme des V o r s t a n d e s zu
'Praediktive Medizin: Analyse des menschlichen Genoms', Deutsches
Aerzíeb/ott, 85 (Heft 50, 15. Dez. 1988), p. 3595.

B u n d e s r e g i e r u n g ( 1 9 9 0 ) . Abschlu bericht der Bund-Laender A r b e i t -

sgruppe 'Genomanalyse', (Mai 1990) manuscript.

B u n d e s t a g ( 1 9 8 7 ) . Bericht der Enqute Kommission 'Changen und Risi-

ken der Gentechnologie', Deutscher Bundesíog Drucksache 10/6775.

B u n d e s t a g ( 1 9 8 9 ) . Stenographischer Bericht, 122. Sitzung, 26. Jan.

1989, Plenarprotokoll 11/122, 8937-8943.

B u e l o w , E . ( 1 9 9 0 ) . Die Arbeitsgruppe 'Genomanalyse', Genomona/yse

und Gentherapie, ed. H.M. Sass, Springer, Heidelberg, pp. 125-151.

D ¡ e G r u e n e n ( 1 9 8 6 ) . Public Statement on Gene Technology and on the

human Applications of reproductive and genetic Engineering, A d o p t e d
by the 8th. National Assembly, Febr. 15/16, 1986, manuscript.

E u r o p e a n C o m m u n í t y , C o m m i s s í o n ( 1 9 8 8 ) . Proposal f o r a C o u n -
cil Decisión adopting a specific research Programme in t h e field of
health: Predictive Medicine: Human Genome Analysis (1989-1991),
Com (88) 4 2 4 f/naZ-S/N / 4 6 (July 20, 1988).

G e s e l i s c h a f t f u e r H u m a n m e d i z i n ( 1 9 8 9 ) . Analyse des menschli-

chen Genoms, Stellungnahme der Geselischaft fuer Humangenetik,
Sept. 29, 1989, manuscript.

S a s s , H . M. ( 1 9 8 7 ) . Philosophical and Moral Aspects of Risk and Mani-

pulation, Swiss Biotech, 5, (2a), pp. 50-56.

S a s s , H . M. ( 1 9 8 8 ) . T h e G e r m á n Enquete C o m m i s s i o n R e p o r t on
Gene Technology, 6;oeíh;'cs, 2, pp. 264-275.

S a s s , H . M., e d . ( 1 9 9 0 a ) . Genomono/yse und Gentherop/e, Ethische

Herausforderungen in der Humanmedizin, Springer, Heidelberg.

S a s s , H . M., V í e f h u e s H . , e d . ( 1 9 9 0 ) . Vierte Jahrestagung der ESPMH

(Medizinethische Materialien, Heft 59), Z e n t r u m fuer Medizinische
Ethik, Bochum.

S i n g e r , P . ( 1 9 9 0 ) . Bioethics and A c a d e m i c F r e e d o m , 6/oeíh;cs, 4,

pp. 33-44.
 75

A BRITISH A P P R O A C H

Tony Wckers

D i r e c t o r o f t h e H u m a n G e n o m e P r o j e c t in t h e U n i t e d K i n g d o m .
H G M P Resource Centre.
Harrow, Middx (United Kingdom)

ABSTRACT

The author suggests t h a t the meaning o f ethics is

not univocal a n d that by shielding themselves behind
it, m a n y could deprive m a n k i n d o f the i m p o r t a n t
benefíts the H u m a n Genome Project could contribute,
a project which on the other hand poses no more
risks than any other h u m a n activity. The efficiency o f
the project should be judged on the strength o f the
resulting equilibrium b e t w e e n benefíts a n d d r a w -
backs it may offer. The author moreover insists on
the planning o f the control o f its possible dangers
a n d this could be comed out a t three leverls: profes-
sional ethics, legisiative c o n t r o l a n d by means o f
international agreements.
The H u m a n Genome Project in the United Kingdom
is o modest one a n d importance is currently given to
the work o f coordination a n d facilitating research, as
likewise to p o t e n t i a t i n g existing capacities a n d
encouraging interest in British industry. It is o/so
considered that any discoveries made should be pub-
lic property.
A view from the 77
United Kingdom

It is w o r r y i n g t h a t t h e w o r d " e t h i c s " has n o single o r s i m p l e m e a n -

i n g . T h e r e w a s an a r t i c l e in A p r i l ' s S c i e n t i f i c E u r o p e a n about
" E t h i c s a n d b i o t e c h n o l o g y " ; I c o u l d see n o t h i n g in it t h a t I i m m e d i -
a t e l y u n d e r s t o o d t o b e i n h e r e n t l y an e t h i c a l issue.

I have u s e d t h a t p a r t i c u l a r e x a m p l e t o t r y t o f o c u s m y o w n c o n -
c e r n s a b o u t t h e p r e s e n t d e b a t e . T h e r e is n o w a m a j o r e t h i c s i n -
d u s t r y . L a r g e s u m s a r e s p e n t o n e t h i c a l d e b a t e . It is s e l f - e v i d e n t
t h a t an e t h i c a l f o r u m such as t h i s ¡s a challenge t o i d e n t i f y p r o b -
l e m s . A c l o u d is c r e a t e d b e h i n d w h i c h t h o s e w h o - f o r w h a t e v e r
r e a s o n - w i s h t o o p p o s e i n v e s t m e n t in g e n o m e analysis can h i d e
m o t i v e s o t h e r t h a n e t h i c a l c o n c e r n s . If any lesson d e r i v e d f r o m
t h e g e n e t i c m a n i p u l a t i o n d e b a t e o f t h e m i d - 7 0 s can b e a p p l i e d
h e r e , i t m a y b e t h a t t h e real issue is c o m p l i c a t e d b y t h e h i d d e n
agendas o f t h e p r o t a g o n i s t s . T h e v e r y w o r d " e t h i c s " is itself p o -
t e n t : if I o p p o s e y o u o n t h e g r o u n d s t h a t y o u r ideas o r a c t i o n s
a r e u n e t h i c a l , I a m c l a i m i n g t h e m o r a l high g r o u n d in a w a y t h a t is
o n l y a l i t t l e m o r e s o p h i s t i c a t e d t h a n saying y o u a r e " w i c k e d " .

I b e l i e v e t h a t s t u d i e s o f h u m a n g e n e t i c s have a g r e a t p o s i t i v e p o -
t e n t i a l t h a t c o u l d be u n n e c e s s a r i l y f r u s t r a t e d if t o o m u c h e t h i c a l
s o n g a n d d a n c e is m a d e i r r e s p o n s i b l y . A s in m o s t h u m a n a c t i v -
ities, t h e r e is n o d o u b t a b o u t t h e h a r m f u l p o t e n t i a l in k n o w l e d g e
o f g e n e t i c s . If t h a t l a t t e r p o t e n t i a l c o u l d n o t b e c o n t r o l l e d , t h e n
w e have a p r o b l e m , b u t I r e m a i n u n c o n v i n c e d t h a t t h a t is t h e case.

T h e m o s t p r e s s i n g e t h i c a l q u e s t i o n is w h e t h e r i t can be r i g h t t o
d e n y access t o p o t e n t i a l l y available a n d a f f o r d a b l e k n o w l e d g e . By
" a f f o r d a b l e " I m e a n t h a t t h e n e c e s s a r y m o n e y is t h e r e a n d t h e r e
is n o b e t t e r w a y t o s p e n d it. B u t t h o s e a r e n o t e t h i c a l c o n s i d e r a -
t i o n s . It s e e m s a s h o r t s t e p f r o m t h e refusal o f access t o t h i s n e w
k n o w l e d g e , because i t m i g h t b e m i s u s e d ( h o w e v e r t h a t is d e f i n e d
o r j u d g e d ) , t o r e s t r i c t i o n o f access t o e x i s t i n g k n o w l e d g e : t o b u r n -
ing b o o k s a n d t o c e n s o r s h i p .

T h e effectiveness of t h e U K H u m a n G e n o m e Project will be

j u d g e d o n t h e scale a n d t h e balance o f b e n e f i t s a n d d i s b e n e f i t s
t h a t stem f r o m t h e application of t h e knowledge t h a t accrues.
T h e P r o j e c t i t s e l f has n o i n h e r e n t d i s b e n e f i t s . T h e r e m u s t be n o
confusión w i t h the debate 15 y e a r s ago a b o u t w h e t h e r g e n e t i c
manipulation, as a l a b o r a t o r y practice, m i g h t be i n h e r e n t l y hazardous.
T h e o n l y r o l e o f t h e d e b a t e n o w is t o d e f i n e w h a t disbenefits
might result f r o m t h e application o r misapplication o f t h e k n o w -
ledge a n d , s o f a r as is p r a c t i c a b l e , t o be p r e p a r e d t o s e t u p safe-
guards t o elimínate unnecessary disbenefits and t o limit u n a v o i d -
able o n e s - i f t h e r e a r e s u c h - t o s o m e a c c e p t a b l e level. If t h e r e
are m a j o r p o t e n t i a l s f o r g o o d , t h e n t h e emphasis m u s t be o n
78 planning f o r c o n t r o l , t o r e s t r i c t questionable o u t c o m e s , n o t o n
w h e t h e r t h e w o r k s h o u l d g o ahead a t all.

T h e r e a r e t w o o b v i o u s levéis o f c o n t r o l . I a c c e p t t h a t t h e e x l s t -
Ing p o w e r o f m e d i c a l g e n e t l c s raises q u e s t i o n s o f professional
e t h i c s - t h e r e l a t i o n s h l p b e t w e e n d o c t o r a n d p a t i e n t - t h a t have
n o t b e e n r e s o l v e d . I see n o t h i n g in t h i s p r o b l e m t h a t is q u a l i t a -
tively n e w o r insoluble.

T h e r e is a s e c o n d level - a s i l l u s t r a t e d by t h e reléase o f g e n e t i c -
ally-engineered m i c r o - o r g a n i s m s - w h e r e t h e r e are strong finan-
cial i n c e n t i v e s t o c o u r s e s o f a c t i o n t h a t a r e socially u n d e s i r a b l e .
Legislative c o n t r o l is t h e o n l y p o s s i b l e s o l u t i o n .

T h e r e m a y b e a t h i r d level o f c o n t r o l by m e a n s o f I n t e r n a t i o n a l
c o n v e n t i o n s , o f t h e s o r t a p p r o p r i a t e f o r biological o r chemical o r
n u c l e a r w a r f a r e , if i t is t h o u g h t t h a t states m a y m i s u s e t h e k n o w -
ledge.

T h e p l a n n i n g o f t h e U K P r o j e c t has h a d t o t a k e a c c o u n t o f t h e
r e l a t i v e l y m o d e s t scale o f s u p p o r t a n d o f t h e p o s s i b i l i t y o f a m a -
j o r US p r o g r a m m e . T h e fact t h a t o t I I million was explicitly
e a r m a r k e d by t h e G o v e r n m e n t f o r this particular Project implies
t h e i m p o r t a n c e (in t e r m s o f i n t e r n a l scientific p o l i t í c s ) o f d e v e l -
o p i n g , w i t h i n t h e t h r e e - y e a r initial t i m e span, a significant U K p o s i -
t i o n . T h e k e y t o t h e U K p r o g r a m m e is t h e s e l e c t i v e e x p a n s i ó n o f
e x i s t i n g s t r e n g t h s c o u p l e d w i t h an e f f o r t t o c o o r d í n a t e a n d facilí-
t a t e all s u c h w o r k . It is s e l f - e v i d e n t t h a t t h e p r e s e n t f o r m o f o p -
e r a t i o n in U K m o l e c u l a r an clinical g e n e t i c s is i n e f f i c i e n t , in t h a t a
n u m b e r o f r e l a t i v e l y small t e a m s a r e l o o k i n g f o r a f e w genes o r
n e e d l e s - t h e o n e s t h a t i n t e r e s t t h e m - in a g e n e t i c haystack. A
m a j o r s t r a t e g i c t h r u s t in t h e U K P r o j e c t is a s y s t e m a t i c n e e d l e -
p i c k i n g e x e r c i s e , t o save t i m e a n d e f f o r t a n d give w o r k e r s a chance
t o g e t m o r e d i r e c t l y i n t o clinical a n d b i o l o g i c a l analysis. A n o t h e r
a n a l o g y w o u l d b e w i t h t h e s o r t o f i n d e x i n g s y s t e m t h a t gives y o u
s o m e i d e a w h a t a p a r t i c u l a r b o o k is a b o u t - a n d w h e r e i t is o n
t h e s h e l v e s - It is still u p t o y o u t o f i n d o u t w h e t h e r t h e c o n t e n t s
are really w h a t y o u w a n t , and d o s o m e t h i n g w i t h t h e m .

h i e r e is w h a t I a c c e p t t o be a m a j o r e t h i c a l c o n s i d e r a r o n : t h a t i t
w o u l d be m o r a l l y w r o n g f o r t h e data deriving f r o m g e n o m e m a p -
p i n g p r o j e c t s n o t t o b e in t h e p u b l i c d o m a i n . T h a t is c e r t a i n l y
strogly believed by t h e U K scientific c o m m u n i t y . O u r datábase
w i l l b e a p r í v a t e o n e , in t h a t i t w i l l h o l d o n l y t h e o u t c o m e o f o u r
(and any c o l l a b o r a t o r s ' ) p r o g r a m m e : a listing o f t h e p a r t i a l l y c h a r -
a c t e r í z e d f r a g m e n t s o f genes w e have p u l i e d o u t o f t h e haystack.
B u t i t w i l l b e p u b l i c t o o . W o r k e r s w i l l b e able t o have t h o s e f r a g
m e n t s as t o o l s t o m a p t h e g e n o m e ; t h a t in t u r n w i l l f u r t h e r c h a r -
a c t e r í z e t h e f r a g m e n t s , a n d t h o s e w h o s e o b j e c t í v e is genes r a t h e r
t h a n m a p - d r a w i n g w i l l b e a b l e t o have b o t h any n e e d l e t h a t l o o k s
interesting and t h e means t o build up a p i c t u r e o f t h e c o m p l e t e
gene. O n e e x p l i c i t c o n d i t i o n will be t h a t t h e r e s u l t i n g data 79
t h e m s e l v e s g o i n t o o n e o f t h e p u b l i c databases.

W e are enjoined t o further the interests of U K industry: the

m a i n c o m m e r c i a l b e n e f l t s w i l l p r e s u m a b l y c o m e e l t h e r f r o m diag-
n o s t i c s o r , a t l o n g e r - r a n g e , f r o m r a t l o n a l d r u g d e s l g n . I see n o
p r o b l e m In i n d u s t r y t a k i n g a w a y d a t a o r m a t e r i a l s f r o m o u r c o l -
l e c t i o n . T h e c o n d i t i o n , in any case, w i l l be t h a t t h e U K Project
r e t a i n s o w n e r s h i p o f t h e o r i g i n a l n e e d l e s a n d , e v e n if o n i y as a
f o r m a l i t y , a say a n d a s t a k e in s u b s e q u e n t c o m m e r c i a l e x p l o i t a -
t i o n a n d t h a t I n f o r m a t i o n c o m e s back.

It is d i f f i c u l t t o assess t h e e x i s t i n g level o f s u p p o r t in t h e U K f o r
t h e t o t a l i t y o f w o r k t h a t m i g h t be h e l p e d b y t h e U K P r o j e c t ; i t
can h a r d l y b e less p e r y e a r t h a n 3 t i m e s t h e annual a m o u n t b e i n g
c o m m i t t e d t o t h e P r o j e c t . W h a t w e have t o i n c r e a s i n g e f f i c i e n c y
a n d e f f e c t i v e n e s s , t h e p r o j e c t m o n e y has y i e l d e d an i n c r e m e n t in
p e r f o r m a n c e g r e a t e r than was likely t o have been achieved
simply by spending t h e extra o n " m o r e o f t h e same".

W h e t h e r t h i s w i l l w o r k r e m a i n s t o b e s e e n . If i t d o e s , t h e n t h e
positive consequences might be i m p r o v e d understanding o f t h e
m e c h a n i s m o f disease, n o t j u s t t h o s e r e s u l t i n g f r o m single-gen
defects, b e t t e r diagnosis and t h e r a p y , and m o r e precisely-tar-
g e t e d p r e v e n t i v e m e d i c i n e . Each o f t h o s e h o p e s g e n e r a t e s s o m e
a m b i v a l e n c e . T h i s i n h e r e n t c o m p l e x i t y o f t h e issues m a y b e a fac-
t o r in d a m p i n g d o w n i n t e r e s t . T h e r e is n o c l e a r r a l l y i n g p o i n t f o r ,
say, t h e a n t i - a b o r t i o n l o b b y : b e t t e r diagnosis o f g e n e t i c defects
m i g h t r e d u c e t h e d e m a d f o r a b o r t i o n s o r m i g h t increase it.

T h e m o d e s t scale o f t h e U K v e n t u r e a n d t h e s t y l e o f d e c i s i o n -
m a k i n g a r e t w o o t h e r p o s s i b l e r e a s o n s w h y t h e level o f p u b l i c i n -
t e r e s t is l o w : c o n c e r n s , in s o f a r as t h e y s u r f a c e a t all, e i t h e r d o
s o in t h e c o n t e x t o f t h e US p r o g r a m m e o r a l r e a d y e x i s t , in t e r m s
o f w o r r i e s a b o u t o n - g o i n g g e n e t i c r e s e a r c h a n d clinical p r a t i c e .
T h e p e r c e p t i o n , r i g h t l y , is t h a t w h a t w e a r e p u t t i n g i n t o e f f e c t is
a plan t o d o m o r e o f w h a t is a l r e a d y g o i n g o n , m o r e e f f i c i e n t l y ,
e c o n o m i c a l l y a n d e f f e c t i v e l y . So n o n e w p r o b l e m s a r i s e .

It w o u l d b e r e g r e t t a b l e if i n h i b i t i o n s in o n e c o u n t r y w h e t h e r t h e y
arise f r o m p a r t i c u l a r e t h i c a l sensitivities o r f r o m a l a r m a t t h e scale
o f w h a t is p r o p o s e d - s p i l l e d o v e r i n t o o t h e r s . T h a t is o n e r e a s o n
w h y t h e misleading i m p r e s s i o n o f a single H u m a n G e n o m e M a p p i n g
P r o j e c t s h o u l d be a v o i d e d . A h e a d l i n e in t h e " N e w Scientist"
shouting " W h a t ' s w r o n g w i t h t h e H u m a n G e n o m e P r o j e c t " jars
n o less w h e n i t t u r n s o u t t h a t i t is t h e U S p r o g r a m m e t h a t is
b e i n g c r i t i c i s e d , a n d by an A m e r i c a n : p o l i t i c i a n s r e s p o n d t o h e a d -
lines. It s e e m s b e s t - a s w e l l as a c c u r a t e - t o see t h e c u r r e n t a c t i v -
i t y w o r l d w i d e as r e p r e s e n t i n g a w h o l e s e r i e s o f i n d i v i d u a l a n d
independent programmes, within the context of a widespread
perception that Human Genome m a p p i n g is a f i e l d r i p e for
development.
80 S o m e issues o n t h e a g e n d a f o r t h i s m e e t i n g - f o r e x a m p l e t h e i m -
p l i c a t i o n s o f g e n e t i c s c r e e n i n g f o r life a s s u r a n c e o r as a p r e l i m i -
n a r / t o e m p l o y m e n t - s e e m t o be m a t t e r s o f social p o l i c y r a t h e r
t h a n e t h i c s , a n d b e s t d e a l t w i t h in an e v o l u t i o n a r y a n d p r a g m a t i c
w a y . It m a y b e t h a t w h a t I a m a c c e p t i n g in t h a t s t a t e m e n t is t h a t
in p r a c t i c e e t h i c a l c o n s i d e r a t i o n s a r e o n l y m a t e r i a l in l o o k i n g a t
activities t h a t are dispensable o r w h e r e t h e r e are clear alterna-
t i v e w a y s t o a g i v e n e n d : f o r e x a m p l e , r e s e a r c h can be i n h i b i t e d if
i t is p a i n t e d as " u n e t h i c a l " . B u t G o v e r n m e n t s have a w i d e range
o f a c c e p t a b l e f r e e d o m f o r t a k i n g a c t i o n t h a t damages i n d i v i d u á i s .

W h e n a n y s u b s t a n t i a l a d v a n c e in m e d i c a l r e s e a r c h is d e l i v e r e d i n -
t o p r a c t i c e , in t h e c o n t e x t o f i n e v i t a b l y l i m i t e d r e s o u r c e s , d e c i -
s i ó n - p e r h a p s life a n d d e a t h d e c i s i o n s - a r e i m p l i e d t h a t f a v o u r
s o m e persons at o t h e r s ' expense. Individual o r g r o u p ethics are
t h e n d i s p l a c e d b y t o u g h c o r p o r a t e p r a g m a t i s m ; if t h e y w e r e n o t ,
t h e N a t i o n a l H e a l t h S e r v i c e w o u l d cease t o o p é r a t e .

T h e life a s s u r a n c e business, t o t a k e a n o t h e r e x a m p l e o f c o r p o -
r a t e a c t i v i t y , is n o t t h e r e t o a c t as a c h a r i t y a n d t h e r e is n o p r e s -
c h p t i v e h g h t t o life a s s u r a n c e . If t h e a p p l i c a t i o n o f g e n e t i c a d -
vances m e a n s t h a t m o r e p e o p l e t h a n a t p r e s e n t a r e d e e m e d t o
r e p r e s e n t high o r e v e n u n a c c e p t a b l e risks, t h a t raises q u e s t i o n s
s u c h as w h e t h e r t h e m o n e y t h e r e s t save b y a m o r e p r e c i s e d e f i -
n i t i o n o f t h e a c t u a r i a l risks t h e y r e p r e s e n t s h o u l d n o t b e balanc-
e d by s o m e e x t e n s i ó n o f s t a t e u n d e r p i n n i n g .

In t h e U K , s o m e , a t least, o f t h e e t h i c a l c o n c e r n s I i n f e r f r o m t h e
p r o g r a m m e of this meeting are already t h e subject of s t a t u t o r y
c o n t r o l ( f o r e x a m p l e , t h e D a t a P r o t e c t i o n A c t , a n d t h e legislation
g o v e r n i n g e m b r y o r e s e a r c h , w h i c h w i l l ban g e r m - l i n e g e n e t h e r -
a p y ) o r o f e t h i c a l g u i d a n c e o f g r e a t e r o r lesser f o r c é , f r o m b o -
dies such as t h e B r i t i s h M e d i c a l A s s o c i a t i o n o r t h e M e d i c a l R e -
s e a r c h C o u n c i l . It m a y b e i n n o c e n t t o say t h a t t h o s e c o n s t r a i n t s
a r e effective, b u t , t o t a k e t h e e x a m p l e o f r e c e n t p r o p o s a l s f o r leg-
i s l a t i o n in t h e U S , t o r e q u i r e w r i t t e n c o n s e n t f r o m an e m p l o y e e
b e f o r e his m e d i c a l h i s t o r y is d i s c l o s e d t o an actual o r potential
e m p l o y e r , m y u n d e r s t a n d i n g is t h a t t h i s is t h e well-established
p r a c t i c e in t h e U K a n d , m o r e o v e r , d i s c l o s u r e is l i m i t e d t o m e d i -
cal p r a c t i t i o n e r s . In t h i s c o n t e x t " e t h i c s " r e a l l y m e a n s an e l e m e n t
o f professional c o n d u c t : h o w , f o r example, medical data relating
t o an i n d i v i d u a l a r e h a n d l e d by his m e d i c a l p r a c t i t i o n e r .

Ethical issues, w i t h i n a f o r u m s u c h as t h i s , can be t r e a t e d in a w a y

t h a t is b o t h t o o s u b t l e a n d o v e r s t r e s s e d . T h i s p r o b l e m has b e e n
c o m p o u n d e d by t h e n a t u r e a n d scale o f t h e US p r o g r a m m e - a t
least as c o m m o n l y p e r c e i v e d .

In aggregate, t h e e x p e n d i t u r e o f m e d i c a l r e s e a r c h c h a r i t i e s in t h e
U K e x c e e d s t h e b u d g e t o f t h e M R C ; t h e y a r e a p o t e n t f o r c é in
d e t e r m i n i n g w h a t t h e r e s e a r c h a g e n d a is. S o m e a r e explicitly
c o n c e r n e d w i t h s i n g l e - g e n e c o n d i t i o n s such as cystic f i b r o s i s a n d
m u s c u l a r d y s t r o p h y ; o t h e r s - f o r e x a m p l e , t h o s e t h a t deal w i t h 8 i
h e a r t disease, diabetes, a r t h r i t i s and r h e u m a t i s m , c á n c e r and
s o m e f o r m s o f p s y c h i a t r i c i i l n e s s - n o w have a m a j o r i n t e r e s t a n d
i n v e s t m e n t in g e n e t i c s . So f a r as I a m a w a r e , n o n e o f t h e charieties
has m a j o r r e s e r v a t i o n s a b o u t s u p p o r t i n g t h e o b j e c t i v e s o f t h e
U K H u m a n G e n o m e M a p p i n g P r o j e c t . T h e g e n e r a l publíc in t h e
U K a r e g e n e r o u s in s u p p o r t i n g t h e w o r k o f t h o s e c h a r i t i e s . Even
m o r e i m p o r t a n t , t h o s e w h o a r e d i r e c t l y a f f e c t e d , as s u f f e r e r s a n d
t h e r e l a t i v e s o f t h o s e a f f e c t e d , a r e g e n e r a l l y s t r o n g in s u p p o r t o f
p u r s u i t o f t h e cause o f diseases. T h e r o b u s t n e s s o f t h e a t t i t u d e s
o f t h o s e m o s t d i r e c t l y a f f e c t e d is s o m e t h i n g t h a t s h o u l d n o t be
o v e r l o o k e d . T h e r e s p o n s e o f a p a t i e n t asked w h e t h e r he w i l l
a g r e e t o ' h i s ' cells b e i n g u s e d f o r r e s e a r c h is s u r p r i s e t h a t such
e t h i c a l d e l i c a t y surfaces in t h e r o u g h a n d t u m b l e o f n o r m a l m e d i -
cal r o u t i n e . I s u p p o s e if I w e r e s e r i o u s l y ill I m i g h t n o t be a w a r e
e n o u g h t o feel d e g r a d e d b y b e i n g t r u n d l e d in m y b e d t h r o u g h t h e
m a i n p u b l i c c o r r i d o r s o f a h o s p i t a l , b u t t h a t is a d i s t r e s s i n g sight I
a m e x p o s e d t o as an o b s e r v e r e v e r y w o r k i n g day. W h e t h e r or
n o t t h o s e p a t i e n t s ' cells o r D N A o r w h a t e v e r g e t i n t o o u r l a b o r -
a t o r y s e e m s an u t t e r l y t r i v i a l issue b y c o m p a r i s o n . W h a t d o " p r i -
v a c y " , " c o n f i d e n t i a l i t y " a n d " i n f o r m e d c o n s e n t " m e a n in t h a t c o n -
text?

T h e r e is all t h e d i f f e r e n c e in t h e w o r l d b e t w e e n , o n t h e one
h a n d , g u i d i n g t h e m e d i c a l p r o f e s s i o n i n t o h a n d l i n g individuáis s e n -
sitively w i t h awareness o f t h e ramifications o f c o m p l e x issues
a n d , o n t h e o t h e r h a n d , t a k i n g b l o c k d e c i s i o n s o n b e h a l f o f all i n -
d i v i d u á i s . T h e q u e s t i o n w h e t h e r m y d o c t o r s h o u l d t e l l m e if I
have c á n c e r o r t h e g e n f o r H u n t i g t o n ' s disease o r w h a t e v e r is
o n e t h a t in t h e last r e s o r t I w a n t t o a n s w e r . I feel s t r o n g l y a b o u t
t h a t , b u t I feel equally s t r o n g l y t h a t o t h e r s have a r i g h t t o d i f f e r e n t
individual views. I d o n o t w i s h e i t h e r t o impose m y o w n p r e f e r -
ences o n o t h e r s o r t o have o t h e r s p r e s c r i b e w h a t is " r i g h t " f o r m e .

If t h e d i s c u s s i o n a t t h e p r e s e n t m e e t i n g e x t e n d s p o s i t i v e l y t o t h e
f o r m u l a t i o n , n o t j u s t o f p r o b l e m s , b u t o f s o l u t i o n s , in a f o r m t h a t
a c t u a l l y m e s h e s w i t h t h e p r o c e s s e s by w h i c h t h e s o l u t i o n s m i g h t
be i m p l e m e n t e d , w e l l a n d g o o d . M y a p p r e h e n s i o n is t h a t t h e d e -
b a t e w i l l a b o r t a t t h e stage w h e r e i t d o e s n o t h i n g b u t raise o b -
jections, and, m o r e o v e r , t h a t t h e same will be t r u e t h e n e x t t i m e
t h e issue is d i s c u s s e d , a n d t h e n e x t t i m e , and... A n d t h e d a n g e r is
t h a t g o v e r n m e n t s w i l l c h o o s e t h e easy o p t i o n , w h i c h is t o s t o p
t h e r e s e a r c h , n o t because t h e n o i s e g e n e r a t e d b y t h e e t h i c a l d e -
bate looks m o r e i m p o r t a n t - i n t e r m s o f electoral c a l c u l a t i o n s -
t h a n b e n e f l t s t h a t m a y be a l o n g w a y in t h e f u t u r e .
 83

SCIENTIFIC AND ETHICAL

ASPECTS OF THE HUMAN
CENOME PROJECT
IN I T A L Y

Paolo Vezzoni *

Istituto di T e c n o l o g i e b i o m e d i c h e Avánzate, C N R (Institute o f

Advanced Bio-medical Technology, C N R )

ABSTRACT

Within the scientific ambit o f the H u m a n Genome

Project, Italy thought it preferable to potentiate ex-
isting centres and research teams. M oreo ver, it was
dedded to concéntrate work on one specific genomic
región: t h e t e r m i n a l p o r t i o n o f t h e ¡ong a r m of
chromosome X , called X q 2 4 - q t e r . Tunnel-effect
microscope techniques are o/so being developed.
As for the ethical aspects o f the project, an agree-
ment has been reached in Italy, by which genother-
apy o f somatic cells is permitted, but not that o f ger-
minal cells. A n d as for the danger o f any possible
discrimination o f bearers o f abnormal features, it is
thought t h a t this could be regulated by laws a n d
professional ethical codes.

* Paper w r i t t e n in c o l l a b o r a t i o n w i t h
Elena R e d o l f i , A n n a l i s a F r a t t i n i and
Monica R e p e t t o .
I w o u l d llke t o t h a n k t h e organisers f o r giving m e t h e o p p o r t u - 85
nity t o speak a b o u t t h e sclentlfic organizatlon o f t h e Human
G e n o m e p r o j e c t in I t a l y a n d a b o u t t h e e t h i c a l p r o b l e m s that
can be r a i s e d in t h i s á r e a a n d t h e w a y i t has b e e n t a c k l e d in o u r
country.

T h e Italian p r o j e c t s t a r t e d in 1987 a n d i t w a s f u n d e d by t h e m a i n
s c i e n t i f i c a g e n c y in Italy, w h i c h is t h e C o n s i g l i o N a z i o n a l e della
Ricerche (National Research C o u n c i l , C N R ) . T h e N o b e l Prize
R e n a t o D u l b e c c o , an Italian s c i e n t i s t w h i c h is n o w P r e s i d e n t o f
t h e Salk I n s t i t u t e , w a s a s k e d t o a c t as c o o r d i n a t o r t o provide
scientific advice and t o ensure t h e internationality o f project,
since w e f e l t f r o m t h e b e g i n n i n g t h a t t h i s p r o j e c t s h o u l d be c a r -
r i e d o u t o n l y in a I n t e r n a t i o n a l c o n t e x t .

F o r t h e f i r s t t h r e e y e a r s w e have a l l o c a t e d a b o u t 1.7 million

d o l l a r s f o r e a c h y e a r in a p r o g r a m t h a t w a s e v a l u a t e d y e a r b y
y e a r . N o w t h i s p r o j e c t has b e e n i n s e r t e d in a w i d e r p r o j e c t o n
m o l e c u l a r b i o l o g y t h a t lasts f r o m 1991 t o 1 9 9 5 , a n d in t h i s w a y
t h e s u r v i v a l o f t h e p r o j e c t has b e e n a s s u r e d f o r a t last 5 y e a r s
w i t h t h e s a m e a m o u n t o f a b o u t 2 m i l l i o n d o l l a r s . If i t is t a k e n
i n t o a c c o u n t t h a t t h e s e figures d o n o t i n c l u d e salaries f o r ¡n-
v e s t i g a t o r s , i t is p o s s i b l e t o s e e t h a t , e v e n if t h e y c a n n o t be
c o m p a r e d t o t h e a m o u n t o f m o n e y t h a t is s p e n t in t h e United
S t a t e s , t h e y a r e in t h e s a m e o r d e r o f m a g n i t u d e as o t h e r E u r o -
pean initiatives.

It w a s d e c i d e d t h a t t h e p r o j e c t w o u l d f o c u s o n a single specific
r e g i ó n , t h a t is t h e t e r m i n a l p o r t i o n o f t h e l o n g a r m o f t h e X c h r o -
m o s o m e , and instead of building a new centre f o r genome
studies, w e t r i e d t o p o t e n t i a t e e x i s t i n g units already w o r k i n g o n t h e
g e n e t i c s o f t h i s c h r o m o s o m e o r plannig t o w o r k o n t e c h n o l o g i c a l
d e v e l o p m e n t s o n m a p p i n g a n d s e q u e n c i n g , since i t w a s f e l t t h a t
t e c h n o l o g i c a l advances w e r e a b s o l u t e l y n e e d e d t o c a r r y o n t h i s
project.

T a b l e I s u m m a r i z e s s o m e o f t h e r e s e a r c h aspects t h a t have b e e n
c a r r i e d o u t u n d e r t h e aegis o f t h e p r o j e c t as w e l l as s o m e p u b -
lished r e s u l t s a l r e a d y o b t a i n e d . T h e t a b l e s h o w s also s o m e I n t e r -
n a t i o n a l c o l l a b o r a t i o n s t h a t have b e e n set u p in t h e framework
o f t h e p r o j e c t , since w e s t r o g l y t h i n k t h a t l a r g e r b e n e f l t s t o t h e
scientific p r o g r e s s can c o m e f r o m c o o p e r a t i o n in t h i s á r e a .

In t h i s r e g a r d w e w i l l m e n t i o n h e r e o n l y t h e c o l l a b o r a t i o n b e -
t w e e n i t a l i a n r e s e a r c h e r s a n d t h e W a s h i n g t o n U n i v e r s i t y in St
Louis, t h a t led t o t h e c o n s t r u c t i o n o f a Y A C library f r o m the
cell line X . 3 0 0 0 . 1 I, a h u m a n / h a m s t e r h y b r i d c o n t a i n i n g t h e c h r o -
mosomal región Xq24-qter as t h e o n l y h u m a n component.
U n d e r t h e d i r e c t i o n o f D r . D. Schlessinger a l o t o f w o r k has
b e e n d o n e in m a p p i n g t h i s g e n o m e r e g i ó n w i t h t h i s powerful
n e w t o o l , as w i l l b e d i s c u s s e d in S c h l e s s i n g e r a n d D'Urso
p a p e r s in t h i s s a m e m e e t i n g .
36 Table I: Partial list of activities of the Italian Human
Genome Project and of the international collaboratíons.

Mapping, Y A C v e c t o r s ( 1 , 2 ) D r . D. Schlessinger, St. Louis, M O

Mapping, traditional v e c t o r s (3-6) D r . J. L. Mandel, Strasbourg, France
D r . G. Evans, La Jolla, C A
D r . F. Giannelli, L o n d o n , U K
D r . A . Ballabio, H o u s t o n , T X
In situ hybridization
A u t o m a t i o n (7, 8)
STS map o f t h e Z q 2 4 - q t e r
Scanning tnneling m i c r o s c o p y (9)
C o m p u t e r sequence analysis D r . N . Kolchanov, N o v o s i b i r s k , URSS
Ethical evaluation (10)
References
1) W a d a e t al. Am.J. Hum. Genet., 46:95, 1990
2) Little R. et al. Proc. Nati. Acad. Se/., 86:1598, 1989
3) Ballabio A . et al. Genomics, 8:263, 1990
4) Maestrini C. et al. Genomics, 8:664, 1990
5) Manoni M. e t al. Genomics, 9:553, 199!
6) Rousseau F. et al. Am. J. H u m . Genet, 48:108, 1991
7) D e bellis G. et al. N u d . Ac. Res., 18:4951, 1990
8) C a r m i n e ! P. et al. N u d . Ac. Res., 18:204, 1990
9) C r i c e n t i A . e t al. Science, 245: 1226, 1989
10) Brovedani E. Agg/'ornamení/ sociali, 40:487, 1989

In a d d i t l o n , t h e c o n s t r u c t i o n o f c o n v e n t i o n a l phage a n d c o s m i d l i -
b r a r l e s f r o m t h e s a m e h y b r i d has led t o t h e p r o d u c t i o n o f m a n y
useful c l o n e s t h a t have b e e n u s e d in linkage analysis a n d physical
m a p p i n g . S o m e c l o n e s have b e e n m a p p e d t o c h r o m o s o m a l bands
and are c u r r e n t l y investigated f o r association w i t h genetic dis-
eases. In situ h y b r i d i z a t i o n w i t h n o n r a d i o a c t i v e p r o b e s has b e e n
extensively used t o map Y A C and o t h e r clones.

A n o t h e r p r o g r a m p u r s u e d in t h e f r a m e w o r k o f t h e p r o j e c t is
t h e c o n s t r u c t i o n o f an STS ( S e q u e n c e T a g g e d Sit) m a p o f t h e
X q 2 4 - q t e r . T h e m a i n f e a t u r e o f t h i s a p p r o a c h is t o sequence
s m a l l pieces o f D N A m a p p i n g in t h i s r e g i ó n a n d e s t a b l i s h t h e i r
o r d e r a l o n g t h e c h r o m o s o m e , as p r o p o s e d b y O l s o n a n d c o -
w o r k e r s in 1989. T h e c h o l e e o f s e g m e n t s f o r STS m a p c o u l d b e
c o m p l e t e l y r a n d o m , b u t w e plan t o s e q u e n c e f r a g m e n t s c i ó s e t o
t h e s o c a l l e d C p G islands. In t h i s r e g a r d , Eag I s i t e c o n t a i n i n g
c l o n e s have b e e n o b t a i n e d b y c o n s t r u c t i n g a s p e c i a l i z e d l i b r a r y
and by subcloning c o s m i d s digested w i t h r a r e c u t t e r enzymes,
m a p p e d t o c h r o m o s o m a l b a n d s w i t h a p a n e l o f h y b r i d s a n d se-
q u e n c e d w i t h a u t o m a t e d d e v i c e s . T h e a d v a n t a g e o f t h i s C p G is-
l a n d - b a s e d m a p is t h a t t h e d e r i v i n g STS m a p is, a t least in s o m e
way, gene-associated.

A c o m p l e t e l y n e w a p p r o a c h t o t h e analysis a n d s e q u e n c e o f t h e
g e n o m e is also i n v e s t i g a t e d in t h e p r o j e c t . T h i s p r o g r a m is based
o n a n e w t e c h n o l o g y , t h e scanning t u n n e l i n g m i c r o s c o p y . D i r e c t
v i s u a l i z a t i o n o f t h e d o u b l e h e l i x o f D N A is o b t a i n e d ( ) a n d i t is
n o t i m p o s s i b l e t h a t in f u t u r e s e q u e n c e s c o u l d be o b t a i n e d w i t h
these means. This w o u l d a l l o w t o increase t h e speed o f sequenc- 87
ing t h a t is r e a l l y n e e d e d if w e w a n t t o e x t e n s i v e l y s e q u e n c e t h e 3
billion nucieotides-long human genome.

Ethical p r o b l e m s a s s o c i a t e d w i t h t h i s p r o j e c t have b e e n discussed

f r o m t h e b e g i n n i n g . D e f i n i t i o n o f all t h e g e n e s o f t h e Human
G e n o m e c o u l d p r o v i d e b e t t e r diagnosis a n d p e r h a p s t h e r a p y o f
m a n y g e n e t i c diseases, a n d e v e r y o n e agrees o n t h e p o t e n t i a l b e n -
eflts f o r t h e m a n k i n d t h a t can d e r i v e f r o m t h e H u m a n Genome
P r o j e c t . T h e r e a r e h o w e v e r s e v e r a l aspects o f t h i s r e s e a r c h t h a t
d e s e r v e c a r e f u l e v a l u a t i o n . A m o n g t h e m w e w i l l discuss b r i e f l y
t w o p r o b l e m s : gene t h e r a p y and results disclosure.

A s f a r as g e n e t h e r a p y is c o n c e r n e d , a w i d e a g r e e m e n t has b e e n
r e c e n t l y r e a c h e d o n t h i s m a t t e r by a panel o f e x p e r t s including
s c i e n t i s t s , p o l i t i c i a n s , e t h i c i s t s as w e l l as t h e o l o g i a n s f r o m t h e R o -
m á n C a t h o l i c C h u r c h . T h e panel r e c o g n i z e d t h e l i c e i t y o f s o m a t i c
cell g e n e t h e r a p y since in t h i s case t h e t h e r a p y d o e s n o t d i f f e r in
priciple f r o m o t h e r kinds of therapy, f o r example b o n e marrow
t r a n s p l a n t a t i o n ; g e r m l i n e g e n e t h e r a p y is n o t a l l o w e d f o r t h e
m o m e n t , since t h e p o t e n t i a l b e n e f i t s a r e c o u n t e r b a l a n c e d b y t h e
p o s s i b i l i t y t o h a r m t h e e m b r y o (especially b y i n s e r t i o n a l muta-
genesis t h a t o c c u r f r e q u e n t l y in t r a n s g e n i c m o u s e m o d e l s ) ; in a d d i -
t i o n , t h e r e a r e fears t h a t t h e s e t e c h n i q u e s c o u l d be used f o r
changing t h e H u m a n G e n o m e .

D i s c l o s u r e o f g e n e t i c a l t e s t s f o r e m p l o y m e n t as w e l l as f o r m e d i -
cal a n d life I n s u r a n c e is a n o t h e r p o s s i b i l i t y . C o n t r a r y t o what
h a p p e n s in U n i t e d States, access t o m e d i c a l i n s u r a n c e is n o t a
p r o b l e m in Italy s i n c e h e a l t h c a r e is all g o v e r n m e n t supported
a n d n o b o d y c a n b e e x c l u d e d f r o m h e a l t h c a r e o n t h e basis o f
genetic diagnosis.

Disclosure of results obtained w i t h new genetics techniques

c o u l d b e u s e d t o d i s c r i m í n a t e p e o p l e c a r r y i n g an a b n o r m a l t r a i t
m a n i f e s t i n g i t s e l f o n l y l a t e r in life, as i t h a p p e n s in H u n t i n g t o n ' s
disease, b o t h in e m p l o y m e n t a n d in life i n s u r a n c e , b u t i t is f e l t
t h a t again t h e s e i n f o r m a t i o n s a r e n o t v e r y d i f f e r e n t f r o m other
I n f o r m a t i o n a l r e a d y available w i t h o t h e r c o n v e n t i o n a l m e a n s ( f o r
example, predictive tests f o r predisposition t o diabetes). This
á r e a can b e easily r e g u l a t e d b y law, k e e p i n g in m i n d t h e o í d m e d i -
cal r u l e o f p r o f e s s i o n a l s e c r e t . In a d d i t i o n , i t is n o t i m p o s s i b l e t o
t h i n k t h a t in f u t u r e individual life insurance b e c o m e s a g e n e r a l fea-
t u r e s u p p o r t e d by t h e state.

In c o n c l u s i ó n , t h e H u m a n G e n o m e P r o j e c t in Italy is n o w w e l l es-
t a b l i s h e d , e v e n if n o t in t h e large scale as in U n i t e d States. N o big
Genome Centres have been established, b u t small existing
g r o u p s have b e e n e n c o u r a g e d t o w o r k f o c u s i n g o n a d e f i n i t e p o r -
t i o n o f t h e H u m a n G e n o m e . In s o m e aspects t h e m o n e y a l l o c a t e d
f o r t h e p r o j e c t is n e w m o n e y f o r g e n e t i c s r e s e a r c h community
a n d t h e p r o j e c t w i l l g r e a t l y b e n e f i t b o t h basic a n d a p p l i e d g e n e t i c
r e s e a r c h in Italy.
 89

P O L I C Y IN R E L A T I O N
TO THE HUMAN
CENOME PROJECT.
T H E V I E W FROM T H E USSR

Alexander Bayev

Engelhardt Institute of Molecular Biology, A c a d e m y of

Sciences o f t h e USSR, M o s c o w

ABSTRACT

The ethics developed in the USSR has been impreg-

nated with orthodox M a r x i s m a n d has h a d a strong
political component. A t present, ethics a n d moráis
are guiding Soviet society in a more h u m a n way.
Today, the H u m a n Genome Project is o/so being
developed in the USSR, bes/des being the first in this
field o f human genetics. The scientists in charge o f
the project consider that it will characterize man as
a species a n d not as an individual. Other additional
methods o f analysis are required to this latter end.
Therefore, it would seem that the possible influence
on society o f knowledge o f the human genome, and
o/so on the destiny o f m a n , would be the final stage
o f the project on a far more long-term basis. Yet in
provisión for the f u t u r e Soviet scientists consider
a person's genome to be his or her own exclusive
property, as part o f h u m a n rights.
T h e standards o f ethics and t h e c o d e o f moráis are historical cat- 91
e g o r i e s a n d d e p e n d o n a social e n v i r o n m e n t w h i c h c r e a t e s t h e m
a n d w h e r e t h e y o p é r a t e . R e l i g i o u s We/tonschouung lays c l a l m t o
t h e l r a b s o l u t e I m p o r t a n c e a l t h o u g h , If o n e t a k e s an u n p r e j u d i c e d
attitude, t h e i r historical origin becomes obvious. T h e moral prin-
cipies o f C h r i s t i a n i t y a n d Judaism a r e d i f f e r e n t inspite o f t h e i r
c o m m o n history and succession.

T h e i n t e r p r e t a r o n o f m o r á i s as a h i s t o r i c a l a n d social p h e n o m e -
n o n justifies analysing t h e m o r á i s o f o u r S o v i e t y s o c i e t y in r e l a -
t i o n t o h u m a n g e n o m e s t u d i e s . T h i s is n o t a s i m p l e e n t e r p r i s e ,
b u t o n e c a n t r y t o o v e r e ó m e t h e difficulties a l o n g t h i s r o u t e .

It a p p e a r s t o m e t h a t t h e e t h i c d e v e l o p e d b y o u r p h i l o s o p h e r s
has n o t i g n o r e s its u n i v e r s a l h i s t o r y a n d valúes p r o c u r e d b y t h e
w o r k o f g r e a t i n t e l l e c t s in t h e past. Y e t t h e s p i r i t o f o r t h o d o x
M a r x i s m g o v e r n s this ethic and i t always o b e y e d political o r d e r s ,
w h i c h m a d e i t s o p e c u l i a r a n d a c c o u n t s f o r its d e c l i n e '. T h e p r o -
p o n e n t s o f t h i s e t h i c c l a i m e d t h a t its s t a n d a r d s a n d t h e c o d e o f
moráis w e r e entirely dependent o n historical-social factors and
t h a t e t h i c a l p r i n c i p i e s h a d a class a n d p o l i t i c a l c h a r a c t e r .

M a r x i s m a d v o c a t e s t h a t t h e class c a p i t a l i s t s o c i e t y m u s t e v e n -
t u a l l y b e c o m e a m o r e p e r f e c t classless s o c i e t y a n d t h e class m o r -
áis m u s t g i v e w a y t o a classless e t h i c c o m m o n t o all m a n k i n d .
M a r x h e l d t h a t t h i s w o u l d b e d o n e b y t h e p r o l e t a r i a t , i.e. t h e
w o r k i n g class, b y seizing p o w e r a n d v i a its d i c t a t o r s h i p . T h i s d o g -
m a w a s officially a d o p t e d in t h i s c o u n t r y a f t e r t h e O c t o b e r R e v o -
l u t i o n in 1 9 1 7 w h e n t h e f i r s t s t a t e o f w o r k e r s a n d peasants w a s
declared. Later o n , after W W I I , this definition was extended ( b u t
again n o t a l w a y s ) t o " t h e p e o p l e ' s i n t e l l i g e n t s i a " ( t h a t is n o t t h e
w h o l e i n t e l l i g e n t s i a , b u t a p a r t o f i t , w h i c h has n e v e r b e e n d e f i n e d
p r e c i s e l y : w h a t d o e s " p e o p l e s " m e a n in t h i s c o n t e s t ? ) . N o w , in
t h e e r a o f perestroika, t h e official p h r a s e o l o g y has i n v e n t e d a n e w
t e r m , "a man of labour".

A l l w h a t I have said a b o v e is d i r e c t l y a s s o c i a t e d w i t h t h e p r o b -
l e m s o f m o r á i s since t h e S o v i e t s o c i e t y w a s a r t i f i c i a l l y s e g r e g a t e d
i n t o ( I ) w o r k e r s a n d peasants w h o w e r e c l a i m e d t o e n j o y f u l !
r i g h t s a n d t h e b e n e f i t s o f t h i s m o r a l c o d e , a n d ( 2 ) all t h e o t h e r s
w h o w e r e d e p r i v e d o r social r i g h t s .

For a long t i m e t h e ethics o f o u r society was o u v e r t l y utilitarian.

N o t t h a t t h e c o n c e p t s o f g o o d a n d evil, k i n d n e s s a n d h a r m , c o n -
science a n d h o n o u r d i d n o t e x i s t , b u t t h e y w e r e r u l e d b y p o l i t i c a l
o r d e r s and t h e only c r i t e r i o n f o r t h e m was t o benefit t h e revolu-
tion and t h e dictatorship o f t h e proletariat.

T h e actual reality w a s even m o r e biased. T h e state o f w o r k e r s

a n d peasants w a s n o t h i n g else b u t a p r o p a g a n d i s t slogan because
t h e w o r k e r s w e r e e x p l o i t e d in t h i s s o c i e t y w h e r e a s t h e peasants
w e r e n o t o n l y e x p l o i t e d b u t e v e n d e s t r o y e d ( c o l l e c t i v i s a t i o n ) . In
92 fact, t h e Soviet s o c i e t y w a s t y r a n n i s e d by a small oligarchical
g r o u p o f p a r t y leaders h e a d e d b y Stalin, a n d t h e s t a t e m o r á i s s e r v -
ed t h e interests o f this g r o u p w h o dictated t h e i r ideology and t h e
standards o f behaviour.

T h e s i t u a t i o n in t h e c o r r i d o r s o f s c i e n c e w a s c o m p l i c a t e d b y
t h e d i c t a t o r s h i p o f political leaders a n d , p a r t l c u l a r l y in t h e fieid
o f g e n e t i c s , b y t h e d o m i n i ó n o f L y s e n k o a n d his a g r o b i o l o g i c a l
ideas 2...

N o w t h e s i t u a t i o n has c h a n g e d d r a s t i c a l l y . A l t h o u g h t h e o l i g a r c h y
is t r y i n g h a r d t o t h r u s t b e n e f i c i a l t o its e t h i c a l s t a n d a r d s o n o u r
s o c i e t y , t h i s d o e s n o t w o r k . T h e s o c i e t y lives n o w b y t h e c o d e o f
m o r á i s a d v o c a t e d b y Russian i n t e l l e c t u a l s in t h e past a n d in t h e
p r e s e n t as w e l l as a c c o r d i n g t o t h e t r a d i t i o n s o f Russian h i s t o r y .

T h e u n i v e r s a l p r i n c i p i e s o f e t h i c s a n d m o r á i s again g u i d e o u r s o -
c i e t y n o w . It is in t h e i r t e r m s t h a t t h e p r o b l e m o f H u m a n C e -
n ó m e s t u d i e s is c o n s i d e r e d n o w . Radical p o l i t i c a l a n d e c o n o m i c a l
reforms in o u r c o u n t r y (perestroika) have m o d i f i e d t h e
Weltanschauung a n d , in p a r t i c u l a r , t h e e t h i c s t a n d a r d s . T h i s is n o t
a D r . Jekyll a n d M r . H y d e p h e n o m e n o n , b u t a p r o f o u n d a l t e r a -
tion of o u r way of thinking forever.

T h e s t a t e p o l i c y a n d social t r e n d s a r e h u m a n e n o w in a pleasant
c o n t r a s t t o t h e past. T h e p r o g r a m m e H u m a n g e n o m e is an i n t e -
g r a l p a r t o f ideas a n d a c t i o n s p r e v a i l i n g n o w d a y s in t h i s c o u n t r y .

T h e USSR h a d n o c o m p r e h e n s i v o p r o g r a m m e o f H u m a n G e -
n o m e i n v e s t i g a r o n t i l l 1 9 8 9 , a n d t h e p r e s e n t p r o j e c t is t h e f i r s t
o n e in t h i s f i e i d 3.

T h e programmes of studying H u m a n G e n o m e are primarily aimed

a t i t s m a p p i n g a n d s e q u e n c i n g . Y e t g e n o m e analysis c a n n o t b e
c o n f i n e d t o t h i s p u r p o s e a l t h o u g h its r e a l i s a t i o n w i l l t h r o w more
light o n g e n o m e a r c h i t e c t u r e and possibly reveal many secrets
b u r i e d by t h e n a t u r e in its w o n d e r f u l c r e a t i o n .

C h e m i c a l s y m b o l s per se a r e d e a d a n d m u s t n e c e s s a r i l y b e c o m -
pared w i t h functions, w i t h dynamic factors which w e understand
as t h e m e a n i n g a n d c o n c e a l e d essence o f life. F u n c t i o n a l d e c o d i n g
o c c u r s n o w , t o o , b u t i t w i l l b e c o m e m o r e c o m p r e h e n s i v o a n d ef-
f e c t i v e as s t r u c t u r a l I n f o r m a t i o n is b e i n g a c c u m u l a t e d . F u n c t i o n a l
d e c o d i n g is a s e c o n d , p r o b a b l y e v e n m o r e i m p o r t a n t a n d d i f f i c u l t ,
p r o b l e m in t h e p r o g r a m m e o f H u m a n C e n ó m e studies. W e
s h o u l d l e a r n h o w t o r e a d s t r u c t u r a l t e x t s o f H u m a n C e n ó m e in
t e r m s o f f u n c t i o n s . L e . pass f r o m t h e s y n t a x o f t h e g e n o m e t o its
semantics. O n l y in t h a t case o u r k n o w l e d g e a b o u t H u m a n C e n ó m e
w i l l b e u s e f u l a n d c a p a b l e o f i n f l u e n c i n g t h e social a n d m o r a l -
e t h i c a l aspects o f h u m a n e x i s t e n c e . H o w e v e r t h e c o m p r e h e n s i o n
o f H u m a n G e n o m e m u s t pass t h r o u g h y e t a n o t h e r stage b e f o r e
i t b e c o m e s capable o f i n f l u e n c i n g t h e s o c i e t y a n d its i n d i v i d u á i s .
W h a t shall w e g e t as a r e s u l t o f s e q u e n c i n g H u m a n G e n o m e a t 93
t h e f i r s t step? T h e s e q u e n c e o f c h e m i c a l s y m b o l s ( i t d o e s n o m a t -
t e r w i t h i n t h i s c o n t e x t w h e t h e r t h e y a r e d e c o d e d o r n o t ) can b e
c o n s i d e r e d m e r e l y as a m o d e l o f H u m a n G e n o m e b e l o n g i n g t o
n o n e o f h u m a n i n d i v i d u á i s in t h e past, p r e s e n t a n d f u t u r e . T h i s
depends o n t h e m e t h o d o f sequencing d e v e l o p e d by t h e universal
a s s o c i a t i o n o f r e s e a r c h e r s . T h e m a t e r i a l f o r analysis is o b t a i n e d
n o t f r o m a particular individual, b u t f r o m quite different sources,
a n d t h e analysis is d o n e b y v a r i o u s s c i e n t i s t s s o t h a t a n a l y t i c a l
e r r o r a r e u n a v o i d a b l e . T h a t is w h y a s e q u e n c e o b t a i n e d after
10-15 y e a r s o f c o m m o n t i r e l e s s e f f o r t s m a y b e c o n s i d e r e d o n l y
as a m o d e l o f H u m a n G e n o m e as a species, a n d i t w i l l b e used as
a s t a n d a r in t h e f u t u r e .

T h i s s i t u a t i o n can b e i l l u s t r a t e d b y t h e f o l l o w i n g s c h e m e :

civills / V Homo
Homo

individualis

T h e m o d e l o f H u m a n G e n o m e c r e a t e d as a r e s u l t o f t h e p r o -
g r a m m e w i l l c h a r a c t e r i s e t h e m a n as a species ( H o m o sap/ens).
T h e c h a r a c t e r i s a t i o n o f an i n d i v i d u a l ( H o m o individualis) r e q u i r e s a
special m e t h o d o r m e t h o d s , s o m e t h i n g like f i n g e r p r i n t i n g , t o d e -
s c r i b e t h e m o s t i m p o r t a n t f e a t u r e s o f an i n d i v i d u a l g e n o m e . T h e
individual d i f f e r e n c e s o f H u m a n G e n o m e a r e r a t h e r small in t e r m s
o f its c o m p o s i t i o n : 0.1 % o r ca. 3 x 10 6 b p f o r t w o u n r e l a t e d i n -
dividuáis. H o w e v e r these differences are intensified by g r e a t e r
sequence m o d i f i c a t i o n caused by r e a r r a n g e m e n t s , inserís, dele-
tions, etc. Then t h e comprehension o f Human G e n o m e enriched
w i t h f u n c t i o n a l ideas w i l l m a k e i t p o s s i b l e t o c h a r a c t e r i s e real h u -
m a n beings, w i t h all t h e i r i n d i v i d u a l b i o l o g i c a l p r o p e r t i e s under
t h e c o n d i t i o n s o f t h e i r social e n v i r o n m e n t ( H o m o c/V;7;s).

O n l y a t t h e last s t e p , scientific ¡deas a b o u t H u m a n G e n o m e w i l l

be a b l e t o i n f l u e n c e its social s t a t u s a n d p e r s o n a l d e s t i n y . A n d
h e r e w e shall face a g r e a t n u m b e r o f s i t u a t i o n s .

L e t us f i r s t c o n s i d e r p o s s i b l e effects o n t h e s o c i e t y as s u c h . W e
s h o u l d h a r d l y use h e r e t h e a b s t r a c t c o n c e p t s o f g o o d a n d evil: i t
w o u l d b e easier t o s t a n d o n t h e g r o u n d o f u t i l i t a r i a n i s m a n d e m -
ploy t h e c r i t e r i o n o f public well-being and benefit.

O n c e o f t h e p o s s i b l e c o n s e q u e n c e s in d e c o d i n g H u m a n G e n o m e
m a y b e c o n c e r n e d w i t h a n o t h e r o u t b u r s t o f e u g e n i c ideas, p r e -
s u m a b l y s i m i l a r t o t h o s e p u t f o r w a r d in t h e past. T h e r e is n o
d o u b t t h a t t h e advocates o f eugenics will t r y t o t a k e n u c l e o t i d e
s e q u e n c e s as o b j e c t i v e c r i t e r i a f o r c l a i m i n g s o m e individuáis.
94 g r o u p s a n d races e i t h e r s u p e r i o r o r i n f e r i o r . T h e appeal by G e r -
m á n nazi f o r r a c e h y g i e n e because o f t h e N o r d i c r a c e s u p e r i o r i t y
w e r e m o s t l y based o n m y s t i c c o n c e p t s . T h e a d h e r e n t s o f eugenics
h e l d t h a t g e n e t i c f a c t o r s e x e r t e d an a b s o l u t e e f f e c t o n mental
d e v e l o p m e n t , m o r a l status, criminality and d r u g a d d i c t i o n .

T h e possession o f a m o d e l (standard) g e n o m e , t h e possibility t o

c h a r a c t e r i s e an i n d i v i d u a l g e n o m e a n d t o i n t e r p r e t i t in f u n c t i o n a l
t e r m s w i l l , n o d o u b t , t e m p t s o m e p e r s o n s t o use t h i s I n f o r m a -
t i o n f o r e u g e n i c d e d u c t i o n s . T h a t is w h y w e m a y e x p e c t a n e w
o u t b u r s t o f e u g e n i c ideas a n d o í d m i s t a k e s r e p e a t i n g t h e m s e l v e s
n o w d a y s . T h i s is e v e n m o r e p o s s i b l e n o w because h u m a n sur-
vival b e c o m e s a real p r o b l e m a n d e u g e n i c s can b e u s e d in t h e
struggle f o r existence r a t h e r than f o r ideological purposes.

H e r e d i t a r y diseases a r e a n o t h e r p r o b l e m a s s o c i a t e d w i t h H u m a n
G e n o m e s t u d i e s a n d i n v o l v i n g t h e s o c i e t y as a w h o l e . Genome
m a p p i n g a n d s e q u e n c i n g can b r i n g a b o u t radica! changes in t h i s
field o f h u m a n p a t h o l o g y . H e r e d i t a r y diseases s o m e t i m e e n g e n -
d e r h u m a n beings w h o lack t h e m o s t i m p o r t a n t p r o p e r t i e s o f t h i s
biological species, namely, t h e intellect, t h e capability t o work
a n d t o e n j o y life. S u p p o r t i n g t h e i r e x i s t e n c e o n m e r c i f u l g r o u n d s
is a h e a v y financial b u r d e n f o r t h e s o c i e t y . T h e b i r t h o f s u c h a
baby is a an i n f i n i t e m i s e r y f o r t h e f a m i l y .

H e r e d i t a r y disease

Society: Family:
financial b u r d e n misery

Y e t e v e n less s e r i o u s m a n i f e s t a t i o n s o f h e r e d i t a r y p a t h o l o g y o f -
t e n a r e h a r d t o c u r e , m a k e t h e p a t i e n t physically d i s a b l e d a n d , a t
t h e late stages o f p a t h o l o g y , c r é a t e t h e f e e l i n g o f d o o m . W e may
hope t h a t t h e p r o g r a m m e o f H u m a n G e n o m e studies will a l l o w
us t o c o m p r e h e n d t h e p a t h o g e n e s i s o f h e r e d i t a r y diseases, t o i m -
p r o v e t h e i r diagnostics, t o p r e v e n t and t o cure t h e m , thus mak-
ing a social c o n t r i b u t i o n t o social b e n e f i t .

A n y w a y genetic p r o b l e m s b e c o m e m o r e and m o r e acute and i m -

p o r t a n t as t h e e n v i r o n m e n t is d e s t r o y e d a n d p o l l u t e d a t an e v e r
i n c r e a s i n g scale, t h e i n d u s t r y a n d p o p u l a t i o n d e n s i t y rise, a n d t h e
p r o g r a m m e o f H u m a n G e n o m e studies may help t o solve t h e m .

Now I w o u l d l i k e t o say s e v e r a l w o r d s a b o u t h o w t h i s pro-

g r a m m e r e l a t e s t o an i n d i v i d u a l . A s I has n o t e d a b o v e , i t w i l l b e
possible s o o n e r o r l a t e r t o pass f r o m a g e n o m e m o d e l t o individual
g e n o m e s a n d t o c o n s t r u c t an i n d i v i d u a l g e n e t i c p o r t r a i t . W e may
o n l y guess n o w w h a t t h i s p o r t r a i t w i l l be a n d h o w c l o s e l y i t can
describe t h e original. A p p a r e n t l y , at t h e beginning, it will contain
o n l y a f e w available g e n e t i c c h a r a c t e r i s t i c s , b u t g r a d u a l l y m o r e o f
t h e s e w i l l b e a d d e d t o it.
T h i s p o r t r a i t m a y w a r n us against p o s s i b l e diseases, i n d í c a t e m u - 95
t a n t g e n e s t h r e a t e n i n g w i t h h e r e d i t a r y diseases in d e s c e n d a n t s ,
c o n t a i n a p r e d i s p o s i t i o n f o r diseases, p s y c h o p a t h o l o g y . More-
o v e r , i t can i n c l u d e i n f o r m a t i o n c h a r a c t e r i z i n g n o t h u m a n p a t h o l -
o g y , b u t s u c h f a c t u r e s o f t h e i n d i v i d u a l as its b e h a v i o u r , emo-
tions, inclinations, intellectual potential, etc.

All these characteristics relate t o many partly intímate features of

an i n d i v i d u a l a n d m a y b e m i s u s e d a g a i n s t its i n t e r e s t s in s u c h
fields as social I n s u r a n c e , w o r k , m a r r i a g e a n d f a m i l y r e l a t i o n s , e s -
t á t e i n h e r i t a n c e a n d o t h e r social i n s t i t u t i o n s w h e r e physical, i n t e l -
lectual a n d s p i r i t u a l p r o p e r t i e s o f an i n d i v i d u a l a r e s o i m p o r t a n t .
G e n e t i c p r o g n o s t i c a t i o n s have a p r o b a b i l i t y character, b u t may
be used w i t h malicious intents t o suppress and e x p l o i t individ-
uáis. A n y w a y w e c a n n o t be c e r t a i n w h e t h e r p e o p l e b e n e f i t f r o m
knowing their future.

T h e r e f o r e t h e g e n e t i c p o r t r a i t o f an i n d i v i d u a l s h o u l d a p p a r e n t l y
b e c o n s i d e r e d as h i s / h e r e x c l u s i v e a n d c o n f i d e n t i a l p r o p e r t y . T h e
altitudes o f Soviet scientists t o w a r d s t h e p r o g r a m m e o f H u m a n
G e n o m e s t u d i e s is g o v e r n e d b y h u m a n i s t i c m o r a l - e t h i c s t a n d a r d s
placing t o p p r i o r i t y o n i n d i v i d u a l r i g h t s a n d p u b l i c b e n e f i t . T h e s e
w i l l b e c o m e a s u b j e c t o f legislation t o be o p e n l y discussed in p u b -
lic in t h i s c o u n t r y .
 97

THE HUMAN CENOME

P R O G R A M M E IN T H E
UNITED STATES

Norton D. Zinder

The Rockefeller University, N e w Y o r k (USA)

ABSTRACT

In the United States, the H u m a n Genome Project is a

well-established, specific large-scale reality, with
prospects for future expansión a n d clear aims that
define it: high-resolution m a p p i n g o f the H u m a n
Genome; complete sequencing o f the h u m a n D N A
and o f model biológica! organisms; a physical m a p o f
human chromosomes and that o f models; the
creation o f computer programmes and high-technology,
high<apacity a n d development data-bases.
In order to follow through the p r o g r a m m e a n d its
aims, certain scientific procedures to be followed
have been d r a w n up, which could be periodically
modified in the light o f the discovery o f new technol-
ogies and o f experimental result
W h i l e w e have a l r e a d y h e a r d f r o m s p e a k e r s discussing t h e G e n - 99
orne Program f r o m a number of counthes, they've devoted m o s t
o f t h e i r p r e s e n t a t i o n s t o e t h i c a l issues. Since b o t h D r . E. Jungst,
D i r e c t o r o f t h e Ethical, Legal, Social I m p l i c a t i o n s o f t h e Human
G e n o m e P r o g r a m o f t h e U.S. a n d D r . N a n c y W e x l e r , C h a i r o f
t h e N . I . H . ELS! w o r k i n g g r o u p w i l l b e a d d r e s s i n g t h i s m e e t i n g , l'll
t a l k m a i n l y a b o u t t h e G e n o m e P r o g r a m o f t h e U.S. I j u s t n o t e
t h a t a v e r y large ELS! p r o g r a m is b u i l t i n t o t h e g e n o m e e f f o r t s o f
b o t h t h e N . I . H . and D.O.E. and will be f u n d e d at a p p r o x i m a t e l y
5 % o f t h e i r a n n u a l b u d g e t s . It is p r o b a b l y w h e r e i t b e l o n g s f o r in
t h i s w a y i t is f u l l y i n t e g r a t e d a n d s t a y s c o o r d i n a t e d w i t h the
scientific e n d e a v o r s .

I w a n t t o a s s u r e t h e p h i l o s o p h e r s a n d e t h i c i s t in t h i s g r o u p t h a t
t h e r e is a s u b s t a n t i a l s c i e n t i f i c g e n o m e p r o g r a m b o t h o n g o i n g
a n d b e i n g f u r t h e r d e v e l o p e d in t h e U.S. t o d a y .

W e c o n s i d e r t h e H u m a n G e n o m e i n i t i a t i v e t o be a w o r l d w i d e
effort t o map and sequence t h e entire human g e n o m e . T h e H u m a n
G e n o m e c o n s i s t s o f 2 3 pairs o f c h r o m o s o m e s each containing
b e t w e e n 5 0 t o 2 5 0 megabases o f D N A . T h e t o t a l H u m a n G e n o m e
is 3 x 1 0 ( 9 ) base p a i r s o f D N A . T h e s e m o l e c u l e s c o n t a i n some
100,000 g e n e s w h i c h c o d e f o r specific p r o t e i n s . T h e s t r u c t u r e o f
t h e genes, w h i c h are alternating sequences of coding DNA
( e x o n s ) s e q u e n c e s a n d o f n o n - c o d i n g s e q u e n c e s , ( i n t r o n s ) is such
t h a t only a b o u t 5% of D N A encodes protein. Transcriptional
units t h a t include b o t h exons and introns are, h o w e v e r , very
large a n d a r e r e d u c e d t o m e s s e n g e r R N A by R N A splicing. T h u s ,
t h e gene, f o r e x a m p l e t h e gene w h o s e m u t a t i o n s cause cystic
f i b r o s i s c o n t a i n s s o m e 2 5 0 , 0 0 0 base pairs o f D N A o f w h i c h o n l y
about 4500 are coding.

W h e n in t h e late s e v e n t i e s a n d e a r l y eighties t e c h n i q u e s f o r m a -
nipulating and sequencing D N A became so efficient t h a t several
scientists e n v i s i o n e d s e q u e n c i n g t h e e n t i r e H u m a n G e n o m e . A f t e r
a b o u t f o u r y e a r s o f d i s c u s s i o n s a n d w o r k s h o p s c u l m i n a t i n g in a
positive r e p o r t f r o m t h e N a t i o n a l Research C o u n c i l , a j o i n t p r o -
g r a m o f t h e D e p a r t m e n t o f Energy and t h e N a t i o n a l Institutes o f
H e a l t h w a s e s t a b l i s h e d t o a c c o m p l i s h t h i s goal in t h e U.S.

T h e N I H ' s p r o g r a m is m a i n l y an e x t r a - m u r a l o n e a n d is c u r r e n t l y
f u n d e d by t h e U.S. C o n g r e s s a t a b o u t $ 6 0 , 0 0 0 , 0 0 0 f o r F Y 9 0 a n d
$ 8 8 , 0 0 0 , 0 0 0 f o r F Y 9 I . T h e D O E p r o g r a m is p r i m a r i l y an i n t r a -
mural (about $46,000,000) one at Lawrence L i v e r m o r e , Lawrence
Berkeley, and t h e Los A l a m o s N a t i o n a l L a b o r a t o r i e s . Working
t o g e t h e r , t h e D O E a n d t h e N I H A d v i s o r y C o m m i t t e e s have p u t
t o g e t h e r a f i v e y e a r plan o f a c t i o n f o r t h e U.S. C o n g r e s s . T h e
plan is t o b e u s e d p r i m a r i l y a g u i d e a n d w i l l be r e v i s e d a n n u a l l y
o n t h e basis o f n e w t e c h n o l o g i c a l a n d e x p e r i m e n t a l r e s u l t s o f
s c i e n c e . In t h i s á r e a , as in m o s t áreas o s c i e n c e , any a t t e m p t t o
s e t specific plans a r e o v e r t a k e n b y e v e n t s . F o r e x a m p l e w h i l e t h e
N C R r e p o r t w a s w r i t t e n o n l y t h r e e y e a r s ago, t w o techniques
00 t h a t a r e n o w v e r y i m p o r t a n t w e r e n o t e v e n d i s c u s s e d , t h a t is t h e
p o l y m e r a s e chain r e a c t i o n ( P C R ) and high r e s o l u t i o n in situ h y b r i d -
¡ z a t i o n . Since, as n o t e d b e l o w , o n e p r o g r a m goal is t o s t i m u l a t e
n e w t e c h n o l o g y , d e v e l o p m e n t s events may even m o r e faster. For
example, PCR at t h e 100 k b level w o u l d r e v o l u t i o n i z e t h e a p -
proaches t o the p r o b l e m .

T h e p r o g r a m goals a r e :

• c o n s t r u c t i o n o f a high-resolution genetic map of t h e Human

Genome;

• p r o d u c t i o n o f a v a r i e t y o f physical maps o f all h u m a n c h r o m o -

somes and of the D N A of selected model organisms, w i t h
emphasis o n maps t h a t m a k e t h e D N A o f s e l e c t e d m o d e l o r g a n -
isms, w i t h e m p h a s i s o n m a p s t h a t m a k e t h e D N A accessible t o
i n v e s t i g a t o r s f o r f u r t h e r analysis;

• d e t e r m i n a r o n of t h e c o m p l e t e sequence of human D N A and

of t h e D N A of selected m o d e l organisms;

• d e v e l o p m e n t o f capabilities f o r collecting, storing, distributing,

a n d analyzing t h e d a t a p r o d u c e d ;

• creation of a p p r o p r i a t e technologies necessary t o achieve

these objectives.

A n o t h e r p r o g r a m g o a l is t o p r o v i d e , f r o m t h e o u t s e t , t h e m e a n s
b y w h i c h t h e p u b l i c can b e m a d e a w a r e a n d have i n p u t i n t o t h e
c o n s e q u e n c e s o f t h e legal a n d e t h i c a l i m p l i c a t i o n s o f t h e findings.

It is c u r r e n t l y a s s u m e d t h a t t h e goals can b e a c h i e v e d in a b o u t 15
years w i t h the d o c k starting at O c t . I, 1990 (FY 9 1 ) . S o m e
$ 2 0 0 , 0 0 0 , 0 0 0 ( 1 9 8 8 ) a y e a r w i l l be r e q u i r e d . T h e e x a c t e x p e n -
d i t u r e s n e c e s s a r y in t h e U.S. w i l l d e p e n d in p a r t o n t h e a c t i v i t i e s
o f t h e r e s t o f t h e w o r l d . Significant a c t i v i t y o u t s i d e t h e U.S. w i l l
b o t h s h o r t e n t h e t i m e n e e d e d a n d r e d u c e t h e p r o p o r t i o n o f U.S.
expenditures.

A seat o f f i v e y e a r Scientific G o a l s have b e e n e s t a b l i s h e d as a w a y

of proceeding:

Quote

k C o m p l e t e a fully c o n n e c t e d human genetic map w i t h mark-

e r s spaced a n d a v e r a g e o f 2 t o 5 c e n t i m o r g a n s a p a r t . I d e n -
t i f y each m a r k e r [ w h e n e v e r p o s s i b l e ] w i t h an STS. [STS, se-
q u e n c e t a g g e d sites. F o r any D N A f r a g m e n t 3 0 0 bases f r o m
one end are sequenced, t w e n t y nucleotide oligonucleotides
a r e m a d e f o r each e n d o f t h e 3 0 0 bases a n d b y P C R t h e f r a g -
 m e n t v e r i f i e d . T h i s w o u l d a l l o w all f r a g m e n t s t o be s t o r e d 101
e l e c t r o n i c a l l y b y s e q u e n c e a n d m a k e s u p e r f l u o u s large a n d
expensive collections of biological D N A c l o n e s . It t h u s
p r o v i d e s a sigle language f o r d e s c r i b i n g f r a g m e n t s m a d e in
any l a b o r a t o r y a t any t i m e ] .

la) D e v e l o p t e c h n i q u e s f o r p r o d u c i n g t i s s u e specific a n d
developmental stage specific c - D N A librarles with
e q u i v a l e n t c o n c e n t r a t i o n s . C o n v e r t c - D N A i s o l a t e d in
any l a b o r a t o r y i n t o STSs.

Ib) In t w o t o t h r e e y e a r s d e v e l o p an i n d e x m a p o f a b o u t
300 makers approximately 10 megabases a p a r t f o r all
chromosomes of the Human Genome.

2. Assemble STS m a p s o f all h u m a n chromosomes with

m a r k e r s at a p p r o x i m a t e l y 100,000 bases pair intervals.
Genérate ovelapping sets o f c l o n e d DNA or closely
spaced unambiguously ordered markers with continuity
o v e r lengths o f 2 x 1 0 ( 5 ) b p .

2a) D e t e r m i n e in r e g i o n s o f 2 x 1 0 ( 6 ) b p all p o s s i b l e c o d i n g
genes.

3. Improve current methods and/or develop new methods for

D N A sequencing t h a t will a l l o w sequencing f o r $0.50 per bp
[ o r less]. [ L a r g e scale s e q u e n c i n g d e c i s i ó n f o r h u m a n DNA
t o be m a d e a t 4 t o 5 y e a r s o u t ] .

4. P r e p a r e a g e n e t i c m a p o f t h e m o u s e g e n o m e based o n DNA
m a k e r s . S t a r t physical m a p p i n g o f I o r 2 c h r o m o s o m e s .

S e q u e n c e an a g g r e g a t e o f a b o u t 2 0 x I O6 b p f r o m a v a r i e t y o f
o r g a n i s m s f o c u s s i n g o n s t r e t c h e s t h a t a r e 10(6) bp l o n g [ M o d -
el o r g a n i s m s a r e £. coíi, y e a s t (S. cerevisiae), D. melanogaste,
C. elegans a n d t h e lab m o u s e ] .

5. [Utilize a "Joint Informatics Task Forcé", D O E & N I H ] t o :

D e v e l o p e f f e c t i v e s o f t w a r e a n d datábase designs t o s u p p o r t
large-scale m a p p i n g a n d s e q u e n c i n g p r o j e c t s .

C r é a t e datábase t o o l s t h a t p r o v i d e easy acces t o u p - t o - d a t e

physical m a p p i n g , c h r o m o s o m e m a p p i n g , a n d s e q u e n c e i n -
f o r m a t i o n s o as t o a l l o w r e a d y c o m p a r i s o n o f t h e d a t a in
t h e s e several STS.

D e v e l o p t h e a l g o r i t h m s a n d analytical t o o l s t h a t can be used

in t h e i n t e r p r e t a r o n o f g e n o m i c i n f o r m a t i o n .

6. Develop [through a joint N I H - D O E w o r k i n g group] programs

[research grants, w o r k s h o p s , t o w n meetings, educational
02 m a t e r i a l s ] a d d r e s s e d a t u n d e r s t a n d i n g t h e e t h i c a l , legal, a n d
social i m p l i c a t i o n s o f t h e H u m a n G e n o m e P r o j e c t . Identify
a n d d e f i n e t h e m a j o r issues a n d d e v e l o p initial p o l i c y o p t i o n s
t o address t h e m .

7. S u p p o r t research training of pre- and p o s t d o c t o r a l fellows

s t a r t i n g in FY 1990 ( u p t o 6 0 0 / y e a r , s t e a d y s t a t e ) . E x a m i n e
needs f o r o t h e r types o f training.

8. S u p p o r t i n n o v a t i v e and high r i s k t e c h n o l o g i c a l develop-

ments... t o m e e t t h e needs of t h e G e n o m e Project.

9. E n c o u r a g e a n d facilítate t r a s f e r o f t e c h n o l o g i e s a n d o f m e d i -
cally i m p o r t a n t I n f o r m a t i o n t o t h e [ r e l e v a n t ] c o m m u n i t i e s .

Unquote

C u r r e n t l y t h e N I H p r o g r a m is s u p p o r t i n g m o r e t h a n a b o u t 150
g r a n t s in all o f t h e a b o v e áreas. In F Y 9 0 / 9 I w e a r e e s t a b l i s h i n g
up t o nine research centers w i t h 20-50 persons focussed o n ge-
n o m e r e s e a r c h ; t o r e a c h 10-15 c e n t e r s in t h e n e x t 5 y e a r s . T h e
D O E s u p p o r t s t h e physical analysis o f c h r o m o s o m e s 16, 19, a n d
2 ! a t t h r e e N a t i o n a l labs. In a d d i t i o n t e c h n o l o g i e s s u c h as s c a n -
n i n g t u n n e l i n g e l e c t r ó n m i c r o s c o p y o f D N A , láser d e t e c t i o n of
D N A a n d s t u d i e s o n a v a r i e t y o f datábase s t r u c t u r e s a n d t o o l s
are being s u p p o r t e d .

Each c e n t e r w i l l h a v e an o u t r e a c h p r o g r a m . F a c i l i t i e s w i l l be
m a d e available f o r d o i n g lay scale m a p p i n g , datábase a n d s o f t w a r e
updates and exchange of I n f o r m a t i o n . T h e centers will thus serve
as a w a y t o p a r t i a l l y d e c e n t r a l i z e m a n a g e m e n t o f t h e p r o g r a m .

T w o questions are a l m o s t always raised. T h e first, w h o s e ge-

n o m e w i l l be m a p p e d a n d s e q u e n c e d ? T h e r e w i l l b e n o p a r t i c u l a r
i n d i v i d u a l . L a b o r a t o r i e s all o v e r t h e w o r l d a r e s t u d y i n g d i f f e r e n t
isolates o f h u m a n cell lines, c h r o m o s o m e s a n d D N A segments.
T h o s e w h o w i l l m a p a n d s e q u e n c e w i l l use t h e i r o w n favorite
pieces. T h u s , t h e map and sequences w i l l p r o v i d e a r e f e r e n c e
s t a n d a r d t o w h i c h all o t h e r f r a g m e n t s f o r m t h e s a m e g e n e t i c r e -
g i ó n can b e c o m p a r e d . F o r e x a m p l e , analysis o f f r o m 100 d i f f e r -
e n t p e o p l e o f specific 100 k i l o b a s e s e g m e n t s w i l l p r o v i d e d e t a i l e d
I n f o r m a t i o n o f h u m a n v a r i a b i l i t y . If a highly c o n s e r v e d r e g i ó n is
s t u d i e d , t h e c o m p a r i s o n w i l l p r o v i d e insight i n t o t h e e v o l u t i o n a r y
input of this región.

T h e o t h e r q u e s t i o n is, w h y d o i t as a p r o g r a m . T w o p a r t s o f t h e
a n s w e r a r e g i v e n a b o v e . By f o c u s s e d e f f o r t w e m o r e r e a d i l y w i l l
derive deep understanding o f human variability and e v o l u t i o n a r y
h i s t o r y . M a n y n e w genes o f i m p o r t w i l l b e a s c e r t a i n e d i n c l u d i n g
t h o s e p r o d u c i n g disease. G i v e n t h e s e q u e n c e s a t a n y t i m e in t h e
f u t u r e w h e n a g e n e t i c p r o b l e m anises, i t w i l l be s i m p l e t o s t u d y 103
t h e genes i n v o l v e d , m o r e e f f i c i e n t l y a n d c o s t - e f f e c t i v e l y t h a n a
p r e s e n t . M o r e o v e r a high r e s o l u t i o n g e n e t i c m a p has g r e a t v a l u é
e v e n w i t h o u t t h e D N A s e q u e n c e . W h e n w e t r a n s í a t e all o f t h e
nucleotide sequences i n t o proteins and t h e n i n t o gene functions,
w e will ascertain n u m e r o u s i m p o r t a n t modulating and develop-
m e n t a l p r o t e i n s a n d t h e r e f o r e t h e y ' l l be available f o r s t u d y a n d
use. T h e m a j o r p r o b l e m t h a t w e f o r e s e e is t h a t w e ' l l have genes
b e f o r e w e have f u n c t i o n s and t h e r e f o r e diagnosis o f genetic diseases
b e f o r e w e have t h e r a p i e s .

T h a t is w h y w e have e s t a b l i s h e d a large p r o g r a m r e l a t i n g t o e t h i -
cal a n d legal p r o b l e m s as an o u t r e a c h t o b e s u r e t h e i m p l i c a t i o n s
o f t h e results are made clear t o o u r relevant g o v e r n o r s and t h e
public. H o w e v e r , at b o t t o m w e m u s t r e m e m b e r t h a t o u r ge-
n o m e is a p a r t o f us a n d in large m e a s u r e m a k e us, us a n d t h e r e f o r e
w o r t h y o f d e t a i l e d s t u d y in its o w n r i g h t .
 105

W H Y ISOLATE THE
THIRD WORLD?
W H A T PART DOES
U N E S C O H A V E T O PLAY?

Claude Rosenfield

A d v i s e r t o t h e D i r e c t i o n o f U N E S C O , Paris ( F r a n c e )

ABSTRACT

The T h i r d W o r l d covers most o f m a n k i n d . The

H u m a n Genome Project is o f an international nature
a n d as such, demands the participation o f scientist
f r o m all nations, including those f o r m developing
countries. On the other hand, r é s p e d for human dig
nity and human rights is consubstantial to the Project
from all points o f view: ethical, religious or genetic
engineering. UNESCO intends to promote international
co-operation f o r Education, Science, Culture a n d
Communication; it is therefore obvious that the re-
sult o f research in agriculture, genetics or in other
fields have implications for the whole o f m a n k i n d
and, in some cases, particularly for the Third World.
There should therefore be no doubt about participa-
tion a n d exchange between developing a n d devel-
oped countries.
C o n s i d e r i n g t h e potential public impact o f t h e H u m a n G e n o m e 107
M a p p i n g a n d S e q u e n c i n g P r o j e c t , i t is i m p o s s i b l e n o t use t h e a d -
j e c t i v e P r o m e t h e a n t o d e s c r i b e it. A s t h e m o s t p r e s t i g i o u s p r o -
d u c t o f t h e p o s s i b i l i t i e s o p e n e d u p b y genetic engineering, i t calis
f o r t h e i n v o l v e m e n t , t o p a r a p h r a s e Frangois G r o s s 1 n o t o n l y o f
philosophers, "theologicians", jurists, legislators and politicians
b u t also o f m e n a n d w o m e n g e n e r a l l y .

T h e r e m a r k s o f t h e p h i l o s o p h e r M i c h e l S e r r e s 2 m a y usefully b e
applied t o t h e subject: " t h e t h i r d área o f ethics focuses o n t h e
transition f r o m potentiality t o existence. A m a t t e r o f divine deci-
s i ó n in t h e classical age, a n a t u r a l m e c h a n i s m o p e r a t e d b l i n d l y b y
n a t u r e o r b y t i m e since D a r w i n , a r e s p o n s i b i l i t y e n t r u s t e d increas-
ingly t o o u r s e l v e s since w e f i s r t began t o ¡ n t e r v e n e a c t i v e l y in t h e
w o r l d - n o d o u b t since t h e age o f homo faber- i t has s u d d e n l y b e -
c o m e a m u c h g r e a t e r b u r d e n since w e a c q u i r e d t h e c a p a c i t y t o
créate possible w o r l d s . O n this m a t t e r w e a r e n o longer divided,
be w e p h i l o s o p h e r s , s c i e n t i s t s , j u r i s t s o r p o l i t i c i a n s . W h e t h e r w e
see i t as t a k i n g p a r t in G o d ' s c o u n c i l s o f o í d o r in n a t u r e ' s s o w i n g
o f seeds, i t m a y b e w i t h i n o u r p o w e r t o m o r r o w t o shape t h e
w o r l d f o r t h e best".

T h e s e r e m a r k s s u m u p t h e r e a s o n s w h y i t is n o t p o s s i b l e t o e x -
clude f o r m this apex o f knowledge, judgement and decisión - t a k i n g
qualified representatives o f t h e m a j o r i t y o f humankind: t h e
T h i r d W o r l d . U n e s c o ' s r o l e is t o facilítate exchanges o f k n o w l e d g e
b e t w e e n t h e r i c h m i n o r i t y a n d t h e p o o r m a j o r i t y in o r d e r t o
p r e v e n t t h e injustice o f t h e majority's being subordinated t o a
f e w , an i n j u s t i c e t h a t is d e h u m a n i z i n g , " a n e t h i c a l " a n d a n t i d e m o -
cratic, generating envy and hatred a m o n g t h o s e w h o happen by
lack o f r e s o u r c e s t o b e r e d u c e d t o passivity a n d i m p o t e n c e .

T h e r o l e s c i e n t i s t f r o m d e v e l o p i n g c o u n t r i e s can play in t h e H u -
m a n G e n o m e P r o j e c t , w i t h U n e s c o ' s assistance, has b e e n s u m -
m e d u p b y J. E. A l l e n d e o f C h i l e 3 : " M o s t s c i e n t i s t s a g r e e t h a t i t is
highly d e s i r a b l e t h a t t h e H u m a n G e n o m e P r o y e c t b e a t r u l y g l o b -
al u n d e r t a k i n g , o p e n t o p a r t i c i p a t i o n b y s c i e n t i t s f r o m all n a t i o n s ,
i n c l u d i n g t h e d e v e l o p i n g c o u n t r i e s . It also seems logical that
Unesco, e n t r u s t e d by t h e w o r l d c o m m u n i t y w i t h t h e charge o f
p r o m o t i n g I n t e r n a t i o n a l c o - o p e r a t i o n in s c i e n c e , e d u c a t i o n a n d
c u l t u r e , should m a k e efforts t o facilítate t h e participation o f t h e
d e v e l o p i n g c o u n t r i e s in t h i s p r o g r a m m e . T h e q u e s t i o n is h o w .

M y p r o p o s i t i o n is t h a t s u c h p a r t i c i p a t i o n w o u l d b e g r e a t l y s t i m u -
lated b y b r i n g i n g t o g e t h e r t o small c o m m u n i t i e s o f h u m a n g e n e t i -
cists o f T h i r d W o r l d r e g i o n s f o r t h e specific p u r p o s e s o f g e n e r -
a t i n g realistic r e g i o n a l p r o g r a m m e s t h a t w o u l d i n c o r p ó r a t e t h e m
an t h e i r c o u n t i r e s i n t o t h e H u m a n G e n o m e P r o j e c t " .

H o w e v e r , t h e issue is o n e t h a t t r a n s c e n d s t h e s c o p e o f s c i e n c e .
In a w o r l d f i r s t i n v e n t e d a n d d i s c o v e r e d b y h u m a n beings b e f o r e
being f a s h i o n e d b y t h e m science is n o m o r e t h a n t h e m o s t p o w -
08 e r f u l t o o l available t o a t t a i n t h e i r goals. T h e H u m a n G e n o m e is
t h e mythical and ultímate c u l m i n a t i o n o f this search f o r t h e se-
c r e t s o f life, a n d i t is p a r t i c u l a r l y i m p o r t a n t t h a t t h e I n s t r u m e n t s
a n d f i n d i n g s o f t h a t s e a r c h b e r e g a r d e d as t h e c o m m o n heritage
of humankind, o f w h i c h no o n e must be deprived.

T h e scientists a r e fully a w a r e o f this fact and are anxious f o r it t o

b e c o m e a p u b l i c issue. In t h e i r r e p o r t t o t h e P r e s i d e n t o f t h e
F r e n c h R e p u b l i c in 1979, f o r e x a m p l e , P r o f e s s o r J a c o b , P r o f e s s o r
Royer and Professor Gros w r o t e : " C o n t r a r y t o what some
w o u l d have us b e l i e v e , i t is n o t t h r o u g h b i o l o g y t h a t a c e r t a i n
idea o f h u m a n beings can b e g a i n e d . O n t h e c o n t r a r y , i t is in t h e
l i g h t o f a c e r t a i n idea o f h u m a n beings t h a t b i o l o g y c a n b e u s e d in
t h e i r s e r v i c e " . 4 " W h a t a t y p e o f a n s w e r s have b i o l o g i s t s t o o f f e r ,
as b i o l o g i s t s , t o t h e q u e s t i o n t h e y a r e t o d a y b e i n g u r g e n t l y a s k e d
by o r d i n a r y citizens and decision-makers?"5.

Federico M a y o r , at a U n e s c o s y m p o s i u m held at t h e T r i e s t e Insti-

t u t e o f H u m a n Rights ( w h o s e D i r e c t o r is G u i d o G e r i n ) , p o i n t e d
o u t in c o n n e c t i o n w i t h t h e r e l a t i o n s h i p b e t w e e n g e n e t i c m a n i p u -
l a t i o n a n d h u m a n r i g h t s : " G e n e t i c m a n i p u l a t i o n , in its b r o a d
sense, has m a n y p o t e n t i a l i m p l i c a t i o n s f o r h u m a n r i g h t s as i t m a y
have u n f o r e s e e a b l e e f f e c t t h a t can i n f r i n g e t h e h u m a n r i g h t s n o t
o n l y o f t h e c h i l d b u t o f all his o r h e r d e s c e n d a n t s ... C o n c e r n i n g
r e s e a r c h , its risks s h o u l d be carefully c o n s i d e r e d in o r d e r t o
a v o i d i n a d v e r t e n t effects t h a t m a y i m p a i r h u m a n r i g h t s ... T h e r e -
quirements of human dignity are t h e roots of human rights.
E v e r y b o d y s h o u l d b e able t o d e v e l o p his o r h e r p o t e n t i a l as f u l l y
as p o s s i b l e " 6.

W i t h regard t o this c o n c e r n felt by scientists t o ensure respect

f o r h u m a n d i g n i t y i t m a y be a p p r o p r i a t e t o q u o t e p a r a g r a p h I o f
t h e Valencia Deciaration o n t h e H u m a n G e n o m e Proyect, w h i c h
i n c i d e n t a l l y also calis f o r p u b l i c d i s c u s s i o n o f t h e issue a n d t h e
specific p a r t i c i p a t i o n o f all c o u n t r i e s : " T h e m e m b e r s o f t h e
w o r k s h o p b e l i e v e t h a t k n o w l e d g e g a i n e d f r o m m a p p i n g an s e -
q u e n c i n g t h e H u m a n G e n o m e can have g r e a t b e n e f i t f o r h u m a n
health and well-being. T o w a r d s these ends, participating scien-
tists a c k n o w l e d g e t h e i r responsibility t o help ensure t h a t genetic
I n f o r m a t i o n b e u s e d o n l y t o e n h a n c e h u m a n d i g n i t y . T h e y also
e n c o u r a g e p u b l i c d e b a t e o n e t h i c a l , social a n d legal i m p l i c a t i o n s
o f t h e use o f genetic I n f o r m a t i o n . T h e m e m b e r s e n d o r s e t h e
concept o f International collaboration f o r t h e p r o j e c t and urge
t h e w i d e s t possible participation o f countries t h r o u g h o u t t h e
w o r l d , w i t h i n t h e r e s o u r c e s a n d i n t e r e s t s o f each c o u n t r y " 7

It is c l e a r t h a t t h e c o n c e p t s o f human rights a n d human dignity in

connection w i t h t h e H u m a n G e n o m e and genetic manipulation
a r e o f c o n c e r n t o r e l i g i o u s t h i n k e r s a n d j u r i s t s s e e k i n g t o engage
in a d i a l o g u e w i t h s c i e n t i s t s . F o r e x a m p l e , in h e r a r t i c l e e n t i t l e d
"Genetic screening, f r o m newborns to D N A typing" Bartha
K n o p p e r s concludes: " i n t h e c o n t e x t o f t h e n e w genetics, t h e
assurance o f and r e s p e c t f o r h u m a n dignity c a n n o t be limited t o a 109
c o n c e p t i o n o f natural rights o f t h e person t h a t d e t e r m i n e the
genetic i m m u t a b i l i t y o f h u m a n k i n d and o f t h e individual at b i r t h ,
ñ o r t o a single r i g h t s u c h as t h a t o f i n v i o l a b i l i t y , o r p r i v a c y , o r
i n d e e d l i b e r t y . R e s p e c t f o r h u m a n d i g n i t y m e a n s t h a t i t is essential
t o t a l k n o t in t e r m s o f g e n e t i c r i g h t s b u t r a t h e r in t e r m s of
p r o t e c t i o n o f t h e genetic heritage, o f individual c o n t r o l o v e r and
access t o t h e H u m a n G e n o m e , a n d o f d u t i e s a n d collective
r e s p o n s i b i l i t y in r e g a r d t o it. Such an a p p r o a c h s h o u l d s e r v e as a
s o u r c e o r a p p r e c i a t i o n o f t h e specific, intrinsic valué o f each h u m a n
b e i n g as s u c h , f o r t h e i n d i v i d u a l in his o r h e r g e n e t i c m a k e - u p a n d
human n a t u r e and f o r t h e collective a t t a i n m e n t o f such ' h u m a n -
i t u d e ' " 8.

T h e c o u n c i l o f E u r o p e , in t h e 1989 r e p o r t o f its ad hoc expert

c o m m i t t e e o n t h e p r o g r e s s o f t h e b i o m e d i c a l sciences ( C A H B ! )
in t h e f i e l d o f a r t i f i c i a l p r o c r e a t i o n , s t r e s s e d t h e f a c t t h a t " t h e es-
sential basis o f h u m a n d i g n i t y is t h a t all h u m a n beings a r e equal
a n d t h a t e v e r y o n e h a d his o r h e r o w n i n t r i n s i c w o r t h " . T h e h u -
m a n b e i n g m u s t n o t b e r e g a r d e d as " a m e a n s " o r as " a n o b j e c t " .
T h e principies put f o r w a r d are aimed at ensuring recognition of
t h e essential c o n c e p t o f h u m a n d i g n i t y a n d h u m a n r i g h t s as e m -
b o d i e d in t h e E u r o p e a n C o n v e n t i o n f o r t h e P r o t e c t i o n o f H u m a n
Rights a n d F u n d a m e n t a l F r e e d o m s 9.

In t h e r e p o r t s q u o t e d b y B a r t h a K n o p p e r s 10 p r o d u c e d b y v a r -
ious N o r t h A m e r i c a n scientific bodies o n gene t h e r a p y and o n
t h e use o f h u m a n g e n e t i c m a t e r i a l , such r e s p e c t f o r h u m a n d i g -
nity, " a l t h o u g h l i t t l e m e n t i o n e d as s u c h , is p e r c e i v e d as an i n d i v i d -
ual a n d s u b j e c t i v e c o n c e p t " . C o m p l e m e n t i n g this n o t i o n of hu-
m a n d i g n i t y , as a g u a r a n t e e o f i n d i v i d u a l s u b j e c t i v e r i g h t s , is t h a t
o f the i n h e r e n t dignity o f h u m a n k i n d , of t h e c o m m u n i t y , and t h e
r e q u i r e m e n t t o r e s p e c t s u c h d i g n i t y as t h e f o u n d a t i o n o f a n y
t r u l y h u m a n s o c i e t y . T h i s l a t t e r a p p r o a c h is p a r t i c u l a r l y e v i d e n t in
r e c e n t s t u d i e s p r o d u c e d in F r a n c e , t h e F e d e r a l R e p u b l i c o f G e r -
m a n y a n d S w i t z e r l a n d l2. T h e s e t h r e e c o u n t r i e s h a v e b e g u n t o
r e g a r d t h e s u r v i v a l o f t h e d i g n i t y o f h u m a n k i n d as p a r t o f t h e
p r o t e c t i o n o f t h e h u m a n s p e c i e s as a w h o l e . A r e p o r t b y t h e
F r e n c h G o v e r n m e n t a n d a r e c e n t d r a f t l a w have g i v e n r e n e w e d
expression t o t h e overall c o n c e r n regarding t h e limits o n t h e free-
d o m an i n d i v i d u a l m a y e x e r c i s e in d e c i d i n g t h e fate o f his o r h e r
g a m e t e s o r e m b r y o s a n d t h e f u t u r e uses t o w h i c h t h e y a r e p u t " .
In a c c o r d a n c e w i t h t h a t v i e w , " i n d i v i d u á i s a r e f r e e t o a c t as t h e y
c h o o s e b u t t h e y are also a c c o u n t a b l e t o o t h e r s and t o t h e m -
selves a n d h e n e e m a y n o t a t t a c k h u m a n k i n d t h r o u g h t h e i r own
p e r s o n s . A c c o r d i n g l y , n o a c t i o n t h a t is i n c o m p a t i b l e w i t h h u m a n
dignity a n d t h a t p r e v e n t s t h e individual f r o m d e v e l o p i n g and fulfilling
his o r h e r h u m a n p o t e n t i a l c a n be p e r m i s s i b l e " l3. It is o f c o u r s e
n o t p o s s i b l e t o r e p o r t h e r e all he d i s c u s s i o n s t h a t a r e s u m m a r i z -
e d in t h e e x c e l l e n t s y p n o t i c a r t i c l e . I shali c o n f i n e m y s e l f t o q u o t -
ing, in r e g a r d o n c e again t o U n e s c o ' s r o l e , t h a t p l a y e d b y t h e dif-
f e r e n t nations f o r and t h r o u g h t h e i r citizens and t h e need t o t a k e
a c o o u n t in d i s c u s s i o n s o f all t h e c u l t u r a l , m o r a l a n d r e l i g i o s fac-
t o r s I n v o l v e d In o r d e r t o e n a b l e d e c i s l o n - m a k e r s t o be g u i d e d b y
t h e p r i n c i p i e s e m e r g i n g f r o m t h e scientific d e b a t e , t h e f o l l o w i n g
p a r a g r a p h s : " E v e n a s s u m i n g t h a t , a t a s o c i e t a l level, t h e p r o t e c t i o n
o f t h e c o m m o n genetic heritage o f humanity and t h e necessary
genetic responsibilty t o w a r d s future generations take t h e f o r m o f
t h e b a n n i n g a t n a t i o n a l a n d i n t e r n a t i o n a l levéis o f t h e t w o ex-
t r e m e positions, namely genetic manipulation f o r non-therapeutic
purposes and eugenic applications, t h e postúlate o f human dignity
in its clinical a p p l i c a t i o n in h u m a n g e n e t i c s r e q u i r e s 'a p r e f e r e n c e
f o r p e r s u a s i ó n r a t h e r t h a n c o e r c i ó n ' ... t h e f u t u r e o f h u m a n g e -
n e t i c s lies n o t in t h e o b v i o u s c o n t r o v e r s i e s s u r r o u n d i n g m a n i p u -
l a t i o n o r e l i m i n a t i o n b u t r a t h e r in t h e c o m m u n i c a t i o n o f g e n e t i c
I n f o r m a t i o n in g e n e t i c e d u c a t i o n a n d in t h e m a k i n g o f i n f o r m e d
g e n e t i c c h o l e e s . . . " F o r " t h e p u r s u i t o f h u m a n d i g n i t y as a g o a l
c o n s i s t s in s e e k i n g t h e m e a n s o f r e d u c i n g h u m a n affairs t o l a w s
t h a t m a i n t a i n t h e g r e a t e s t p o s s i b l e l i b e r t y " l4.

In o r d e r t o p r e s e r v e w h a t is u n i q u e l y h u m a n , t o p r e v e n t the
loss o f w h a t is s a c r e d , t o e n s u r e t h a t t h e h u m a n b o d y o r its
c o n s t i t u e n t p a r t s o r e v e n its cells t h e m s e l v e s d o n o t become
c o m m e r c i a l p r o d u e t s o r r e s e a r c h m a t e r i a l s u s e d in n o n - t h e r a -
p e u t i c s c i e n t i f i c e x p e r i m e n t a t i o n , i t is e s s e n t i a l t h a t human
rights should exercise t h e i r n e w f u n c t i o n o f " m e d i a t i n g b e t w e e n
ethics, t h e law, and politics, t h e r e b y enabling a dividing-line to
be d r a w n b e t w e e n w h a t is j u s t a n d w h a t is u n j u s t , a n d a i m e d a t
e s t a b l i s h i n g w h a t m i g h t b e t e r m e d . . . a legal i d e n t i t y h a v i n g a
v a r i a b l e c o n t e n t " l5. T h e p o s i t i o n s q u o t e d a b o v e a r e n o t f a r
r e m o v e d f r o m t h o s e of t h e C a t h o l i c theologian Klaus Demmer
a n d t h e s c i e n t i s t Jean D a u s s e t , w h e t h e r s p e a k i n g o f t h e i n d i v i d -
uaiity o r uniqueness of the human person f r o m a religious,
transcendental point of view o r f r o m the standpoint of genetic
engineering.

A c c o r d i n g t o Klaus D e m m e r i t is essential w i t h i n a p l u r a l i s t s o -
ciety t o reitérate t h e presuppositions of Catholic theology w h e n
dealing w i t h p r o b l e m s o f h u m a n genetic m a n i p u l a t i o n . " T h e key
c o n c e p t t o w h i c h t h e e t h i c a l a r g u m e n t r e f e r s is r e f l e c t e d in t h e
n o r m a t i v e n a t u r e o f t h e h u m a n p e r s o n . It is in t h i s c o n c e p t t h a t
t h e t h i n k i n g o f t h e m o r a l t h e o l o g i a n s is r o o t e d : f o r reveíation
d o e s n o t b y itself p r o v i d e a c r i t e r i o n t h a t can be d i r e c t l y a p p l i e d
t o t h e i n t r a m u n d a n e o r d e r , e v e n if t h i s d o e s n o t m e a n t h a t i t
cannot p r o p o s e a general f r a m e w o r k w i t h i n w h i c h t o develop
t h e ethical discourse. In o r d e r t o a v o i d all possible m i s u n d e r s t a n d i n g
i t s h o u l d be a d d e d t h a t t h i s f r a m e w o r k c o n s i s t s o f a s e r i e s o f e l e -
ments structuring a comprehensive Christian anthropology that
still r e m a i n s t o be w o r k e d o u t a n d analysed ... A t t h e c o r e lies
t h e d i g n i t y o f t h e h u m a n p e r s o n in so f a r as i t is a r e l a t i o n s h i p t o
G o d . . . W h a t m u s t b e b o r n e in m i n d h e r e is t h e i n d i v i d u a l , u n r e -
p e a t a b l e n a t u r e o f t h e h i s t o r y o f each h u m a n b e i n g , a n d t h e p r o -
t e c t i o n t h a t m u s t a c c o r d i n g l y be g i v e n t o his o r h e r personal
i d e n t i f y t h r o u g h o u t t h a t p e r s o n ' s e x i s t e n c e ..." I6.
These postúlales enable D e m m e r t o w r i t e f u r t h e r o n : " T h e c o n - | |
v i c t i o n is b e g i n n i n g t o p e r m e a t e c o n t e m p o r a r y t h e o l o g i c a l t h i n k -
i n g o n m o r a l Issues t h a t a c t l o n t o m o d i f y t h e g e n e t i c c o d e Is
l e g i t í m a t e w h e n t h e i n t e n t l o n Is s t h c t l y t h e r a p e u t i c ... Y e a r s ago
Plus X I I t o o k a f a v o u r a b l e v l e w o f t h e c o n t e m p o r a r y prospects
o p e n e d up by negatlve eugenlcs deslgned t o elimínate h e r e d l t a r y
dlseases ... T h e d o c t r i n e o f t h e p r e s e n t p o p e f o l l o w s m u c h t h e
same Unes, ... e x p l i c l t l y a p p r o v l n g t h e use o f g e n e t i c e n g i n e e r l n g
for therapeutic purposes."

E m p h a s l s , h o w e v e r , Is p l a c e d o n p r o b l e m s r e l a t l n g t o prenatal
diagnosis o f g e n e t i c dlsease: " I n a c c o r d a n c e w i t h t h e principies
t h a t a r e v a l i d f o r all f o r m s o f diagnosis, t h e m o r a l l t y o f s u c h diag-
nosis Is c o n t i n g e n t u p o n t h e m o t i v a t i o n o f t h e p e r s o n a s k i n g f o r
a n d t h e p e r s o n u n d e r t a k l n g t h e diagnosis, a n d u p o n t h e g o a l a i m -
ed at. W h a t nevertheless poses a p r o b l e m f r o m the moral
s t a n d p o l n t in t h e s e l e c t i o n o f e m b r y o s a n d f o e t u s e s f o r e u g e n i c
p u r p o s e s , if In t h e e v e n t o f an u n f a v o u r a b l e diagnosis a t e r m i n a -
r o n o f p r e g n a n c y Is d e s i r e d o r r e q u i r e " .

K l a u s D e m m e r , in his c o n c l u s i ó n , r e m i n d us t h a t t h e human
being, t h r o u g h his o r h e r s c l e n t i f l c c o n q u e s t s , is a c o - c r e a t o r a n d
h e n e e G o d ' s c o l l a b o r a t o r . H e also calis f o r an interdlsclplinary
d i a l o g u e , w i t h j u r i s t s a m o n g t h e p a r t i c i p a n t s , in o r d e r t o a c h i e v e
a c o n s e n s u s a n d t o p r e v e n t d a n g e r o u s abuses.

T h i s c o n c e p t o f t h e u n q u e n e s s o f t h e h u m a n p e r s o n is f u r t h e r
r e c a l l e d a t t h e b i o l o g i c a l a n d g e n e t i c l e v é i s b y Jean Dausset:
" W i t h e a c h g e n e r a t l o n t h e r e f o r e a r e b o r n beings - p r o d u e t s of
t h e g e n e t i c l o t t e r y - t h a t a r e n e w a n d u n i q u e i n a s m u c h as t h e y
are f o r m e d o f entirely n e w combinations of genetic characteris-
t i c s " 17.

Thus t h e r e are points o f a g r e e m e n t a m o n g people of t h e same

c u l t u r e , be t h e y sclentists, religious t h i n k e r s , phllosophers o r j u -
rists, c o n c e r n i n g t h e unqueness o f t h e h u m a n p e r s o n and t h e
permissibillty of modifying the H u m a n G e n o m e f o r a therapeutic
p u r p o s e l i m i t e d t o t h a t single ( a n d u n i q u e ) p e r s o n , t h a t Is, an i n -
t e r v e n t l o n a f f e c t i n g t h e s o m a t l c cells b u t n o t t h e g e r m cells. B e -
y o n d this, p r o b l e m s arise, and t h e definitlon o f r i g h t and w r o n g
r e l a t e s t o c o n c e p t u a l f r a m e w o r k s o r e x p e r i e n c e t h a t cali f o r e x -
planatlons, pooling o f I n f o r m a t i o n and h o n e s t a t t e m p t s t o c o m -
pare views.

F o r e x a m p l e . James W a t s o n s t a t e d his p o s i t l o n a t t h e Unesco

s y m p o s l u m h e l d a t t h e I n t e r n a t i o n a l I n s t i t u t e o f H u m a n Rights In
T r i e s t e ( r e f e r r e d t o a b o v e ) in t h e f o l l o w i n g t e r m s : " A s a s c i e n t l s t
I a m h e s i t a n t t o m a k e s w e e p i n g g e n e r a l i z a t i o n s as t o t h e m o r a l
Implicatlons o f o u r Increasing mastery o f D N A and t h e mole-
c u l e s t h a t m a k e Ufe p o s s i b l e . D i f f e r e n c e s b e t w e e n r i g h t and
w r o n g o f t e n a p p e a r m o r e i n t u i t i v e t h a n d e d u c t i v e . . . A s each o f
us possesses s o m e h u n d r e d t h o u s a n d d i f f e r e n t g e n e s i t Is c l e a r
| |2 t h a t n o n e o f us possesses o n l y ' g o o d ' e x a m p l e s o f t h e s e g e n e s .
In s o m e cases a g i v e n g e n e w i l l a l w a y s b e b a d , b u t in m a n y cases
t h e final effect w i l l d e p e n d w h e r e a n d h o w w e live. I fear, h o w e v e r ,
t h a t m a n y o f us w i l l n o l o n g e r have t h i s f r e e d o m t o a p p e a r as
n o n - c o n t r o v e r s i a l g o o d guys ... W e t h u s have n o c h o l e e b u t t o
t a l k o p e n l y a b o u t t h e s e d i s c o v e r i e s s o t h a t t h e y can b e seen as
o p p o r t u n i t i e s f o r f u r t h e r h u m a n a d v a n c e m e n t r a t h e r t h a n as
l i n c h p i n s f o r t h e u n d e r m i n i n g o f t h e J u d a e o - C h r i s t i a n ideáis t h a t
have s o s u c c e s s f u l l y p r o m o t e d t h e d e v e l o p m e n t o f W e s t e r n c i v -
i l i z a t i o n ... M u c h m o r e d i f f i c u l t t o r e s o l v e w i l l b e t h e q u e s t i o n o f
w h e t h e r selective a b o r t i o n of genetically disabled foetuses
should oceur.

H e r e again, t h e h e a r t o f t h e p r o b l e m lies in h o w w e p e r c e i v e h u -
m a n life p e r s e " l8.

Q u i t e r e c e n t l y , Frangois G r o s m a d e t h e p o i n t , in a s t a t e m e n t t o
t h e political d e c i s i o n - m a k e r s at t h e M e e t i n g o f European Minis-
ters f o r Research o n Bioethics, t h a t "sciences t h a t are c o n c e r n e d
w i t h g e n e t i c s a n d r e p r o d u c t i o n d i r e c t l y challenge t h e individual
and society and consequently arouse t h e interest o f t h e politi-
c i a n s " l9'20. H e gave f o u r reasons f o r t h i s , w h i c h I shall s u m m a r i z e
as f o l l o w s :

1. G e n e t i c m e t h o d s p e r m e a t e all b r a n c h e s o f b i o l o g y , a n d t h e
pace o f p r o g r e s s in t h e s e fields f r e q u e n t l y m a k e s i t d i f f i c u l t
f o r t h e general public t o u n d e r s t a n d and keep up w i t h w h a t
is g o i n g o n . " H e n e e i t is a m a t t e r o f c o m m u n i c a t i o n a n d e d u -
c a t i o n as m u c h as o n e o f r e s p o n s i b i l i t y . "

2. B i o l o g y has m o v e d o n f r o m t h e c o n t e m p l a t i v e stage t o t h e
a n a l y t i c a l s t a g e , a n d t h e n c e t o t h a t o f i n t e r v e n t i o n . Its a p -
p l i c a t i o n s n o w lie w i t h i n t h e r e a l m o f t h e a d v a n c e d t e c h -
nology.

3. T h e t h i r d r e a s o n lies in " t h e m o r e o r less c o n s c i o u s c o l l e c -

t i v e m e m o r y o f t o t a l i t a r i a n i d e o l o g i e s , in p a r t i c u l a r during
t h e S e c o n d W o r l d W a r , r e l a t i n g t o s o - c a l l e d scientific d a t a
t h a t led t o a f o r m o f eugenics raised t o t h e s t a t u s o f a p o l i c y
o r system. Henee the fear that the n e w biology may serve
o n c e again t o p r o m o t s u c h designs r e m a i n s v e r y s t r o n g " .
T h i s f e a r leads t o p o s i t i o n s b e i n g t a k e n t h a t a r e a i m e d a t
ensuring p r o t e c t i o n o f individuáis and t h e i r ethnic diversity.

4. " T o all t h e s e r e a s o n s m u s t be a d d e d t h o s e d r a w n f r o m e c o l -
o g y in t h e b r o a d s e n s e " . T h e b i o l o g i c a l sciences a r e s u s p e c t -
e d o f p a v i n g t h e w a y f o r a n e w m e r c a n t i l e o r d e r in w h i c h i t
w i l l be t h e t u r n o f h u m a n beings t o b e c o m e consumer
goods.

" F o r all t h e s e r e a s o n s a n e w c h a p t e r o f m o r a l i t y , k n o w n as ' b i o -

e t h i c s ' , has b e e n o p e n e d . "
W i t h r e g a r d t o genetíc engineering a n d íhe exploration o f the H u m a n \ \ 3
G e n o m e , t h e d o c u m e n t " E t h i c a l issues i n v o l v e d in g e n o m e re-
s e a r c h p r o u c e d by t h e S t a n d i n g C o m m i t t e e f o r Legal A f f a i r a n d
C i t i z e n s " Rights o f t h e E u r o p e a n P a r l i a m e n t a s s e r t t h a t n o t all
t h a t is t e c h n o l o g i c a l l y feasible ¡s necessarily d e s i r a b l e f o r t h e h u -
m a n species.

Concerning the exploration of the Human Genome, Frangols

G r o s s d r a w s a t t e n t i o n , a f t e r c o n s i d e r i n g t h e advantages o f a n d
c r i t i c i s m s l e v e l l e d a t t h i s p r o j e c t , t o t h e usefulness o f adopting a
concerted attitude a t international level in o r d e r t o o r g a n i z e suffi-
ciently rapidly t h e process o f t h i n k i n g a b o u t t h e individual and
social c o n s e q u e n c e s o f such r e s e a r c h , " s o t h a t i t m a y be u n d e r -
t a k e n in o p t i m a l c o n d i t i o n s , t h e r e by o b v i a t i n g u n d u e a n d useless
e x p e n d i t u r e o n r e d u n d a n t p r o g r a m m e s a n d a b o v e all p r e v e n t i n g
t h e r e s u l t s o f such r e s e a r c h f r o m b e i n g ' t a k e n o v e r ' by d u b i o u s
i d e o l o g i e s o r f o r essentially m e r c a n t i l e p u r p o s e s " .

A m o n g t h e e t h i c a l p r i n c i p i e h e m e n t i o n s as b e i n g p a r t i c u l a r l y
useful, t h e f o l l o w i n g m a y be h i g h l i g h t e d as r e l e v a n t t o Unesco's
r o l e : t h e e s t a b l i s h m e n t o f an a d e q u a t e n u m b e r o f d a t a b a n k s , a
d e t e r m i n a r o n t o ensure that biotechnology, agriculture, research
o n t r o p i c a l diseases, e t c . b e n e f i t f r o m t h e m e t h o d o l o g i c a l and
t e c h n o l o g i c a l s p i n - o f f such r e s e a r c h , t h i s b e i n g o f p a r t i c u l a r i n t e r -
e s t t o t h e T h i r d W o r l d , a n d , finally, r e f l e c t i o n o n c o p y r i g h t a n d
p o s s i b l y r i g h t s o f u t i l i z a t i o n in r e s p e c t o f g e n e t i c d a t a o n h u m a n
beings in o r d e r t o e n s u r e t h a t t h e s e b e c o m e an inalienable i n t e r -
n a t i o n a l h e r i t a g e , as i n d e e d w a s a l r e a d y s u g g e s t e d a t t h e last
Unesco meeting21.

These techniques f o r t h e study o f t h e H u m a n G e n o m e , devised

in t h e c o u n t r i e s o f " t h e N o r t h " , c o n c e r n - i n s o f a r as t h e i r f u t u r e
d e v e l o p m e n t , t h e i r results and t h e i r applications are c o n c e r n e d -
h u m a n k i n d as a w h o l e .

N e v e r t h e l e s s , i t is c l e a r f r o m a p e r u s a l o f t h e m a n y w o r k s t h a t
have a l r e a d y b e e n p u b l i s h e d t h a t o n e o f t h e m a j o r p r i o r i t i e s is t o
establish c o l l a b o r a t i o n w i t h T h i r d W o r l d c o u n t r i e s o n a s o u n d
footing.

T h e f a c t is t h a t scientific I n f o r m a t i o n , a n d a c t i v e p a r t i c i p a t i o n in
highly c o s t l y a n d highly c o m p e t i t i v e r e s e a r c h p r o j e c t s a n d a p p l i -
c a t i o n s , a r e a m a t t e r o f vital c o n c e r n t o t h e p e o p l e o f t h e T h i r d
W o r l d , w h o c o n s t i t u t e t h e g r e a t m a j o r i t y o f h u m a n k i n d . Such
p a r t i c i p a t i o n s h o u l d m a k e it possible b o t h f o r t h e scientists o f
t h e c o u n t r i e s c o n c e r n e d t o be a c t i v e p a r t n e r s in d e v e l o p i n g a n d
e x t e n d i g such k n o w l e d g e and f o r t h e specific needs o f t h o s e
countries t o be fulfilled.

H o w e v e r , if i t is t h e b i o l o g i s t s ' t a s k t o d e c i p h e r " t h e b o o k o f t h e
h u m a n b e i n g " , i t is t h e t h e o l o g i a n s , t h e p h i l o s o p h e r s , t h e j u r i s t s ,
t h e l e g i s t l a t o r s , t h e p o l i t i c i a n s a n d i n d e e d t h e p u b l i c a t large t h a t
| 14 have t h e d u t y o f discussing t h e issues a f f e c t i n g t h i s c o m m o n h e r -
itage.

U n e s c o , t h e interdisciplinary agency o f t h e U n i t e d N a t i o n s for

e d u c a t i o n , s c i e n c e , c u l t u r e a n d c o m m u n i c a t i o n , w h i c h has o v e r
159 M e m b e r S t a t e s t h e m a j o r i t y o f w h i c h a r e i n t h e Third
W o r l d , has r e c e i v e d r e c o m m e n d a t i o n s f r o m t h e scientific c o m -
m u n i t y a i m e d a t p r o m o t i n g a n d f a c i l i t a t i n g all aspects o f i n t e r n a -
tional collaboration relating t o the H u m a n G e n o m e - m e d i c a l ,
t e c h n o l o g i c a l , scientific and e t h i c a l - special p r o m i n e n c e being
g i v e n t o its r o l e in r e l a t i o n t o t h e T h i r d W o r l d 22.

O n t h e basis o f t h e s e r e c o m m e n d a t i o n s , a n d f o l l o w i n g c o n s u l t a -
t i o n s w i t h M e m b e r States a n d a p p r o v a l b y t h e E x e c u t i v e Board
a n d t h e G e n e r a l C o n f e r e n c e o f U n e s c o a t t h e i r last sessions, t h e
H u m a n G e n o m e S e q u e n c i n g P r o g r a m m e w a s i n c l u d e d in M a j o r
P r o g r a m m e A r e a II f o r 1 9 9 0 - 1 9 9 5 . Its a i m is t o p r o m o t e i n t e r n a -
t i o n c o - o p e r a t i o n w i t h t h e national, regional and International
organizations c o n c e r n e d , b o t h g o v e r n m e n t a l and n o - g o v e r n m e n -
t a l , s u c h as I C S U a n d H U G O , a n d t h e r e b y t o facilítate p a r t i c i p a -
t i o n and exchanges b e t w e e n developing and developed c o u n t r i e s .
Finally, a Scientific C o - o r d i n a t i o n C o m m i t t e e , c h a i r e d b y P r o f e s -
s o r Santiago G r i s o l i a , has b e e n s e t u p t o s t e e r U n e s c o ' s a c t i o n in
this field.
 I 15

REFERENCES

11 G r o s , F : Les secreís du gene, Editions O d i l e Jacob, Seuil, Paris,

1986, p.173.

2. S e r r e s , M: Colloque génétique: Procréation et droits. Actes Sud, H.

Nyssen, 1985, p. 23.

3. A l l e n d e , J . E . : The partidpation o f developing countries in the Hu-

mon Genome Project. Presentad at the meeting of the Human Ge-
nome Advisory C o m m i t t e e , Moscow, June 27, 1989.

4. Q u o t e d by F. Gross in Lo civilisation du gene. Hachett, 1989. p. 95.

5. Ibid. D o m i n i q u e Lecour. I n t r o d u c t i o n t o Lo civilisation du gene,

p. 14.

6. M a y o r , F . 'Genetic manipulation and human rights' in Modifizioni

genetiche e diritti dell'uomo. Edited by Guido Gerin. 2 C E D A M , Pa-
dua, 1987, pp. 128-150. See also by the same author 'Gene-etica'
in Etica y medicina. Espasa Calpe, pp. 178-99. 15 EU 1988.

7. Valencia D e c l a r a t i o n on t h e H U M A N G E N O M E PROJECT.
W o r k s h o p o n International C o - o p e r a t i o n f o r the H U M A N GE-
N O M E PROJECT; O c t o b e r 24-26, 1988; Valencia, Spain.

8. K n o p p e r s , B . M. a n d L a b e r g e , G . M., Genetic screening from

newborns to DNA typing, Elsevier, A m s t e r d a m , 1990, pp. 257-277.

9. Council of Europe, Human artificial procréation ( C A H B I ) , Stras-

bourg, 1989, pp. 3-4.

10. Op. cit

11. National Research Council: Mapping and sequencing the human ge-
nome, Washington, National Academy Press, 1988, p. 28. O . T A
Mapping our genes (genome project how big, how fast?). Congress of
t h e United States, 1988. Medical Research Council of Canadá, Dis-
cussion papen Reseorch on gene therapy in humans: background and
guidelines 199, 36 pp.
116 '2. C o n s e i l d ' E t a t : D e l'ethique a u droit, Paris, Documentation
f r a n g a i s e , 1988, p. 8 4 .

R e p o r t of the Commission of Inquiry of the Bundestag of the Fed-

eral Republic of Germany, 'Prospects and risks of gene technol-
ogy', 1987, 2(3): bioethics, 254 pp.

Expert commission on human genetics and r e p r o d u c t i o n medi-

cine. Report t o the Federal Department of the I n t e r i o r and t o the
Justicie and Pólice Department, Berne, Switzerland, August 1988,
p. 97.

13. Q u o t e d by B.M. Knoppers. See Sass, H.M.: 'A critique of the re-
p o r t of the C o m m i s i o n of Inquiruy on Gene Technology (1988-
2(3) 6/oeíh;'cs, p. 264). W a r n o c k , M. ' D o human cells have rights?',
1987 1(1) 6/oeth/cs /.

C o m i t é Consultatif National d'Ethique pour les Sciences de la Vie

et de la Santé, Recherche biomédicale eí respect de la personne hú-
mame, París, 1987.

14. McDougall, quoted by B . M . K n o p p e r s . From: M c D o u g a l l M. S . ,

Laswel and Chen L : Human rights and world public order: the basic
policies o f on International law of human dignity. Newhaven, Yale U n i -
versity Press, 1980, p. 4 1 1 . [Translator's n o t e : t h e e x t r a c t has
been retranslated f r o m t h e French translation, the original n o t
being available.]

15. D e l m a s - M a r t y M. 'Un nouvel usage des droits de l'homme1, Paris,

Actes Sud, 1988, p. 318.

16. K l a u s D e m m e r , 'Le génie génétique et l'homme: implications

éthiques d'un défí nouveau', in Débuts biologiques de la vie humaine:
des chercheurs chrétiens s'interrogent. Catalyses. Ciacco Editeur,
Louvain, 1988. pp. 315-31.

17. J e a n D a u s s e t . ' G é n i e g é n é t i q u e e t t o l é r a n c e ' , C a h i e r s du

M.U.R.S., N o . 5, La Différence, Nécessité biologique et richesse cultu-
relle, pp. 3-8, Paris, 1986.

18. W a t s o n , J . D . I n t r o d u c t o r y lecture at the Symposium on Medici-

ne and Genetic Engineering, in Modification genetiche e diritti dell'uo-
mo, pp. 120-27, op. cit.

19. G r o s , F r a n j é i s : Statement made at the meeting of European m i -

nisters f o r research on bioethics, March 9 and 10, 1990, Kronberg.

20. See aiso Guido Guerin: 'Le legislazioni Europa', in Materia d'ingene-
ria genética e biotechnolocia, pp. 151 -64, op. cit.

Livre Blanc des Recommendations: Patrimoine génétique et droits

de l'humanité. Symposium, Paris, O c t o b e r 25-28, 1989. Editions
Osiris, Paris.

21. Symposium on Human G e n o m e Research: Strategies and Priori-

ties, January 29-3 1, 1990. Unesco, Paris.
22. Recommendations t o the D i r e c t o r - G e n e r a l o f Unesco f r o m the | | /
Consultative G r o u p convened in Moscow, June 26-27, 1989. Scien-
tist's message on the Human G e n o m e Project t o Unesco's Gen-
eral Conference at its twenty-fifth session.
RELIGIOUS
C O N S I D E R A T I O N S
 21

THE CATHOLIC POINT

O F V I E W A N D ITS
ETHICAL IMPLICATIONS

Angelo Serró

I n s t i t u t e o f H u m a n G e n e t i c s , Faculty o f M e d i c i n e " A . G e m e l l i " ,

U.C.S.C., R o m e .

ABSTRACT

The Catholic Church recognizes the voíue o f basic

scientific research and gives great importace to prog-
ress derived form applied research in general a n d
f r o m t h e H u m a n G e n o m e Project in p a r t i c u l a r .
However, the Church is against selective abortion
which it fears will increase once pre-natal diagnosis
facilitates the detection o f a great number o f genetic
disorders. Likewise, it considers g e r m i n a l t h e r a p y
a n d in vitro production o f embroys to be morally
unacceptable. Nevertheless, it accepts genetic ther-
apy in somatic cells a n d supports the approach o f a
predictive medicine designed to safeguard the family
and population, even though it knows that this will
genérate conflicts between the right to freedom o f
cholee on the one hand, and the rights o f other pro-
grammes or communities on the other.
A s a h u m a n g e n e t i c i s t I have e n j o y e d t h e a d v e n t u r e o f f o l l o w i n g , | 23
s t e p by s t e p , t h e r a p i d a n d e x t r a o r d i n a r y d e v e l o p m e n t o f h u m a n
g e n e t i c s , f r o m t h e f o r m a l level u p t o t h e m o l e c u l a r o n e , c u l m i n a t -
ing n o w in t h l s " b i g s c i e n c e " w h l c h is t h e P r o j e c t o f m a p p i n g a n d
s e q u e n c i n g t h e H u m a n G e n o m e . A l l along, It has gradually b e c o m e
c l e a r e r t o m e t h a t e v e r y p r o g r e s s has b e e n a c c o m p a n i e d by n e w
r e s p o n s i b i l i t i e s , d u e t o t h e e m e r g e n c e o f n o v e l e t h l c a l a n d social
i m p l i c a t i o n s . T h i s is e x p e c t e d t o o c c u r a t still h i g h e r r a t e w h e n
t h e H u m a n G e n o m e P r o j e c t w i l l b e c a r r i e d o u t . T h e r e f o r e , all
o f t h e p e o p l e i n v o l v e d in p r o m o t i n g s u c h p r o j e c t , b o t h in t h e
scientific a n d a d m i n i s t r a d v e áreas, r e p e a t e d l y s t r e s s t h e n e e d t o
t a k e i n t o c o n s i d e r a r o n all t h e c o n s e q u e n c e s o f t h e i n e v i t a b l e i n -
c r e a s e o f k n o w l e d g e a n d its r e s u l t a n t p o w e r , as w e l l as o f t h e
many foreseeable applications o f t h e n e w findings.

T h e C a t h o l i c C h u r c h , like all o t h e r r e l i g i o u s g r o u p s , is p a r t i c u -
larly s e n s i t i v e t o t h i s u r g e n c y . She r e c o g n i z e s , a n d highly a p p r e -
ciates t h e i n t r i n s i c v a l u é o f basic s c i e n t i f i c r e s e a r c h , a n d a t t r i -
b u t e s g r e a t i m p o r t a n c e t o a p p l i e d i n v e s t i g a t i o n : i n d e e d , as f a r as
its r e l i g i o u s v i e w o f t h e w o r l d is c o n c e r n e d , t h e y " c o n s t i t u t e a sig-
n i f i c a n t e x p r e s s i o n " o f t h e " d o m i n i ó n o v e r c r e a t i o n " w h i c h is e n -
t r u s t e d b y t h e C r e a t o r t o m a n '. A s t h e s a m e t i m e , h o w e v e r , she
feels i t as h e r essential d u t y t h a t t w o t a s k s be a c c o m p l i s h e d : f l r s t ,
t o e x a m i n e all t h e aspects c o n c e r n i n g h u m a n r e s p o n s i b i l i t y , b o t h
in t h e m a n n e r o f a c q u i r i n g k n o w l e d g e , a n d in t h e applications
t h a t i n e v i t a b l y f o l l o w n e w d i s c o v e h e s ; s e c o n d , t o he!p, t h r o u g h
h e r t e a c h i n g , f i r s t o f all t h e c a t h o l i c s , a n d t h e n all o t h e r s who
w i s h , t o see w h a t s h o u l d b e t h e r i g h t a n d c o n s i s t e n t c o n d u c t in
a c q u i r i n g s c i e n c e as w e l l as a p p l y i n g it. In t h e specific case o f t h e
H u m a n G e n o m e P r o j e c t , t h e c o n c e r n o f t h e C a t h o l i c C h u r c h is
n o t t h e P r o j e c t itself. W e l l a w a r e o f h e r lack o f c o m p e t e n c e in
t h e á r e a o f e x p e r i m e n t a l s c i e n c e s , she t r u s t s t h e e x p e r t s who
can e v a l ú a t e t h e p r o s a n d c o n s o f t h e P r o j e c t , discuss t h e m a n y
p r o b l e m s i n v o l v e d in its e x e c u t i o n f r o m t h e s c i e n t i f i c , p o l i t i c a l
a n d financial s t a n d p o i n t s , a n d d e c i d e a b o u t p r i o r i t i e s 2"5, c o n f i -
d e n t t h a t a great a m o u n t o f n e w and i m p o r t a n t k n o w l e d g e will
be a c q u i r e d f o r t h e g o o d o f m a n k i n d . T h e C h u r c h ' s m a i n c o n -
c e r n is t h e use t h a t can be m a d e o f t h i s k n o w l e d g e . I w i l l b r i e f l y
r e f e r t o t h r e e áreas, t h a t I d e e m o f p a r t i c u l a r i n t e r e s t , w h e r e t h e
n e w findings c o u l d b e a p p l i e d , a n d w i l l o u t l i n e t h e p o s i t i o n o f t h e
Catholic C h u r c h o n s o m e ethical implications. I d o this w i t h sin-
c e r e r e s p e c t t o all o t h e r p o i n t s o f v i e w a n d e t h i c a l p o s i t i o n s ,
w h i c h are expressions o f different cultural o u t l o o k s , and deserve
full c o n s i d e r a r o n 6.

A f i r s t á r e a in w h i c h t h e h i g h - r e s o l u t i o n m a p p i n g o f H u m a n G e -
n o m e ( w h i c h s e e m s t o b e t h e first a n d n e a r e s t t a r g e t o f t h e P r o -
j e c t ) w i l l have i m m e d i a t e e f f e c t is t h a t o f p r e n a t a l diagnosis o f g e -
n e t i c diseases 7"12. O t h e r p a r t i c i p a n t s w i l l deal w i t h t h e s c i e n t i f i c
and technical aspects. I w i l l simply m e n t i o n t h a t t h e n u m b e r of
d e l e t e r i o u s genes f o r w h i c h e i t h e r t h e h o m o z y g o u s o r t h e h e t e r -
o z y g o u s s t a t e c o u l d be d e t e c t e d a t t h e e m b r y o n i c o r fetal stage.
| 24 o r e v e n p r i o r t o i m p l a n t a t i o n in case o f in v i t r o c o n c e p t i o n l3'16,
w i l l g r e a t l y increase, n o t w i t h standing t h e m a n y scientific, t e c h n i c a l
an/d i o g i s t i c a l p r o b l e m s t h a t r e m a i n t o b e s o l v e d . A s a c o n s e -
q u e n c e , in t h e p r e s e n t s t a t e o f k n o w l e d g e , t h e n u m b e r o f cases
in w h i c h t h e c u r r e n t p o l i c y o f s e l e c t i v e p r e n a t a l , o r p r e i m p l a n t a -
t i o n , t e r m i n a t i o n m i g h t be a p p l i e d , is e x p e c t e d t o raise c o n s i d e r -
a b l y . T h i s is, n o t o r i o u s l y , a p o i n t o f e t h i c a l t e n s i ó n l7"18. T h e
p o s i t i o n o f t h e C a t h o l i c C h u r c h is n o t o f a b s o l u t e c o n d e m n a t i o n
o f p r e n a t a l d i a g n o s i s l9. H o w e v e r , a c c o r d i n g t o h e r doctrine,
p r e n a t a l diagnosis is g o o d if " t h e life a n d i n t e g r i t y o f t h e e m b r y o
a n d t h e h u m a n f o e t u s " a r e r e s p e c t e d , a n d i t is " d i r e c t e d t o w a r d s
its s a f e g u a r d i n g a n d healing as an i n d i v i d u a l " . T h i s p o s i t i o n , t h a t is
c l e a r l y c o n t r a r y t o s e l e c t i v e t e r m i n a t i o n o f f e t u s o r e m b r y o , is
based o n t h e f o l l o w i n g p r i n c i p i e t h a t she c o n s i d e r s t o be a
fundamental one: " T h e fruit of human generation f r o m the first
m o m e n t o f its e x i s t e n c e . . . d e m a n d s t h e u n c o n d i t i o n e d respect
t h a t is m o r a l l y d u e t o t h e h u m a n b e i n g in his b o d i l y a n d s p i r i t u a l
t o t a l i t y . . . a n d t h e r e f o r e f r o m t h a t s a m e m o m e n t his r i g h t s as a
p e r s o n m u s t be r e c o g n i z e d , a m o n g w h i c h in t h e f i r s t place is t h e
inviolable right o f every innocent human being t o life". A c c o r d i n g
t o t h i s v i e w p o i n t , t h e " q u a l i t y o f l i f e " is c e r t a i n l y a g r e a t v a l u é ,
t h a t science, m e d i c i n e and society m u s t strive t o i m p r o v e f o r and
in e v e r y h u m a n s u b j e c t ; b u t i t is n o t t h e m a n ' s r i g h t t o establish
a t w h i c h p o i n t in t h e range o f t h e " q u a l i t y o f l i f e " o n e can d i s p o s e
o f an o t h e r m a n ' s " l i f e " .

A s e c o n d á r e a w h e r e p r o g r e s s in t h e k n o w l e d g e o f t h e H u m a n
G e n o m e w i l l o p e n n e w p e r s p e c t i v e s is t h a t o f p r e v e n t i v e m e d i -
c i n e t h r o u g h c a r r i e r s ' d e t e c t i o n a n d p r e v e n t i v e c o u n s e l i n g 20.
A g o o d p a r t o f t h e W o r k s h o p is d e d i c a t e d t o t h i s t o p i c , a n d
c e r t a i n l y t h e g r e a t possibilities, b u t also difficulties and prob-
lems, f o r t h e a c h i e v e m e n t o f t h e s e goals w i l l be p r e s e n t e d and
d i s c u s s e d . I shall o n l y a d d t h a t t h i s l i n e o f a p p r o a c h , a i m e d a t
a v o i d i n g t h e c o n c e p t i o n o f i n d i v i d u a l lives l o a d e d w i t h suf-
f e r a n c e , a n d a t p r e s e r v i n g a n d p r o m o t i n g t h e q u a l i t y o f life o f
families and populations, by reducing t h e b u r d e n of genetic
d i s o r d e r s , is w a r m l y s u p p o r t e d a n d f a v o r e d b y t h e Catholic
C h u r c h . T h e engagement o f science t o discover t h e d e t e r m i n -
ing f a c t o r s o f m a n y d i s r u p t i n g diseases; t h e e n d e a v o r o f m e d i -
cine t o identify and responsibly advise subjects at risk, helping
t h e m in t h e i r d e c i s i ó n ; t h e e f f o r t s o f s o c i e t y t o c r é a t e all t h e
facilities f o r a p r i m a r y p r e v e n t i v e medicine, and f o r t h e indis-
pensable e d u c a t i o n ; and, finally, t h e care o f t h e subjects at risk
t o reach m a t u r e personal cholees, altogether constitute the
s o l i d a r i t y t h a t , in t h e v i e w o f t h e C a t h o l i c C h u r c h , s h o u l d c h a r -
a c t e r i z e a h u m a n e e n t e r p r i s e a n d s h o u l d be t h e e x p r e s s i o n o f
t r u e humanness.

In t h i s l a r g e c o o p e r a t i o n a n u m b e r o f e t h i c a l p r o b l e m s may
a r i s e 2I"23, d u e c h i e f l y t o p o s s i b l e c o n f l i c t s b e t w e e n individual's
right t o f r e e d o m of cholee and privacy, o n one hand, and o t h e r
p e o p l e o r c o m m u n i t y r e q u i r e m e n t s , o n t h e o t h e r , as f o r i n -
s t a n c e in t h e case o f f a m i l y o r , e v e n , p o p u l a t i o n s c r e e n i n g s . N o 125
g e n e r a l s o i u t i o n a p p e a r s t o b e p o s s i b l e . H o w e v e r , in t h e l i g h t o f
t h e basic e t h i c a l p r i n c i p i e s o f t h e C a t h o l i c Church, justice,
equity, respect o f t h e dignity o f any human being, and t r u e love
m u s t all b e t a k e n i n t o c o n s i d e r a t i o n in t h e a t t e m p t t o f i n d a
p r u d e n t a n d w i s e a n s w e r t o e v e r y single p r o b l e m in a n y single
case.

A t h i r d área, w h e r e research w i l l be accelerated by t h e achieve-

m e n t s o f t h e H u m a n G e n o m e P r o j e c t is t h a t o f g e n e t h e r a p y 24"28,
t h a t shall also be e x a m i n e d in o u r W o r k s h o p . In a c c o r d a n c e w i t h
t h e p r i n c i p i e s w h i c h a r e a t t h e basis o f t h e m o r a l i t y o f t h e r a p e u t i c
t r e a t m e n t a n d e x p e r i m e n t a t i o n in h u m a n s , t h e C a t h o l i c Church
p a r t i c i p a t e s in t h e g e n e r a l e t h i c a l c o n s e n s u s n o w r e a c h e d for
s o m a t i c cell g e n e t h e r a p y , t h a t c o u l d even be e x t e n d e d t o e m b r y o s
w i t h d u e r e s p e c t f o r t h e i r life a n d i n t e g r i t y b y a v o i d i n g d i s p r o -
p o r t i o n a t e risks 29. Y e t , t h e f a c t t h a t t h e C a t h o l i c C h u r c h 30 c o n -
s i d e r s t h e p r o d u c t i o n o f h u m a n e m b r y o s in v i t r o , f o r w h i c h e v e r
r e a s o n , t o be a v i o l a t i o n o f h u m a n d i g n i t y , a n d t h e r e f o r e m o r a l l y
illicit, m a k e s any t y p e o f g e r m - c e l l t h e r a p y i n v o l v i n g t h e f e r t i l i z a -
t i o n in v i t r o also e t h i c a l l y u n a c c e p t a b l e .

I have s i m p l y p r o p o s e d t h e e s s e n t i a l t e a c h i n g o f t h e Catholic
C h u r c h c o n c e r n i n g a f e w e t h i c a l aspects i m p l i c a t e d in t h e m e d i -
cal a p p l i c a t i o n o f n e w findings o f g e n e t i c s , w h i c h a r e e x p e c t e d t o
g r o w and expand very rapidly u n d e r t h e p o w e r f u l impulse of t h e
developing Human G e n o m e Project. Undoubtedly, one cannot
avoid t h e impression o f a rigorous and intransigent d o c t r i n e . This
is p r o b a b l y o n e r e a s o n w h y n o t all c a t h o l i c s a g r e e . H o w e v e r , i t is
only honest of m e t o q u o t e a f e w sentences f r o m t h e i n t r o d u c -
t i o n t o a r e c e n t p e r t i n e n t d o c u m e n t , f r o m w h i c h o n e can p e r -
ceive t h e s p i r i t u n d e r l y i n g t h a t d o c t r i n e 3 " T h e C h u r c h ' s Magiste-
rium... having taken account of the data of research and
t e c h n o l o g y , i n t e n d s t o p u t f o r w a r d , by v i r t u e o f its evangelical
mission and apostolic duty, t h e m o r a l teaching c o r r e s p o n d i n g t o
t h e d i g n i t y o f t h e p e r s o n a n d t o his o r h e r i n t e g r a l v o c a t i o n . . .
T h e criteria o f m o r a l judgment... are t h e respect, defense and
p r o m o t i o n o f m a n . T h e C h u r c h ' s i n t e r v e n t i o n in t h i s f i e l d is i n -
s p i r e d also b y t h e l o v e she o w s t h e m a n , h e l p i n g h i m t o r e c o g -
nize a n d r e s p e c t his r i g h t s a n d d u t i e s " .

T o c o n c l u d e : s o m e o f t h e s t a t e m e n t s I have m a d e s o f a r , r e p r e -
senting t h e t r u e teaching of t h e Catholic C h u r c h , probably will
c o n t r i b u t e t o maintain the ethical tensión t h a t permeates the
m o s t advanced f r o n t i e r s of human and medical genetics; a t e n -
s i ó n t h a t c a n b e f e l t as a d i s t u r b i n g f o r c é b y t h o s e w h o a r e e n -
gaged in t h i s f i e l d . H o w e v e r , i t m u s t be r e c o g n i z e d t h a t a g r e a t
deal o f a d v a n c e s in s c i e n c e in g e n e r a l , a n d in m e d i c i n e a n d m e d -
ical g e n e t i c s in p a r t i c u l a r , a l w a y s o c c u r r e d in an atmosphere
o f ethical t e n s i ó n . T h e f u n d a m e n t a l , h i d d e n cause o f this t e n -
s i ó n is, I b e l i e v e , t h e e x i s t i n g , i n e v i t a b l e d i f f e r e n c e in t h e c u l -
tural backgrounds u p o n w h i c h individuáis o r societal groups
26 f o u n d t h e i r ethical principies of behavior. For this v e r y reason
t h e t e n s i ó n w i l l n o t easily s u b s i d e . B u t , p e r h a p s , i t c a n g r a d u a l l y
lessen if w e c o u l d s u c c e e d , as i t h a p p e n s in m o s t f i e l d s o f r e -
search, t o make, o u t of t h e plurality of opinions, a m a t t e r of
c o n s t r u c t i v e , r e c i p r o c a l u n d e r s t a n d i n g , s o t h a t basic a n d a p p l i e d
r e s e a r c h m i g h t h a v e a still s t r o n g e r i m p a c t f o r t h e t r u e well-
being o f mankind.
 127

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244, 1275-1281, 1989.

28. O r k i n , S . H . a n d W i l l i a m s , D . A . Gene therapy of somatic

cells: status and prospects. Progr. Med. Genet, New Series, 7, 130-142,
1988.

29. C o n g r e g a t i o n f o r t h e D o c t r i n e of t h e F a i t h . Cit., p. 15.

30. Ibid., pp. 29-30.

31. ¡bid., p. 6.
 129

ARTIFICIAL REPRODUCTION:
AN ISLAMIC POINT O F V I E W

Azeddine Guessous

M o r o c c a n A m b a s s a d o r t o Spain

ABSTRACT

The position o f ¡síam is to support sc/ence and scien-

tific development by encouraging m a n to acquire
greater knowledge in alí fields. However, based on
the commandments o f the Coran - t h e Sacred Book
o f Laws which governs all activities o f Muslim m e n -
Islamic theologians categorically reject any form o f
artificial reproduction that uses the sperm o f a do-
nar who is not the husband, as ¡ikewise any that
brings about the destruction o f the embryo.
M u s l i m moralists consider t h a t sc/ence has to co-
exist alongside religión a n d ethics a n d believe that
its múltiple applications should be controlled. To be
more precise, they support a moratorium o f genetic
engineering a n d artificial reproduction as applied to
man.
I a m v e r y m u c h h o n o u r e d a n d d e l i g h t e d t o have b e e n i n v i t e d t o |3 I
j o i n in t h i s i m p o r t a n t g a t h e h n g t h e I n t e r n a t i o n a l C o o p e r a t i o n f o r
the H u m a n G e n o m e Project.

T h e r e p u t a t l o n o f t h e "Fundación Valenciana de Estudios Avanza-

d o s " is a l r e a d y w e l l k n o w n a n d w e l l e s t a b l i s h e d a n d o n t h i s
g r o u n d a l o n e , i t is a p r i v i l e g e t o p r e s e n t a p a p e r h e r e .

T h e t h e m e of o u r symposium interrogated every man's cons-

c i e n c e : s c l e n t i t s , physicians a n d b i o l o g i s t s in p a r t i c u l a r , political
m e n a n d p o p u l a t i o n s c o n c e r n e d , ¡t i n t e r r o g a t e s t h e conscience
o f t h e r e l i g i o u s families. N o t b e i n g a f o r m a l delégate o f any m u s l e m
c o m m u n i t y a n d n o t b e i n g a specialist in m u s l e m t h e o l o g y , I shall
l i m i t m y s e l f t o t h e e t h i c a l aspects r e l a t e d t o a r t i f i c i a l h u m a n p r o -
c r e a r o n , seen f r o m t h e p o i n t o f v i e w o f Islam, k n o w i n g t h a t i t
r e p r e s e n t s o n l y an a s p e c t o f t h e v e r y w i d e t h e m e w h i c h is s u b -
m i t t e d in o u r r e f l e x i ó n . B u t i t is a f a c t t h a t islamic s c h o l a r y have
n o t w e l c o m e d a r t i f i c i a l f o r m s o f p r o c r e a t i o n w h i t h a g r e a t deal
o f e n t h u s i a m . W h a t is t h e e x p l a n a t i o n o f t h i s n e g a t i v e a t t i t u d e ?

B u t f i r s t , l e t us s e e t h e i s l a m i c a t t i t u d e t o w a r d s s c i e n c e and
scientific d e v e l o p m e n t

Islam d o e s a c c e p t t h e t h e o l o g i c a l d o c t r i n e o f n a t u r a l law, t h a t t o
say t h e t h e o r y t h a t a f f i r m s t h a t t h e u n i v e r s e a n d , m o r e g e n e r a l l y ,
n a t u r e , is d e s i g n e d b y G o d f o r t h e f u l f i l l m e n t o f specific goals. Is-
lam b e l i e v e s t h a t i n t e l l i g e n c e is e v i d e n t in t h e laws o f n a t u r e a n d
t h a t c r e a t i o n is d e s i g n e d f o r a p u r p o s e . B u t Islam r e j e c t s t h e n o -
t i o n c o n t a i n e d in t h e d o c t r i n e o f n a t u r a l l a w t h a t m a n should
n o t , t h a n k s t o his skill a n d i n t e l l i g e n c e , t r a n s f o r m n a t u r e a n d a c t
u p o n t o in o r d e r t o i m p r o v e h u m a n c o n d i t i o n .

In t h e ñ a m e o f t h i s p r i n c i p i e , o n e c o u l d o p p o s e any i n t r u s i ó n o f
h u m a n k n o w l e d g e in t h e d e t e r m i n a r o n o f t h e living. O n t h e c o n -
t r a r y . Islam, as f r o m t h e b e g i n n i n g , has b e e n in f a v o u r o f a n t i b i -
otics a n d s u r g e r y . Islam is f o r t h e p r o g r e s s o f science t h a t can c u r e
s t e r i l e c o u p l e s , p r e v e n t a n o m a l i e s , fight s p o n t a n e o u s a b o r t i o n o r
the hsks o f p r e m a t u r e d abortions. N e v e r , even at t h e v e r y begin-
ning o f t h e caesarian s u r g e r y . Islam o p p o s e d its p r a c t i c e o n w o m -
e n . Islam e n c o u r a g e s m a n t o s e e k m o r e k n o w l e d g e in all fields
a n d places t h e s c i e n t i f i c in a special level o f d i v i n g c o n s i d e r a t i o n s .
A v e r s e o f t h e C o r a n says " H o w can t h e s e w h o k n o w a n d t h o s e
w h o d o n o t k n o w be equale?".

So Islam d e n l e s t h e n o t i o n o f n a t u r a l l a w w h i c h legislates against

t h e t h w a r t i n g a n d m a n i p u l a t i o n o f n a t u r e . Since Islam e n c o u r a g e s
science a n d scientific d e v e l o p m e n t s a n d since t h e r e can b e n o t
o p p o s i t i o n o n g r o u n d s o f n a t u r a l law, w h y t h i s r e s e r v e t o w a r d s
artificial f o r m s o f p r o c r e a t i o n ?

It has t o b e r e m i n d e d t h a t a l t h o u g h islam i n t e r p r e t a t i o n s a r e n o t
m o n o l i t h i c a n d t h a t w i t h i n Islam t h e r e a r e d i f f e r e n t o p i n i o n s w i t h
I 32 r e g a r d s t o m a n y issues a m o n g s c h o l a r e ( u l é m a u ) , t h i s r e l i g i ó n in
f i r s t a n d a b o v e all a r e l i g i ó n o f l a w . A s s u c h , t h e basic p r i n c i p i e is
t h a t if t h e C o r a n d o e s n o t p r o s c r i b e any a c t as a c o n t r a v e n t i o n
o f d i v i n e p r o h i b i t i o n , t h e n t h e a c t i o n is p e r m i t t e d o r , a t least, n o t
condonnable.

W h a t a r e t h e n t h e g r o u n d s f o r t h e n e g a t i v e a t t i t u d e o f Islam t o -
w a r d s t h e m o s t c r i t i c a ! o f t h e n e w t e c h n i q u e s , t h a t is t o say t h e
in vitro f e r t i l i z a t i o n o f o v u m a n d s p e r m a n d t h e r e p l a c e m e n t o f
t h e e m b r y o t h u s e n g e n d o r e d in t h e u t e r u s o f an otherwise
c h i l d l e s s wife? P a r t o f t h e a n s w e r lies in t h e p r i m a c y o f t h e v a l u é
o f t h e f a m i l y a n d f a m i l y t i e s in islamic c o n c e p t i o n , Islam has a l -
ways had t h e hlghest r e s p e c t and t h e highest c o n s i d e r a t i o n f o r
t h e i n t e g r i t y o f t h e f a m i l y . B u t o n e can p o i n t o u t t h a t t h e p r o -
m o t i o n o f f a m i l y v a l ú e s is o f g r e a t c o n c e r n t o m o r a l i s t s o f v a r -
i o u s r e l i g i o n s t h r o u g h t o u t t h e w o r l d a n d c o n s e q u e n t l y is n o t a
m o n o p o l y o f Islam.

In m a n y v e r s e s o f t h e C o r a n , A d a m Is o r d e r e d t o p r o c r é a t e a n d
t h i s c o m m a n d m e n t is specifically d i r e c t e d t o h i m , t h a t is t o say:
t h e male.

T h e d i v i n e i m p e r a t i v e is c o n s e q u e n t l y a c o m m a n d m e n t t o engage
In sexual a c t i v i t y w i t h i n t h e m a r i t a l f r a m e w o r k w i t h e n o u g h f r e -
q u e n c y u n t i l c h i l d r e n a r e c o n c e i v e d . T h u s , t h e essence o f t h e d i -
v i n e c o m m a n d m e n t is t h e s e x u a l a c t itself a n d t h e o n l y a c t w h l c h
is o r d e r e d is t h e a c t w h i c h is n a t u r a l . T h e o n l y m a n d a t e d f o r m o f
p r o c r e a t i o n is t h a t w h i c h s t e m s d i r e c t l y f r o m sexual u n i ó n .

A s f a r as a r t i f i c i a l f o r m s o f p r o c r e a t i o n a r e c o n c e r n e d , t h e y
m i g h t , a t least in t h e n a r r o w legal sense, b e r e g a r d e d as p e r m i s -
sible unless a v i o l a t i o n o f s o m e s p e c i f i c d i v i n e commandments
is c o m m i t t e d . A n d i t is a f a c t t h a t s o m e f o r m s o f a r t i f i c i a l p r o -
c r e a t i o n d o t r a n s g r e d e t h e limits precisely defined by t h e Holy
Book.

Insemínatíon of a married woman

wíth the sperm of a donor other
than her husband

T h e m a i n r e a s o n t o t h e o p p o s i t i o n o f Islam t o t h i s f o r m o f a r -
tifical p r o c r e a t i o n is n o t t h e t r a n s g r e s s i o n o f m a r i t a l obliga-
t i o n s as t h e r e is n o s e x u a l p r o h i b i t e d i n t e r c o u s e b e t w e e n t h e
d o n o r a n d t h e w o m a n . A n d t h e s e x u a l a c t in all theological
s y s t e m s is d e f i n e d as p e n e t r a t i o n . W h a t m o t i v a t e s Islam p o s -
t u r e is Its c o m m a n d m e n t a g a i n s t a d u l t e r y . A n d t h e prohibition
a g a i n s t a d u l t e r y is b a s e d u p o n t h e n e c e s s i t y t h a t p a t e r n a l i d e n -
t i t y be a b s o l u t e l y c e r t a i n , w i t h o u t t h e least a m b i g u i t y , least
p r o g e n y , u n k n o w i n g l y , have i n c e s t u o u s r e l a t i o n s h i p .
A n d the insemination of a married w o m a n w i t h the semen of a | 33
d o n o r m i g h t lead t o i n c e s t u o u s r e l a t i o n s h i p . T h a t is w h y , a c c o r d -
ing t o t h e o v e r w h e l m i n g m a j o h t y o f Islam t h e o l o g i s t s , t h e u t i l i z a -
t i o n o f t h e semen o f a male o t h e r than t h e husband t o inseml-
n a t e a m a r r i e d w o m a n is p u r é a n d s i m p l e a d u l t e r y . T h a t is w h y
t h i s r e l i g i ó n c a t e g o r i c a l l y r e j e c t s any f o r m o f a r t i f i c i a l p r o c r e a t i o n
w h i c h involves t h e i n t r o d u c t i o n o f semen o t h e r t h a t t h e hus-
band's i n t o t h e g e n i t a l t r a c t o f a m a r r i e d w o m a n .

Destruction of the zygote

T h e in vitro f e r t i l i z a t i o n i m p l i e s a s e c o n d s e r i o u s p r o b l e m w h i c h
d e r i v e s f r o m t h e d e s t r u c t i o n o f a living e m b r y o . A s a m a t t e r o f
fact, e v e r y t i m e an o v u m f e r t i l i z e d w i t h t h e s e m e n o f t h e h u s b a n d
is i m p l a n t e d in t h e u t e r u s o f his w i f e , t h e r e d o e s n o t arise a p r o b -
lem, f r o m the theological point of view. T h e problem arises
w h e n a certain n u m b e r of o v u m are simultaneously fertilized, and
s o m e o f t h e m a r e n o t i m p l a n t e d in t h e m o t h e r ' s u t e r u s . W h a t
w i l l be t h e d e s t i n y o f t h e s e ova? K i l l i n g a life, e v e n t h a t o f a f o e -
t u s , is t o t a l l y p r o h i b i t e d by m u s l e m r e l i g i ó n . T o t a k e s o m e b o d y ' s
life, e v e n t h a t w h i c h m a n has c o n t r i b u t e d t o c r é a t e a n d c o u l d n o t
have e x i s t e d w i t h o u t his skill a n d k n o w l e d g e , is c r i m i n a l .

T h e q u e s t i o n is w h e n d o e s t h e f e r t i l i z e d o v u m begins t o be c o n -
s i d e r e d as a h u m a n being? H e r e , t h e o p i n i o n s d i f f e r a n d w e c o n -
tinué no attend a on-going debate and disagreement a m o n g m o s -
lem scholars.

A s c h o o l o f t h e o l o g i s t headed by Abdallah G u e n n o u n , taking

ground on a versus of the C o r a n which considered that man
bears inside h i m s e l f his p r o g e n y , has g o n e s o f a r as t o a f f i r m t h a t
life is in t h e s e m e n a n d t h e o v a b e f o r e t h e p h e n o m e n o n o f f e r t i -
l i z a t i o n t a k e s place.

A t the other extreme, others consider that the embryo becomes

a h u m a n o r g a n i s m o n l y w h e n i t b e c o m e s visible t o t h e n a k e d e y e
a n d c o n s e q u e n t l y , t h e l a w d o e s n o t g i v e i t a legal recognition
w h e n t h e o r g a n i s m is still s u b - v i s u a l .

T h e difficulties t o i d e n t i f y t h e m o m e n t w h e n t h e h u m a n o r g a n i s m
is f o r m e d , as f r o m t h e m o m e n t o f f e r t i l i z a t i o n , have l e d o t h e r
m o s l e m s c h o l a r s t o r e c o m m e n d t h a t ali f e r t i l i z e d o v a s h o u l d b e
i n t r o d u c e d i n t o t h e w i f e ' s u t e r u s a n d if t h i s is n o t m e d i c a l l y ac-
ceptable f o r reasons related t o the m o t h e r ' s o r the foetus'
h e a l t h , t h e y suggest t o t a k e f r o m t h e w o m a n o n l y t h e n u m b e r o f
o v a t h a n can be safely r e i m p l a n t e d o n c e a r t i f i c i a l l y f e r t i l i z e d .

T h e c o n s e r v a t i v e m o s l e m t h e o l o g i s t s claim f o r t h e e m b r y o , f r o m
t h e t i m e o f c o n e p t i o n , t h e s a m e status a n d t h e r e f o r e t h e same
fight t o p r o t e c t i o n as in d u e t o all h u m a n beings t h r o u g h o u t life.
I 34 T h e y , t h e r e f o r e , absolutely p r o h i b i t t h e taking o f " i n n o c e n t " e m b r y o s
life, n o m a t t e r w h a t t h e e s t i m a t e d b e n e f i t e i t h e r t o a t h i r d p a r t y o r
t o medical p r o g r e s s in g e n e r a l . Because o f its genetic p o t e n t i a l t o
b e c o m e a h u m a n being o r a h u m a n p e r s o n , t h e e m b r y o m u s t be
t r e a t e d as t h o u g h i t actually w a r e o n e f r o m t h e beglnning.

A n o t h e r f u n d a m e n t a l m o t i v a t i o n t h a t s u p p o r t s t h e r e s e r v e o f Islam
w i t h r e g a r d t o in vitro f e r t i l i z a t l o n a n d o t h e r f o r m s o f p r o c r e a t i o n
e x p e r i m e n t s is t h e p r i n c i p i e t h a t o r d e r us " t o d o n o h a r m " .

M a n is n o t m o r a l l y e n t l t l e d t o c r é a t e life in o r d e r t o Inflict h a r m
o r i n j u r y u p o n t h e b e a r e r o f t h a t Ufe. F o r Islam, all e x p e r i m e n t a -
r o n u p o n u n b o r n f o e t u s e s is i m m o r a l a n d u n e t h i c a l .

Such e x p e r i m e n t a t i o n is u n e t h i c a l because i t is i m p o s s i b l e t o p r e -
d i c t w h e t h e r i t w l l l r e s u l t in t h e b i r t h o f a d e f e c t i v e c h i l d w h o ,
o t h e r w i s e , w o u l d n o t have b e e n b o r n . Life s h o u l d n o t be a r t i f i -
cially g e n e r a t e d w h e n s u c h g e n e r a t i o n c a r r i e s w i t h i t t h e r i s k o f
s u f f e r i n g o r pain.

D a t e r e l a t i v e t o t h e c o n g e n i t a l d e f e c t s in t h e t h o u s a n d s o f b i r t h s
w h i c h r e s u l t e d f r o m in vitro f e r t l l l z a t i o n a r e n o t available a n d l i t t l e
I n f o r m a t i o n a b o u t i t has b e e n p u b l i s h e d in m e d i c a l l i t e r a t u r e .

B u t i t s e e m s r e a s o n a b l e t o t h i n k t h a t , a t least in t h e f l r s t p e r l o d
o f t h e use o f in vitro f e r t l l l z a t i o n , t h e b i r t h o f d e f e c t i v e c h i l d r e n
h a d t o be a n t i c i p a t e d .

T h e s i m p l e physical m a n i p u l a t i o n o f t h e o v u m a n d t h e z y g o t e a n d
t h e r e i n s e r t i o n o f t h e d e v e l o p i n g e m b r y o in t h e m o t h e r ' s u t e r u s
c o u l d have r e s u l t e d in g e n e t i c a c c i d e n t s . O n t h e o t h e r h a n d , f o r
m o s l e m scholars, t h e fact t h a t t h e fertilized o v u m remained, even
f o r a l i m l t e d t i m e , o u t s i d e t h e u t e r u s c o u l d have p r e v e n t e d t h e
i n t e r v e n t i o n o f m e c h a n i s m s e m p l o y e d by n a t u r e , specially a t t h e
e a r l y stages o f g e s t a t i o n w h i c h a r e a i m e d a t e l i m i n a t i n g d e f e c t i v e
foetuses.

D e f e c t i v e c h i l d r e n m i g h t have b e e n b o r n . T h e y w o u l d n o t have
b e e n if a r t i f i c i a l t e c h n i q u e s h a d n o t i n t e r f e r e d w i t h t h e n a t u r a l
process of gestation.

A s a m a t t e r o f f a c t , t h e h i s t o r y o f m e d i c a l d e v e l o p m e n t is full o f
e x a m p l e s o f u n e t h i c a l acts w h i c h , l a t e r , have led t o substancial
b e n e f i t s f o r m e n a n d , m o s t p r o b a b l y , t h i s w l l l also be t h e case f o r
a r t i f i c i a l p r o c r e a t i o n . B u t w h a t m a k e s t h e in vitro f e r t l l l z a t i o n m a -
n i p u l a t i o n s s u s p i c i o u s t o e t h i c s is t h a t t h e y a r e a p p l i e d t o the
v e r y c r e a t l o n o f h u m a n life a n d t h a t any e r r o r can r e s u l t in i r r e -
versible damage t o t h e foetus.

Because o f t h e s h o r t t i m e t h a t is a l l o w e d t o m e , I c a n n o t t a c k l e
o t h e r aspects o f c e r t a i n f o r m s o f artificial p r o c r e a t i o n w h i c h m o -
t í v a t e t h e n e g a t i v e a t t i t u d e o f Islam, such as:
 T h e i m p a c t u p o n t h e c h i l d w h e n he learns t h e t e c h n i q u e used | 35
in g e n é r a t e h i m o r o n c e he learns he is n o t t h e b i o l o g i c a l s o n
o f his p a r e n t s .

T h e f a c t t h a t in vitro f e r t i l i z a t i o n s e e m s t o r e s u l t in t h e p r e -
p o n d e r a n t e o f female births o v e r male births.

T h e p o s s i b i l i t y , in t h e f u t u r e , t o p r e - s e l e c t t h e c h i l d ' s sex o r a
s p e c i f i c g e n e t i c c h a r a c t e r . T h e s e a r e áreas in w h i c h legisla-
t i o n s have t o b e p r o m u l g a t e d in o r d e r t o a v o i d social evils
t h a t might t h r e a t e n t h e structures o f o u r societies.

Conclusión

F o r m o s l e m m o r a l i s t s , s c i e n c e w i t h its m ú l t i p l e applications
s h o u l d n o t e be l e f t t o itself. A s t h e w a t e r o f t h e t o r r e n t that
goes d o w n f o r t h e m o u n t a i n , i t can r u i n a n d d e a t h , i t has t o be
canalized a n d o r i e n t e d t o w a r d s specific o b j e c t i v e s .

T h e genetic engeneering and t h e v e r y techniques o f artificial fer-

t i l i z a t i o n , if a p p l i e d t o a g r i c u l t u r e a n d b r e e d i n g a n d p u t a t t h e
service o f a w o r l d - w i d e d e v e l o p m e n t , instead o f being t h e m o n o -
poly of a f e w countries, could c o n t r i b u t e t o better the condition
at " a l l m e n a n d all t h e m a n " , as said H i s H o l i n e u s Paul V I .

T h e m o s l e m t h e o l o g i s t s c o n s i d e r t h a t s c i e n c e has t o g o o n b e i n g ,
a l o n g w i t h r e l i g i ó n a n d e t h i c s , a basic f a c t o r o f p r o g r e s s a n d u n i -
v e r s a l peace, b e t w e e n m e n in all c o n t i n e n t s , w h o d o n o t n e e d
a d d i t i o n a l ¡nequalities, y e t n e e d , o n t h e c o n t r a r y , a d e e p e r a n d
m o r e visible s o l i d a r i t y .

T h e y j o i n t h e i r v o l e e s t o t h a t o f t h o s e a d v ó c a t e a m o r a t o r y in
t h e fleld o f genetic engeneering and artificial p r o c r e a t i o n applied
t o m a n . T h i s i n v i t a t i o n , a l t h o u g h o n l y e x p r e s s e d , is a sign o f w i s -
d o m w h i c h d e s e r v e s t o b e s c r u t i n i z e d a t least as c a r e f u l l y a n d
w i t h t h e s a m e p r e o e c u p a t i o n as t h e p r o d u c t i o n a n d e x p e r i m e n -
t a r o n o f nuclear arms.

A s said t h e p r o f e s s o r T e s t a r t , p i o n e e r in t h e IVF, a m o r a t o r y in
t h e i n v e s t i g a t i o n in h u m a n "in vitro f e r t i l i z a t i o n " is n e c e s s a r y b e -
cause i t c a r r i e s t h e r i s k t o lead t o a radical change o f t h e h u m a n
person.

O n e s h o u l d n o t f o r g e t t h e c e n t e r s o f c o n s e r v a t i o n called " e m -
bryos' bank" certain o r will contain a great number of potential
h u m a n beings, a w h o l e p o p u l a t i o n in e x p e c t a t i o n o f life. It s h o u l d
n o t be a l l o w e d , u n d e r a n y p r e t e x t , t o have h u m a n i t y s t o r e d in
diplicate, t o m a k e h u m a n r e s e r v e s t h a t can be used f o r God
K n o w s w h i c h p u r p o s e s . T h i s s h o u l d i n d u c e us, w h a t e v e r t h e r e l i -
g i ó n w e b e l o n g t o , t o a d v ó c a t e t h e p r o m u l g a t i o n o f a specific leg-
| 36 i s l a t i o n . Possibilities e x i s t in a s h o r t f u t u r e t o m u l t i p l y i d e n t i c a l l y
t h e s a m e i n d i v i d u a l (and t h i s is called c l o n i n g ) t o c r é a t e n e w e s p e -
cies a n d p r e d e t e r m i n e i n d i v i d u á i s ( a n d t h i s is g e n e t i c m a n i p u l a -
t i o n ) . W h o c a n n o t see t h a t i t is a b s o l u t e l y necessary, if w e w i s h
t o p r e s e r v e m a n in his s i n g u l a r i t y , t o s e t u p b a r r i e r s against t h e s e
g r e a t d a n g e r s . T h e law, h e r e , s h o u l d play fully t h e p r o t e c t i v e r o l e
i t is m a d e f o r .
 137

ETHICAL ATTITUDES OF A
JEWISH SCIENTIST W I T H
REGARD T O GENETIC
INTERVENTION

Haim Aviv

President o f t h e A v i v Investment C o m p a n y and Associates,

and of t h e Pharmos C o m p a n y

ABSTRACT

Knowledge o f the h u m a n genome and the possibility

that this information be used to modify h u m a n ge-
netics pose certain ethical problems. The fact that
creation is not perfect opens the door to m a n to in-
tervene with the aim o f perfecting, but never h a r m -
ing i t ¡ f God created one so/e m a n in His own image
and likeness, the concept o f geneticaüy inferior races
is irrational. In this sense, knowledge o f the human
g e n o m e w i l l clearíy show the equaiity o f h u m a n
beings.
As far as genetic therapy is concerned, its applica-
tion to somatic cells is no different to other thera-
pies. However, the genetic intervention o f germinal
cells requires a somewhat more complex analysis.
L e t m e s t a r t by t e l l i n g y o u t h a t I a m n o t in any w a y a r a b b i o r | 39
t h e o l o g i a n . I have a l o n g i n t e r e s t in J e w i s h s t u d i e s a n d t r a d i t i o n .
T h e f o l l o w i n g a r e m y p e r s o n a l t h o u g h t s o n t h e s u b j e c t as a J e w -
ish s c i e n t i s t . T h e y a r e based o n m y u n d e r s t a n d i n g a n d i n t e r p r e t a -
r o n o f Jewish t r a d i t i o n and philosophy. T o s o m e e x t e n t t h e y are
also based o n c e r t a i n legal d i s c u s s i o n s . T h e s e t h o u g h t s d o not,
h o w e v e r , c o n s t i t u t e a f o r m a l legal o p i n i ó n o n J e w i s h l a w ( " H a l a -
c h a " ) . L e t m e also a d d t h a t in t h e g o o d t r a d i t i o n o f J e w i s h c u l -
t u r e , o n e can find o p i n i o n s w h i c h a r e d i f f e r e n t f r o m m i n e , b u t I b e -
lieve t h a t t h e s e r e m a r k s t h a t I a m g o i n g t o s h a r e w i t h y o u a r e in
line w i t h J e w i s h t r a d i t i o n a n d p h i l o s o p h y . W i t h g r e a t r e l u c t a n c e
and hesitance did I u n d e r t a k e t o share these r e m a r k s w i t h y o u .

L e t m e o u t l i n e t h e p r o b l e m s a n d issues t h a t I a m g o i n g t o d i s -
cuss: D e t a i l e d k n o w l e d g e o f t h e H u m a n G e n o m e a n d t h e t e c h -
niques a n d p o s s i b i l i t i e s o f using t h i s I n f o r m a t i o n t o i n t e r v e n e g e -
n e t i c a l l y in t h e h u m a n g e n e t i c m a k e - u p p r e s e n t a t l e a s t t h r e e
main ethical/theological p r o b l e m s :

1. K n o w i n g t h e detailed H u m a n G e n o m e , may reveal I n f o r m a -

t i o n t h a t s u p p o r t s t h e n o t i o n t h a t c e r t a i n races a r e g e n e t i -
cally i n f e r i o r t o o t h e r s , t h u s causing racial d i s c r i m i n a t i o n .

2. G e n e t i c i n t e r v e n t i o n in " G o d ' s C r e a t i o n " is an a r r o g a n t h u -

m a n act. U s i n g g e n e t h e r a p y is " p l a y i n g G o d " a n d s h o u l d n o t
be practiced.

3. T h e t e c h n i q u e s o f g e n e t i c m a n i p u l a t i o n can potentially be m i s -
used t o h a r m and t o damage c r e a t i o n . They, therefore,
s h o u l d n o t b e d e v e l o p e d a t all.

I w i l l discuss t h e s e issues f i r s t o n a p h i l o s o p h i c a l level, a n d t h e n

o n a s o m e w h a t m o r e legalistic l e v e l .

Philosophical approach

T h e J e w i s h a t t i t u d e is t h a t M a n plays a c e n t r a l r o l e in t h e w o r l d .
M a n is t h e " c r o w n " o f c r e a t i o n . A s t h e b o o k o f G é n e s i s p u t s i t :
M a n w a s c r e a t e d in G o d ' s i m a g e . F u r t h e r m o r e , w i t h o u t Man,
G o d ' s k i n g d o m in t h e u n i v e r s e is l i m i t e d . M a n is an important
partner t o G o d . M a n y J e w i s h p h i l o s o p h e r s s h a r e t h e o p i n i ó n t h a t
c r e a t i o n is, in fact, n o t p e r f e c t . T h i s is a v e r y i n t e r e s t i n g c o n c e p t .
T h e A l m i g h t y has left t h i n g s f o r M a n t o c o m p l e t e , p e r h a p s p u r -
posely.

T h i s places v e r y i m p o r t a n t r e s p o n s i b i l i t i e s o n M a n . M a n s h o u l d
be a r e s p o n s i b l e p a r t n e r a n d b e h a v e a c c o r d i n g l y . In m y o p i n i ó n ,
t h e r e is n o t h i n g w r o n g w i t h " p l a y i n g G o d " if i t m e a n s i m p r o v i n g
C r e a t i o n a n d if i t is d o n e in a r e s p o n s i b l e w a y as a g o o d p a r t n e r .
40 M a n has t o w o r k as a p a r t n e r w i t h t h e A l m i g h t y in o r d e r to
p e r f e c t H i s c r e a t i o n a n d t o a v o i d c a u s i n g i t h a r m . A s M a n is
c e n t r a l , s o is his life, his h e a l t h , his w e l l - b e i n g , a n d d i g n i t y . Sav-
ing h u m a n life is o n e o f t h e h i g h e s t p r i o r i t i e s in J e w i s h l a w , s u -
perceding m o s t o t h e r laws. Healing and reducing human suf-
fering are c o n s i d e r e d means of helping and caring f o r God's
i m a g e . R a b b i M o s h e , t h e s o n o f M a i m ó n k n o w n as M a i m o n i d e s ,
t h e great Jewish scholar, philosopher and physician, w h o was
b o r n in C o r d o v a ( I I 3 5 A C ) a n d l a t e r f l e d w i t h his f a m i l y f r o m
Spain, w r o t e 8 0 0 y e a r s a g o : " A h e a l t h y b o d y in G o d ' s w i l l , b e -
cause o n e c a n n o t k n o w a n d u n d e r s t a n d G o d if o n e is sick. T h e r e -
fore, one should avoid things w h i c h are harmful t o the body
and should behave and d o things w h i c h p r o m o t e well-being and
good health".

J e w i s h p h i l o s o p h y d o e s n o t a s s u m e an " O r i g i n a l S i n " t h a t n e e d s
t o be dealt w i t h . W e b e l i e v e t h a t M a n can p o t e n t i a l l y b e v e r y
e l e v a t e d a n d c i ó s e t o G o d . " A n d Y o u have m a d e M a n a little l o w -
e r t h a n G o d " (Psalms). T h e Kabalistic Messianic c o n c e p t is t h a t
a t t h e e n d o f t i m e . M a n w i l l a c h i e v e a high m o r a l s t a t u s . C r e a t i o n
has a p o s i t i v e d i r e c t i o n . M a n , t h r o u g h his b e h a v i o u r , has e n o r -
m o u s p o w e r t o a c c e l e r a t e t h i s p r o c e s s . T h i s is a v e r y positive
a n d optimistic a p p r o a c h . I m a y g o as f a r as saying t h a t using m o d -
e r n genetics t o b e t t e r u n d e r s t a n d C r e a t i o n and t o i m p r o v e C r e -
a t i o n is w h a t t h e A l m i g h t y e x p e c t s f r o m us.

Specífíc ¡ssues addressed

/. Genetic Information

A s t h e w o r l d is G o d ' s c r e a t i o n , k n o w i n g c r e a t i o n is a w a y of
k n o w i n g G o d and perhaps b e t t e r appreciating H i m . K n o w l e d g e
o f c r e a t i o n is, t h e r e f o r e , h i g h l y d e s i r a b l e . T h e c o n c e p t o f genet-
/co//y " i n f e r i o r " r a c e s is o b v i o u s l y i m p r o p e r a n d u n r e a s o n a b l e .
T h e b o o k o f G é n e s i s t e l l s us t h a t G o d c r e a t e d o n l y o n e man
( A d a m ) . Jewish c o m m e n t a t o r s asked: W h y did G o d créate only
one m a n ? In o r d e r t o t e a c h us t h a t a l l m a n k i n d is e q u a l .
M a i m o n i d e s w r o t e t h e f o l l o w i n g : "... A n d A d a m w a s , t h e r e f o r e ,
c r e a t e d a l o n e in t h e w o r l d , t o t e a c h t h a t e n d i n g a s i n g l e life is
l i k e e n d i n g a w h o l e w o r l d , w h e r e a s s a v i n g a s i n g l e life is l i k e
s a v i n g a w h o l e w o r l d . . . a n d e v e r y p e r s o n c a n , t h e r e f o r e , say
and feel t h a t t h e w o r l d was created f o r himself." A c c o r d i n g t o
G é n e s i s , Eve w a s a s o m a t i c c l o n e , n o t e v e n a d i f f e r e n t g e n e t i c
organism.

I p r e d i c t t h a n o n c e t h e H u m a n G e n o m e is c o m p l e t e l y k n o w n , i t
w i l l s h o w h o w r e m a r k a b l y equal h u m a n beings a r e a n d t h e r e w i l l
n o t b e a scientific basis f o r r a c i s m based o n i n t e l l e c t u a l o r b e h a v -
ioral genetic differences.
2. Gene Therapy 141

T w o aspects o f g e n e t h e r a p y w i l l be d i s c u s s e d , s o m a t i c t h e r a p y
and g e r m line t h e r a p y .

a) Somatic T h e r a p y

In m y o p i n i ó n , t h i s is in essence n o t d i f f e r e n t f r o m any o t h e r t h e r -
apy, i t is v e r y p o s i t i v e a n d desirable. T h i s is j u s t a long-lasting t h e r -
apy. U v e v a c c i n a t j o n is also a l o n g - l a s t i n g t h e r a p y . H e a l i n g sick-
ness can b e a life-saving a c t a n d is, t h e r e f o r e , l o n g lasting. E l i m i -
n a t i o n o f s u f f e r i n g is g r e a t l y d e s i r a b l e . A l t h o u g h sickness a n d suf-
f e r i n g can a l s o b e v i e w e d as a p u n i s h i n g signal f r o m G o d , m a n
s h o u l d n e v e r t h e l e s s d o e v e r y t h i n g he can t o r e d u c e h u m a n suf-
f e r i n g and t o p r e s e r v e h u m a n life. P r e s e r v a t i o n o f life, saving
G o d ' s i m a g e , is o n e o f t h e m o s t i m p o r t a n t c o m m a n d m e n t s a n d
s u p e r c e d e s a l m o s t all o t h e r c o m m a n d m e n t s . M a i m o n i d e s w r o t e :
" I f o n e b e c o m e s s i c k a n d m a y d i e , a n d t h e physicians say t h a t his
r e c o v e r y r e q u i r e s d o i n g s o m e t h i n g w h i c h is f o r b i d d e n b y t h e
laws o f t h e T o r a h , w e a r e p e r m i t t e d t o d o e v e r y t h i n g , i n c l u d i n g
t h a t w h i c h is usually f o r b i d d e n , e x c e p t f o r t h r e e t h i n g s ( o n e o f
w h i c h is k i l l i n g a n o t h e r p e r s o n ) .

A s in a n y o t h e r f o r m o f t h e r a p y , t h e p r o p o r t i o n b e t w e e n b e n -
efit and r i s k s h o u l d be e v a l u a t e d . N o o b v i o u s h a r m s h o u l d be
done, of course. T h e Jewish approach is t o evalúate the
r i s k / b e n e f i t r a t i o v i s - a - v i s t h e i n d i v i d u a l p a t i e n t , n o t in g e n e r a l i -
t i e s . T h e p h y s i c i a n has r e s p o n s i b i l i t i e s t o w a r d s t h e individual
p a t i e n t in q u e s t i o n . T h e r e is less c o n c e r n in t e r m s o f " p o t e n -
t i a l " h a r m . W h e n i m m e d i a t e h e l p t o an i n d i v i d u a l is c o n t r a s t e d
w i t h potential l o n g - t e r m damage, immediate help, particularly
t h a t w h i c h p r e s e r v e s life, t a k e s p r i o r i t y a c c o r d i n g t o Jewish
law.

b) G e r m line i n t e r v e n t i o n

T h i s m a y b e p e r h a p s a m o r e c o m p l e x issue. T h i s is a v e r y l o n g
lasting t h e r a p y w h i c h w i l l i n f l u e n c e g e n e r a t i o n s t o c o m e .

I b e l i e v e t h a t , in m a n y w a y s , t h i s is also n o t t o o d i f f e r e n t in es-
sence f r o m o t h e r t h e r a p e u t i c a p p r o a c h e s t h a t w e a r e t a k i n g .

T r e a t i n g i n f e r t i l i t y p r o b l e m s , f o r e x a m p l e , is a l o n g - l a s t i n g i n t e r -
v e n t i o n w h i c h w i l l g r e a t l y i n f l u e n c e g e n e r a t i o n s t o c o m e . Life sav-
ing can have l o n g - l a s t i n g effects in g e n e r a t i o n s t o c o m e .

O n a m o r e t e c h n i c a l / l e g a l level, t h e m a n i p u l a t i o n o f e m b r y o n i c
cells a n d e m b r y o s m a y p r e s e n t p r o b l e m s b y e n d a n g e r i n g t h e
"life" o f t h e i m m e d i a t e , individual e m b r y o .
42 T h e J e w i s h a p p r o a c h d o e s n o t d e f i n e t h e e m b r y o as a l i v i n g i n d i -
v i d u a l d u r i n g t h e f i r s t m o n t h ( o r 4 0 days) o f g e s t a t i o n - i t is a
special t i s s u e . T h e r e f o r e , a c c o r d i n g t o J e w i s h l a w , t h i s is n o t a
m a j o r o b s t a c l e t o g e n e t i c m a n i p u l a t i o n . In fact, u p t o t h e mo-
m e n t o f b i r t h , t h e e m b r y o is n o t legally d e f l n e d in t h e s a m e w a y
as a l i v i n g h u m a n b e i n g in t h e c o n t e x t o f m u r d e r , f o r e x a m p l e . I
must, h o w e v e r , emphasize t h a t a c c o r d i n g t o Halacha, t e r m i n a t -
ing pregnancy w i t h o u t a g o o d reason should n o t be a n o r m a l
p r a c t i c e . O n t h e o t h e r h a n d , i t is n o t c o n s i d e r e d m u r d e r f o r l e -
gal p u r p o s e s .

T h e v i e w , held by s o m e , t h a t w e should n o t even develop t h e

t e c h n o l o g y o f g e n e m a n i p u l a t i o n because t h i s t e c h n o l o g y m a y b e
e x p l o i t e d a n d m i s u s e d in t h e f u t u r e is v e r y pessimistic a n d is n o t
c o n s i s t e n t w i t h o u r a t t i t u d e a n d basic t r u s t in M a n . W e assume
t h a t M a n is o r i g i n a l l y g o o d , a n d t h a t he c a n , a n d w i l l be, e v e n b e t -
t e r . O f c o u r s e , w e have t o w a t c h a n d s e t up r u l e s a n d f e n c e s
t o avoid t h e misuse o f knowiedge. T h e v e r y fact t h a t meetings
such as t h i s t a k e place raises c o n s c i o u s n e s s a n d a w a r e n e s s o f t h e
problems.

T e c h n o l o g y , in p r i n c i p i e , is n e u t r a l . T h e way in w h i c h t e c h n o l o g y
is u s e d b y M a n d e t e r m i n e s w h e t h e r o r n o t i t is g o o d o r evil.
Rabbi M o s h e , t h e s o n o f N a c h m a n ( N a c h m a n i d e s ) ( I 1 9 4 - 1 2 7 0 ) ,
a n o t h e r s c h o l a r a n d p h y s i c i a n w h o lived in G e r o n a a n d also f l e d
f r o m Spain 7 5 0 y e a r s ago, c o m m e n t e d in his i n t e r p r e t a r o n o f t h e
b o o k o f G é n e s i s (in r e l a t i o n t o L e m e c h , p r e s u m a b l y t h e i n v e n t o r
o f m e t a l l u r g y ) t h a t b u i l d i n g s w o r d s is n o t a sin b u t k i l l i n g is a sin.

Interestingly, N a c h m a n i d e s also w r o t e t h a t a physician who

k n o w s t o heal is o b l i g e d t o heal, a n d if he a v o i d s d o i n g so, he w i l l
be v i e w e d as s h e d d i n g b l o o d . D r a w i n g t h i s s t a t e m e n t t o a logical
c o n c l u s i ó n , i t m e a n s t h a t if a physician k n o w s h o w t o c u r e a d i s -
ease b y g e n e t i c m e a n s , he has an o b l i g a t i o n t o d o so w i t h o u t any
delays.

In c o n c l u s i ó n , t h e challenge is t o g u i d e a n d t e a c h o u r c o m m u n i -
t i e s a n d i n d e e d all m a n k i n d t o b e r e s p o n s i b l e a n d t o a d h e r e t o
m o r a l valúes in g e n e r a l . W e h o p e t h a t o u r basic o p t i m i s m a n d
b e l i e f in M a n , w h o is c r e a t e d in G o d ' s i m a g e , w i l l b e j u s t i f i e d .
Being c r e a t e d in G o d ' s image is a g r e a t h o n o u r b u t also c a r r i e s
w i t h i t t h e u t m o s t r e s p o n s i b i l i t y . T h e Kabala w h i c h f l o u r i s h e d in
Spain 5 0 0 - 6 0 0 y e a r s ago d e v e l o p e d t h e c o n c e p t t h a t Hochma,
W i s d o m , K n o w i e d g e a n d P r o g r e s s , have t o g o h a n d in h a n d a n d
be c o m b i n e d w i t h H e s e d , M e r c y , in t h e sense o f h e l p i n g p e o p l e .
If t h i s f a n t a s t i c k n o w i e d g e a n d w i s d o m t h a t is c u r r e n t l y e v o l v i n g
is n o t u s e d t o c u r e diseases a n d e l i m í n a t e s u f f e r i n g , i t w i l l b e an
i m b a l a n c e d k n o w i e d g e a n d w i l l n o t f u l f i l l its m e r c i f u l aspect.
H o w e v e r , I m a y a d d t h a t in t h i s p r o c e s s o f " p l a y i n g G o d " , w e
s h o u l d n o t lose p e r s p e c t i v e a n d s h o u l d b e h u m b l e a n d s e n s i t i v e
t o h u m a n life and h u m a n dignity. W e s h o u l d w o r k t o w a r d i m p r o v i n g
creation rather than damaging creation.
I w o u l d like t o finish w i t h a little tale f r o m t h e Midrash: W h e n 143
G o d c r e a t e d M a n , h e s h o w e d h i m all t h e t r e e s in t h e C a r d e n o f
Edén a n d said t o h i m , " S e e h o w b e a u t i f u l a n d e x c e l l e n t t h e y a r e .
Be c a r e f u l n o t t o d a m a g e o r d e s t r o y m y w o r l d , because if y o u
d a m a g e t h i s w o r l d , t h e r e w l l l be n o b o d y else t o f i x i t a f t e r y o u " .
 45

PROTESTANTISM
AND T H E HUMAN
CENOME PROJECT

jack L Stoíts

Austin Presbyterin Theological Seminary, Austin, Texas (USA)

ABSTRACT

"Genetic Science in the benefit o f M a n k i n d " a n d

"Biotechnology: its challenges to the Churches a n d
the W o r l d " are two documents published respec-
tively by the N a t i o n a l Council o f the Churches o f
Christ o f the United States and by the W o r l d Council
o f Ecclesiastical Sub-unities. Both reports consider
ethical a n d legal aspects derived f r o m projects on
human genetics, such as the one concerning the hu-
man genome. The latter o f these considers matters
such as the prohibition o f cholee o f sex or warnings
on possible social discrimination which knowledge o f
the human genome m a y give rise to, amongst oth-
ers. Protestont/sm holds that h u m a n Ufe is sacred. At
o given moment, this Protestant dogma could restrict
scientific research. However, the H u m a n Genome
Project, as a source o f knowledge, does not in princi-
pie viólate the sacred aspect o f Ufe; on the contrary,
it may contribute to health.
P r o t e s t a n t i s m is v e r y m u c h l i k e a s p e e c h I o n c e gave. S o m e o n e 147
g r a c i o u s l y c h a r a c t e r i z e d t h a t s p e e c h a t h i r t e e n p o i n t s in s e a r c h
o f an o u t l i n e . E x c e p t P r o t e s t a n t i s m is w o r s e . It defies r e s t r i c t e d
by any o u t l i n e . It is b y its n a t u r e an e x p l o d i n g star, n o t a p o l a r
m a g n e t . O r , t o c h a n g e t h e i m a g e , i t is always b i r t h i n g n e w social
and religious m o v e m e n t s .

It is t h i s m u l t i p l i c i t y t h a t m a k e s d e f i n i n g P r o t e s t a n t i s m a n d P r o t -
e s t a n t i s m o p e r s p e c t i v e o n any issue a l i t t l e like t r y i n g t o nail a
pudding t o the wall.

Y e t b r a v e r a n d w i s e r p e r s o n s t h a n I have t r i e d . T h e y have s o u g h t
f o r c e n t r a l , u n d e r l y i n g p r i n c i p i e s . T h e y have s e a r c h e d f o r u n i f y i n g
p o i n t s . O n e such t h i n k e r w a s t h e late Paul T i l l i c h , a t h e o l o g i a n
b o r n in G e r m a n y w h o i m m i g r a t e d t o t h e U.S.A. in t h e I 9 3 0 ' s . T i l -
lich c h a r a c t e r i z e d P r o t e s t a n t i s m in t h i s w a y : " W h a t m a k e s Prot-
estantism Protestant is the fact t h a t is transcends its own religious a n d
confessional character, t h a t it c a n n o t be i d e n t i f i e d wholly w i t h any
o f its particular historical f o r m s . " ( T h a t m a k e s an asset o u t o f a lia
b i l i t y ) H e c o n t i n ú e s , " T h e Protestant principie, in ñ a m e derived f r o m
the protest o f the 'protestant' [ o f the l ó t h century] against decisions
o f the Catholic majority, contains the divine a n d h u m a n protest against
any absolute claim m a d e for a relative reality, even i f this claim is m o -
da by a Prostestant c h u r c h . " ( T i l l i c h , p p . 162, 163).

T i l l i c h ' s d e s c r i p t i v e a n d n o r m a t i v e p e r s p e c t i v e is t h i s : the P r o t e s -
t a n t p r i n c i p i e is t h e refusal o f a n d t h e r e j e c t i o n o f any a t t e m p t t o ,
absolutize t h e relative. T h a t negative assertion rests, o f course,
u p o n a p o s i t i v e c l a i m o f f a i t h , t h a t is, t h a t h u m a n s a r e r i g h t l y r e -
latad t o G o d w h e n t h e y a c k n o w l e d g e t h e m s e l v e s g r a s p e d b y a
P o w e r w h i c h is u n c o n d i t i o n a l a n d w h i c h m a n i f e s t s itself as t h e
g r o u n d a n d j u d g e o f t h e i r e x i s t e n c e a n d o f all t h a t is. So s t a t e d ,
t h i s d o u b l e - s i d e d P r o t e s t a n t p r i n c i p i e has b o t h c r i t i c a l a n d c o n s -
tructive elements.

T i l l i c h ' s P r o t e s t a n t P r i n c i p i e is, o f c o u r s e , in r e a l i t y a u n i v e r s a l
and f o r m a l principie, n o t l i m i t e d t o P r o t e s t a n t c h u r c h e s . Indeed,
i t has o f t e n b e e n f o r g o t t e n a n d c a s t aside b y P r o t e s t a n t s . B u t i t
r e m a i n s as a p r i n c i p i e t o b e b r o u g h t t o b e a r o n all o f life. T h e
w a r n i n g against a b s o l u t i z i n g t h e r e l a t i v e - w h e t h e r i t b e a t h e o l -
ogy o r p h i l o s o p h y , an i n s t i t u t i o n , a p o l i t i c a l s t a t e , a m o d e o f i n -
q u i r y , an i d e o l o g y , o r a p a r t i c u l a r p e r s o n - is a s e n t i n e l against
a b s o l u t i s m a n d t o t a l i t a r i a n i s m . It is a d e f l a t o r o f all h u m a n p r e -
t e n s i o n s . T h e p r i n c i p i e begins a t t h e t h r e s h o l d o f o n e ' s s e l f h o o d
a n d t h a t s e l f s p r e t e n s i o n s . B u t i t r o a m s w i d e l y o v e r all a r e n a s o f
life. In t h e o l o g i c a l t e r m s i t is a r e j e c t i o n o f i d o l s - p e n u l t i m a t e
p o w e r s , forces, people and t h e o r i e s t h a t claim, o r t o w h i c h w e
a t t r i b u t e , u l t i m a c y . "You shall have no other gods befare m e . " T h e
P r o t e s t a n t p r i n c i p i e can b e l o o s e d f r o m its m o o r i n g s in t h e P r o t -
e s t a n t c o m m u n i t i e s , b u t i t is t o b e n o u r i s h e d a n d promulgated
t h e r e . B u t w h e n e v e r i t a p p e a r s i t is t h e r e l i g i o u s d i m e n s i ó n of
h u m a n life.
48 Faith c l a i m s o f P r o t e s t a n t i s m g i v e m a t e r i a l c o n t e n í t o t h i s r e l i -
g i o u s d i m e n s i ó n . T h e p o s i t i v e c l a i m is s t a t e d in a v a r i e t y of
w a y s . B u t a p e r s i s t e n t P r o t e s t a n t w a y o f s p e a k i n g is t o affirm
t h a t t h e U l t i m a t e P o w e r is g o o d , s e e k i n g t h e f r u i t i o n o f t h e
w h o l e c r e a t i o n a n d d i s c l o s i n g in Jesús o f N a z a r e t h a n d his d e a l -
ings, o u t o f his t r a d i t i o n , w i t h his c o n t e m p o r a r i e s , t h e w a y t o
a n d t h e g o a l o f t h a t f r u i t i o n . F u r t h e r t h i s G o d - s p i r i t - is s t i l l a t
w o r k , calling and enabling t h e c o m m u n i t y o f c r e a t i o n t o realize
t h a t f r u i t i o n . Such o n g o i n g a c t i v i t y r e q u i r e s t h a t h u m a n s take
n e w I n f o r m a t i o n and historical d e v e l o p m e n t s be t a k e n i n t o ac-
c o u n t and be e v a l u a t e d in t h e light o f n o r m a t i v e theological
a n d e t h i c a l t r a d i t i o n s . It r e q u i r e s a c o m m u n i t y u n d e r t h e d i s c i -
pline o f refórmala, semper reformando, " r e f o r m e d , always being
reformed."

G i v e n t h e P r o t e s t a n t principie, it w o u l d be m o r e t h a n p r e s u m p -
t u o u s , i t w o u l d be l u d i c r o u s , f o r any o n e p e r s o n t o c l a i m t o r e p -
r e s e n t P r o t e s t a n t i s m . It w o u l d be a c o n t r a d i c t i o n in t e r m s ,
since t h e d y n a m i c in t h e P r o t e s t a n t r e l i g i o u s m o v e m e n t has l e d
t o t h e b u r g e o n i n g o f r e l i g i o u s g r o u p s , each o n e f l y i n g t h e flag o f
P r o t e s t a n t , b u t n o t necessarily s a l u t i n g o t h e r s t a n d a r d s w i t h t h e
same m a r k i n g . So f o r a p r e s e n t a t i o n like t h i s t h e f i r s t d e c i s i ó n t o
b e m a d e is t o d e t e r m i n e t h a t s o u r c e o r s o u r c e s o n e invokes
w h e n inquiring a b o u t Protestantism and t h e H u m a n Cenóme
Project.

F o r t u n a t e l y , o n e s o u r c e r e a d i l y a t h a n d is d o c u m e n t s o f c o n -
c i l i a r b o d i e s . T w o in p a r t i c u l a r a r e p e r t i n e n t . T h e f i r s t is a P o l i c y
Statement of the National Council of Churches of Christ in
t h e U.S.A. e n t i t l e d " G e n e t i c Science f o r H u m a n B e n e f i t " . T h e
s e c o n d is a r e p o r t b y t h e W o r l d C o u n c i l o f C h u r c h e s S u b u n i t
o n C h u r c h a n d S o c i e t y , e n t i t l e d " B i o t e c h n o l o g y : Its C h a l l e n g e s
t o t h e C h u r c h e s and t h e W o r l d " . T h e date o f t h e f o r m e r is
1986, t h e l a t t e r 1989. B o t h d o c u m e n t s r e v i e w issues a r i s i n g
f r o m t h i s a n d o t h e r p r o j e c t s , i d e n t i f y i n g e t h i c a l issues a n d b r i n g -
ing e t h i c a l j u d g m e n t s t o b e a r o n t h o s e issues. A s t h e latter
d o c u m e n t is m o r e c o m p r e h e n s i v e a n d r e c e n t , I w i l l use i t as a
basic s o u r c e . It s h o u l d b e u n d e r s c o r e d t h a t t h e Identification
o f issues a n d t h e e t h i c a l r e s p o n s e s p r o p o s e d h a v e n o c o e r c i v e
s t a n d i n g f o r P r o t e s t a n t s . T h e i r e f f e c t i v e n e s s , if a n y , lies in t h e i r
persuasiveness. T h e r e are no institutional religious enforce-
m e n t p r o c e d u r e s , no external disciplines built i n t o a Protes-
tant perspective, no matter w h o develops o r propounds it.
" G o d alone is L o r d o f t h e c o n s c i e n c e " r e m a i n s a b o t t o m l i n e a f f i r -
mation for Protestants.

In t u r n i n g t o t h e W o r l d C o u n c i l p a p e r , I w i l l s u m m a r i z e t h e p a -
per's r e c o m m e n d a t i o n s and offer brief c o m m e n t s a b o u t ethical
concerns and principies t h a t i n f o r m these judgments:
Recommendations and proposals 149

The W o r l d Council of Churches, recognizing the potentlal dan-

g e r s as w e l l as t h e p o t e n t i a l b e n e f i t s o f m a n y f o r m s o f b i o t e c h -
n o l o g y , e n c o u r a g e s ¡ts m e m b e r c h u r c h e s t o t a k e appropriate
a c t l o n in t h e i r o w n c o u n t r i e s t o d r a w t h e s e m a t t e r s t o public
a t t e n t i o n , and t o help g o v e r n m e n t s , scientists, universities, hos-
pitals a n d c o r p o r a t i o n s t o d e v e l o p s u i t a b l e s a f e g u a r d s a n d c o n -
trols.

In p a r t i c u l a r it:

a) Calis f o r t h e p r o h i b i t i o n o f g e n e t i c t e s t i n g f o r s e x s e l e c t i o n ,
a n d w a r n s a g a i n s t t h e p o t e n t i a l use o f g e n e t i c t e s t i n g f o r
o t h e r f o r m s o f i n v o l u n t a r y social e n g i n e e r i n g .

b) D r a w s a t t e n t i o n t o w a y s in w h i c h k n o w l e d g e o f an i n d i -
viduals's g e n e t i c m a k e - u p can be, a n d in s o m e cases, is b e i n g
a b u s e d b y b e c o m i n g t h e basis f o r u n f a i r d i s c r i m i n a t i o n , f o r
e x a m p l e , in w o r k , h e a l t h c a r e , I n s u r a n c e a n d e d u c a t i o n .

c) Stresses t h e n e e d f o r p a s t o r a l c o u n s e l l i n g f o r i n d i v i d u á i s fac-
e d w i t h d i f f i c u l t r e p r o d u c t i v e c h o l e e s as w e l l as p e r s o n a l a n d
family decisions resulting f r o m genetic i n f o r m a t i o n c o n c e r n -
ing t h e m s e l v e s o r o t h e r s .

d) P r o p o s e s a ban o n e x p e r i m e n t s i n v o l v i n g g e n e t i c e n g i n e e r -
ing o f t h e h u m a n g e r m l i n e a t t h e p r e s e n t t i m e , a n d e n c o u r -
ages t h e e t h i c a l r e f l e c t i o n n e c e s s a r y f o r d e v e l o p i n g f u t u r e
g u i d e l i n e s in t h i s á r e a ; a n d u r g e s s t r i c t c o n t r o l o n e x p e r i -
m e n t s i n v o l v i n g genetically e n g i n e e r e d s o m a t i c cells, d r a w -
ing a t t e n t i o n t o t h e p o t e n t i a l m i s u s e o f b o t h techniques
as a m e a n s o f d i s c r i m i n a t i o n against t h o s e h e l d t o b e " d e -
fective".

e) C a l i s f o r t h e b a n n i n g o f c o m m e r c i a l i z e d c h i l d b e a r i n g (i.e.
p a r t i a l a n d full s u r r o g a c y ) as w e l l as t h e c o m m e r c i a l sale o f
ova, e m b r y o s o f foetal parts and s p e r m .

f) A d v i s e s g o v e r n m e n t s t o p r o h i b i t e m b r y o r e s e a r c h , w i t h any
e x p e r i m e n t s , if a g r e e d , o n l y u n d e r w e l l d e f i n e d c o n d i t i o n s .

g) E n c o u r a g e s its m e m b e r c h u r c h e s a n d o t h e r g r o u p s t o k e e p
t h e m s e l v e s i n f o r m e d o n h o w n e w d e v e l o p m e n t is r e p r o d u c -
t i v e t e c h n o l o g y affect f a m i l i e s , a n d especially w o m e n , a n d d e -
v e l o p a p a s t o r a l m i n i s t r y t o c o u n s e l p e o p l e facing t h e s e is-
sues, i n c l u d i n g t h o s e w h o c h o o s e , o r a r e p r e s s u r i z e d i n t o ,
u t i l i z i n g such r e p r o d u c t i v e t e c h n i q u e s .

h) Believes t h a t a n i m a l l i f e - f o r m s s h o u l d n o t b e p a t e n t e d a n d
calis f o r f u r t h e r s t u d y o f t h e p r o f o u n d m o r a l a n d social i m -
p l i c a t i o n s o f p a t e n t i n g life f o r m s .
I 50 i) Urges the swift adoption of strict international controls on
t h e reléase o f g e n e t i c a l l y e n g i n e e r e d o r g a n i s m s i n t o t h e e n v i -
ronment.

j) Calis o n n a t i o n s t h r o u g h o u t t h e w o r l d t o cease all use o f g e -

n e t i c e n g i n e e r i n g as p a r t o f any b i o l o g i c a l o r c h e m i c a l w a r f a r e
research p r o g r a m m e , and t o reconvene conventions o n bio-
logical a n d c h e m i c a l w e a p o n s in o r d e r t o c r é a t e n e w a n d ef-
fective p r o t o c o l s w h i c h p r o h i b i t their development, produc-
t i o n a n d use.

k) Resolves t o i n i t i a t e c o n s u l t a t i o n s b e t w e e n i n t e r n a t i o n a l or-
ganisations, n o n - g o v e r n m e n t a l organisations and scientists,
w i t h t h e churches and o t h e r , t o reflect o n t h e political e v o -
l u t i o n o f b i o t e c h n o l o g y a n d its i m p a c t o n g l o b a l j u s t i c e , a n d
t o make proposals f o r maximizing the benefit t o those w h o
a r e m o s t in n e e d .

( A p p r o v e d b y W C C C e n t r a l C o m m i t t e e , July 1989)

These r e c o m m e n d a t i o n s and proposals refer t o m a t t e r s t h a t in-

clude b u t are n o t restricted t o t h e H u m a n G e n o m e Project. T h a t
such is t h e case r e f l e c t s t h e p e r s p e c t i v e t h a t t h e H u m a n G e n o m e
Project s h o u l d b e d e a l t w i t h as a s u b c a t e g o r y o f t h e n e w b i o l o g y
a n d its t e c h n o l o g y . B u t i t is t o t h e specific r e f e r e n c e s t o t h e H u -
man G e n o m e Project that I t u r n n o w .

A m a j o r c o n c e r n o f t h e W C C p a p e r arises f r o m Francis B a c o n ' s

o b s e r v a t i o n t h a t k n o w l e d g e is p o w e r . C e r t a i n l y t h a t is t h e case
in a p r o j e c t t h a n c h a r t s t h e H u m a n G e n o m e . T o k n o w t h e h u m a n
g e n e t i c m a p a n d h o w t o m a n i p ú l a t e i t is p o w e r i n d e e d . S u c h
k n o w l e d g e m a y also b e i n t e r e s t i n g , a e s t h e t i c a l l y pleasing, d e l i g h t -
ful a n d satisfying o f c u r i o s i t y . B u t i t is a l w a y s p o w e r . A n d power
is t o be u s e d . T h e q u e s t i o n s a b o u t p o w e r a r e r e c u r r i n g . T h r e e
are: " W h a t p u r p o s e will this p o w e r serve?", " W h o will benefit?"
a n d " W h a t l i m i t s a r e t h e r e t o is?". T h e p u r p o s e t o be s e r v e d a n d
t h e d i s t r i b u t i o n o f benefits are critical ethical questions f o r P r o -
t e s t a n t s as f o r o t h e r s . T h e s e e n d u r i n g issues o f g o a l ( s ) t o be
sought and o f d i s t r i b u t i v e justice (the p r o p e r allocation o f bene-
fits) a r e c e n t r a l f o r t h e W C C paper.

A n issue p r e v i o u s t o specific goal a n d t o j u s t i c e is t h a t o f t h e legit-

i m a c y o f t h e H u m a n G e n o m e P r o j e c t itself. Because t h e f o c u s o f
t h e W C C p a p e r is o n t h e e t h i c a l issues a r i s i n g f r o m t h e a p p l i c a -
t i o n o f Information already o r prospectively attained, it does n o t
address this question. But t h e paper f r o m t h e National Council
o f t h e U n i t e d C h u r c h e s o f C h r i s t in t h e U.S.A. d o e s g i v e i t a
glancing b l o w .

U n d e r t h e heading o f " L i m i t s t o K n o w l e d g e , Limitation o n Re-

search and P r o d u c t i o n " , t h e policy s t a t e m e n t c o m e s d o w n firmly
on t h e appropriateness o f limiting inquiry and research. T h e 151
d o c u m e n t r e a d s as f o l l o w s :

Límíts to knowledge, limítation on research

and productíon

" W e c a n n o t a g r e e w i t h t h o s e w h o a s s e r t t h a t scientific inquiry

and r e s e a r c h s h o u l d a c k n o w l e d g e n o limits. A l l t h a t can be
k n o w n n e e d n o t be k n o w n ¡f in a d v a n c e i t c l e a r l y a p p e a r s t h a t
t h e p r o c e s s o f gaining such k n o w l e d g e v i o l a t e s t h e s a n c t i t y o f h u -
m a n life. R e m e m b e r i n g its o w n h i s t o r y , t h e c h u r c h s h o u l d not
o p p o s e s c i e n t i f i c a d v a n c e , b u t i t m u s t s p e a k o u t in j u d g m e n t
w h e n t h e q u e s t f o r n e w k n o w l e d g e s u p e r s e d e s all e t h i c a l c o n -
c e r n s . W e d o n o t a l l o w t h i s s t a n c e t o be c a l l e d , n o t t o b e c o m e ,
o n e o f a n t i - i n t e l l e c t u a l o r a n t i s c i e n t i f i c bias. N e i t h e r d o w e i m p l y
that genetic scientists are m o r a l l y irresponsible, o r t h a t institu-
tional r e v i e w boards cannot make p r o p e r decisión on research
protocols."

In t h i s p a r a g r a p h t h e f i r s t p r i n c i p i e i n v o l v e d is t h e a f f i r m a t i o n o f
t h e p o s i t i v e v a l u é o f scientific i n q u i r y a n d r e s e a r c h . It is a s s e r t e d ,
n o t a r g u e d . T h e s e c o n d is t h e s a n c t i t y o f h u m a n life. T h e l a t t e r is
the limiting principie f o r t h e f o r m e r . For this Protestant policy,
t h e s a n c t i t y o f h u m a n life p r o v i d e s j u s t i f i c a t i o n f o r determining
w h e n scientific i n q u i r y a n d r e s e a r c h m u s t cease a n d desist. T h a t
l i m i t a t i o n cashes o u t in s u b o r d i n a t e p r o p o s i t i o n s t h a t w o u l d , f o r
e x a m p l e , r e j e c t i n q u i r y w i c h r e q u i r e s t h e use o f h u m a n s as u n -
w i l l i n g g u i n e a pigs f o r e x p e r i m e n t a r o n . In brief, t h e controlling
ethic o f t h i s l i m i t i n g p o s i t i o n is o n e called d e o n t o l o g i c a l . T h a t r e -
fers t o t h e e l e v a t i o n o f c e r t a i n o b l i g a t i o n s o r r u l e s as r e q u i r i n g
c o n s e n t a n d o b e d i e n c e in a n d o f t h e m s e l v e s . T h e r e is n o r e f e r -
e n c e t o j u s t i f i c a t i o n b y a g o a l , t h a t is, o f a t e l e o l o g i c a l prefer-
ence, w h i c h m e a s u r e s t h e v a l i d i t y o f a c t i o n s t o be t a k e n s o l e l y b y
their c o n t r i b u t i o n t o t h e end t o be obtained, w h e t h e r t h a t end
be k n o w l e d g e f o r its o w n sake o r k n o w l e d g e in o r d e r t o a d v a n c e
the greatest g o o d f o r t h e greatest n u m b e r . T h e sanctity o f h u -
man life is, t h e r e f o r e , a p r i n c i p i e t h a t r e j e c t s calculations o f m e r i t /
d e m e r i t in t e r m s o f acts t o b e d o n e in t h e l i g h t o f goals t o be
r e a l i z e d . N o e n d can j u s t i f y in a d v a n c e any m e a n s . T h e s a n c t i t y o f
h u m a n life s t a n d s as t h e l i m i t i n g p r i n c i p i e o f scientific i n q u i r y . It
leads t o an e t h i c o f r e s t r a i n t a n d c a u t i o n w i t h r e f e r e n c e t o a p -
proving inquiry.

Given, however, that t h e mapping of the H u m a n G e n o m e does

n o t v i ó l a t e t h e s a n c t i t y o f t h e self, e.g., its a u t o n o m y , t h e r e is n o
r e a s o n in p r i n c i p i e t o r e f r a i n f o r m u n d e r t a k i n g , p a r t i c i p a t i n g i n ,
and c o m p l e t i n g t h e v e n t u r e .

W h a t n e i t h e r o f t h e P r o t e s t a n t s t a t e m e n t s t a c k l e is t h e issue o f
t h e l e g i t i m a c y o f t h e p r o j e c t in t e r m s o f its w o r t h c o m p a r e d t o
I 52 o t h e r p r o j e c t s . T h a t d e t e r m i n a t i o n is a j u s t i c e issue, o n e o f e s t i -
m a t i n g its v a l u é in t e r m s o f p o t e n t i a l c o n s e q u e n c e s o f o n e i n -
q u i r y o v e r against a n o t h e r , a n d t h e c o n s e q u e n t e s t a b l i s h i n g o f
phorities f o r research.

T o r e t u r n t o t h e q u e s t i o n o f goals t o be s o u g h t a n d o f j u s t i c e t o
be d o n e , t w o p r o m i n e n t P r o t e s t a n t e t h i c a l d i r e c t i v e s can be seen
a t w o r k in t h e W C C paper. T h e first t r e a t s goals, t h e second
justice.

U n d e r goals t h e r e is m o r e a w a r n i n g t h a n a d i r e c t i v e . It is t h a t
t h e p r o j e c t i o n o f goals t o be s e r v e d b y I n f o r m a t i o n a b o u t t h e
H u m a n G e n o m e is i n e v i t a b l y s u b j e t t o bias. "The history o f genetic
movements, f r o m Plato to the present doy, sfiows m a n y examples o f
individuáis a n d groups, including scientific leaders a n d often so-called
experts, w h o institutionalized their prejudice o f race, sex, a n d class
through p r o g r a m s t h a t causad tragic h a r m " ( W C C , p. 14) Such a
r e c o g n i t i o n e l e v a t e s c a u t i o n a n d r e s t r a i n t o v e r against any p a r t i c -
ular p o s i t i n g o f goals. K n o w l e d g e is p o w e r . T h a t is o n e f a m i l i a r
saying. B u t a n o t h e r is also p e r t i n e n t . "Power tends to corrupt a n d
absolute p o w e r tends to corrupt obso/ute/y". T h e r e is a h e a l t h y s k e p -
t i c i s m t o c o m e i n t o play w h e n any o n e p e r s o n o r g r o u p pro-
p o s e s a g o a l t o be s o u g h t t h r o u g h t h e a p p l i c a t i o n o f a b o d y o f
k n o w l e d g e . T h e t e m p t a t i o n t o a b s o l u t i z e t h e r e l a t i v e is t e s t i f i e d
t o b y t h e h i s t o r y o f eugenic p o l i c i e s .

O n a m o r e p o s i t i v e n o t e t h e P r o t e s t a n t c o n c e r n f o r j u s t i c e as a
p r i m a r y v a l u é leads t h e a u t h o r s o f t h e W C C paper t o speak a
s t r o n g w o r d o n b e h a l f o f t h o s e w h o a r e r e l a t i v e l y p o w e r l e s s . It
does so by advocating t h a t t h e t h e r a p e u t i c benefits o f t h e H u m a n
G e n o m e f i n d i n g s n o t be r e s t r i c t e d t o t h e w e a l t h y n a t i o n s w h o s e
p o w e r f u l m o n e y leads t o p o w e r f u l k n o w l e d g e f o r t h e i r use. Ñ o r
t o t h o s e individuáis only able t o afford. T h e c r i t e r i a f o r d i s t r i b u -
t i o n o f benefits p r o p o s e d by t h e W C C include t h e utilization o f
s u c h k n o w l e d g e o n t h e basis o f n e e d . T h i s P r o t e s t a n t n o t e of
bias o n b e h a l f o f t h o s e p o t e n t i a l l y left o u t o f t h e b e n e f i t s o f r e -
s e a r c h leans a g a i n s t t h e w i n d o f b e n e f i t s f o r t h e f a v o r e d few
- p e r h a p s t h o s e p e o p l e s a n d n a t i o n s t h a t f u n d t h e p r o j e c t . Such a
bias recalls t h e scientific a n d h u m a n c o m m u n i t y t o its u n i v e r s a l i s -
t i c c h a r a c t e r . It elevates t h e issue o f t h e social r e s p o n s i b i l i t y o f
scientific i n q u i r y , t h e fact t h a t use f o r w h o m a n d f o r w h a t is i n e v -
itably p a r t o f t h e q u e s t i o n o f " t o i n q u i r e o r n o t t o i n q u i r e " . A n d
w h e n such e n o r m o u s f u n d i n g is i n v o l v e d f r o m p u b l i c s o u r c e s , t h e
n a t u r e o f the public t o b e n e f i t is p r o p e r a n d necessary.

T h e l a r g e j u s t i c e issue f o r t h e H u m a n G e n o m e P r o j e c t is its
valué p o r humans w h e n c o m p a r e d w i t h o t h e r scientific p r o j e c t s .
T h e H u m a n G e n o m e P r o j e c t as t h e r e c i p i e n t o f extraordinary
benefits ( f u n d i n g , status, prestige) b e c o m e s itself, q u i t e ap-
p r o p r i a t e l y , t h e c e n t e r o f justice debates and struggles. But t h a t
issue is n o t a d d r e s s e d by e i t h e r o f t h e p a p e r s b e f o r e us.
In c o n c l u s i ó n , t h e P r o t e s t a n t p r i n c i p i e o f r e f u s i n g t o a b s o l u t i z e 153
t h e relative introduces t h e principie of skepticism i n t o t h e p r o -
j e c t i o n o f any goals t o be realized t h r o u g h t h e h a r v e s t i n g o f
k n o w l e d g e a n d / o r its a p p l i c a t i o n s , a n d f o r m o n i t o r i n g f r o m the
beginning f o r c o n s e q u e n c e s , m e t h o d o l o g y and benefits. A s a f o r m -
ative m o v e m e n t t h a t carries f o r w a r d h u m a n valúes, P r o t e s t a n t
policies affirm scientific inquiry and t h e c o n t r i b u t i o n t o health
w h i l e t h e y a d v ó c a t e f o r a fair d i s t r i b u t i o n o f t h e b e n e f i t s o f al!
such scientific i n q u i r y a n d r e s e a r c h , i n c l u d i n g t h a t p e r t a i n i n g t o
the H u m a n G e n o m e Project.

A P r o t e s t a n t d e n o m i n a t i o n a l p o l i c y s t a t e m e n t a d o p t e d in 1989
c o n t a i n s t h e s e w o r d s , a n d t h e y a r e p e r h a p s an a p p r o p r i a t e place
t o conclude:

" W i t h o u r n e w knowledge comes new responsibilities. As

Jesús f e d t h e h u n g r y a n d h e a l e d t h e sick, w e a r e c a l l e d t o
f o l l o w his e x a m p l e a n d t o use o u r n e w [ k n o w l e d g e a n d ] a b i l -
ities t o b r i n g healing a n d s u s t e n a n c e t o p e o p l e e v e r y w h e r e " .
(The Church a n d Genet/c Engineering, p. 3)

T h e a f f i r m a t i o n m a y b e seen as a c o u n s e l o f n a i v e t e a n d s e n t i -
m e n t a l i t y b y t h e c y n i c a l . B u t i t m a y b e g r a s p e d as a c o u n c e l o f
p r o f o u n d i m p o r t a n c e by t h o s e w h o s e search f o r h u m a n well
b e i n g is b o t h t h e s h i n i n g s t a r g u i d l n g t h e i r r e s e a r c h a n d also t h e
subterranean motive of their often unexamined, unnamed but
powerful faith.
154

REFERENCES

" B i o t e c h n o l o g y : Its Challenge t o t h e Churches and t h e W o r l d " . The

W o r l d Council of Churches, Subunit on Church and Society. Geneva,
Switzerland, 1989.

" T h e C h u r c h and Genetic Engineering". A Proposed Pronouncement.

N e w Y o r k : The United C h u r c h of Christ, U.S.A., 1989.

" G e n e t i c Science f o r Human Benefit". A Policy Statement of the N a -

tional Council of t h e Churches of Christ in the U.S.A., N e w Y o r k ,
N Y , U.S.A., 1986.

T i l l í c h , P a u l . The Protestant Era (abridged). Chicago: The University of

Chicago Press, 1957.
T H E C O N C E P T
OF T H E "I"
 !57

BIOLOGICA!. DETERMINISM
AND THE CONCEPT OF SOCIAL
RESPONSIBILITY.
THE LESSON OF CARRIE BUCK

j . DaWd Smith

Dept. of Human Development, Lynehburg College, Lynehburg,

Virginia (USA)

ABSTRACT

Carrie Buck, a y o u n g girl who was diagnosed as

being m e n t a l l y defícient, was s t e r i l i z e d to a v o i d
transmission o f this defíciency to her descendants.
Her case passed into the history o f law. The idea o f
ochieving improvements a n d eradicating problems
enveloped the case, both these ideas being o f a so-
cial type. Nevertheless, this a n d other experiences
have shown how erroneous it is to a t t e m p t to reduce
human Ufe to biology, disregarding ethical a n d social
considerations on which human rights are based. In
this sense, the H u m a n Genome Project must display
respect f o r Ufe a n d o v e r e ó m e t h e diverse i n a c -
curacies o f the eugenesic m o v e m e n t
In 1 9 2 7 a y o u n g w o m a n n a m e d C a r r i e B u c k w a s i n v o l u n t a r i l y | 59
s t e r i l i z e d . She w a s t h e f l r s t p e r s o n t o b e s u b j e c t e d t o t h a t s u r -
gery u n d e r t h e a u t h o r i t y o f a Virginia law. T h e law a l l o w e d t h e
s t a t e t o i m p o s e s t e r i l i z a t i o n o n p e r s o n s d i a g n o s e d as b e i n g i n -
c o m p e t e n t a n d f o u n d t o b e l i k e l y t o g e n e t i c a l l y t r a n s m i t physical,
p s y c h o l o g i c a l o r social d e f i c i e n c i e s t o t h e i r o f f s p r i n g . C a r r i e B u c k
had ben c o m m i t t e d t o an i n s t i t u t i o n f o r p e o p i e d i a g n o s e d as " f e e -
b l e m i n d e d " . T h e c o m m i t m e n t f o l l o w e d h e r g i v i n g b i r t h t o an
illegitimate child. C a r r i e ' s m o t h e r had been c o m m i t t e d t o the
same i n s t i t u t i o n s o m e y e a r s e a r l i e r . H e r i n s t i t u t i o n a l i z a t i o n a p p a r -
e n t l y r e s u l t e d f r o m p r o s t i t u t i o n a n d o t h e r socially u n a c c e p t a b l e
behavior. It was r e p o r t e d t h a t C a r r i e ' s infant d a u g h t e r aiso
s h o w e d signs o f b e i n g m e n t a l l y d e f i c i e n t .

T o t h e physicians, l a w y e r s a n d p o l i t i c i a n s w h o w i s h e d t o see t h e
Virginia sterilization law constitutionally validated, C a r r i e Buck
seemed t o be t h e p e r f e c t p e r s o n f o r t h e t e s t o f t h e law. T h e ar-
g u m e n t c o u l d be m a d e t h a t h e r m o t h e r w a s m e n t a l l y d e f i c i e n t ,
t h a t C a r r i e was mentally r e t a r d e d and t h a t her baby showed
signs o f f e e b l e m i n d e d n e s s . T h i s e v i d e n c e o f g e n e t i c t r a n s m i s s i o n
o f t h e i r i n f e h o r i t y w o u l d t h e n b e p r e s e n t e d as i l l u s t r a t i n g t h e
n e e d f o r an i n v o l u n t a r y s t e r i l i z a t i o n s t a t u t e . T h e j u d g e m e n t of
t h o s e w h o s e l e c t e d C a r r i e f o r t h e t e s t case p r o v e d t o be s o u n d .
T h e S u p r e m e C o u r t u p h e l d t h e c o n s t i t u t i o n a l i t y o f t h e l a w in t h e
case w h i c h c a m e t o b e k n o w n as Buck /. Be//. In d e l i v e r i n g t h e
m a j o r i t y o p i n i ó n in t h e d e c i s i ó n , Justice O l i v e r W e n d e l l Holmes
wrote:

"We have seen m o r e t h a n o n c e t h a t t h e p u b l i c w e l f a r e my

cali u p o n t h e b e s t c i t i z e n s f o r t h e i r lives. It w o u l d be s t r a n g e
if i t c o u l d n o t cali u p o n t h o s e w h o a l r e a d y sap t h e s t r e n g t h o f
t h e State f o r t h e s e lesser sacrifices, o f t e n f e l t t o be m u c h b y
t h o s e c o n c e r n e d , in o r d e r t o p r e v e n t o u r b e i n g s w a m p e d
w i t h i n c o m p e t e n c e . It is b e t t e r f o r all t h e w o r l d , if i n s t e a d o f
waiting t o execute degenerate offspring f o r crime, o r t o let
t h e m starve f o r t h e i r i m b e c i l i t y , s o c i e t y can p r e v e n t those
w h o are manifestly unfit f r o m continuing t h e i r kind. T h e p r i n -
c i p i e t h a t sustains c o m p u l s o r y v a c c i n a t i o n is b r o a d e n o u g h t o
c o v e r c u t t i n g t h e Fallopian t u b e s . . . "

T h e s t e r i l i z a t i o n o f C a r r i e B u c k a c h i e v e d a place in legal h i s t o r y
and in t h e annals o f t h e social sciences. T h e saga o f sociaj D a r -
w i n i s m a n d eugenics in t h e U n i t e d States, i n d e e d in t h e w o r l d ,
simply c a n n o t be t o l d w i t h o u t r e f e r e n c e t o t h e S u p r e m e Court
d e c i s i ó n in h e r case. T h e f a c t t h a t t h e legal i n t e g r i t y o f c o m p u l -
s o r y s t e r i l i z a t i o n w a s e n d o r s e d b y t h e h i g h e s t c o u r t in a c o u n t r y
t h a t p r i d e d itself o n its c o m m i t m e n t t o i n d i v i d u a l f r e e d o m had a
global i m p a c t . C a r r i e , as t h e s u b j e c t o f t h e case, b e c a m e an his-
t o r i c a l figure o f I n t e r n a t i o n a l f a m e . C a r r i e , t h e p e r s o n , l i v e d a life
m a r k e d by w h a t had b e e n e r r o n e o u s l y c l a i m e d o f h e r a n d w h a t
was d e c i d e d a b o u t h e r by p e o p l e o f p o w e r a n d i n f l u e n c e . T h e s e
60 people, h o w e v e r , had little u n d e r s t a n d i n g o f her t r u e character
a n d abilities. I w i l l t r y t o ¡ I l ú s t r a t e t h i s l a t e r In m y r e m a r k s .

C a r r i e was f o l l o w e d by t h o u s a n d s o f o t h e r p e o p l e w h o were
s t e r i l i z e d u n d e r t h e p r o v l s l o n s o f t h e law. V i r g i n i a ' s l a w also b e -
c a m e t h e m o d e l f o r s t e r l l l z a t i o n s t a t u t e s in o t h e r states. A c o n -
s e r v a t i v e e s t í m a t e Is t h a t 5 0 , 0 0 0 p e o p l e w e r e s t e r i l i z e d in t h e
U n i t e d States b y t h e a u t h o r i t y o f t h e s e s t a t u t e s . U l t i m a t e l y t h e
V i r g i n i a l a w w a s t h e m o d e l u s e d as p a r t o f t h e N a z i Race H y -
g i e n e P r o g r a m . O n July 14, 1 9 3 3 , t h e m o d e l s t e r i l i z a t i o n act
d e v e l o p e d b y e u g e n i c s a d v ó c a t e H a r r y Laughlin, t h e s a m e m o d e l
u s e d b y V i r g i n i a , b e c a m e l a w in G e r m a n y .

T h e N a z i l a w w a s i m p l e m e n t e d s w i f t l y a n d b r o a d l y . By t h e e n d
o f t h e f i r s t y e a r t h a t i t w a s in e f f e c t , a c c o r d i n g t o S.J. H o l m e s ,
o v e r 5 6 , 0 0 0 p e o p l e h a d b e e n f o u n d t o b e d e f e c t i v e b y special
h e r e d i t a r y health c o u r t s and had been sterilized. H i t l e r ' s race
hygiene p r o g r a m s w e r e applauded by A m e r i c a n eugenicists. Ste-
r i l i z a t i o n p r o p o n e n t Paul P o p e n o e f e l t t h a t t h e N a z i s w e r e f o l -
l o w i n g a policy t h a t was consistent w i t h t h e best t h i n k i n g o f euge-
nicists t h r o u g h o u t t h e w o r l d . K . M . L u d m e r e r q u o t e s an e d i t o r i a l
s t a t e m e n t f r o m t h e A m e r i c a n p u b l i c a t i o n , Eugenical N e w s , t h a t
c o n c l u d e d , " I t is d i f f i c u l t t o see h o w t h e n e w G e r m á n S t e r i l i z a -
t i o n L a w c o u l d , as s o m e have s u g g e s t e d , b e d e f l e c t e d f r o m its
p u r e l y e u g e n i c a l p u r p o s e , a n d m a d e an ' i n s t r u m e n t o f t y r a n n y '
f o r the sterilization of n o n - N o r d i c r a c e s " . It w o u l d b e many
years b e f o r e m o s t A m e r i c a n eugenicists w o u l d c o m p r e h e n d t h e
c o n n e c t i o n b e t w e e n t h e i r o w n w o r k and t h e stark atrocities o f
t h e N a z i r e g i m e . It is e s t i m a t e d t h a t b e t w e e n 1933 a n d 1945,
t w o million people w e r e declared defective and w e r e sterilized
b y t h e N a z i s . P e r h a p s i t is b e c a u s e o f t h e a w f u l n e s s o f t h e o t h e r
a t r o c i t i e s c o m m i t t e d d u r i n g this p e r i o d t h a t so little attention
has b e e n f o c u s e d o n t h i s r e a l i t y . T h e d i m e n s i o n s o f t h i s i n f r i n g e -
m e n t o n t h e basic r i g h t s o f s o m a n y h u m a n beings a r e , h o w e v e r ,
staggering. R e c o g n i z i n g t h a t t h e legal, social a n d scientific s o u r c e s
o f t h i s p r a c t i c e w e r e l a r g e l y A m e r i c a n is, f o r t h i s A m e r i c a n ,
chilling.

O t t o H o f m a n n , a high r a n k i n g SS o f f i c e r , w a s o n e o f t h e facilita-
t o r s o f p o l i c i e s a i m e d a t w h a t t h e N a z i s c o n c e p t u a l i z e d as t h e " f i -
nal s o l u t i o n t o t h e J e w i s h q u e s t i o n " . H e has h e a d o f t h e Race a n d
Settlement Main Office o f t h e Reichsfuehrer-SS. T h e fifth v o l u m e
o f Triáis o f the W a r Crimináis Before the N u r e m b e r g M i i i t a r y Tribu-
nais c o n t a i n s r e c o r d s o f t h e c o n v i c t i o n f o r w a r c r i m e s o f Otto
H o l f m a n n . It states t h a t t h e e v i d e n c e " e s t a b l i s h e s b e y o n d any r e a -
sonable d o u b t Holfann's guilt and criminal responsibility f o r t h e
f o l l o w i n g c r i m i n a l a c t i v i t i e s p u r s u e d in t h e f u r t h e r a n c e o f t h e
G e r m a n i z a r o n p r o g r a m : "... f o r c i b l e a b o r t i o n s o n E a s t e r n w o r k -
e r s ; t a k i n g a w a y i n f a n t s o f E a s t e r n w o r k e r s ; t h e ¡Ilegal an u n j u s t
p u n i s h m e n t o f f o r e ¡ g n nat¡onals f o r sexual ¡ n t e r c o u r s e w ¡ t h G e r -
mans; [and] h a m p e h n g t h e r e p r o d u c t i o n o f fore¡gn populatlons
[ f o r c e d steril¡zat¡ons]...".
W h i l e t h e fifth v o l u m e o f r e c o r d s o f t h e N u r e m b e r g Tribunals | 6
contains t h e conviction o f O t t o H o f m a n n , t h e f o u r t h v o l u m e in-
c l u d e s d o c u m e n t s w h i c h w e r e e n t e r e d in his d e f e n s e . A m o n g
t h e m is an a b s t r a c t p r e p a r e d in 1937 b y t h e I n f o r m a t i o n S e r v i c e
o f t h e Racial-Political O f f i c e o f t h e Reich A d m i n i s t r a r o n . It c o n -
cerns w h a t are called "Race P r o t e c t i o n Laws of O t h e r Coun-
t r i e s " a n d a p p e a r s t o h a v e b e e n e n t e r e d as e v i d e n c e o n Hof-
m a n n ' s b e h a l f t o s h o w t h a t t h e p r a c t i c e s he engaged in d u r i n g
t h e w a r w e r e based o n p r e c e d e n t s f r o m o t h e r " c i v i l i z e d " na-
t i o n s . It c o n t a i n s a l i t a n y o f s t e r i l i z a t i o n p o l i c i e s f r o m countries
i n c l u d i n g D e a m a r k , F i n l a n d , N o r w a y a n d S w e d e n . T h e litany e n d s
w i t h a d e t a i l e d d i s c u s s i o n o f s t e r i l i z a t i o n l a w s in t h e United
States. It r e f e r e n c e s t h e d e c i s i ó n in C a r r i e B u c k ' s case.

" U N I T E D STATES O F A M E R I C A

... T h o s e a f f e c t e d by t h e l a w w e r e p r i m a r i l y c r i m i n á i s , f e e b l e -
m i n d e d , insane, e p i l e p t i c s , a l c o h o l i c a n d n a r c o t i c a d d l c t s , as
w e l l as p r o s t i t u t e s . A l t h o u g h a l m o s t all states t r y t o c a r r y o u t
s t e r i l i z a t i o n o n a v o l u n t a r y basis t h e c o u r t s have m o r e t h a n
o n c e o r d e r e d c o m p u l s o r y s t e r i l i z a t i o n s . In a j u d g e m e n t o f t h e
S u p r e m e C o u r t o f [ 1 9 2 7 ] . . . i t says, a m o n g o t h e r t h i n g s : ' I t is
b e t t e r f o r e v e r y b o d y if s o c i e t y , i n s t e a d o f w a i t i n g u n t i l i t has
t o e x e c u t e d e g e n e r a t e o f f s p r i n g o r leave t h e m t o s t a r v e b e -
cause o f f e e b l e - m i n d e d n e s s , can p r e v e n t o b v i o u s l y i n f e r i o r i n -
dividuáis f r o m p r o p a g a t i n g t h e i r o w n k i n d . T h e p r i n c i p i e j u s -
t i f y i n g c o m p u l s o r y v a c c i n a t i o n is b r o a d e n o u g h t o c o v e r t h e
s e v e r i n g o f t h e Fallopian t u b e s " .

T h e w o r d s o f Justice O l i v e r W e n d e l l H o l m e s in t h i s c o n t e x t a r e
a sobering r e m a i n d e r o f t h e credibility b e s t o w e d u p o n eugenic
p h i l o s o p h y a n d p o l i c y , a n d t h e a t r o c i t i e s c o m m i t t e d , as D a n i e l
K e v l e s has s o w e l l d e s c r i b e d it, " i n t h e ñ a m e o f e u g e n i c s " .

H o l m e s in w r i t i n g t h e m a j o r i t y o p i n i ó n in Buck v. Bell used t h e

n o w famous phrase, " t h r e e generations o f imbéciles are e n o u g h " .
His r e a s o n i n g and language w e r e c o n s i s t e n t w i t h t h e eugenic
v i e w t h a t m a n y socially u n d e s i r a b l e t r a i t s , i n c l u d i n g m e n t a l r e t a r -
d a r o n , w e r e largely h e r e d i t a r y . I n h e r e n t in t h i s v i e w w a s t h e idea
that even c o m p l e x h u m a n traits c o u l d be t r a c e d t o simple genet-
ic causes. Eugenicists b e l i e v e d , in fact, t h a t m o s t h u m a m c h a r a c -
t e r i s t i c s c o u l d be l i n k e d d i r e c t l y t o single g e n e s . T h e y h e l d t h a t
n o t o n l y physical t r a i t s like e y e c o l o r a n d h e i g h t , b u t also p e r s o n -
ality a t t r i b u t e s w e r e d e t e r m i n e d b y a single g e n e . T h i s c o n f i d e n c e
in M e n d e l i a n g e n e t i c s w a s e x t e n d e d t o t h e d e t e r m i n a t i o n of
occupational preferences, academic interests, talents, and even
c h a r a c t e r s t r e n g t h s a n d w e a k n e s s e s . It w a s c l a i m e d t h a t m e c h a n i -
cal skill, a r t i s t i c a n d m u s i c a l a b i l i t y w e r e s i m p l e r e c e s s i v e g e n e
t r a i t s . " S h i f t l e s s n e s s " w a s also i n c l u d e d in t h i s list o f r e c e s s i v e
traits. V i o l e n t t e m p e r a m e n t , it was reasoned, m u s t be a d o m i -
n a n t g e n e t r a i t since i t d o e s n o t s k i p g e n e r a t i o n s . In a s t u d y e n -
t i t l e d The N o m family: a study in Cacogenics C h a r l e s D a v e n p o r t r e -
I 62 p o r t e d t h a t laziness w a s a d o m i n a n t t r a i t , w h i l e a b u s i v a d r i n k i n g
and shyness w e r e simple recessives. T h e s e enthusiastic excur-
sions i n t o biological d e t e r m i n i s m and r e d u c t i o n i s m may s o u n d
h u m o r o u s w h e n viewed f r o m o u r c u r r e n t perspectiva but they
w e r e t h e basis f o r g r e a t h u m a n t r a g e d y . Such s i m p l i s t i c views
a b o u t h u m a n beings w e r e i n h e r e n t in t h e c o n v i c t i o n t h a t s t e r i l i -
zation w o u l d help stem a feared f l o o d o f i n c o m p e t e n c e resulting
f r o m genetic blight, and t h e y w e r e used t o s t e r e o t y p e whole
classes o f p e o p l e .

W h i l e t h e eugenics m o v e m e n t was obsessed w i t h race and e t h -

n i c i t y , i t a l s o f o c u s e d o n p e r c e i v e d d i f f e r e n c e s in social classes
w i t h i n r a c i a l a n d e t h n i c g r o u p s . In h e r b o o k , W h i t e Trash: The
Eugenic Family Studies, N i c o l e H a h n R a f t e r p o r t r a y s t h e f a m i l y
d e g e n e r a c y s t u d i e s w h i c h w e r e c o n d u c t e d as p a r t o f t h e e u g e n -
ics m o v e m e n t In t h e U n i t e d States as having b e e n f o c u s e d p r i -
m a r i l y o n l o w e r class c a u c a s i a n f a m i l i e s , o n t h e " p o o r white
t r a s h " o f early t w e n t i e t h c e n t u r y A m e r i c a . W h e n C a r r i e Buck's
case w a s f i r s t h e a r d a r e p o r t w a s s u b m i t t e d as t e s t i o m o n y by
H a r r y Laughlin, t h e a u t h o r o f t h e m o d e l sterilization law t h a t V i r -
ginia has a d o p t e d . H e h a d a n a l y z e d I n f o r m a t i o n o n C a r r i e a n d
h e r f a m i l y a n d he o f f e r e d his r e p o r t in s u p p o r t o f h e r b e i n g s t e r i -
lized. In c o m m e n t i n g o n h e r heritage, Laughlin, said, " T h e s e p e o p l e
b e l o n g t o t h e shiftless, i g n o r a n t a n d w o r t h l e s s class o f a n t i - s o c i a l
w h i t e s o f t h e S o u t h . . . [ t h e y a r e a n ] i g n o r a n t a n d m o v i n g class o f
people...".

H e n r y G o d d a r d in his b o o k o n t h e K a l l i k a k f a m i l y m a d e t h e f o l -
l o w i n g c o m m e n t s a b o u t t h e k i n d o f l o w e r s o c i o - e c o n o m i c class
p e o p l e w h o w e r e t h e s u b j e e t s o f his s t u d y : " I f all o f t h e s l u m d i s -
triets o f o u r cities w e r e r e m o v e d t o m o r r o w and m o d e l t e n e -
m e n t s b u i l t in t h e i r places, w e w o u l d still have s l u m s in a w e e k ' s
t i m e because w e have t h e s e m e n t a l l y d e f e c t i v e p e o p l e w h o can
n e v e r b e t a u g h t t o live o t h e r w i s e t h a n as t h e y have b e e n living.
N o t u n t i l w e t a k e c a r e o f t h i s class a n d see t o i t t h a t t h e i r lives
a r e g u i d e d b y i n t e l l i g e n t p e o p l e , shall w e r e m o v e t h e s e sores
f r o m o u r social l i f e " .

It w a s o n t h e basis o f t h e s e beliefs a n d t h i s r e a s o n i n g t h a t C a r -
rie Buck was sterilized. T h u s the p r e c e d e n t was established f o r
t h e s u s p e n s i ó n o f t h e r i g h t s o f s o m e i n d i v i d u á i s a n d classes f o r
t h e p r o t e c t i o n o f s o c i e t y . T h e s e v i e w s , w i t h t h e c r e d i b i l i t y af-
f o r d e d t h e m b y b e i n g g r o u n d e d in w h a t w a s a c c e p t e d as s c i e n -
t i f i c f a c t , b e c a m e p o w e r f u l f o r c e s in s h a p i n g p u b l i c o p i n i ó n a n d
social policy.

T h e e u g e n i c e v i d e n c e a n d p r e d i c t i o n s in C a r r i e B u c k ' s case have

p r o v e n in m y o w n i n v e s t i g a t i o n s , a n d t h o s e o f o t h e r s , t o be
g r o s s l y i n a e c u r a t e . C a r r i e ' s c h i l d , V i v í a n , alleged t o r e p r e s e n t t h e
" t h i r d g e n e r a t i o n o f i m b é c i l e s " , a c t u a l l y g r e w t o be an a t t r a c t i v e
child w h o was a h o n o r roll student. C a r r i e , charged w i t h being
t h e second generation of imbéciles, was paroled after her sterili-
z a t i o n t o a m o u n t a i n village w h e r e s h e s o o n m a r r i e d t h e d e p u t y | 63
sheriff. T h e r e s h e Üved a m o d e s t , b u t p r o d u c t i v e a n d r e s p e c t a b l e ,
life. F o l l o w i n g t h e d e a t h o f h e r h u s b a n d s h e m o v e l t o a l a r g e r
t o w n w h e r e she earned her living caring f o r elderly and c h r o n i -
cally ¡11 p e o p l e . F r i e n d s a n d e m p l o y e r s a t t e s t e d t o t h e f a c t t h a t
Carrie Buck was n o t mentally deficient. Indeed, mental health
p r o f e s s i o n a l s w h o o b s e r v e d h e r late in h e r life f o u n d n o e v i d e n c e
o f m e n t a l r e t a r d a t i o n . A b i t m o r e r e s e a r c h , in fact, o n t h e p a r t o f
t h o s e w h o c l a i m e d t o have f o u n d d e f e c t i v e n e s s t o b e i n n a t e in
C a r r i e ' s g e n e a l o g y w o u l d have u n c o v e r e d a q u i t e d i f f e r e n t pie-
t u r e . If t h e e u g e n i c f i e l d r e s e a r c h e r s in h e r case h a d l o o k e d j u s t
t w o m o r e branchings back o n Carrie's family t r e e t h e y would
have d i s c o v e r e d t h a t h e r g r a n d f a t h e r a n d g r e a t g r a n d f a t h e r in t h e
B u c k line w e r e b o t h p r o s p e r o u s f a r m e r s . Analysis o f a n o t h e r
b r a n c h i n g b a c k w o u l d have r e v e a l e d t h a t , i r o n i c a l l y , she w a s d e s -
c e n d e n t f r o m o n e o f t h e m o s t p r o m i n e n t f a m i l i e s in V i r g i n i a ' s
history.

C a r r i e ' s s t o r y is a t r a g i c saga o f o n e i n j u r e d life. I t is a l s o an

i m p o r t a n t illustration o f t h e allure and dangers o f biological
d e t e r m i n i s t i c t h o u g h t . T h e lawyers, physicians and scientists i n -
v o l v e d w i t h t h e case w e r e n o t sinister figures intent upon
d o i n g h a r m t o t h i s w o m a n o r t h e class o f p e o p l e s h e r e p r e s e n t -
ed. T h e y w e r e convinced t h a t t h e y w e r e serving t h e best inter-
ests o f s o c i e t y b y t h e i r a c t i o n s . T h e y s a w in C a r r i e ' s life w h a t
t h e y e x p e c t e d t o see, and t h e y used it t o advance a scientific
and political p o s i t i o n t h a t t h e y felt w o u l d lead t o t h e eradica-
t i o n o f social p r o b l e m s and p r e v e n t i o n o f suffering. T h e y w e r e
w r o n g . T h e idea t h a t c r e a t e d t h e m i s f o r t u n e of C a r r i e Buck
has r e p e a t e d l y p r o d u c e d t r a g i c r e s u l t s . T h a t i d e a is t h a t h u m a n
life c a n b e g u i d e d b y t h e r e a l i t i e s o f b i o l o g i c a l determinism.
T h e r e s u l t has b e e n t h a t s o m e f a m i l i e s , s o m e nationalities,
s o m e r a c e s , s o m e e t h n i c g r o u p s a n d s o m e s o c i a l classes h a v e
b e e n v i e w e d as b e i n g n a t u r a l l y , i n h e r e n t l y , a n d u n m o d i f i a b l y I n -
f e r i o r . It has b e e n o n t h i s basis t h a t t h e y h a v e b e e n deprived
of their dignity and rights.

R o b e r t C y n k a r has n o t e d t h a t J u s t i c e O l i v e r W e n d e l l Holmes
in 1920, s e v e n y e a r s b e f o r e t h e d e c i s i ó n in Buck Bell, o b s e r v -
e d , " T h e l a w is t h e w i t n e s s a n d e x t e r n a l d e p o s i t o f o u r moral
life. Its h i s t o r y is t h e h i s t o r y o f t h e m o r a l d e v e l o p m e n t o f t h e
r a c e " . C y n k a r a l s o q u o t e s H o l m e s ' s b o o k p u b l i s h e d in 1881 e n -
t i t l e d The C o m m o n Law. O n t h e f i r s t page o f t h a t b o o k H o l m e s said:

"... T h e life o f t h e l a w has n o t b e e n logic; i t has b e e n e x p e -

r i e n c e . T h e f e l t necessities o f t h e t i m e , t h e p r e v a l e n t moral
and political t h e o r i e s , intuitions o f public policy, a v o w e d or
unconscious, even t h e prejudices w h i c h judges share with
t h e i r f e l l o w - m e n , have had a g o o d deal m o r e t o d o t h a n t h e
s y l l o g i s m in d e t e r m i n i n g t h e r u l e s by w h i c h m e n s h o u l d b e
g o v e r n e d . . . i t c a n n o t be d e a l t w i t h as if i t c o n t a i n e d o n l y t h e
axioms and corollaries of a b o o k o f mathematics".
64 T h e H u m a n G e n o m e P r o j e c t w i l l m o s t c e r t a i n l y r e s u l t in s c i e n -
tific k n o w l e d g e and medical capabilities w h i c h will bring into
q u e s t i o n t h e issue o f " f e l t n e c e s s i t i e s " in r e l a t i o n t o f u n d a m e n t a l
valúes. T h e t e c h n o l o g y o f t u b a l l i g a t i o n a n d v a s e c t o m y w e r e d e -
v e l o p e d in t h e 1890s, b y 1927 i t w a s a " f e l t n e c e s s i t y " o f s o c i e t y
t h a t t h o s e d e e m e d d e f e c t i v e o n t h e basis o f e u g e n i c science
must be sterilized. T h e H u m a n G e n o m e Project will provide in-
sights i n t o h u m a n n a t u r e w i t h a v a l i d i t y i n c o m p a r b l e t o t h e inac-
c u r a c i e s o f t h e e u g e n i c s m o v e m e n t . It w i l l p r o v i d e f o r t h e d e -
v e l o p m e n t of technologies w h i c h will eclipse anything that
m e d i c i n e has k n o w n b e f o r e . T h e p o t e n t i a l s f o r h u m a n benefit
are obviously e n o r m o u s . I t seems t o this observer, however,
t h a t t h e greatest challenge posed by t h e H u m a n G e n o m e Pro-
j e c t w i l l b e t o c o n d u c t its w o r k a n d p r o v i d e t h e b e n e f i t s o f its
e f f o r t s t o a w o r l d o f p e o p l e w h o a r e s e e n as m u c h m o r e t h a n
t h e s u m t o t a l o f t h e i r biological c o m p o n e n t s . T o rise above t h e
t e m p t a t i o n s and dangers o f biological d e t e r m i n i s m w e m u s t c o n -
t i n u é t o see p e o p l e , w i t h all d u e r e s p e c t t o B.F. S k i n n e r , as
agents o f f r e e d o m a n d d i g n i t y .

O u r f i r s t c o m m i t m e n t m u s t be, I b e l i e v e , t o basic h u m a n r i g h t s
a n d valúes. Even w h e n t h e c a p a c i t y t o i n t e r v e n e e x p e d i e n t l y in
t h e lives o f o t h e r s s e e m s t o be b e s t f o r t h e m a n d s o c i e t y ; e v e n
w h e n t h e " f e l t necessities o f o u r t i m e s " s e e m t o u r g e us s o c o m -
pellingly t o a c t q u i c k l y a n d e f f i c i e n t l y , t h i s m u s t be t r u e . T h e e t h i -
cal f o u n d a t i o n s o f h u m a n life a r e t o be f o u n d in h u m a n s o u r c e s .
T h e eugenicists l o o k e d t o e v o l u t i o n a r y t h e o r y a n d M e n d e l i a n g e -
netics f o r m o r a l t r u t h s . T h e y felt t h a t natural selection and M e n -
delian g e n e d i s t r i b u t i o n s c o u l d p r o v i d e m o d e l s f o r social e t h i c s .
T h e f a i l u r e o f t h i s a p p r o a c h w a s e v i d e n c e d in t h e needless i n s t i -
t u t i o n a l i z a t i o n o f t h o s e d e e m e d t o be " u n f i t " f o r t h e social
" s t r u g g l e " , in t h e s t e r i l i z a t i o n o f p e o p l e i n a c c u r a t e l y assessed t o
be t h e c a r r i e r s o f d e f e c t i v e g e n e s a n d in t h e m o r a l h o r r o r s o f t h e
holocaust.

M o r a l a n d e t h i c a l a g e n c y is an a t t r i b u t e o f p e o p l e , n o t o f s c i -
ence o r t h e scientific m e t h o d . T h e r e c o g n i t i o n t h a t w e are e t h i -
cal a n d m o r a l a g e n t s , a n d t h a t t h e d e c i s i o n s o f w h a t w e sould
d o , as o p p o s e d t o w h a t w e c a n d o , r e s t s w i t h us as p e o p l e in
i n t i m i d a t i n g . O n t h e o t h e r h a n d , i t is e x c i t i n g . I believe t h i s m e e t -
i n g is a n e x p r e s s i o n of that recognition. As the p o w e r of
science f o r human benefit g r o w s t h r o u g h t h e w o r k o f t h e H u -
man G e n o m e P r o j e c t , so g r o w s t h e i m p o r t a n c e of ethical
q u e s t i o n s a b o u t t h e u s e a n d y i e l d o r t h a t p o w e r . T h e g r e a t sig-
nificance of this c o n f e r e n c e may be t h e o p p o r t u n i t i e s it p r o -
vides f o r exchanges b e t w e e n p e o p l e w h o a r e m o t i v a t e d by t h e
making of discoveries, and t h o s e w h o seek t o understand t h e
human t r u t h o f t h o s e discoveries. I am h o n o r e d t o be a partic-
i p a n t in t h i s f o r u m , a n d I f e e l a s e n s e o f e x h i l a r a t i o n a t t h e
p o t e n t i a l t h a t t h e s e c o n v e r s a t i o n s w i l l have f o r t h e f u t u r e . I am
also g r a t e f u l f o r t h e i m p o r t a n c e t h a t t h e o p p o r t u n i t y t o s p e a k | 65
w i t h t h i s d i s t i n g u i s h e d g a t h e r i n g b e s t o w s o n t h e life o f a p o o r ,
u n e d u c a t e d w o m a n w h o d e v o t e d h e r life t o c a r i n g f o r o t h e r s ,
m y p r e s e n t a t i o n t o y o u is d e d i c a t e d t o C a r r i e B u c k .
66

REFERENCES

B u c k v. B e l l . 1927. 274 U.S. 200. 47 S. Ct. 584.

C y n k a r , R. J . 1981. "Buck v. Bell: 'Felt Necessities' v. Fundamental Va-

lúes". Columbia Law Rev/ew. 8 1 . pp. 1418-1461.

E s t a b r o o k , A . H . a n d D a v e n p o r t , C . 1912. The Nom Family: A Study

in Cacogenics. C o l d Spring Harbor, N.Y.: Eugenics Record Office.

Holmes, O. W . 1881. The Common Law. Boston: Little, B r o w n and

Company.

H o l m e s , O . W . 1920. Coi/ecíed Legal Papers. Buffalo, N.Y.: W.S. Hein.

H o l m e s , S . J . 1936. Human Genet/cs ond Its Social Impon. N e w Y o r k :

McGraw-Hill.

K e v l e s , D . J . 1984. In the Nome of Eugenics: Genetics and the Uses o f Hu-

man Hereditary. N e w Y o r k : Knopf.

L u d m e r e r , K. M. 1972. Genet/cs and American Society. Baltimore: Johns

Hopkins University Press.

L a u g h l i n , H . H . 1929. The Legal Status o f Eugenical Sterilization. Chica-

go: Psychopathic Laboratory of the Municipal C o u r t of Chicago.

R a f t e r , N . H . 1988. White Trash: The Eugenic Family Studies, 1877-1919.

Boston: N o r t h e a s t e r n University Press.

S m l t h , J . D . 1985. Minds Made Feeble: The Myth and Legacy o f the Kal-
likaks. Austin, Texas: Pro-Ed.

S m i t h , J . D . a n d N e l s o n , K . R . 1989. The Sterilization o f Carrie Buck.

Far Hills, N.J.: N e w H o r i z o n Press.

Triáis o f W a r Crimináis Before t h e N u r e m b e r g M i i i t a r y Tribunals.

( 1 9 5 0 ) . V o l . 4 . W a s h i n g t o n D . C . : U.S. G o v e r n m e n t P r i n t i n g O f -
fice.

Triáis o f W a r Crimináis Before t h e N u r e m b e r g M i i i t a r y Tribunals.

( 1 9 5 0 ) . V o l . 5. W a s h i n g t o n D . C . : U.S. G o v e r n m e n t P r i n t i n g O f -
fice.
 67

THE HUMAN: A PROTESTANT

CHRISTIAN VIEW

Jack L Stotts

Austin Presbyterian Theological Seminar/, Austin, Texas (USA)

ABSTRACT

The deciphering o f human genetic composition prob-

ably poses once more the question o f what m a n re-
ally is. This is an oíd question on the human that can
clearly be interpreted from a religious viewpoint. This
analysis begins with the premise that man was cre-
ated in the image and likeness o f God, from which so-
lutions derive that can be understood from the politi-
cal-social a n d biological points o f view. However,
Protestantism o/so gronts man an active role as the
administrator o f creation. This function can be under-
stood as a capacity to m a n i p ú l a t e a n d it is this
interpretation that should be carefully analysed i f it is
not to become a moral justification for certain appli-
cations o f science a n d technology. On the contrary, it
is a capacity that should be impregnated with humil-
ity, o/so bearing in m i n d that m a n , the scientist, con-
fronts problems with the category o f mysteries that
are h a r d to so/ve. Religión a n d science, therefore,
have a common aim: man.
T h i s p a p e r w i l l begin w i t h M i g u e l C e r v a n t e s a n d c o n c l u d e w i t h a | 69
reference t o W . H . A u d e n , distinguished authors, representatives
o f d i s t i n c t i v e h i s t o r i c a l eras. In b e t w e e n a p e r s p e c t i v e based o n a
Protestant construal o f t h e w o r l d w i l l be offered. T h e intended
r e s u l t is an e x p l o r a t i o n o f h o w o n e r e l i g i o u s t r a d i t i o n , a n d t h a t
far r i c h e r a n d v a r i e d t h a n can be s u g g e s t e d , m a y , can a n d s h o u l d
respond t o the Human G e n o m e Project w i t h reference t o the
question of the human.

Religión as I a m using t h e t e r m m e a n s t h e h u m a n a t t e m p t t o af-

firm a n d t o deal w i t h , t h r o u g h r i t u a l , i n t e l l e c t u a l a c t i o n s , a n d m o r -
al b e h a v i o r , an U l t í m a t e P o w e r w h o s e i n t e n t i o n is g o o d . By U l t í -
m a t e P o w e r I m e a n a f o r c é t h a t is able t o a c c o m p l i s h its o w n
p u r p o s e s a n d is finally n o t s u b j e c t t o t h e c o n t r o l o r m a n i p u l a t i o n
o f o t h e r p o w e r s . T h e a p p r o p r i a t e t e r m i n o l o g y f o r such an U l t í -
m a t e P o w e r is G o d .
\

T h e o l o g y , t a l k a b o u t t h e U l t í m a t e P o w e r , is u n d e r s t o o d h e r e as a
w a y o f c o n s t r u i n g t h e w o r l d s o t h a t t h e c r i t i c a ! r e f e r e n c e p o i n t is
w h a t is c o n f e s s e d t o b e g o d . A P r o t e s t a n t c o n s t r u a l o f t h e w o r l d
means t h a t t h e c r i t i c a l r e f e r e n c e p o i n t is t h e G o d w h o is k n o w n
u n i q u e l y in Jesús C h r i s t as m e d i a t e d t h r o u g h a p a r t i c u l a r t r a d i t i o n .
T h a t t r a d i t i o n gives u n c o m m o n place o f i m p o r t a n c e t o t h e r e f l e c -
t i o n a n d b e h a v i o r o f t h o s e r e f o r m i n g m o v e m e n t s in W e s t e r n Eu-
r o p e o f t h e s i x t e e n t h c e n t u r y , C.E., m o v e m e n t s w i t h leaders such
as M a r t i n L u t h e r a n d J o h n C a l v i n . T o l ó c a t e o n e s e l f in t h a t t r a d i -
t i o n is n o t t o c l a i m s u p e r i o r i t y f o r it. Ñ o r is i t t o r e s t r i c t o n e ' s r e -
s o u r c e s t o it. It is t o r e c o g n i z e t h a t o u r r e f l e c t i o n a b o u t G o d a n d
h u m a n s is i n e v i t a b l y a n d s e l f - c o n s c i o u s l y h i s t o r i c a l .

M i g u e l C e r v a n t e s , 1547 t o 1616, l i v e d in t h e m i d s t o f an h i s t o r i -
cal e a r t h q u a k e , o n e w h e r e t h e t e c t o n i c plates o f h u m a n d e f i n i -
t i o n w e r e shifting. M i l á n K u n d e r a , a c o n t e m p o r a r y C z e c h born
n o v e l i s t has w r i t t e n :

" A s G o d s l o w l y d e p a r t e d f r o m t h e s e a t w h e r e he had d i r e c t -
e d t h e u n i v e r s e a n d its o r d e r o f v a l ú e s , d i s t i n g u i s h e d g o o d
f r o m e v i l , e n d o w e d each t h i n g w i t h m e a n i n g , D o n Quixote
s e t f o r t h f r o m his h o u s e t o a w o r l d he c o u l d n o l o n g e r r e -
c o g n i z e . In t h e a b s e n c e o f t h e S u p r e m e Judge, t h e w o r l d s u d -
d e n l y a p p e a r e d in its f e a r s o m e a m b i g u i t y ; t h e single d i v i n e
t r u t h d e c o m p o s e d i n t o myriad relative t r u t h s parceled o u t by
man. Thus was b o r n t h e w o r l d of the M o d e r n Era".

James W a l l , e d i t o r o f The Christian Century, a w e e k l y r e l i g i o u s p e -

r i o d i c a l , c o m m e n t i n g o n t h e a b o v e q u e s t i o n , suggests t h a t t h e
p u b l i c a t i o n o f D o n Quixote a n t i c i p a t e d t h e a g o n y o f a c i v i l i z a t i o n
t h a t t r a d e d c e r t a i n l y a b o u t G o d f o r t h e t a i n t e d ecstasy o f h u m a n
c o n t r o l . ( W a l l , p. 5 3 1 ) .

If t h e r e w e r e w i n d m i l l s r a t h e r t h a n k n i g h t s t o b e c h a l l e n g e d b y
t h e m a n f r o m La M a n c h a , t h e r e a l i t y w a s n o t in t h e external
70 b u t in t h e ¡ n t e r n a l l a n d s c a p e . It w a s t h e w a y o n e s a w t h a t m a d e
all t h e d i f f e r e n c e . A n d t h e M o d e r n E r a h a d a w a y o f s e e i n g t h e
w o r l d , including the human, that differed f r o m its histórica!
p r e d e c e s s o r s . It h a d as w e l l , s i n c e s e e i n g a n d v a l u i n g a r e r e l a t -
ed, a d i f f e r e n t h i e r a r c h y o f valúes. N o w t h e f r e e d o m and a u -
t o n o m y o f t h e i n d i v i d u a l s e l f as a d e c i s i ó n m a k e r w a s a f f i r m e d
r a t h e r t h a n his o r h e r s u b o r d i n a t i o n t o e x t e r n a l c e n t e r s of
authority. Liberation f r o m oppressive institutions was proclaim-
ed and Consolidated. H u m a n reason broke the constrictive
bonds o f c u s t o m and religious pretensions t o be t h e mediator
o f t r u t h in t h e d i v e r s e r e a l m s o f life. A n d t h e n e w h u m a n , e x -
u l t i n g in a n e w s e l f - u n d e r s t a n d i n g , b e c a m e t h e e x p l o r e r a n d c o l -
o n i z e r o f w o r l d s vast and m i n u t e , at o n c e f e a r s o m e and beaut-
ful. T h e n e w self b e c a m e s i m u l t a n e o u s l y a h u m b l e servant,
indeed a mendicant, before knowledge, and a Promethean h e r o
w h o w o u l d d o all t h i n g s . M o d e r n s c i e n c e a n d t e c h n o l o g y w e r e
t h i s s e l f s e x t e n s i o n s a n d e x p r e s s i o n s . A n d if m o d e r n science
a n d t e c h n o l o g y w e r e as a t t a c h e d t o t h e p u r p o s e s a n d p o w e r s
o f c o m m e r c e a n d n a t i o n a l i n t e r e s t s as t o d i s i n t e r e s t e d e n d e a v -
o r s , t h e pay off w a s clearly f o r all. O r so it w a s assumed,
t h o u g h t h e spoils o f the n e w era w e r e unevenly distributed
a n d t h e s t r u g g l e o f t h e s c i e n t i s t s w a s n o t w i t h o u t its s e t b a c k s .
B u t in t h e m o d e r n e r a , w i t h all its d r e a d f u l a m b i g u i t y , h u m a n s
w e r e in c o n t r o l .

D o n Q u i x o t e was confused. His s t o r y was question m a r k a b o u t

t h e c o n t o u r s and consequences o f t h e m o d e r n w o r l d . Later c o l -
o n i z e r s o f t h e n e w e r a w o u l d see clearly w h a t D o n Q u i x o t e vague-
ly s e n s e d . T h e i c o n s o f t h e n e w e r a w e r e n e i t h e r cathedrals
ñ o r t h r o n e s . T h e y w e r e laboratoires and factories, symbols of
t h e rule o f science and t e c h n o l o g y .

In t h e m o d e r n e r a s c i e n c e a n d t e c h n o l o g y ( a p p l i e d s c i e n c e ) w e r e
r e g a r d e d n o t o n l y as w a y s o f k n o w i n g a n d d o i n g . T h e y b e c a m e a
d o m i n a n t a n d in s o m e cases an e x c l u s i v e p a r a d i g m f o r knowing
a n d f o r b e i n g in t h e w o r l d . T o be h u m a n w a s t o k n o w b y m e a n s
o f o b s e r v a t i o n a n d m e a s u r e m e n t , u n d e r c o n d i t i o n s o f causality,
a n d t h e n t o a p p l y w h a t had b e e n o b s e r v e d a n d m e a s u r e d t o s p e -
cific goals. Its y i e l d has b e e n i n c r e d i b l e advances in t h e w a y w e
live - m o d e r n m e d i c i n e is b u t o n e , b u t s u r e l y o n e p r o f o u n d l y i m -
p o r t a n t , e x a m p l e o f its a c h i e v e m e n t .

T h e consequences o f this w a y o f being human w e r e n o t w i t h o u t

t h e i r costs. T o t h e surprise o f many, irrational forces w e r e un-
yielding b e f o r e reason's advances. Indeed such forces found
s l i g h t r e s i s t a n c e in r e c r u i t i n g t h e m o s t a d v a n c e d o f w h a t w a s
k n o w n , a n d its m o s t skillful a p p l i c a t i o n , t o t h e engines o f d e s t r u c -
t i o n and t o n a r r o w commercial interests. T h e dark underside o f
t h e h u m a n lay b e y o n d t h e g r a s p o f t h i s m o d e r n w a y o f b e i n g h u -
m a n . I n d e e d i t is t h e v e r y c o n s e q u e n c e s o f m o d e r n s c i e n c e a n d
t e c h n o l o g y t h a t have p r o v o k e d t h e h u m a n q u e s t i o n r a t h e r t h a n
a n s w e r i n g it. N e g a t i v e e x a m p l e s o f t h a t p r o v o c a t i o n w e r e the
N a z i m o v e m e n t ' s use eugenics, a n d H i r o s h i m a , t h o u g h I d o n o t | 71
e q u a t e t h e s e in any o t h e r w a y t h a n t h i s : b o t h raised d r a m a t i c a l l y
t h e q u e s t i o n o f w h a t i t m e a n s t o be h u m a n .

T h e p r o j e c t w e a d d r e s s t h i s w e e k has a s i m i l a r f u n c t i o n . It is t h e
q u e s t i o n o f t h e h u m a n t h a t is s t i m u l a t e d , n o t a n s w e r e d , b y t h e
k n o w l e d g e o f o u r genetic s t r u c t u r e . Surely the philosopher's
mándate, " K n o w t h y s e l f , meant m o r e than the injuction to
k n o w o u r biological c o m p o s i t i o n , its s t r u c t u r e , p r o c e s s , and
c o n t e n t . It m e a n t m o r e t h a n t o m e a s u r e t h e g e n e t i c s t u f f w h i c h
shapes us. It m e a n t r a t h e r t o t a k e f u l l m e a s u r e o f o u r s e l v e s , o f
w h o w e a r e as h u m a n beings. T h e a n c i e n t q u e s t i o n stimulates
m o d e r n i t y t o b e c o m e p o s t - m o d e r n . Such an e r a incorporates
observation, measurements, and application into a m o r e com-
p r e h e n s i v e v i e w o f t h e h u m a n . It r e f u s e s t h e r e d u c t i o n i s m o f e x -
clusivistic e p i s t e m o l o g i e s . It e n c o u r a g e s us t o p r o b é q u e s t i o n s o f
w h o w e a r e , a n d w h y a n d h o w w e a r e t o live, f r o m a v a r i e t y o f
angles.

T o say as m u c h is in n o w a y t o r e p u d í a t e t h e m o d e r n e r a w i t h
its h u m a n l y l i b e r a t i n g i n t e n t i o n s a n d c o n t r i b u t i o n s . It is n o t to
s e e k a t i m e w h e n e x t e r n a ! i n s t i t u t i o n s r e p u d í a t e as i l l e g i t i m a t e
t h e s c i e n t i f i c , i m p o s i n g b y f o r c é a l t é r n a t e w o r l d v i e w s . It is t o af-
f i r m t h a t any d o m i n a n t w o r l d v i e w o f t h e h u m a n finally yields
b o t h positive benefits and perennial questions. " M o d e r n medi-
cine", a philosopher once noted, "refreshes the problem of evil".
H e m e a n t t h a t f o r e v e r y c u r e o f a d r e a d e d d i s e a s e , t h e r e is
a n o t h e r disease w a i t i n g in t h e w i n g s t o d r a m a t i z e n o t o n l y its
p o t e n c y b u t its a g e n t r y o f a d e s t r u c t i v e p o w e r t h a n r e f u s e s t o
be s u b d u e d , o n e quaintly called t h e d e m o n i c . For e x a m p l e , t o
p r o l o n g life s o t h a t t h e n o r m a l W e s t e r n l i f e - e x p e c t a n c y e x c e e d s
t h e w i l d e s t d r e a m s o f a I 9 t h c e n t u r y r e s i d e n t is s u r e l y a p o s i t i v e
gain. B u t i t is also t o fill n u r s i n g h o m e b e d s w i t h t h o s e w h o s e
h a b i t a t i o n p e r s o n a l l y is t h e past, s o m e l o n g ago e r a p a c k e d i n t o
chemical c o m p o s i t i o n s m o r e p o w e r f u l than c u r r e n t stimuli, into
electhcal circuitry no longer receptive t o new stimuli. A n d w h e n
t h a t c o n d i t i o n o c c u r s , t h e d e f i n i t i o n o f t h e h u m a n is p r o v o k e d ,
n o t a n s w e r e d . O r , w h e n " n o t h i n g " is p o s s i b l e , as i t is a n u c l e a r
age, o r w h e n h u m a n m u t a t i o n is in h u m a n h a n d s , as i t is i n c r e a s -
ingly, t h e n t h e q u e s t i o n o f t h e g e n u i n e l y h u m a n s c u r r i e s into
t h e p i c t u r e . It begins t o w h i s p e r a n d t h e n t o d e c l a i m , " I t is o n e
t h i n g t o say o f a s c i e n t i f i c t h e o r y . It is t r u e . It is q u i t e a n o t h e r t o
say, s c i e n c e t e a c h e s us w h a t ' t r u e ' m e a n s " ( H a r t t , p. 9 ) . In t h a t
q u e r y a b o u t w h a t is m e a n s t o b e t r u l y h u m a n , s c i e n t i s t s j o i n all
t h e i r n e i g h b o r s in a d e b a t e s i m u l t a n e o u s l y t r a n s c e n d i n g a n d u n d e r -
girding t h e scientific and technological endeavors, questioning
the view of the s e l f as p r i m a r i l y one w h o is d e f i n e d by
k n o w i n g by m e a s u r e m e n t and d o i n g by a p p l i c a t i o n o f such
measurements.

In such a s e a r c h , o n e is g r a t e f u l t o p r o j e c t s like t h e H u m a n C e -
n ó m e P r o j e c t f o r raising t h e issue o f t h e h u m a n so f o r c e f u l l y a h d
| 72 concretely. W h o is t h e h u m a n w h o s e b i o l o g i c a l b e i n g w e are
c o m m i t t e d t o understanding and t o w h o s e benefit, presump-
tively, this understanding will contribute?

In t h e P r o t e s t a n t h e r i t a g e , t h o u g h b y n o m e a n s in i t e x c l u s i v e l y ,
t h e r o o t m e t a p h o r s o f t h e h u m a n as " C r e a t e d in t h e Image o f
G o d " a n d t h e h u m a n as " S t e w a r d o f C r e a t i o n " have provided
n o r m a t i v e m o d e l s . I w i l l s k e t c h o u t aspects o f t h e s e m o d e l s o f
h u m a n i t y , p r o p o s i n g essential e l e m e n t s a n d suggestions o f h u m a n
beingness.

First, t h e h u m a n as " I m a g e o f G o d " .

This m e t a p h o r "Image of G o d " draws f r o m t h e Génesis account,

t h a t a f f i r m s : " S o G o d c r e a t e d A d a m in his o w n i m a g e , in t h e
image of G o d he c r e a t e d h i m ; m a l e and f e m a l e he created
t h e m " (Génesis 1:27). In t h e o v e r a l l c o n t e x t o f t h i s v e r s e t h e
t h e o l o g i c a l c o n s t r u a l is o f G o d as a g e n e r a t i v e , n u r t u r i n g , a n d
o r d e r i n g p o w e r . T h i s G o d is t h e s o u r c e o f h u m a n life, a n d ac-
c o r d s a special place in t h e u n i v e r s e t o t h e h u m a n species a n d
t o t h e i n d i v i d u a l . B o t h t h e h u m a n self a n d t h e h u m a n species
e m b o d y d e r i v a t i v e v a l u é a n d w o r t h f r o m t h i s C r e a t o r . T h i s giv-
e n n e s s o f v a l u é a n d w o r t h is n o t d e p e n d e n t o n achievement,
a c c o m p l i s h m e n t , o r g o o d d e e d s , ñ o r is i t g e n e t i c a l i y d e t e r m i n e d .
It is a c c o r d e d b y an U l t í m a t e P o w e r . T h u s , t h e s e l f s d i g n i t y is
n o t in itself a n d its a c c o m p l i s h m e n t s . It is b e s t o w e d . A s t h e P r o t -
e s t a n t r e f o r m e r s c l a i m e d , life is j u s t i f i e d b y g r a c e , i.e., p u r é giv-
enness ( C r e a t i o n ) and p u r é acceptance (forgiveness). A basic
v a l u é w a r r a n t e d b y t h e v i e w o f G o d is t h a t o f t h e i n d i v i d u a l i t y o f
t h e self a n d its i m m u n i t y f r o m e n f o r c e d d e f i n i t i o n o r d e t e r m i n a -
r o n b y o t h e r h u m a n s . T o b e h u m a n is t o r e c e i v e o n e ' s o w n life
a n d t h e w h o l e c r e a t i o n in g r a t i t u d e a n d t o a f f i r m t h e s e l f s d i g -
n i t y . James G u s t a f s o n w r i t e s :

" T h e G é n e s i s a c c o u n t o f t h e c r e a t i o n gives us, f r o m a r e l i -

gious perspective, t h e m o s t solid g r o u n d s f o r human dignity.
C a l v i n , like m o s t t h e o l o g i a n s w h o have a t t e n d e d t o t h a t ac-
c o u n t , finds i t an a s s u r a n c e o f t h e special d i g n i t y o f o u r s p e -
cies, a n d a r e c o r d o f t h e d i v i n e b e n e v o l e n c e t h a t is d i r e c t e d
t o w a r d us. ' W e o u g h t ' he w r o t e , 'in t h e v e r y o r d e r o f t h i n g s
diligently t o c o n t é m p l a t e G o d ' s fatherly love t o w a r d mankind,
in t h a t h e d i d n o t c r é a t e A d a m u n t i l h e h a d lavished u p o n t h e
u n i v e r s e all m a n n e r o f g o o d t h i n g s ' . If G o d had p u t A d a m o n
t h e e a r t h w h i l e i t w a s still ' s t e r i l e a n d e m p t y ' he w o u l d not
have p r o v i d e d s u f f i c i e n t l y f o r h u m a n w e l f a r e . ' L e t us m a k e
m a n in o u r i m a g e , a f t e r o u r likeness a n d l e t h i m have d o m i n -
i ó n o v e r t h e fish o f t h e sea, a n d o v e r t h e b i r d s o f t h e air,
a n d o v e r t h e c a t t l e , a n d o v e r all t h e e a r t h , a n d o v e r every
c r e e p i n g t h i n g t h a t c r e e p s u p o n t h e e a r t h , says G o d . W h i l e
t h e o l o g i a n s have d i s p u t e d t h r o u g h t h e ages a b o u t w h i c h h u -
m a n c a p a c i t y m a k e s m a n in t h e image o f G o d , t h e have n o t
 d i s p u t e d t h e n o t i o n t h a t t h e passage w a r r a n t s t h a t high d i g - 173
n i t y w h i c h w e c l a i m f o r o u r species. Ñ o r have t h e y d i s p u t e d
t h a t all t h e r e s t o f t h e c r e a t i o n e x i s t s f o r o u r s e r v i c e . W h a t
h i g h e r c l a i m f o r d i g n i t y can b e m a d e , f r o m a r e l i g i o u s per-
s p e c t i v e , t h a n t h a t m a n is m a d e in t h e image a n d likeness o f
G o d ? " ( G u s t a f s o n , p. 100).

A s e c o n d c h a r a c t e r i s t i c o f t h e h u m a n is t h a t t h e self m i r r o r s t h e
C r e a t o r in its f r e e d o m . T h e n o n - n e c e s s i t y o f t h e c r e a t i o n , its giv-
e n n e s s , leads t o an a f f i r m a t i o n t h a t w h a t w a s c r e a t e d a n d is
b e i n g c r e a t e d arises a n d is s u s t a i n e d o u t o f t h e f r e e d o m o f t h e
C r e a t o r . T h e P r o t e s t a n t emphasis o n individual f r e e d o m and a u -
t o n o m y m i r r o r s t h e f r e e d o m a n d a u t o n o m y o f G o d . It is an affir-
m a t i o n o f f r e e d o m o f c h o i c e as a h u m a n c a p a c i t y .

In t h e G é n e s i s s t o r i e s o f c r e a t i o n t h e p r e s e n c e o f t h e c o m m a n d ,
" O f t h e t r e e o f t h e k n o w l e d g e o f g o o d a n d evil y o u shall n o t e a t "
(2:17) presupposes f r e e d o m o f choice o n t h e p a r t o f t h e one
b e i n g a d d r e s s e d . Such f r e e d o m ¡s t h e g i v e n c a p a c i t y o f a self t o
e x e r c i s e c h o i c e w i t h i n a m o r e o r less b r o a d / n a r r o w b a n d o f
o p t i o n s . B u t t h e c a p a c i t y f o r f r e e d o m m a y , i r o n i c a l l y , also lead t o
bondage.

F o r P r o t e s t a n t s , g e n u i n e f r e e d o m has a te/os, a p u r p o s e . A c c o r d -
ing t o a P r o t e s t a n t p e r s p e c t i v e , t o b e f r e e i n v o l v e s r e s p o n s i b i -
lity. T o b e f r e e is t o e n t e r i n t o a r e l a t i o n s h i p o f b e i n g f r e e f o r
others. D i e t r i c h Bonhoeffer, G e r m á n theologian and martyr,
w r o t e , " T h e f r e e d o m o f t h e C r e a t o r is p r o v e d b y t h e f a c t t h a t
he a l l o w s us t o b e f r e e f o r h i m , a n d t h a t m e a n s n o t h i n g e x c e p t
t h a t h e c r e a t e s his i m a g e o n e a r t h " . ( C r e a t i o n a n d Fall, p. 3 8 )
W h a t B o n h o e f f e r g o e s o n t o cali t h e p a r a d o x o f " c r e a t e d f r e e -
d o m " links d e p e n d e n c e ( d e t e r m i n i s m ) w i t h f r e e d o m (indeter-
m i n i s m ) . I t is a g a i n s t " c r e a t e d f r e e d o m " t h a t h u m a n s rebel,
m a k i n g f r e e d o m as a c a p a c i t y t o c h o o s e a s o u r c e o f isolation
and loneliness, a g r o u n d o f p o w e r o v e r against, r a t h e r than
p o w e r w i t h . B u t t h e positive valué called f r e e d o m embraces t h e
n o r m a t i v e a f f i r m a t i o n t h a n t h e h u m a n g i f t o f c h o o s i n g ¡s b a s i -
cally a d e c l a r a t i o n o f a n o r m a t i v e telas g r o u n d e d in t h e p o s s i b i l -
ity o f d i r e c t i n g one's self-generative capacities t o w a r d t h e w e l l
b e i n g o f t h e o t h e r . O n e is f r e e f o r o t h e r s , as G o d f r e e l y is f o r
others.

T h i r d , t o c r e a t e d in t h e i m a g e o f G o d is t o b e c r e a t e d social.
" M a l e a n d f e m a l e h e c r e a t e d t h e m . " B e c r e a t e d in G o d ' s image is
t o be c r e a t e d as a r e l a t i o n a l beings, a social self. W e c a n n o t b e
h u m a n a l o n e . W e c a n n o t b e h u m a n w i t h o u t o t h e r h u m a n beings.
T h a t is t r u e b i o l o g i c a l l y , p s y c h o l o g i c a l l y , a n d s p i r i t u a l l y . W e be-
c o m e o u r s e l v e s in an I n t e r a c t i v e , t r a n s a c t i o n a l w o r l d . W e have
no w a r r a n t t o act unilaterally, w i t h o u t reference t o o t h e r s . W e
gain o u r h u m a n i t y in d e a l i n g w i t h o t h e r h u m a n s . O u r f u n d a m e n t a l
h u m a n c o n d i t i o n is o n e o f p l u r a l i t y . I n d i v i d u a l i t y a r i s e s o u t of
social m a t r i c e s .
74 T h i s u n d e r s t a n d i g o f t h e as s o c i a l m e a n s t h a t a c h a r a c t e r i s t i c
a n d d i s t i n c t i v e h u m a n b e h a v i o r is w h a t H a n n a h A r e n d t called
" a c t i o n . " ( A r e n d t , The H u m a n Condition, p p . 155 ff.) A c t i o n is
t h e c r e a t i o n o f a h u m a n w o r l d by c o n v e r s a t i o n a b o u t t h e h u -
m a n g o o d , e n g a g e d in by a p u b l i c c o m m u n i t y . It is t h e l e g i t í m a t e
" p u b l i c " t h a t has e x p a n d e d d o w n t h r o u g h t h e c e n t u r i e s . T h e
p u b l i c n o w e m b r a c e s all m e m b e r s o f a c o m m u n i t y , n o t j u s t t h e
rich, t h e noble, males, o r a particular r a c e . I t is t h e public
w h i c h d e t e r m i n e s its o w n c o r p o r a t e life. T h u s t h e r o l e o f n e w
p r o s p e c t / t h r e a t s f o r life m u s t b e s u b m i t t e d t o t h e f o r u m of
public debate and decisión. This public f o r u m makes imperative
t h e i n t r o d u c t i o n , f o r example, of educational p r o g r a m s so t h a t
t h e public may i n d e e d by i n f o r m e d and give c o n s e n t t o prac-
t i c e s t h a t a f f e c t it. A l l , in s o f a r as p o s s i b l e , a r e t o b e s u b j e c t s o f
policies and p r o c e d u r e s affecting t h e m , n o t objects o f such. T o
be c r e a t e d in t h e i m a g e o f G o d is t o a f f i r m t h a t all p e o p l e - a l l
human c r e a t u r e s - are intended members of the body politic,
agents o f t h e i r o w n and o t h e r f u t u r e s n o m a t t e r h o w esoteric
the knowledge.

T h e h u m a n as a social self is always a p o l i t i c a l self, d e a l i n g w i t h

t h e c o n t e n t o f w h a t life is t o be a n d h o w life is t o be s h a p e d , t r e a t -
ing issues b o t h o f d e f i n i t i o n a n d o f p o w e r . It is t h i s p u b l i c w h i c h
bears b o t h t h e p o w e r and t h e responsibility t o d e t e r m i n e its
o w n life. O n e c o n s e q u e n c e is t h a t d e c i s i ó n m a k i n g a b o u t t h e h u -
m a n a n d w h a t affects t h e h u m a n c a n n o t e t h i c a l l y b e l e f t t o an
é l i t e , w h e t h e r s c i e n t i s t s o r e t h i c i s t s , b u t is t o be l o d g e d w i t h t h e
entire b o d y politic. T h e t r a j e c t o r y o f appropriate decisión makers
w h e n i t c o m e s t o h u m a n g e r m line m a n i p u l a t i o n , f o r e x a m p l e , is
the universal human c o m m u n i t y . A c c o r d i n g t o this under-
s t a n d i n g , e f f i c i e n c y as a v i r t u e g i v e s w a y t o t h e o b l i g a t i o n of
consensus f o r m a t i o n .

F o u r t h , t o b e c r e a t e d in t h e image o f G o d is t o a c k n o w l e d g e t h e
b r o k e n n e s s o f t h a t i m a g e . H u m a n s a r e , in t h e f i r s t i n s t a n c e , f i -
nite, living u n d e r t h e c o n d i t i o n s o f l i m i t a t i o n and death. B u t t h a t
is n o b r o k e n n e s s . B r o k e n n e s s is t h e s e l f - i n d u c e w o u n d in t h e
h u m a n s p e c i e s . It is t h e p e r s i s t e n t p r e t e n s i ó n o f t h e self i n d i v i -
dually and colectively t o assert m o r e t h a n it k n o w s , claiming, f o r
e x a m p l e , universal perspectives f o r one's o w n local and p a r o -
chial v i e w p o i n t . It is also t h e h u m a n i n c l i n a t i o n t o use w h a t falls
i n t o its h a n d s f o r t r i v i a l a n d d e s t r u c t i v e p u r p o s e s . In b r i e f , t h e
h u m a n is o n e w h o s e c o n d i t i o n is d i s t o r t e d as t o p u r p o s e , w i l l
a n d a f f e c t i o n s . T h e h u m a n is o n e w h o d i s t o r t s t h e lives o f o t h -
e r s , as w e l l as n a t u r e . W h y t h i s e m p h a s i s h e r e u n d e r " I m a g e o f
G o d ? " . Because o n e k n o w s one's b r o k e n n e s s w h e n o n e c o m -
p a r e s o n e ' s self w i t h t h e i m a g e o f G o d , w h o s e p o w e r , wisdom
and g o o d n e s s humans are called t o reflect. A l s o , t o a c k n o w l e d g e
o n e ' s o w n a n d o t h e r s ' b r o k e n n e s s is t o i n t r o d u c e a h e r m e n e u -
t i c o f s k e p t i c i s m a b o u t all m o r a l c l a i m s , i n c l u d i n g o n e ' s o w n . A f -
f i r m a t i v e l y , i t a c k n o w l e d g e s t h e h u m a n as a v a l u i n g / d i s v a l u i n g
being, w h o s e image is c r u c i a l l y Jesús o f N a z a r e t h , f u l l y h u m a n , | 75
fully G o d .

A s t r o n g , b u t again n o t e x c l u s i v e c h a r a c t e r i s t i c o f t h e h u m a n t h a t
r e f l e c t s t h e image o f G o d , c o r r e i a t e s w i t h b r o k e n n e s s . It is f o r -
giveness. F o r g i v e n e s s is t h e p o w e r o f r e s t o r i n g b r o k e n r e l a t i o n -
ships, o f b e g i n n i n g again, o f b e i n g o p e n , n o evasive, a b o u t e r r o r s
a n d w r o n g d o i n g . F o r g i v e n e s s d i s m i s s e s w h a t has b e e n h u r t f u l ,
w h e t h e r i n t e n d e r o r n o t , a n d releases t h e f o r g i v e n a n d t h e f o r -
g i v e r f r o m t h e w e b o f t h e i r d e s t r u c t i v e r e l a t i o n s h i p s . It u n i t e s
t h e m constructively, b o t h personally and c o r p o r a t e l y . Forgive-
ness d o e s n o t m a k e " t h i n g s " r i g h t . It m a k e s p e r s o n s able t o live
in m u t u a l i t y d e s p i t t h i n g s t h e y have d o n e a n d w i l l d o t o each
o t h e r . T h e a s s u m p t i o n o f f o r g i v e n e s s is t h a t h u m a n n e s s r e q u i r e s i t
f o r personal fulfillment and f o r c o r p o r a t e endeavors. Protestants
a s s e r t t h a t t o f o r g i v e is i n d e e d d i v i n e a n d t h e r e f o r e a h u m a n p o s -
sibility a n d r e s p o n s i b i l i t y .

Finally, t h e i m a g e o f G o d f o r P r o t e s t a n C h r i s t i a n s is o n e t h a t e m -
b o d i e s a c t i v i t y . H u m a n s a r e t o image G o d ' s a c t i v i t y . T h e y d o s o
by l o v i n g n e i g h b o r s a n d c a r i n g f o r n a t u r e . T h e y d o s o by s t r u g -
gling f o r j u s t i c e . T h e y d o by o b e d i e n t a c t i v i t y in al! r e a l m s o f life.
T h i s a c t i v e p e r s p e c t i v e is in c o n t r a s t t o t h o s e f o r w h o m St. T h o -
mas A q u i n a s a r t i c u l a t e d a d i f f e r e n t s t a n d , n a m e l y , " [ O u r ] ultí-
m a t e f e l i c i t y c o n s i s t s o n í y in t h e c o n t e m p l a t i o n o f G o d . " T o be a
P r o t e s t a n t C h r i s t i a n is t o be, i n d i v i d u a l l y a n d w i t h o t h e r s , an ac-
t i v e agent. It m e a n s t o b e a s t e w a r d o f G o d ' s c r e a t i o n .

A s e c o n d r o o t m e t a p h o r t h a t has c o n s e q u e n c e s f o r t h e H u m a n
G e n o m e P r o j e c t is t h a t o f t h e h u m a n as t h e S t e w a r d o f t h e C r e -
a t i o n . In G é n e s i s t h e w o r l d is c a l l e d g o o d a n d h u m a n s a r e called
t o t e n d t h e g a r d e n o f life.

T h e P r o t e s t a n t shaping o f h u m a n n e s s a n d t h e w o r l d has b e e n d i -
v e r s e . P r o t e s t a n t i s m as a t e r m p o i n t s t o a c l u s t e r o f reforming
m o v e m e n t s t h a t r u n o n parallel t r a c k s in t h e 16th c e n t u r y a n d d i -
verge increasingly thereafter. B u t o n e e l e m e n t o f t h e Protestant
understanding o f t h e human p o i n t e d t o by t h e sociologist Max
W e b e r is t h e d e s a c r a l i z i n g o f n a t u r e . Because G o d c r e a t e s a n d
t r a s c e n d s t h e c r e a t i o n , c r e a t i o n , itself has n o s a c r e d p r e c i t s . T h i s
means t h a t n o a r e n a o f life, h u m a n n a t u r e o r o t h e r w i s e , is o u t
o f b o u n d s , e x e m p t in p r i n c i p i e f r o m i n v e s t i g a r o n a n d m a n i p u l a -
r o n . T h e h u m a n curiosity t o k n o w and t h e human desire to
apply k n o w l e d g e have b e e n l e g i t i m a t e d by a r e l i g i o u s p e r s p e c t i v e
t h a t a f f i r m e d t h e h u m a n as an a c t i v e a g e n t w h o is called b o t h t o
u n d e r s t a n d a n d t o r e s h a p e t h e w o r l d . I n d e e d , such h i s t o r i a n s o f
ideas as P r o f e s s o r L y n n W h i t e have a r g u e d t h a t P r o t e s t a n t i s m is
t o be b l a m e d f o r t h e r a p e o f n a t u r e , e l e v a t i n g t h e h u m a n t o a
status so f a r a b o v e t h e r e s t o f n a t u r e t h a t i t o v e r w h e l m e d the
p e r s p e c t i v e o f t h e h u m a n as p a r t o f n a t u r e . L i m i t e d t r a s c e n d e n c e
of t h e human o v e r nature was expanded t o absolute transcen-
| 76 d e n c e . T h e p h r a s e d e s c r i b i n g h u m a n s as " U n d e r G o d , o v e r n a -
t u r e " m a d e f o r c o n s i d e r a b l e mischief.

P r o f e s s o r W h i t e ' s p o i n t m a y be w e l l t a k e n w i t h o u t Protestant-
ism's b e i n g u n d e r s t o o d as t h e s o l é p e r p e t r a t o r o f t h e m i s u s e o f
n a t u r e a n d w h i l e r e c o g n i z i n g t h a t t h e r e w e r e c o u n t e r f o r c e s in
t h e t r a d i t i o n as w e l l . B u t t h e S t e w a r d o f C r e a t i o n as a m e t a p h o r
f o r h u m a n responsibllity f o r t h e planet e a r t h and f o r wherever
o u r p o w e r t a k e s us r e m a i n s suggestive w h e n c o n s l d e r i n g t h e H u -
man G e n o m e Project. I wlll briefly assert s o m e Implications aris-
Ing f r o m t h e m e t a p h o r .

First, t h e c r e a t i o n is n o t o u r o w n . It is G o d ' s . W e h o l d i t in t r u s t
f o r f u t u r e g e n e r a t i o n s a n d f o r all w h o a r e c u r r e n t l y residents.
W e a r e t o r e s p e c t i t a n d t o c a r e f o r it. H u m a n s a r e c a r i n g c r e a -
tures.

S e c o n d , t o c a r e f o r a n y t h i n g i n v o l v e s u n d e r s t a n d i n g it. F o r s t e w -
ards, t o understand becomes n o t just a function of curiosity
b u t a m o r a l c l a i m . T o u n d e r s t a n d o u r g e n e t i c c o m p o s i t i o n is
c o n s o n a n t w i t h t h e s t e w a r d s h i p o f t h e c r e a t i o n . In p r i n c i p i e t h e r e
is n o r e a s o n n o t t o s e e k t o u n d e r s t a n d . In fact, q u i t e t h e o p p o -
s i t e is t h e case. J o h n U p d i k e , t h e A m e r i c a n n o v e l i s t , w r o t e , " M y
theory was t h a t G o d knows everyth/ng a n d cannot be shocked. A n d
only t r u t h is useful." T h e a p p r o p r i a t e a t t i t u d e f o r s t e w a r d s is r e s -
p e c t a n d e v e n a w e f o r w h a t has b e e n " r e c e i v e d , " a n d f o r using
t h a t w e k n o w f o r caring purposes. A w e and respect f o r m t h e ap-
p r o p r i a t e c o n t e x t f o r curiosity and investigation.

A t h i r d c h a r a c t e r i s t i c o f s t e w a r d s h i s is m a n i p u l a t i o n . M a n i p u l a t i o n
m e a n s l i t e r a l l y p u t t i n g o n e ' s h a n d i n t o t h e m i x , t r a n s f o r m i n g it.
T h e s t e w a r d c a r e s f o r t h a t w h i c h is t h e o w n e r ' s . T o d o s o m e a n s
b e i n g engaged w i t h p r o c e s s e s , s t r u c t u r e s a n d p r o d u c t s . It m e a n s
a l t e r i n g w h a t is, s o t h a t t h e r e m a y b e an i m p r o v e m e n t in t h e
p r o d u c t o r an i n c r e a s e in t h e p r o d u c t i o n o r a c h a n g e in t h e
s t r u c t u r e . It m e a n s n o t playing G o d , b u t b e i n g engaged for a n d
with G o d . T h a t is, o f c o u r s e , a p r e s u m p t u o s c l a i m a n d o n e s u b -
j e c t t o abuse.

T h e issue o f m a n i p u l a t i o n is o n e w h i c h r e f e r s t o t h e use o f a p -
p r o p r i a t e t e c h n o l o g y t o achieve stated purposes. But f o r the
s t e w a r d o f c r e a t i o n t h e q u e s t i o n is n o t m a n i p u l a t i o n o r n o t , b u t
w h a t kind o f manipulations and f o r w h a t purposes. W h e n it c o m e s
t o genetic engineering, cautious u n d e r w r i t i n g o f therapeutic inter-
v e n t i o n s (gene t h e r a p y ) by all r e l i g i o u s c o m m u n i t i e s is a r e f l e c -
t i o n o f t h e positive stance t o w a r d manipulation. O n t h e other
h a n d , t h e d e t e r m i n a r o n t o r e j e c t h u m a n g e r m line i n t e r v e n t i o n s
m a y b e u n d e r s t o o d also as a p r u d e n t j u d g e m e n t , n o t a p r i n c i p l e d
o n e f o r t h e s t e w a r d . T h e issue as t o w h e r e t o d r a w t h e line in
t e r m s o f s u c h p o s s i b l e m a n i p u l a t i o n is a s l i p p e r y s l o p e i n d e e d ,
b u t i t is p e r h a p s a p p r o a c h e d m o s t p r o d u c t i v e l y o n a case by case
basis r a t h e r t h a n b y a g e n e r a l p r i n c i p i e r e p u d i a t i o n . F o r the
s t e w a r d , t h e b u r d e n o f p r o o f o f positive consequences f o r such a | 77
risky v e n t u r e m u s t be o n t h e i n n o v a t o r w h o p r o p o s e s change.
T h a t p r o o f m u s t b e s u b m i t t e d t o t h e j u d g e m e n t s b o t h o f scientific
élites a n d t h e p u b l i c .

F u r t h e r , the ability t o i n t e r v e n e m u s t n o t b e a c c e p t e d as t h e m o r -
al j u s t i f i c a t i o n for i n t e r v e n l n g . T h a t t e c h n o l o g l c a l m e n t a l l t y is p o w -
e r f u l in t h e w o r l d , t a k i n g o n its o w n f o r c é . B o n h o e f f e r wrote,
" T e c h n o l o g y ¡s t h e p o w e r w l t h w h l c h t h e e a r t h g r l p s m a n a n d
s u b d u e s h i m " . In such a s t a t e h u m a n s d o n o t r u l e , t h e y a r e r u l e d ,
sacrificing f r e e d o m as c h o l e e a n d as r e s p o n s i b i l i t y . T h e t e c h n o -
loglcal i m p e r a t i v e o v e r r i d e s o t h e r i n j u c t l o n s .

For example, t h e negative evidence o f eugenic practice w e i g h t s

t h e scales heavily in f a v o r o f r e s t r a i n t a n d e v e n refusal w h e n it
c o m e s t o h u m a n g e r m line m a n i p u l a t i o n . o v e r a l l , t h e r e f o r e , w h a t
D r . M a x i n e F. S i n g e r , P r e s i d e n t o f t h e C a r n e g i e I n s t i t u t i o n of
W a s h i n g t o n , C . C . , has c a l l e d o u r " n o v e l c o m p e t e n c e : t h e h e r i t a -
ble a l t e r a t i o n o f cells a n d w h o l e o r g a n i s m s . . . a p r o c e d u r e q u a l i t a -
tively different f r o m w h a t was previously possible", argües f o r
p r o c e e d i n g o n l y u n d e r t h e m o s t c a r e f u l c o n t r o l s . Because i t is a
novel c o m p e t e n c e a n d because i t is a q u a l i t a t i v e d i f f e r e n c e f r o m
p r e v i o u s p r a c t i c e , a s t e w a r d s h i p o f c r e a t i o n in t h i s á r e a leads t o
a c o n s e r v i n g e t h i c a n d an e t h i c o f r e s t r a i n t w h i c h t a k e s i t n o ac-
c o u n t t h e s a n c t i t y o f t h e species, n o t j u s t o f t h e i n d i v i d u a l self.
Still, t h e issue is n o t , in p r i n c i p i e , c l o s e d f o r p u b l i c d e b a t e a n d d e -
c i s i ó n . Such is t h e d i z z y i n g h e i g h t s o f h u m a n f r e e d o m t h a t no
s u c h q u e s t i o n c a n b e c l o s e d . W h a t is i m p o r t a n t is t h a t such
questions be " v e r y o p e n " , n o t r e s t r i c t e d t o t h e esoteric v o c a b u -
laries a n d d e c i s i ó n m a k i n g b y t h e i n i t i a t e d f e w .

Finally, a s t e w a r d o f t h e c r e a t i o n u n d e r s t a n d s t h a t his o r h e r p o -
s i t i o n is o n e n o t o f a r r o g a n c e b u t o f h u m i l i t y [ m o d e s t y ] . W h e n i t
c o m e s t o b i o l o g y a n d t h e H u m a n G e n o m e P r o j e c t in p a r t i c u l a r
t h a t h u m i l i t y has a t least t w o s o u r c e s . O n e d e r i v e s f r o m t h e d i s -
cipline itself. It is t h e r e c o g n i t i o n o f h o w l i t t l e w e k n o w . L e w i s
T h o m a s , physician a n d essayist, has w r i t t e n :

The only solid piece o f scientific t r u t h a b o u t which I feel totally con-

fident is t h a t we are profoundly ignorant a b o u t nature. Indeed, I
regard this as the m a j o r discovery o f the past one h u n d r e d years
o f biology. (Thomas, p. 73).

T h e r e is so m u c h y e t t o k n o w t h a t o u r c u r r e n t k n o w l e d g e is r a d i -
cally r e l a t i v i z e d . A s e c o n d o u t e o m e o f h u m i l i t y is t h e r e c o g n i t i o n
of the difference b e t w e e n realms of k n o w i n g - e v e n w h e n c o n -
f r o n t e d by t h e same data. O n e r e a l m o f k n o w i n g l o o k s a t o u r c u r -
r e n t b i o l o g i c a l k n o w l e d g e a n d sees p r o b l e m s t o b e s o l v e d . A sec-
o n d l o o k s a t t h e l i v i n g w o r l d a n d a f f i r m s , " N o t h i n g in the living
world remains mysterious. W e do not yet understand all we see a b o u t
us, b u t we are reassured t h a t it is all understandable, all describable in
terms o f chemistry - o f molecular structure a n d the interacüon o f mole-
78 cu/e." O n t h e o t h e r h a n d , t h i s k n o w l e d g e , as w a s a s s e r t e d e a r l i e r ,
raises t h e q u e s t i o n , " W h a t is t h e h u m a n ? " O r b e t t e r , " W h o is
t h e h u m a n ? " A n t h e c a t e g o r y o f m y s t e r y is i n t r o d u c e d by s c i e n t i s t
a n d o t h e r w h o see in t h e m a t e r i a l b e f o r e t h e m w h a t t h e y cali
beautiful, a w e s o m e , and humbling.

If a p r o t e s t a n t m a y q u o t e a Jesuit, a n d a Jesuit p o e t a t t h a t , as p a r t
o f p r o t e s t a n t p r e s e n t a t i o n , t h e n i t is t o G e r a l d M a n l y Hopkins
t h a t I w o u l d t u r n . In a l e t t e r t o his f r i e n d R o b e r t B r i d g e s w h o
had a p p a r e n t l y w r i t t e n h i m a b o u t s o m e t h i n g b e i n g a " m i s t e r y " ,
H o p k i n s w r o t e : "You do n o t m e a n by mystery w h a t a Catholic does.
You m e a n a n interesting uncertainty. But a Catholic by mystery means
a n d incomprehensible certainty". ( D e b o r a h D o u g l a s , p. 10.) T o t h a t
t h i s C a t h o l i c P r o t e s t a n t says " A m e n " .

F o r P r o t e s t a n t s a n d C a t h o l i c s t h i s i n c o m p r e h e n s i b l e c e r t a i n t y is
n o t a passive o b j e c t , t o b e e x p l o r e d a n d e x p l a i n e d w i t h o u t r e -
m a i n d e r . It is an a c t i v e f o r c é b e a r i n g d o w n u p o n us in v a r i o u s
shapes a n d f o r m s , c o m i n g t o us, calling t o us, i n q u i r i n g o f us as
t o w h o w e a r e , e v e n as i t p r o v o k e s t h e r e s p o n s e o f a j o u r n e y
i n t o an u n d e r s t a n d i n g , w i t h o u t d e f i n i t e c o m p r e h e n s i o n , o f its
n a t u r e . A m y s t e r y a l w a y s has s u r p l u s o f m e a n i n g s . W e live w i t h
a m y s t e r y , l i k e J a c o b , w r e s t l i n g w i t h it, s t r u g g l i n g w i t h t h e q u e s -
t i o n s m y s t e r y p u t s t o us a n d l i v i n g i n t o w h a t a n s w e r s w e are
g i v e n . F o r m y s t e r y , an a n s w e r is p r e c e d e d a n d f o l l o w e d b y q u e s -
t i o n s , f o r m i n g a dynamic relationship. F r o m t h e a n s w e r s w e give
and are given f l o w o u r fundamental self-understandings. T o be
e n g a g e d b y m y s t e r y is t o b e v u l n e r a b l e t o p e r s o n a l a n d social
transformaron.

G a b r i e l M a r c e l , t h e F r e n c h p h i l o s o p h e r , has m a d e a u s e f u l d i s -
tinction b e t w e e n the categories of p r o b l e m and mystery. He
writes:

A p r o b l e m is something which I meet, which I f i n d complete before

m e , b u t which I can therefore lay siege to a n d reduce. But a mys-
tery is something in which I a m m y s e l f involved... A genuine p r o b -
l e m is subject to a n a p p r o p r i a t e technique by t h e exercise o f which
it is defeated: whereas a mystery, by defmition, transcends every
conceivable technique. It is, no doubt, always possible... to degrade
a m y s t e r y so as t o t u r n it into a p r o b l e m . B u t this is a f u n d a -
m e n t a l l y vicious proceeding... ( R o b e r t M c A f e e B r o w n , p. 2 6 2 ) .

So u n d e r s t o o d , l o v e is a m y s t e r y , h o p e is a m y s t e r y ; w e a r e m y s -
t e r i e s t o o u r s e l v e s . W e a r e n o t m y s t e r i e s t h a t can be " s o l v e d " .
W e a r e m y s t e r i e s in w h i c h w e live a n d m o v e a n d have o u r b e i n g .
R e l i g i ó n a n d s c i e n c e e n c o u n t e r t h e s a m e r e a l i t i e s , s e p á r a t e in f o -
cusing a t t e n t i o n o n particular presentations o f w h a t " i s " , and in-
s t r u c t each o t h e r as t h e y m e e t in t h e t r a n s a c t i o n o f m y s t e r y a n d
p r o b l e m . P r o t e s t a n t s c l a i m o n l y t o cali f o r a c o n t e x t o f u n d e r -
s t a n d i n g m o r e inclusive t h a n " p r o b l e m " a n d n o t as o b s c u r a n t i s t
as an u n e x p l o r e d m y s t e r y , t h e r e b y o p e n i n g t h e w a y t o t r a n s f o r - 179
m a t i o n o f w h a t i t m e a n s f o r us t o be h u m a n .

Perhaps t h e m o s t a w e s o m e m y s t e r y t h a t P r o t e s t a n t s p r o c l a i m f o r
h u m a n s is t h e r e a l i t y t h a t w e a r e c o - c r e a t o r s w i t h t h e ultimate
P o w e r in a d y n a m i c c o s m o s . O u r calling as s t e w a r d s is n o t t o fit
i n t o an assigned s l o t in a passive w o r l d , b u t t o s h a r e w i t h o t h e r s
a n d w i t h t h e p o w e r w e P r o t e s t a n t s cali G o d in c o n t i n u i n g t h e
d e v e l o p m e n t and hopefully t h e maturation o f t h e w o r l d .

A c o n c l u d i n g w o r d is p e r h a p s in o r d e r b e f o r e s u m m a r i z i n g . F o r
s o m e o f us P r o t e s t a n t s t h e w a y t o t h i n k a b o u t t h e h u m a n is t o
think f r o m the future backward. The human t o w a r d which we
live is t h e e s c h a t o l o g i c a l , t h e p r o m i s e d e n d , w h e r e h u m a n s live
w i t h each o t h e r an G o d in f r e e d o m a n d m u t u a l i t y , w h e r e t h e r e is
n o w e e p i n g o r crying o r death, neither rejection ñ o r loneliness,
b u t all d w e l l in d y n a m i c h a r m o n y , j u s t i c e , a n d t r a n q u i l i t y with
t h e i r neighbors and w i t h nature. T h a t mystery, that p r o m i s e d f u -
t u r e has r e f e r e n c e f o r life a n d f o r life b e y o n d d e a t h . O u r life
s h u d d e r s o n t h e p r e s e n c e o f d e a t h . B u t i t is t h e f o r m e r w h i c h I
shall a d d r e s s .

W e are, according t o this perspective f r o m t h e end of history,

c u r r e n t l y p r o t o - h u m a n , n o t y e t fully h u m a n , o n t h e w a y t o our
humanity. W e are pilgrims e x p l o r i n g emerging w o r l d s . W e re-
side in t h e t e n s i ó n b e t w e e n w h a t w e shall b e a n d w h o w e a r e
now. W e m a k e d e c i s i o n s in t h e l i g h t o f w h a t w e a r e c a l l e d t o
b e , b u t a l s o u n d e r t h e c o n d i t i o n s o f w h a t has b e e n . T h u s , t h i s
f u t u r e is n o t w i t h o u t c o n t e n t . It is t h e f u l l e s t e x p r e s s i o n o f t h e
life lived b y Jesús o f N a z a r e t h in his d e a l i n g w i t h his c o n t e m p o r a -
r i e s . Its q u a l i t i e s a r e l o v e o f G o d a n d n e i g h b o r a n d d o i n g j u s t l y .
Its specific c o n t o u r s w e a r e t o u n f o l d , b u t n o t w i t h o u t r e f e r e n c e
t o t h e i m a g e o f G o d w i t h us in Jesús o f N a z a r e t h a n d m a d e p o s -
sible t o d a y a n d t o m o r r o w b y t h e s a m e S p i r i t o f G o d w h i c h a n i -
m a t e d Jesús a n d t h e c o m m u n i t y c e n t e r e d a r o u n d a n d w i t h h i m .
P r e c i s e l y in t h e m i d s t o f t h e t e n s i ó n b e t w e e n past a n d f u t u r e w e
m a k e o u r decisions a b o u t w h o w e are and w h o w e are t o be,
a n d t h e n a b o u t w h a t w e shall d o . O u r h a b i t a t i o n is, w e P r o t e s -
t a n t C h r i s t i a n s a f f i r m , t h e f u t u r e as p o w e r f u l l y as t h e p a s t a n d
t h e p r e s e n t . T h e r e f o r e t h e r e is an o p e n m o r p h o l o g y o f t h e h u -
man. W e u n d e r s t a n d o u r s e l v e s a n d all h u m a n as " n o t knowing
w h a t w e shall b e , " b u t c o n f i d e n t in t h e p o w e r o f t h e o n e c a l l e d
C r e a t o r , R e d e e m e r , and Ruler. O u r decisions are laced w i t h
a m b i g u i t y . T h e y a r e o f t e n h a r m f u l in t h e i r c o n s e q u e n c e s , d i l u t e d
in t h e i r p o w e r b y o u r l i m i t e d i n t e r e s t s . B u t t h e P r o t e s t a n t a f f i r -
m a t i o n o f g r a c e is t h a t , f o r t u n a t e l y , t h e w a y o f h u m a n s lies n o t
in t h e m s e l v e s , b u t in an U l t i m a t e P o w e r w h o s e w i l l is g o o d n e s s
for the whole creation.

In c o n c l u s i ó n , t h e n a q u o t a t i o n f r o m W . H . A u d e n . H i s o b s e r v a -
r o n reflects t h e m o d e r n and, I believe, t h e p o s t - m o d e r n w o r l d ' s
80 grasping o f t h e nettle o f ambiguity, responsibility, and anxiety. H e
writes:

" T h e Distresses o f choice a r e our chance o f being blessed. ( F o r

the T i m e Being)."

T h a t w e have a c h a n c e a t all is g r o u n d s f o r g r a t i t u d e , h o p e , a n d
courage.

S u m m a r y : I have c o n t e n d e d t h a t w e a r e r e s i d e n t s o f an e m e r g i n g
p o s t - m o d e r n w o r l d , o n e t h a t concedes s o m e t i m e s grudgingly and
s o m e t i m e s gladly, t h e m ú l t i p l e w a y s o f k n o w i n g a n d b e i n g in t h e
w o r l d . T h e f a c t t h a t t h i s d i v e r s e g r o u p is g a t h e r e d h e r e is t e s t i -
m o n y t o t h a t n e w e r a . !t is, in fact, i r o n i c t h a t t h e v e r y successes
o f t h e s o called scientific w o r l d v i e w have e l i c i t e d f r o m w i t h i n a n d
f r o m w i t h o u t t h e scientific c o m m u n i t y t h e q u e s t i o n o f t h e h u m a n .

In i l u s t r a t i n g o n e w a y o f t h i n k i n g a b o u t t h e h u m a n I have d r a w n
f r o m a particular histórica! t r a d i t i o n , o n e called P r o t e s t a n t C h r i s -
tian, w i t h o u t claiming exclusive rights by t h a t t r a d i t i o n , and w i t h -
o u t p r e s u m i n g t o r e p r e s e n t t h e P r o t e s t a n t p e r s p e c t i v e , an o x y -
m o r o n if e v e r t h e r e w a s o n e . T h e s u m o f t h i s p r e s e n t a t i o n is
p e r h a p s t h a t t h e h u m a n is a c o m p l e x n o t a s i m p l e r e a l i t y , o n e
w i t h many characteristics. A t various times various characteris-
t i c s have b e e n e l e v a t e d as " t h e h u m a n c h a r a c t e r i s t i c , " e.g., r e a -
s o n , v a l u i n g , c o n s c i o u s n e s s o f its o w n d y i n g . D i f f e r e n t P r o t e s t a n t
p e r s p e c t i v e s o n t h e h u m a n have b e e n a d v a n c e d - t h e self as p i l -
g r i m , t h e self as c i t i z e n , e t c . B u t w h a t s e e m s a p p a r e n t is t h a t t h e
h u m a n self is a c l u s t e r o f c h a r a c t e r i s t i c s all o f w h i c h m u s t b e af-
f i r m e d , p r o t e c t e d and advance. Some of these w e r e asserted
w i t h t h e assistance o f t w o r o o t m e t a p h o r s .

T w o r o o t m e t a p h o r s g i v e n p r o m i n e n c e in P r o t e s t a n t C h r i s t i a n i t y
a n d n u a n c e d d i f f e r e n t l y b e c a u s e o f t h a t s e t t i n g , have b e e n u s e d .
O n e is t h e h u m a n as c r e a t e d in t h e Image o f G o d . T h e o t h e r is
t h e h u m a n as t h e S t e w a r d o f C r e a t i o n .

U n d e r t h e h u m a n as c r e a t e d in t h e image o f G o d t h e f o l l o w i n g
w e r e a f f i r m e d as essential f o r h u m a n n e s s : I ) T h e i n d i v i d u a l i t y o f
each h u m a n b e i n g a n d t h e d i g n i t y o f t h e self a n d t h e s p e c i e s ; 2 )
f r e e d o m as a c a p a c i t y t o c h o o s e a m o n g o p t i o n s a n d t o t a k e r e s -
p o n s i b i l i t y f o r o n e s e l f a n d G o d ' s w o r l d ; 3) t h e s o c i a l i t y o f t h e h u -
m a n , r e s u l t i n g in s h a r e d d e c i s i ó n f o r o n e s e l f a n d G o d ' s w o r l d ; 3)
t h e s o c i a l i t y o f t h e h u m a n , r e s u l t i n g in s h a r e d d e c i s i ó n making
a n d w i d e d i s t r i b u t i o n o f p o w e r ; 4 ) t h e b r o k e n n e s s o f t h e self in
t e r m s o f s e p a r a t i o n f r o m its s o u r c e o f b e i n g , its o w n f r e e d o m ,
a n d its n e i g h b o r s a n d t h e r e f o r e a h e r m e n e u t i c o f skepticism
a b o u t m o r a l c l a i m s ; 5 ) a n d t h e h u m a n as a c t i v e l y engaged in t h e
w o r l d and w i t h neighbors.

U s i n g S t e w a r d o f t h e C r e a t i o n as a h e u r i s t i c d e v i c e , I have d e s i g -
nated these elements of humanness: I) understanding the ere-
a t i o n as n o t o u r o w n , b u t as h a v i n g its s o u r c e a n d b e i n g in an U l - 181
t i m a t e P o w e r , w i t h o u r cali b e i n g t o c a r e f o r t h e c r e a t i o n ; 2 ) t o
c a r e f o r r e q u i r e s u n d e r s t a n d i g ; 3) m a n i p u l a t i o n is an o b l i g a t i o n ,
as is r e s t r a i n t , in d e a l i n g w i t h t h e c r e a t e d c o s m o s ; a n d 4 ) t h e v i r -
t u e o f h u m i l i t y has c o n s e q u e n c e s t h a t s i m u l t a n e o u s l y p r o p e l b o t h
s c i e n c e a n d t e c h n o l o g y w h i l e d e - i m p e r i a l i z i n g t h e m as w a y s o f
being h u m a n .

In c o n c l u s i ó n , I a f f i r m t h e p r o t o - h u m a n n a t u r e o f t h e h u m a n , a n d
r e a s s e r t t h e d y n a m i c a n d p i l g r i m a g e q u a l i t y o f life, i n d i v i d u a l l y
a n d c o r p o r a t e l y . O u r c o n f i d e n c e is finally n o t in o u r s e l v e s , b u t in
O n e w h o s e p o w e r is p r o p o r t i o n a t e t o t h e p u r p o s e s o f f r u i t i o n
f o r life as w e r e c e i v e it, d i s c o v e r it, c o n s t r u c t , a n d r e c o n s t r u c t it.
182

REFERENCES

A r e n d t , H a n n a h . The Human Condition. T h e U n i v e r s i t y of Chicago

Press, 1958.

B o n h o e f f e r , D i e t r i c h . Creation and Fall. N e w Y o r k : T h e McMillan

Company, 1967.

G u s t a f s o n , J a m e s M. Ethics from a Theocentric Perspectíve: Theology and

Ethics. Chicago: The University of Chicago Press, 1981.

H a r t t , Julián. A Christian Critique o f American Culture. N e w Y o r k : H a r p e r

and Row, 1967.

C i t e d by R o b e r t McAfee B r o w n f r o m 6e;ng an Having, "Puzzles, Pro-

blems, and Mysteries", Christianity and Crisis, August 1, 1988, p. 262.
See Also Gabriel Marcel, Homo Viator, Chicago: H e n r y Regnery C o m -
pany, 1951, and the review by Jeremy Bernstein of W a l t e r Moore's
Schrodinger: Life a n d Thought ( C a m b r i d g e ) , in The N e w Yorker,
N o v e m b e r 5, 1990. M o o r e quotes this distinguished scientist in this
fashion: [Schrodinger sid], " T h e r e is one thing the Greeks knew and
t h a t w e have forgotten...'Modesty!"' l[Bernstein] t h i n k that w h a t he
meant by this sibylline remark... is t h a t science is necessary but n o t
sufficient, in estabiishing one's view o f t h e w o r l d . "

S i n g e r , M a x i n e R. " T h e N e w Biology." A n unpublished paper present-

ed a t t h e Bicentennial S y m p o s i u m , P r e s b y t e r i a n C h u r c h ( U S A ) ,
Philadelphia, Pennsylvania, U.S.A., 1989.

Thomas, Lewis. The Snail and the Medusa. N e w Y o r k : T h e Viking

Press, 1979.

W a l l , J a m e s . The Chr/st/on Century, June I, 1988.

D o u g l a s , D e b o r a h . "Exploring the C o s m o s , " unpublished manuscript.

 83

M A N K I N D IN S E A R C H
OF MEANING

Jomes S. Grisolía

M. S., P r o f e s s o r o f t h e D e p a r t m e n t o f N e u r o s c i e n c e s , M e r c y
H o s p i t a l a n d M e d i c a l C e n t e r , San D i e g o ; A s s i s t . Prof. o f t h e
D e p a r t m e n t o f N e u r o s c i e n c e s , U n i v e r s i t y o f C a l i f o r n i a , San
Diego, C A . (USA)

ABSTRACT

The H u m a n Genome Project attempts to intégrate

the biological point o f view with that o f the social
sciences or, in other words, it attempts to link the
subjective h u m a n w o r l d to t h e objective n a t u r a l
worid. The discoveries in molecular genetics support
the unicity o f the individual; t h a t is, each h u m a n
being is the unique product o f genes a n d experience.
It may be asked whether scientific knowledge in the
modern era will be able to shape our beliefs.
I a m s p e a k i n g t o y o u n o t as a m o l e c u l a r b i o l o g i s t ñ o r as a p h i l o - 185
s o p h e r , b u t as a c l i n i c a l n e u r o l o g i s t . A n e u r o l o g i s t d e v e l o p s a
speclal p e r s p e c t i v e r e g a r d i n g t h e h u m a n i m p a c t o f science, a
perspective w h i c h I h o p e t o share w i t h y o u today. This p o i n t o f
v i e w derives f r o m o u r clinical w o r k , w h i c h involves seeing pa-
t i e n t s w i t h physical b r a i n lesions t h a t a f f e c t a w a r e n e s s a n d b e -
h a v i o r in a s t a r t l i n g v a r i e t y o f w a y s . Each day w e m u s t i n t e r p r e t
w h a t is k n o w n o f m o d e r n b r a i n s c i e n c e t o p a t i e n t s a n d t h e i r f a m -
ilies, d e a l i n g w i t h m a n y issues a t a v e r y p r a c t i c a l level. F r o m t h i s
v i e w p o i n t , a t o n c e i n t r o s p e c t i v e y e t p r a g m a t i c , I have t r i e d to
examine h o w the genome projects will impact o u r view of the
m e a n i n g o f life a n d o u r place in it.

T o p r i m i t i v e m a n , t h e w h o l e w o r l d is alive, w i t h w i n d , r a i n a n d
mountain aware and purposeful. A s culture develops, this anim-
i s m gives w a y t o a d u a l i s m w h i c h d i v i d e s t h e w o r l d i n t o t h e living
and t h e non-living, t h e soul and t h e body, t h e sacred and t h e
p r o f a n e . In m o d e r n t i m e s w e p r e s e r v e t h i s d u a l i s m as s p l i t
b e t w e e n m i n d and body, o r b e t w e e n consciousness and t h e phys-
ical w o r l d . T h i s m i n d - b o d y s e p a r a t i o n c o n t i n ú e s t o permeate
o u r thinking, o u r literature, and o u r philosophy, w h a t e v e r else
w e b e l i e v e o r d o n ' t b e l i e v e a b o u t h e a v e n o r an a f t e r l i f e .

A s scientific r e d u c t i o n i s m advances, dualism breaks d o w n . In-

c r e a s i n g l y , q u a n t u m m e c h a n i c s c a n e x p l a i n c h e m i s t r y in a l a w -
ful fashion, c h e m i s t r y explains m o l e c u l a r biology, molecular
b i o l o g y e x p l a i n s c e l l p h y s i o l o g y a n d b i o c h e m i s t r y in a c h a i n o f
k n o w l e d g e l i n k i n g s u b a t o m i c e v e n t s t o t h e l i v i n g w o r l d . In m y
f i e l d , I s e e an i n c r e a s i n g a b i l i t y o f p h y s i o l o g y a n d n e u r o p h a r m a -
cology t o explain the various phenomena of consciousness.
W i t h t h e i n t e r p e n e t r a t i o n of scientific k n o w l e d g e f r o m one
l i n k o f t h e c h a i n t o t h e n e x t , c o n s c i o u s n e s s b e c o m e s an e m e r -

Figure I
186

Figure 2

gent p r o p e r t y o f ¡norganic m a t t e r r a t h e r than s o m e t h i n g distinct

and soul-like.

T o ¡ I l ú s t r a t e s o m e t h i n g o f w h e r e w e a r e n o w , t h i s slide s u m m a -
rlzes d a t a o n b r a i n e l e c t r i c a l a c t i v i t y in n o r m a l s u b j e c t s b y G e v i n s '
g r o u p in San F r a n c i s c o . T h e s e lines r e p r e s e n t c o v a r i a n c e in e v o k -
ed potential data f r o m pilots squeezing a trigger w i t h t h e i r left
i n d e x finger a f t e r s e e i n g a n u m e r i c a l c u e . T h i s m e t h o d p e r m i t s us
t o see t h e e l e c t r i c a l a c t i v i t y passing f r o m v e r b a l p r o c e s s i n g t o d e -
c i s i o n - m a k i n g c e n t e r , t h e n b a c k w a r d s t o a c t í v a t e b r a i n cells i n -
v o l v e d in a c t u a l l y s q u e e z i n g t h e t r i g g e r .

Figure 3
O f c o u r s e , h e r e w e analyze a single s p l i t - s e c o n d d e c i s i ó n , n o t a 187
detailed i n w a r d debate o n e c o n o m i c t h e o r y , o r even o n w h a t t o
have f o r l u n c h . U n t i l w e fill in m o r e d e t a l l a t m a n y levéis, t h e u l t í -
m a t e r e d u c t i o n o f c o n s c i o u s n e s s t o p h y s i o l o g y is n o t y e t p r o v -
e n ; s o far, w e still a c c e p t t h i s r e d u c t i o n o n f a i t h . N e v e r t h e l e s s ,
this faith c o n t i n ú e s t o be justified by t h e b u r d e n o f evidence.
N e u r o s c i e n t i s t s w h o s t u d y b r a i n f u c t i o n in t h e l a b o r a t o r y , or
n e u r o l o g i s t s w h o s t u d y " N a t u r e ' s e x p e r i m e n t s " in t h e clinic,
l o o k a t t h e b r a i n as t h e t i s s u e o f m i n d , w i t h o u t h a v i n g t o p o s t ú -
late a " g h o s t in t h e m a c h i n e " o r a d u a l u n i v e r s e t o e x p l a i n c o n -
sciousness.

P a r t o f t h e e n o r m o u s m y t h i c p o w e r o f t h e G e n o m e P r o j e c t s lies
in t h e s y m b o l i c c o m p l e t i o n o f t h i s c h a i n o f k n o w l e d g e which
connects human consciousness t o t h e inanimate universe. T h e
ability t o u n c o d e t h e g e n o m e , t o w r i t e a " c o m p l e t e r e c i p e " f o r a
human being, creates a p o w e r f u l metaphor, p o w e r f u l enough t o
i m p a c t m o d e r n t h o u g h t a t e v e r y level in s o c i e t y . Initially, d e c i -
phering t h e H u m a n G e n o m e seems t o s o m e h o w diminish our
humanity, perhaps i m p l y i n g t h a t w e can be c o n t r o l l e d o r t r a n s -
m u t e d , as b y an a l c h e m i s t ' s f o r m u l a o r spell. C e r t a i n l y t h i s g e n e t i c
metaphor l i n k s us f i r m l y a n d i n e x t r i c a b l y t o t h e r e s t o f t h e
b i o s p h e r e , i m p l y i n g s t r o n g l y t h a t e v e r y t h i n g a b o u t us, i n c l u d i n g
o u r c o n s c i o u s e x p e r i e n c e , m a y b e e x p l a i n e d in b i o l o g i c a l , i n d e e d
genetic, t e r m s .

O n c e w e v i e w c o n s c i o u s n e s s as an e m e r g e n t p r o p e r t y o f a b i o -
logic s y s t e m , i t b e c o m e s i n c r e a s i n g l y d i f f i c u l t t o b e l i e v e in t h e
soul as s o m e t h i n g d e t a c h a b l e f r o m t h e b o d y a n d e n d o w e d w i t h
an a f t e r l i f e . H o w d o w e c o m e t o t e r m s w i t h o u r s c i e n c e a t t h e
level o f r e l i g i ó n , o f m y t h o l o g y , o f o u r daily self-image? U l t i m a t e l y
o u r w o r l d v i e w m u s t a c c o m o d a t e t h e s e c o n c e p t s o r else f i n d a
w a y t o r e p u d í a t e s c i e n c e , o u r single m o s t successful a c t i v i t y as
h u m a n beings.

Many people will indeed remaín ignorant of o r reject t h e implíca-

t i o n s o f t h i s n e w I n f o r m a t i o n , c l i n g i n g t o o í d beliefs, p o s s i b l y in
distorte f o r m s . T o o t h e r w h o accept t h e n e w I n f o r m a t i o n , it will
p r e s e n t an i n v í t a t i o n t o n i h i l i s m o r " e x i s t e n t i a l " despair. O u r c h a l -
lenge as a s p e c i e s w i l l b e t o m o v e b e y o n d b o t h r e j e c t i o n a n d
despair, w o r k i n g t o s e a r c h f o r valúes a n d m e a n i n g a r i s i n g f r o m
o u r o w n biologic nature r a t h e r than simply a t t r i b u t e d t o divine
a u t h o r i t y . W i t h o u t t h e idea o f an a f t e r l i f e , r e l i g i ó n loses its u n f a i r
íeverage o n t h e b e l i e v e r . In t h e f u t u r e , r e l i g i ó n o r m y t h o l o g y w i l l
have t o p r o v e its v a l u é t o us b y i m p r o v i n g o u r sense o f m e a n i n g
and s e l f - w o r t h h e r e a n d n o w , w i t h o u t appeal t o an a f t e r l i f e w h e r e
amends w i l l be made f o r earthly w r o n g s .

O u r m o d e r n crisis o f valúes arises in p a r t f r o m o u r enormous

success in t h e n a t u r a l sciences. It is w o r t h r e v i e w i n g t h e d i f f e r -
ence b e t w e e n n a t u r a l science a n d p h i l o s o p h y . Science studies n a t u -
ral p h e n o m e n a o b j e c t i v e l y . P r o g r e s s o c c u r s b y r e d u c t i o n i s m , t h a t
188

Figure 4

is by t a k i n g c o m p l e x p h e n o m e n a a n d r e d u c i n g t h e m t o simpler
p h e n o m e n a w h i c h can t h e n b e e x a m i n e d q u a n t i t a t i v e l y . W e ob-
s e r v e a n d d e s c r i b e t h e p h e n o m e n a as o b j e c t i v e l y as w e c a n , a n d
w e e x e l u d e t h e p e r s p e c t i v e a n d effeets o f t h e o b s e r v e r , e x c e p t a t
t h e q u a n t u m level as a r t i c u l a t e d in t h e H e i s e n b e r g Uncertainty
Principie.

Science explicitly exeludes valúes; scientific p h e n o m e n a are

s t u d i e d because all t h i n g s a r e i n t e r e s t i n g , n o t because o f specific
u t i l i t y o r v a l u é t o m a n k i n d . P a r t o f o u r s o c i e t y ' s malaise m a y arise
f r o m t h e t r i u m p h o f o b j e c t i v i t y as e m b o d i e d in s c i e n c e a n d t e c h -
n o l o g y w i t h o u t a c o r r e s p o n d i n g success in o u r u n d e r s t a n d i n g o f 189
valué a n d m e a n i n g .

In c o n t r a s t t o t h e o b j e c t i v e n a t u r a l sciences, p h i l o s o p h y s t u d i e s
mankind's subjective relation t o t h e universe of natural things.
Valúes a n d m e a n i n g s a r e i n t e g r a l t o t h e h u m a n w o r l d , a n d as o n e
o f its goals, p h i l o s o p h y t r i e s t o p r o v i d e a r a t i o n a l s y s t e m f o r d e -
t e r m i n i n g valúes. F r o m this arise meaning and meaningfulness.
M y t h o l o g y and religión are instinctive, visceral a t t e m p t s t o find
meaning in o u r lives, w h i l e p h i l o s o p h y a t t e m p t s t o satisfy t h e same
desires a t a logical, r a t i o n a l l e v e l .

P h i l o s o p h y a n d s c i e n c e a r e i n t e r d e p e n d e n t as h u m a n a c t i v i t i e s .
Philosophy c a n n o t créate a realistic w o r l d v i e w w i t h o u t re-
course t o t h e findings o f natural science. O n e o f t h e reasons f o r
c o n t i n u i n g c h a n g e a n d f e r m e n t in p h i l o s o p h y is t h e continued
need t o a c c o u n t f o r scientific progress. T h e great p h i l o s o p h e r s
H e g e l a n d K a n t m a d e e r r o r s in t h e n a t u r a l s c i e n c e s t h a t a f i r s t
year g r a d ú a t e s t u d e n t w o u l d f i n d laughable t o d a y , and despite
the inellectual v i r t u o s i t y of these and o t h e r giants w e must
c o n t i n u o u s l y r e - m a k e o u r p h i l o s o p h y w i t h w h a t w e l e a r n in t h e
Iabo r a t o ry.

T h e c r i t i c a l j u n c t u r e b e t w e e n p h i l o s o p h y a n d n a t u r a l s c i e n c e lies
in t h e s c i e n t i f i c s t u d y o f h u m a n i t y , i n c l u d i n g n o t o n l y b i o l o g i c a l
b u t also p s y c h o l o g i c a l , a n t h r o p o l o g i c a l a n d s o c i o l o g i c a l p e r s p e c -
tives o n m a n . In t h e s e áreas, w e t r a i n t h e r e d u c t i o n i s t p a r a d i g m
o n o u r s e l v e s , a n d t h e r e a l m o f t h e s u b j e c t i v e b e c o m e t h e legití-
m a t e t o p i c o f o b j e c t i v e s t u d y . N o t o n l y can valúes a n d m e a n i n g -
fulness be s t u d i e d and t o s o m e e x t e n t q u a n t i t a t e d , b u t t h e s e
studies can be e x t e n d e d c r o s s - c u i t u r a l l y t o e x a m i n e universal
c h a r a c t e r i s t i c s o f h u m a n s as i n d i v i d u á i s a n d in social g r o u p s .

F r o m o u r p e r s p e c t i v e in t h i s g a t h e r i n g t o d a y , w e c a n p r e s u m e
t h a t m u c h o r ali o f w h a t is u n i v e r s a l in m a n k i n d is i m p l i c i t in
the Human G e n o m e . " H u m a n n a t u r e " w o u l d n o t be human
n a t u r e if i t d i d n o t s p r i n g f r o m o u r b i o l o g i c o r i g i n s a n d c a r r y
s o m e m e a s u r e o f s e l e c t i o n a d v a n t a g e , a t l e a s t in t h e p a s t . W e
must bring this perspective t o bear o n such intrinsically hu-
m a n c h a r a c t e r i s t i c s as o u r p e n c h a n t f o r v i o l e n c e , o u r r o m a n -
tic and f a m i l y a t t a c h m e n t s , o u r t r i b a l i s m , a n d o u r religious i m p u l s e .

A c o h e r e n t "science o f h u m a n i t y " integrating perspectives f r o m

b i o l o g y a n d t h e s o c i a l s c i e n c e s w i l l t e l l us w h a t is f u n d a m e n t a l
and n o u r i s h i n g t o t h e s p i r i t o f m a n k i n d as w e l l as t o o u r b o d i e s .
T h i s is t h e c r i t i c a l j u n c t u r e w h e r e o u r s e l f - k n o w l e d g e f r o m p h i l o s -
ophy, religión and a r t m u s t m e e t and join o u r self-knowledge
f r o m t h e n a t u r a l a n d social sciences, s o t h a t w e can c r é a t e a n d
d i r e c t o u r s t r u g g l e t o find v a l u é a n d m e a n i n g . In t h i s c o n t e x t , t h e
Human G e n o m e Projects provide a critical link and a symbolic
link c o n n e c t i n g t h e subjective h u m a n w o r l d w i t h t h e objective
natural w o r l d .
190
TWINS REARED APART & TOGETHER
PERSONALITY VARIANCE FACTORS
SCALE SHARED F A M I L 1 A L

WELL-BEING
SOCIAL POTENCY
ACHIEVEMENT
SOCIAL .19
CLOSENESS
STRESS RXN .00
ALIENATION . 11
AGGRESSION .00
CONTROL .00
AVOIDS HARM .55 .00
TRADITIONALISM .65 .12
ABSORBTION .03
+ EMOTIONALITY .22
(-)EMOTION .02 .43
CONSTRAINT .00
.58 . 43
Tellegen et a l J Pers Soc Paych 54:1031(88

Figure 5

I w o u l d like t o p r e s e n t s o m e e x a m p l e s o f t h e biology o f m e n t a l
p r o c e s s e s , h o p i n g t h a t s u c h c l u e s w i l l lead us t o s o m e under-
standing o f t h e genetic possibilities and limitations o f human
thought. Many recent developments point t o t h e i m p o r t a n t ge-
n e t i c c o n t r i b u t i o n t o p e r s o n a l i t y . T h i s a u d i e n c e is a l r e a d y q u i t e
familiar w i t h t h e i m p o r t a n t evidence f o r a genetic contribution
in a l c o h o l i s m , b i p o l a r a f f e c t i v e d i s o r d e r , s c h i z o p h r e n i a a n d o t h e r
m e n t a l illness. T h e s e c o n d i t i o n s d e v i a t e m a r k e d l y e n o u g h f r o m
n o r m a l m e n t a l f u n c t i o n i n g t o b e called illnesses, a l t h o u g h a l c o h o l -
i s m lies v e r y c i ó s e t o t h e l i m i t s o f w h a t w e i n t u i t i v e l y c o n s i d e r
t h e n o r m a l r a n g e o f h u m a n b e h a v i o r . M e n t a l illness has b e e n
studied earlier t h a n genetic aspects o f n o r m a l personality be-
c a u s e o f t h e g r e a t e r ease o f d i a g n o s i s a n d t h e g r e a t e r medical
i m p o r t a n c e o f m e n t a l d i s o r d e r s , y e t w e have n o r e a s o n f o r t h i n k -
ing t h a t t h e i n t r i n s i c f e a t u r e s o f n o r m a l p e r s o n a l i t y d e p e n d any
less o n g e n e t i c c o n t r i b u t i o n s .

A n u m b e r o f fascinating studies have l o o k e d at f r a t e r n a l and

identical t w i n s raised t o g e t h e r o r separately. By p e r f o r m i n g
studies o f t h e p e r s o n a l i t y t r a i t s o f t h e s e subjects, reliable e s t i m a t e s
can b e m a d e o f t h e g e n e t i c a n d " e n v i r o n m e n t a l " c o n t r i b u t i o n s t o
e x p l a i n i n g v a r i a n c e in p e r s o n a l i t y . In o n e large s t u d y , f o r e x a m -
ple, r a t h e r s t a r t l i n g e s t a m a t e s o f 4 0 t o 5 5 % g e n e t i c c o n t r i b u t i o n
w e r e f o u n d in s u c h c o m p o n e n t s as self-image a n d e v e n t r a d i t i o n -
a l i s m . A n i n t e r e s t i n g f e a t u r e o f t h i s a n d o t h e r s t u d i e s is t h e o b -
s e r v a t i o n t h a t " e n v i r o n m e n t a l " i n f l u e n c e v a r i e d significantly even
w i t h i n t h e same family and household. This implies strongly that
i n d i v i d u a l e x p e r i e n c e a n d p e r s p e c t i v e a r e still c r i t i c a l l y i m p o r t a n t
f o r personality f o r m a t i o n , b u t w i t h i n constraints d i c t a t e d b y ge-
netic inheritance.

A f e w e x a m p l e s f r o m clinical n e u r o l o g y w i l l f u r t h e r illustrate
something about t h e functional organization and limitations of
t h e h u m a n brain. Perhaps t h e m o s t o b v i o u s limitations relate t o 19
p e r c e p t i o n . V e r y clearly, w e never directly experience reality,
b u t o n l y k n o w i t i n d i r e c t l y t h r o u g h o u r sense o r g a n s . A n e x t e n s i v e
l i t e r a t u r e e x i s t s f o r e a c h s e n s o r y m o d a l i t y , o f c o u r s e , b u t in a
g e n e r a l sense o u r p e r c e p t i o n s a r e l i m i t e d b o t h in r a n g e a n d in
modality. For example, o u r ears r e s p o n d o n l y t o limited sound
f r e q u e n c i e s , o u r r e t i n a s t o l i m i t e d f r e q u e n c i e s o f light. O u r n o s e s
a r e m e a s u r a b l y less a c u t e t h a n in m a n y o t h e r a n i m á i s . O t h e r p e -
culiarities díctate m a n y salient features of o u r p e r c e p t i o n . For
e x a m p l e , t h e o v e r l a p p i n g p a t t e r n o f c o n e r e c e p t o r s in t h e r e t i n a
seems t o explain w h y t h e c o l o r y e l l o w l o o k s b r i g h t e r t o t h e h u -
man eye than o t h e r c o l o r s .

T h e b r a i n a c t i v e l y p r o c e s s e s its s e n s o r y i n p u t b e f o r e s e n s a t i o n
c o m e s t o consciousness. Examples have been best detailed f o r
t h e visual s y s t e m , w h e r e t h e b r a i n n o t o n l y e x t r a c t s c e r t a i n f e a -
t u r e s o f i n t e r e s t s u c h as lines o r s p e c i f i e d o r i e n t a t i o n , e t c . , b u t
t h a t t h e b r a i n uses f e e d b a c k p a t h w a y s t o t h e p e r i p h e r y t o c o n -
t r o l and limit sensory input. T h e pupillary reflex causing c o n -
s t r i c t i o n o f t h e p u p i l t o b r i g h t l i g h t is o n l y t h e c r u d e s t o f m a n y
physicological m e c h a n i s m s t o r e d u c e s e n s o r y i n p u t t o a level
w h i c h t h e b r a i n c a n h a n d l e . A l l t h e s e m e c h a n i s m s have e f f i c i e n t
data, b u t w i t h o u t a d o u b t p r o v i d e serious l i m i t a t i o n s o n our
v i e w o f r e a l i t y . By e x a m i n i n g t h i s d e t a i l f r o m an Impressionist
p a i n t i n g , w e s e e t h i s p r o c e s s in a c t i o n . O u r v i s u a l b r a i n uses
c o n t e x t t o t u r n a m e a n i n g l e s s p a t t e r n i n t o a visual i m p r e s s i o n o f
w a t e r . I m a g i n e h o w d i f f e r e n t t h e h u m a n w o r l d v i e w m i g h t b e if
w e had t h e s o n a r capabilities o f t h e bat, t h e high frequency
h e a r i n g o f t h e d o g , o r t h e a b i l i t y t o sense m a g n e t i c fields d e m o n -
strated by m i g r a t o r y birds!

Many e x a m p l e s can ¡Ilústrate f u n c t i o n a l p r i n c i p i e s o f human

thought. T h e m o s t celebrated of these principies remains the
d i s t i n c t i o n in p r o c e s s i n g b e t w e e n l e f t a n d r i g h t c e r e b r a l hem-
ispheres (fig. 6 ) . Slmply p u t , t h e d o m i n a n t (usually left) hem-
i s p h e r e s h o w s a p r e d i l e c t i o n f o r r e a s o n i n g w h i c h is s e q u e n t i a l ,
including logic, mathematlcs, s p o k e n , w r i t t e n o r signed g r a m -
mar, etc. T h e n o n - d o m i n a n t (usually right) h e m i s p h e r e s h o w s a
p r e d i l e c t i o n f o r p a r a l l e l r e a s o n i n g , s u c h as t h a t i n v o l v e d in
reading a map, recognition of faces, n o n - v e r b a l gestures,
inflections, etc. Both hemispheres normally process spoken
s p e e c h , f o r e x a m p l e . T h e l e f t h e m i s p h e r e analyzes t h e g r a m m a r
o f w h a t is said, w h i l e t h e e q u i v a l e n t s t r u c t u r e s in t h e r i g h t h e m -
isphere a t t e n d t o t h e e m o t i o n a l o v e r t o n e s c o n v e y e d by t o n e o f
v o l e e , facial e x p r e s s i o n , b o d y m o v e m e n t s , e t c . If a g e s t u r e e x -
presses e m o t i o n o r emphasis, t h e right h e m i s p h e r e analyzes
t h i s a s p e c t ; h o w e v e r , p e r f o r m t h e s a m e g e s t u r e f o r an i n d i -
v i d u a l w h o k n o w s A m e r i c a n Sign Language, a n d its g r a m m a t i c a l
c o n t e n t w i l l b e a n a l y z e d in t h e l e f t h e m i s p h e r e . C l i n i c a l b r a i n i n -
juries shed f u r t h e r light o n t h e c o m p l e m e n t a r y f u n c t i o n o f b o t h
h e m i s p h e r e s ; c o n s i d e r t h e e x a m p l e o f a r i t h m e t i c c a l c u l a t i o n in
s t r o k e patients. W i t h left h e m i s p h e r e lesions t h e n u m b e r s may
92
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Figure 6

n o t be read o r added c o r r e c t l y , b u t w i t h right h e m i s p h e r e le-

sions t h e c o l u m n s o f figures m a y be aligned i m p r o p e r l y d u e t o
d e f e c t i v e spatial r e l a t i o n s .

O f i n t e r e s t , w e have g r e a t e r c o n s c i o u s access t o l e f t h e m i s p h e r e
functions, and m u c h o f right hemisphere processing occurs w i t h -
o u t o u r a w a r e n e s s . T h i s leads t o i n t e r e s t i n g s p e c u l a t i o n s t h a t
t h e F r e u d i a n u n c o n s c i o u s lies in t h e r i g h t h e m i s p h e r e , a l t h o u g h
t h i s i d e a has n o t b e e n p r o v e n o r r e f u t e d s o far. T h e i n t e r p l a y o f
linear a n d parallel p r o c e s s i n g , as w e l l as t h e g r e a t e r c o n s c i o u s ac-
cess t o l e f t h e m i s p h e r e f u n c t i o n , p r o v i d e i m p o r t a n t parameters
o f human mental activity.

Although m o s t o f us w o u l d c o n s i d e r l a n g u a g e a n d left-right
hemispheric specialization t o be critical biological features of
w h a t m a k e s us h u m a n , g r o s s e x a m i n a t i o n o f t h e h u m a n brain
reveáis oníy v e r y subtle a n a t o m i c changes t o a c c o u n t f o r t h e s e
dramatic developments. O n t h e o t h e r hand, be immediately
s t r u c k by t h e rapid e n l a r g e m e n t of t h e f r o n t a l (sometimes
c a l l e d p r e f r o n t a l ) l o b e s , c o m p r i s i n g f u l l y 3 0 % o f t h e b r a i n in
H o m o sapiens ( f i g . 7 ) .

C l e a r l y s o m e t h i n g a b o u t t h e f r o n t a l l o b e s m u s t have d e c i d e d s u r -
vival a d v a n t a g e , a n d in e v o l u t i o n a r y t i m e t h e i r c o n t i n u e d e n l a r g e -
m e n t p r e d a t e s o t h e r c r i t i c a l h u m a n f e a t u r e s s u c h as u p r i g h t p o s -
t u r e , p r e h e n s i l e t h u m b o r language a c q u i s i t i o n . T h e f u n c t i o n o f
t h e f r o n t a l l o b e s is q u i t e s u b t l e , s o s u b t l e t h a t large i n j u r i e s m a y
o c c u r t h e r e w i t h o u t i m m e d i a t e l y o b v i o u s effects o n o u r b e h a v i o r ,
accounting f o r t h e o í d , e r r o n e o u s belief t h a t w e "fail t o u s e "
m u c h o f o u r b r a i n . S i m p l y p u t , t h e h u m a n c o r t e x is g e n e r a l l y
o r g a n i z e d i n t o a p o s t e r i o r " s e n s o r y h a l f ' a n d an a n t e r i o r " m o t o r
h a l f . Information f r o m visión, hearing, t o u c h and o t h e r sensory
m o d a l i t i e s c o m e s t o t h e p r i m a r y s e n s o r y c o r t i c e s in t h e p o s t e r i o r
 93

T f. \ . SQUIRREL
MONKEY

RHESUS
MONKEY

CHIMP

Figure 7

halves t o e a c h h e m i s p h e r e (fig. 8 ) . T h i s i n f o r m a t i o n undergoes

f u r t h e r p r o c e s s i n g a n d u l t i m a t e l y is s y n t h e s i z e d i n t o a c o h e r e n t ,
integrated awareness of t h e e x t e r i o r w o r l d and o u r o w n body's
r e l a t i o n t o it. T h i s i n f o r m a t i o n is t h e n p r o j e c t e d f o r w a r d t o t h e
p r e f r o n t a l lobes w h e r e f u r t h e r processing initiates action, w h i c h
t h e n p r o j e c t s slightly b a c k w a r d s t o reach t h e m o t o r strip. T h e
m o t o r s t r i p acts l i k e a s e t o f m a r i o n e t t e s t r i n g s t o c o n t r o l t h e
final m o t i o n o f a r m s , legs a n d face.

W h a t p r o c e s s i n g o c c u r s in f r o n t a l l o b e s p r i o r t o a c t i o n ? D a t a
f r o m a n i m a l w o r k a n d t h e r e s u l t s o f c l i n i c a l l e s i o n s in h u m a n s
suggest s t r o n g l y t h a t t h e f r o n t a l l o b e s a r e t h e s e a t o f d e c i s i o n -
making, judgement, planning and p r o j e c t i o n into t h e f u t u r e . In-
j u r i e s t o t h e f r o n t a l l o b e s in h u m a n s r e s u l t in s u b t l e p r o b l e m s
w h i c h m a y n o t b e o b v i o u s t o p h y s i c i a n o r lay o b s e r v e r , but
m a y r e s u l t in a loss o f a m b i t i o n , a f a i l u r e t o gauge o n e s e l f a n d
a s s u m p t i o n o f u n r e a l i s t i c g o a l s , o r i m p o r t a n t d e f e c t s in j u d g e -
94 Premotor
área

Frontal
eye field

Language
understandíng
área

Figure 8

m e n t in a v a r i e t y o f á r e a s r e l a t e d t o s u s t a i n e d h u m a n a c t i o n . It
is a p p a r e n t t h a t t h e f r o n t a l l o b e f u n c t i o n s a r e r e c e n t l y a c q u i r -
ed f r o m an e v o l u t i o n a r y perspective, indeed are probably
c o n t i n u i n g t o e v o l v e e v e n in o u r p r e s e n t s o c i e t y . T h e f r e q u e n t
lapses o f e t h i c s , o f j u d g e m e n t a n d o f " c o m m o n s e n s e " w h i c h
r i d d l e o u r b e h a v i o r as i n d i v i d u á i s a n d as l a r g e r g r o u p s speak
eloquently t o t h e biological fragility o f frontal lobe functions.
F r o m a r a c i a l p e r s p e c t i v e t h e s e f u n c t i o n s a r e s t i l l in t h e pro-
cess o f b e c o m i n g . Y e t n a t u r a l s e l e c t i o n c l e a r l y f a v o r s t h e f r o n -
t a l l o b e s in a s u s t a i n e d d r i v e f o r e l a b o r a t i o n . In h u m a n s they
b e c o m e highly d e v e l o p e d agents o f s p o n t a n e o u s a c t i o n , sifting
t h r o u g h t h e k a l e i d o s c o p e o f s e n s o r y images c o l l e c t e d by t h e
b a c k half o f t h e b r a i n t o d e t e r m i n e w h a t is r e l e v a n t a n d w h a t
is n o t , t o c o m p a r e t h e s e i m a g e s w i t h p r i o r r e c o l l e c t i o n , to
p r o j e c t various courses o f action i n t o t h e f u t u r e , and finally t o
select, initiate and sustain a c o u r s e o f a c t i o n . T h e f r o n t a l lobes
a r e t h e e n g i n e s o f f r e e c h o l e e , l i b e r a t i n g us f r o m a r e f l e x r e s -
p o n s e t o t h e w o r l d a r o u n d us. F u r t h e r s t u d y o f t h e i r subtíe
f u n c t i o n s w i l l be critical t o a biological u n d e r s t a n d í n g o f h u -
man ity.

I will m o v e away f r o m strictly neurologic concerns n o w t o t o u c h

o n a b e h a v i o r a l issue w h i c h is c r i t i c a l f o r u n d e r s t a n d í n g o u r na-
t u r e , even t h o u g h t h e a n a t o m i c and physiologic underpinning
r e m a i n s less c l e a r t h a n f o r w h a t w e have j u s t d i s c u s s e d . T h i s is
t h e n e e d t o belief, f o r m e a n i n g in o u r Uves. T h i s n e e d arises t o
v a r y i n g d e g r e e in each o f us, y e t s e e m s t o c u t a c r o s s ai! s o c i e t i e s
and epochs.

T o p r i m i t i v e man, t h e survival valué o f a p r e d i s p o s i t i o n t o w a r d s a

c o m m o n b e l i e f s y s t e m a p p e a r s e v i d e n t ; s h a r e d r e l i g i o u s beliefs
have c l e a r v a l u é in p r o m o t i n g f a m i l y a n d t r i b a l c o h e s i ó n . Y e t t h e
n e e d f o r a belief, f o r m e a n i n g , f o r an o r i e n t a t i o n b e t w e e n t h e i n -
d i v i d u a l a n d t h e w o r l d a r o u n d h i m a p p e a r s t o be s t u b b o r n l y p e r - 195
s i s t e n t , e v e n In m o d e r n s o c i e t y . In f a c t m u c h o f t h e malaise t h a t
afflicts i n d u s t r l a l i z e d s o c i e t y a p p e a r s t o r e s u l t f r o m t h e loss o f
belief, r o b b i n g o u r lives o f m e a n i n g b e y o n d t h e s i m p l e a c c u m u l a -
t i o n of w o r l d l y goods. A n examination of mythic and religious
t h e m e s f r o m d i f f e r e n t c u l t u r e s p e r m i t s us t o d r a w s o m e c o n -
clusions a b o u t t h e h u m a n need f o r meaning. M u c h o f o u r reli-
g i o u s i d e a t i o n s p r i n g s f r o m an a u g m e n t a t i o n o f e m o t i o n s e v o k e d
by o u r e a r l i e s t c h i l d h o o d c o n t a c t s w i t h o u r p a r e n t s . T h e a w e o f
t h e t i n y c h i l d f o r his f a t h e r ' s m i g h t b e c o m e s t h e r o l e o f t h e w a r
g o d o r s t e r n p a t r i a r c h ; t h e c h i l d ' s d e s i r e f o r c l o s e n e s s w i t h his
m o t h e r ' s w a r m t h a u g m e n t s t o b e c o m e an image o f a n u r t u r i n g
e a r t h m o t h e r . T h e s e a n d o t h e r t h e m e s o f b i r t h a n d d e a t h , loss
a n d r e d e m p t i o n , r u n t h r o u g h all t h e s t o r i e s o f all t h e p e o p l e s o f
this planet.

W h a t n e e d s d o t h e s e m y t h s fulfill? W e evidently have a need

f o r c o n n e c t i o n w i t h t h e w o r l d a r o u n d us, a n e e d f o r s t o r i e s t o
h e l p us in o u r p e r s o n a l t r a n s i t i o n s f r o m c h i l d h o o d t o a d u l t h o o d
t o o í d age t o d e a t h , a n d a n e e d t o access c e r t a i n s p e c i a l s t a t e s
o f c o n s c i o u s n e s s . In W e s t e r n c i v i l i z a t i o n , t h e s e n e e d s w e r e f i r s t
f i l l e d b y l o c a l m y t h o l o g i e s , t h e n by C h r i s t i a n i t y , t h e n l a t e r ( f o r
many people) by a variety o f secular faiths, including a t y p e o f
f a i t h in h i s t o r i c a l p r o g r e s s i t s e l f w h i c h i n c l u d e d v a r y i n g e l e m e n t s
o f b e l i e f in s c i e n t i f i c p r o g r e s s , in e v o l u t i o n a r y p r o g r e s s , in d i a -
l e c t i c a l m a t e r i a l i s m . T h i s s e c u l a r f a i t h in t h e c o n t i n u i n g p r o g r e s s
o f m a n has b e e n t h r e a t e n e d b y m a n y m o d e r n d e v e l o p m e n t s , i n -
cluding t h e d o m i n a t i o n o f E u r o p e by H i t l e r and Stalin, t h e V i e t -
n a m W a r a n d g r o w i n g e c o l o g i c a l signs t h a t w e a r e r e a c h i n g t h e
limits o f unchecked expansión o n this planet. N e i t h e r a simple
r e t u r n t o C h r i s t i a n i t y in its c u r r e n t f o r m s ñ o r a r e t u r n t o n a i v e
p r o g r e s s i v i s m a r e p o s s i b l e f o r m a n y p e o p l e in o u r m o d e r n w o r l d .

S o m e p e o p l e " o p t o u t " by l o s i n g t h e m s e l v e s in i m m e d i a t e daily

c o n c e r n s ; t h e " w o r k a h o l i c " f i n d s m e a n i n g in w o r k t o t h e n e g l e c t
o f o t h e r valúes a n d t h e h e d o n i s t finds m e a n i n g in sensual e x p e -
riences associated w i t h sports, material possessions o r drugs.
Y e t m a n y p e o p l e f i n d s o m e t h i n g m i s s i n g in t h e i r lives a n d t h i s ac-
c o u n t s f o r t h e r e n e w e d i n t e r e s t in O r i e n t a l r e l i g i o n s , in t h e o c -
c u l t , in a v a r i e t y o f s o - c a l l e d N e w A g e b e l i e f s . H o w w i l l our
scientific k n o w l e d g e o f o u r s e l v e s , s y m b o l i z e d b y t h e u n r i d d l i n g o f
t h e H u m a n G e n o m e , m a k e i t p o s s i b l e f o r us t o shape o u r beliefs
and m y t h s f o r t o m o r r o w ?

My o w n qualifications are minimal f o r adding t o t h e f u t u r e o f this

d i s c u s s i o n ; I a m n e i t h e r a p h i l o s o p h e r ñ o r an e x p e r t in r e l i g i o u s
studies. N e v e r t h e l e s s , t o c i ó s e t h i s t a l k I w o u l d like t o s k e t c h in
s o m e p r e l i m i n a r y ideas o f h o w w e m a y shape o u r valúes in t h e
future.

Respect f o r t h e e n v i r o n m e n t and f o r o u r c o n n e c t i o n t o the

b i o s p h e r e m u s t be i m p o r t a n t e l e m e n t s o f o u r f u t u r e m y t h o l o g y .
96 As stated, t h e H u m a n G e n o m e Project créate t h e symbolic link
b e t w e e n humanity and t h e biosphere, and a variety o f ecological
c r i s e s a r e a l r e a d y c o n f r o n t i n g us f o r c i b l y w i t h o u r dependence
o n t h e e n v i r o n m e n t . T h i s sense o f o u r s t e w a r d s h i p o f t h e E a r t h
is n o t i n t e g r a l t o C h r i s t i a n i t y as i t has b e e n p r a c t i c e d in t h e past.
T h e J u d e o - C h r i s t i a n denigration o f n a t u r e motifs had m u c h to
d o w i t h t h e s u b j u g a t i o n o f t h e a g r i c u l t u r a l Canaanites by t h e
n o m a d i c H e b r e w s , w h o s e r e l i g i ó n p r o m o t e d t r i b a l c o h e s i ó n as
t h e C h o s e n P e o p l e w h i l e s u b o r d i n a t i n g o n e n e s s w i t h N a t u r e as
an i d e a f i t o n l y f o r t h e s u r r o u n d i n g a g r i c u l t u r a l p e o p l e s . J u d a i s m
and later C h r i s t i a n i t y cont i núes t h e m o t i f t h a t Man was t h e link
b e t w e e n G o d and a baser N a t u r e , a N a t u r e t h a t m u s t be subju-
g a t e d t o G o d ' s w i l l ( o r a t least t h e w i l l o f his t r u e f o l l o w e r s ) . F o r
c e n t u r i e s t h i s e t h i c o f t h e c o n q u e s t o f N a t u r e w a s a successful
idea, p r o m o t i n g e x p a n s i ó n , a c h i e v e m e n t a n d c o n q u e s t , e v e n a t
t h e expense o f f o r e s t s and w a t e r . N o w t h a t w e are reaching t h e
limits of expansión o n this planet, a r e t u r n t o a m o r e integrated
v i e w o f o u r p l a c e in t h e w o r l d is n o t o n l y t i m e l y , b u t i t m a y
b e c o m e a m a t t e r o f immediate survival. A r e t u r n t o some of
t h e a g r a r i a n m y t h s , t o an e m o t i o n a l c o n n e c t i o n t o t h e land o r t o
the n u r t u r i n g Earth M o t h e r , will resonate w i t h these practical
needs.

O n t h e o t h e r h a n d , a n o t h e r legacy o f o u r W e s t e r n c i v i l i z a t i o n is
t h e e m p h a s i s o n t h e i n d i v i d u a l , w h i c h c a m e t o its first fruition
w i t h t h e e m e r g e n c e o f t h e Renaissance f r o m t h e M i d d l e A g e s .
This emphasis o n t h e valué o f t h e personal perspective proved
t h e s t i m u l u s t o u n p r e c e d e n t e d i n d i v i d u a l a c h i e v e m e n t in t h e a r t s ,
in s c i e n c e a n d t e c h n o l o g y , a n d in c o m m e r c e . T h i s f u n d a m e n t a l
change underlay t h e eventual o v e r t h r o w o f t y r a n n y and t h e b i r t h
o f d e m o c r a c y . T o m o s t o f us, t h e e m p h a s i s o n t h e w o r t h o f t h e
i n d i v i d u a l is i n t e g r a l t o o u r e t h i c s a n d s e e m s w o r t h preserving,
d e s p i t e t h e e l e m e n t o f c o n f l i c t w i t h o u r ideal o f re-integration
w i t h t h e w o r l d a r o u n d us. I see t h e advances in m o l e c u l a r g e n e t -
ics s u p p o r t i n g t h e v a l u é a n d u n i q u e n e s s o f t h e i n d i v i d u a l , n o t
o n l y because o f t h e special n a t u r e o f each g e n e t i c p a t r i m o n y b u t
because o f t h e d e m o n s t r a t e d u n i q u e n e s s o f each e n v i r o n m e n t a l
i n t e r a c t i o n e v e n w i t h i n t h e s a m e f a m i l y u n i t , as w e discussed
e a r l i e r in t h e t w i n s t u d i e s . If each h u m a n is a u n i q u e p r o d u c t o f
g e n e a n d e x p e r i e n c e , t h e n t h i s r e i n f o r c e s o u r u n i q u e w o r t h as
individuáis.

A s r e l i g i o u s f a i t h a n d naive p r o g r e s s i v i s m have c o l l a p s e d . E x i s t e n -
t i a l i s m s t a n d s as o n e o f t h e m o s t i m p o r t a n t m o d e r n answers.
Jean Paul S a r t r e a n d his c o l l e a g u e s c o r r e c t l y s a w t h e c o l l a p s e o f
t r a d i t i o n a l valúes, e m b r a c e d t h e anxiety o f having t o find t h e i r
o w n m e a n i n g in a m e a n i n g l e s s w o r l d a n d c h o s e t o c o n f r o n t t h i s
a n x i e t y and deliberately c o n s t r u c t t h e i r o w n valúes. W h i l e ap-
p l a u d i n g t h e c o u r a g e a n d i n c i s i v e n e s s o f S a r t r e , I f e e l t h a t Ex-
i s t e n t i a l i s m as first e n u n c i a t e d o f f e r s m u c h , b u t falls s h o r t o f t h e
answers w e seek today.
F i r s t o f all, S a r t r e e m p h a s i z e d t h e f r e e m a n ' s u n l i m i t e d f r e e d o m 197
t o c h o o s e . W e have a l r e a d y seen t h a t m a n in f a c t is f r e e t o m a k e
c e r t a i n c h o i c e s , b u t t h a t t h e s e c h o i c e s a r e c o n s t r a i n e d by b i o l o g -
ical f á c t o r s , m a n y o p e r a t i n g u n c o n s c i o u s l y . T h e s e f a c t o r s c a n n o t
be c h a n g e d w i t h o u t a l t e r i n g o u r g e n e t i c h e r i t a g e . By a c k n o w l -
e d g i n g c e r t a i n b i o l o g i c c o n s t r a t i n t s o n o u r m e n t a l a n d physical
beings, w e f i n d o u r s e l v e s m u c h c l o s e r t o t h e Spanish p h i l o s o p h e r
O r t e g a y Gasset t h a n t o t h e Existentialists.

F r o m o u r i n s p e c t i o n o f t h e f r o n t a l l o b e s , w e can see t h e i m p o r -
tance of self-directed behaviours, which are only triggered in-
d i r e c t l y a n d u n p r e d i c t a b l y by e n v i r o n m e n t a l s t i m u l i . T h i s means w e
r e a l l y d o have t h e f r e e d o m o f c h o l e e t h a t w e f e e l w e have. W i t h -
in o u r b i o l o g i c c o n s t r a i n t s , w e a r e r e s p o n s i b l e f o r o u r c h o i c e s ,
a n d a t t h i s p o i n t m u c h t h a t E x i s t e n t i a l i s m has t o o f f e r b e c o m e s
useful in e x a m i n i n g t h e s e c h o i c e s . S a r t r e e m p h a s i z e d a " p r o j e c t " ,
a s e t o f goals a n d o u t s i d e r e l a t i o n s t h a t each o f us c h o o s e s t o
give m e a n i n g t o o u r life. T h i s e m p h a s i s s e e m s w e l l c h o s e n t o us
after o u r examination of man's g r o w i n g p r e f r o n t a l lobes. M o r e
t h a n any o t h e r a n i m a l , t h e h u m a n is a d o e r a n d a p l a n n e r , a n d
t h e emphasis o n a l o n g - t e r m goal resonates w i t h o u r biologic and
i n t u i t i v e sense o f w h a t gives m e a n i n g t o a h u m a n life. T o be sat-
isfying, o u r f u t u r e m y t h o l o g y w i l l have t o i n c o r p ó r a t e f e a t u r e s o f
p r o g r e s s , o f b e c o m i n g , o f p r o v i d i n g a d i r e c t i o n , t o satisfy w h a t
a p p e a r s t o b e an i m p o r t a n t h u m a n n e e d .

O f c o u r s e , this a t t e m p t t o f o r e s e e o u r f u t u r e valúes borrows

m u c h f r o m t h e Existential c o n f r o n t a r o n w i t h t h e a n x i e t y o f m e a n -
inglessness a n d t h e d e l i b é r a t e c o n s t r u c t i o n o f h u m a n m e a n i n g .
Y e t i m p o r t a n t differences remain. W e are looking f o r a biological
basis f o r o u r v a l u é s y s t e m , u n l i k e t h e t r u e E x i s t e n t i a l i s t . W e w i s h
t o predict o u r collective need f o r meaning, while t h e Existen-
t i a l i s t s t r u g g l e is i n t e n s e l y p e r s o n a l , w i t h e a c h s e e k e r rearching
his o w n i n d e p e n d e n t s o l u t i o n . F u r t h e r , t h e individual c o n f r o n t a t i o n
a d v o c a t e d b y S a r t r e r e q u i r e s a g r e a t deal o f i n d i v i d u a l c o u r a g e ,
w h i l e t h e n e e d f o r m e a n i n g s p r i n g s u p in m a n y p e o p l e w h o a r e
n o t equal t o t h e b l e a k n e s s o f t h e l o n e E x i s t e n t i a l q u e s t . Each o f
us a v o i d s a l o t o f p a i n f u l i n t r o s p e c t i o n if w e can c h o o s e t o b e -
lieve in a s h a r e d r e l i g i ó n o r m y t h o l o g y ( p r o v i d e d i t r e m a i n s c o n -
g r u e n t w i t h t h e r e m a i n d e r o f o u r k n o w l e d g e , including scientific
knowledge). T o d a y w e are simply trying t o predict some of t h e
features o f t h a t necessary m y t h o l o g y .

We have already m e n t i o n e d t h e so-called N e w A g e notions,

w h i c h t r y t o fill t h e v o i d o f meaninglessness in m o d e r n life.
A m o n g these n o t i o n s , I w o u l d like t o m e n t i o n t h e Gaia h y p o t h e -
sis as a m y t h o l o g y w h i c h s e e m s t o m e e t m a n y o f o u r c r i t e r i a f o r
an i m p o r t a n t v e h i c l e o f h u m a n m e a n i n g . S i m p l y p u t , t h i s h y p o t h e -
sis, first a d v a n c e d b y L o v e l o o k , suggests t h a t t h e e n t i r e b i o s p h e r e
o f p l a n e t E a r t h is alive as a single s u p e r - o r g a n i s m , s t a t i n g t h a t t r e -
m e n d o u s c o r r e c t i v e f o r c e s e x i s t w i t h i n o u r e c o - s y s t e m because
198 t h e e c o - s y s t e m i t s e l f is a single b e i n g w i t h its o w n homeostatic
m e c h a n i s m s (fig. 9 ) . T h i s h y p o t h e s i s is p s e u d o - s c i e n t i f i c , s o u n d i n g
c o n s i s t e n t w i t h m u c h o f n a t u r a l s c i e n c e , y e t is c o n v e n i e n t l y u n -
t e s t e d o n a s c i e n t i f i c basis b e c a u s e o f t h e vagueness o f t h e c o n -
c e p t . T h e e m p h a s i s o n t h e e n v i r o n m e n t is w h o l e s o m e f r o m an
ecological standpoint, and provides a convenient f r a m e w o r k f o r
r e l a t i n g h u m a n i n d i v i d u á i s t o a l a r g e r e n t i t y as g r a n d as t h e l i v i n g
p l a n e t , y e t as p e r s o n a l a n d n u r t u r i n g as a n y V i r g i n M a r y o r E a r t h
M o t h e r f i g u r e . Lastly, t h e c h o l e e o f a f e m i n i n e d e i t y m a y have i m -
p o r t a n t advantages in r e d u c i n g a g g r e s s i o n , a n d e n c o u r a g i n g c o -
o p e r a t i o n r a t h e r t h a n c o m p e t i t i o n a m o n g believers. Perhaps this
w o u l d s u p p o r t a creative, n u r t u r i n g stance r a t h e r than t h e c o n -
q u e r i n g e x p l o i t i v e image f o s t e r e d by Christianity and by many r e -
ligions u p u n t i l n o w .

In c o n c l u s i ó n , a s e a r c h f o r m e a n i n g m u s t o c e u r t o fulfill i m p o r -
t a n t h u m a n n e e d s , a n d an i n t e l l i g e n t analysis o f t h i s n e e d f o r
meaning should p r e c e d e any large-scale a t t e m p t t o alter
mankind's nature, w h e t h e r t h r o u g h genetic o r environmental
m a n i p u l a r o n . T h e H u m a n G e n o m e P r o j e c t p r o v i d e a useful s y m b o l
o f o u r l i n k t o t h e o b j e c t i v e w o r l d , causing t h e o b j e c t i v e ( n a t u r a l
sciences) a n d t h e s u b j e c t i v e ( p h i l o s o p h y a n d r e l i g i ó n ) t o i n t e r s e c t
at t h e p o i n t o f o u r s e l f - k n o w l e d g e .

I w o u l d like t o c i ó s e w i t h t w o images, a n i g h t m a r e a n d a d r e a m
(fig. 10). T h e first is a c a r t o o n s h o w i n g o u r d a r k e s t f e a r s r e g a r d -
ing t a m p e r i n g w i t h D N A a n d t h e n a t u r e o f life. T h i s t h e m e o f t h e
d e s t r o y i n g m o n s t e r , often o u r o w n c r e a t i o n , dates at least
f r o m Frankenstein and r e c u r s t h r o u g h o u t science fiction t o t h e

y.

Figura 9
 199

^> mí
VAT 20

What i d i o t f l u s h e d r a d i o a c t i v e
DNA i n t o o u r n u t r i e n t tanks?
The c r o p ^ f i n i s h e d f o r s u r e ! _ I
Figure 10

p r e s e n t day. I b e l i e v e t h e s e m o n s t e r s r e p r e s e n t t h e a r t i s t s ' f e a r s
t h a t in o u r t e c h n o l o g i c a l s o c i e t y , o b j e c t i v e s c i e n c e has t r i u m p h e d
o v e r s u b j e c t i v e h u m a n valúes, a n d t h a t s o m e t h i n g essential a b o u t
o u r h u m a n i t y is p l a c e d in e x t r e m e p e r i l , n o t b y physical d e s t r u c -
t i o n b u t by r e d u c t i o n , by t h e daily m o r a l e r o s i ó n t h a t a c c o m -
panies a loss o f v a l u é a n d o f m e a n i n g .

In c o n t r a s t , c o n s i d e r t h i s Biblical m e t a p h o r (fig. I I ) . T h e d o u b l e
h e l i x has s o m e t i m e s b e e n l i k e n e d t o Jacob's l a d d e r , f o r e x a m p l e
in t h i s p a i n t i n g b y Salvador Dalí. In t h e s t o r y o f Jacob, he fell asleep
and d r e a m e d o f a l a d d e r ascending t o H e a v e n . T h u s Jacob's
Ladder becomes t h e p o i n t o f ascensión, t h e intersection o f t h e
material, objetive w o r l d w i t h the w o r l d of the spiritual, the
200

Figure 11

w o r l d o f m e a n i n g . A n d t h i s , p r e c i s e l y , is t h e m e t a p h o r I w o u l d
like t o leave in y o u r r i g h t h e m i s p h e r e s , t h a t w e as s c i e n t i s t s a r e
c l i m b i n g Jacob's L a d d e r by s t u d y i n g t h e H u m a n G e n o m e , and
t h a t t h e r e s u l t a n t s e l f - k n o w l e d g e w i l l h e l p us t o r e a c h t h e w o r l d
o f s p i r i t u a l valúes, u n i t i n g i t w i t h t h e o b j e c t i v e w o r l d o f s c l e n c e .
T H E IMPACT
O F T H E H U M A N
C E N O M E PROJECT
O N MEDICINE
 203

GENETIC THERAPY

Theodor Friedmann

C e n t e r f o r Molecular Genetics, School of Medicine. University

o f C a l i f o r n i a , San D i e g o .
La Jolla, C a l i f o r n i a ( U S A )

ABSTRACT

The H u m a n Genome Project wiíl bring new know-

ledge on the therapy o f disorders with a high genetic
component, although it is true that in general there
is a certain delay between knowledge o f h u m a n ge-
netics a n d the dinical a n d therapeutic application o f
this knowledge. Although the project aims to dis-
cover the structure a n d functíon o f the H u m a n Ge-
nome, ¡t is to be hoped that all this will be translated
into therapeutic programmes. The history o f medi-
cine, as f a r as genetic disorders a r e c o n c e r n e d ,
shows t h a t therapy has been directed at all places
except at the root of the probíem, that is, at the gene
which causes the disorder. Today, genetic therapy is
being used, especially in the somatic field. Genetic
theropy in the germinal field is onother motter for it
aims at genetic a n d metabolic correction, not on/y in
the patient b u t o/so in his/her descendants.
However, both therapeutic modalities pose ethical
problems which will gradually change as our techno-
logical stockpile changes.
G o o d m o r n i n g . It's m y pleasure t o s t a r t t h e discussion this 205
m o r n i n g o n t h e m e d i c a l a p p l i c a t i o n s o f s o m e o f t h e issues t h a t
w e h a v e b e e n d i s c u s s i n g . A n d i t is m y p l e a s u r e t o i n t r o d u c e t o
y o u a n d r e v i e w f o r y o u s o m e o f t h e a s p e c t s o f o n e o f t h e is-
sues t h a t has s o m e t h i n g t o d o w i t h t h e H u m a n G e n o m e Pro-
j e c t , b u t w h i c h is n o t n e c e s s a r i l y i n t i m a t e l y i n v o l v e d w i t h i t . I'd
iike t o r e v i e w f o r y o u s o m e issues r e l a t e d t o h u m a n g e n e t h e r -
apy a n d its r e l a t i o n t o t h e g e n o m e p r o j e c t . If o n e is l o o k i n g f o r
histórica! o r literary equivalents of m o d e r n molecular genetics
a n d t h e issues o f g e n e t h e r a p y , o n e m i g h t t h i n k o f t h i n g s Iike
" G r e a t E x p e c t a t i o n s " o r " T h e A g e of A n x i e t y " , o r even the
p r o m i s e s a n d e x p l o i t s o f El C i d . " T h e A g e o f A n x i e t y " is o b -
v i o u s l y t h e basis o f s o m e o f t h e d i s c u s s i o n s t h a t w e a r e h a v i n g .
G e n e t i c s d o e s p o s e p r o b l e m s f o r us. " G r e a t Expectations"
speaks f o r i t s e l f a n d r e f l e c t s t h e h o p e , o f c o u r s e , t h a t w h a t w e
are d o i n g w i l l lead t o e n o r m o u s l y n e w and useful t e c h n i q u e s
for the human condition. W e have h e a r d and w i l l c o n t i n u é to
h e a r t h a t g e n e t i c s has a v e r y special place in raising e t h i c a l Issues,
t h e issues d e a l i n g w i t h t h e n a t u r e o f m a n a n d t h e h u m a n c o n d i -
t i o n , in g e n e r a l . T h e e x p l o s i ó n in h u m a n g e n e t i c s has c o m e t o
r e m i n d us t h a t g e n e t i c k n o w l e d g e r e p r e s e n t s in o n e w a y a p a r -
ticularly íiberating kind of knowledge f o r t h e promise of the re-
lief o f h u m a n s u f f e r i n g . It a l s o p r o m i s e s , a t t h e s a m e t i m e , t o
s o m e o f us a p a r t i c u l a r l y t h r e a t e n i n g k i n d o f k n o w l e d g e with
r e s p e c t t o t h e k n o w l e d g e o f o u r s e l v e s as i n d i v i d u á i s a n d as a
society. T h e vulnerability o f genetics t o mischievous and even
evil a p p l i c a t i o n has b e e n k n o w n f o r a l o n g t i m e , i l l u s t r a t e d b y
t h e B i r t h o f Eugenics m o v e m e n t in B r i t a i n in t h e nineteenth
c e n t u r y , a n d its f u r t h e r p e r v e r s i ó n in t h e U n i t e d States t h r o u g h
the w o r k o f Charles D a v e n p o r t and o t h e r s at the C o l d Spring
H a r b o r Eugenics R e c o r d o f f i c e . T h e w o r k t h e r e l e d t o m i s g u i d -
e d s o c i a l p o l i c i e s , i m m i g r a t i o n p o l i c i e s a n d t h e s o r t s o f disas-
ters that w e heard of yesterday f r o m D o c t o r Smith, dealing
w i t h C a r r i e B u c k a n d t h e c o m p u l s o r y s t e r i l i z a t i o n l a w s in t h e
U n i t e d States. A n d , o f c o u r s e , t h e u l t í m a t e s u r r e n d e r o f science
r e a c h e d i t s a t r o c i o u s e x t r e m e in t h e e v i l p u b l i c p o l i c i e s and
p r o g r a m s o f N a z i G e r m a n y a n d t h e L y s e n k o p e r i o d in Russia.
A n d w e w i l l h e a r m o r e o f t h a t l a t e r in t h e p r o g r a m . T h i s m e e t -
ing is t a k i n g place b e c a u s e w e i n t u i t , w e u n d e r s t a n d t h a t t h e r e
a r e p r o b l e m s w i t h s o m e o f t h i s g e n e t i c k n o w l e d g e a n d w i t h its
a p p l i c a t i o n . T h o s e p r o b l e m s a r e in t h e r e a l m o f s c i e n c e p o l i c y ,
in t h e uses a n d abuses o f p e r s o n a l g e n e t i c I n f o r m a t i o n f o r s c r e e n -
ing a n d m o n i t o r i n g p r o g r a m s .

O n e of t h e expected and often stated expectations and p r o m -

ises o f t h e g e n o m e p r o j e c t , o f c o u r s e , is t h e d e l i v e r y o f i m m e n s e
n e w k n o w l e d g e o f g e n e t i c disease a n d t h e t r a n s l a t i o n o f t h a t i n -
t o p o w e r f u l n e w k i n d s o f t h e r a p y f o r diseases w i t h m a j o r g e n e t -
ic c o m p o n e n t s . I t h i n k t h a t w e hall k n o w t h a t m a n y o f t h e f i r s t
206 a n d e a r l i e s t d e l i v e r i e s o f t h a t p r o m i s e w i l l t a k e t h e shape o f ef-
fective screening and m o n i t o r l n g programs rather than t h e r a -
p e u t i c p r o g r a m s . T h e r e Is a l w a y s a v e r y m a y o r a n d l o n g h i a t u s
b e t w e e n w h a t w e l e a r n in g e n e t i c s a n d h o w w e a p p l y i t in t h e
clinical and t h e t h e r a p e u t i c setting. I m i g h t just r e m i n d y o u t h a t
t h e case in p o i n t is t h a t o f h e m o g l o b i n a n d its d i s o r d e r s . T h e r e
is n o g e n e a n d n o g e n e p r o d u c t as w e l l u n d e r s t o o d as h e m o g l o -
b i n . Its m o l e c u l a r b i o l o g y is as p r o f o u n d l y p r o d u c t i o n a r e t r e a t -
e d , e v e n t o d a y , I t h i n k y o u w i l l see t h e g r e a t d i s c r e p a n c y b e -
t w e e n t h e k n o w l e d g e t h a t w e have o f t h e disease a n d o u r a b i l i t y
t o treat.

W e l l , w h a t d o e s all t h i s h a v e t o d o w i t h t h e H u m a n Genome
Project. W e heard yesterday f r o m N o r t o n Z i n d e r t h a t t h e ge-
n o m e p r o j e c t is n o t a i m e d e n t i r e l y o r e v e n largely a t u n d e r s t a n d -
ing all o f h u m a n b i o l o g y a n d all o f h u m a n m e d i c i n e , b u t rather
a t t h e s t r u c t u r e a n d f u n c t i o n o f t h e H u m a n G e n o m e . It is t r u e
t h a t t h a t is o f t e n t r a n s l a t e d i n t o p r o m i s e s o f t h e r a p y . I w o u l d
l i k e t o d e s c r i b e t o y o u in t h e s e f e w m o m e n t s a b i t o f t h e s t a t e
o f t h e a r t o f g e n e t h e r a p y , w h e r e i t is a n d w h e r e i t is l i k e l y t o b e
g o i n g in t h e n e a r f u t u r e . I w i l l t h e n l o o k a t s o m e o f t h e p r o b -
l e m s a n d c o n c é n t r a t e o n t w o o f t h e issues t h a t I see t o b e o f
i n t e r e s t and w o r t h y o f f u r t h e r discussion by this g r o u p , and o t h -
er groups.

G e n e t h e r a p y is n o t a c h i l d o f t h e H u m a n G e n o m e P r o j e c t . It's
b e e n w i t h us f o r s o m e t i m e a n d is an i n d e p e n d e n t c r e a t u r e b o m
o f o t h e r p a r e n t s . A l t h o u g h t h e r e is n o q u e s t i o n w h a t s o e v e r t h a t
Information gathered f r o m the Human Genome Project will im-
m e n s e l y c a t a l y z e t h e a c t i v i t i e s t o w a r d n o v e l t h e r a p y . W e l l , in f a c t
t h a t , w h e n t h e c o n c e p t o f g e n e t h e r a p y c a m e t o b e a g l e a m in
t h e eyes, s o m e t w e n t y years ago, it w a s n ' t really possible to
s t a n d in a r e s p e c t a b l e scientific a u d i e n c e a n d u t t e r t h o s e w o r d s
a n d , I t h i n k , y o u w i l l r e c o g n i z e an i m m e n s e c h a n g e since t h e n ,
o n e t h a t p r o b a b l y r e p r e s e n t s as e p o c h a l a n d as a m a j o r a c h a n g e
in m e d i c a l t h i n k i n g as has e v e r o c c u r r e d in t h e h i s t o r i c a l o f m e d i -
c i n e . I'll t r y a n d c o n v i n c e y o u o f t h a t in t h e n e x t f e w slides, t h a t
t h i s c h a n g e i n v o l v e s a 180 d e g r e e t u r n in t h e w a y w e t h i n k a b o u t
t h e t r e a t m e n t o f disease. I c a n ' t see v e r y w e l l f r o m h e r e , b u t I
t h i n k t h e first slide p r e s e n t s a v e r y s i m p l i s t i c s c h e m e o f g e n e t i c
disease. W e all k n o w t h a t g e n e t i c disease r e f l e c t s d e f e c t s in t h e
g e n e t i c m a t e r i a l a n d t h a t i t r e s u l t s in t h e p r o d u c t i o n o f a b n o r m a l
gene p r o d u c t s - p r o t e i n s , enzymes and o t h e r gene products.
N o r m a l g e n e p r o d u c t s a l l o w n o r m a l cell f u n c t i o n a n d p h y s i o l o g y .
B u t w h e n t h e y a r e a b e r r a n t o f m u t a n t , cell o r o r g a n d a m a g e t a k e s
place a n d disease r e s u l t s . In all o f m e d i c a l h i s t o r y u p t o t h e p r e s -
e n t t i m e , all t h e r a p i e s h a v e b e e n a i m e d e v e r y w h e r e e x c e p t a t
t h e s i t e o f t h e d e f e c t . W e have b e e n able o n l y t o i m a g i n e t r e a t -
m e n t o f diseases by m a n i p u l a t i n g t h e r e s u l t s o f t h e m e t a b o l i c a n d
physical c o n s e q u e n c é s of g e n e t i c d e f e c t s a n d b i o c h e m i c a l d e f e c t s . 207
It has "ftever b e e n p o s s i b l e t o i m a g i n e t r e a t i n g w h a t r e a l l y is t h e
p r o b l e m in t h e m u t a n t g e n e .

O n e can i m a g i n e t h e g e n e t o b e a d a m a n d a m u t a n t g e n e t o b e a
leak in t h e d a m . T h a t r e s u l t s in a f l o o d d o w n s t r e a m . T h i s f l o o d is
disease. M e d i c a l t h e r a p y , in all its f o r m s u n t i l n o w , has b e e n a
f r a n t i c e f f o r t t o clean u p t h e m e s s t h a t o c c u r s f r o m t h i s b r o k e n
d a m , a n d s u c h an a t t e m p t a t t h e r a p y b e c o m e s v e r y ineffective
and a f t e r a w h i l e t h e d a m c o n t i n ú e s t o leak. W h a t is h a p p e n i n g
n o w - i n a v e r y s i m p l i s t i c v i e w - is t h a t w e a r e n o w able t o c h a n g e
t h e t h e r a p e u t i c approach into o n e t h a t involves a repair o f t h e
d e f e c t , t h e b r o k e n d a m . A t t e m p t s t o t r e a t disease b y f i x i n g t h e
d a m itself a r e n o w w h a t I t h i n k o f as an e p o c h a l c h a n g e in m e d i -
c i n e . T h e c o n c e p t is " f i x w h a t ' s b r o k e n ! " T h e g e n e is b r o k e n , s o
let's l e a r n t o f i x t h e g e n e . W e l l , t h e r e a r e p e o p l e w h o a r e , in
fact, t r y i n g t o d o w h a t . M a n y o f t h e m o d e l s i n v o l v e removing
cells f r o m a p a t i e n t , i n t r o d u c i n g f o r e i g n genes i n t o t h e n in vitro,
t h e n r e t u r n i n g t h e m t o t h e p a t i e n t i n t o an a p p r o p r i a t e site, o r
possibly, e v e n using g e n e t r a n s f e r r i n g t e c h n i q u e s d i r e c t l y i n t o t h e
patient.

T h e r e a r e t w o p r i n c i p a l k i n d s o f t a r g e t cells f o r t h i s k i n d o f m a n i -
p u l a r o n - s o m a t i c cells a n d g e r m cells. T r e a t m e n t o f t h e s o m a t i c
cells o f t h e p a t i e n t r e s u l t s in g e n e t i c c o r r e c t i o n o f o n l y t h e i n d i -
vidual p a t i e n t - h o p e f u l l y a p e r m a n e n t t r e a t m e n t o f t h a t p a t i e n t
and only t h a t patient. T h e o t h e r possible a p p r o a c h involves t r e a t -
m e n t o f t h e g e r m cells o f a p a t i e n t , s o t h a t t h e g e n e t i c a n d m e t a -
bolic c o r r e c t i o n and c o m p l e m e n t a t i o n of t h e defect becomes
e v i d e n t n o t o n l y in t h e p a t i e n t b u t in t h e p r o g e n y a n d f u t u r e g e n -
erations.

M a n y o f y o u w i l l r e c o g n i z e t h e s o m a t i c cell a p p r o a c h as t h e basis
f o r t h e s e v e r a l p r o p o s a l s t h a t have b e e n a p p r o v e d n o w b y t h e
R e c o m b i n a n t A d v i s o r y C o m m i t t e e ( R A C ) , N I H , and by t h e o t h e r
r e g u l a t o r y a g e n c i e s in t h e U.S. In o n e o f t h o s e experiments,
A n d e r s o n a n d his colleagues are r e m o v i n g l y m p h o c y t e s f r o m a child
w i t h A d e n o i s e Deaminase ( A D A ) deficiency, introducing that
gene i n t o t h e l y m p h o c y t e s o f t h e p a t i e n t a n d t h e n r e t u r n i n g t h e
cells t o t h e p a t i e n t t o t r y t o p r o v i d e p e r m a n e n t n e w A D A f u n c -
t i o n . A n o t h e r a p p r o v e d p r o t o c o l in o n e in w h i c h t u m o r n e c r o s i s
f a c t o r ( T N F ) genes a r e i n t r o d u c e d i n t o cells a r e r e t u r n e d t o t h e
p a t i e n t . T h e r e a r e o t h e r m o d e l s t h a t p e o p l e have b e e n w o r k i n g
o n in o u r o w n l a b o r a t o r y - i n an a t t e m p t t o c o r r e c t c a n c e r s t h a t
r e s u l t f r o m d e f e c t s in c á n c e r s u p p r e s s o r genes. H e r e is a r e t i n o -
b l a s t o m a t u m o r cell t h a t has b e e n c o r r e c t e d b y h a v i n g a n o r m a l
r e t i n o b l a s t o m a g e n e i n t r o d u c e d i n t o it. T h e s e cells n o w b e c o m e
n o n - t u m o r i g e n i c . T h e c o r r e c t e d cells a r e p u t i n t o n u d e m i c e a n d
208 t h e y are n o w r e - e x p r e s s i n g t h e RB gene p r o d u c t and are no
l o n g e r able t o p r o d u c e t u m o r s .

Similar a p p r o a c h e s have been t a k e n t o c o r r e c t d i s o r d e r s such

as L D L r e c e p t o r d e f i c i e n c y , w i t h its r e s u l t i n g hypercholester-
o l e m i a . N e w g e n e s c a n a l s o b e p u t i n t o m u s c l e c e l l s . T h i s is
an a p p r o a c h t o t r e a t m e n t o f t h i n g s l i k e D u c h e n n e ' s muscular
d y s t r o p h y . So t h e s e p r o m i s e s w o u l d , a t f i r s t g l a n c e , r e p r e s e n t
an u n q u a l i f i e d g o o d . B u t t h e r e a r e p r o b l e m s . W e all r e c o g n i z e
that we've run into ethical situations, diiemmas that were
s o m e w h a t f a c e t i o u s l y c a l l e d " p l a y i n g G o d " , y e s t e r d a y . In f a c t ,
" p l a y i n g G o d : is a n o t h e r p h r a s e f o r M e d i c i n e . T h e a p p r o a c h o f
t h e a r r o g a n c e o f t h e h u b r i s o f m e d i c i n e in d e c i d i n g t h a t t h e r e
a r e s u c h t h i n g s as m i s t a k e s in n a t u r a l a n d o u r r e q u i r e m e n t , in
f a c t , o u r i n j u n c t i o n t o c o r r e c t t h o s e m i s t a k e s , is c a l l e d the
p r o f e s s i o n o f m e d i c i n e . S o m e o f us r e g a r d t h i s i n j u n c t i o n to
h e a l a n d c u r e an i m p o r t a n t d e f e n s i b l e t h i n g t o d o . E r i c L a n d e r
d e s c r i b e d t h e p l a c e o f c h a n g i n g t e c h n o l o g y in o u r changing
ethical landscape. W e ' v e seen r a t h e r r e m a r k a b l e changes in
gene t h e r a p y , s t e m m i n g f r o m t h e early fears and t h e disasters
o f t h e e x p e r i m e n t s o f M a r t i n Cline and Stanfield Rodgers be-
fore that.

W e a r e n o w c o m i n g t o a p o i n t w h e r e g e n e t h e r a p y is n o t o n l y
d e f e n s i b l e b u t i m m i n e n t a n d , in f a c t , t a k i n g p l a c e . T h e r e are
t w o sets o f p r o b l e m s t h a t I w o u l d l i k e t o b r i n g t o y o u r a t t e n -
t i o n , p r o b l e m s t h a t still r e m a i n s in g e n e t h e r a p y . T h e f i r s t is t h e
p r o b l e m o f s o m a t i c c e l l v e r s u s g e r m l i n e t h e r a p y , an issue t h a t I
t h i n k has s o f a r b e e n p o o r l y e x a m i n e d a n d t o o easiiy d i s m i s s e d .
I suggest t o y o u t h a t t h e level o f t h e ethical d i s c o u r s e w i t h res-
pect t o germ line t h e r a p y has b e e n e x t r e m e l y p o o r , even
t h o u g h i t is a p r o b l e m t h a t r e q u i r e s v e r y c a r e f u l a n d c o n s i d e r e d
d i s c u s s i o n . T h e s e c o n d v e r y d i f f i c u l s e t o f issues r e l a t e s t o c o n -
t e n t i o u s q u e s t i o n s o f " w h a t is d i s e a s e " a n d w h a t a r e t h e t a r g e t s
at w h i c h w e should be aiming o u r therapeutic armamentarium.
S o m e p h e n o t y p e s , s u c h as T a y - S a c h s d i s e a s e , r e p r e s e n t clear
a n d o b v i o u s diseases, a n d m o s t m o r a l a g e n t s a m o n g us w o u l d
a g r e e t h a t t h e r e is v e r y l i t t l e b e n e f i t a n d v e r y l i t t l e g o o d t o be
derived f r o m t h o s e kinds of human traits. But t h e r e are many
human characteristics and o t h e r qualities, of intelligence and
p e r s o n a l i t y t h a t d o n o t n e c e s s a r i l y r e p r e s e n t diseases t o b e e l i m -
i n a t e d , b u t c h a r e a c t e r i s t i c s t h a t may be d e l e t e r i o u s , b u t t h a t
also m a y serve i m p o r t a n t and useful p u r p o s e s . T h e s e t o o c o m e
under attack o r b e c o m e vulnerable o r susceptible t o modifica-
t i o n . T h e y are t h e k i n d o f qualities t h a t w e may be able t o m o d -
ify b u t o b v i o u s l y s h o u l d n o t u n t i l w e a r e a b l e t o understand
m o r e about the long t e r m consequences of these modifications.
I t h i n k m y t i m e is u p . I w o u l d l i k e t o e n d b y r e i t e r a t i n g f o r y o u
the immense need f o r continued discussion, n o t only of the
t e c h n o l o g y , b u t o f t h e i m p a c t o f t h e s e m a n i p u l a t i o n s . W e have 209
a t least t w o m a j o r e t h i c a l p r o b l e m s t h a t r e m a i n b e f o r e us, b u t I
t h i n k t h a t e v e n t h e s e p r o b l e m s w i l l c h a n g e as o u r t e c h n o l o g i c a l
a r m a m e n t a r i u m changes. T o d a y ' s p r o b l e m s w i l l disappear or
m o d i f y In t h e f u t u r e b u t I w o u l d l i k e t o s u g g e s t t h e Fundación
p a r a los E s t u d i o s A v a n z a d o s m i g h t c o n s i d e r t h e f u t u r e m e e t i n g s
will concéntrate on these.
 21 I

THE IMPACT OF HUMAN

C E N O M E MAPPING O N T H E
DOCTOR-PATIENT
RELATIONSHIP

Albert R. jonsen

D e p t . o f M e d i c a l H i s t o r y a n d Ethics, U n i v e r s i t y o f W a s h i n g t o n .
Seattle, W a s h i n g t o n ( U S A )

ABSTRACT

ñearing in m i n d t h a t the genetic m a p is as yet a

non-fulfilled future, the author describes a probable
discourse for this m o m e n t o f the relationship be-
tween doctor a n d patient, which entails the following:
a future illness wiíl be experienced as a present rea-
lity; the potential wiíl become the present; the inter-
ventionist, active medicine o f today will change to
become a comtemplative science; a n d the duration
o f the current doctor-patient relationship will give
way to a doctor-community relationship.
The present limits to the doctor-relationship will be
renewed a n d modified to the extent that the elabo-
ration o f a genetic m a p progresses.
M y r o l e is t o discuss t h e i m p l i c a t i o n s o f m a p p i n g t h e h u m a n g e - 21 3
n o m e f o r t h e r e l a t i o n s h i p b e t w e e n physicians a n d p a t i e n t s . O n l y
a t i n y f r a g m e n t o f t h e g e n o m e has y e t b e e n m a p p e d a n d o n l y a
f e w h u m a n diseases have b e e n l l n k e d t o t h a t small m a p . T h u s ,
any i m p l i c a t i o n s f o r t h e r e l a t i o n s h i p b e t w e e n p a t i e n t a n d p h y s i -
cian a r e s p e c u l a t i v e a n d p r o b a b l e . A l l o w m e t o m a k e t h i s s p e c u -
lative and p r o b a b l e t o p i c c o n c r e t e and visible t h r o u g h a m e t a
p h o r : t h e m e t a p h o r o f m a p m a k i n g . T h i s is, o f c o u r s e , t h e m a s t e r
m e t a p h o r f o r t h e e n t i r e s c i e n t i f i c e n t e r p r i s e k n o w n l o o s e l y as
T h e G e n o m e P r o j e c t . James W a t s o n a n d N o r t o n Z i n d e r v i v i d l y
e m p l o y e d t h e m e t a p h o r in a r e c e n t l e t t e r t o t h e N e w York
T i m e s [ O c t . 13, 1990, p. 14]: " L i k e t h e s y s t e m o f s t a t e h i g h w a y s
spanning o u r c o u n t r y , t h e map o f t h e H u m a n G e n o m e w i l l be
c o m p l e t e d s t r e t c h by s t r e c h " .

T h e s c i e n t i f i c w o r k o f c r e a t i n g linkage m a p s a n d p h y s i c a l m a p s ,
w h e r e b y genes a r e assigned t o c h r o m o s o m e s a n d t h e i r n u c l e o -
t i d e s e q u e n c e i d e n t i f e d is s o m e w h a t l i k e , b u t n o t v e r y much
like, t h e d r a w i n g o f squiggly lines w i t h i n M e r c a t o r projections
t o d e s í g n a t e c o a s t s , islands, m o u n t a i n s , a n d t h e b o u n d a r i e s of
p o l i t i c a l e n t i t i e s . S o m e o f t h e p r o d u c t s t h a t issue f r o m t h e d e -
c o d i n g o f t h e g e n o m e maps e v e n l o o k like geographical maps: l o w
r e s o l u t i o n physical maps m a d e u n d e r light m i c r o s c o p y r e s e m b l e
t o high r e s o l u t i o n p h o t o g r a p h s m a d e b y r e m o t e s e n s i n g s a t e l -
lites s u c h as t h i s o n e of... t a k e n f r o m SpaceLab. H i g h r e s o l u t i o n
g e n o m i c m a p s o f E C o l i o r phage T 4 l o o k r a t h e r l i k e t h e c i r c u -
lar m a p p a m u n d i o f t h e M i d d l e A g e , s u c h as t h i s s p l e n d i d C a t a l o -
nian m a p t h a t b e l o n g e d t o t h e B o r g i a f a m i l y . Y e t f o r t h e most
p a r t , t h e i n v e s t i g a t i v e m e t h o d s , t h e physical m a t e r i a l s a n d t h e
biochemical references o f g e n o m i c maps are quite unlike g e o -
graphical maps and m a p p i n g . T h e i n t e r m i n a b l e series o f c o d e
letters and w o r d s t h a t express sequences w o u l d n e v e r be mis-
t a k e s f o r a r o a d m a p . Still, t h e m e t a p h o r is a u s e f u l o n e - i t m a k e s
c o n c r e t e and visible a highly c o m p l e x and elusive s t r u c t u r e of
matter.

T h e m a p p i n g m e t a p h o r is m o s t a p p r o p r i a t e t o Spain, t h e s i t e
o f t h i s c o n f e r e n c e . In t h e I 5 t h a n d I 6 t h c e n t u r i e s , Spanish a n d
Spanish-sponsored e x p l o r e r s t o u c h e d far c o r n e r s of t h e globe.
Their explorations made n e w maps possible and made new
methods of mapping necessary. T h e first m o d e r n Atlas was
p r o d u c e d by O r t e l i u s , g e o g r a p h e r t o Felipe Segundo. T h e art
and s c i e n c e o f m a p p i n g o w e s m u c h t o Spain ( a n d t o its n e i g h -
b o r , P o r t u g a l ) . By t h e m i d d l e o f t h e I 6 t h c e n t u r y , al! t h e lines
on t h e surface o f t h e g l o b e had been r e d r a w n , n e w ones a d d e d
and o í d o n e s r e n d e r e d m o r e a c c u r a t e . T h e gradual discovery
of t h e locus and sequence o f t h e H u m a n G e n o m e w i l l be like
t h e E u r o p e a n d i s c o v e r y o f u n k n o w n lands: it w i l l , a m o n g o t h e r
214 e f f e c t s , r e q u i r e t h e r e d r a w i n g o f t h e lines t h a t m a r k t h e p r e s -
ent boundaries of the relationship between physicians and
t h e i r p a t i e n t s . By t h e m i d d l e o f t h e 2 l s t c e n t u r y , t h e g e n o m i c
physician and t h e g e n o m i c p a t i e n t w i l l l o o k u p o n each other
f r o m quite different standpoints than they do today. Naturally,
l i k e t e r r i t o r i a l b o u n d a r i e s in r e m o t e á r e a s , t h e b o u n d a r i e s of
t h e p a t i e n t - p h y s i c i a n r e l a t i o n s h i p as i t has e x i s t e d a n d as i t w i l l
e x i s t in t h e g e n o m i c e r a w i l l o f t e n o v e r l a p . S o m e territories
w i l l r e m a i n in t h e o í d d o m a i n ; m a n y o f t h e n e w f e a t u r e s w i l l
r e s e m b l e t h e o í d . S t i l l , i t is m y c o n t e n t i o n t h a t t h e m a p o f t h e
r e l a t i o n s h i p w i l l b e c o m e a n e w o n e as t h e s c i e n t i f i c w o r k of
m a p p i n g t h e g e n o m e p r o c e e d s . It is m y i n t e n t i o n t o describe
t h a t f u t u r e m a p , r e c a l l i n g , h o w e v e r , t h a t s i n c e w e d e s c r i b e an
as y e t u n r e a l i z e d f u t u r e , m y w o r d s are s o m e w h a t like the
w o r k o f t h e m e d i e v a l c a r t o g r a p h e r s w h o d r e w m a p s o f places
t h e y had n o t seen.

The map of the relation between physician and patient has

b e e n r e d r a w n s e v e r a l t i m e s in t h e h i s t o r y o f w e s t e r n m e d i c i n e .
T h e r e v i s i ó n has b e e n m a d e n e c e s s a r y b y n e w Information,
s o m e t i m e s at t h e level o f t h e o r y , s o m e t i m e s due t o n e w data,
t h a t has r a d i c a l l y m o d i f i e d t h e w a y d i s e a s e a n d h e a l i n g were
u n d e r s t o o d . T h e m o s t r e c e n t r e v i s i ó n c a m e in t h e l a t t e r half
o f t h e 19th c e n t u r y . P r i o r t o t h a t era, physicians learned a b o u t
t h e i r p a t i e n t ' s illness p r i m a r i l y f r o m t h e p a t i e n t ' s o w n report-
ing o f t h e i r s y m p t o m s and t h e y linked t h o s e r e p o r t s t o ebbs
and f l o w s o f internal fluids t h a t themselves responsed t o ex-
t e r n a l , c o s m i c f o r c e s . In a l m o s t all a n c i e n t m e d i c a l t h e o r y , t h e
p a t i e n t w a s a m i c r o c o s m e n g u l f e d in t h e m a c r o c o s m . I n t e r v e n -
tions w e r e designed t o redress imbalances n o t only w i t h i n , b u t
b e t w e e n w i t h i n and w i t h o u t . T h e r e existed no reliable w a y t o
l i n k signs a n d s y m p t o m s t o t h e m a l f u n c t i o n o f d i s c r e t e organ
systems.

In t h e I 9 t h c e n t u r y , m e d i c a l sciences b e c a m e i n c r e a s i n g l y capable
o f r e l a t i n g t h e p a t i e n t ' s signs a n d s y m p t o m s t o an o r g a n i c a l l y
based p a t h o l o g y . T h e single disease o f m i c r o c o s m i c imbaiance f r a c -
t u r e d i n t o m ú l t i p l e diseases s i t e d in specific o r g a n s a n d c a u s e d by
specific agents. T h e p a t i e n t w a s n o l o n g e r a m i c r o c o s m b u t r a t h -
e r a site f o r disease p r o c e s s e s . T h i s r e q u i r e d a r e d r a w i n g o f t h e
m a p b e t w e e n p a t i e n t a n d p h y s i c i a n . In t h e f o r m e r e r a , t h e p h y s i -
cian s t o o d b e f o r e t h e p a t i e n t as a l i s t e n e r , o b s e r v e r a n d c o u n s e l -
l o r . In t h e n e w age o f p h y s i o l o g i c a l p a t h o l o g y , t h e physician g r a -
d u a l l y b e c a m e an i n t e r v e n e r , seeking o u t the organic or
o r g a n i s m i c s o u r c e o f disease a n d e x t i r p a t i n g it. T h e n e w p h y s i -
cian b e c a m e able t o e n t e r t h e living b o d y , f i r s t b y s t e t h o s c o p i c
a u s c u l t a t i o n , t h e n b y x - r a y a n d all its r a d i o l o g i c a l a n d e n d o s c o p i c
s u c c e s s o r s ; t h e b o d i l y cavities w e r e physically e n t e r e d b y s t e r i l e ,
painless s u r g e r y . A s t h e physicai b o u n d a r i e s w e r e passed, t h e r e - 215
l a t i o n a l b o u n d a r i e s c h a n g e d . I shall cali t h e r e l a t i o n a l m a p t h a t
carne a b o u t a f t e r t h e m i d d l e o f t h e I9th century, the map of
m o d e r n medicine.

T h e m a p t o o k o n t h e f o l l o w i n g c o n f i g u r a t i o n . It s h o w s a p a t i e n t
p r e s e n t l y s u f f e r i n g f r o m an a i l m e n t p r e s e n t i n g h i m s e l f o r h e r s e l f
t o a physician w h o sets o u t t o d i s c o v e r a n d e x t í r p a t e t h e cause
o f t h e a i l m e n t . T h e r e l a t i o n s h i p w a s e s t a b l i s h e d o n t h e basis o f
an actual c o m p l a i n t a t t h e p r e s e n t t i m e , r e q u i r i n g a c t i v e i n t e r v e n -
t i o n f o r diagnosis and t r e a t m e n t and u n i t e d t w o persons, t h e
physician a n d t h e p a t i e n t . T h u s , t h e r e l a t i o n s h i p c o u l d be d e s c r i b -
ed s u c c i n c t l y as an a c t u a l , p r e s e n t , a c t i v e d u a l i t y . Spain's g r e a t
p h i l o s o p h e r o f m e d i c i n e , t h e late P e d r o Laín E n t r a l g o , r e f l e c t e d
o n t h e s t r u c t u r e o f t h i s r e l a t i o n s h i p a n d d e f i n e d i t as " a q u a s i - d i -
adic a n d h e l p f u l c o o p e r a t i o n , w h o s e p u r p o s e is t h a t t h e p a t i e n t
s h o u l d a c h i e v e t h e p s y c h o s o m a t i c s i t u a t i o n w e calis h e a l t h . "
[ D o c t o r a n d P a t i e n t . T r a n s . Francés P a r t r i d g e . N e w Y o r k : M c -
G r a w - H i l l , 1968, p. 152]

T h e r e a r e , o f c o u r s e , m a n y n u a n c e s in t h i s d e s c r i p t i o n t h a t w e
c a n n o t e x p l o r e : I r e f e r y o u t o D r . Laín E n t r a l g o ' s b e a u t i f u l l i t t l e
b o o k . D o c t o r a n d P a t i e n t , f r o m w h i c h t h e a b o v e d e f i n i t i o n is
d r a w n , f o r t h a t e x p l o r a t i o n . M y p u r p o s e is s k e t c h i n g t h e m o d e r n
f o r m o f t h e r e l a t i o n s h i p is p r e c i s e l y t o suggest h o w t h e g r a d u a l
r e v e l a t i o n o f g e n o m i c I n f o r m a t i o n w i l l m o d i f y it, w i l l r e d r a w t h e
boundaries of the relational map.

G e n o m i c I n f o r m a t i o n w i l l e f f e c t m a n y c h a n g e s in t h e w a y s in
w h i c h w e u n d e r s t a n d t h e b i o c h e m i c a l basis o f h u m a n d e v e l o p -
m e n t a n d o f h e a l t h a n d disease. P u t in t h e m o s t g e n e r a l w a y , g e -
n o m i c I n f o r m a t i o n w i l l i n c r e a s e t h e s p e c i f i c i t y w i t h w h i c h w e can
identify and p r e d i c t t h e biochemical determinants of d e v e l o p m e n -
tal a n d p h y s i o l o g i c a l n o r m a l c y a n d a b n o r m a l i t y . T h e inevitable
d e v e l o p m e n t o f disease a n d t h e p r e s e n c e o f risks f o r disease, as
w e l l as p o s s i b i l i t i e s f o r p r e v e n t i o n , c u r e a n d r i s k r e d u c t i o n w i l l
b e c o m e m u c h m o r e visible a n d p r a c t i c a l t h a n e v e r b e f o r e . T h i s
w i l l b r i n g m a j o r shifts in t h e lines t h a n d e m á r c a t e t h e r e l a t i o n s h i p
b e t w e e n physician a n d p a t i e n t .

B e f o r e d e s c r i b i n g t h e n e w m a p itself, w e m u s t d e s c r i b e t h e p a t h s
t h a t scientifíc e x p l o r a t i o n i n t o t h e g e n o m e is t a k i n g . T h e speak-
ers a t t h i s c o n f e r e n c e w i l l r e l a t e t h o s e p a t h in d e t a l l . A l l o w m e
t o d o so in r o u g h o u t l i n e a n d w i t h r e f e r e n c e t o t h e p o s s i b l e c l i n i -
cal a p p l i c a b i l i t y o f scientifíc d i s c o v e r y .

It a p p e a r s t h a t t h e f i r s t v o y a g e s o f d i s c o v e r y i n t o t h e g e n o m e w i l l
achieve t h e m a p p i n g a n d s e q u e n c i n g o f m a n y a n d u l t i m a t e l y all, o f
21 6 t h o s e c o n d i t i o n s k n o w n t o be m o n o g e n i c . This will expand t h e
capacity f o r c a r r i e r screening and p r e s y m p t o m a t i c d e t e c t i o n t h a t
w e a l r e a d y have. T h u s , t h e e t h i c a l issues t h a t have a p p e a r e d f o r
H u n t i n g t o n ' s o r p o l y c y s t i c k i d n e y disease w i l l a p p e a r f o r a b r o a d
range o f late c h i l d h o o d o r a d u l t o n s e t diseases, such as Fabry's
Disease, retinitis pigmentosa, ocular albinism o r adult o n s e t mus-
cular d y s t r o p h y . Prenatal diagnosis and p r e s y m p t o m a t i c detec-
t i o n w i l l r e n d e r clinically p r e s e n t m a n y c o n d i t i o n s , o f v a r y i n g se-
verlty, that would otherwise not be perceived, felt or
e x p e r i e n c e d by t h e a f f e c t e d p e r s o n f o r r e l a t i v e l y l o n g p e r i o d s o f
time. This s o r t of genomic knowledge will precipítate the first
shift in t h e p a t i e n t - p h y s i c i a n r e l a t i o n s h i p .

T h e f i r s t shift w i l l be f r o m Present t o F u t u r e , o r m o r e a c c u -
r a t e l y , t h e d r a w i n g o f t h e F u t u r e i n t o t h e P r e s e n t . In m o d e r n
medicine, a person b e c o m e s a patient at t h e p o i n t w h e n a p r e s e n t
a i l m e n t m a n i f e s t s i t s e l f (I a b s t r a c t f r o m t h e b r o a d e r s e n s e o f
" p a t i e n t " that covers the quasi-constractual relationships involv-
e d in f i n d i n g a n d s e l e c t i n g s o m e o n e t o p r o v i d e p h y s i c i a n ser-
vices w h e n n e e d e d ) . P e o p l e c o m e t o t h e d o c t o r w i t h a " p r e s e n t -
ing c o m p l a i n t " . T h e activities o f diagnosis and t r e a t m e n t are
i n i t i a t e d in t h i s w a y . G e n o m i c I n f o r m a t i o n w i l l signal f u t u r e d i s -
ease o r desease risks. A s t h e m o l e c u l a r basis f o r single-gene i n -
h e r i t a n c e o f c o m m o n d e b i l i t a t i n g diseases u n f o l d s , d i a g n o s i s a n d
p r o g n o s i s w i l l c o l l a p s e i n t o each o t h e r . W e a l r e a d y k n o w t h a t
t h e r e a r e f a m i l i e s in w h i c h b r e a s t c á n c e r , c o l o n c á n c e r , A l z h e i -
m e r ' s disease o c c u r s in a u t o s o m a l d o m i n a n t f a s h i o n . F u t u r e d i s -
ease w i l l e n t e r t h e p a t i e n t p h y s i c i a n r e l a t i o n s h i p . P e r s o n s w i l l
b e c o m e patient's b e f o r e t h e i r t i m e . T h e y w i l l be d e s c r i b e d in
disease t e r m s b u t " f e e l f i n e " a n d " b e f i n e " , f o r y e a r s , p e r h a p s a l -
w a y s . T h e f u t u r e , h o w e v e r , w i l l be m a d e m o r e v i v i d l y present
than ever before.

A s e c o n d s h i f t w i l l be v e r y m u c h like t h e f i r s t : n o t o n l y w i l l t h e
Future b e c o m e Present, b u t the Potential will b e c o m e Actual.
M o d e r n m e d i c i n e k n o w s e n o u g h a b o u t " r i s k f a c t o r s " t o b e able
t o i n f o r m p a t i e n t s w i t h c e r t a i n c h a r a c t e r i s t i c o r Ufe styles t h a t
t h e y m a y b e c o m e ill in t h e f u t u r e . Classic g e n e t i c s d e s c r i b e d t h e
p a t t e r n s o f i n h e r i t a n c e t h e c o n s t i t u t e d r i s k f o r disease o r for
t r a n s m i s s i o n o f disease. Still, t h e d e v e l o p m e n t o f a c t u a l disease
lay in t h e f u t u r e a n d r e m a i n e d a p r o b a b i l i t y , n o t o n l y in t h e s t a -
t i s t i c a l b u t in t h e p s y c h o l o g i c a l sense. G e n o m i c I n f o r m a t i o n w i l l ,
a t least f o r m o n o g e n e t i c M e n d e l i a n d i s o r d e r s , m a k e t h a n p o t e n -
t i a l i t y an a c t u a l i t y . Even t h o u g h t h e illness has n o t y e t a p p e a r e d ,
i t has b e e n f o u n d b i o c h e m i c a l l y p r e s e n t . In a s i m i l a r w a y , t h e
r i s k s a s s o c i a t e d w i t h m u l t i - f a c t o r i a l disease w i l l b e c o m e much
m o r e p a l p a b l e . G e n o m i c i n f o r m a t i o n w i l l i d e n t i f y an i n c r e a s i n g
n u m b e r o f g e n e t i c l o c i in w h i c h t h e p r e s e n c e o f a specific DNA
sequence, perhaps o n e o f several variant sequences o r alíeles
f o u n d a t t h a t l o c u s , is a s s o c i a t e d w i t h i n c r e a s e d r i s k f o r a c o n d i - 2 I 7
t i o n , s u c h as c a r d i o v a s c u l a r d i s e a s e , c á n c e r , d i a b e t e s , d e p r e s -
sion. S o m e o f these c o n d i t i o n s w i l l be polygenlc; o t h e r w i l l r e -
q u i r e e n v i r o n m e n t a l a n d b e h a v i o r a l c o - f a c t o r s ; in b o t h cases,
t h e n u m b e r o f t h e s e m a y be v a s t a n d t h e i r n a t u r e o b s c u r e . Still,
p e r s o n s c a n b e d e s i g n a t e d p a t l e n t s in an a n t i c i p a t o r y sense, as a
schizophrenic o r cardiac o r cáncer patient long b e f o r e any ill-
ness is f e l t o r a n y p a t h o l o g y d a m a g e s t h e o r g a n i s m . Even t h o u g h
p r e d i c t i o n o f clinical m a n i f e s t a t i o n s in t h e i n d i v i d u a l w i l l n o t b e
h i g h l y a c c u r a t e , s i n c e i t w i l l d e r i v e f r o m p o p u l a t l o n d a t a , still t h e
reality o f risk w i l l be m u c h m o r e palpable. T o d a y these risks are
w r i t t e n in a b s t r a c t n u m b e r s t h a t have b u t r e m o t e i m p a c t o n a
person's p e r c e p t i o n o f themselves; t o m o r r o w they will be w r i t -
t e n in t h e g e n o m e , an i n d e l i b l e p a r t o f t h e self. A s an a n t i c i p a t o r y
patient, t h e y w i l l w a t c h themselves and physicians will watch
t h e m f o r t h e a p p e a r a n c e o f disease. T h i s , o f c o u r s e , m a y be o f
b e n e f i t , s h o u l d p r e v e n t i o n o r e a r l y t r e a t m e n t be p o s s i b l e . B u t ,
w h e t e r b e n e f i c i a l o r n o t , p o t e n t i a l disease w i l l b e c o m e a c t u a l , as
never before.

In t h e o r y , g e n o m i c I n f o r m a t i o n s h o u l d p r o v i d e n o t o n l y t h e diag-
nostic and p r o g n o s t i c aspects o f t h e patient-physician relation-
ship. It s h o u l d also p o i n t t o w a r d t h e t h e r a p e u t i c . W e have m a n y
p o s s i b l e r o u t e s t o p r e v e n t i o n . W e have a l r e a d y e m b a r k e d u p o n
gene therapy. W e can g l i m p s e w a y s in w h i c h g e n o m i c Informa-
t i o n can g u i d e a n d e n h a n c e c u r r e n t p h a r m a c o t h e r a p y . Still, t h e
t h e o r e t i c a l p o t e n t i a l f o r t h e r a p y is n o t likely t o be r e a l i z e d in any
b r o a d , m u c h less u n i v e r s a l w a y . U n q u e s t i o n a b l y , t h i s has a l w a y s
b e e n t r u e o f m e d i c i n e : m a n y diseases have b e e n r e c o g n i z e d a n d
even well u n d e r s t o o d w i t h o u t the faintest hope o f curing or
c h a n g i n g t h e i r c o u r s e . T h i s b e c a m e d r a m a t i c a l l y t r u e in t h e m i d -
n i n e t e e n t h c e n t u r y , w h e n m e d i c a l s c i e n c e t o r e t h e veil o f i g n o -
r a n c e b e t w e e n disease a n d o r g a n i c p a t h o l o g y . So m u c h became
k n o w n a b o u t t h e causes o f disease a n d s o l i t t l e w a s available t o
t r e a t it effectively t h a t " t h e r a p e u t i c n i h i l i s m " became t h e prevail-
ing m e d i c a l p h i l o s p h y . G r a d u a l l y , w i t h t h e a p p e a r a n c e o f e f f e c t i v e
pharmaceuticals and efficient surgery, this nihilism was c o n v e r t e d
i n t o a t h e r a p e u t i c a c t i v i s m . Even t h o u g h m a n y d i s o r d e r s defy
m e d i c a l i n t e r v e n t i o n , i n t e r v e n t i o n o f s o m e s o r t has become
man dato ry.

T h i s suggests t h e t h i r d shift o f b o u n d a r i e s o n t h e m a p o f t h e pa-

t i e n t - p h y s i c i a n r e l a t i o n s h i p : a s h i f t f r o m a Scientia A c t i v a t o a
Sdentia Contemplativa. M o d e r n m e d i c i n e is p r e d o m i n a n t l y a Scientia
Activa, a c o l l e c t i o n o f diagnostic and t h e r a p e u t i c a c t i o n s that
s t a r t in t h e logic o f clinical j u d g e m e n t a n d t e r m í n a t e in i n t e r v e n -
tions. M o d e r n medicine reluctantly acknowledges the presence
of u n t r e a t a b l e disease, but assumes t h a t at s o m e t i m e the
2 18 u n t r e a t a b l e w i l l e successfully t r e a t e d . G e n o m i c i n f o r m a t i o n , h o -
w e v e r , w i l l a n n o u n c e t h e p r e s e n c e o r t h e p o s s i b i l i t y o f disease
w í t h o u t t h e a p p l l c a t l o n o f t h e loglc o f cllnlcal j u d g e m e n t a n d f o r
w h l c h t h e r a p e u t l c i n t e r v e n t i o n m a y be unavallable. W e have a l r e -
a d y s e e n t h i s in o n e o f m o d e m g e n e t i c s f l r s t cllnical t r l u m p h s ,
siting t h e locus o f H u n t i n g t o n ' s Disease. A s t h e m a p p e d g e n o m e
o p e n s u p b r o a d vistas o f i n f o r m a t i o n , i t w i l l , in a s t r a n g e sense,
r e t u r n t o m e d i c i n e ' s i m p o t e n t past. G e n o m i c i n f o r m a t i o n , w h i l e
p r o m i s i n g many means o f c u r e and p r e v e n t i o n w i l l unravel b e f o r e
us m a n y m o r e t h r e a t e n i n g c o n d i t i o n s t h a t w i l l l o n g remain
untreatable. Perhaps t h e ancient a r t of prognosis, o f predicting
t h e n a t u r a l c o u r s e o f disease, i n c u l c a t e d b y H i p p o c r a t e s , w i l l be
t h e p r i n c i p i e b e n e f i c i a r y o f g e n o m i c i n f o r m a t i o n , a t least f o r t h e
f o r s e e a b l e f u t u r e . T h i s i m p l i e s t h a t t h e Scientia Activa m a y b e -
c o m e a Scientia Contemplativa: m a n y diseases w i l l b e u n d e r s t o o d
m o r e r a d i c a l l y t h a n e v e r b e f o r e , b u t t h e disease c o u r s e c a n n o t
b e c h a n g e d , a t least w i t h c u r r e n t k n o w l e d g e , t h u s i t can o n l y be
e x p e c t e d , w a t c h e d and w o n d e r e d a b o u t , by b o t h p a t i e n t and
physician.

T h e f o u r t h s h i f t w i l l be f r o m D u a l i t y t o C o m m u n i t y . Modern
m e d i c i n e is, as Laín E n t r a l g o e x p r e s s e d , a d u a l i t y b e t w e e n a p a -
t i e n t a n d a p h y s i c i a n . H e e v e n w i s h e d t o d e s c r i b e i t as a s p e -
cies o f p h i l i a , t h a t is, f r i e n d s h i p . G e n o m i c i n f o r m a t i o n w i l l p u s h
back t h e bounds of t h a t duality into w i d e r c o m m u n i t i e s o r p o p -
ulations. G e n e t i c i n f o r m a t i o n by definition ties and individual
i n t o his o r h e r h e r i t a g e a n d t o his o r h e r h e i r s . T h e diseases
linked t o genetic loci f l o w t h r o u g h families f r o m g e n e r a t i o n t o
g e n e r a t i o n . T h e i n d i v i d u a l w h o s t a n d s b e f o r e his o r h e r p h y s i -
c i a n s e e k i n g i n f o r m a t i o n a n d h e l p is, in t h e g e n e t i c v i e w , a n
instance o f a g r o u p linked t o g e t h e r t h r o u g h social instituions
s u c h as m a r r i a g e a n d h e r i t a g e a n d t h r o u g h s h a r e d b i o c h e m i c a l
c h a r a c t e r i s t i c s . W e a l r e a d y see t h i s in t h e t e c h n i q u e s u s e d t o
d e v e l o p RFLP l i n k a g e m a p s : w h o l e f a m i l i e s a n d d i f f e r e n t g e n e r -
a t i o n s m u s t be d r a w n i n t o t h e diagnostic p r o c e s s . W e even
s e e t h i s in t h e t e r m i n a t i o n of pregnancy following prenatal
d i a g n o s i s : a p o t e n t i a l h e i r is e l i m i n a t e d . W e a l s o c a n g l i m p s e
the presence of others, genetically unrelated, but intensely in-
t e r e s t e d in t h e i n d i v i d u a l o r f a m i l y u n d e r i n v e s t i g a t i o n : i n s u r -
ers, e m p l o y e r s , public health officials, pólice, g o v e r n m e n t . In-
dividual risk profiles will find t h e i r w a y into many computers
a n d f i l e d r a w e r s : t h e i n t r i n s i c d i f f i c u l t y o f i n t e r p r e t i n g t h e m ac-
c u r a t e l y w i l l b e i g n o r e d as t h e y b e c o m e useful I n s t r u m e n t s f o r
s o r t i n g o u t t h e f i t f r o m t h e w e a k , t h e safe f r o m t h e d a n g e r o u s ,
t h e c o s t - e f f e c t i v e f r o m t h e costly. M o r e and m o r e , a large
p o p u l a t i o n w i l l stand a r o u n d each patient, p r o v i d i n g essential
i n f o r m a t i o n , posing possibilities f o r p r e v e n t i o n and seeking o u t
p r e v i o u s l y prívate i n f o r m a t i o n f o r p u r p o s e s o f social o r eco-
nomic utility. T h e duality of the m o d e r n relation b e t w e e n phy- 219
sician and p a t i e n t w i l l w i d e n into a broad community. The
Duality will become a Multitude.

T h i s , t h e n , is m y n e w m a p o f t h e p a t i e n t p h y s i c i a n relationship
t h a t w i l l b e d r a w n as t h e e x p l o r a t i o n o f t h e H u m a n G e n o m e p r o -
ceeds. T h e c u r r e n t m a p o f a duality dealing actively w i t h a pres-
e n t d i s o r d e r w i l l be r e d r a w n t o s h o w a c o m m u n i t y contemplat-
ing a f u t u r e d i s o r d e r o r p r o b a b i l i t y t h e r e o f . O b v i o u s l y , t h e o í d
and t h e n e w maps o v e r l a p at m a n y points: t h e r e are w i t h i n t h e
c u r r e n t r e p e r t o i r e o f m e d i c i n e s i t u a t i o n s w h i c h l o o k m u c h like
t h e s i t u a t i o n s o f t h e f u t u r e . O b v i o u s l y , as w e l l , f u t u r e s i t u a t i o n s
will o f t e n be q u i t e similar t o t h e present. Y e t , I a m suggesting
t h a t a m j o r shift w i l l t a k e place. T h e m a p s o f t h e I 6 t h c e n t u r y d i d
sharpen many o f t h e geographical boundaries: these w e r e b u t m i -
n o r shifts. M u c h m o r e i m p o r t a n t l y , t h e y r e v e a l e d " t h e r e s " t h a t
had b e e n p r e v i o u s l y u n k n o w n a n d s h o w e d h o w i t w a s p o s s i b l e
t o g e t f r o m h e r e t o t h e r e in p r e v i o u s l y u n s u s p e c t e d w a y s . T h e s e
w e r e t h e m a j o r shifts.

The mapping of the Human G e n o m e , the, will require a remap-

p i n g o f t h e r e l a t i o n s h i p b e t w e e n physician a n d p a t i e n t . U n l i k e t h e
m a p p i n g o f t h e g e n o m e , w h i c h is a scientifíc v o y a g e o f d i s c o v e r y ,
t h e r e m a p p i n g o f t h e r e l a t i o n s h i p is a p o l i t i c a l a d v e n t u r e . It w i l l
r e q u i r e d i p l o m a c y a n d m a y r e s u l t in r e v o l u t i o n s in social i n s t i t u -
t i o n s , legal p r o v i s i o n s a n d e c o n o m i c a r r a n g e m e n t s . N e w claims
o f r i g h t s a n d d u t i e s w i l l e m e r g e . A b o v e all, j u s t as w h e n p o l i t i c a l
b o u n d a r i e s a r e r e d r a w , l o y a l t i e s a n d allegiences w i l l b e c h a l l e n g -
e d . T h e b o n d t h a t has t i g h t l y l i n k e d physician a n d p a t i e n t f o r s o
m a n y c e n t u r i e s w i l l be s t r e t c h e d w i t h i n t h e e m e r g i n g n e t w o r k o f
t h e m u l t i t u d e s t o w h o m g e n o m i c I n f o r m a t i o n is v a l u a b l e . T h e
t r a d i t i o n a l e t h i c a l f e a t u r e s o f t h e r e l a t i o n s h i p w i l l have t o be r e -
d e s i g n e d in s o m e r e s p e c t s a n d s t r e n g t h e n e d in o t h e r s . M y c o l -
league, J o h n F l e t c h e r , has w r i t t e n s e n s i t i v e l y o f t h e e t h i c a l i m p l i -
cations o f g e n o m i c I n f o r m a t i o n f o r medical genetics. [ F l e t c h e r , J. C.,
W e r t z , D . C . Ethics, l a w a n d m e d i c a l g e n e t i c s : a f t e r t h e human
g e n o m e is m a p p e d . E m o r y L a w Journal 1990; 3 9 : 7 4 7 - 8 0 8 ] . H o w -
e v e r , t h o s e i m p l i c a t i o n s g o b e y o n d t h e s p e c i a l t y w e cali m e d i c a l
g e n e t i c s : g e n o m i c I n f o r m a t i o n w i l l t r a n s f o r m all m e d i c a l p r a c t i c e
into medical genetics.

I a m s u r e t h a t m u c h o f w h a t I have said s o u n d s r a t h e r n e g a t i v e .
H o w e v e r , t h e shifts I h a v e d e s c r i b e d a r e , l i k e all m a j o r changes
in social a n d i n s t i t u t i o n a l Ufe, a m i x t u r e o f p o s i t i v e a n d n e g a t i v e .
G e n o m i c I n f o r m a t i o n p r o m i s e s significant t h e r a p e u t i c possibili-
ties, b u t w e m u s t n o t delude ourselves by believing t h a t t h e y w i l l
c o m e q u i c k l y o r t h a t t h e y w i l l be u n i v e r s a l . S i m i l a r l y , t h e shifts
f r o m t h e highly i n t e r v e n t i o n a l scientia activa t o s o m e t h i n g m o r e
220 üke a s c i e n t i a c o n t e m p l a t i v a m a y n o t be ail b a d , g i v e n t h e n o t a -
ble p o w e r o f i n t e r v e n t i o n t o h a r m o r t o d o n o t h i n g f o r t h e pa-
t i e n t . Finally, t h e s h i f t f r o m d u a l i t y t o m u l t i t u d e m i g h t press m o d -
ern medicine o u t of the excessive individualism that ignores
social a n d c o m m u n i t y r e s p o n s i b i l i t i e s . Each shift, like each d i s -
c o v e r y o f n e w lands a n d each m o v e m e n t o f p e o p l e s f r o m an o í d
w o r l d into a new, will bring a m i x of benefits and burdens,
g o o d s a n d evils.

A g a i n w e recall t h e ships t h a t sailed f r o m C á d i z f o u r centuries

ago. T h e i r v o y a g e s n o t o n l y m a p p e d t h e w o r l d , t h e y i n a u g u r a t e d
social, political and e c o n o m i c events t h a t radically changed h u -
mankind's v i e w o f itself and nations' views o f t h e i r destinies. T h e
m a p o f t h e n e w w o r l d w a s n o t d r a w n by C r i s t ó b a l C o l ó n , V a s c o
N ú ñ e z d e B a l b o a a n d F e r n a n d o Magellan: i t w a s also d r a w n by
t h e t h e o l o g i a n s , s u c h as F r a n c i s c o V i t o r i a a n d B a r t o l o m e o d e las
Casas, w h o e x p o u n d e d , in a c a d e m i c a n d p o l e m i c t e r m s , o n t h e
n e w ethical imperatives and responsibilities o f rulers, settlers and
explorers Some o f those events w e r e glorious. T h e discoveries
t h a t w i l l lead t o t h e m a p p i n g o f t h e g e n o m e w i l l have s i m i l a r d r a -
m a t i c effects o n o u r p e r c e p t i o n o f o u r n a t u r e a n d o u r r e l a n t i o n -
ships w i t h each o t h e r .

W e m u s t p r o c e e d w i t h t h e s e e x p l o r a t i o n s b u t , as o n e o f o u r f i n e
clinical g e n e t i c i s t s , N e i l H o l z m a n n has said, p r o c e e d w i t h c a u t i o n .
If I m a y a n n o t a t e his w a r n i n g , I w o u l d recall a d i c t u m o f St. T h o -
mas A q u i n a s , w h o said a b o u t c a u t i o n , b y w h i c h he m e a n t n o t t i -
m i d i t y b u t carefulness, " c a u t i o n is r e q u i r e d because h u m a n behav-
i o r is s o c o m p l e x t h a t g o o d a n d evil a r e i n e x t r i c a b l y m i x e d : t h e
p r u d e n t m a n c a n n o t a v o i d evil a l t o g e t h e r , b u t he s h o u l d be c a r e -
f u l t o a v o i d by f o r e s i g h t t h e c o m m o n pitfalls so t h a t as l i t t l e h a r m
as p o s s i b l e is d o n e " . T h i s w i s e c o m m e n t applies as w e l l t o t h e
p r u d e n t s c i e n t i s t : as t h e s e c r e t s o f t h e g e n o m e a r e u n r a v e l l e d ,
h u m a n g o o d a n d evil w i l l a p p e a r : l e t us a v o i d b y f o r e s i g h t t h e
c o m m o n pitfalls so t h a n m o r e g o o d t h a n h a r m c o m e s o f this
extraordinary effort t o expand the boundaries of human know-
ledge. L e t t h i s final s k e t c h by C o y a a n d its m o t t o , " e v e n y e t , I a m
l e a r n i n g " , p r o v i d e an image f o r t h e p r o j e c t : m a n y o f t h e s c i e n t i s t s
in t h i s r o o m w i l l l o o k like t h i s a n c i e n t l o n g b e f o r e t h i s p r o j e c t ' s
implications f o r science and medicine will be exhausted.
 221

THE IMPACT OF HUMAN

GENOME STUDIES ON
CLINICAL GENETICS

Michele D'Urso

T h e I n t e r n a t i o n a l I n s t i t u t e o f G e n e t i c s a n d B i o p h y s i c s , C.N.R.,
N a p l e s (Italy)

ABSTRACT

On account o f growth in the scale o f the work invol-

ved, huge benefits are to be derived from the Human
Genome Project; the speed a n d effidency with which
h e r e d i t a r y c o m p o n e n t s o f m o n o g e n i c disorders
are analysed will increase, as ¡ikewise accuracy o f
diagnosis; it wiü facilitate the etioiogical study o f
complex a n d polygenic disorders, a n d will clarify the
role played by gene in processes such as cáncer and
self-immune illnesses.
On a long-term basis, the concept o f molecular ill-
ness will be better understood, a great deal o f the
h u m a n m e t a b o l i s m a n d development biology will
be explained, thus increasing possibilities for genic
therapy.
Genetics t o d a y impacts o n agriculture, ecology, sociology, phil- 223
o s o p h y a n d l a w ; b u t p r o b a b l y its g r e a t e s t i m p a c t is in clinical g e -
n e t i c s . T h e r o l e o f clinical g e n e t i c s a t m e d i c a l c e n t e r s increases
w i t h appeals f r o m f a m i l i e s w h o cali l o o k i n g f o r h e l p . T h e i n c r e a s e
parallels t h e i n c r e a s e in I n f o r m a t i o n : t h e e n t r i e s in Mckusick's
s t a n d a r d c a t a l o g u e i n c r e a s e d f r o m a b o u t 1300 in 1966 t o a b o u t
4600 currently (Mckuslck, V A M e n d e l i a n I n h e r i t a n c e in M a n . 8 t h
e d . B a l t i m o r e , J o h n s H o p k i n s U n i v e r s i t y Press, 1988). T h l s e n o r -
m o u s i n c r e a s e is m o s t p a t e n t in a c a d e m i c e n v i r o n m e n t s a t t e r -
t i a r y c a r e c e n t e r s , w h e r e t h e clinical g e n e t i c i s t s a r e c o n s u l t a n t s
in r a r e diseases. A s a r e s u l t , i t has b e e n suggested t h a t m e d i c a l
s c h o o l s m a y c o m e t o b e k n o w n as g e n e t i c s s c h o o l .

It is n o t a b l e t h a n b o t h b e c a u s e w e can n o w m a n a g e l o w birth
w e i g h t a n d because s o m a n y d i f f e r e n t r a r e diseases a r e k n o w n ,
t h e leading cause o f i n f a n t d e a t h ( 2 0 % o f t h o s e w h o die in t h e
f i r s t y e a r ) is b i r t h d e f e c t / m a l f o r m a t i o n (see, f o r example,
R o b e r t s , D.F., C h a v e z , J. V o u t y , D . F . Z M . S t v h . Fid. Vhilf. 5 6 : 4 4 - 4 8
[ 1 9 7 0 ] . A n e w - b o r n has a 2 t o 5 % c h a n c e o f having a m a j o r m a l -
f o r m a t i o n s y n d r o m e (see H a l l , J.G., P o w e r s , E.K., M c l l v a i n e , R.T.
and Ean, V . H . A m . J. M e d . G e n e t . 1:417-436 [ 1 9 7 8 ] f o r an assess-
m e n t o f f r e q u e n c i e s o f c h r o m o s o m a l , single g e n e , a n d p o l y g e n i c
d i s o r d e r s ) . A t a large m e d i c a l c e n t r e , o f t h e o r d e r o f 1,000 pa-
tients are seen p e r year, w i t h increases of t h e o r d e r o f 3 0 % year
in r e c e n t y e a r . T h e a v e r a g e t i m e s p e n t w i t h a clinical g e n e t i c s pa-
t i e n t is in t h e r a n g e o f 3 t o 8 h o u r s w i t h m o s t o f i t s p e n t in c o u n -
selling. T h i s t i m e is p o o r l y c o m p e n s a t e d , c o m p a r e d t o q u i c k p r o -
c e d u r e s l i k e e n d o s c o p y o f t h e t h r o a t , a n d c l i n i c a l g e n e t i c s is
expensive, d i f f k u l t specialty f o r a medical c e n t r e t o sustain. This
p r o b l e m w i l l n o t g o a w a y , a n d is a v i t a l c o n c e r n f o r t h e h e a l t h
s y s t e m s o f all c o u n t r i e s .

T h e f u n c t i o n s o f a clinical g e n e t i c i s t have, h o w e v e r , r e m a i n e d lar-

gely t h e s a m e : a c c u r a t e d i a g n o s i s ; t h e b e s t t h e r a p y p o s s i b l e ; m a n -
agement o f associated p r o b l e m s ; achieving reliable prognosis; and
d e t e r m i n i n g and discussing w i t h patients/families t h e risk of
r e c u r r e n c e a n d t h e i r o p t i o n s . H u m a n g e n e t i c s has b e e n t h e s u b -
stance o f t h e s e a c t i v i t i e s ; a n d t h e H u m a n G e n o m e P r o j e c t w i l l
t h e r e f o r e b e d i r e c t l y g e r m a n e . I w i l l discuss h e r e t h e i m p l i c a t i o n s
o f t h e scale o f g e n o m e analysis, t h e r e s u l t i n g d i f f e r e n c e t h a t can
be m a d e b y g e n o m e s t u d i e s , a n d w a y s in w h i c h t h a t difference
can be t r a n s l a t e d i n t o p a t i e n t b e n e f i t s .

G e n o m e s t u d i e s have n o t w a i t e d f o r t h e H u m a n G e n o m e P r o -
ject t o be o f e x t r a o r d i n a r y i m p o r t a n c e f o r diagnostic activities.
O n e o f t h e m o s t r e c e n t examples o f t h e usefulness o f n e w In-
f o r m a t i o n c o m i n g f r o m g e n o m e s t u d i e s is t h e r e c e n t isolation
224 o f t h e g e n e in w h i c h l e s i o n s l e a d t o c y s t i c f i b r o s i s (Rommens,
J . M . e t al. S c i e n c e 2 4 5 , 1 0 5 9 - 1 0 6 5 [ 1 9 9 0 ] ) . In t h i s case 1/2500
b i r t h s in c e r t a i n p o p u l a t i o n s h a v e C F , w i t h a c u r r e n t median
s u r v i v a l age o f 2 6 y e a r s . Since t h e g e n e is an a u t o s o m a l r e c e s -
sive, t h e r e is 1/4 c h a n c e o f o c c u r r e n c e in siblings o n an a f f e c t e d
i n d i v i d u a l . U s i n g l i n k e d m a r k e r s a n d l i n k a g e m a p p i n g in f a m i l i e s ,
c o n s i d e r a b l e p r o g r e s s has b e e n a c h i e v e d in d i a g n o s i s ; b u t re-
c o m b i n a t i o n always limited t h e accuracy o f t h e inferred Infor-
mation. W i t h the establishment that 70% of the CF patients
h a v e t h e 3 base p a i r p h e 5 0 8 d e l e t i o n , d i r e c t - g e n e t e s t i n g w h i c h
is f a r m o r e a c c u r a t e is a v a i l a b l e f o r t h o s e f a m i l i e s . ( T h i s c a n b e
d o n e in g e n e r a l b y o l i g o - m i s m a t c h h y b r i d i z a t i o n , b y t h e c h a n g e
in r e s t r i c t i o n e n z y m e s i t e s , o r b y c o m p a r i n g t h a t r e g i ó n o f n o r -
mal and p a t i e n t D N A s by PCR-based t e c h n i q u e s . A t least t w o
o f t h e s e tests are c u r r e n t f o r C F , and can be c a r r i e d o u t by
c h o r i o n i c villus biopsy [at 9 t o 13 w e e k s ] o r a m n i o c e n t e s i s [at
16 t o 18 w e e k s ] ) .

Such g e n o m e s t u d i e s aid d i r e c t l y in p r e n a t a l diagnosis, t h e p r i m e

t o o l o f t h e clinical g e n e t i c i s t . D i a g n o s i s has m a n y j u s t i f i c a t i o n s ;
b u t p e r h a p s t h e m o s t i m p o r t a n t is t h e a l l e v i a t i o n o f a n x i e t y .
W i t h t h e i n t r o d u c t i o n of non-directive counselling t o ensure that
t h e f a m i l y can m a k e its o w n c h o l e e s , diagnosis p r o v i d e s a c c u r a t e
I n f o r m a t i o n a n d also p e r m i t s t h e p r e p a r a t i o n o f a p p r o p r i a t e c a r e
f o r a f f e c t e d infants, p a r t i c u l a r l y in t h e p e r i o d d i r e c t l y a f t e r b i r t h .
F o r a disease like t h e s e x - l i n k e d H u n t e r ' s s y n d r o m e , c h i l d r e n can
die y o u n g , a n d s u p p o r t is n e e d e d f r o m t h e s t a r t ; a n d f o r c y s t i c f i -
b r o s i s , e a r l y diagnosis p e r m i t s a d e q u a t e p r e p a r a t i o n s a n d c a r e t o
b e o r g a n i z e d as s o o n as p o s s i b l e .

I t is h o w e v e r , t r u e t h a t c y s t i c f i b r o s i s l e s i ó n - l i k e s o m a n y o t h -
e r h e r e d i t a r y s c o u r g e s o f h u m a n i t y - w a s f o u n d largely by t h e
application o f s t a n d a r d linkage m a p p i n g and m o l e c u l a r biology
t e c h n i q u e s . In f a c t , as t h e c o m p i l a t i o n o f D r . M c k u s i k s h o w s , a
real and i n c r e a s i n g n u m b e r o f analyzed w i t h o u t t h e use or
b e n e f i t o f t h e H u m a n G e n o m e P r o j e c t . B o t h t h e l e s i o n s in a
n u m b e r o f h e r e d i t a r y m a l a d i e s a n d in a n u m b e r o f c a n c e r s c a n
n o w b e d e t e c t e d b y s p e c i f i c m o l e c u l a r p r o b e s ; a n d i t is a r a r e
g e n e t i c disease w h i c h d o e s n o t h a v e s e v e r a l r e s e a r c h groups
a t t e m p t i n g t o f a t h o m its basis a t t h e m o l e c u l a r l e v e ! . W h a t dif-
f e r e n c e is m a d e b y t h e c u r r e n t I n t e r n a t i o n a l e f f o r t t o c a r r y o u t
systematic analysis of t h e g e n o m e , and t o bring together
g r o u p s l i k e t h i s o n e t o d i s c u s s t h e e x t r a o r d i n a r y e t h i c a l issues
t h a t are entailed?

M a j o r benefits o f t h e H u m a n G e n o m e P r o j e c t accrue by v i r t u e of
t h e i n c r e a s e in t h e s c a l e o f w o r k . W e are n o t talking simply
a b o u t an e x p a n s i ó n o f t h e n u m b e r o f g r o u p s a c t i v e in t h e s t u d y 225
o f i n d i v i d u a l diseases; b u t r a t h e r a b o u t t h e i n v e s t m e n t u p f r o n t
o f e n o u g h r e s o u r c e s t o f a c i l i t a t e disease g e n e s t u d i e s in g e n e r a l .

T o see t h e d i f f e r e n c e , c o n s i d e r t h a t each l a b o r a t o r y w h i c h has

d e t e r m i n e d a l i k e l y l o c a t i o n f o r a g e n e b y linkage m a p p i n g o r
o t h e r m e a n s m u s t usually i n i t i a t e a l a b o r i u s s e a r c h f o r t h e DNA
that corresponds t o that región of the genome. Only w h e n that
r e g i ó n o f t h e D N A has b e e n p i e c e d t o g e t h e r f r o m a n u m b e r o f
c l o n e s can t h e s e a r c h f o r t h e disease g e n e c o n t i n u é full f o r c é . In
c o n t r a s t , s u p p o s e t h a t an o v e r a l l c o l l e c t i o n o f c l o n e d D N A has
b e e n a s s e m b l e d t o c o v e r m u c h o r all o f t h e g e n o m e : any p a r t i c u -
lar i n v e s t i g a t o r w o u l d a u t o m a t i c a l l y have a t his disposal t h e s t a r t -
ing D N A f o r his r e g i ó n o f i n t e r e s t , a n d c o u l d i m m e d i a t e l y g e t o n
with the w o r k of particular interest.

A s a r o u g h e s t í m a t e , t h e a v a i l a b i t i t y o f such a r e s o u r c e o f m a p -
p e d D N A w o u l d s h o r t e n t h e s e a r c h f o r a disease g e n e by u p t o
8 0 % , w i t h a s h a r p r e d u c t i o n in n e c e s s a r y e f f o r t a n d c o s t as w e l l
as t i m e . T h e e f f i c i e n t e x p a n s i ó n o f large-scale g e n o m e w o r k n e -
cessitates a c o r r e s p o n d i n g d e v e l o p m e n t of n e w technology,
w h i c h w o r k s y n e r g i s t i c a l l y t o aid in t h e s e a r c h f o r any i n d i v i d u a l
gene. F o r e x a m p l e , I have b e e n v e r y i m p r e s s e d w i t h t h e w o r k a t
t h e C e n t r e f o r G e n e t i c s in M e d i c i n e a t t h e W a s h i n g t o n Univer-
sity in St. L o u i s . W o r k e r s t h e r e have p i o n e e r e d in t h e d e v e l o p -
m e n t o f y e a s t a r t i f i c i a l c h r o m o s o m e s as a c l o n i n g v e c t o r and
mapping t o o l , and have already substantively a c c e l e r a t e d t h e studies
of t h e regions of D N A including t h e loci f o r Neurofibroma-
t o s i s I, W i l m s t u m o r , H u n t i n g t o n ' s disease, a n d p o l y c y s t i c k i d n e y
disease. I c o n s i d e r t h a t a f o r e t a s t e o f w h a t is t o c o m e as t h e G e -
n o m e P r o j e c t gets u n d e r w a y .

S i m i l a r c o n s i d e r a t i o n s a p p l y t o c u r r e n t e f f o r t s in t h e Genome
Project t o increase t h e resolving p o w e r and coverage o f t h e ge-
netic linkages m a p ( D o n i s - K e l l e r , H. e t al. C e l l , 51:310-337,
1987). T h e linkage m a p r e m a i n s t h e r e l i a b l e w a y t o b r i d g e inves-
tigations f r o m pedigree studies o f t h e inheritance o f a c o n d i t i o n
t o r e s p o n s i b l e D N A ; a n d its r e f i n e m e n t c o u l d y i e l d m u c h c l o s e r
l o c a l i z a t i o n o f a disease g e n e b e f o r e physical m a p p i n g s t a r t s .

O n e m a j o r impact o f t h e G e n o m e P r o j e c t w i l l thus be o n t h e
s p e e d a n d e f f i c i e n c y w i t h w h i c h h e r e d i t a r y c o m p o n e n t s in d i s -
ease can b e a n a l y z e d , a n d in t h e r e s u l t a n t d e p e n d a b i l i t y o f diag-
nosis: t h e risks t o c h i l d r e n , t h e h s k s f o r t h e n e x t c h i l d , e t c .

A s e c o n d m a j o r i m p a c t is c l e a r if o n e c o n s i d e r s t h a t t h e d i s c u s -
sions t h u s f a r has t u r n e d o n diseases c a u s e d b y lesions in single
226 l o c i ; b u t in fact, t h e e x p e c t e d i m p a c t o f g e n o m e s t u d i e s is e v e n
m o r e e x t r e m e f o r t h e case o f p o l y g e n i c diseases. F o r t h o s e , i n -
cluding schizophrenia and t h e h e r e d i t a r y c o m p o n e n t o f a l c o h o l -
i s m , t h e r e m a y be 4 t o 8 genes w h i c h have a m a j o r i n f l u e n c e ; a n d
it seems intuitively o b v i o u s t h a t global I n f o r m a t i o n a b o u t the
g e n o m e -as d e t a i l e d as p o s s l b l e - w l l l facilítate s u c h s t u d i e s ; a n d
t h a t t h e I d e n t i f i c a t i o n o f a g r o u p o f genes I n v o l v e d In t h e e t i o l o g y
o f s u c h c o m p l e x c o n d i t i o n s m a y b e p o s s l b l e only If i t c a n b e
based o n e x t e n s i v e g e n o m e analysis. O n c e again, diagnosis can
c e r t a i n l y be a i d e d .

It m a y b e w o r t h n o t i n g t h a t in a t h l r d m a j o r i m p a c t , t h e b e n e -
f i t s o f g e n o m e analysis a r e n o t l i m i t e d t o t h e r o l e a n d n a t u r e o f
d a m a g e d g e n e s . In p a r t i c u l a r , f o r t h e o u t c o m e o f c h r o n i c and
a c u t e o r g a n i c disease a n d i n f e c t i o u s disease as w e l l , t h e m a k e -
u p o f h o s t d e f e n s e s is c r l t l c a l . A l r e a d y n e w t e c h n o l o g y a s s o c i -
ated w i t h long-range yeast artificial c h r o m o s o m e - b a s e d mapping
o f t h e g e n o m e has p r o d u c e d a g r e a t d e a ! o f n e w Information
about the Major Histocompatibility Locus ( C h a p l i n , D., and
B r o n s o n , S., w o r k In p r o g r e s s ) ; a n d c o m p a r a b l e Information
a b o u t viral and bacterial resistance, antybody r e p e r t o i r e s , etc.
w l l l n o t b e f a r b e h i n d . In m a n y o f t h e s e cases, w e a r e n o t d i s -
cussing " a f f e c t e d " and " u n a f f e c t e d " genes; but v a r i a n t constella-
t i o n s o f g e n e s t h a n can h a v e v e r y d i f f e r e n t ( p o s i t i v e o r nega-
t i v e ) e f f e c t s f o r p a t i e n t s in s p e c i f i c i n s t a n c e s . T h i s t y p e of
I n f o r m a t i o n w l l l b e i m p o r t a n t In d e t e r m i n i n g t h e r a n g e o f g e n e t -
ic e f f e c t s in t h e r e s p o n s e t o e n v i r o n m e n t a l c h a l l e n g e s a n d to
c á n c e r , a n d in t h e c a u s a t i o n o f a u t o i m m u n e a n d o t h e r s y s t e m i c
diseases.

In t h e l o n g e r t e r m , o f c o u r s e , o n e e x p e c t s a f o u r t h a n d final i m -
p a c t o n t h e H u m a n G e n o m e P r o j e c t t h a t is f o u n d e d o n the
c o n c e p t o f m o l e c u l a r disease. It has b e e n d e m o n s t r a t e d many
t i m e s t h a t m u t a t i o n a l analysis can y i e l d c o n s i d e r a b l e i n s i g h t a b o u t
s t r u c t u r e / f u n c t i o n o f c o m p o n e n t s o f t h e b o d y . In f a c t , i t s e e m s
certain t h a t m u c h o f human metabolism and developmental biol-
o g y w l l l b e e x p l i c a t e d by g e n o m e s t u d i e s , a n d t h a t t h e i n c r e a s e d
level o f u n d e r s t a n d i n g w l l l s h i f t t h e w e i g h t o f t h e v a l u é f o r g e -
n o m e s t u d i e s f r o m diagnosis t o p r e v e n t i o n o r e v e n g e n e t h e r a p y .
H e r e c u r r e n t p r a c t i c e ; b u t i t is s u r e l y r e l e v e a n t t h a t y e a s t a r t i f i -
cial c h r o m o s o m e s have b e e n isolated c o n t a i n i n g large human
g e n e s in i n t a c t f o r m a n d w i t h n o r m a l n e i g h b o u r i n g s e q u e n c e s ,
a n d t h a t t h e s e c h r o m o s o m e s can be e x p r e s s e d w h e n t r a n s f e c t e d
i n t o m a m m a l i a n cells. T h i s p r o v i d e s a f i r s t s t e p b o t h t o w a r d u n -
derstanding and t o w a r d conceivable c o r r e c t i o n of some genetic
m a l a d i e s . In t h i s c o n t e x t , I have n o special c o m p e t e n c e t o c o m -
m e n t o n t h e ethical c o n s i d e r a t i o n s t h a t arise and are t h e focus
o f d i s c u s s i o n h e r e ; b u t I h o p e t h a t as g r o u n d w o r k f o r t h o s e d i s - 227
cussions, I have helped t o f u r t h e r o u t l i n e t h e e x p e c t a t i o n of
w h a t is s c i e n t i f í c a l l y p o s s i b l e b a s e d o n t h e H u m a n G e n o m e I n i -
tiative.
T H E IMPACT
OF T H E H U M A N
G E N O M E PROJECT
O N B I O L O G Y
 231

THE HUMAN CENOME

P R O J E C T : IN D E F E N C E
OF BASIC SCIENCE

Giorgio Bernardi

Laboratoire de Génétique Moléculaire,

I n s t i t u t Jacques M o n o d , París ( F r a n c e )

ABSTRACT

T h e H u m a n Genome Project aims t o m a p a n d se-

quence the human genome. However, the develop-
ment o f both these objectives will not mean absolute
knowledge o f h u m a n genetics. M a p p i n g a n d se-
quencing the genome means acquiring knowledge,
and knowledge, as such, is basic science. Neverthe-
less, this basic knowledge w i l l shed light on n e w
paths o f research for specific aspects o f the genome.
Introductíon 233

A l t h o u g h t h e H u m a n G e n o m e P r o j e c t has b a r e l y t a k e n off, i t has

been t a l k e d a b o u t so m u c h o v e r t h e past f e w years t h a t at
p r e s e n t , i t p r o b a b l y is t h e m o s t w i d e l y k n o w n p r o j e c t in B i o l o g y .
A s f a r as o n e can see, t h e r e a r e t h r e e m a j o r r e a s o n s f o r such p o p -
u l a r i t y : (i) t h e "largest biological project ever c o n t e m p l a t e d " (as i t is
called in t h e a d v e r t i s i n g o f H u m a n G e n o m e c o n f e r e n c e s ) is m o s t
i m p r e s s i v e ; i n d e e d , t h e p r o j e c t is s u p p o s e d t o lead t o k n o w l e d g e
o f t h e full s e q u e n c e o f t h e o v e r 3 G b (Gigabases, o r b i l l i o n s o f
base pairs) o f D N A t h a t m a k e u p t h e H u m a n G e n o m e ; (ii) i t is a
b r u t e f o r c é a p p r o a c h ; as s u c h , i t can b e u n d e r s t o o d w e l l b e y o n d
t h e n a r r o w c i r c l e o f t h e s c i e n t i f i c c o m m u n i t y ; (iii) t h e n o t i o n has
b e e n s p r e a d t h a t , o n c e t h e p r o j e c t is c o m p l e t e d , e v e r y t h i n g w i l l
be k n o w a b o u t m a n a n d his diseases. T h e s e p o i n t s d e s e r v e s o m e
comments.

T h a t t h e p r o j e c t is i m p r e s s i v e has t o b e a d m i t t e d e v e n b y its
s t r o n g e s t o p p o n e n t s . S e q u e n c i n g o v e r 3 b i l l i o n base p a i r s is, in
fact, s u c h a f o r m i d a b l e t a s k t h a t i t r e c e n t l y w a s p u t aside f o r
five y e a r s , h o p i n g t h a t d r a m a t i c i m p r o v e m e n t s in e x i s t i n g t e c h -
n i q u e s w i l l o c c u r in t h e m e a n t i m e . T h e r e f o r e , f o r t h e n e x t f i v e
y e a r s , . t h e H u m a n G e n o m e P r o j e c t w i l l basically b e a m a p p i n g
project.

A s f a r as physical m a p p i n g is c o n c e r n e d , i t is p r e s e n t l y intended
t o p u t physical m a r k e r s ( r e c o g n i z a b l e s e q u e n c e s , l i k e g e n e s or
a n o n y m o u s s i n g l e - c o p y s e q u e n c e s ) a t d i s t a n c e s o f 100 k b o r s o
( I k b , o r k i l o b a s e , is o n e t h o u s a n d base pairs) a l o n g t h e o n e m e -
tre thread of D N A w h i c h runs t h r o u g h t h e 22 autosomes (chro-
mosomes I t o 22) and t h e 2 sex c h r o m o s o m e s ( X and Y) of t h e
h u m a n k a r y o t y p e . P u t t i n g o n a m a p o v e r 3 0 , 0 0 0 l a n d m a r k s is still
a huge t a s k , r e q u i r i n g t h e c o l l a b o r a t i v e w o r k o f m a n y l a b o r a t o -
ries a r o u n d t h e w o r l d . T h e t e c h n o l o g y f o r e s t a b l i s h i n g t h e p h y s i -
cal m a p is essentially available; m o r e o v e r , a n u m b e r o f n e w t e c h -
niques a r e l i k e l y t o b e d e v e l o p e d in o r d e r t o p r o c e e d a t a f a s t e r
pace. Basically, w h a t is n e e d e d is a s e r i e s o f o v e r l a p p i n g DNA
s e g m e n t s , w h i c h m a y be c l o n e d in a n u m b e r o f w a y s , as y e a s t a r -
tificial c h r o m o s o m e s ( Y A C s ) , as c o s m i d s , o r as p l a s m i d . P a r t i c u -
lar u n i q u e s e q u e n c e s w i l l t h e n b e p l a c e d o n t h e s e o r d e r e d a r r a y s
of segments.

Genet;c m a p p i o n g is a m u c h m o r e l a b o r i o u s e n t e r p r i s e a n d its r e -
s o l u t i o n ( h o p e f u l l y I c e n t i m o r g a n ) w i l l b e a b o u t 10 t i m e s l o w e r
t h a n t h a t p l a n n e d f o r t h e physical m a p p i n g .

T h e f a c t t h a t t h e h u m a n g e n o m e p r o j e c t is a b r u t e f o r c é a p -
p r o a c h raises t h e q u e s t i o n as t o w h e t h e r i n t e l l i g e n t a p p r o a c h e s
c a n n o t b e u s e d t o d e v e l o p s h o r t c u t s in o r d e r t o a t t a i n i m p o r -
t a n t g o a l s , s u c h as g e n e l o c a l i z a t i o n . O n e s h o u l d n o t f o r g e t t h a t
t h e H u m a n G e n o m e is f o r m e d o f o v e r 9 0 % n o n - c o d i n g , i n t e r g e -
nic s e q u e n c e s ( c o n s i d e r e d as " j u n k D N A " b y c e r t a i n b i o l o g i s t s ) ,
234 a n d t h a t t h e r e is a n e e d t o c i r c u m v e n t t h e p r o b l e m o f i n v e s t i n g
a l o t o f s e q u e n c i n g e f f o r t o n t h o s e r e g i o n s , a t least in a f i r s t i n -
stance.

A n u m b e r o f s t a t e m e n t s have b e e n m a d e p u s h i n g t h e idea t h a t
k n o w l e d g e o f t h e p r i m a r y s t r u c t u r e o f t h e H u m a n G e n o m e is
equivalent t o k n o w i n g e v e r y t h i n g a b o u t a human being. N o no-
t i o n c o u l d b e m o r e m i s l e a d i n g , as w i l l be seen f r o m t h e f o l l o w i n g
examples. W e k n o w the sequence of mitochondrial genomes
f r o m o v e r 2 0 d i f f e r e n t species o f e u k a r y o t e s . In s p i t e o f t h i s , w e
d o n o t y e t u n d e r s t a n d m a n y f u n c t i o n a l aspects o f t h i s small g e -
n o m e ( 1 6 k b in size in a n i m a l cells) a n d o f its i n t e r a c t i o n w i t h t h e
n u c l e a r g e n o m e . L i k e w i s e , w e k n o w a large n u m b e r o f s e q u e n c e d
v i r a l g e n o m e s , a n d y e t w e a r e still v e r y f a r f r o m understanding
m a n y basic p r o b l e m s in v i r o l o g y . Such e x a m p l e s c o u l d be
m u l t i p l i e d t o i n c l u d e p l a s m i d s , as w e l l as t h e g e n o m e s o f c h l o r o -
plasts. T h e s e r e m a r k s simply serve t o stress t h e fact t h a t t h e
availability o f a g e n o m e s e q u e n c e is a necessary, y e t f a r f r o m suf-
ficient, condition f o r understanding the underlying biological
problems.

T h e p o i n t s m a d e in t h e p r e v i o u s t w o p a r a g r a p h s s u g g e s t t h a t
w e c a n n o t h o p e t o u n d e r s t a n d w h a t w e w o u l d like t o about
t h e H u m a n G e n o m e s i m p l y b y k n o w i n g its m a p a n d , l a t e r o n ,
its s e q u e n c e , a l t h o u g h s u c h a k n o w l e d g e w i l l d e f i n i t e l y expand
the number of known h u m a n genes and clarify a n u m b e r of
g e n e t i c d i s e a s e s . If t h e g o a l is u n d e r s t a n d i n g h u m a n genetics
a n d t h e r o l e o f v a r i o u s g e n e s in h e a l t h a n d d i s e a s e , t h e effort
made o n t h e H u m a n G e n o m e Project should be paralleled by a
m u c h l a r g e r o n e o n t h e basic m o l e c u l a r g e n e t i c s o f m a n and
o t h e r organisms.

W h a t w i l l b e a t t e m p t e d h e r e is t o s h o w t h a t basic s c i e n c e is
not only conducive t o a deeper understanding of the Human
G e n o m e t h a n b i o t e c h n o l o g y , b u t also t o t h e d e v e l o p m e n t of
n e w w o r k i n g hypotheses and e x p e r i m e n t a l approaches having a
d i r e c t impact o n t h e strategies t o f o l l o w and t h e priorities to
c h o o s e in t h e H u m a n G e n o m e P r o j e c t . T h i s w i l l b e d o n e by
u s i n g , as an e x a m p l e , w o r k c a r r i e d o u t in t h e a u t h o r ' s l a b o r a -
t o r y . B u t , f i r s t , l e t us d i s c u s s t h e h i s t o r y o f t h e w o r d genome
a n d its m e a n i n g .

A brief history of the word genome

T h e w o r d g e n o m e w a s c o i n e d in 1920 b y W i n k l e r ( I I y e a r s a f t e r
t h e w o r d gene w a s c r e a t e d b y J o h a n s s e n ) t o d e n o t e t h e s u m t o -
tal o f t h e genes o f an o r g a n i s m , b u t o n l y began t o s p r e a d several
d e c a d e s l a t e r , because f o r m a n y y e a r s i t w a s n o t f o u n d useful by
either geneticists o r cytogeneticists, t h e f o r m e r being interested
in g e n e s , t h e l a t t e r in c h r o m o s o m e s .
In 1948, i t w a s d i s c o v e r e d t h a t t h e a m o u n t o f D N A p e r cell is 235
t h e s a m e ¡n all d i p l o i d cell t y p e s o f a g i v e n species f r o m m u l t i -
c e l l u l a r e u k a r y o t e s , w h e r e a s t h e a m o u n t Is half in g a m e t e s . T h e
c o n s t a n t a m o u n t o f D N A In a h a p l o l d cell o f a g l v e n species w a s
c a l l e d c - v a l u e , o r g e n o m e size. T h e c o n s t a n c y o f g e n o m e size
w i t h i n a species w a a s , h o w e v e r , a c c o m p a i n e d b y large v a r i a t i o n s
w i t h i n o r d e r s , f a m i l i e s a n d g e n e r a . Such v a r i a t i o n s w e r e unlikely
t o be a s s o c i a t e d w i t h d i f f e r e n c e s in o r g a n i s m i c c o m p l e x i t y , ñor
w i t h t h e p r e s u m e d n u m b e r s o f genes, so raising t h e c-value para-
d o x . M o r e o v e r , t h e g e n o m e size o f m o s t e u k a r y o t e s obviously
w a s in large e x c e s s r e l a t i v e t o t h e l i k e l y n u m b e r s o f g e n e s . N e g -
l e c t i n g p o l y p l o i d y , w h i c h w a s t h e m a i n f a c t o r in a n u m b e r of
cases, t h e c-value p a r a d o x and t h e large size o f e u k a r y o t i c g e n o m e s
w e r e explained by t w o n o t mutually exclusive reasons: gene d u -
p l i c a r o n , and t h e expansión c o n t r a c t i o n p h e n o m e n a affecting in-
t e r g e n i c s e q u e n c e s . B o t h e x p l a n a t i o n s w e r e c o r r e c t . In t h e e v o -
l u t i o n o f e u k a r y o t i c g e n o m e s , g e n e d u p l i c a t í o n is c o m m o n , a n d
intergenic sequences d o c o n t r a c t and e x p a n d . Since intergenic
sequences r e p r e s e n t t h e vast m a j o r i t y o f t h e g e n o m e o f m u l t i -
c e l l u l a r e u k a r y o t e s (as w e s a i d , o v e r 9 0 % i n m a m m a l s ) , the
expansión c o n t r a c t i o n p h e n o m e n a a r e quantitatively by far t h e
most important factor.

A m u c h w i d e r s p r e a d i n g o f t h e w o r d g e n o m e in t h e I960s and
I970s was due t o investigations o n t h e sequence organization o f
e u k a r y o t i c g e n o m e s , using m e t h o d s s u c h as d e n s i t y g r a d i e n t c e n -
t r i f u g a r o n and reassociation kinetics. These pioneering efforts
w e r e f o l l o w e d , after the advent of recombinant D N A techno-
logy, b y an e x p l o s i v e d e v e l o p m e n t o f m o l e c u l a r g e n e t i c s . T h i s e x -
p e c t e d l y l e d t o an e x p o n e n t i a l i n c r e a s e in o u r k n o w l e d g e of
genes, f r o m b o t h p r o k a r y o t e s and e u k a r y o t e s , including the
u n f o r e s e e n d i s c o v e r y o f i n t r o n s in t h e l a t t e r . M o r e r e c e n t l y , t h e
use o f r e s t r i c t i o n e n z y m e s c u t t i n g a t r a r e s e q u e n c e s a n d t h e s e p -
a r a t i o n o f large D N A f r a g m e n t s b y p u l s e d f i e l d gel e l e c t r o p h o r e -
sis p a v e d t h e w a y t o l o n g - r a n g e p h y s i c a l m a p p i n g , w h i c h be-
c a m e an i n d i s p e n s a b l e a d j u n c t t o g e n e t i c a l m a p p i n g . W h i l e all
t h e s e d e v e l o p m e n t s l e d t o an i n c r e a s i n g use o f t h e w o r d g e n o m e ,
w h a t recently made it a household w o r d was t h e H u m a n G e n o m e
Project.

The meaning of the word genome

O v e r a l i f e t i m e o f 7 0 y e a r s , t h e w o r d g e n o m e has g r o w n from
t o t a l o b s c u r i t y t o e n o r m o u s p o p u l a r i t y . T h i s success w a s n o t p a r -
alleled, h o w e v e r , b y an i n c r e a s e d u n d e r s t a n d i n g o f t h e g e n o m e
itself. I n d e e d , t h e g e n o m e still s e e m s t o b e largely p e r c e i v e d as
j u s t t h e s u m t o t a l o f t h e genes o f an o r g a n i s m ( a n d o f t h e i n t e r -
genic s e q u e n c e s , if p r e s e n t , as in t h e case o f e u k a r y o t e s ) . T h i s
v i e w w a s c a l l e d t h e b e a n bag m o d e l o f t h e g e n o m e . A c c o r d i n g t o
236 ¡t t h e g e n o m e is j u s t a c o l l e c t i o n o f g e n e s , w h i c h , in e u k a r y o t e s ,
a r e r a n d o m l y s c a t t e r e d o v e r t h e v a s t e x p a n s e s o f j u n k D N A , es-
sentially f o r m e d b y i n t e r g e n i c s e q u e n c e s .

E v i d e n c e f r o m o u r l a b o r a t o r y , h o w e v e r , has s h o w n t h a t the
g e n o m e is m u c h m o r e t h a n t h a t . I n d e e d , t h e g e n o m e is an i n -
t e g r a t e d s t r u c t u r a l , functional and e v o l u t i o n a r y system that
o b e y s p r e c i s e r u l e s , w h i c h a m o u n t t o a g e n o m i c code. T h i s v i e w
aróse f r o m investigations on the compositional properties of
vertébrate genomes. The tacit assumption f o r this w o r k was
t h a t base c o m p o s i t i o n is a v e r y i m p o r t a n t p r o p e r t y o f t h e g e -
nome.

A l t h o u g h this approach was already extensively applied t o the

study o f t h e m i t o c h o n d r i a l g e n o m e o f yeast and o f o t h e r nuclear
g e n o m e s , t h e d i s c u s s i o n h e r e w i l l be c e n t r e d o n t h e v e r t é b r a t e
g e n o m e , lagerly using t h e H u m a n G e n o m e as an e x a m p l e .

Compositional patterns an the genome

phenotype

DNA preparations f r o m warm-blooded vertebrates (mammals

a n d b i r d s ) a r e m a d e u p o f large f r a g m e n t s (usually h a v i n g a size
around 100 k b ) t h a t can be s e p a r a t e d i n t o a n u m b e r o f families
c h a r a c t e r i z e d b y d i f f e r e n t G C levéis (fig. I ) . T h e f r a g m e n t s d e -
rive, by t h e unavoidable mechanical and enzymatic degradation
that occurs during D N A p r e p a r a t i o n , f r o m m u c h l o n g e r seg-
ments ( o v e r 300 kb o n average), t h a t exhibit a remarkable c o m -
p o s i t i o n a l h o m o g e n e i t y a n d w e r e , t h e r e f o r e , called isochores ( f o r
"equal regions").

T h e c o m p o s i t i o n a l d i s t r i b u t i o n o f large D N A f r a g m e n t s , w h i c h
c o r r e s p o n d s , by far and large, t o t h e c o m p o s i t i o n a l distribution
o f i s o c h o r e s , d e f i n e s a c o m p o s i t i o n a l p a t t e r n . In m a n , GC-poor
D N A f r a g m e n t s f r o m i s o c h o r e f a m i l i e s L l a n d L 2 (fig. I ) r e p r e -
sent a b o u t t w o t h i r d s of t h e g e n o m e ; G C - r i c h D N A fragments
f r o m i s o c h o r e f a m i l i e s H l , H 2 , H 3 (fig. I ) c o r r e s p o n d t o the
remaining t h i r d . G C - p o o r and G C - r i c h isochores are interspersed
w i t h e a c h o t h e r , as w e l l as w i t h t h e i s o c h o r e s correspond-
ing t o s a t e l l i t e ( s i m p l e s e q u e n c e ) D N A s a n d c l u s t e r e d repeat-
e d g e n e s ( l i k e r i b o s o m a l g e n e s ) , t o f o r m a mosaic g e n o m e . T h e
strong compositional compartmentalization of the Human
G e n o m e (and o f t h e g e n o m e of w a r m - b l o o d e d v e r t e b r a t e s in
g e n e r a l ) is in s h a r p c o n t r a s t w i t h t h e w e a k c o m p o s i t i o n a l c o m p a r t -
mentalization of the genome of cold-blooded vertebrates (see
fig. I ) , w h i c h is m a d e u p o f i s o c h o r e s t h a t c o v e r a n a r r o w e r
G C range, and w i t h t h e even n a r r o w e r , unimodal compositional
patterns of m o s t invertebrates l o w e r (unicellular) eukaryotes
and p r o k a r y o t e s .
 GC% 237

40 40 45 50 55
t—i—i—r "i i i i i i i i i i i i i r~

Xenopus

I I I I I I 1 I f I
L2 H1

c 3
u O
o
E E
CD
> i i i i r >

ce ce

n i ¡ i ¡ i i i i i i i i

1.700 1.705 1.710 1.715

Buoyant density, g/cm3

Figure l . - H i s t o g r a m s s h o w i n g t h e relative a m o u n t s , modal bouyant densities in

CsCI and G C levéis o f t h e m a j o r D N A c o m p o n e n t s f r o m X e n o p u s , c h i c k e n ,
mouse and man. M a j o r D N A c o m p o n e n t s consist o f D N A fractions, obtained by
density gradient centrifugation in t h e presence of sequence-specific Kgands, w h i c h
are p o o l e d according t o t h e i r modal b o u y a n t density in C s C I . M a j o r D N A c o m -
ponents derive f r o m c o r r e s p o n d i n g i s o c h o r e families. T h e CsCI profiles o f t h e
major c o m p o n e n t s are c e n t e r e d o n t h e i r modal bouyant densities, but overlap
w i t h each o t h e r t o some e x t e n t , particularly in t h e case o f t h e c o m p o n e n t s t h a t
are m o s t a b u n d a n t and c l o s e r in density. Satellite and m i n o r (e. g. r i b o s o m a l
D N A ) c o m p o n e n t s are n o t s h o w n ( F r o m Bernardi, 1989).

O t h e r c o m p o s i t i o n a l p a t t e r s a r e r e p r e s e n t e d by t h e c o m p o s i t i o n -
al d i s t r i b u t i o n s o f e x o n s ( o r o f t h e i r i n d i v i d u a l c o d o n p o s i t i o n s )
and i n t r o n s . In t h e g e n o m e o f w a r m - b l o o d e d v e r t e b r a t e s , t h e
c o m p o s i t i o n a l d i s t r i b u t i o n o f e x o n s is s k e w e d t o w a r d s high G C
valúes (fig. 2 ) , in c o n t r a s t w i t h t h a t o f D N A f r a g m e n t s w h i c h is
s k e w e d t o w a r d s l o w G C valúes (fig. I ) . By c o n t r a s t , genes (as
w e l l as large D N A f r a g m e n t s ; see a b o v e a n d fig. I ) f r o m cold-
b l o o d e d v e r t e b r a t e s e x h i b i t a m o r e symmetrical and narrower
c o m p o s i t i o n a l d i s t r i b u t i o n (fig. 2 ) .

The compositional patterns corresponding t o the compositional

d i s t r i b u t i o n s (figs. I a n d 2 ) o f large D N A f r a g m e n t s ( o r o f i s o -
chores), of exons ( o r o f individual c o d o n positions), and i n t r o n s
define, in fact, g e n o m e phenotypes.
238
Positions third codon

3allus177

111
z
LU
O
LL
O
ce
LU

m
D
Z

Figure 2 . - C o m p o s i t i o n a l d i s t r i b u t i o n o f t h i r d c o d o n positions f r o m v e r t é b r a t e
genes. (This d i s t r i b u t i o n is t h e m o s t informative because o f its w i d e r spread in
c o m p o s i t i o n c o m p a r e d t o coding sequences and first o r second c o d o n positions.)
T h e n u m b e r o f genes under c o n s i d e r a r o n is indicated. T h e b r o k e n line at 60 %
G C is s h o w n t o p r o v i d e a reference (Modified f r o m Bernardi, 1989).
Composítíonal correlatíons and 239
the genomic code

T h e physical s e p a r a t i o n o f large D N A f r a g m e n t s c h a r a c t e r i z e d b y
d i f f e r e n t G C levéis, p r o v l d e d an o p p o r t u n i t y t o l o c a l i z e g e n e s , o r
o t h e r s e q u e n c e s , In d i f f e r e n t I s o c h o r e famllies b y h y b r i d l z a t i o n o f
a p p r o p h a t e p r o b e s . In t u r n , t h i s led t o t h e d i s c o v e r y t h a t g e n e
d i s t r l b u t i o n is s t r i k i n g l y n o n - u n l f o r m in t h e h u m a n g e n o m e , t h e
h i g h e s t g e n e c o n c e n t r a t i o n b e i n g f o u n d in t h e G C - r i c h e s t ¡so-
c h o r e s , t h e H 3 f a m i l y , w h i c h r e p r e s e n t s less t h a n 5 % o f t h e g e -
n o m e . T h e g e n e c o n c e n t r a t i o n in t h e H 3 f a m i l y can b e e s t i m a t e d
as a t least 15 t i m e s h i g h e r t h a n t h a t in t h e L l a n d 12 f a m l l i e s .

A s e c o n d d i s c o v e r y a s s o c i a t e d w i t h t h e l o c a l i z a t i o n o f genes in
D N A f r a c t i o n s w a s t h a t t h e G C levéis o f e x o n s a n d i n t r o n s a r e
linearly c o r r e l a t e d w i t h t h e G C levéis o f t h e D N A f r a g m e n t s in
w h i c h t h e c o r r e s p o n d i n g genes are e m b e d d e d (fig. 3). Since

6^
ü
O

(/>
c
O
H—'

"(O
O
Q.
C
O
"D
O
O

y = 2.74 y - 64.6 R = 0.78

Fractions or sequences, G C %

Figure 3 . - P l o t o f G C levéis o f human codlng sequences against t h e G C levéis o f

D N A fractions o r o f e x t e n d e d , sequenced, D N A segments in w h i c h t h e y w e r e
localized ( F r o m M o u c h i r o u d D., ATssani B., D ' O n o f r i o G., Macaya G., G a u t i e r C ,
Bernardi G., 1991, Gene, in press).
240 D N A f r a g m e n t s are m a d e by m o r e t h a n 9 0 % i n t e r g e n i c se-
q u e n c e s , t h e r e l a t i o n s h i p links, in fact, c o d i n g a n d i n t e r g e n i c se-
quences. C o r r e l a t i o n s basically similar t o t h o s e d e s c r i b e d for
m a n a p p l y t o all v e r t e b r a t e s , w h e r e a s in t h e case o f p l a n t s , t h e
basic f e a t u r e s a r e t h e s a m e , b u t w i t h q u a n t i t a t i v e d i f f e r e n c e s .

In c o n c l u s i ó n , t h e c o m p o s i t i o n a l c o r r e l a t i o n s j u s t d i s c u s s e d a r e
v e r y g e n e r a l , s i n c e t h e y c o n c e r n w h o l e classes o f l i v i n g o r g a n -
isms, a l t h o u g h n o t u n i v e r s a l . B y c o n t r a s t , t h e c o r r e l a t i o n that
links t h e t h r e e c o d o n p o s i t i o n s o f all g e n o m e s (fig. 4 ) is a u n i v e r -
sal o n e . T h e c o r r e l a t i o n s b e t w e e n genes a n d i s o c h o r e s a n d t h o s e
a m o n g c o d o n p o s i t i o n s a m o u n t t o a genomic code. It s h o u l d be
stressed that compositional pattern ( o r t h e g e n o m e phenotype
and c o m p o s i t i o n a l c o r r e l a t i o n s ( o r t h e g e n o m i c code) are due t o
c o m p o s i t i o n a l constraints, a c t i n g o n b o t h c o d i n g a n d non-coding
sequences o f t h e g e n o m e .

S=1.7, R=0.7

oh
O
O

co
c
o
-I—'

"co
o
Ql
c
o
"O
o
ü
A Amph.+Rept.
* Fishes
A Inv.+Low.Euk.
I- • Virusas
a Bacteria

n l l l l l i l l l l l l l l l
20 30 40 50 60 70 80 90 100

First and second codon positions, % G C

Figure 4 . - P l o t o f G C levéis o f t h i r d c o d o n positions f r o m genes o f c o l d - b l o o d e d

v e r t e b r a t e s , i n v e r t e b r a t e s , l o w e r e u k a r y o t e s , viruses and bacteria against G C
levéis o f first + second c o d o n positions (stands f o r slope and R f o r t h e c o r r e l a t i o n
coefficient). T h e last square line o b t a i n e d is practica!!/ colncident w i t h t h a t o b -
tained f o r human and bacterial genes ( F r o m Bernardi G., Bernardi G., I 9 9 I , J.
Mol. Evo/., in press).
Isochores, chromosomal bands and 241
compositional mappíng

Isochores are c o r r e l a t e d w i t h c h r o m o s o m a l G-bands (Glemsa

positive o r Giemsa-dark bands; these are equivalent t o Q-
bands o r Q u i n a c r i n e b a n d s ) a n d R-bands ( R e v e r s e b a n d s ; e q u i v -
alent t o Glemsa-negatlve o r G l e m s a - l i g h t bands). T h e s e bands
are p r o d u c e d by t r e a t i n g metaphase c h r o m o s o m e s w i t h f l u o -
rescent dyes proteases o r d e n a t u r i n g agents, G C - p o o r and
G C - r i c h isochores largely c o r r e s p o n d t o t h e D N A of G - and
R-bands r e s p e c t i v e l y , as i n d i c a t e d b y t h e p r o p e r t i e s t h a t t h e y
share (see t a b l e I ) . G - and R-bands represent, therefore, a
c o m p o s i t i o n a l p a t t e r n basically c o r r e s p o n d i n g t o t h e isochore
p a t t e r n . It s h o u l d b e s t r e s s e d t h a t , in c o n t r a s t t o w a r m - b l o o d -
ed v e r t e b r a t e s , c o l d - b l o o d e d v e r t e b r a t e s a r e c h a r a c t e r i z e d b y
a p o o r n e s s o r a b s e n c e o f d i s t i n c t G - a n d R- b a n d s , r e f l e c t i n g
the lower compositional compartmentalization of their ge-
nomes.

A m o r e detailed understanding of t h e correlations b e t w e e n iso-

c h o r e p a t t e r n s a n d c h r o m o s o m a l b a n d i n g p a t t e r n s can be g a i n e d
t h r o u g h a n o v e l a p p r o a c h : compositional m a p p i n g . W h e n e v e r l o n g -
range physical maps a r e available, c o m p o s i t i o n a l maps can be
c o n s t r u c t e d by assessing G C levéis a r o u n d l a n d m a r k s t h a t can be
probed. This simply requires t h e hybridization o f the probes o n
D N A f r a c t i o n a t e d a c c o r d i n g t o base c o m p o s i t i o n a n d leads t o
t h e a s s e s s m e n t o f G C levéis o f D N A s e g m e n t s 2 0 0 k b o r s o in
size a r o u n d t h e s e q u e n c e p r o b e d .

T h i s a p p r o a c h , as a p p l i e d t o t h e l o n g a r m o f h u m a n c h r o m o s o m e
21 (see fig. 5 ) , has p r o v i d e d a d i r e c t d e m o n s t r a r o n f o r t h e r e -
markable c o m p o s i t i o n a l h o m o g e n e i t y of G-bands and f o r the
c o m p o s i t i o n a l h e t e r o g e n e i t y o f R-bands. T h e l a t t e r a r e k n o w n t o
c o r r e s p o n d t o d i f f e r e n t f a m i l i e s o f G C - r i c h i s o c h o r e s a n d also t o
c o m p r i s e a large n u m b e r o f t h i n G - b a n d s o n l y visible a t high r e -
solution.

Table I: T h e Human Genome (a)

The Pofeogenome The Neogenome

(G-bands, G C - p o o r isochores) (R-bands, G C - r i c h isochores)

Scarcity o f genes A b u n d a n c e o f genes

(esp. in H 3 )
G C - p o o r genes G C - r i c h genes
Scarcity o f C p G islands A b u n d a n c e o f C p G islands
T A T A box p r o m o t o r s G/C box promotors
Less f r e q u e n t h o m o g e n e i t y Compositional heterogeneity
Late replication Early replication

(a) Modified f r o m Bernardi ( 1 9 8 9 ) ; see this reference f o r additional details.

242 Fraction P 1 2 3 4 5 6 7 8 9

% DNA 28 5.4 21 10 8.6 11 4 2.4 4.2 1.6

% G+C 38 40 41 43 44 46 48 51 52 54 Región

11.1 A1
ACEM. JC6
11.2 . 6; 21,6918
MRC2
4; 21

3; 21
1;21

ACEM
- JC6

6918. MCR2
8; 21

21; 22
7; 21

Figure 5 . - C o m p o s i t i o n a l map o f t h e l o n g a r m o f h u m a n c h r o m o s o m e 2 1 . Long

h o r i z o n tal lines indícate p o s i t i o n s o f t h e b r e a k p o i n t s d e f i n i n g c h r o m o s o m e
segments. S h o r t h o r i z o n t a l bars indícate t h e D N A f r a c t i o n s in w h i c h sequences
f r o m given c h r o m o s o m a l segments h y b r i d i z e d . T h i s p r o v i d e s I n f o r m a t i o n o n
t h e c o m p o s i t i o n of D N A segments 0.2-0.3 M b (Megabases, millions of
base pairs) in size ( F r o m G a r d i n e r K., Aissani B., B e r n a r d i G., 1990, E M B O
J. 9, 1853-1858).

Compositional m a p p i n g has a l s o s h o w n t h a t t h e GC-richest

i s o c h o r e s o f t h e l o n g a r m o f c h r o m o s o m e 2 1 , w h i c h has t h e
h i g h e s t g e n e c o n c e n t r a t i o n , a r e l o c a t e d in t h e t e l o m e r i c re-
g i ó n . In f a c t , t e l o m e r e s a l m o s t a l w a y s c o r r e s p o n d t o R-bands,
and t h e t e r m i n a l r e g i ó n o f a b o u t half o f t h e m ( i n c l u d i n g t h a t of
the long a r m o f c h r o m o s o m e 21) are t h e m o s t denaturation-
resistant r e g i o n s o f h u m a n c h r o m o s o m e s . W e have suggested,
therefore, that the GC-richest isochores correspond t o such
t e l o m e r i c regions, a p o i n t a l r e a d y s u p p o r t e d by p r e l i m i n a r y results.

The compositional mapping of human c h r o m o s o m e 2 1 , carried

o u t as i t w a s w i t h o n l y 5 0 p r o b e s t a r g e t e d a t l o c i s c a t t e r e d o v e r
a b o u t 4 0 M b (megabases o r m i l l i o n s o f base pairs) o f D N A , can
o n l y be c o n s i d e r e d as p r e l i m i n a r y w o r k . A s m o r e d e t a i l e d c o m -
p o s i t i o n a l maps b e c o m e available, t h e y s h o u l d p r o v i d e t h e best
high-resolution banding maps o f c h r o m o s o m e s , w i t h o u t t h e un-
certainties of cytogenetics.

Isochores and genome functíons

A l t h o u g h w e are only beginning t o understand the functional

r e l e v a n c e o f i s o c h o r e s , s o m e i m p o r t a n t p o i n t s a r e a l r e a d y estab-
lished: (i) I n t e g r a t e d m o b i l e a n d v i r a l s e q u e n c e s a r e p r e f e r e n t i a l l y 243
l o c a t e d in c o m p o s i t i o n a l l y m a t c h i n g i s o c h o r e s ; (ii) t r a n s l o c a t i o n s ,
sister c h r o m a t i d exchanges, c h r o m o s o m a l abnormalities, hot-
s p o t s f o r m i t o t i c c h i a s m a t a a n d fragile sites a r e p r e f e r e n t i a l l y l o -
c a t e d a t G / R b a n d b o r d e r s a n d w i t h i n R bands, n a m e l y a t c o m p o -
sitional d i s c o n t i n u i t i e s ; (iii) G C levéis of i s o c h o r e s largely
d e t e r m i n e c o d o n usage ( t h e d i f f e r e n t i a l usage o f synonymouys
c o d o n s ) a n d t h e p r e f e r e n t i a l u t i l i z a t i o n o f half o f t h e a m i n o a c i d s
( t h o s e o n l y haing G / C o r A / T in f i r s t a n d s e c o n d c o d o n posi-
t i o n s ) ; (iv) C p G d o u b l e t s , t h e o n l y p o t e n t i a l sites o f D N A m e t h y l -
ation, and " C p G islands" (sequences w h i c h c o m p r i s e G/C-rich
p r o m o t o r s ) , i n c r e a s e f r o m G C - p o o r t o G C - r i c h i s o c h o r e s ; (v)
G C - r i c h i s o c h o r e s a n d R-bands r e p l í c a t e e a r l y a n d c o n d e n s e late
in t h e cell c y c l e ; t h e o p p o s i t e is t r u e f o r G C - p o o r i s o c h o r e s a n d
G-bands.

Isochores and genome evolution

T h e c o m p o s i t i o n a l p a t t e r n s o f v e r t e b r a t e s d e f i n e t w o m o d e s in
g e n o m e e v o l u t i o n . In t h e conservot/Ve mode, w h i c h is p r e d o m i n a n t
in m a m m a l s a n d b i r d s , m u t a t i o n s a c c u m u l a t e w i t h o u t causing a l -
m o s t any c o m p o s i t i o n a l changes in t h e g e n o m e . T h i s can be seen
by i n v e s t i g a t i n g t h e c o m p o s i t i o n a l d i s t r l b u t i o n o f D N A f r a g m e n t s
and t h e c h r o m o s o m a l b a n d i n g p a t t e r n s , o r , in t h e m o s t r i g o r o u s
way, by c o m p a r i n g h o m o l o g o u s c o d i n g sequences. For instance,
in p h y l o g e n e t i c a l l y d i s t a n t m a m m a l s , h o m o l o g o u s c o d i n g s e -
q u e n c e s d o n o t s h o w c o m p o s i t i o n a l changes, n o t o n l y in f i r s t a n d
s e c o n d , b u t also in t h i r d c o d o n p o s i t i o n s .

By c o n t r a s t , in t h e transitional m o d e large c o m p o s i t i o n a l changes

t a k e place, i n d e p e n d e n t l y o f g e o l o g i c a l t i m e a n d s o m e t i m e s o v e r
short time intervals. T w o independent, major compositional
t r a n s i t i o n s o c c u r r e d in v e r t é b r a t e g e n o m e s , b e t w e e n n o w ex-
t i n c t reptiles (therapsids) and mammals a b o u t 200 million years
ago, a n d b e t w e e n o t h e r e x t i n c t r e p t i l e s ( d i n o s a u r s ) a n d b i r d s
a b o u t 150 m i l l i o n y e a r s ago. T h e s e t r a n s i t i o n s a r e e v i d e n t w h e n
l o o k i n g at t h e c o m p o s i t i o n a l d i s t r l b u t i o n of D N A fragments
(fig. I ) , a n d o f c o d i n g s e q u e n c e s (fig. 2 ) , i n c l u d i n g homologous
c o d i n g s e q u e n c e s , a n d also a t c h r o m o s o m a l b a n d s . I n d e e d , t h e s e
t r a n s i t i o n s led t o t h e f o r m a t i o n o f a n e w c o m p o s i t i o n a l c o m p a r t -
m e n t in t h e g e n o m e s o f w a r m - b l o o d e d v e r t e b r a t e s , t h e neogenome
(see t a b l e I ) . In t h i s c o m p a r t m e n t , t h e a n c e s t r a l , G C - p o o r i s o -
chores w e r e changed into G C - r i c h isochores t h a t contain abun-
d a n t G C - r i c h g e n e s , v e r y f r e q u e n t l y a s s o c i a t e d w i t h " C p G is-
l a n d s " . By c o n t r a s t , t h e o t h e r c o m p a r t m e n t o f t h e g e n o m e of
w a r m - b l o o d e d v e r t e b r a t e s , t h e po/eogenome (see t a b l e I ) , is
c h a r a c t e r i z e d b y its s i m i l a r i t y t o w h a t i t w a s , a n d still is, in c o l d -
blooded vertebrates. The G C - p o o r isochores contain rela-
t i v e l y sparse G C - p o o r genes t h a t a r e o n l y r a r e l y a c c o m p a i n e d b y
" C p G islands".
244 Conclusíons

T h e findings o b t a i n e d in o u r l a b o r a t o r y w e r e p r e s e n t e d h e r e in
o r d e r t o stress t w o points.

T h e f i r s t is t h a t basic s c i e n c e can g o f a s t e r a n d d e e p e r t h a n a n y
b r u t e f o r c é a p p r o a c h , if t h e g o a l is t o push o u r knowledge
f u r t h e r . A w h o l e series o f n e w i m p o r t a n t c o n c e p t s have been
d e v e l o p e d d u r i n g t h e investigations discussed h e r e : composition-
a l contraints a c t o n b o t h c o d i n g a n d n o n - c o d i n g s e q u e n c e s of
t h e e u k a r y o t i c g e n o m e a n d lead t o t h e f o r m a t i o n o f composition-
al patterns ( c o r r e s p o n d i n g t o a genome phenotype) and t o com-
positional correlations ( c o r r e s p o n d i n g t o a g e n o m i c code) b e t w e e n
c o d i n g a n d n o n - c o d i n g s e q u e n c e s , as w e l l as a m o n g codon
positions.Compositional patterns at t h e D N A level have a
c o u n t e r p a r t a t t h e c h r o m o s o m a l level, G C - p o o r , G C - r i c h and
GC-richest isochores corresponding t o the D N A segments
p r e s e n t in G - , a n d T - b a n d s . T h e f u n c t i o n a l significance o f i s o -
c h o r e s is m a i n l y s t r e s s e d b y t h e d i s t r i b u t i o n o f g e n e s which
a r e s c a r e in G C - p o o r i s o c h o r e s , i n t e r m e d í a t e in f r e q u e n c y in
G C - r i c h i s o c h o r e s , v e r y a b u n d a n t in t h e G C - r i c h e s t i s o c h o r e s ,
a n d b y t h e f a c t t h a t b o t h c o d o n usage a n d a m i n o a c i d c o m p o s i -
t i o n c h a n g e in g e n e s p r e s e n t in t h e s e t h r e e compositional
compartments of the genome. From the evolutionary view-
p o i n t , t w o m o d e s o f g e n o m e e v o l u t i o n have b e e n r e c o g n i z e d :
t h e conservot/Ve m o d e in w h i c h n u c l e o t í d e c h a n g e s o c c u r w i t h -
o u t any c o n c o m i t a n t c o m p o s i t i o n a l change, a n d t h e transition-
a l m o d e , in w i c h n u c l e o t i d e c h a n g e s a r e a c c o m p a n i e d b y c o m -
positional changes. T h e c o n s e r v a t i v e mode predominates in
the genome of warifhblooded vertebrates which s h o w similar
c o m p o s i t i o n a l p a t t e r n s . T h e t r a n s i t i o n a l m o d e w a s at w o r k at
the time warm-blooded vertebrates evolved f r o m cold-blood-
e d v e r t e b r a t e s a n d is r a t h e r w i d e s p r e a d in c o l d - b l o o d e d ver-
tebrates.

T h e s e c o n d p o i n t s is t h a t , in s p i t e o f t h e f a c t t h a t n o g o a l o t h e r
t h a n f u r t h e r i n g OUr k n o w l e d g e m o t i v a t e d o u r w o r k , t h e basic
findings j u s t o u t l i n e d have led t o n o t i o n s w h i c h are extremely
i m p o r t a n t f o r t h e H u m a n G e n o m e P r o j e c t : a) g e n e c o n c e n t r a -
tiúfí i n t h e g e n o m e is c h a r a c t e r i z e d b y a c o m p o s i t i o n a l gra-
d i e n t ; génes a r e a t least 15 t i m e s m o r e f r e q u e n t in t h e GC-
r i c h e s t i s o c h o r e s w h i c h r e p r e s e n t less t h a n 5 % o f t h e g e n o m e
t h a n in t h e G C - p o o r i s o c h o r e s w h i c h r e p r e s e n t o v e r 6 0 % o f
t h e g e n o m e ; this puts a high p r i o r i t y o n m a p p i n g and sequencing
of the GC-richest i s o c h o r e s w h i c h appear t o be located in
T - b a n d s o f m e t a p h a s e c h r o m o s o m e s ; b) c o m p o s i t i o n a l map-
ping defines t h e c o m p o s i t i o n a l p a t t e r n t h a t D N A f o l l o w s along
t h e c h r o m o s o m e ; as s u c h i t i d e n t i f i e s , m u c h b e t t e r t h a n c y t o -
genetics can d o , t h e u l t í m a t e b a n d i n g p a t t e r n o f c h r o m o s o m e s
a n d p i n s d o w n t h e r e g i o n s c h a r a c t e r i z e d by t h e h i g h e s t g e n e
concentrations.
 245

REFERENCES

Mapping our genes, Genome projects: how long, how many. Office of Tech-
nology Assessment, Congress o f the United States.

Mapping and sequencing the human genome. Commission on Life Sciences,

National Research Council.

W a t s o n , J . ( 1 9 9 0 ) . The human genome project: past, present and fu-

ture. Science, 248, 44-49.

B e r n a r d i , G . ( 1 9 8 9 ) . The isochore organization of the human genome.

Ann. Rev. Genet, 23, 637-661.

This paper has been published in Impact o f Science and Society and is re-
printed here w i t h U N E S C O permission.
 247

NO TIME F O R KNITTING:
THE GENETIC QUEST
OF THE ARGENTINIAN
GRANDMOTHERS

Mary-Claire King

D e p t . o f B i o m e d i c a l a n d Envi r o n m e n t a l H e a l t h Sciences,
Universlty of California, Berkeley, California (USA)

ABSTRACT

A blood reiationship can be specified by means o f a

genetic test that entails the m y t h o c o n d r i a l A D N .
This kind o f tests hove been comed out in Argentina
in order for their families to recover newbom child-
ren who h a d been kidnapped or h a d disappeared
between 1976 and 1983. The human mythocondrial
A D N is inherited through the mother a n d has been
totally sequenced. Consequently, it is particularly
useful when it is a question o f establishing an indi-
vidual's maternal blood relationships. The technique
consists o f the analysis o f this A D N m t by means o f
restriction enzymes or by the chain-reaction by poly-
merasa (PCR). All this is just one instance o f the use-
fulness a n d use o f genetic information.
Introductíon: the hístoncal context 249

Between March 1976 a n d D e c e m b e r 1983, t h e R e p u b l i c o f A r -

gentina w a s c o n t r o l l e d by a series o f m i l i t a r / juntas t h a t a b d u c t -
ed, t o r t u r e d , and m u r d e r e d thousands o citizens ( A m n e s t y In-
ternational 1980; I n t e r a m e r i c a n C o m m i s i o n o n H u m a n Rights
1980). T h e m i l i t a r / g o v e r n m e n t u l t i m a t e l y fell f o l l o w i n g t h e i r d e -
f e a t in t h e M a l v i n a s - P a l k l a n d s W a r . T h e t o t a l n u m b e r o f v i c t i m s
o f e x t r a j u d i c i a l e x e c u t i o n w i l l p r o b a b l y n e v e r be k n o w n , b u t in
D e c e m b e r 1983, t h e n e w l y - e l e c t e d d e m o c r a t i c g o v e n m e n t e s t a b -
lished t h e N a t i o n a l C o m m i s s i o n o n t h e D i s a p p e a r a n c e o f P e r -
sons ( C O N A D E P ) , w i t h t h e r e q u e s t t h a t t h i s c o m m i s s i o n d o c u -
m e n t , i n s o f a r as p o s s i b l e , t h e h i s t o r y o f d i s a p p e a r a n c e s of
c i t i z e n s d u r i n g t h e p e r i o d o f m i l i t a r y r u l e . By S e p t e m b e r 1984,
C O N A D E P had p r e p a r e d evidence o n 8800 victims. C O N A D E P
and h u m a n r i g h t s o r g a n i z a c t i o n b e l i e v e t h e a c t u a l n u m b e r o f " d i s -
a p p e a r e d " persons t o be m u c h higher ( N a t i o n a l C o m m i s s i o n o n
Disappeared Persons, 1984).

W e h a v e b e e n i n v o l v e d in h e l p i n g t o i d e n t i f y a s p e c i a l s u b s e t o f
these victims. These are the 210 children w h o w e r e kidnapped
a t b i r t h o r as i n f a n t s b y m i l i t a r y a n d p ó l i c e w h o m u r d e r e d t h e i r
parents and retained o r sold t h e children. Unlike t h e o l d e r vic-
tims of the " D i r t y W a r " , many of these very young children re-
m a i n e d a l i v e , b u t w e r e m a d e t o " d i s a p p e a r " ( A b u e l a s d e Plaza
d e M a y o , 1 9 8 5 ) . In 1 9 7 7 , d u r i n g t h e p e r i o d o f m i l i t a r y r u l e , t h e
surviving relatives o f kidnapped children f o r m e d t h e G r a n d m o t h -
e r s o f t h e Plaza d e M a y o , a h u m a n r i g h t s g r o u p d e v o t e d t o f i n d -
ing k i d n a p p e d c h i l d r e n a n d r e u n i t i n g f a m i l i e s . T h r o u g h persis-
t e n t collection and f o l l o w - u p of circumstantial evidence, t h e
Grandmothers began t o l ó c a t e t h e i r k i d n a p p e d g r a n d c h i l d r e n ,
p r i m a r i l y in t h e h o u s e h o l d s o f m i l i t a r y a n d p ó l i c e o f f i c i a l s a n d
their c o l l a b o r a t o r s (Nosiglia 1985).

It s o o n b e c a m e a p p a r e n t t o t h e G r a n d m o t h e r s t h a t i t w a n e c -
essary, b u t n o s u f f i c i e n t , t o e s t a b l i s h t h a t a s p e c i f i c c h i l d w a s a
kidnap v i c t i m . It w a s also necessary t o establish each child's
t r u e i d e n t i f y b y o b j e c t i v e m e a n s . A f t e r t h e fall o f t h e military
and t h e e l e c t i o n o f a d e m o c r a t i c g o v e r n m e n t , it b e c a m e possi-
ble t o b r i n g c h a r g e s in A r g e n t i n i a n c o u r t s a g a i n s t t h e kidnap-
pers o f t h e c h i l d r e n . T h e G r a n d m o t h e r s t h e r e f o r e asked g e n e t -
icists f o r h e l p in e s t a b l i s h i n g o b j e c t i v i l y t h e i d e n t i t i e s o f t h e s e
g r a n d c h i l d r e n . In J u n e 1 9 8 4 , a t t h e r e q u e s t o f t h e G r a n d m o t h -
e r s o f t h e Plaza d e M a y o a n d C O N A D E P , w e f i r s t t r a v e l l e d t o
Buenos A i r e s t o help d e v o t e d p r o c e d u r e s f o r genetic Identifica-
tion of kidnapped children.

In 1984, g e n e t i c r e l a t i o n s h i p s w e r e m o s t e f f e c t i v e l y e s t a b l i s h e d
using s e r o l o g i c a l t e s t i n g o f H L A a n t i g e n s a t t h e A , B, C ; a n d D R
loci ( A l b e r t e t al. 1984). T h e i n m u n o g e n e t i c s l a b o r a t o r y o f A n a
Maria D i L o n a r d o at t h e Durand Hospital in B u e n o s Aires,
250 w h i c h w a s e x p e r i e n c e d in H L A s e r o l o g i c t y p i n g , a g r e e d t o u n d e r -
take the identification project. That laboratory has been
s u c c e s s f u l ¡n e s t a b l i s h i n g t h e i d e n t i t i e s o f a l a r g e n u m b e r of
c h i l d r e n a n d in p r e s e n t i n g e v i d e n c e t o t h e A r g e n t i n i a n courts
t h a t has l e d t o t h e r e u n i f i c a t i o n o f f a m i l i e s ( D i L o n a r d o e t al.
1984; D i a m o n d 1987).

In t h e i n t e r v e n i n g s i x y e a r s , w e have e x t e n d e d t h e g e n e t i c a p -
proaches applied t o establishing t h e identity o f these kidnapped
c h i l d r e n . T w o d e v e l o p m e n t s m o t i v a t e d t h i s w o r k . First, a t t h e r e -
quest o f t h e G r a n d m o t h e r s and o t h e r human rights organiza-
t i o n s , in 1985 t h e g o v e r n m e n t o f A r g e n t i n a e s t a b l i s h e d t h e N a -
tional Genetic Data Bank. This v o l u n t a r / service offers
g r a n d p a r e n t s , a u n t s , úneles, c o u s i n s , a n d o t h e r s u v i v i n g r e l a t i v e s
o f d i s a p p e a r e d c h i l d r e n t h e o p p o r t u n i t y t o have t h e i r b l o o d s a m -
p l e d , H L A s e r o l o g y d e t e r m i n e d , a n d w h i t e cells s t o r e d f o r e x -
t r a c t i o n o f D N A . Pedigrees d o c u m e n t i n g t h e relationships o f sur-
viving relatives t o t h e m u r d e r e d parents and missing c h i l d r e n are
also c o n s t r u c t e d . T h e i n t e n t o f t h e l e g i s l a t i o n is t h a t as c h i l d r e n
a r e d i s c o v e r e d w h o a r e k i d n a p v i c t i m s , t h e i r i d e n t i t i e s can b e d e -
t e r m i n e d b y m a t c h i n g t o c h i l d t o s u r v i v i n g r e l a t i v e s . Several h u n -
d r e d s u r v i v i n g r e l a t i v e s have c o n t r i b u t e d t o t h e D a t a B a n k in t h e
p a s t f i v e y e a r s . C o n s e q u e n t l y , as k i d n a p v i c t i m s a r e f o u n d for
w h o m l i t t l e c i r c u m s t a n t i a l e v i d e n c e o f i d e n t i t y e x i s t s , each m u s t
be m a t c h e d against m ú l t i p l e f a m i l i e s . T o establish i d e n t i t y w i t h a
s u f f i c i e n t l y high level o f s t a t i s t i c a l c e r t a i n t y u n d e r t h e s e c i r c u m -
s t a n c e s usually r e q u i r e s m a t c h i n g t o m o r e t h a n o n e g e n e t i c l i n k -
age g r o u p .

T h e s e c o n d d e v e l o p m e n t d u r i n g t h e p r o j e c t has b e e n t h e a p -
pearance o f families w i t h f e w surviving relatives: deaths during
t h e m i l i t a r y p e r i o d , f e a r o n t h e p a r t o f s o m e s u r v i v o r s , a n d subse-
q u e n t d e a t h s f r o m n a t u r a l causes have all t a k e n t h e i r t o l l . It is
n o u n c o m m o m f o r a family searching f o r a missing child t o in-
c l u d e o n l y t h e m a t e r n a l lineage, s o m e t i m e s o n l y t h e m o t h e r o r
a sister o r b r o t h e r o f t h e m u r d e r e d m o t h e r of a kidnap victim.
T h e r e f o r e , i t has b e e n n e c e s s a r y t o d e v e l o p a g e n e t i c a p p r o a c h
t h a t p e r m i t s t h e i d e n t i t y o f a c h i l d t o b e d e t e r m i n e d e v e n if
o n l y a single m a t e r n a l r e l a t i v e is a l i v e . W e h a v e a p p p l i e d t h e se-
quencing of mitochondrial DNA t o this task ( N e w Scientist
1989; O r r e g o e t a l . 1 9 8 8 ) .

Mitochondrial D N A (mtDNA)
as a genetic system for testing
relationship

A w i d e v a r i e t y o f h u m a n sequences w i l l u n d o u b t e d l y be used
eventually t o t e s t w h e t h e r t w o individuáis are related. W e chose
m t D N A f o r t h i s p r o j e c t f o r s e v e r a l r e a s o n s . M t D N A is h a p l o i d , 25 I
m a t e r n a l l y i n h e r i t e d ( G i l e s e t al. 1980; H e c h t e t al. 1984),
a n d h o m o p l a s t i c w i t h l n i n d i v i d u á i s ( W i l s o n e t al. 1985; K o c h e r
e t a l . 1 9 8 9 ) . T h e r e f o r e , e a c h i n d i v i d u a l has e x a c t l y t h e same
mtDNA as his s i b l i n g s , m a t e r n a l a u n t s a n d ú n e l e s , maternal
g r a n d m o t h e r , c o u s i n s v i a t h e m o t h e r ' s s i s t e r s , a n d s o o n , as
i l l u s t r a t e d in F i g u r e I. S e c o n d , h u m a n m t D N A has b e e n c o m -
pletely s e q u e n c e d ( A n d e r s o n e t al. 1981). T h i r d , h u m a n mt-
DNA has e v o l v e d m o r e r a p i d l y t h a n n u c l e a r D N A a n d is e x -
t r e m e l y v a r i a b l e a m o n g i n d i v i d u á i s . T h i s d i v e r s i t y has e n a b l e d t h e
c o n s t r u c t i o n o f e v o l u t i o n a r y t r e e s f o r h u m a n s based o n r e s t r i c -
t i o n e n z y m e analysis o f m t D N A ( C a n n e t al. 1 9 8 4 ; W i l s o n e t al.
1985; C a n n e t al. 1 9 8 7 ; W i l s o n e t al. 1 9 8 7 ) . Finally, t h e i n t r o -
d u c t i o n of t h e p o l y m e r a s e chain r e a c t i o n , o r PCR, greatly sim-
p l i f i e d s e q u e n c e analysis b y e l i m i n a t i n g t h e n e e d t o c h a i n r e a c -
t i o n , o r P C R , g r e a t l y s i m p l i f i e d s e q u e n c e analysis b y e l i m i n a t i n g
the need t o clone the target D N A in o r d e r t o g e n é r a t e s u f f i -
c i e n t D N A f o r s e q u e n c i n g (Scharf e t al. 1986; M u l l i s a n d R a b o n a
1987; G y l l e n s t e n 1989).

T h e c o n t r o l r e g i ó n o f m t D N A , n e a r t h e o r i g i n o f r e p l i c a t i o n , is
particularly diverse a m o n g individuáis. T h e m t D N A c o n t r o l r e -
g i ó n (also called t h e displace m e n t o r D - l o o p ) is a r e g i ó n of
1200 base p a i r s f l a n k e d b y t R N A ( P r o ) a n d t R N A ( P h e ) g e n e s .
T h e c o n t r o l región does n o t c o d e f o r any genes, w h i c h perhaps
has r e l e a s e d i t f r o m s t r i c t n u c l e o t i d e c o n s e r v a t i o n . In t h e c o n -
t r o l región, blocks of sequences conserved a m o n g mammalian
species a r e s e p a r a t e d b y r e g i o n s o f h i g h s e q u e n c e d i v e r s i t y ( A n -
d e r s o n e t al. 1 9 8 1 ) . O b v i o u s l y , m t D N A s e q u e n c e s w i l l s e r v e t o
i d e n t i f y t h e m a t e r n a l l e n e a g e s d i f f e r in s e q u e n c e in t h e target
r e g i ó n . T h e r e f o r e i t is c r u c i a l t o b e a b l e t o d e t e r m i n e t h e p r o b -
ability t h a t u n r e l a t e d individuáis w o u l d be identical by chance
alone. W e have c o m p a r e d h y p e r v a r i a b l e p o r t i o n s o f t h e mt-
DNA control región f r o m 14 u n r e l a t e d C a u c a s i a n individuáis
( A n d e r s o n e t al. 1 9 8 1 ; A q u a d r o a n d G r e e n b e r g 1983; G r e e n -
b e r g e t al. 1983; O r r e g o a n d K i n g 1 9 9 0 ) . O f t h e 3 4 7 n u c l e o t i d e
sites c o m p a r e d , 3 2 w e r e v a r i a b l e . W h e n t h e s e q u e n c e s were
c o m p a r e d b e t w e e n i n d i v i d u á i s in p a i r s , t h e n u m b e r o f differ-
ences ranged f r o m o n e t o 13 n u c l e o t i d e s ; t h e a v e r a g e p a i r w i s e
d i f f e r e n c e w a s 5.9 n u c l e o t i d e s . F o r t h e s e 3 4 7 base p a i r s , t h e
probability that t w o u n r e l a t e d individuáis w o u l d be indentical
by c h a n c e is a p p r o x i m a t e l y o n e in 3 7 0 ( O r r e g o a n d K i n g 1 9 9 0 ) .
T h e r e f o r e , this sequence of m t D N A could c o n t r i b u t e t o identi-
f i c a t i o n o f m a t e r n a l lineages. By s e q u e n c i n g m o r e o f t h e mt-
D N A c o n t r o l r e g i ó n , w e can i m p r o v e t h e statistical p o w e r of
Identification.

In o r d e r t o t e s t w h e t h e r h y p e r v a r i a b l e sequences o f t h e mtDNA
c o n t r o l r e g i ó n a r e i n d e e d c o n s e r v e d in h u m a n families, a n d in o r -
der t o c o n f i r m t h e maternal inheritance of m t D N A , w e selected
D N A samples f r o m t h r e e u n r e l a t e d Caucasian c h i l d r e n a n d t h e u n -
d i s p u t e d m a t e r n a l g r a n d m o t h e r o f each. T h e six samples w e r e a m -
252 plified a n d s e q u e n c e d w i t h o u t labels indicating w h o w a s r e l a t e d t o
w h o m . Matching children t o their grandmothers was unambiguous.

Testíng relationships ín Argentina

As t h e result of the efforts of the G r n a d m o t h e r s , 48 of the 210

c h i l d r e n k n o w n t o have b e e n k i d n a p p e d a t b i r t h o r in i n f a n c y
have b e e n i d e n t i f i e d , 12 I d e n t i f i c a t i o n s a r e n o w in p r o g r e s s , a n d
150 c h i l d r e n a r e n o t y e t f o u n d . S o m e o f t h e s e cases w i l l b e dis-
c u s s e d in d e t a l l a t t h e s y m p o s i u m M e a n w h i l e , b l o o d samples
c o n t i n u é t o be collected f r o m t h e h u n d r e d s o f surviving relatives
w h o are searching f o r kidnapped c h i l d r e n . T h e s e b l o o d samples
a r e f r o z e n in B u e n o s A i r e s , t h e n s e n t t o us f o r D N A extraction
a n d m t D N A s e q u e n c e analysis.

T h e m a j o r c o n c e r n u n d e r l y i n g t h i s w o r k is t o d o w h a t is b e s t
f o r t h e c h i l d r e n ( A b u e l a s d e Plaza d e M a y o 1 9 8 4 ) . C l e a r l y , c i r -
cumstances vary e n o r m o u s i y and t h e c u s t o d y of each child
m u s t be d e c i d e d individually. A f e w o f t h e c h i l d r e n b o r n in
c a p t i v i t y o r k i d n a p p e d as i n f a n t s w e r e a d o p t e d in f o o d f a i t h by
families w i t h no ties t o t h e military. T h e resolutions o f these
e x c e p t i o n a l cases h a v e g e n e r a l l y b e e n a m i c a b l e , w i t h t h e c h i l d -
ren being t o l d the t r u t h about their biological parents and
spendig t i m e w i t h b o t h t h e i r biological and a d o p t i v e families.
H o w e v e r , t h e cases o f c h i l d r e n l i v i n g w i t h m i l i t a r y o r p ó l i c e of-
f i c e r s i n v o l v e d in t h e t o r t u r e a n d m u r d e r o f t h e i r p a r e n t s a r e
far m o r e dificult. T h e s e have c o m p r i s e d t h e vast m a j o r i t y of
c h i l d r e n d i s c o v e r e d so far. C e r t a i n l y u n d e r n o r m a l circum-
s t a n c e s , a c h i l d w o u l d n o t b e l e f t w i t h k i d n a p p e r s o r t h e i r ac-
c o m p l i c e s r e g a r d i e s s o f his age a t a b d u c t i o n . T h e n o t i o n o f as-
sessing w h e t h e r p e r s o n s i n v o l v e d in k i d n a p p i n g , t o r t u r e , or
m u r d e r are suitable parents f o r t h e children of t h e i r victims
appears highly unlikely.

K i d n a p p i n g has u n i v e r s a l l y b e e n c o s i d e r e d a c r i m e . Is t h e situa-
t i o n d i f f e r e n t in A r g e n t i n a because k i d n a p p i n g o c c u r r e d o n a large
scale? T h e h u m a n r i g h t s g r o u p s w i t h w h o m w e w o r k suggest t h a t
t o abandon t h e search f o r t h e kidnapped children o f A r g e n t i n a
is t o a b a n d o n a g r o u p o f c h i l d r e n w h o w i l l n o t g r o w u p in c a r e -
f r e e i n n o c e n c e . A s t h e s e c h i l d r e n b e c o m e a d u l t s , w h a t w o u l d be
t h e i r a t t i t u d e t o w a r d relatives w h o k n e w t h e y had disappeared
b u t d i d n o t h i n g ? W h a t w o u l d be t h e e f f e c t o n a y o u n g p e r s o n t o
l e a r n he has l i v e d w i t h p e o p l e i n v o l v e d in t h e m u r d e r s o f his p a r -
e n t s a n d t h a t his s u r v i v i n g r e l a t i v e s d i d n o t h i n g t o f i n d him?
W o u l d failing t o a t t e m p t t o i d e n t i f y t h e k i d n a p p e d c h i l d r e n i m p l i c -
itly g r a n t i m m u n i t y t o kidnappers? W o u l d this increase the
sense o f i n v u l n e r a b i l i t y o f a b u s e r s o f h u m a n r i g h t s in o t h e r c o u n -
tries? T h e historical s i t u a t i o n t h a t led t o this application of
g e n e t i c s t o h u m a n r i g h t s is u n p r e c e d e n t e d . T h u s , a n s w e r s to
t h e s e q u e s t i o n s o f e t h i c s , law, a n d m e n t a l h e a i t h a r e d e v e l o p i n g 253
with our current experience.

A s o f t h i s t i m e (fall 1990), t h e p o l i t i c a l s i t u a t i o n in A r g e n t i n a is
much m o r e hostile t o the G r a n d m o t h e r s ' efforts than during the
Alfonsin presidency of 1984-1989.

In p a r t i c u l a r , i t is i n c r e a s i n g l y d i f f i c u l t t o w o r k w i t h i n t h e A r g e n -
tinian judicial system. H o w e v e r , t h e G r a n d m o t h e r s remain un-
d a u n t e d . T h e y p o i n t o u t t h a t t h e a v e r a g e age o f t h e kidnapped
c h i l d r e n is n o w 15 y e a r s . V e r y s o o n , t h e s e c h i l d r e n w i l l have t h e
legal r i g h t t o d e t e r m i n e f o r t h e m s e l v e s t h e i r i d e n t i t i e s . F o r t h i s
purpose, m t D N A s e q u e n c e s w i l l be available. Even t h o u g h the
grandparents o f a kidnapping v i c t i m may die b e f o r e t h e g r a n d -
c h i l d is f o u n d , t h e y o u n g a d u l t ' s m a t e r n a l lineage w i l l be i d e n t i f i a -
ble u s i n g t h e g e n e t i c I n f o r m a t i o n t h e G r a n d m o t h e r s h a v e l e f t
b e h i n d . A y o u n g p e r s o n can t h e r e b y be p u t in t o u c h w i t h his
f a m i l y - h i s s u r v i v i n g a u n t s , úneles, a n d c o u s i n s - a n d his h i s t o r y .
F o r t h e p a s t 13 y e a r s , t h e G r a n d m o t h e r s have b e e n s e a r c h i n g f o r
their kidnapped grandchildren. Very soon, these grandchildren
will come looking for t h e m .
254

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G i l e s , R. E . , B l a n c h , H . , C a n n . H . , a n d W a l l a c e , D . C . 1980.
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 257

P A R T I C I P A T I O N IN A N D A C C E S S
TO THE DATA OF THE HUMAN
CENOME PROJECT

Elke Jordán

National C e n t e r f o r H u m a n G e n o m e Research, Bethesda,

Maryland (USA)

ABSTRACT

The H u m a n Genome Project is a biológica! research

project with certain specific aspects derived from the
scope o f its aim, it is predsely this broad scope that
justifies the need for diverse w o r k i n g or research
groups to particípate in i t
The participation o f diverse scientists in a common
aim means the production o f numerous data that
should be made available to all the scientific com-
munity participating in the project
H u m a n G e n o m e P r o j e c t a d v o c a t e s have e m p h a s i z e d t h e i m p o r - 259
t a n c e o f r a p i d s h a h n g o f r e s o u r c e s a n d r e s u l t s as an i n t e g r a l p a r t
o f this p r o j e c t . W i t h o u t sharing of resources a m o n g g e n o m e r e -
s e a r c h e r s , t h e p r o j e c t w¡!l b e ¡ n e f f i c i e n t a n d w i l l t a k e t o o long
a n d c o s t t o o m u c h . S h a r i n g w i t h o t h e r s is also s t r e s s e d because
t h e r e s u l t s a r e t o o i m p o r t a n t t o r e m a i n in t h e hands o f a f e w . I
w o u l d like t o discuss h e r e w h y b o t h s h a r i n g a m o n g g e n o m e I n -
v e s t i g a t o r s a n d s h a r i n g w i t h o t h e r s a r e c r u c i a l t o t h e success o f
the H u m a n G e n o m e Project.

A l t h o u g h s h a r i n g r e s u l t s as r a p i d l y as p o s s i b l e is i n t u i t i v e l y "a
g o o d t h i n g " a n d a b e h a v i o r t h a t w e v a l u é , i t has n o t b e e n i n s i s t e d
o n in o t h e r fields o f b i o l o g i c a l r e s e a r c h t o t h e e x t e n t t h a t i t has
b e e n p r o m o t e d vis á vis t h e H u m a n G e n o m e P r o j e c t . In o r d e r t o
u n d e r s t a n d w h y t h i s is s o , s e v e r a l q u e s t i o n s n e e d t o b e a d -
dressed:

• H o w does t h e H u m a n G e n o m e Project differ f r o m biological

s c i e n c e in general?

• H o w d o t h e s e d i f f e r e n c e s r e l a t e t o t h e issue o f sharing?

• W h a t a r e t h e p r o s a n d c o n s o f sharing?

In discussing t h e s e q u e s t i o n s , I have a v e r y p r a c t i c a l o b j e c t i v e . I
a m t h e m a n a g e r o f a large g e n o m e g r a n t s p r o g r a m a t t h e N a t i o n -
al I n s t i t u t e s o f H e a l t h , c o n f r o n t e d w i t h t h e n e e d t o s e t p o l i c i e s
t h a t w i l l h e l p a n d n o t h i n d e r t h e H u m a n G e n o m e P r o j e c t . I find
m y s e l f a t t h e c e n t e r o f a g r e a t deal o f d i s c u s s i o n o f issues o f
s h a r i n g a n d in r e c e i p t o f a d v i c e f r o m i n d i v i d u á i s w i t h opposing
i n t e r e s t s . I n e e d t o deal w i t h t h e q u e s t i o n - w h a t is o p t i m a l sharing
b o t h w i t h i n t h e g e n o m e c o m m u n i t y and w i t h others? A t this
t i m e , I d o n o t b e l i e v e t h e r e is a s i m p l e a n s w e r t o t h i s q u e s t i o n .

First, I w o u l d l i k e t o discuss h o w t h e H u m a n G e n o m e Project

differs f r o m s t a n d a r d biological research, a q u e s t i o n I a m f r e -
q u e n t l y a s k e d . In s o m e w a y s , t h e H u m a n G e n o m e P r o j e c t is dif-
f e r e n t , b u t in o t h e r s i t is j u s t a n a t u r a l c o n t i n u a t i o n o f b i o l o g i c a l
traditions.

T h e g e n o m e p r o j e c t has a large o b j e c t i v e : t o o large f o r a n y single

i n v e s t i g a t o r t o a t t e m p t t o a c h i e v e in a l i f e t i m e . A l t h o u g h t h e o b -
j e c t i v e is large, i t is f a i r l y c l e a r a n d a p p r o a c h a b l e a n d lends itself
t o an o r g a n i z e d , c o l l a b o r a t i v e p r o g r a m . Because o f t h e large o b -
j e c t i v e , t h e H u m a n G e n o m e P r o j e c t has b e e n called " b i g s c i e n c e "
and a c c u s e d o f b e i n g a t h r e a t t o " l i t t l e s c i e n c e " . In fact, t h e H u -
m a n G e n o m e P r o j e c t is d i s t i n g u i s h e d f r o m o t h e r b i o l o g i c a l p r o -
j e c t s n o t s o m u c h b e c a u s e i t is big, b u t b e c a u s e i t has a c l e a r
goal, e m p h a s i z e s t e c h n o l o g y d e v e l o p m e n t a n d a t t e m p t s central
c o o r d i n a t i o n . T h e s e characteristics have, i n d e e d , caused some
p u r i s t s t o r e j e c t i t as n o t " s c i e n c e " a t all. B i o l o g i s t s have n e v e r
a t t e m p t e d an o r g a n i z e d p r o j e c t o f t h i s s c o p e a n d v i s i b i l i t y b e f o r e
260 and t h u s t h e y v i e w it w i t h alarm. H o w w e l l w e succeed w i l l cer-
t a i n l y i n f l u e n c e t h e l i k e l i h o o d o f any f u t u r e a t t e m p t s a l o n g t h e s e
lines.

A l t h o u g h t h e H u m a n G e n o m e P r o j e c t is d i f f e r e n t in having a big-
g e r goal a n d b e i n g m o r e s t r u c t u r e d a n d c o o r d i n a t e d , i t can also
be v i e w e d as a n a t u r a l o u t g r o w t h o f a l o n g t r a d i t i o n . G e n e t i c i s t s
have a l w a y s b e e n m a k i n g m a p s - m a p s a r e a n a t u r a l organlzing
p r i n c i p i e o r i n f r a s t r u c t u r e o n w h i c h g e n e t i c k n o w l e d g e can be
b u i l t . Maps o f s i m p l e o r g a n i s m s c o u l d be m a d e by a single i n d i v i d -
ual, t h o s e o f m o r e c o m p l e x o r g a n i s m s r e q u i r e d s o m e d e d i c a t e d
s o u l w h o w o u l d c o l l e c t , o r g a n i z e , c h e c k , a n d p u b l i s h t h e m a p as
w e l l as r e s o l v e d i s c r e p a n c i e s . T h i s k i n d o f a c t i v i t y w a s a t o n e
t i m e highly v a l u e d , t h o u g h i t w a s n e v e r e v e r y o n e ' s c u p o f t e a . T o -
day, w h e n t h e r e a r e s o m a n y g l a m o r o u s t h i n g s t h a t g e n e t i c i s t s
can d o , m a p p i n g a n d a s s e m b l y o f maps is c o n s i d e r e d somewhat
p e d e s t r i a n b y c o m p a r i s o n , b u t t h e m a p is stiil j u s t as i m p o r t a n t .

T h e h u m a n m a p is d i s t i n g u i s h e d f r o m p r e v i o u s m a p s b y g r e a t e r
size a n d c o m l e x i t y a n d by t h e g r e a t e r d e t a l l w e a r e s t r i v i n g f o r .
U n t i l n o w , s o m e o n e like V i c t o r M c K u s i c k c o u l d k e e p t r a c k o f all
g e n e t i c diseases o f m a n a n d t h e H u m a n G e n e M a p p i n g W o r k -
s h o p s k e p t t h e w h o l e m a p u p t o d a t e o n a biannual basis. B u t t h e
r a t e o f d a t a a c q u i s i t i o n a n d t h e a m o u n t o f d a t a is g o i n g t o i n -
crease vastly a n d m a n u a l m e t h o d s a n d i n f o r m a l g e t - t o g e t h e r s w i l l
n o l o n g e r be a b l e t o c o p e . T h u s t h e h u m a n m a p p i n g e n t e r p h s e is
n o t d i f f e r e n t f r o m p r e v i o u s a c t i v i t y b u t o n l y g r e a t e r in s c o p e .
T h e r e f o r e , it requires m o r e organization and c o o r d i n a t i o n to
flourish.

W h y d o e s t h i s c r é a t e a m á n d a t e f o r m o r e s h a r i n g t h a n is t r a d i -
t i o n a l in biology?

In s t a n d a r d b i o l o g i c a l r e s e a r c h , t h e e m p h a s i s is o n innovative,
o r i g i n a l ideas a n d t h e c r e a t i o n o f n e w k n o w l e d g e t h r o u g c l e v e r -
ness a n d s e r e n d i p i t y . S h a r i n g o f r e s u l t s is e x p e c t e d a f t e r t h e y a r e
m a t u r e e n o u g h t o p u b l i s h a n d f r e e e x c h a n g e o f ideas a l o n g t h e
w a y is l a u d e d , b u t w e d o n o t see any p a r t i c u l a r v i r t u e t o insisting
o n m o r e . It is g e n e r a l l y b e l i e v e d t h a t t h e a u t o n o m y o f i n d i v i d u a l
i n v e s t i g a t o r s is n e e d e d f o r t h e b e s t p a y o f f a n d is i n d e e d essential
t o creative research.

A l t h o u g h t h e r e is r o o m f o r t h e i d i o s y n c r a t i c a n d s e r e n d i p i t o u s in
th H u m a n G e n o m e Project, much of w h a t w e are trying t o do
lends itself v e r y w e l l t o t e a m w o r k , c o o r d i n a t i o n a n d s h a r i n g o f
m a t e r i a l s a n d ideas. I n d e e d , t h e v e r y a m b i t i o u s goal t h a t has b e e n
s e t w i l l b e d i f f i c u l t t o a c h i e v e unless s c i e n t i s t s w o r k together.
F u r t h e r m o r e , w i t h o u t t h e benefits o f m u t u a l r e i n f o r c e m e n t , it
m a y b e d i f f i c u l t t o k e e p u p t h e m o m e n t u m f o r 15 y e a r s ! Sharing
w i l l also k e e p t h e c o s t d o w n b y a v o i d i n g u n p r o d u c t i v e d u p l i c a -
r o n o f e f f o r t . Since t h e H u m a n G e n o m e P r o j e c t is r e l a t i v e l y e x -
p e n s i v e , i t is i m p o r t a n t t o b e as e c o n ó m i c a ! as p o s s i b l e .
O n e t h i n g I have b e c o m e a c u t e l y a w a r e o f in t h e past y e a r , is t h e 26
c o n c e r n o f i n v e s t i g a t o r s n o t i n v o l v e d in t h e H u m a n Genome
P r o j e c t t h a t all t h e e x c i t i n g r e s u l t s w i l l be available t o o n l y a s e -
l e c t f e w a n d t h a t o t h e r s c i e n t i s t s w i l l b e l e f t o u t . T h i s f e a r is I
t h i n k m i s p l a c e d , because t h e r e is n o w a y t o h o l d o n t o s o m u c h
I n f o r m a t i o n p r o d u c e d in so m a n y d i f f e r e n t l a b o r a t o r i e s . How-
e v e r , unless w e a c t t o allay t h e f e a r , t h e p r o j e c t m a y lose s u p p o r t
and fail o n t h i s a c c o u n t . W e m u s t m a k e c l e a r t h a t t h e p u r p o s e o f
t h e g e n o m e p r o j e c t is t o d e v e l o p f u n d a m e n t a l I n f o r m a t i o n t o be
s h a r e d w i t h t h e b r o a d e r c o m m u n i t y so t h a t i t can be used f o r i n -
n o v a t i v e r e s e a r c h a n d t o d e v e l o p m e d i c a l a p p l i c a t i o n s . It is i n -
c u m b e n t o n us t o s h a r e t h e r e s u l t s o f H u m a n G e n o m e r e s e a r c h
as r a p i d l y as p o s s i b l e j u s t because t h e y p r o m i s e t o be s o v a l u a b l e
t o h u m a n k i n d . I n f o r m a t i o n t h a t c a n b e n e f i t all o f us m u s t be
quickly disseminated.

Since r a p i d s h a r i n g is s u c h a v i r t u e a n d t h e a r g u m e n t s f o r i t so
c o m p e l l i n g , h o w c o u l d t h e r e b e a n y t h i n g w r o n g w i t h it? Far be i t
f r o m m e t o suggest t h a t t h e r e is, b u t I w a n t t o r e l a y s o m e c o n -
cerns t h a t are being v o i c e d by t h o u g h t f u l people.

• H o w can w e k e e p a s c i e n t i s t i n t e r e s t e d in a line o f w o r k , if t h a t
s c i e n t i s t d o e s n o t have t h e o p p o r t u n i t y , a t least f o r a l i m i t e d
t i m e , t o analyze t h e d a t a he o r she l a b o r e d f o r a l o n g t i m e t o
obtain?

• In o r d e r t o p r e s e r v e t h e i n c e n t i v e f o r c o m m e r c i a l e x p l o i t a t i o n
of H u m a n G e n o m e Project research, w e need t o p r o t e c t intel-
e c t u a l p r o p e r t y r i g h t s . Rapid s h a r i n g can lead t o m e s s y t r a i l s
f o r claims o f o w n e r s h i p , r e m o v i n g t h e p r o t e c t i o n needed to
p r o v i d e an i n c e n t i v e f o r i n v e s t m e n t . W i t h o u t investment,
m u c h o f t h e benefit o f t h e H u m a n G e n o m e Project may not
occur.

Both o f these o b j e c t i o n s are valid and real. W e have a s s e r t e d

t h a t w e are pursuing t h e H u m a n G e n o m e Project f o r t h e public
g o o d , b u t w h a t is t h e p u b l i c g o o d in t h i s c o n t e x t ? Is i t m á x i m u m
c o m m e r c i a l e x p l o i t a t i o n ? F r e e a n d r a p i d access t o all w h o w a n t
t h e data? T h e m o s t i n c e n t i v e f o r t h o s e c a r r y i n g o u t t h e w o r k s o
it gets d o n e ? T h e s e goals a r e n o t all c o m p a t i b l e w i t h each o t h e r .

I s u b m i t i t is n o n e o f t h e s e a l o n e , b u t a c a r e f u l balance a m o n g
t h e m . A s a manager faced w i t h setting sharing policies, I need t o
develop policies t h a t avoid interfering either w i t h progress on
the H u m a n G e n o m e Project o r w i t h e x p l o i t a t i o n o f t h e results
f o r t h e p u b l i c b e n e f i t . Such p o l i c i e s also m u s t b e f l e x i b l e e n o u g h
t o a c c o m m o d a t e t h e n e e d s o f d i f f e r e n t t y p e s o f r e s e a r c h , e.g.,
mapping i n f o r m a t i o n may need different rules f r o m sequencing
I n f o r m a t i o n o r c o m p u t e r a l g o r i t h m s . C u r r e n t l y , at t h e N I H , w e
ask each g r a n t e e t o d e s c r i b e h o w t h e y w i l l s h a r e t h e i r results
and n e g o t i a t e w i t h t h e m if t h e plans d o n o t s e e m r e a s o n a b l e o r
are o u t o f line w i t h w h a t o t h e r s a r e d o i n g . Eventually, w e hope
262 t h a t t h e v a r i o u s scientific c o m m u n i t i e s w i t h i n t h e g e n o m e p r o -
gram will c o m e t o a consensus o n t h e a p p r o p r i a t e length o f t i m e
investigators may hold various types of data b e f o r e releasing
t h e m t o a datábase o r p u b l i s h i n g t h e m .

A n y s h a r i n g p o l i c y w e c o m e u p w i t h m u s t be f a i r a n d e q u i t a b l e
a n d a c c e p t e d a n d a b i d e d by w o r l d w i d e . W i t h o u t a g r e e m e n t o n
c o m m o n p r i n c i p i e s , I c a n n o t see h o w w e can have I n t e r n a t i o n a l
cooperation. T r u e collaboration requires agreement on some
g r o u n d r u l e s . If w e d o i t r i g h t , t h e H u m a n G e n o m e P r o j e c t c o u l d
b e c o m e an e x a m p l e o f h o w p l a n n i n g , c o o p e r a t i o n a n d s h a r i n g
can b e beneficial t o t h e a t t a i n m e n t o f s e l e c t e d , i m p o r t a n t s c i e n -
t i f i c goals w i t h o u t b e i n g d e t r i m e n t a l t o t h e s c i e n t i f i c e n t e r p r i s e as
a whole.
IDENTIFICATION
A N D DIAGNOSIS
 265

ETHICS AND HUMAN GENETICS

ONCE T H E HUMAN CENOME
HAS BEEN MAPPED

john Fletcher

H e a l t h Sciences C e n t e r , U n i v e r s i t y o f V i r g i n i a ,
Charlottesvllle, Virginia (USA)

ABSTRACT

In principie, advances in the scientific-technoíogicaí

field occur so rapidly that it seems difficult to draw
up a n e t h i c a í code or a t t a i n e t h i c a l consensus
among specialists in appiied genetics. However, this
would pose the foliowing question: is it technology
that dictates ethical norms or is it ethics itself that
governs the application o f science a n d technology?
Logically, an international ethical code should be set
up for specialists in genetics that takes into account
problems such as free cholee in the m a t t e r o f abor-
tion, confidentiality, respect for privacy or the use o f
parental diagnosis, amongst others.
T h a n k y o u , D r . Scriver. M y s i n c e r e t h a n k s t o t h e o r g a n i z e r s o f t h i s 267
meeting f o r the invitation t o c o m e here. The title o f m y t a l k ¡s
" E t h i c s a n d H u m a n G e n e t i c s A f t e r t h e H u m a n G e n o m e is M a p -
ped." A f t e r a brief description of the most prevalent ethical
p r o b l e m s in a p p l i e d h u m a n g e n e t i c s , I c o n c l u d e w i t h a p r o p o s a l
o f s o m e r u d i m e n t a r y e l e m e n t s o f an i n t e r n a t i o n a l c o d e o f e t h i c s
f o r human genticists.

A p p l i e d h u m a n g e n e t i c s has f o u r s e r v i c e a c t i v i t i e s : g e n e t i c s c r e e n -
ing ( o f c a r r i e r s a n d n e w b o r n s ) , c o u n s e l i n g , p r e n a t a l diagnosis,
and t r e a t m e n t o r medical m a n a g e m e n t o f genetic d i s o r d e r s . A n y
analysis o f e t h i c a l p r o b l e m s in t h i s f i e l d a n d a n y p r o p o s e d c o d e o f
ethics m u s t p r e s u p p o s e and encompass these activities.

A n y c o n s i d e r a r o n o f e t h i c a l issues in h u m a n g e n e t i c s m u s t b e g i n
w i t h t h e unique position of human geneticists today. H u m a n - o r
m e d i c a l - geneticists are unquely situated at t h e first m a j o r sub-
speciality t o i n t e r a c t w i t h individuáis and families a b o u t genetic
p r o b l e m s and decisions t o be made a b o u t genetic p r o b l e m s and
decisions t o be made a b o u t t h e m . Medical geneticists are t h e
mediators of genetic knowledge, gleaned f r o m mapping and
sequencing, t o patients, families, and w h o l e populations. They
also have t h e m o s t c o l l e c t i v e e x p e r i e n c e in r e s p o n d i n g t o t h e s e
p r o b l e m s . A n y study o f these p r o b l e m s w o u l d w i s e l y begin w i t h
t h e m - a n d t h e i r p a r e n t s - t o understand t h e dynamics and o u t -
comes.

T h e u n i q u e p o s i t i o n o f h u m a n g e n e t i c i s t s in s c i e n c e a n d s o c i e t y
leads t o m y m a j o r t h e s i s , n a m e l y , t h a t t h i s g r o u p o f p r o f e s s i o n a l s
in m a n y n a t i o n s have a special r e s p o n s i b i l i t y t o t a k e t h e lead t o
w o r k o u t approaches t o t h e ethical p r o b l e m s t h a t t h e y share
w i t h t h e i r p a t i e n t s . W h o can d o t h i s t a s k b e t t e r t h a n t h e g e n e t i -
cists, in r e f l e c t i o n w i t h p a t i e n t s , t h e i r families, a n d o t h e r s i n t e r e s t -
e d in s t u d y o f e t h i c a l p r o b l e m s ?

F o u r p r e m i s e s u n d e r l i e m y c o m m e n t s , based o n social s c a n n i n g
o f t h e f u t u r e , w h i c h is a r i s k y business. T h e f i r s t p r e m i s e is t h a t
t h e H u m a n G e n o m e Project will succeed technically. Whether
t h e t i m e t a b l e w i l l b e s h o r t e r (as D r . G i l b e r t b e l i e v e s ) o r longer
(as I believe, given h u m a n n a t u r e , r e b e l l i o n s w i t h i n science, political
p r o b l e m s , e t c . ) is i m m a t e r i a l t o t h e p r e m i s e . A n o t h e r s o u r c e o f
d e l a y i n g clinical b e n e f i t s o f t h e H u m a n G e n o m e P r o j e c t , in t h e
U n i t e d States, in m o r a t o r i a , bans, a n d lack o f s u p p o r t in f e d e r a l
science f o r a p p l i e d g e n e t i c r e s e a r c h '.

S e c o n d l y , g e n e t i c Services ( t h e f o u r a c t i v i t i e s l i s t e d a b o v e ) w i l l
g r a d u a l l y b e c o m e p a r t o f t h e n a t i o n a l h e a l t h plans o f all d e v e l -
oped and developing nations. T h i r d , genetic k n o w l e d g e will grad-
ually b e c o m e a n o r m a l p a r t o f e v e r y d a y life, because g e n e t i c i n -
formation will transform the practice of medicine. Professor
Jonsen has d e s c r i b e d t h i s t r a n s f o r m a r o n e l o q u e n t l y t o d a y . C h i l d -
268 r e n w i l l b e r a i s e d w i t h t h e ¡ n t u i t i o n t h a t i t is g o o d t o w a n t t o
k n o w a b o u t themselves genetically t o prevent harms t o t h e m -
selves, t h e i r c h i l d r e n , a n d t o f u t u r e g e n e r a t i o n s . T h e f o u r t h p r e -
m i s e is t h a t a s e t o f e t h i c a l a g r e e m e n t s a b o u t t h e use o f g e n e t i c
k n o w l e d g e in m e d i c i n e a n d s o c i e t y is a l r e a d y p r e s e n t in t h e
p r a c t i c e s o f h u m a n g e n e t i c i s t s in m a n y n a t i o n s .

E v e r y o n e w h o has s t u d i e d e t h i c a l p r o b l e m s in h u m a n g e n e t i c s
agrees t h a t t h e p r o b l e m s t h a t o c c u r n o w a n d t h e p r o b l e m s w h e n
t h e g e n o m e is m a p p e d w i l l n o t be s i g n i f k a n t l y d i f f e r e n t in k i n d ,
b u t t h e y w i l l b e d i f f e r e n t in m a g n i t u d e . T h e e t h i c a l p r o b l e m s o f
t h e " o í d a n d n e w " g e n e t i c s a r e n o t d i f f e r e n t in t y p e b u t in s c o p e
and t h e vast n u m b e r s of individuáis and families affected. A n
international s t u d y in 19 n a t i o n s 2 h a s s h o w n t h a t human
g e n e t i c i s t s a n d t h e i r p a t i e n t s in m a n y n a t i o n s f r e q u e n t l y face a
s e t o f e i g h t e t h i c a l p r o b l e m s , a l s o i l l u s t r a t e d in t h e following
table.

Table I. Ethical Problems in Human Genetics

1. Fairness o f access t o genetic services.

2. A b o r t i o n choices.
3. Confidentially p r o b l e m s w h e n o t h e r family m e m b e r s ' interests are involved.
4. P r o t e c t i o n o f privacy f r o m institutional t h i r d parties: insurers, employers, etc.
5. Disclousre dilemmas in counseling.
6. Indications f o r prenatal diagnosis: sex selection, benefit t o t h i r d parties.
7. V o l u n t a r y o r m a n d a t o r y screening policies.
8. Counseling incapacitated patients: directive vs. n o n - d i r e c t i v e approaches.

I r a n k t h e p r o b l e m - i n t e r m s o f f r e q u e n c y a n d i m p o r t a n c e - in t h i s
o r d e r based o n I n f o r m a t i o n f r o m g e n e t i c i s t s o b t a i n e d in an i n t e r -
n a t i o n a l s t u d y , f r e q u e n c y o f d i s c u s s i o n in t h e l i t e r a t u r e , a n d in
t e r m s o f n u m b e r s o f p e r s o n s w h o m i g h t b e a d v e r s e l y a f f e c t e d by
t h e p r o b l e m itself. T h e s e p r o b l e m s have b e e n t h o r o u g h l y d e s -
cribed elsewhere3.

M y t h e s i s is, t h a t s i n c e a s t r o n g t o m o d é r a t e c o n s e n s u s e x i s t s
among medical geneticists' approaches t o these problems in
m a n y n a t i o n , t h e y have a special r e s p o n s i b i l i t y t o t a k e t h e lead t o
lay t h e f o u n d a t i o n s , in t h i s g e n e r a t i o n , f o r t h e a p p r o a c h e s t h a t
t h e y a n d t h e i r s u c c e s s o r s w i l l t a k e in t h e f u t u r e w h e n t h e g e -
n o m e is m a p p e d . N o w is t h e t i m e f o r c l a r i f i c a t i o n a n d shaping
approaches t o ethical p r o b l e m s t h a t will serve w e l l i n t o t h e fu-
ture.

Is an i n t e r n a t i o n a l c o d e o f e t h i c s a n d p r a c t i s e a m o n g g e n e t i c i s t s
really p o s s i b l e - o r e v e n needed? T h e n e e d arises f r o m t h e p r o b -
lems, listed a b o v e , w h i c h are significant. T h e r e are arguments
against t h e c o n c e p t a n d u t i l i t y o f a c o d e o f e t h i c s , w h i c h a r e :
I ) " e t h i c s " is t o o s u b j e c t i v e a n d c u l t u r a l l y v a r i a b l e t o establish a
consensus, 2) t e c h n o l o g y changes t o o fast t o establish ethical
c o n s e n s u s , 3) r i s k o f legal l l a b l l l t y if g e n e t i c i s t s a c t In a w a y t o 269
devlate f r o m t h e code's speclfled practicas, and 4) o t h e r sub-
specialtles In m e d i c i n e d o n o t have c o d e s o f e t h i c s .

Each o f t h e s e a r g u m e n t s can be, in m y v i e w , successfully m e t a n d

r e b u t t e d . First, e v i d e n c e f r o m t h e s t u d y c i t e d a b o v e s h o w s t h a t
medical geneticists across several cultures n o t only identify a
highly similar set o f p r o b l e m s b u t share similar a p p r o a c h e s to
m a n y o f t h e m . T h e y d o n o t n e c e s s a r i l y a g r e e o n specific resolu-
tions o f s o m e e t h i c a l p r o b l e m s (especially c o n f l i c t s o f c o n f i d e n t i a l -
i t y b e t w e e n t h e p a t i e n t a n d f a m i l y m e m b e r s , d i s c l o s u r e o f psy-
chologically sensitive I n f o r m a t i o n , and indications f o r prenatal
diagnosis) b u t t h e y d o s h a r e s i m i l a r valúes in h o w t h e s e p r o b -
lems o u g h t t o be c o n s i d e r e d a n d e v a l u a t e d . A s l o n g as a c o d e o f
e t h i c s d i d n o t a t t e m p t t o d í c t a t e o u t c o m e s f o r p a r t i c u l a r cases
and a c k n o w l e d g e d w i d e l y accepted exceptions t o m o r a l princi-
pies, a c o d e f o r m e d i c a l g e n e t i c i s t s , l i k e I n t e r n a t i o n a l c o d e s f o r
r e s e a r c h i n v o l v i n g h u m a n s u b j e c t s 4, w o u l d b e a c c e p t a b l e a n d
useful.

S e c o n d l y , a l t h o u g h t e c h n o l o g y d o e s change a n d e v o l v e , t e c h n o l -
o g y itself o u g h t n o t t o d í c t a t e w h a t e t h i c a l s t a n d a r d s s h o u l d b e
e m p l o y e d f o r its p r o p e r u s e . U n l e s s t h i s is t r u e , " e t h i c s " is a
s h a m a n y w a y . T h i r d l y , if g e n e t i c i s t s a c t c o n t r a r y t o a c o d e ' s g e n -
e r a l e x p e c t a t i o n s , t h e y s h o u l d have e t h i c a l l y d e f e n s i b l e reasons
t h a t w o u l d likely be c o v e r e d b y t h e e x c e p t i o n s r e c o g n i z e d b y t h e
c o d e . A í s o , t o c i t e legal risks begs t h e q u e s t i o n o f w h e t h e r t h e
a c t i o n s o f s u c h g e n e t i c i s t s w o u l d be e t h i c a l l y a c c e p t a b l e in t h e
f i r s t place. F o u r t h l y , e v e n if o t h e r subspecialities d i d n o t ( w h i c h is
n o t t r u e ) have b o d i e s o f e t h i c a l r e f l e c t i o n a n d g u i d a n c e , i t w o u l d
still be a w e a k a r g u m e n t . O t h e r s u b s p e c i a l i t i e s a r e n o t in t h e
unique position of geneticists, namely, t h a t they medíate know-
ledge t o p a t i e n t s a b o u t t h e i r d e s t i n i e s a n d w e l l b e i n g . O t h e r s u b -
s p e c i a l i t i e s have, in f a c t , s u r v e y e d t h e i r m e m b e r s a b o u t e t h i c a l
p r o b l e m s , analysed t h e data, and shaped guidelines f o r their
m e m b e r s o n s o m e p r o b l e m s 5.

A r g u m e n t s f o r a c o d e o f ethics a r e : I ) geneticists in this g e n e r a t i o n

need t o c o n s o l í d a t e t h e i r m o r a l e x p e r i e n c e , w h i c h is c o n s i d e r a b l e ,
t o t r a n s m i t t o t h e n e x t g e n e r a t i o n , 2) achieving consensus on
less c o m p l e x e t h i c a l issues can be a f l o o r f r o m w h i c h g e n e t i s c i s t s
can c o n s i d e r m o r e c o m p l e x issues t o c o m e , w h e n t h e g e n o m e is
m a p p e d , 3) g e n e t i c i s t s have an i m p o r t a n t o p p o r t u n i t y t o i n f l u e n c e
e v o l v i n g p u b l i c p o l i c y w i t h a c o d e o f e t h i c s , a n d 4 ) since m e d i c a l
g e n e t i c i s t s in m a n y n a t i o n s w o u l d like t o d e v e l o p a s p e c i a l t y in
t h i s f i e l d , a c o d e o f e t h i c s is a m a r k o f a p r o f e s s i o n a n d speciality.

T h e r u d i m e n t a r y e l e m e n t s o f an I n t e r n a t i o n a l c o d e o f e t h i c s f o r
h u m a n g e n e t i c i s t s w o u l d i n c l u d e a p r e a m b l e d e s c r i b i n g t h e is-
sues, p r o b l e m s , valúes, p r i n c i p i e s , a n d r e l a t i o n s h i p s t h a t g e n e t i -
cists a n d t h e i r p a t i e n t s , f a m i l i e s , a n d s o c i e t i e s face in t h i s f i e l d o f
270 endeavor. T h e r e could f o l l o w sections that address the eight
p r o b l e m áreas d e s c r i b e d a b o v e . Based o n t h e k n o w l e d g e t h a t w e
have a b o u t m e d i c a l g e n e t i c i s t s ' a p p r o a c h e s t o t h e s e problems,
t h e f o l i o w i n g sections are p r o p o s e d .

I. Access to Genetíc Services

S e c u r i n g access t o a d e q u a t e g e n e t i c services is an e t h i c a l o b l i g a -
t i o n o f s o c i e t y t o p e r s o n s a n d f a m i l i e s as p a r t o f a g e n e r a l o b l i g a -
t i o n t o s e c u r e access t o a d e q u a t e h e a l t h c a r e . E q u i t a b l e d i s t r i b u -
t i o n o f g e n e t i c s e r v i c e s is o w e d f i r s t t o t h o s e w h o s e n e e d is
greatest, t h o s e at higher genetic risk. Geneticists should do
e v e r y t h i n g w i t h i n t h e i r l e g i t í m a t e a u t h o r o i t y t o i n s u r e t h a t pa-
t i e n t s w h o m o s t n e e d s e r v i c e s a n d have t h e g r e a t e s t o p p o r t u n i t y
t o b e n e f i t r e c e i v e such s e r v i c e s .

2. Respect for and Safeguardíng Parental

Cholees

G e n e t i c i s t s in all n a t i o n s c o n s i d e r i t essentiai t o p r o t e c t rights o f

p a r e n t a l c h o l e e . M e d i c a l g e n e t i c i s t s s h o u l d safeguard t h e o p t i o n s
o f p a r e n t s in g e n e t i c services, i n c l u d i n g t h e o p t i o n s o f a b o r t i o n o r
t o c a r r y t o t e r m a fetus w i t h a m a l f o r m a t i o n o r a genetic disorder.

A n e x c e p t i o n t o t h i s d u t y s h o u l d b e m a d e in d e c i s i o n s t h a t i n -
v o l v e I n f o r m a t i o n a b o u t t h e g e n d e r o f t h e f e t u s , u n r e l a t e d t o ge-
n e t i c diseases, t h a t m a y lead t o a b o r t i o n . G e n e t i c i s t s h a v e n o
duty t o c o o p e r a t e w i t h parental desires t o a b o r t f o r gender
s e l e c t i o n , because I ) g e n d e r is n o t a g e n e t i c disease, 2 ) e q u a l i t y
b e t w e e n m a l e s a n d f e m a l e s is v i l a t e d , a n d 3) s e x s e l e c t i o n is a
p r e c e d e n t f o r eugenics (i.e., i n t e r v e n t i o n s in h u m a n r e p r o d u c t i o n
w i t h r e g a r d t o c h a r a c t e r i s t i c s u n r e l a t e d t o a g e n e t i c disease). Sex
s e l e c t i o n d i s c r e d i t s t h e r o l e o f p r e n a t a l diagnosis in m e d i c i n e .

3. Confldentlallty When Other Family

Members are at High Risk

C o n f i d e n t i a l i t y is a vital b u t n o t a b s o l u t e n o r m in m e d i c i n e a n d in
m e d i c a l g e n e t i c s . If t h e p a t i e n t r e f u s e d t o d i s c l o s e p r o v e n risks o f
harms t o relatives, t h e imperative o f p r e v e n t i o n o f h a r m t o o t h -
ers limits a physician's o r c o u n s e l o r ' s duty o f confidentiality.
T h e P r e s i d e n t ' s C o m m i s s i o n f o r t h e S t u d y o f Ethical P r o b l e m s in
M e d i c i n e r e c o m m e n d s t h a t c o n f i d e n t i a l i t y b e b r e a c h e d o n l y in 271
e x c e p t i o n a l c i r c u m s t a n c e s t h a t m e e t f o u r c o n d i t i o n s 6.

Legal p r o t e c t i o n s f o r g e n e t i c i s t s w h o b r e a c h c o n f i d e n t i a l i t y to
w a r n o t h e r s a t high r i s k , a f t e r h a v i n g c o m p l i e d w i t h t h e s e c o n d i -
t i o n s , m a y b e n e c e s s a r y in t h e f u t u r e .

4. Protection of Patients' Pnvacy from

Instítutional Third Partíes

W i t h o u t e f f e c t i v e legal p r o t e c t i o n f r o m g e n e t i c d i s c r i m i n a t i o n in
e m p l o y m e n t , e m p l o y e r s s h o u l d n o t have access t o p e r s o n a l g e -
n e t i c d a t a . Even w h e n legal p r o t e c t i o n s have b e e n a d o p t e d , ac-
cess t o p e r s o n a l g e n e t i c d a t a s h o u l d o n l y o c c u r w i t h t h e i n f o r m -
ed c o n s e n t o f t h e i n d i v i d u a l i n v o l v e d . In n a t i o n s w h e r e prívate
h e a l t h I n s u r a n c e is a m a j o r i n d u s t r y a n d t h i r d p a r t y p a y e r f o r
h e a l t h c a r e , t h e i n d u s t r y s h o u l d be r e g u l a t e d by g o v e r n m e n t t o
discourage excessively costiy p r e m i u m s f o r t h o s e at k n o w n high-
e r g e n e t i c r i s k . Refusal o f p r í v a t e h e a l t h I n s u r a n c e t o f a m i l i e s a t
h i g h e r r i s k f o r g e n e t i c disease s h o u l d be illegal. A n o t h e r a l t e r n a -
t i v e is g o v e r n m e n t u n d e r w r i t i n g o f h e a l t h I n s u r a n c e f o r t h o s e a t
genetic risk.

5. Full Disclosure of all Clínícally Relevant

Information

M e d i c a l g e n e t i c i s t s s h o u l d d i s c l o s e all clinically r e l e v a n t I n f o r m a -
t i o n t o patients and family m e m b e r s , c o n s i s t e n t w i t h c o n s i d e r a -
t i o n s o f i m m a t u r i t y a n d p s y c h o l o g i c a l w e l l - b e i n g . A l s o , t h e ca-
pacity of counselees t o c o m p r e h e n d I n f o r m a t i o n and make
v o l u n t a r y c h o l e e s a r e m o r a l l y r e l e v a n t f a c t o r s in d i s c l o s u r e d i -
l e m m a s . P s y c h o l o g i c a l a s s e s s m e n t s o f c a p a c i t y a r e b e s t d o n e in
consultation w i t h mental health professionals. Psychologically
sensitive I n f o r m a t i o n , s u c h as X Y g e n o t y p e in a f e m a l e , s h o u l d b e
d i s c l o s e d o n l y t h e c o n t e x t o f full o n s u p p o r t i v e c o u n s e l i n g a n d
patient education.

6. Indicatíons for Prenatal Diagnosis

Prenatal diagnosis s h o u l d be u s e d o n l y t o give p a r e n t s a n d p h y s i -

cians I n f o r m a t i o n a b o u t t h e h e a l t h o f t h e f e t u s . A n y o t h e r use,
such as f o r s e x s e l e c t i o n ( e x c e p t f o r X - l i n k e d disease) o r f o r t i s -
272 sue t y p i n g t o plan f o r t r a n s p l a n t a t i o n t o b e n e f i t a n o t h e r person
a f t e r b i r t h , s h o u l d b e a v o i d e d . If p a t i e n t s have a g e n e t i c reason
f o r diagnosis a n d also s h o w e x c e s s i v e i n t e r e s t in t h e g e n d e r o f
t h e f e t u s , g e n e t i c i s t s can c o n s i d e r d e l a y e d d i s c l o s u r e o f g e n d e r
a f t e r t i m e l y d i s c l o s u r e o f clinical findings.

Laws p r o h i b i t i n g a b o r t i o n f o r sex selection are a p p r o p r i a t e only

w h e r t h e r e is e v i d e n c e t h a t abuse o f t h e m e d i c a l i n d i c a t i o n s f o r
prenatal diagnosis exists. W h e r e abuse does n o t exist, laws
p r o h i b i t i n g s e x s e l e c t i o n a b o r t i o n s a r e n o t o n l y u n n e e d e d b u t set
harmful precedents restricting a b o r t i o n cholees.

7. Voluntar/ Approach to Genetícs

Services: One Exceptíon

G e n e t i c s e r v i c e s p r o g r a m s s h o u l d b e v o l u n t a r y in n a t u r e , w i t h
o n e e x c e p t i o n , Le., s c r e e n i n g n e w b o r n s w h e n t r e a t m e n t is availa-
ble t o h e l p t h o s e a f f e c t e d b y g e n e t i c d i s o r d e r s . F o r c i n g p e r s o n s
t o s u b m i t t o genetic services t o p r e v e n t genetic d i s o r d e r s v i o -
lates t h e p r i n c i p i e o f r e s p e c t f o r p e r s o n s a n d d i s r u p t s t h e i r r e -
l a t i o n s h i p s in f a m i l i e s . C o e r c i ó n , a r b i t r a r i n e s s , a n d d i s c r i m i n a t i o n
against p e r s o n s a t h i g h e r g e n e t i c r i s k s h o u l d be illegal in t h e c o n -
t e x t o f e m p l o y m e n t and educational o p p o r t u n i t i e s .

8. Non-dírectíve Counseling:
wíth One Exceptíon that Requíres
Further Study

N o n - d i r e c t i v e c o u n s e l i n g , i.e., t o r e f r a i n f r o m d i r e c t m o r a l advice
t o p r o t e c t a n d e n h a n c e t h e a u t o n o m o u s c h o l e e s o f p a t i e n t s , is a
c o m m i t m e n t o f m e d i c a l g e n e t i c i s t s , a s s u m i n g t h a t all r e l e v a n t faets
a r e k n o w n t o t h e c o u n s e l e e t o c o n s i d e r t h e faets in t h e c o n t e x t
o f his o r h e r beliefs a n d valúes.

A p o s s i b l e e x c e p t i o n t o n o n - d i r e c t i v e c o u n s e l i n g c a n a r i s e in
genetic counseling w i t h incapacited patients, especially when
g e n e t i c h a r m t o o t h e r s is a c l e a r a n d p r e s e n t d a n g e r . T h e ac-
tual incidence of this t y p e of situation and geneticists' response
t o i t n e e d s c a r e f u l s t u d y , in p r i n c i p i e , g i v i n g d i r e c t m o r a l a d -
vice t o relatives o f incapacitiated counselees o r t o impaired
c o u n s e l e e s t h e m s e l v e s is e t h i c a l l y a c c e p t a b l e , if t h e likelihood
o f h a r m t o o t h e r s is g r e a t a n d in t h e g e n e t i c i s t has i n f o r m e d
t h e p a t i e n t a n d / o r r e l a t i v e s in a d v a n c e o f c o u n s e l i n g t h a t " d i -
r e c t i v e c o u n s e l i n g " m a y be i n d i c a t e d . G e n e t i c i s t s s h o u l d f o l -
l o w e s t a b l i s h e d p r o t o c o l s in d e t e r m i n i n g t h e c a p a c i t y o f t h e i r
patients.
 273

REFERENCES

1. The effects of prohibitions, m o r a t o r i a and lack of support f o r re-

search on fetal, e m b r y o and fetal tissue transplantation in the A m e r i -
can scientific field are a t h r e a t t o the clinical benefits which the H u -
man Genome initiative seemed t o hold out. Certain references are
t o be found which r e c o r d t h e history of these actions and the se-
rious harm they have caused t o clinical research in the field of genet-
ics and e m b r y o l o g y in: F l e t c h e r , J . C . a n d R y a n , K. J . , 1987:
Federal Regulations for Fetal Research: A Case for Reform, Law, Medicine
and Health Care, 15: 126-138; F l e t c h e r , J . C , 1990, Conírovers/es
in Research Ethics affecting the Futura o f Human Gene Therapy, Human
Gene Therapy 1: 307-324; F l e t c h e r , J . C , Fetal Tissue Transplanta-
t i o n Research and Federal Policy: A G r o w i n g W a l l of Separation,
Fetal Diagnosis and Therapy (published in the press); F l e t c h e r , J .
C , 1974-1990: Restriction and Suppresion: Fetal and Embryo Research
in Proceedings of Symposium on the Beginnings o f Human Life, U n i -
versity of lowa, N o v e m b e r 1990 (published in press).

2. W e r t z , D. C , a n d F l e t c h e r , J . C , 1989: £íh/cs and Human Genet-

ics: A Cross-Cultural Perspective (Heidelberg, Springer-Verlag). This
study was carried o u t between 1985 and 1986 under the direction
of specialists in medical genetics in the following countries: Austra-
lia, Brazil, Ganada, Denmark, United States, France, Greece, H u n -
gary, India, Israel, Italy, Japan, N o r w a y , United Kingdom, East and
W e s t Germany, Sweden, Switzerland, Turkey.

3. F l e t c h e r , J . C , a n d W e r t z , D . C , 1990: £íh/cs, Law and Medical

Genetics: After the Human Genome is Mapped, Emory Law Journal 39:
747-809.

4. For instance, the Helsinki Declaration of the W o r l d Medical Asso-

ciation, a d o p t e d by t h e I 8 t h W o r l d Medical Assembly (Helsinki,
1964) and revised by t h e 2 0 t h W o r l d Medical Assembly ( T o k y o ,
1975), and the International Gode of Experimental research on hu-
man beings, of the W o r l d Health Organization, 1984.

5. Gf. Tbsk Forcé on £íh/cs o f the Society o f Critical Care Medicine: Consen-
sus repon on the ethics o f foregoing life-sustaining treatments in the criti-
cally ill, Gritical Gare Medicine 18: 1435-1439, 1990: also P a r m l e t ,
W . W . , ¡ 9 9 0 : The Bethesda Conference; £íh/c in Cardiovascular Medi-
cine (sponsored by the American Academy o f Cardiology) Journal of the
American Gollege o f Gardiology 16 ( I ) : 1-36.
274 6. P r e s í d e n t í a l C o m m í s s í o n , 1983: Screening and Counseling for Ge-
neí/c Conditions (Washington, D.C., U.S G o v e r n m e n t Printing Office,
p. 44. These conditions are as follows: I) that all reasonable effort
t o obtain v o l u n t a r / consent t o reveal the situation have failed; 2)
that t h e r e is a high probability both that serious harm will be entail-
ed is information is concealed, and t h a t the information revealed
will be used t o avoid such harm; 3) t h a t certain identifiable indi-
viduáis could suffer serious harm and 4) that adequate precaution
has been taken t o guarantee that the necessary genetic information
w i l l only be revealed f o r t h e diagnosis a n d / o r t r e a t m e n t o f the
disease in question.
 275

DIAGNOSTIC TESTING
OF GENETIC DISORDERS
IN T H E E A R L Y S T A G E S O F
PREGNANCY: SOCIAL AND
ETHICAL IMPLICATIONS

Bruno Brambati

Institute o f Obstetrics and Gynaecology,

U n i v e r s i t y o f M i l á n (Italy)

ABSTRACT

There are currently two options for the prevention o f

genetic disorders: the donation o f gametes together
with assisted r e p r o d u c t i o n a n d p r e - n a t a l genetic
diagnosis followed by se/ect/Ve abortion o f an affect-
ed fetus. Diagnosis can o/so be carried out prior to
the implantation o f the egg (post-conceptional diag-
nosis), a n d it has recent/y been suggested that the
biopsy o f the polar corpuscuie will facilítate predic-
tion o f the genetic constitution o f the ovum to be
fertilized.
On the ethicai aspects o f pre-natal diagnosis, the
author thinks that use for eugenesic ends is unac-
ceptable a n d that the fundamental aim o f this diag-
nosis is to accurately inform parents and offer them
all options that could fit their case, thus making it
possible for t h e m to come to a decisión.
D u r i n g t h e last t w o d e c a d e s t h e r e has b e e n an i n c r e a s i n g i n t e r e s t 277
in c o n g e n i t a l d i s o r d e r s a n d h u m a n g e n e t i c s . C o n g e n i t a l d i s o r d e r s
have n o t o n l y b e c o m e t h e m a j o r cause o f i n f a n t m o r t a l i t y , but
a r e also r e s p o n s i b l e f o r a c o n s i d e r a b l e p r o p o r t i o n o f l o n g t e r m
physical a n d / o r m e n t a l handicaps. M o r e o v e r , a g r o w i n g number
o f c o u p l e s w a n t t o l i m i t t h e i r f a m i l y size a n d p r o t e c t t h e q u a l i t y
o f life, a n d t h e y a r e less i n c l i n e d t o c o n s i d e r t h e b i r t h o f a h a n d i -
c a p p e d c h i l d as an u n a v o i d a b l e risk. T h e r e f o r e , t h e y w a n t t o be
i n f o r m e d a b o u t t h e g e n e t i c r i s k s a n d h o w t o a v o i d having an af-
fected child.

T o face r e p r o d u c t i o n a n d p r e v e n t g e n e t i c d i s o r d e r s a s s o c i a t e d
w i t h p o o r q u a l i t y o f life t w o o p t i o n s a r e m a i n l y available ( t a b . I ) :
g a m e t e d o n a t i o n t o g e t h e r w i t h assisted p r e g n a n c y procedures,
o r p r e n a t a l g e n e t i c diagnosis f o l l o w e d by s e l e c t i v e a b o r t i o n o f an
a f f e c t e d c o n c e p t u s . In t h e r e c e n t y e a r s w e have w i t n e s s e d t h e
g r o w t h o f a n u m b e r o f p r e n a t a l diagnosis m e t h o d s f r o m a p p l i e d
research t o being a r o u t i n e c o m p o n e n t of genetic couselling and
obstetric management. A b o u t t w o hundred genetic conditions
can a c t u a l l y b e d i a g n o s e d in ú t e r o b y a p p l y i n g invasive s a m p l i n g
t e c h n i q u e s ( c h o r i o n i c villus s a m p l i n g , a m n i o c e n t e s i s , c o r d o c e n t e -
sis), a n d c y t o g e n e t i c , e n z y m a t i c a n d D N A analysis m e t h o d s . In
addition, m o r e than t w o h u n d r e d structural defects of t h e e m -
b r y o / f e t u s a r e d e t e c t a b l e by s o n o g r a p h y , a n d n e u r a l t u b e d e f e c t s ,
a n d D o w n s y n d r o m e can be s c r e e n e d o n m a t e r n a l b l o o d in t h e
early s e c o n d t r i m e s t e r o f pregnancy (tab. 2).

Table I: Reproductíve options available to genetic

risk individuáis for avoiding an affected child

BEFORE C O N C E P T I O N :

- In t h e case o f autosomal recessive disease: d o n o t r e p r o d u c e w i t h a c a r r i e r o f

t h e same a b n o r m a l genetic t r a i t (i.e.: c o n t r a c e p t i o n , sterilization).
- In t h e case o f X - l i n k e d o r autosomal d o m i n a n t disease: d o n o t r e p r o d u c e at all.
- O v u l a t i o n i n d u c t i o n , first polar b o d y biopsy and genetic analysis, t o g e t h e r w i t h
IVF-ET.

AFTER C O N C E P T I O N :

- Unselective a b o r t i o n .
- Preimplantation genetic diagnosis and transfer o f only n o n affected e m b r y o s .
- Post-implantation genetic diagnosis f o l l o w e d by selective a b o r t i o n o f affected
embryo/fetus.

IN THE FUTURE:

- Fetal t h e r a p y ( s t e m m cell transplantation, gene therapy).

In all t h r e e invasive s a m p l i n g p r o c e d u r e s , w h e n c o r r e c t l y a p p l i e d ,
m a t e r n a l a n d f e t a l r i s k has p r o v e d u n u s u a l , w h i l e in s k i l l e d hands
t h e s a m p l i n g success r a t e is v i r t u a l l y a h u n d r e d p e r c e n t a n d a b o r -
278 t i o n r a t e is a b o u t o n e p e r c e n t ( t a b . 3 ) . H o w e v e r , s u r g i c a l or
medical selective a b o r t i o n after amniocentesis o r cordocentesis
can n o t b e p e r f o r m e d b e f o r e t h e fifth m o n t h , o f p r e g n a n c y a n d
i m p l i e s n o t o n l y significant m a t e r n a l m o r t a l i t y a n d m o r b i d i t y b u t
is also a p s y c h o l o g i c a l l y t r a u m a t i c e v e n t w i t h f r e q u e n t l o n g t e r m
b e h a v i o u r a l a n d e m o t i o n a l sequélae. In f a c t m a t e r n a l - f e t a l b o n d -
ing has a l r e a d y o c c u r r e d a t t h e f i f t h g e s t a t i o n m o n t h a n d p r e n a -
tal a t t a c h m e n t t o a w a n t e d c h i l d e x i s t s . F o r t u n a t e l y , chorionic
villus s a m p l i n g ( C V S ) a l l o w s p r e n a t a l diagnosis t o b e m a d e m u c h
e a r l i e r in p r e g n a n c y : a t t h a t t i m e g e s t a t i o n is still a p r í v a t e e v e n t
and n o h u m a n f e a t u r e s can be r e c o g n i z e d in t h e s o n o g r a p h i c r e p -
r e s e n t a r o n o f t h e e m b r y o . T h e psychological advantages, c o m -
pared t o amniocentesis and cordocentesis, seem obvious.

Table 2 : Currently avaílable methods for in útero

diagnosing congenital abnormalities

ULTRASOUND*: > 2 0 0 abnormalities have already

been identifled

CVS Biochemical
> 100 metabolic diseases
anal/sis

AMNIOCENTESIS Cytogenetic
Chromosome Aberrations
anal/sis

FBS D N A analysis > 50 monogenic diseases

M A T E R N A L BIOCHEMISTRY**: - N T D s Screening
- A n e u p l o i d i e s Screening

* mainly in t h e 2nd and 3 r d t r i m e s t e r .

* * at i 5 t o 18 gestation weeks.

Table 3 : Characteristics of the invasive prenatal

diagnosis methods

Method Earliest Time

Abortion Maternal Fetal
week for to
risk risk risk
sampling diagnose

CVS I day t o I % excep- excep-

2-3 w k s tional tional

Amniocentesis 15 2-4 w k s I %

FBS 17 I -3 days 1-4%

F i r s t t r i m e s t e r g e n e t i c diagnosis by C V S has b e c o m e a w i d e l y ac-

c e p t e d a l t e r n a t i v e t o t h e s e c o n d t r i m e s t e r p r o c e d u r e s . C V S has
o f f e r e d t h e o p p o r t u n i t y t o g r e a t l y r e l i e v e t h e a n x i e t y c a u s e d by
t h e l o n g w a i t o f a diagnosis c o n c l u d e d n e x t t o t h e f i f t h m o n t h of
pregnancy, and t o minimize t h e obstetrical and psychological
c o m p l i c a t i o n s o f a late s e l e c t i v e a b o r t i o n . M o r e o v e r , because o f 279
its p r e c o c i t y f i r s t t h m e s t e r diagnosis has f r e q u e n t l y a l l o w e d e v e n
legal a n d r e l i g i o u s o b s t a c l e s t o be o v e r e ó m e . C V S has r e c e n t l y
b e e n a n t i c i p a t e d as e a r l y as t h e 6 t h a n d 7 t h g e s t a t i o n week,
t h e r e f o r e b y t h e use o f r a p i d d i a g n o s t i c m e t h o d s ( e . g . d i r e c t
k a r y o t y p i n g , e n z y m a t i c analysis o f f r e s h t i s s u e , D N A analysis b y
p o l y m e r a s e chain r e a c t i o n ) g e n e t i c diagnosis m i g h t b e available in
f e w days a n d m e d i c a l t e r m i n a t i o n o f an u n w a n t e d p r e g n a n e y suc-
cessfully o b t a i n e d b y t h e a d m i n i s t r a t i o n o f a n t i p r o g e s t a g e n s a n d
p r o s t a g l a n d i n s l•2.

A l t h o u g h t h e p u b l i c g e n e r a l l y a p p e a r s t o have a f a v o r a b l e o p i n i ó n
a b o u t t h e o p t i o n o f C V S , in a n u m b e r o f cases s e l e c t i v e a b o r t i o n
remains unacceptable o n m o r a l , e m o t i o n a l and religious grounds,
o r its p o s s i b i l i t y is r e f u s e d as a c o n s e q u e n c e o f p r e v i o u s g r i e v o u s
e x p e r i e n c e s o f r e p e a t e d p r e n a t a l t e s t s . It is t h e r e f o r e u n d e r s t a n d -
able t h a t f o r t h e s e p e o p l e s p r e i m p l a n t a t i o n diagnosis c o u l d r e p -
resent a f u r t h e r remarkable contribution t o make post-concep-
t i o n a l diagnosis a m o r e a c c e p t a b l e t o o l t o save t h e f a m i l y f r o m
g e n e t i c d i s e a s e s . In v i t r o f e r t i l i z a t i o n a n d n o n - s u r g i c a l uterine
lavage m a k e p o s s i b l e t h e access t o t h e p r e - e m b r y o . B l a s t o m e r e s
m a y be r e m o v e d f r o m t h e 4 - 8 cell stage 3 o r f r o m trophecto-
d e r m o f t h e e x p a n d e d b l a s t o c y s t 4, a n d g e n e t i c analysis c a r r i e d
o u t o n o n e o r a f e w cells by a m p l i f y i n g specific D N A sequenced
(tab. 4 ) . M o r e o v e r , f i r s t p o l a r b o d y b i o p s y a n d analysis has also
b e e n r e c e n t l y s u g g e s t e d a n d successfully a p p l i e d t o p r e d i c t t h e
g e n e t i c c o n s t i t u t i o n o f t h e o o c y t e t o be f e r t i l i z e d 5. H o w e v e r ,
diagnostic reliability and c o n c e p t u a l risks o f gametes and p r e -
e m b r y o m a n i p u l a t i o n have b e e n e v a l u a t e d o n l y in a n i m á i s : b y e x -
t r a p o l a t i n t h e r e s u l t s t o h u m a n s , t e r a t o g e n i c effeets m i g h t b e e x -
cluded, w h i l e a l o w e r implantation rate and reduced growth
p o t e n t i a l s h o u l d be e x p e c t e d 6. A t p r e s e n t p r e i m p l a n t a t i o n a n d
p r e c o n c e p t i o n a l d i a g n o s t i c p r o c e d u r e s can o n i y b e o f f e r e d to
highiy m o t i v a t e d a n d f u l l y i n f o r m e d c o u p l e s a t r i s k o f h e r e d i t a r y
disease.

T h e a c t u a l m a t e r n a l age c r i t e r i a , l i m i t i n g t h e o f f e r o f g e n e t i c diag-
nosis t o w o m e n 35 o r m o r e y e a r s o í d , has l i t t l e i m p a c t o n t h e i n -
c i d e n c e o f c h r o m o s o m e a n o m a l i e s a t b i r t h : since u p t o 9 0 % o f
b i r t h a r e in f a c t f r o m l o w e r age class w o m e n as w e l l as 7 0 % o f
D o w n S. n e w b o r n s . O n t h e o t h e r side t h e l i m i t e d l a b o r a t o r y fa-
cilities, w h i c h a r e u n l i k e l y t o b e significantly i n c r e a s e d in t h e f u -
t u r e , m a k e i t u n r e a l i s t i c t o e x t e n d p r e n a t a l t e s t s t o all p r e g n a n t
w o m e n . T h e r e f o r e , t h e avaliability o f inexpensive and simple
s c r e e n i n g t e s t s c o u l d have a b e n e f i c i a l e f f e c t t o i d e n t i f y higher
r i s k p r e g n a n c i e s w i t h o u t c o n s i d e r i n g m a t e r n a l age. A c c u m u l a t i n g
e v i d e n c e s u p p o r t t h e a s s o c i a t i o n b e t w e e n a b n o r m a l m a t e r n a l se-
r u m valúes o f a l f a - f e t o p r o t e i n ( A F P ) , h u m a n c h o r i o n i c gonado-
t r o p h i n ( H C G ) , a n d u n c o n j u g a t e d o e s t r i o l (uE3) in t h e e a r l y sec-
o n d t r i m e s t e r a n d v i a b l e fetal t r l s o m i e s . T h e d a t a e a r l y s e c o n d
t h m e s t e r and viable fetal t r i s o m i e s . T h e data s h o w t h a t by of-
fering amniocentesis t o only 5% of the total pregnant population.
280 Table 4: Methods that are beíng considered for
preimplantatíon genetic diagnosis
OVULATION NATURAL
INDUCTION CONCEPTION

1ST P O L A R IVF
U T E R I N E LAVAGE
BODY BIOPSY
AND BLASTOCYST
RECOVERY

GENETIC B I O P S Y AT
DIAGNOSIS 4-6 C E L L
TROPHECTODERM
(few hours) STAGE
BIOPSY

GENETIC
DIAGNOSIS
IVF
GENETIC
DIAGNOSIS
EMBRYO (few hours)
FREEZING

IN U T E R O N O R M A L
EMBRYO TRANSFER

o v e r 6 0 % o f D o w n S, w o u l d be d e t e c t e d 1. H o w e v e r , t h e p r e v e n
t i o n o f a n e u p l o i d i e s b y s e c o n d t r i m e s t e r p r o g r a m m e a n d late t e r -
m i n a t i o n is a v e r y d i s t r e s s i n g t a s k , a n d t h e d e v e l o p m e n t o f an
e q u a l l y e f f i c i e n t s c r e e n i n g in t h e f i r s t t r i m e s t e r w o u l d b e highly
desirable. P r e l i m l n a r y studies suggest t h e high sensitity of
fetal/placenta! p r o t e i n s (AFP, PAPP-A, SP-I) b e t w e e n 8 and 10
g e s t a t l o n w e e k s : in 8 5 % o f f e t a l a n e u p l o i d y cases t h e maternal
level has b e e n r e p o r t e d b e l o w t h e 5 t h p e r c e n t i l e o f t h e n o r m a l
d i s t r i b u t i o n in a t least o n e o f t h e m a r k e r s 8. F u r t h e r improve-
m e n t s in s e n s i t i v i t y a r e e x p e c t e d by u s i n g I n f o r m a t i o n derived
f r o m assay o f o t h e r p r e g n a n c y m a r k e r s (e.g. C A 125, uE3) in m a -
ternal serum. Thus, measuring first trimester concentration of
m a t e r n a l s e r u m g e s t a t i o n a l p r o t e i n s is l i k e l y c a n d i d a t e t o b e -
c o m i n g an e f f e c t i v e m e a n s o f i d e n t i f y i n g p r e g n a n t w o m e n in t h e
g e n e r a l p o p u l a t i o n w h o a r e a t i n c r e a s e d r i s k o f b e a r i n g a fetus
w i t h c h r o m o s o m a l a b e r r a t i o n and t o w h o m c h o r i o n i c tissue kar-
y o t y p i n g should be o f f e r e d .

In a d d i t i o n , t h e n e w m e t h o d s f o r h u m a n D N A analysis p r o m i s e
r a d i c a l a d v a n c e s in t h e p r e v e n t i o n o f i n h e r i t e d d i s o r d e r s . T h e
c h r o m o s o m a l l o c a t i o n o f d e f e c t i v e g e n e s , t h a t cause a b o u t 6 0 0
single-gene d i s o r d e r s , have n o w been identified and many of
t h e m , including t h e m o s t i m p o r t a n t ones, may be d e t e c t e d during
p r e g n a n c y . A w i d e n i n g r a n g e o f d e t e c t a b l e diseases is b e c o m i n g
accessible a n d m o l e c u l a r s t u d i e s by D N A recombinant technol-
o g y w i l l p r o v i d e in t h e n e x t t w e n t y y e a r s a c o m p l e t e linkage m a p 281
o f t h e H u m a n G e n o m e . T h e r e f o r e , d i s o r d e r s w i t h life t h r e a t e n i n g ,
m o d é r a t e o r hardly noticable symptoms, o r w h i c h manifest later
in life (e.g. H u n t l n g t o n ' s disease, p o l l c y s t l c k i d n e y ) , g e n e t i c p r e -
d i s p o s i t l o n f o r c e r t a i n diseases (e.g. d i a b e t e s , c a r d i o v a s c u l a r d i s -
eases), a n d e v e n c o s m e t i c c h a r a c t e r i s t i c s c o u l d b e r e c o g n i z a b l e
p r e n a t a l l y in t h e f u t u r e . O n t h e o t h e r h a n d , t h e methodological
advances in p r e n a t a l diagnosis a r e u n d o u b t e d l y s p e e d i n g t h e e v o -
l u t i o n o f n e w áreas o f in ú t e r o m e d i c a l i n t e r v e n t i o n , n a m e l y s o -
m a t i c / g e r m i n a l gene t h e r a p y and s t e m cell t r a n s p l a n t a t i o n , t o
c u r e g e n e t i c diseases a n d e n s u r e t h e q u a l i t y o f life.

In t h i s c o n t e x t a n u m b e r o f i m p l i c a t i o n s a r e c o n t r o v e r s i a l e n o u g h
and need t o be fully d e b a t e d b o t h professionally and a m o n g t h e
w i d e r public. T h e y arise f r o m , a m o n g o t h e r things, t h e fact t h a t
e a r l y C V S , p r e i m p l a n t a t i o n e m b r y o b i o p s y , s o r t i n g o f f e t a l cells in
m a t e r n a l b l o o d , s e l e c t i o n f o s p e r m a t o z o a , etc., w i l l m a k e g e n e t i c
diagnosis a m o r e a c c e p t a b l e t o o l f o r a w i d e r n u m b e r o f p e o p l e
t o select w h e t h e r t h e c o n c e p t u s be b o r n . M o r e o v e r , genetic
manipulation of the pre-embryo is p o t e n t i a l l y a v e r y positive
d e v e l o p m e n t t h a t help t o c o r r e c t n u m e r o u s devastating genetic
d i s o r d e r s in t i m e . It c o u l d also have t h e p o t e n t i a l h a r m f u l e f f e c t
o f e n g i n e e r i n g h u m a n s in t h e l a b o r a t o r y a c c o r d i n g t h e f o r m u l a e
of supermen o r bizarre monsters.

S h o u l d p r e n a t a l t e s t i n g b e p r o v i d e d f o r all w o m e n w i s h i n g t o
have a " n o r m a l " b a b y o r r e s t r i c t e d t o h i g h e r g e n e t i c r i s k couples?

S h o u l d a p r e g n a n t w o m a n d o w h a t she can t o e n s u r e t h e b i r t h o f
a n o r m a l r a t h e r t h a n a h a n d i c a p e d child?

D o e s i t m a k e sense t o e s t a b l i s h c r i t e r i a t o d i s c r i m í n a t e b e t w e e n
m i n o r and m a j o r disorders w i t h regard t o t h e admission t o pre-
natal t e s t i n g a n d / o r s e l e c t i v e a b o r t i o n ?

W i t h t h e n e w d e v e l o p m e n t o f fetal and gene t h e r a p y t h e c o n c e p -

t u s has t h e p o t e n t i a l t o b e c o m e a p a t i e n t w h o m i g h t n o t o n l y b e
d i a g n o s e d , b u t also t r e a t e d . Fetal t r e a t m e n t b r i n g s t h e m a t e r n a l -
fetal c o n f l i c t issue i n t o s h a r p f o c u s : can f e t a l a b n o r m a l i t y be c o r -
r e c t e d ; t o w h a t e x t e n t ; a n d a t w h a t m a t e r n a l a n d f e t a l risk? Is
g e r m cell g e n e t h e r a p y a c c e p t a b l e in h u m a n beings?

T o h e l p t h e g e n e r a l d e b a t e o n e t h i c a l issues r a i s e d b y g e n e t i c
diagnosis in e a r l y p r e g n a n c y e a c h p a r t i c i p a n t s h o u l d be s c i e n t i f i -
cally i n f o r m e d , f i r m l y c o m m i t t e d t o i n d i v i u d a l r i g h t s a n d h u m a n
dignity and should openly accept a free society of pluralistic
valúes.

T h e use o f p r e n a t a l diagnosis f o r a d i r e c t e d eugenic pro-

g r a m m e a t t h e p o p u l a t i o n level is u n a c c e p t a b l e . A c c e s s t o p r e n a t a l
t e s t i n g s h o u l d in p r i n c i p i e b e m a d e a v a i l a b l e t o all i n d i v i d u á i s .
T h e o n l y l i m i t i n g f a c t o r m i g h t be r e p r e s e n t e d by t h e availability
282 o f f i n a n c i a l r e s o u r c e s in t h e c o n t e x t o f t h e h e a l t h p o i i c y o f t h e
society (selective c r i t e r i a should be d e t e r m i n e d by t h e com-
munity).

T h e o b j e c t i v e s o f p r e n a t a l diagnosis a r e t o a l l o w t h e w i d e s p o s -
sible r a n g e o f i n f o r m e d c h o i c e r e g a r d i n g t h e p r o s p e c t o f h a v i n g a
genetically defective child. For t h e vast m a j o r i t y o f c o n d i t i o n s
t h a t can be d i a g n o s e d in ú t e r o n o c u r e s o r t r e a t m e n t s are
k n o w n , t h e r e f o r e s e l e c t i v e a b o r t i o n is t h e d e c i s i ó n t o interrupt
p r e g n a n c y is p a r t o f a w o m a n ' s r i g h t t o an a b o r t i o n is a l w a y s ab-
s o l u t e , t h e d i s p u t e a b o u t m a j o r a n d m i n o r d e f e c t s a n d t h e at-
t e m p t t o establish g e n e r a l c r i t e r i a a c c o r d i n g t o w h a t a c o n c e p t u s
s h o u l d b e a b o r t e d b e c o m e i r r e l e v a n t . O n t h e o t h e r s i d e , any
ethical j u s t i f i c a r o n t o selective a b o r t i o n should be fundamentally
f o u n d ín t h e c o m p l e x i t y o f facts a n d m o t i v a t i o n s p e c u l i a r t o each
individual.

T h e e f f e c t s o f i n d u c e d a b o r t i o n as a r e s u l t o f p r e n a t a l d i a g -
n o s i s a r e f r e q u e n t l y r e p o r t e d as p s y c h o l o g i c a l l y t r a u m a t i c : f o r
m o s t w o m e n t h e e v e n t i n v o l v e s t h e loss o f a d e s i r e d c h i l d t o
which they directly contributed by t h e i r a c t i v e d e c i s i ó n to
a b o r t . T h e r e is n o d o u b t s t h a t t h e access t o t h e n e w f e t a l t h e r -
apy a p p r o a c h e s , n a m e l y s t e m cell t r a n s p l a n t a t i o n and s o m a t i c
gene therapy, w o u l d p r o v i d e t h e great advantage of avoiding
the moral pain of selective a b o r t i o n . H o w e v e r , in n o way
s h o u l d fetal t h e r a p y be u n d e r t a k e n f o r c i b l y o r w h e n causing
harm t o the mother.

Table 5: Future directíons to prevent, diagnose,

and cure the genetic dísease

- C a r r i e r d e t e c t i o n o f a b n o r m a l genetic t r a i t .
- Maternal s e r u m biochemical screening o f e m b r y o aneuploidies in t h e first t r i -
mester.
- Magnetic nuclear resonance o f t h e fetus.
- Genetic diagnosis o n fetal cells in maternal circulation.
- Separation o f X - and Y - bearing spermatozoa.
- Medical t h e r a p y (drugs a d m i n i s t r a r o n in fetal circulation).
- Surgical t h e r a p y (open uterus surgery).
- Stem cell transplantation.
- Somatic cell gene therapy.
- G e r m cell line t h e r a p y .

G e r m l i n e g e n e t i c e n g i n e e r i n g is n o t y e t w i t h us, n e v e r t h e l e s s
t h e r e a r e real causes f o r m c o n c e r n a b o u t it. T h e e v e n t u a l m a p -
ping and sequencing o f t h e H u m a n G e n o m e , t o g e t h e r w i t h k n o w -
ledge o f h o w genes d e t e r m i n e diseases a n d a f f e c t c h a r a c t e r i s t i c s ,
m a y o n e day m a k e g e n e t i c m a n i p u l a t i o n o f t h e h u m a n embryo
p o s s i b l e . It has b e e n c l a i m e d t h a t t h e w r o n g d e c i s i o n s in t h e ap-
p l i c a t i o n o f t h i s r e s e a r c h c o u l d have d i s a s t r o u s c o n s e q u e n c e s o n
t h e h u m a n species a n d s o c i e t y . T h i s c o n c e r n is n o t substantially
d i f f e r e n t f r o m t h a t r e s u l t i n g f r o m o t h e r r e s e a r c h áreas (e.g. n u - 283
clear e n e r g y ) . T h e n , is t h i s f e a r a v a l i d m o t i v a t i o n t o ban a n y g e -
n e t i c r e s e a r c h o n e m b r y o s ? A s a g e n e r a l r u l e t o face t h e s e p r o b -
lems c o r r e c t l y " a n y c o n s t r u c t i v e d i a l o g u e a n d r e a s o n a b l e p o l i c y
d e v e l o p m e n t s h o u l d be p u r s u e d b y p u t t i n g r e s e a r c h o v e r s i g h t i n -
t o a multidisciplinary r e v i e w b o d y suitably c o n s t i t u t e d t o evalúate
n o t o n l y t e c h n i c a l r i s k s , b u t p o l i t i c a l , social a n d m o r a l a s p e c t as
well"9-10.
284

REFERENCES

1. B r a m b a t i , B . , T u l u í , L . , S i m o n i , G . , a n d T a v i , M. (1988).
Prenatal diagnosis at 6 weeks. Lancet ii: 397.

2. U . K. M u l t í c e n t r e T r i a l ( 1 9 9 0 ) . T h e efficacy and tolerance of

mifepristone and prostaglandin in first t r i m e s t e r t e r m i n a t i o n of
pregnancy. 6r j Obstet Gynaecol 97: 480-6.

3. H a n d y s i d e , A . H., K o n t o g í a n n i , E h . , H a r d y , K., a n d W i n s t o n ,
R. M. L . ( 1 9 9 0 ) . Pregnancies f r o m biopsied human preimplantation
embryos sexed by Y-specific D N A amplification. Nature 344:768-
70.

4. B r a m b a t i , B . , a n d F o r m i g l i , L . ( 1 9 9 0 ) . Obstetrical aspects of
a preimplantation genetic program. First International Symposium
on Preimplantation Genetics. Chicago, September 14-19.

5. S t r o m , C h . M., V e r l i n s k y , Y . , Mi l a y e v a , S . , e t a l . ( 1 9 9 0 ) .
Preconception genetic diagnosis of cystic fibrosis. Loncet ii: 306-7.

6. S u m m e r s , P. M., C a p b e l l , J . M., a n d Millar, M. W . ( 1 9 8 8 ) .

N o r m a l in-vivo development of marmoset monkey embryos after
t r o p h e c t o d e r m biopsy. H u m Reprod 3: 389-93.

7. W a l d , N. J . , C u c k l e , H. S . , D e n s e m , J . W . , et al. (1988).
Maternal serum screening f o r Down's syndrome in early pregnancy.
6r M e d J. 297: 883-7.

8. B r a m b a t i , B . ( 1 9 9 0 ) . Fate of Human Pregnancy. In: RG Edwards

(ed), Estabíishing a successful human pregnancy. Serono Symposia
Publications, Raven Press, N e w Y o r k , pp 2 6 9 - 8 ! .

9. C u l l i t o n , B . J . ( 1 9 8 5 ) . Gene Theraphy: research in public. Science

227:493-6.

10. E l i a s , S . , a n d A n n a s , G . J . ( 1 9 8 7 ) . Reproductive Genetics and the

Law. Year B o o k Medical Publisher, Inc., Chicago, pp. 2 6 9 - 7 ! .
PROFESSIONAL
S E C R E C Y A N D
CONFIDENTIALITY
 287

CONFIDENTIALITY

josé Elizalde

Legal A d v i s e r t o t h e C o m m i s s i o n o f E u r o p e a n C o m m u n i t i e s ,
G e n e r a l D l r e c t l o n X I I , Brussels.

ABSTRACT

The European Community is currently fínancing a

p r o g r a m m e o f research a n d development for the
study o f the H u m a n Genome. This project is o f a cer-
tain confidential nature. The EEC guarantees confi-
dential t r e a t m e n t o f technical reports to avoid the
commercialization o f certain information. Besides, in-
tellectual copyright belongs to the researchers and it
musí be them who exploit the information, bearing
in mind that there will be no exclusive exploitation
right as far as the human A D N is concerned. On the
other h a n d , the Commission o/so guorontees the
anonymity o f personal data resulting from genome
research, considerin t h a t the people whose A D N ' s
are being m a p p e d have given their consent to this
end ofter being informed o f the project Finally, the
medical data must only be used for diagnosis a n d
the prevention o f diseases or for research. There-
fore, access to this information must be controlled.
T h a n k y o u , M r . p r e s i d e n t . W h e n j u s t a f e w days a g o , D o c t o r 289
Grísolía r e q u e s t e d m e by telefax t o p r o v i d e a p r e s e n t a t i o n o n
confidentiality f o r this w o r k s h o p , I accepted immediately be-
c a u s e i t p r o v i d e s m e n o w w i t h an o p p o r t u n i t y t o d i s c u s s in
public s o m e r e f l e c t i o n s o n a m a t t e r perhaps small - i n q u a n t i t a -
tive terms of our budget; about 1% of our 1990 European
C o m m u n i t i e s budget f o r R & D - b u t y o u will agree w i t h me t h a t
i t is v e r y i m p o r t a n t in q u a l i t y : t h e legal p r o b l e m s o f Human
G e n o m e research.

M y j o b in t h e last c o u p l e o f y e a r s has b e e n as legal a d v i s e r f o r

t h e Science and Research G e n e r a l D i r e c t o r a t e o f t h e E u r o p e a n
C o m m u n i t y in B r u s s e l s . O f c o u r s e , I s p e a k h e r e o n a p e r s o n a l
basis - t h a t w i l l m a k e t h i n g s e a s i e r . A s y o u a l r e a d y k n o w , the
E C has a l s o a d o p t e d t h i s y e a r a s m a l l , p i l o t R & D programme
f o r H u m a n G e n o m e analysis. A s D o c t o r L o d e r a n d Proffesor
N i e r m e i j e r a r e p r e s e n t in t h i s w o r k s h o p , a n d t h e y a r e f a r m o r e
c o m p e t e n t t o give y o u any I n f o r m a t i o n a b o u t t h e scientific and
t e c h n i c a l c o n t e n t s o f o u r p r o g r a m m e , and w e have a c o u p l e o f
I n f o r m a t i o n packages f o r t h o s e w h o are i n t e r e s t e d , I w i l l c o n -
c é n t r a t e here o n t h e institutional concerns raised, mainly by
t h e E u r o p e a n Parliament, d u r i n g t h e legislative p r o c e s s which
has e v e n t u a l l y m a d e t h e C o m m i s s i o n - t h a t is, t h e a d m i n i s t r a -
tive executive body of the European C o m m u n i t i e s - responsible
f o r a t h o r o u g h d e b a t e o f t h e e t h i c a l , s o c i a l a n d legal p r o b l e m s
o f H u m a n G e n o m e analysis. A s Prof. N i e r m e i j e r t o l d y o u this
m o r n i n g , t h e r e will be a general ethical r e v i e w of t h e p r o g r a m m e
by an i n d e p e n d e n t interdisciplinary committee of thirty
members, to be n o m i n a t e d at t h e b e g i n n i n g o f n e x t year...
w h i c h , by t h e w a y , w i l l also include p a t i e n t s ' r e p r e s e n t a t i v e s , o f
organizations o f relatives o f patients, like cystic fibrosis. We
think that this is a l s o a n i m p o r t a n t aspect for an ethics
committee.

Confidentiality for R&D

The Commission m u s t also e n s u r e - t h a t was a c o m m i t m e n t

t o t h e E u r o p e a n P a r l i a m e n t - specifically t h e exclusión o f any
a l t e r a t i o n o f h u m a n g e r m c e l l s d u r i n g t h e r e s e a r c h . T h i s has
b e e n c r i t i c i z e d h e r e , p e r h a p s r i g h t l y , b u t i t is a legal o b l i g a t i o n
f o r us. A n d t h e C o u n c i l d e c i s i ó n r e q u i r e s f u l l c o n f i d e n t i a l i t y o f
any p e r s o n a l i n f o r m a t i o n c o l l e c t e d in t h e c o u r s e o f t h e re-
search, w h i c h will c o n f o r m t o t h e best data p r o t e c t i o n prac-
t i c e s . I w i l l c o n s i d e r h e r e f b u r ospects o f c o n f i d e n t i a l i t y f o r t h e
H u m a n Genome Programme; t h e t h r e e f i r s t c o n c e r n s t h e r e s e a r c h
itself. First, contractual c o n f i d e n t i a l i t y , s e c o n d medical c o n f i -
d e n t i a l i t y , a n d t h i r d d a t a p r o t e c t i o n . A n d t h e f o u r t h , t h e issues
raised by applications o f any n e w k n o w l e d g e arising f r o m the
research.
290 Contractual confldentíalíty

First, w e begin w i t h contractual confidentiality. O n t h e o n e h a n d ,

t h e r e a r e a d m i n i s t r a t i v a p r o c e d u r e s : all p r o p o s a l s a n d all t e c h n i -
cal r e p o r t s , a r e t r e a t e d c o n f i d e n t i a l l y b y t h e C o m m i s s i o n ' s ser-
vices, b y t h e A d v i s o r y C o m m i t t e e a n d by t h e i r e x p e r t s . H o w e v e r ,
s o m e r e p o r t s s u i t a b l e f o r p u b l i c a t i o n , e x c l u d i n g any c o m m e r c i a l l y
sensitive i n f o r m a t i o n , m u s t be p r o v i d e d . N o publication o f r e -
sults w i i l be m a d e w i t h o u t t h e p r i o r a g r e e m e n t o f t h e c o n t r a c -
t o r . O n c o m p l e t i o n o f t h e p r o j e c t , a c o n f i d e n t i a l r e p o r t m u s t be
s u b m i t t e d t o t h e C o m m i s s i o n , indicating h o w t h e c o n t r a c t o r in-
tends t o e x p l o i t t h e results o f t h e w o r k , including t h e industrial
and intellectual p r o p e r t y rights applied f o r and received. T h e
C o m m i s s i o n m a y s u b m i t t h e full t e c h n i c a l r e p o r t , o n a c o n f i d e n -
t i a l basis, t o o t h e r E C i n s t i t u t i o n s , like t h e E u r o p e a n P a r l i a m e n t ,
a n d in a g r e e m e n t w i t h t h e p a r t n e r s , t o g o v e r n m e n t s o f t h e E C
m e m b e r states o n International organizations.

O n t h e o t h e r hand, t h e contractual obligations include a limita-

t i o n o f o w n e r s h i p . W e have in t h e C o m m i s s i o n t h e g e n e r a l p r i n -
cipie t h a t ideas a n d i n t e l l e c t u a l p r o p e r t y r i g h t s g e n e r a t e d under
t h e research c o n t r a c t are o w n e d by t h e c o n t r a c t o r s , w h o must
e x p l o i t o r c o m m e r c i a l i z e t h e m in c o n f o r m i t y w i t h t h e i n t e r e s t s
o f t h e C o m m u n i t y r e p r e s e n t e d by t h e C o m m i s s i o n . T h e c o n t r a c -
t u a l c o n d i t i o n s p r o v i d e a legal f r a m e w o r k f o r t h e g r a n t i n g o f l i -
c e n s e s a n d use r i g h t s b e t w e e n d i f f e r e n t p r o j e c t s a n d different
R T D (Research and Technological D e v e l o p m e n t ) programmes.
I n f o r m a t i o n w h i c h c a n n o t be p r o t e c t e d by patents - t h a t would
be t h e case in E u r o p e , o f h u m a n D N A s e q u e n c i n g - m u s t be m a d e
available t o o t h e r e n t i t i e s , s u b j e c t t o a g r e e d q u a l i f i c a t i o n s and
r e s t r i c t i o n s . . . t h i s is p e r h a p s a b i t t o o t e c h n i c a l , b u t i t is c a r e f u l l y
r e g u l a t e d in o u r h a r m o n i z e d o r " m o d e l c o n t r a c t s " . In t h e case o f
h u m a n g e n o m e analysis, t h e r e is an a d d i t i o n a l p r i n c i p i e , specific
t o t h i s p r o g r a m m e , n a m e l y t h a t t h e r e shall be n o e x c l u s i v e e x -
p l o i t a t i o n r i g h t s in r e s p e c t o f h u m a n D N A . B u t f o r t u n a t e l y -I
h o p e , b e c a u s e M r . T r i a n a ' s a v a i l a b i l i t y is n o t c o n f i r m e d - I w i l l
leave t h i s d i f f i c u l t s u b j e c t o f i n t e l l e c t u a l p r o p e r t y r i g h t s t o the
last s p e a k e r o f t h e p a n e l , o r o t h e r w i s e w e can discuss i t in t h e
colloquium.

Medical confldentíalíty

T h e s e c o n d a s p e c t I w a n t t o c o n s i d e r h e r e is m e d i c a l confldentía-
líty. T h e C o m m i s s i o n f u l l y r e s p e c t s t h e C o u n c i l o f E u r o p e r e c o m
m e n d a t i o n o f F e b r u a r y 6, 1990, w h i c h shall be i n c l u d e d in a f u t u r e
European convention concerning medical research on human
beings. It is b e i n g d r a f t e d n o w by e x p e r t s f o r t h e C o u n c i l o f Eu-
r o p e . I t h i n k M r . W i t , w h o is h e r e , is w o r k i n g o n t h a t also. P r i n -
cipie 3 o f t h i s r e c o m m e n d a t i o n states t h a t " n o m e d i c a l r e s e a r c h
m a y b e c a r r i e d o u t w i t h o u t t h e i n f o r m e d , f r e e , e x p r e s s a n d spe-
cific c o n s e n t o f t h e p e r s o n u n d e r g o i n g i t " . A n d P r i n c i p i e 9 d e - 29
clares: " A n y I n f o r m a t i o n o f a p e r s o n a l n a t u r e o b t a i n e d d u r i n g m e -
dical r e s e a r c h s h o u l d b e t r e a t e d as c o n f i d e n t i a l " . T h e members
o f t h e 6 0 " l a r g e f a m i l i e s " , w h o s e D N A is c o l l e c t e d a n d m a p p e d
t h r o u g h t h e E u r o p e a n H u m a n G e n o m e P r o g r a m m e , have b e e n
f u l l y i n f o r m e d , a n d all o f t h e m have g i v e n t h e i r f r e e a n d w r i t t e n
c o n s e n t , a f t e r a l o n g i n t e r v i e w in w h i c h c l e a r a n d p e r t i n e n t e x -
planations w e r e given, not only about the c o m m i t m e n t , but
a b o v e all a b o u t t h e possible risks i n v o l v e d . T h e C o m m i s s i o n t h e r e -
f o r e guarantees t h e confidentiality and a n o n y m i t y o f t h e personal
d a t a t o b e o b t a i n e d ; f o r e x a m p l e t h e D N A samples t o be d i s t h b -
u t e d t o l a b o r a t o r i e s engaged in t h e linkage m a p p i n g a r e c o d e d ,
a n d t h e k e y t o t h e c o d e is n o t s t o r e d o n c o m p u t e n

Informatic confidentiality

W e c o m e s n o w t o t h e t h i r d aspect o f confidentiality, namely data

protection. T h i s is p e r h a p s o n e o f t h e m o s t c o n f l i c t i v e o n e s - e v e n
t h e m o s t conflictive o n e - because different and fundamental
r i g h t s a r e a t s t a k e . T h e r i g h t t o p r i v a c y is c e r t a i n l y o n e o f t h e es-
sential h u m a n r i g h t s , b u t y e t i t is n o t an a b s o l u t e o n e , a n d t h e r e
is a c o n s t i t u t i o n a l c a s e - l a w in s e v e r a l E u r o p e a n s t a t e s , p a r t i c u -
larly in t h e F e d e r a l R e p u b l i c o f G e r m a n y , s e t t i n g u p l i m i t s o n t h e
right t o confidentiality f o r personal data. Indeed, t h e European
C o n v e n t i o n o n H u m a n Rights c o n s i d e r s t h e p r o t e c t i o n o f h e a l t h
as a l e g i t í m a t e l i m i t t o t h e r i g h t t o p r i v a c y , w h i c h i t s e l f is aiso a
l i m i t t o t h e f r e e d o m o f e x p r e s s i o n . Y o u w i l l f i n d t h a t in a r t i c l e 10
paragraph 2 of t h e C o n v e n t i o n . A comparative survey of national
and I n t e r n a t i o n a l legislation o n privacy o f data p r o t e c t i o n s h o w s
t h a t a s e t o f p r i n c i p i e s has e m e r g e d t o r e c o n c i l e t w o seemingly
conficting needs: on t h e one hand, f r e e d o m t o receive Informa-
t i o n t h r o u g h t h e n e w c o m p u t e r and t e l e c o m m u n i c a t i o n s means
- w e c o u l d in f a c t s p e a k o f t e l e m a t i e s , t h e m i x t u r e b e t w e e n t e l e -
communications and informatics; and, o n the o t h e r hand, respect
f o r t h e p r í v a t e Uves o f i n d i v i d u á i s . T h e s e p r i n c i p i e s include:
I ) Fair a n d l a w f u l c o i l e c t i o n o f d a t a ; 2 ) Q u a l i t y o f d a t a , í n c l u d i n g
a c c u r a c y a n d p e r t i n e n c e ; 3) T h e p r i n c i p i e l i m i t i n g t h e use o f d a t a
so t h a t d i s s e m i n a t í o n a n d i n t e r c o n n e c t i o n a r e m a d e c o n d í t i o n a l
upon the consent of the persons concerned, o r the existence of
a specific legislative a u t h o r i z a t í o n ; 4 ) T r a n s p a r e n c y , w h e r e b y i n -
f o r m a r o n a b o u t t h e e x i s t e n c e o f d a t a banks, t h e i r p u r p o s e a n d
use, a r e t o b e m a d e p u b l i c ; 5) T h e p r i n c i p i e o f i n d i v i d u a l p a r t i c i -
p a t i o n , b y v í r t u e o f w h i c h t h e i n d i v i d u á i s c o n c e r n e d s h o u l d have
access t o files, a n d e v e n a r i g h t t o have such d a t a c o r r e c t e d or
e r a s e d , a l t h o u g h in s o m e c o u n t r i e s t h e r e a r e l i m i t s f o r correc-
t i o n o f m e d i c a l d a t a b y t h e i n d i v i d u a l ; a n d finally, t h e p r i n c i p i e o f
r e s p o n s i b i l i t y o f t h o s e in charges o f files.

T h e s e a r e d i f f e r e n c e s b e t w e e n t h e l a w s . S o m e a r e g e n e r a l ; in
o t h e r n a t i o n s t h e y o n l y c o v e r s p e c i f i c á r e a s - t h i s is m a i n l y t h e
292 U S a p p r o a c h . G r e a t i m p o r t a n c e t h e r e f o r e , a t l e a s t in t h e E u -
ropean setting accrues t o the Council of Europe Convention
o n the p r o t e c t i o n o f individuáis w i t h regard t o t h e automatic
p r o c e s s i n g o f p e r s o n a l d a t a - t h i s is t h e o f f i c i a l t i t l e - o f 1 9 8 1 ,
w h i c h t h e C o m m i s s i o n fully i n t e n d s t o r e s p e c t , a n d w h i c h can
b e s a f e l y t a k e n as a m o d e l s e t o f I n t e r n a t i o n a l s t a n d a r d s in
this área.

T h e r e f o r e , ¡ n t e r n a t i o n a l access t o h u m a n s e q u e n c i n g s h o u l d ¡n-
clude full respect f o r data p r o t e c t i o n , and o f c o u r s e o f Interna-
t i o n a l s t a n d a r d i z a r o n in t h i s á r e a , a n d g u a r a n t e e s against u n d u e
access t o p r í v a t e d a t a .

O f c o u r s e , a u t o m a t i c m e d i c a l d a t a banks s h o u l d o n l y be s t o r e d
f o r t h e p u r p o s e s o f m e d i c a l c a r e , diagnosis a n d p r e v e n t i o n o f dis-
ease, a n d scientific r e s e a r c h in t h i s á r e a . A c c e s s t o m a p a n d se-
q u e n c e i n f o r m a t i o n in d a t a b a n k s a n d c l o n e r e p o s i t o r i e s m u s t be
o p e n t o scientists and t h e r e f o r e subject t o unavoidable c o n t r o l s .
H o w e v e r , long-term s t o r a g e o f such d a t a r e q u i r e s specific a n d i n -
creased security - a l p h a n u m e r i c passwords, electronic signatures,
e t c . A s t h e data f o r t h e H u m a n G e n o m e P r o g r a m m e m a y c o n c e r n
s e v e r a l g e n e r a t i o n s e v e n t u a l l y , a n d in a d d i t i o n c e r t a i n g e n e t i c
d i s o r d e r s ( H u n t i n g t o n ' s c h o r e a f o r example, w h i c h may o n l y ap-
p e a r a t l a t e r stages in t h i s life o f a p a t i e n t , b e t w e e n 35 a n d 5 5 ) ,
l o n g - t e r m c o n s e r v a t i o n o f d a t a is j u s t i f i e d o n a n u m b e r of
grounds.

C o n s i d e r a t i o n should be given t o t h e need t o ensure t h a t backup

r e c o r d s a r e k e p t a t a safe, r e m o t e s i t e . I t g o e s w i t h o u t saying
t h a t p e r s o n n e l w h o a r e a u t h o r i s e d t o access t h e d a t e s h o u l d be
t r a i n e d t o respect and i m p l e m e n t data security.

T h e r i g h t t o c o n f i d e n t i a l i t y o f p e r s o n a l g e n e t i c i n f o r m a t i o n is
potentially conflictive w i t h t h e rights of o t h e r s : family m e m b e r s ,
f e l l o w - e m p l o y e e s , t h e p u b l i c a t l a r g e . F o r e x a m p l e an i n d i v i d u a l
may have D N A d a t a s u c h as k n o w l e d g e o f a g e n e mutation
causing, say H u n t i n g t o n ' s disease again, w h i c h a n o t h e r m e m b e r o f
t h e f a m i l y needs f o r diagnosis o r p r e v e n t i o n . T h e r e a r e also
r i s k s f o r t h e i n d i v i d u a l h i m s e l f . I n f o r m a t i o n w h i c h is r e l e v a n t t o
h e r o r his w e l l - b e i n g m u s t b e a v a i l a b l e w h e n n e e d e d . Know-
ledge o f s e n s i t i v i t y t o a p a r t i c u l a r a n a e s t h e t i c can save a
p a t i e n t ' s life as l o n g as i t is t h e r e w h e n t h e o c c a s i o n d e m a n d s .
A n a b s o l u t e ban o n d i s c l o s u r e o f genetic i n f o r m a t i o n would
b e u n w o r k a b l e , a n d i t w o u l d n o t b e in t h e i n t e r e s t s o f t h e i n d i -
v i d u a l himself. A s w a s said y e s t e r d a y , o n e s h o u l d n o t make
a b s o l u t e w h a t is o n l y r e l a t i v e . W e d o n ' t n e e d a b s o l u t e b u t o n l y
relative r e s t r i c t i o n s . I q u i t e agree w i t h t h a t . Privacy s h o u l d be a
vital principie o f medical genetics, b u t departures - f o r instance
i n f o r m a t i o n w h i c h may be available t o family m e m b e r s - must
be clearly regulated.
Confidentiality for applications of R&D 293

W e r e a c h h e r e the limits o f futura applications, t h e last p o i n t . It Is

essential t o e n s u r e t h a t I n f o r m a t i o n a b o u t t h e i r g e n e t i c m a k e u p
o r i d e n t l t y , is n o t f o r c e d o n Individuáis, w h i l e g u a r a n t e e i n g t h e m
t h e right t o k n o w w h e t h e r t h e y are at genetic risk, so t h a t t h e y
can m o d i f y t h a t risk, e.g. b y a change in life-style. F o r t h e f u t u r e ,
c o n f i d e n t i a l i t y o f t h e data o b t a i n e d a n d p r o t e c t i o n against u n a u -
t h o r i s e d access b y t h i r d p a r t i e s , w i l l b e c o m e c r u c i a l .

W e a r e c o n s c i o u s , as t h e A m e r i c a n e x p e r i e n c e - w h i c h has b e e n
c l e a r l y s h o w n in t h i s w o r k s h o p - a l r e a d y i n d i c a t e s , t h a t o n e o f
t h e m a i n risks o f f u t u r e g e n e t i c t e s t i n g f o r s u s c e p t i b i l i t y t o disease
in t h e m i s i n t e r p r e t a t i o n o f t e s t r e s u l t s b y i n d i v i d u á i s , f a m i l i e s a n d
social i n s t i t u t i o n s , a n d t h e p o t e n t i a l f o r s t i g m a t i s a t i o n a n d d i s c r i -
m i n a t i o n . T h e s e risks w i l l b r o a d e n as g e n e - b a s e d t e s t f o r m u l t i -
factorial health p r o b l e m s are developed.

But, b e y o n d i m p r o v i n g understanding, t h e main w a y t o prevent

u n f a i r use o f g e n e t i c i n f o r m a t i o n is t o legally p r o t e c t its c o n f i d e n -
t i a l i t y ; a n d several fields m u s t be c o n s i d e r e d ; g e n e t i c t e s t i n g f o r
insurance and f o r e m p l o y m e n t are t h e subject o f f u r t h e r C o m m u -
nications t o d a y and I w i l l n o t g o i n t o it; r e p r o d u c t i v e cholees
have a l r e a d y b e e n d e a l t w i t h ; t h e r i g h t o f p a r e n t s t o full i n f o r m a -
t i o n , in c o m p l e t e c o n f i d e n t i a l i t y a n d f r e e d o m f r o m c o e r c i ó n ; - a t
least t h e ideal; t h e legal issues a r e always ideal a n d o f t e n n o t v e r y
r e a l i s t i c - ; a n d , g i v e n t h e w i d e r availability t o p r e n a t a l diagnosis,
t h e d a n g e r t h a t r e s o u r c e s f o r t h e g e n e t i c a l l y h a n d i c a p p e d m a y be
l i m i t e d . A l l t h e s e f u t u r e a n d n o t - s o - f u t u r e issues, s o m e o f w h i c h
have a l r e a d y b e e n d e a l t w i t h t o d a y , e m p h a s i s e t h e p r i n c i p i e of
c o n f i d e n t i a l i t y . T h e legal c o n s e q u e n c e s o f t h e p r i n c i p i e t h a t p e r -
sonal g e n e t i c i n f o r m a t i o n m u s t r e m a i n c o n f i d e n t i a l , s h o u l d b e t h e
r i g h t f o r e v e r y o n e n o t t o be d i s c r i m i n a t e d against, o n the
g r o u n d s o f one's genetic c o n s t i t u t i o n . Effective p r o t e c t i o n and
access t o j u s t i c e against; g e n e t i c d i s c r i m i n a t i o n a r e n e c e s s a r y a n d
fair.

Some conclusions

I w o u l d like t o a d d t w o concluding remarks: O n e , W e m u s t c o n -

s i d e r all t h e s e issues f r o m t h e full r e s p e c t o f t h e f u n d a m e n t a l p r i n -
cipie o f scientific f r e e d o m , f r e e d o m in m a n y c o u n t r i e s , i n c l u d i n g
S p a i n , b y o w n , is a l s o a c o n s t i t u t i o n a l l y g u a r a n t e e d freedom.
O n l y f r e e d o m can e n t a i l r e s p o n s i b i l i t i e s . A n d w e c a r e a b o u t c o n -
f i d e n t i a l i t y p r e c i s e l y because w e c a r e a b o u t r e s p o n s i b l e f r e e d o m .
It is p r o b a b l y t r u e t h a t h u m a n d i g n i t y w o u l d n o t b e possible
w i t h o u t t h e f r e e d o m o f science.

M y last r e m a r k : H u m a n G e n o m e analysis is a worldwide r e s e a r c h

e f f o r t , l e n d i n g itself p a r t i c u l a r l y t o c o o p e r a t i v e a c t i o n . It w a s said
294 t h i s m o r n i n g t h a t sharing d a t a is an ethical imperative, a n d I a g r e e .
T h e f r e e e x c h a n g e o f d a t a a n d m a t e r i a l s is e x t r e m e l y c r u c i a l in
this e n t e r p r i s e . T h e r e s o u r c e s r e q u i r e d are so large t h a t u n -
necessary d u p l i c a t i o n o r u n d u e c o m p e t i t i o n m u s t be a v o i d e d .
T h e r e f o r e , t h e r i g h t c o m b i n a t i o n , t h e r i g h t balance o f open collabora-
tion in s c i e n t i f i c r e s e a r c h f o r t h e b e n e f i t o f m a n k i n d , w i t h full
respect f o r a n o n y m i t y o f p e r s o n a l d a t a , m u s t b e e n s u r e d . T h a n k
you.
 295

REFERENCES

I. P a r l e m e n t européen/Commissíon des C o m m u n a u t é s eu-

r o p é e n n e s / l n s t í t u t u n í v e r s i t a i r e e u r o p é e n . Conférence "Droits
de l'Homme et Communauté européenne: vers 1992 et au-dela", Stras-
bourg, Nov. 2 0 - 2 1 , 1989 (in particular, A. Cassese, "Rapport général"; S.
Rodota, "Ethique médicale, génétique et problémes //es" and J.P. Jacqué
& G. Knaub, "Liberté d'information et protection des données").

1. C o u n c í l of E u r o p e - C o m m i t t e e of M i n i s t e r s . Recommendot/on
N0 (90) 3, to Member States, concerning medical research o f human
beings.

3. C o m m i s s í o n of the E u r o p e a n C o m m u n i t i e s : C O M (90)
314. Proposal for a council Directive concerning the protection o f indi-
viduáis in relation to the processing o f personal data (1990 to 1991)
( O J C 2 7 7 , 5.11.90. p. 3).

4. E u r o p e a n C o m m u n i t i e s . Council Decisión o f june 29, 1990 adop-

ting a specific research and technological development programme in the
field o f health: human genome analysis (1990 to 1991) (OJ L 196,
25.7.90, p. 8).

5. C a n t l e y , M. F . , a n d E l i z a l d e , J . "Biotechnology and Human Rights".

34th Congress, Union Internationale des Avocats, Strasbourg, Sept.
10-16, 1990, London, B u t t e r w o r t h , 1990: pp. 269-277.
 297

GENETIC TECHNOLOGY,
INSURANCE AND THE FUTURE

G.W. de W/í

Faculteit d e r E c o n o m i s c h e W e t e n s c h a p e n , Erasmus Universiteit,

Rotterdam (Holland)

ABSTRACT

The insurance industry, as far as Ufe, invalidity a n d

sickness insurance are concerned, is a f f e c t e d by
health, the specifying o f the premius for the different
types o f insurance requires statistic analysis o f the
whoie o f p o p u i a t i o n d a t a . The assurer m o r e o v e r
examines the health o f the candidates a n d on the
strength o f both statistic a n d individual Information,
sets a reasonable, fair p r e m i u m . On the other hand,
insurance companies consider genetic informatlon to
be o f interest as far as pre-natal diagnosis a n d genet-
ic manipulation are concerned. The assurer already
has certain genetic Information for medical question-
naires Indude questions or diseases suffered by par-
ents.
The assurer asks whether people who have certain
genetic Information would adjust thelr llfe-style ac-
cording to same. In fact, It Is probable that genetic
research wlll pave the way to a better future, a t
least as far as health Is concerned.
The insurance industry has known a relatively calm period as far 299
as health related insurance policies are concerned. The impor-
tance of health is involved in the following categories of insur-
ance: life insurance (including pensions), disability insurance and
health insurance. O f course certain problems have arisen: the ever
decreasing m o r t a l i t y rates and the coinciding increase in t h e
average age of the population, the increasing number of those
unfit t o w o r k (with a characteristic sensitivity t o economic fluctua-
tions), rising absenteism w i t h definite economic consequences;
f u r t h e r m o r e w e can see a rise in health insurance premiums, not
because the number of hospitalizations has risen, but because of
t h e w i d e range of o p p o r t u n i t i e s t h a t medical technology has
made available; f u r t h e r m o r e the increase in average age has in-
fluenced demand.

If w e examine the underiying risk factors of these forms of insur-

ance (mortality rate, sickness rate, etc.) w e become aware that
nothing has changed in the way we apply these foundations. H o w
and w h e r e do w e get the necessary Information?

In o r d e r t o determine the premiums f o r the various types of in-

surance, one has t o gather statistical material. O f course w e are
only able t o do so f o r periods in the past; one of the fundamental
problems is t o predict the future development of these data.

Data are accumulated either by observing the entire population

(as is often the case in life insurance: the mortality table) o r by
using the material of (joint) insurance companies (often done f o r
o t h e r types of insurance).

The outcome is no more than a mere average. If w e confine our-

selves f o r a m o m e n t t o life insurance: the mortality risk f o r a 40-
year oíd is 0.00174.

This is derived by dividing the number of 40-year olds that died

(d40). It is a deterministic frequency in the meaning as defined by
Laplace. W e can do this f o r each age, thus forming a mortality ta-
ble. The mortality table enables us t o calcúlate what the average
life expectancy of a forty-year oíd is. W e find this t o be 35.8
years, which follows f r o m

e ° = 1/2 + 04, + l42 + + lw)/l4o

This quantity is also an entirely deterministic one,

Obviously n o t every 40-year oíd will have this life expectancy.

Some will have a s h o r t e r life expectancy and others a longer
300 one. O n the basis of the constructed mortality table w e can
compute h o w many forty-year olds have a life expectancy of
one year, of t w o years and so on. This results in the following
picture:

0,04 T
0,035 --
0,03 --
0,025 --
0,02 --
0,015 --
0,01 --
0,005 "

11 16 21 26 31 36 41 46 51 56 61 66

1 6 11 16 21 26 31 36 41

lllustration I

0,04 T
0,035 --
0,03 --
0,025 --

0,015 --
0,01 --
0,005 --

lllustration 2
Such lines can be drawn up for any age. They are not identical f o r 301
each age, they change gradually. This is shown in the graph above
(lllustration 2).

The same applies of other types of Insurance; here was also first
(looking at disabilitytables, tables of medical costs, etc.) a similar
breakdown for each age bracket.

W h a t does the insurer do with such a breakdown and why does

he n o t confine himself t o the average valué? This average will
surely w o r k out if the group is large enough. It is th law of large
numbers.

The insurer is faced with t w o problems in this context:

a) If there are t o o many applicants f r o m the 'left' part of the

distribution, the insurer is faces w i t h t o o many risks which
have an unfavourable impact on the average. The company
cannot sustain the average premium and the result is an un-
favourable position in the market; higher premiums in t u r n
make it difficult t o attract new candidates for insurance policies.

b) The insured himself may know (or possibly anticípate) that

he belongs t o the 'lefthand side' of the distribution; his risk is
a p o o r e r risk than the average. This may t e m p t him t o insure
m o r e than he had originally intended. If this is t r u e for life in-
surance (people taking out higher insurances) this could be
even worse f o r other types of insurance in particular when
the insured can influence the declaration of his disablement
o r illness.

The insurance company must guard itself against such cases,

both in the interest of its competitive position in the market and
in the interest of its o t h e r clients w h o will have t o pay f o r the
extra burden. The insurer has t o make sure that it possesses the
same amount of Information as the client does (=equality of In-
formation).

This is achieved by examining the health of candidates. This is

done w i t h the aid of a health questionnaire which is filled o u t by
the applicant.

Occasionally the answers warrant a physical examination; a phys-

ical examination is always required when large insured amounts
are involved.

This following sketch indicates h o w the company gets the Infor-

mation:
302
RISK 1 RISK2 RISK 3 RISK N

/
statistical information mortality individual basis for
information premium
table or any other table Risk2 Risk2

Flnally the premium may be (sllghtly) adjusted due t o competitive

influences of the free market.

The outcome of the individual information, the medical examina-

r o n (or questionnaire) defines together w i t h the statistical infor-
mation (the mortality table o r so on) the risk.

W h y individual information?

Because it is very easy t o w h t e a health Insurance when the am-

bulance is coming around the córner of the street, o r t o w h t e a
life Insurance just before death is knocked on the door.

A b o u t the particular risk we can distinguished as follows:

- unavoidable.

- difficult t o avoid, and

- avoidable.

o r translated :

1. Unavoidable are inherent circumstances. Some people by na-

t u r e are in better shape than others.

2. Difficult t o avoid are external influences, f o r instance the

place where one lives (air pollution) o r w o r k s (handling cer-
tain substances, etc.)

3. Avoidable are behavioural circumstances such as smoking, al-

cohol consumption, etc.

Insurers cannot take this approach into account, because they

have t o set a reasonable and fair premium. O f course they will
do what they can t o attract as many applicants as possible; it is
their business. In this respect changes have taken place. In the
past the companies w e r e inclined t o ask an additional premium
o r even t o decline the application/conditions, but gradually the
requirements have been set at the lowest level possible so as the 303
offer insurance t o a máximum number of people. This is the goal
of the insurance business.

Generally speaking it may be said that filling o u t a health ques-

tionnaire o r submitting oneself t o a physical examination pres-
ents few problems; even an unfavourable outcome w o n ' t be re-
garded negatively, because people understand t h e rationale
behind it.

Sometimes such a medical examination has an additional positive

effect f o r the applicant, that is if a specific disease of discovered
in an early stage. Naturally this may also have an unpleasant side,
namely if the person involved is c o n f r o n t e d w i t h a disturbing
finding.

W e already noted that the medical examination is just a picture

at a given moment. It is taken at the moment that the insurance
is taken out. The medical adviser tries t o link this t o the best
possible conclusión regarding the future. That future is different
in character for various types of insurance. Concerning whole life
insurance the medical adviser will have t o estimate the chance of
premature death; f o r disability insurance a prediction has t o be
made as t o the ability t o w o r k and this up t o a certain age. In
case of illness it is different again. Someone may cause high medi-
cal expenses and yet be able t o w o r k and live t o reach oíd age.

Usualiy the estimate by a medical adviser will be such that an ac-

tuary will transíate it into a higher mortality risk, higher proba-
bility of medical costs, etc.

The actuary assumes that any abnormality in question will lead

t o an increased risk f o r the entire life span of the insurance. If
w e project this on the picture of the distribution f o r each age
(lllustration 3), the calculation of the (increased) premium will
be done along the line (a).

In some cases, w e possess such extensive experience w i t h spe-

cific abnormalities (knowledge specially accumulated by reinsurers)
that a sepárate mortality line can be constructed f o r specific ab-
normalities. Generally the deviating line (a) will run a p p r o x i -
mately parallel t o the standard one.

Can one alter this situation?

If the person involved is convinced that the reason f o r his pre-

mium increase no longer exists and that his life expectation is
back t o normal, he will apply f o r a re-examination. Sometimes
304 Probability

Age
lllustration 3

Probability

Age
lllustration 4

this right has been agreed upon beforehand (e.g. after some
years) but sometimes it has not. If a re-examination is done and
the Ufe expectation is back t o normal, the relative mortality line
will bend towards the normal one (lllustration 4).

Should t h e health of the person involved f u r t h e r deteriórate,

even by his o w n fault (avoidable), this does n o t affect the pre-
Probability 305

Age

lllustration 5

mium setting. The same applies t o someone w h o starts at the

'right-hand side' of the distribution. Under the influence of bad
habits he may t u r n into a p o o r risk; his particular line will start t o
cross the normal one. Thls does not affect the premium either
(lllustration 5).

A n o t h e r problem arises: the Insurer tries t o set the premium as

fairly as possible; he does so in such a manner that the insured
do n o t have t o carry the burden of additional solidarity f o r each
other, an additional solidarity they never asked for. Yet careless-
ness and bad habits créate a degree of unwanted solidarity. That
rises the question whether a conscious deterioration of the state
of health Insurance the question arises whether others have t o
pay f o r the extra risk p.e. in connection with t o p sports). This
runs parallel w i t h common practice in general Insurance where
an increase in risk results in a new and higher premium.

So far the situation until recent times.

This picture has changed recently when insurers w e r e faced with

the phenomenon AIDS. Suddenly the mortality risk f o r certain
age brackets increased considerably. This made no difference f o r
those already insured, as w e have seen above, but it was a dif-
ferent story for new insurances.

Insurers, just like anybody else, have no experience in dealing with

AIDS, but it is assumed that those infected by the AIDS virus will
in due course develop AIDS and the consequences thereof.
306 AIDS will predominantly be classified in the category of avoidable
diseases; apart f r o m that w e can hardly speak of an uncertain
event any more when the mortality expectation is so evident as
with the AIDS disease.

The reaction of insurers was obvious: insurance companies start-

ing demanding an HlV-test prior t o the underwhting of (life o r
disability) insurance. Unlike in the past the society themselves
particípate in the decisión making process. It was argued that
such an investigation could be very damaging for the person in-
volved. Any negative outcome could be harmful; not only can it
deny access t o life o r other insurances, it could also ruin some-
ones chances of finding employment. Pressure groups opposing
compulsory HlV-testing have argued that the test is not infallible
and that developement of the disease as well as the transforma-
tion f r o m infection t o actual illness isn't thoroughly understood.
Moreover, antidotes may well be developed.

This evidently put the insurance industry in a quandary. O n one

side of the argument there is the public opinión opposed t o test-
ing yet on the other hand the companies must adhere t o sound
business management. In the Netherlands a solution was found in
the f o r m of a compulsory HlV-test f o r larger risks. The future
will show the extent of losses incurred by the insurance com-
panies.

Virtually at the same time the opportunities of genetic Informa-

tion emerged and more than a few people started t o link these
t w o events. There is no actual relationship: AIDS belongs t o the
category of practically avoidable diseases (so why should others
contribute t o the costs involved); genetic abnormalities are inevi-
table, they are built in genetically. Society focused on the similari-
ties between the t w o such as privacy, the confrontation w i t h un-
palatable facts, social consequences, etc.

W h y is genetic information interesting f r o m the insurers point of

view? As far as companies are concerned genetics are divisible in-
t o three subjects:

prenatal genetic genetic

diagnostics information manipulation

non - hereditary hereditary

W h a t is the importance of each of those parts?

Prenatal díagnostícs 307

This subject is the most developed of the three. It is of utmost

importance t o those involved. It is of less importance t o insurers.
Based on the assumption that these diagnostics provide us w i t h
an accurate prediction whether a child will be born with of w i t h -
o u t defects and if w e assume that the parents are entirely free t o
decide whether they want the child (in this scenario society ac-
cepts the coinciding high expenses) the consequences are as
follows:

If a decisión is made in favour of abortion, the coinciding ex-

penses will be paid by the healthinsurer. The other side of the
coin is that the medical expenses f o r an ailing child will in all
probability be many times higher. T o underwrite such costs in
health Insurance is appropriate, and of course morally accepted.

If the parents consciously decide t o accept all medical expenses

for the child that child will be born by the insurer. It seems fully
justified t o make the other policy holders contribute (solidarity),
because otherwise the free cholee of the parents is jeopardized.
This is what w e are seeing in the Netherlands and other euro-
pean countries. A n opposite situation we find in the U.S. where
parents come under pressure f o r abortion, while the child can-
not be insured. These prenatal diagnostics are not of practical
importance f o r life Insurance and disability Insurance; disabled
children have no purpose f o r such insurance.

Genetic ínformatíon

By far the most important part of genetics, for underwriters, is

the use of genetic Information. This Information becomes avail-
able during a person's lifetime. The importance is underlined by
the fact that insurance can only exist if the underwriter has suffi-
cient Information at his disposal. Genetic Information means ad-
ditional Information, obtained f r o m a genetic source.

First I would like t o mention that insurers already possess a cer-

tain amount of hereditary Information. The medical question-
naires include questions about illnesses of ancestors. The stardard
procedures allow us t o assess what the chances are that the per-
son in question will contract hereditary determined diseases. The
insurer is currently not entirely uninformed, although the Infor-
mation is rather rough. Therefore the question arises: does ge-
netic Information provide additional information?

The popular answer t o this question is that in time we will all re-
ceive a genetic C.D., a genetic portrait o r as we say in the Ne-
308 therlands a 'genetic passport', stating exactly which diseases we
will contract and what the chances are of developing such illness.
Barring accidents this knowledge enables us t o plot o u r course
through life. O f course people fear that insurers will use (or rat-
her abuse) this t o form an exact idea of the life expectations of
the person in question. Is this depressing picture of the future
correct?

Since it has been discovered that the genes are made up of D N A ,

are responsible f o r t h e heredity of certain diseases and t h a t
these genes are located in certain places of the chromosomes,
research has endeavoured t o analyze which genes are responsible
for which diseases and has tried t o pinpoint their exact location.

In depth exploration and analysis of the human gene is currently

u n d e r w a y . This huge task has only just begun and although
modern technology will enable us t o speed up the pace, w e must
realize that it will take quite some time before w e can map all
human genes.

Assuming that we succeed in mapping all human genes, we can

apply our knowledge t o any individual's genes. If w e w o u l d have
t o proceed w i t h present day technology such an examination will
prove t o be a cumbersome task, probably only useful in very spe-
cific situations. A so called 'genetic passport' therefore seems un-
likely, unless of course future technology would lend us a hand.

W h a t Information will be available?

T o begin w i t h we should make a distinction between diseases de-

pending on the number of defective genes involved:

a) Diseases caused by one defective gene, e.g. Huntington's

Chorea.

b) Diseases caused by a combination of defective genes; these

may be differentiated according t o the amount of genes in-
volved, i.e. involving 2 genes o r 3 genes etc. Very little is
known about these so called multi-factorial diseases.

Genetic examination w i t h respect t o disease depending on a sin-

gle defective gene will almost certainly provide relevant Informa-
tion. The outcome is that one will either develop the illness or
one won't. This of course seems t o be a sound conclusión, al-
though it may n o t be possible t o predict the onset and severity
of illness in time. W i t h such detailed Information on hand the un-
d e r w r i t e r can't possibly provide the Insurance this is contrast
w i t h the oíd situation w h e r e only heriditary Information was
avaiiable (this probably involves diseases that can't be insured 309
anyway, although - e x p e n s i v e - solutions have been found in a lim-
ited number of cases). In the new situation it is an acceptable risk
or an unacceptable risk.

W h e n m o r e than one defective gene is involved, the case be-

comes rather complicated. It might be possible t o predict the
chance of illness as long as its occurrence depends on no m o r e
than t w o defective genes; Information concerning t h e p r o s -
pect of illness involving t h r e e o r m o r e genes, may be of very
little valué of the insurer. If f o r instance genetic examination
w e r e t o disclose t h a t the likelihood of a person's contracting
a disease w e r e 35% instead of 25% based on the subjects' pre-
vious records, than o u r overall knowledge hasn't notably in-
creased.

Therefore, f r o m an insurance point of view, one must seriously

question t h e relevance of I n f o r m a t i o n on múltiple defective
genes. Nevertheless it seems likely that in certain intances w e
can augment the accuracy of our risk assessments.

It is this aspect that public debate focuses on. The public is in-
clined t o believe that genetic Information is essential and that
such Information may lead t o m o r e accurate risk assessment
(higher premiums o r rejections) than is the case at present.
This in t u r n w o u l d lead t o all sorts of social consequences: it
may cause difficulties in finding e m p l o y m e n t , o r obtaining a
mortgage.

Based on this knowledge certain groups in society have urged that

genetic Information should be disclosed only t o the subjects
themselves and may only be applied for medical purposes. This
movement regards genetic Information as particularly privacy-sen-
sitive; it is their conviction that a person can never be forced t o
particípate in genetic testing, if the person does not want t o do so
(the right not t o know). Others content that this situation would
lead t o inequeal Information and thus have unacceptable conse-
quences w i t h respect t o solidarity. The situation would ultimately
cause disruption of the insurance industry. The champions of the
privacy aspect sometimes take an even bolder standpoint. As
noted before, they are apprehensive of the idea that insurance
may be refused and are w o r r i e d about the social consequences.
O n the other hand they are well aware that t o o much privacy is
the key t o misuse (inequality of Information enables subjects t o
take advantage of the situation at the expense of others).

Proponents argüe that insurers should be prohibited t o gather

any data at all whenever essential forms of insurance are c o n -
310 c e r n e d . These f o r m s of insurance o u g h t t o be available t o
everybody regardless of circumstances. The t r o u b l e w i t h this
idea lies in the fact that only politicians can decided on w h a t
forms of insurance are essential o r not; this in t u r n will créate
an undersirable situation (it may o b s t r u c t the c o r r e c t calcula-
r o n of premiums due t o influences f r o m undesirable elements
of solidarity, p.e. waiting t o take a life insurance just before
death).

Besides, t h e r e is a w i d e degree of variation between various

types of insurance which w e must take into consideraron. W i t h
regard t o health insurance the idea seems reasonable (it is in fact
often the case): health insurance is practically essential (in view of
the high costs hardly anyone can afford n o t t o be insured), and it
is practically impossible t o influence the payments (claims). Here
again a remark on the U.S. situation, where some 15% of the pop-
ulation is not insured for health care costs. However if w e take
life insurance o r disability insurance into account, the case be-
comes different. Here the extent of indemnification (the amount
of money) has been agreed on beforehand; f u r t h e r m o r e n o t
everybody needs t o be insured (doesn't even want t o be insured).
Fraud is likely t o occur much more often if insurers are obliged
t o underwrite all risks whilst the client have no actual obligation
t o take o u t insurance.

Equality of information is the obvious goal of insurers, except

when it is unnecessary (as in health insurance). This means that
an applicant must surrender all information he o r she has ac-
quired with regard t o genetic examination t o the underwriter,
yet that the underwriter may not seek t o iniate compulsory ge-
netic examination.

It is here that I wish t o speak of another aspect. It is not unlikely

that illness will become manifest, w h e r e genetic factors are t o
blame in conjunction w i t h certain negative habits (for instance
living o r nuthtional factors). As I said earlier, changes in the indi-
vidual^ living habits do n o t influence the premium that the indi-
vidual is paying f o r his policy. This observation usually pertains
t o changes f o r the worse.

W e may now see the reverse. Knowledge of your genetically de-

termined susceptibility may p r o m p t you t o change your way of
living. Today smokers aren't entirely sure that smoking is harmful
(apart from the rule of the thumb: smoking is bad f o r your health)
because the smoker is unaware of his o r her (potential) geneti-
cally determined susceptibility t o lungcancer. If the person in
question is aware of a high degree of susceptibility t o lungcancer
then one can ask: shall he o r she continué t o smoke? This of
course raises the opposite question: w i l l a n o n - s m o k e r w h o 3I I
learns of his low genetic susceptibility t o lungcancer, decide t o
start smoking?

The answer t o the next question is essential: given that people

have knowledge of certain genetic information, will they adjust
their way of living accordingly? And that is of major importance
t o the insurer. T o o much attention has focused on claims con-
cerning whole life Insurance (whereby premature death is a dis-
advantage t o the insurer), yet the vast majority of insurance poli-
cies concerns oíd age pensions (i.e. long life risks). If people start
t o adjust their way of living in accordance with their genetic in-
formation, then we must not overlook that people will be aiming
t o increase their average age, which in t u r n has severe financial
consequences f o r pensions.

A longer lifespan induced in this manner should be welcomed

and it seems evident that all forthcoming costs should be paid
for. Again the question arises: w h o is going t o pay, how far can
solidarity be stretched and should w e occasionally adjust pre-
miums accordingly? If behaviour is of such importance, the ques-
tion arises whether o r not the right premium may (must) also be
adjusted during the t e r m of the insurance.

Finally, a few words on genetic manipulation; this subject remind

us of a science fiction-like w o r l d . The political forefront should
stay on the alert. Still, we must make a few distinctions.

Suppose one has a defective gene, w h i c h in t i m e is likely t o

cause illness, and this defect can be 'mended'. Possibilities of
such repair are of the utmost importance t o the person in question,
because it will relieve the person of the disease and its conse-
quences.

Here w e must stress t w o aspects: such 'repair' can be costiy,

costs which will have t o be reimbursed by the health insurer.
This seems quite justified, just as the resulting solidarity. The risk
of disability will decline, thus causing the p r o d u c t t o become
cheaper, which of course must be recommended. As far as life
insurance is concerned: the repair case will prolong a person's
lifespan, and this of course had consequences f o r oíd age pen-
sions. A development we pointed o u t earlier on.

W h a t remains t o be discussed is the genetic manipulation w i t h

distinct hereditary components ('tampering with genes'). W h e t h -
er o r not this is of any consequence f o r underwriters cannot
n o w be determined. Right n o w it looks more like a social and
political problem.
312 In conclusión we can state:

It is highly doubtful whether genetic ¡nformation will be of any

use t o insurers.

Should genetic ¡nformation prove t o be of valué, then w e must

maintain the principie of equality of Information, except f o r types
of Insurance that the entire population depends upon and where
fraud is practically impossible, as is the case In health Insurance.
The insurers will not Inltiate compulsory gentic examinatlon.

Should genetic Information prove t o be of importance, then we

must realise that people will adjust their way of living accordingly.
N o t only will this Influence the Insurance industry, but it will also
influence many others (e.g. food industry).

Both the opportunities of prenatal diagnostics and the 'mending'

of genes should be recommended, although we must give serious
thought t o the consequences.

All in all it is not impossible that genetic research will pave the
way t o a better health future, regardless of the controversy sur-
rounding hereditary genetic manipulation.

Finally some impressions on the situation about this topics in

severa! countries.

Practically in all countries it Is n o w more o r less under discus-

sion. Mostly there Is a tendency t o keep genetic Information con-
fidential f o r the person itself only. The argument: misuse by in-
surers, employers and so on.

First a remark about confidentiality. Confidentiality is primerly

preferred by people w i t h a bad genetic portralt. It is the same as
asklng f o r solidarity, which is also only preferred by the receiving
party. But it is not only confidentiality, it is what people are doing
with their genetic knowledge. W h e n he o r she has a good por-
tralt, will he o r she t r y t o get a good job o r t o buy a low-priced
Insurance?

A b o u t the misuse t w o important remarks should be made:

1. In this argumentaron no distinction Is made between mono-

genetic and multifactorial deseases, while the Information is
totally different: monogenetic (practically) yes o r no, multi-
factorial: a probability (at most).

2. N o distinction is made between several different types of in-

surances, o r other uses such as by employers.
In the U.S. w e k n o w the proposals of the Human Genome Pri- 3I3
vacy Act, which gives individuáis the right t o privacy on genetic
information. Also no information t o insurers, e m p b y e r s , etc.
Congressional hearings will begin next spring.

In full contrast w i t h this proposals w e find in Germany a proposal

f o r law that contains exactly my opinión, w i t h the addition that
there is no obligation on information f o r health Insurance.
 315

THE HUMAN CENOME PROJECT

AND LABOUR RELATIONS

Tomos Sala

Faculty of Law, University of Valencia,

Valencia (Spain)

ABSTRACT

Undoubtendly, knowledge o f the H u m a n Genome

can /nf/uence the world o f work i f it provides infor-
mation on the tendency to develop diseases in a cer-
tain environment or on the individual's aptitude for
work, to give a few exampies. The use o f this type o f
genetic information m a y iead to iegai probiems i f
one considers who is the beneficiary o f the informa-
t i o n . H o w e v e r , anaiysis o f t h e H u m a n Genome
wouid not be the only cause for this type o f prob-
iems. A t present, there is a c o m p a n y policy t h a t
controls occess o f a w o r k e r to the c o m p a n y by
means o f physical and psychologicaí tests, the State
itself makes use o f these tactics for certain w o r k
activities.
1. The analysis and evaluation of the incidence of the genome 3I 7
project f o r labor relations has t o be based on the current
status of scientific research and, at most, on scientific hypo-
thesis that are likely t o be attalned wlthin the near future.

2. Quantitatively, human genome knowledge offers little infor-

mation of actual relevance f o r labor relations. It's likely that
genomic analysis may provide in the future more relevant in-
f o r m a t i o n (for example, tendency f o r develop diseases by
exposure t o the enviroment, sterility in w o m e n o r genetic
markers associated w i t h w o r k i n g aptitudes o r ineptitudes).

This information, certainly, might be important t o select new

w o r k e r s or, later, t o move the w o r k e r geographically o r
functionally within the company.

3. I will not consider here the labor consequences of genetic

manipulation, because this aspect exceeds the labor-juridical
área, falling in the realm o r ethics and politics.

4. The main legal problem that the genome may pose in the fu-
t u r e labor relations is, doubtless, that of possible use of the
information provided. By hypothesis, the information derived
f r o m the genome may be used in the benefit of the w o r k e r ,
his owner; in the benefit of other w o r k e r s and t h i r d parties
outside the company; in the benefit of the comapny itself;
and in the benefit of the general interest of the State. So,
there would be four potential interests playing its role.

5. The w o r k e r might use this i n f o r m a t i o n f o r professional

orientation, as a m e r i t f o r being selected f o r a job o r f o r
promotions, and t o avoid certains changes in the place o r
function of his job.

O t h e r w o r k e r s and t h i r d parties might use this information

t o avoid risks derived f r o m the actions of somebody poten-
tially incompetent of dangerous. The company might use this
information t o justify discriminations in selecting w o r k e r s o r
in assigning them certains tasks.

Finally, the State might us this information in the interest of

health preventive protection.

6. Some of these interests can become rights w i t h o u t major

problems. This is the case w i t h the interest of the w o r k e r t o
use genomic information t o heip him t o choose and find a
job.

But, even in this case, some problems could appear as de-

rived f r o m the fact that voluntary allegations as a merit f o r
being selected f o r a job o r f o r promotion might suppose a
factual and indirect pressure f o r those others w h o w o u l d n ' t
318 t o adduce it because of its negative effect f o r them, as they
w o u l d probably be rejected by the company in use of its
contractual freedom.

However. I don't think that this simple fact will in the future
determine a prohibition f o r those w o r k e r s w h o voluntarily
want t o use the genomic Information in their o w n interest.

7. Nevertheless, other interests may pose greater problems t o

become rights. This is the case in the interest f o r health of
o t h e r w o r k e r s and t h i r d parties "versus" the interests f o r
privacy, t o w o r k and non-discrimination of the w o r k e r .

Doubtless, the Information derived f r o m the genome -as the

Information derived f r o m any other way (the clinical history,
f o r example)-, is within the ambit of the basic right t o privacy
of the w o r k e r and, so, it is necessary t o respect it.

Although no right is absolute o r illimited, the potential o r

tendential character of the Information derived f r o m the ge-
nome appears, in my opinión, not t o be sufficiently solid t o
limit the basic rights of the person.

In fact, it's w o r t h mentioning that the Information about the

tendencies t o develop diseases by exposure t o the environ-
ment o r w o r k i n g aptitudes o r ineptitudes provided by ge-
nome in the future will be always potential o r tendential. So
that w o r k i n g aptitudes o r ineptitudes must be shown after
an apprenticeship and the w o r k i n g experience; and the dis-
eases w i t h the monogenetic exception, can develop o r not in
contact w i t h some environment circumstances.

8. The legal recognition of the interest of the company encoun-

t e r s similar problems of conflict w i t h basic rights of t h e
worker.

The company could adduce reasons of productivity t o con-

tract the best w o r k e r in o r d e r t o justify the w o r k e r exigence
of a genomic Information in the contract m o m e n t o r later
on.

C e r t a i n l y , in a d e m o c r a t i c society, t h e c o m p a n y p o w e r
brings about necessarily some limits, as the respect t o he hu-
man basic rights and, among them, the right t o privacy and
the right of non-discrimination by intímate known facts.

Thus, I don't think that the simple managerial interest t o the

best contract could justify by itself the intromission in the
w o r k e r privacy asklng f o r a genomic analysis.

Nowadays, however, there are several managerial practices

in o r d e r t o clalm, before the contract, some controls and
 physical and psychological tests t o check the conditions and 3 I9
aptitudes of the candidates t o w o r k .

In my opinión, the legal answer could be this: n o t every

managerial practices are legal f r o m the point of view of the
human basic rights. It's necessary a reasonable relation be-
t w e e n t h e I n f o r m a t i o n claimed and the task t o do. For
example, it w o u l d be legal a visual control of lorry-driver o r
t h e w h o l e physical c o n t r o l of a f o o t b a l l - p l a y e r s b u t it
w o u l d n ' t be legal the exigence of some Information about
the sexual Ufe of a miner candidate.

In this way, could be justified certains exigences of Informa-

t i o n about genetic aptitudes; perhaps, but m o r e difficult,
about the tendencies t o develop diseases; but, absolutely,
not about the women's sterility.

9. Finally, the legal recognition of the interest of the State in

the benefit of health necessarily represents an injury t o the
rights of the w o r k e r , which are therefore "colonized" -as it
is said- by the State.

Nowadays, the State stablishes the physical and psychological

conditions of the w o r k e r for certains jobs (nuclear energy
w o r k e r s , f o r example)

The use of Information derived from the genome w o u l d not

be, therefore, a qualitative policy change, but only a further
scientific refinement in the Instruments of c o n t r o l .

10. In sum, t w o conceptions o r positions of law policy w i l l

likely be confronted: I) The first: the genome is entirely prí-
vate and can oly be used for self-benefit. 2) The second: the
Information derived f r o m the genome belongs t o the col-
lectivity and may be used for the collectivity benefit.

T h e r e is no d o u b t t h a t intermedíate positions will likely

domínate in the future, rendering possible the reasonable
use of genomic Information In the Interest of the company,
In the interest of thírd partíes and ín the general Interest
represented by the State. Relativíty is the conclussion.

Thank you
ETHICAL ASPECTS
DERIVED FROM
COMMERCIAL
APPLICATIONS
 323

THE COMMERCIAL ASPECT

OF DIAGNOSTIC TESTING

He/en Donis-Keller

Dept. of Genetics, Washington University Medical School,

St. Louis, Missouri (USA)

ABSTRACT

Clinical diagnosis uses, amongst others, two types o f

tests: linkage tests for congenital disorders and A D N
diagnostic tests to determine propensity to illness.
The former study the genes o f the illness a n d there
are currently any norms for carrying out these tests.
Bes/des, they give rise to errors on account o f the ar-
der a n d distance o f the genetic markers with respect
to the gene o f the illness.
This cartoon depicts at least what some people might think is the 325
ultímate in commercial diagnostics. This wiil probably horrify
some of you, but why? First of all, at least for the Americans in the
audience, I think there is a basic distrust in the US of Corporate
America. Secondly, this cartoon implies that there is no physician
interface between the patient and the diagnosis. Then third and
perhaps most important: h o w feasible is it t o do any of the tests
that are shown here on the sign?

Today, our focus is on the commercial applications of diagnostic

testing; but one point I would like t o make t o you is that testing
that is university based o r commercially based does not differ in
the ethical considerations. I do not believe that university-based
testing is inherently m o r e ethical. The p r o f i t motive in some
cases is replaced by the priority motive, and in some cases in the
commercial sector, there are m o r e safeguards in place, especially
w i t h regard t o quality control and the technical aspects of diag-
nostic testing.

The experience base f r o m which I speak t o you today is fairly

limited; this comes f r o m my experience of having w o r k e d in uni-
versities and having w o r k e d in a small start-up bitotechnology
company, f r o m 1986 t o 1989, on diagnostic testing. I w o r k e d on
basic research f o r the other period of time that I was w i t h this
company, which was a total period of 7 years.

This small biotech company decided t o introduce predictive tests

f o r cystic fibrosis, adult polycystic kidney disease, neurofibroma-
tosis and a few other disorders. My responsibility at this com-
pany was t o develop a test and perform a number of research
case studies, and then t o oversee technology transfer, which
included reading all the test results f o r a year once they made
the technology transfer, t o the commercial reference laboratory.
The commercial reference laboratory was regulated by the State
of Massachusetts and fell under the clinical chemistry reference
laboratory controls and standards. W e had a board of scientific
advisers, we established guidelines, as well as a board of medical
experts.

W e established guidelines, that is criteria f o r diagnostic tests, and

also we made choices as t o which tests t o offer. One decisión
w e made early on was that w e would not perform diagnostic test-
ing f o r diseases if there was no M D referral; w e only w o r k e d
through genetic counsellors and through medical doctors. O n the
other hand, w e performed paternity tests f o r anyone w h o asked.

The purpose of the testing, the reason why we began w i t h adult

polycystic kidney disease and cystic fibrosis, which are actually
fairly rare inherited disorders, was not a profit motive, but rather
t o gain experience in the clinical testing arena, since this biotech-
nology company had no p r i o r experience, w i t h the long-terms
goal of testing f o r m o r e common disorders. I think my experi-
326
ence is probably typical of anyone w o r k i n g in a small biotech 327
startup company, and Jack McConne I think will give you the
perspective of someone w h o w o r k e d f o r a very large, well-estab-
lished company -Johnson & Johnson. So I w o u l d like t o review
first the types of diagnostic tests and then focus on one type of
test which w e implemented.

First of all, there are genetic linkage tests f o r inherited disorders;

in these tests we follow disease genes using genetic markers. W e
require at least one affected individual in a suitable family struc-
ture, and these are the tests that I will be talking about today.
There are direct tests, using D N A analysis, permutations that
are responsible f o r the disease; Norman Fost will focus on this
aspect f o r cystic fibrosis.

Then there are D N A screening tests f o r disease susceptibility.

The company I w o r k e d f o r decided n o t t o offer tests of this
type; these are population-based screening tests, and at the time
we w e r e considering them, there were tests that w e r e being of-
fered f o r atherosclerosis, emphysema, diabetes susceptibility, but
we made the decisión not t o offer these types of test.

Then there are D N A fingerprinting f o r gentyping tests, that are

applied f o r forensics purposes and parentage testing. The com-
pany I w o r k e d f o r decided not t o get into the business of perfor-
ming these tests f o r forensic purposes, mainly because the FBI
entered the testing área and had decided themselves t o set up
testing f o r forensic purposes. So our company supplied the re-
agents f o r the FBI in o r d e r t o perform these tests. There are
several people in the audience w h o I think have much more expe-
rience with this type of testing - D o n Rufo and Eric Lander perhaps
will offer some comments at the end.

There are ethical concerns of course w i t h this type of testing;

one is the source of e r r o r in the tests, and the interpretaron of
results. I am sure you are all aware of the unscrupulous compa-
nies w h o by ineptitude, or simply iying, have really darkened the
ñame of D N A testing. And of course, one of the main problems
is o u r judicial system and not so much the e r r o r rate in these
tests, because it is based on winning and not on getting at the
t r u t h ; the major objective of defence and prosecution is t o dis-
credit expert witnesses, and I guess we should not forget that
we are participants in this, willing o r unwilling.

Here are the issues t o consider. W h a t are the criteria f o r high

quality diagnostic tests? A n d the main point I want t o make is
that determinaron of a high-quality diagnostic test is in itself an
ethical consideraron, which I think is not being addressed in the
academic o r commercial communities today with regard t o D N A
testing. There are no uniform standards that have been estab-
lished in any f o r m f o r the linkage based tests I will be discussing.
328 Secondly, quality c o n t r o l ; there are a lot of labs offering tests.
There have been some attempts t o set up standards in the c o m -
mercial sector, but there has been no agreement on, f o r example
proficiency testing.

A t h i r d point is record-keeping, and this has several dimensions.

First of all, sample-tracking. The samples that are obtained f o r
these tests are often and almost always obtained at some dis-
tance by people not employed by the company o r the universitiy,
then the samples are sent t o where the test performance is done.
This is probably the main source of errors that occur; sample
mix-ups, sample mislabeling at the point, f o r example, where the
blood is being drawn. But the questions are how do w e track the
samples? By ñame? By number? Every lab has a different way of
tracking the samples. And secondly, how long should records be
kept? This is an issue we never resolved at the company where I
w o r k e d ; w e just kept the records and t h o u g h t at some later
point in time w e w o u l d decide when t o destroy the records. A n d
another aspect of this is storage of the sample; invahably there
was D N A left over after the analysis was done. W a s it our res-
ponsibility t o save that sample, t o send it back t o the originator?
Again, this was unresolved.

Then the t h i r d aspect is, h o w public does one become w i t h the

number and types of tests that are performed? In o u r company it
was decided that we would not make public the number of tests
that w e performed f o r any given disorder, because w e did n o t
want o u r competitors t o k n o w how badly w e were doing.

Then there is the communication of results. T o w h o m are the

results given, and in what form? W e had a w r i t t e n r e p o r t f o r m
which w e agonised over in terms of how easy it w o u l d be t o un-
derstand what the risk assessment was, h o w much Information
could w e give out, what was our liability situation. W e often gave
results o u t over the telephone t o genetic counsellors. I t h i n k
were naive initially, f o r example if we t o l d them it w o u l d take
about t w o weeks t o get the results back (this was using a Shout-
hern-based assay) exactly 14 days f r o m the later, cali expect-
ing the result because the patient expected it. W e l l , invariably
things w e n t w r o n g in the lab, w e had t o repeat assays; and so w e
found ourselves in a very difficult situation.

One thing w e also did not do was verify that the caller should
have the Information; it w o u l d have been very easy f o r patients
t o pretend t o be the doctor o r counsellor and get the Informa-
tion themselves. It ended up not being a problem f o r us, but I can
see that it w o u l d have been, perhaps.

A n d there is the issue of timeliness. O u r technicians w e r e not

paid t o w o r k weekends because of the cost; often w e w o u l d get
samples in f o r an amniocentesis in which time was very much an
element.
Then the most sensitive issue probably: the cost and profit, and 329
w h o w o u l d pay f o r testing. I guess often in universities one does
not consider the cost of the development of the diagnostic test,
and the regulatory costs that are involved as well. In the cases
that I was involved In, there was no profit; w e w e r e n ' t even t r y -
ing t o break even. He w e r e simply trying t o introduce the test.
But it may interest you t o k n o w the company that I w o r k e d f o r
considered it unethical that many universities w e r e offering the
test f o r free, which really meant that they w e r e seen as compe-
tí tors and really compromised the ability of small companies t o
get into the business.

W h o can o r should be tested? This was always left t o the deter-

mination of a physician. In the case of linkage tests, of course,
one has t o have an appropriate family structure, and w e sug-
gested t o genetic counsellors and physicians w h a t t h e struc-
t u r e should be. W h o has access t o Information?

... A n d the next point I think is a more serious ethical one. Often
new Information was developed as a result of the test that had
n o t been sought by the originating individuáis at risk o r t h e i r
families. For example w e had a test come in f o r adult polycystic
kidney disease. The lab technician received the samples and pro-
cessed them and by the time the analysis got t o me, what had
happened was that a number of people w h o w e r e at risk, w h o
w e r e n o t requesting Information, had been tested and w e had
the result. W e knew in some cases that people w o u l d be pre-
dicted t o be affected; in this case w e simply turned the Informa-
t i o n over t o the physician; it was an honest mistake, they just
sent in bloodsamples f r o m everyone that came in that day f r o m
that family.

In another case w e sent out an amniocentesis sample and a kar-

yotype was done; this was standard practice by this secondary
lab that w e sent this sample t o , but no-one thought t o ask the
pregnant w o m e n whether o r n o t she wanted it done. W h a t if w e
had found o u t something f r o m having looked at those c h r o m o -
somes?

Then in another case, w e w e r e doing cystic fibrosis diagnosis,

and it became obvious that there was a parentage problem. This
was a very late analysis that was done as an amniocentesis. W e
only had a few days t o return the result, and I noticed the stated
father was probably n o t the father. I communicated w i t h the ge-
netic counsellor and asked f o r a unblood sample f r o m the father.
W e l l , as it turned out, the woman swore that the father was as
stated. Tested a few more probes and verified, t o our satisfac-
t i o n , that the stated father was not the father. So the only result
w e could give was that it unlikely that this foetus was affected.

A n d as I mentioned earlier, participation on family members is

an i m p o r t a n t c o n s i d e r a r o n in linkage-based tests. A n d at this
330 point I w o u l d like t o emphasize the importance of the physi-
cian's attitude. For example, in the case of plycystic kidney dis-
ease, the nephrologists w e r e very much opposed t o genetic
testing - t h e y w e r e n o t educated about t h e valué of genetic
t e s t i n g - and in fact t h e y w e r e v e r y p r o u d of t h e i r surgical
i n t e r v e n t i o n procedures and t h o u g h t t h e r e was no need f o r
genetic testing. W e also found, interestingly enough, that in the
case of adult polycystic kidney disease parents w e r e always w i l -
ling t o particípate. They considered themselves responsible f o r
t h e i r offspring and w e r e very willing t o particípate in the tests
and w e r e very willing kidney donors. O n the o t h e r side, there
is sometimes coerción of the family members t o particípate in
the test.

Fínally, which tests should be offered? For our company there

w e r e s t r o n g e c o n o m í c consideratíons w h e n w e considered
which tests we might w o r k on. Should every company be com-
mítted t o offer all avaílable diagnostic tests? It is very hard t o ac-
quire experience and maintain competence while offering a large
number of tests.

I would like t o move then t o linkage-based tests, t o make my

point again that the quality of the diagnostic tests is an ethical
issue.

W i t h linkage-based tests one uses markers t o foliow the disease

gene. So you can see t h e prediction of affected abnormal o r
carrier status of the affected individual, necessary f o r the perfor-
mance of the test f o r the at-risk individual shown as the question
mark. N o w the only problem w i t h this of course is that there is
recombination as chromosomes are passed on f r o m parent t o
offspring, and you can see here the result: the child at the bot-
t o m has a recombinant chromosome. This is the source of the
inherent e r r o r rate in diagnostic tests of this type, and it just
shows you the result one w o u l d have if one used only one mark-
er on one side of the disease locus. You w o u l d make the w r o n g
prediction, the w r o n g diagnosis, based on following the inheritan-
ce of the marker: you w o u l d n o t have seen the recombinant
events.

The second issue that is very important for linkage-based tests is

informativeness.

The quality of diagnostic testing f o r this type of test depends on

the informativeness of the markers and the genetic distance of
the marker, f r o m the disease locus, because the frequency of re-
combination is related t o h o w cióse the marker is t o the disease
gene.

Sources of e r r o r , then, in the linkage tests are, first of all, incor-

rect marker o r d e r and distances: on assumes for the calculations
t o make a risk assessment, a particular o r d e r of markers w i t h
r e s p e c t t o t h e disease g e n e , and d i s t a n c e s o f t h e c r o s s - 331
overs, which is why markers on both sides of the disease gene
are very important. A n d then of course undetected genetic het-
erogeneity: for so many of these disorders there is the possibility
that different genes on different chromosomes can independently
give the same phenotype. O n e has t o ensure that sufficient test-
ing f o r genetic heterogeneity in the population has been done:
and then of course there are D N A artifacts; when one does a
[Southern-based] test, whether o r not the D N A has been digest-
ed on c o m p l e t i o n is critical. Contamlnation of o t h e r samples
w i t h the genomic D N A of the individual being tested, and in the
case of PCR detection, amplificaron artefacts can be prevalent.
Then of course sample mix-up, which I think is a major source of
e r r o r in testing, and as I m e n t i o n e d before, paternity n o t as
state d.

These are my criteria f o r a high-quality test: First it is very im-

p o r t a n t t h a t t h e markers be very cióse t o t h e disease gene,
(within a few per cent recombination) and that the markers flank
the disease locus that crossovers can be detected. That leaves
the possibility of a double crossover, which is a very rare event.
Second, the markers must be highly informative, o t h e r w i s e I
think you are really deceiving the people f o r w h o m you say you
are providing testing. If in only 30% of cases you give back unambi-
guous answers, the test is hardíy w o r t h doing. A n then again, rea-
sonably rapid test performance and communication results are
important: people expect t o get the answer back the next day.
Genetic heterogeneity studies, as I mentioned: and tolerating
only a low e r r o r rate in these types of tests are also important
¡ssues.

I have raised some of the ethical considerations that are present

in all of these types of diagnostic tests, and the underlying theme,
is that there are no uniform standards that have yet been estab-
lished. O n e can always say that competition, at least in a free
society, provides the best service; the best tests will naturally
come forward because there will be competition f o r them. But
that is not always the case. Someone can do better marketing
and there is a lot of trust in medical doctors, and that should not
be understated.
 333

BIOTECHNOLOGY

E/ad/o Montoya

Technical Dept. of the Quality of Life and Natural Resources,

General Secretariat f o r National Plan I + B, Madrid (Spain)

ABSTRACT

M o n ' s struggíe against nature has given a n d is giving

as a result the accumulatíon o f toxic producís with
h a r m f u i effects, not oniy from the ecológica! but also
the genetic point o f view, for these agents are able
to bring about genic disorders. The development o f
medicine during this century, apart from its benefi-
cial effects, also entails a negative effect on h u m a n
natural selection, in this sense, there has been an in-
crease in the number o f people who are bearers o f
transmissible genetic disorders. Biotechnology, con-
sidered as the third great technological revolution o f
this century, offers solutions to genetic disorders a n d
environmental problems. However, with the use o f
producís, biotechnology is n o t e x e m p t f r o m p r o b -
lems i f it encourages a social imbalance between dif-
ferent countries.
Since man started agriculture, fighting against nature has been a 335
continuous task f o r humankind. This struggle has had deleterious
effects on natural evolution, not only f r o m a general ecological
polnt of view, but also because of the accumulation of noxious
agents, specially after Industrialization. This, together w l t h other
natural factors creating human diversity, has lead t o the accumu-
lation of products that can induce genetic disorders. In the pres-
ent century the t r e m e n d o u s development of medicine, which
beneficial effects are beyond of doubt, has also had a negative ef-
fect upon the natural selection of humans, and therefore more
and more people carrying transmissible diseases are n o w able t o
have descendants. Biotechnology is contributing t o the right of all
human beings t o health, t o have descendents, and a new era has
opened this year w i t h the possibility of performing somatic cells
gene therapy. Antisense RNAs and ribozymes are also n o w con-
sidered as potencial therapeutic agents against viral, neoplasic o r
genetic diseases. O n the other hand Biotechnology is also offer-
ing solutions t o environmental problems by the use of selected
microorganisms o r genetically manipulated ones which, f o r in-
stance, degrade toxic products, accumulate heavy metáis o r pro-
duce biodegradable polymers. Biotechnology is being considered
the third great technological revolution of this century, after nu-
clear energy and the technologies of Information and communi-
cation. In W e s t e r n countries, Biotechnology is supposed t o have
applications t o sectors representing almost a 20% of the gross
national incomes.

In opposition w i t h nuclear energy, technologies of Information

and communication and biotechnology have a better acceptance
by the public opinión, exception made of those groups which pro-
mote a " r e t u r n t o nature". This acceptance, moves between the
hopes and the fears, and depends mostly upon the individual be-
nefits that biotechnology is offering, specially concerning health.
N e v e r t h e l e s s , B i o t e c h n o l o g y , like o t h e r technologies is n o t
exempt of problems related t o the use of its products. Issues
concerning the delivery of genetically engineered organisms, pa-
tent protection of these organisms and social disequilibrium that
these new technologies can p r o m o t e between countries, are
probably the most important aspects of the social ethics of the
new biotechnology.

Here I am going t o address only t w o of these Items, nameiy, in-

creasing differences between developed and underdeveloped
countries and safety.

I. In underdeveloped countries Biotechnology has social and

e c o n o m i c p o s i t i v e efects, i m p r o v i n g t h e p r o d u c t i o n o f
crops, fuels, f o o d like milk, o r providing vaccines against
endemic diseases. Negative implications of biotechnology
are the increase of the economic gap between N o r t h and
South, due t o the difficulties t o develop these technologies
by developing countries w i c h of course will increase t h e
336 debt in these countries. The figures will be aproximately the
same f o r the knowledge of the Human Genome. Does this
means t h a t w e shold s t o p increasing o u r k n o w l e d g e t o
avoid t o magnify these differences? O f course not. I w o u l d
like t o bring here the recent w o r d s of D r . Mangwende, Min-
ister of Lands, Agriculture and Ru al Settlement of Zimbawe
a d d r e s s i n g t h i s s u b j e c t : " I t is t o t a l l y naive and in fact
f o o l h a r d y f o r anyone t h a t w e should stop t h e w h e e l of
technological innovations because the outputs might adverse-
ly effect a group of people". It has been said many times
that because of its very nature, information resulting f r o m
the Human Genome analysis should be in the public domain.
As far as I k n o w n this was one of the points of the so called
Valencia Declaration on the Human Genome Project, t w o
years ago. This expresses the generosity that the scientific
family has always shown. The problem does n o t lie in the
knowledge of h o w genes are all put together o r which is
the base sequence in these genes, the problem is the tech-
nology that will be develop f o r and by the project. A m o n g
these new technologies, it is clear that informatics will be
i m p l e m e n t e d and new methods f o r sequencing and new
vectors f o r genetic therapy will be developed. These tech-
nologies will get applications t o the diagnostic and thera-
peutics of human diseases of different origin, including cán-
cer, and i n f e c t i o u s deseases, and t o many o t h e r
b i o t e c h n o l o g i c a l processes. A t t h e present, 18% o f t h e
pharmaceutical market depends on biotechnology. This in-
cludes of course antibiotics, and represents aproximately
30 billion dollars. From these m o r e than 400 million dollars
are products derived f r o m monoclonal antibodies. Actually
the market of D N A probes is still low, aproximately 19 mil-
lion $ but it is expected t o increase in 1992 t o 600 million
dollars. The Human Genome Project will therefore imple-
ment evolving biotechnologies which will be beneficial f o r
many productive sectors and f o r many countries. The trans-
national character of this project will, w i t h o u t doubt, bene-
fit t h e dissemination of knwoledge and t h e i r profits. The
transfer of these technologies should be done through the
cooperation. FAO, UNESCO, W H O , and the European C o m -
munity STD program are good examples of multilateral co-
operativo frameworks t h a t should be implemented in the
future, as well as bilateral assistance.

2. Safety. Until n o w D N A recombinant technology has been

proved t o be not only a safe technology but safer than pre-
vious ones. For instance endocrinologist can n o w treat child-
ren w i t h G r o w t h H o r m o n e w i t h o u t having the danger of
inoculating diseases, as it was the case of the human hormone.
Vaccines, like hepatitis B can be obtained w i t h o u t mani-
pularon of the virus. This safety is due t o a great extent, t o
the careful way in which researchers have dealt w i t h the
problem. The Berg letter, Asilomar conferences o r the N I H
guidelines, are good examples of the degree of responsability 337
undertaken concerning this topic. Seeing the problem ret-
rospectively, all this measures were perhaps excessive, and
in consequence they have been progressively modified. O n
the o t h e r hand they have had a negative impact on public
opinión, a fact that is very probably influencing negatively
other initiatives, but I think that at that moment they w e r e
necessary.

Safety has special importance when we are dealing w i t h spe-

cies. D o c t o r s frequently have t o take hercio decisions con-
cerning patients.These decisions affect the individual life, but
decisions concerning, f o r instance genetic manipulation of
plants, can affect the evolution of a whole specie, o r an ecol-
ogic system. Therefore genetic manipulations that affect en-
vironment are t o be undertaken carefully and studies of dis-
semination, propagation, e t c . . are needed, and biological
diversity should be mantained. This contrast w i t h the situa-
tion of gene therapy, where only individuáis are the object of
manipulation. Let us consider t h e m o s t compelling t o p i c
concerning gene therapy: germ line of embryo genetic ther-
apy. I am very sorry t o say that f o r me there is no an ethic
o r moral problem involved, but only a problem of uses and
safety. By n o w w e are used t o múltiple surgical procedures,
including grafts that increase life expectancy and quality of
life of people carrying severe diseases. Procedures that m o d -
ify the phenotype of individuáis are also continuously per-
formed and all these manipulations are well accepted by the
general public, although they are painful, and some of them
involve grafting of foreign organs and in some cases they are
life threatening. So, w h y are they accepted? Probably be-
cause their effects are predictible and immediate, because
they do n o t affect descendents and specially because they
can be easily understood. People consider genetic modifica-
tion as something mysterious that manipulates the very es-
sential nature of man and his destiny, instead of considering
it, when feasible, as a simple intervention f o r correcting the
errors of Nature. O f course this is not the moment t o per-
form such type of interventions, because in the present state
of knowledge the results may be impredictible, but we prob-
ably should not cióse the d o o r of terminal o r embryo ther-
apy f o r ever, and w e shall consider the actual prohibitions
in most legislations as a m o r a t o r i u m . Ethical problems will
then arrive, for example, the right t o patent vectors, which
in some way could be compared t o patent surgical procedures.
Fortunatedly, in the future probably there will be no need
f o r such manipulations, because very early diagnostic test of
embryo, like it has been already started, will avoid o t h e r
procedures.

I wish t o finish by quoting samebody w h o has dedicated a

great part of his life t o Bioethics, Prof. Edouard Boné:
338 "Does man have the right t o modify nature, t o claim t o cor-
rect o r t o improve it t o 'arrange' the D N A molecule, artifi-
cially créate new species, t o attempt t o change his o w n indi-
vidual o r specific identlty? ' D o e s n ' t N a t u r e k n o w best'?
Might there not be a limit beyond which we risk everything
getting o u t of control? A n d finally, do we demand that huma-
nity, after having manipulated, altered, and experimented
with everything in this w o r l d , stops in f r o n t of its o w n chro-
mosomes, feeling that by crossing this limit it w o u l d make it-
self gullty of some unaccepted violation?" T o this question,
says Father Boné, "I would think that we have a valid and ex-
plicit answer in our present understanding of scientific evo-
lution. Man, the thinking craftsman has as his privilege t o de-
code and c o m p r e h e n d reality, t o p u t his hand on w h a t
makes the w o r l d w o r k , t o take in hand the destiny and the
competion of the planet and t o exploit its resources...".

Thank you very much f o r your kind atention.

DIAGNOSTIC
POPULATION
 34

DIAGNOSTIC POPULATION
TESTING OF GENE CF

Norman Fost

Program in Medical Ethics,

University of Wisconsin Medical School

ABSTRACT

There ore ot present propasáis to carry out genetic

diagnostic population tests to detect beorers o f cystic
fibrosis.
In the outhor's opinión, almost none o f these propas-
áis follows widely consensed criterio ot the institu-
tional level, such as: adequate experimental design,
p r o o f o f efficiency, study o f toxicity a n d acceptability
o f costs. Therefore, these propasáis require more de-
tailed analysis befare their generalized putting inta
practice.
There is wide consensus on the criteria t o be followed when 343
carrying out programmes of genetic diagnostic population testing
that are ethically acceptable.a consensus that seems t o be reflect-
ed in the similar conclusions reached by the National Acaademy
of Sciences, the Hastings Center and the American Presidential
Commission f o r the study of ethical problems in medicine. Cur-
rent proposals on the carrying o u t of wide-ranging diagnostic
population testing for the detection of CF bearers (CF = cystic
fibrosis), o r diagnostic testing in new-born infants for pre-symp-
tomatic treatment, follow practically none of these recommenda-
tions.

A t present proposals for the detection of bearers should take in-

t o account the following problems:

1. The scant sensitivity of available tests (75 t o 80%) will cause

unsurmountable uncertainty in many couples, for one of the
t w o could be positive and the other give negative results in
the test w i t h o u t their genetic situation being k n o w n . If all
pregnant w o m e n w e r e submitted t o the test, 200.000 of
them w o u l d be in this situation, 97% of this kind of couple
would run no risk at all.

2. The dilemmas posed t o the counsellor are extraordinarily

complex, and yet there is no infrastructure f o r expert coun-
selling t o be made available t o patients. If all genetic coun-
sellors w i t h experience in the United States were recruited,
and if they spent 10 minutes counselling each couple, each
counsellor would have t o devote 17 weeks t o this task. C o n -
sequently, it will be non-qualified people w h o carry o u t the
w o r k of counselling.

3. The costs of diagnostic testing programme of this type would

amount t o over a thousand million dollars. The number of
pregnancies t e r m i n a t e d f o r this reason is u n k n o w n , but
should they be reduced by 50%, costs would be more than 2
million dollars per pregnancy thus terminated. This may be
hard t o justify in a country in which 37 million people have
no basic health Insurance. Obviously, company interests and
conflicts of interests are entailed.

4. The public is little disposed t o participating in this type of

programme: public opinión has little knowledge of cystic fi-
brosis and even the most elementary genetic Information is
barely available t o the consumen Therefore, it is likely that
there will be great confusión and that decisions taken on re-
production will be somewhat irrational.

5. N o pilot studies have been carried out on the efficiency and

toxicity of bearers of cystic fibrosis.Therefore, these propos-
als are experiments that require analysis at institutional le-v-
el, strict rules on the consent of the person Informed and a
344 homologation of results, before it is possible t o carry o u t
testing on a generalizad scale.

In Australia, Colorado and some other communities, diagnostic

testing has been carried o u t on new-born infants for five years,
as presymptomatic testing; yet in no case has either the experi-
mental design, proof that efficiency and toxicity levéis and costs
are acceptable been adequate. In Wisconsin, an aleatory, con-
t r o l l e d , prospective study has been carried o u t that has still
n o t shown any medical benefit after five years, although this
study has not yet been completed.
 345

REFERENCES

W i l f o n d , B . S . , a n d F o s t , N , , 1990. T h e cystic fibrosis gene: medical

and social implications f o r heterozygots d e t e c t i o n . }AN\A. 263(20),
May 23rd, pp. 2777-2783.

F o s t , N . , a n d P a r r e l l , P. M., 1989. A prospective randomized trial o f

early diagnosis and t r e a t m e n t o f cystic fibrosis: a unique ethical d i -
lemma, Clinical Research, 37(3), September, pp. 495-500.
LESSONS FROM
THE PAST:
PROSPECTS FOR
THE FUTURE
 349

BEYOND DECLARATIONS:
IS I T P O S S I B L E T O F I T
ETHICS INTO THE HUMAN
C E N O M E PROJECT?

William G. Bartholome

Medical Center of the University of Kansas,

Kansas City (USA)

ABSTRACT

Knowledge can be used destructively for h u m a n dig-

nity. W h a t can be done to guarantee that genetic in-
formation is used exclusively to increase h u m a n dig-
nity? It is assumed that the new genetic knowledge,
as ¡ikewise technological progress associated with
same, will be applied in a ciinical context, although
there is no mechanism to control this appiication.
The title of my presentation was drawn f r o m the document that 35
was drafted here in Valencia in O c t o b e r of 1988. It is called the
"Valencia Declaration on the Human Genome Project." As I read
this declaration, I was struck with the fact that with one excep-
tion, which I will discuss in detall, most of the valúes informing the
declaration w h e r e what might be called the valúes of good o r
ideal science: the assumption that the pursuit of knowledge is
good; the valúes of collaboration and coordination and the valué
of honesty o r disclosure of Information. The exception is the
acknowledgment that participating scientists have the responsability
"...to help ensure that genetic Information be used oníy t o en-
hance the dignity of the individual." Although the declaration en-
dorsed the Human Genome Organization ( H U G O ) as the: "lead
body... t o p r o m o t e the goals and objectives addressed in this de-
claration," it is silent on the question of specific steps t o be taken
t o achieve these goals.

As w e have been told repeatedly in this conference, human his-

t o r y is replete w i t h examples of the use of the knowledge of hu-
man differences - o f t e n nothing m o r e than beliefs based on igno-
rance, prejudice o r f e a r - t o justify systematic violations of the
welfare, rights and dignity of individuáis, groups and whole socie-
ties. As we have been t o l d , the history of human genetics more
than explains the concern reflected in the Valencia Declaration
that knowledge might be used in ways highly destructive of hu-
man dignity. W h a t should be done t o ensure that genetic Informa-
tion will be used only t o enhance dignity?

One of the concerns that prompted me t o accept the invitation

t o attend this meeting, is that the clinical geneticists I k n o w and
w o r k with struggle t o dea! w i t h the ethical ambiguity, complexity
and conflicts involved in application of existing genetic knowledge
and technology. In fact, the literature describing their on-going
struggle with the demands of ethics contains little of no clarity o r
consensus about the meaning o r demands of ethical declarations
such as: "genetic information be used only t o enhance the dignity
of the individual".

O f proponents and supporters of the Human Genome Project

are correct in their predicitions, it is likely that these efforts will
exponentially increase t h e fund of basic information available
regarding human genetics. It is also assumed that this dramatic in-
crease will "pay o f f ' in the sense of the application of this new
knowledge t o t h e d e v e l o p m e n t o f a w i d e variety o f genetic
technologies and products.

In the second half of the title of my presentation I invocked the

metaphor of knowledge and its development as a building. I asked
"Can Ethics Be Built into the Human Genome Project?" I should
have been m o r e careful in my use of this metaphor. As reflected
in the question I asked yesterday afternoon, I believe - a n d it is
essential that w e acknowledge h e r e - that a wide range of valúes
352 and ethical assumptions have been "built into the Genome Pro-
ject". My question shold have been: " H o w Should Ethics Be Built
into the Genome Project?" Therefore, one of the first tasks must
be undertaken is the identification and critical examination of the
valúes that inform thís project. I see the Identification of these
valúes as a fairly straight-forward task. By engaging in a sustained
dialogue over time w i t h members of the community of scholars
doing-ethics - l o n g after the conclusión of this conference- those
of you w h o are undertaking this project could come t o k n o w the
often hidden valúes that inform what you are doing.

It w o u l d then be necessary f o r you t o "build i n t o " your project a

process by which these valúes w o u l d be subjected t o critical ex-
amination and reformulation over time. Clearly the creators and
masterminds of this ambitious project understood the importance
of this effort. Many i m p o r t a n t and significant steps have been
taken. Clearly the most visible steps in this regard are dedicated
fiscal resources - w e have been t o l d this is t o be at least 3% of
the total funding; the establishment of the "Ethical, Legal and So-
cial Implications (ELS!) P r o g r a m " - ond the recruitment of a highly
qualified philosoper t o manage the program. Eric, in cooperation
with the Joint N I H - D O E W o r k i n g Group, has undertaken impor-
tant steps in the process of providing a mechanism f o r on-going
critical examination of t h e genome projects f r o m an ethical
perspective.

In trying t o prepare myself t o have some practical suggestions

about additional aspects of this process, I have consulted w i t h
Eric and other members of the clinical ethics community w i t h
much more experience and expertise than I in the área of genetic
ethics. In the summary of my presentation, I have proposed a se-
ries of additional steps t o be considered. I will not repeat all of
them here. I would, however, like t o specifically discuss there of
them. First, I suggested that consideraron be given t o the estab-
lishment of what I called an "Ethics Board" t o w o r k w i t h Eric and
the Joint W o r k i n g G r o u p in the ELS! Program. It may well be
that this could best be accomplished by an expansión of the
membership of the W o r k i n g G r o u p t o include additional volees
in clinical ethics. My concern is that the decisions which guide the
w o r k of this program need t o be informed by the critical per-
spective of scholars f r o m the " o u t s i d e " i.e. scholars in ethics
whose w o r k is constantly shaped by having t o w o r k in clinical
contexts and by those whose w o r k is subject t o the scrutinty of
academic peers.

I also suggested that consideraron be given t o the creation of

what I called a National Consortium o r Commission t o develop
and recommend appropriate legislation t o prevent the inappro-
priate, non-clinical uses of genetic knowledge and technology; and
t o recommend appropriate legislation t o combat genetic discri-
mination. Obviously, the model I had in mind in making that sug-
gestion was that of the President's Commission. In fact, the re-
p o r t of that Commission on Ethical Issues in Genetic Screening 353
remains an important document in genetic ethics particularly as it
relates t o ethical issues in screening. I see the need f o r such a
Commission t o supplement the educational and extra-mural re-
search activites of the ELSI Program. O n e obvious and pressing
issue t o be examined is the possible expansión of federal civil
rights and disability legislation t o include individuáis w h o have
been identified as "genetically different".

The third suggestion I would like t o briefly discuss is that of creat-

ing a networking system f o r Institutionai Review Boards faced
with the challenging task of reviewing genetic research at univer-
sities and research centers. This might well be an International
networking system tied administratively t o the Human Genome
Organization through its Ethics Committee. As the chair of my
institutions IRB I have become acutely aware of the difficulty of
providing adequate review of the complex ethical issues raised by
these research projects. It is not possible f o r each IRB t o have of
develop the necessary experience and expertise in genetic ethics.

I would like t o conclude my remarks about "building" ethics into

this project w i t h observations that deal w i t h t w o other meta-
phors f o r knowledge that seem t o have been operative in this
workshop. O n e of the metaphors which appears t o have shaped
many of the presentations and much of the converstation at this
conference appears t o be the metaphor knowledge as power. In
fact, one f o r m of this metaphor appears t o have shaped the deci-
sión t o have the conference in the first place, namely that of
knowledge as weapon o r the even m o r e dramatic metaphor of
knowledge as cannibal o r d e v o u r i n g m o n s t e r , m e n t i o n e d by
Nancy W e x l e r yesterday morning. I would like t o use these met-
aphors t o express my concerns about what appears t o be a very
basic assumption which guides this project. It is the assumption
that this new genetic knowledge and the technological progress
its spawns will be used, ie. applied, in a medical o r clínica! con-
text. It is assumed that it will be utilized by health care profession-
ais working in clinical settings providing health care services t o
their patients. However, there is no existing mechanism by which
the use of this newly developed knowledge and technology can
be controlled, curtailed of limited t o use in this setting. If the con-
cern is that w e do not repeat the experience of " o u r colleges in
nuclear physics after the Second W o r l d W a r " w e must critically
examine this assumption. I hear you claiming that this project will
produce or allow f o r the development of "powerful knowledge"
and a vast armamentarium of powerful new technologies. Absent
some as-yet-to-be developed mechanisms, this knowledge and
technology will be used by those w i t h power t o increase their
power. It will be marketed by its developers t o the powerful - t o
employers, t o corporations, t o Insurance companies, t o law en-
forcement agencies and t o governments. I would draw your at-
tention t o what has happened in the United States t o the newly
developed knowledge and technologies involved in testing human
354 uriñe and blood for organic chemicals- i.e. socalled "drug test-
ing" and t o the use of antibody testing for HIV virus t o prevent
the spread of HIV infection through the transfusión of blood. A t
the present time in my country the vast majority of drug tests
and HIV tests are ordered by non-health care providers and per-
formed on individuáis w h o are not patients. I would also point
o u t that one of major users of this knowledge and technology is
the government of my country.

A n o t h e r of the more prominent metaphors underlying this pro-

ject is that of knowledge as geography - m o s t vividly presented t o
us yesterday by A l Jonsen. Those undertaking the project seek t o
créate a "map". W i t h this map, they claim, we will be better able
t o "find o u r way" in dealing w i t h human genetic difference and
disease. W i t h o u t this " m a p " we will be " l o s t " in ignorance on the
unexplored genetic frontier. W e will be left t o continué t o grope
and stumble along w i t h o u t the knowledge this map promises t o
provide. W i t h the map w e will be better able t o get where we
want t o be in terms of our ability t o control, t o prevent and t o
respond t o genetic disease.

Yet it is not at al! clear t o me that we know where w e are going.

D o we know where we want t o go? D o we seek t o prevent all
genetic difference? D o w e seek only t o prevent or respond t o
certain kinds o r levéis of difference? W h i c h differences? D o we
seek t o prevent of t h w a r t o r even cure all genetic diseases?
W h a t goals shold inform this search, this quest? W h o will deter-
mine which goals should be sought? If w e do not (cannot?) know
where we want t o be of what use is a better map?

This geographical metaphor also invites us t o attend t o the im-

p o r t a n t task of understanding h o w this j o u r n e y fits into the
larger context of humanity's historical quest.

W h a t is clear t o me is that the burden of human suffering in our

w o r l d community is not caused most fundamentally by human ge-
netic difference o r even by human genetic disease. In fact, this
burden is not caused by the lack of what those of us w h o live in
privileged societies cali medical care. Genetic disease may be the
leading cause of of infant mortality in the United Kingdom, but it
is not the leading cause of the death of infants and children in the
w o r l d . The " m a p " w e need t o deal with the this globe's burden
of human suffering is not a genetic map. If our goal is t o find the
way t o respond effectively t o the global burden of human suf-
fering, this quest for a better genetic "map" must be seen as a dis-
traction, a luxury, at best, a noble but certainly not essential hu-
man quest. W h e n we take a wide-view - a w o r l d v i e w — a human
community v i e w - w e see the specter of a crushing burden of
human misery, hunger, homelessness and privation which cha-
racterize life f o r most of those in our global community. W i l l this
project and its " n e w map" help us find the way in seeking t o res-
pond t o these basic human needs? I do not find its potential for
human benefit - i n terms of the common good of a community of 355
nations- t o be either obvious or particularly enormous.

Elke Jordán asked us t o reflect on the question of what concep-

tion of the public good should inform N I H policies on data shar-
ing by Human Genome investigators. Although this seems t o be
an appropriate and i m p o r t a n t question, its asking is also dan-
gerous. As w e seek t o answer it and a host of related questions
about the nature of the "public" o r " c o m m o n good", w h o is the
" w e " w h o will provide the answer? W h o s e volees will be heard
as the answer t o this question is formulated? I am concerned that
our answer may well be just that " o u r " answer - a n answer that
fits the desires and needs of those of us w h o are privileged. W i l l
it fit the aspirations and needs of the billions of those members
of the human community not fortúnate enough t o particípate in
this dialogue?

I am also concerned that many so-called developed nations are

alreaday struggling under the specter of a burden of biotechnol-
ogy and t h e medical-industrial c o m p l e x w h i c h supports and
nourishes its relentless g r o w t h . In many countries, this monster
already grows o u t of c o n t r o l consuming an ever-greater portion
of the social resourses. Its g r o w t h has resulted in a widespread
medicalization of human life in these societies and has distored
social valúes, priorites and programs in pursuit of its utopian
(some w o u l d say demonic) visión of a maximally prolonged hu-
man existence free of all suffering and disease. In at least one of
these countries - m y o w n - this monster has lead us seriously
astray (we are indeed in need of a map, but not a genetic map).
Even as Americans spend m o r e and more hundreds of billions of
dollars each year t o feed the insatiable appetite f o r the latest in
modern medicine, w e must suffer the humiliation of calling our-
selves a developed nation -even a leader in the w o r l d c o m m u -
n i t y - and y e t w e have no health care system; no system by
which we can discharge o u r social obligation t o provide health
care t o our citizens.
 357

GENETIC INEQUALITY AND

S O C I A L INJUSTICE:
A LESSON FROM HISTORY

Benno Müller-Hill

Institute of Genetics of the

University of Cologne (Germany)

ABSTRACT

It is certain t h a t the H u m a n Genome Project will

have social consequences. In N a z i Germany, there
were attempts to apply human genetics with the aim
o f creating a superior, genérica/// selected race. Illegal
sterilization was a habitual practice a n d a law was
defended t h a t allowed euthanasia. But all this be-
longs to the p a s t A t present, we Uve in a world in
which a large part o f the population has no housing,
food or work, a n d within this context o f inequality
the H u m a n Genome Project poses problems. How?
It may be that genetic inequality is translated into
genetic "injustice" a n d that this may justify social in-
justice.
Introductíon 359

The Human Genome Project is a great intellectual and technical

challenge f o r those w h o llke t o w o r k with D N A . One can safely
predlct that those Involved will have little time t o think about the
possible problems the successful project will créate f o r society.
A scientist Is after all judged f o r his scientific accompllshments
and not f o r his worries about the possible misuse of science. So
the proposal that about three percent of the bugdet of the pro-
ject should go t o experts - b i o e t h i c i s t s - w h o make a living of
thinking about such things makes sense.

My experience w i t h bioethicists is limited t o encounters at three

conferences including this one. These encounters have been
deeply disquieting for me. I liked of course the anglosaxon atti-
tude that (almost) all fundamental research is legitímate (I share
this view). But I dislike the corresponding view that (almost) all
application t o man and society is potentially legitímate t o o .

The most disturbing aspect is the apparent absence of any tabus.

According t o this view there is no proposition which can not be
discussed carefully and all propositions are defendable as long as
they are coherent. But what is t r u e for science is - i n my o p i n i o n -
not true f o r the issues trascending science. So economic argu-
ments should be n/7 ab initio when they viólate human hghts.

I will argüe that something can be learned f r o m history in this

respect. Half a century ago, Germán human geneticists ailied
themselves w i t h the antisemitic Nazi Party t o propágate their
common interest: t o apply human genetics f o r the utopian goal
of a w o r l d dominated by a genetically selected, superior nordic
race.

A Short History of the Past of Human Genetics

in Nazi Germany

It is impossible t o present an adequate picture of the history of

human genetics in Nazi Germany in a few pages. I w o u l d like t o
draw the attention of the International readers t o some books
dealing with the phenomenon ,"4. For the situation in the US and
England and some other countries see 5'7. Here I can just summa-
rize: In the twenties and thirties the evidence seemed t o g r o w
that most physical and psychic ailments had some genetic defect
as basis. A large percentage of society seemed t o be made up of
such genetically afflicted persons. Furthermore the notion was
advanced that these afflicted persons bred faster than those with
intact, "valuable" genes. Biological evolution was seen as a pro-
cess where dog eats dog and social evolution was seen in the
same manner. A most readable story is told by an American pro-
360 fessor of zoology w h o in 1915 sat night after night in the Germán
A r m y Headquarters in Brussels and talked with a Germán zoolo-
gist w h o had become an army officer 8. The American arrived as
a pacifist and left deeply convinced that the war against Germany
was justified. A country w h e r e the intellectuals made sociopoliti-
cal Darwinism their religión had t o be contained and, íf neces-
sary, by war.

The Germán human geneticists of the twenties had no connec-

tion any more t o any religión. Darwinism was the surrogate they
used. Thus they advocated that they should become the makers
of human biological and social evolution. They proposed, as a
first measure, sterilization of a large section of the Germán Popu-
lation. In the W e l m a r Republic no party except the Nazis sup-
p o r t e d enforced sterilization. Even sterilization after informed
consent was extremely controversia!. It is thus not astonishing
that almost all Germán geneticists prior t o 1933 asked f o r ster-
ilization with informed consent.

There was one party which openly said that informed consents
was democratic nonsense and this was the Nazi party. In fact the
Nazi party approached the leading Germán human geneticists in
1932 and w e r e warmly received 9. It is thus not astonishing that a
cióse collaboration w i t h the human geneticists began after the
Nazis came t o power in 1933. The geneticists asked f o r support
of their research and got it amply. The Nazis asked f o r theoreti-
cal and practical support f o r their race measures. And they got
what they wanted.

The human geneticists had t o train the medical d o c t o r s w h o

later became involved in the various racial measures. I would just
like t o list a few of these:

• The legal sterilization of about 350 000 Germán citizens ac-

cording t o the law of 1933 which asked f o r the sterilisation
of schizophrenics, manic depressives, alcoholics, idiots and some
others afflicted with rare genetic diseases.

• The nonlegal sterilization of all coloured Germán citizens.

• The nonlegal sterilization of almost all Germán Gypsies. Most

Germán Gypsies perished later in Auschwitz

• The planned sterilization of all Germán citizens with "antiso-

cial" behaviour.

• The planned sterilization of all "quarter-Jews".

• The expert opinión in all cases of questionable Jewish origin.

• The racial evaluation of the whole population in Poland and the

Soviet Union.
• The framing of a law legalizing "euthanasia". 36 I

• The evaluation and killing of psychiatric patients after 1940.

• The life and death decisions in Auschwitz.

W h e n the war ended in 1945 almost all Germán human geneti-

cists and psychiatrists, professors and postdocs alike, w e r e so
deeply entangled in some of these actions that there were just
t w o options:

• T o continué. Then none of them would ever have t o bear w i t -

ness against any collegue.

• T o cióse the fields of human genetics and psychiatry comple-

tely.

Here as elsewhere the first option became reality. The interna-

tional community of human geneticists o r psychiatrists prefered
not t o know - a n d when somebody did know, he kept silent and
shuddered. The Germán anthropologist, human geneticists and
psychiatrists continued t o publish, meet and teach as if nothing
had happened. There was not a single article o r book on the his-
t o r y of human genetics during these years by one of its practi-
tioners. Even those w h o had been in trouble in Nazi Germany
kept silent f o r many years. Only in 1961 did Karl Saller, w h o had
been dismissed as a lecturerer in 1935, daré t o w r i t e his account
on his f o r m e r and present collegues l0. His b o o k made him
promptly a leper among his collegues.

T o ¡ilústrate the situation I w o u l d like t o ñame just t h r e e of

the speakers of the 6th Conference of the Germán A n t h r o p o -
logical Society (6. Tagung der Deutschen Geseílschaft für Anthro-
pologie) in Kiel, July 30 t o August 2, 1958. A m o n g the speakers
are listed 1 ':

• H. Schade on anthropological research in Macedonia: Schade

was an SS officer and member of the SS race office. In this ca-
pacity he was active during the w a r in Yugoslavia. In 1937 he
was involved in the illegal sterilization of coloured children.

• B.K. Schultz on inheritance of variabilities of the foot: Schulz

was an SS general and head of the race buró of the SS. He be-
came responsible f o r the racial screening in all of Europe in
1943. He was author of a proposal t o head an office in which
all "quarter-Jews" had t o be examined f o r possible sterilization.

• H. Fleischhacker on bloodgroups and race mixing in El Salva-

dor. Fleischhacker was an SS officer. In 1943 he selected 79
typ/co/Jews in Auschwitz t o be sent t o the concentraron camp
Natzweiler near Strassburg. There they w e r e all killed t o be-
362 come part of the anthropological collection of the Strasbourg
anatomy of professor Hirt.

The influence of all these geneticists and psychiatrists disappear-

ed only w i t h their retirement and death. This process had come
more or less t o an end in the eighties. Then suddenly a flood of
articles and books appeared in Germany dealing w i t h these hu-
man geneticists, anthropologists, psychiatrists, etc. The articles,
most of them well researched, many in popular journals, comple-
tely destroyed the respectability of geneticists of all sorts. It was
coincidental that some years earlier cloning of D N A was f o r a
short time regarded as dangerous. This was simply t o o much f o r
the Germán public. The oíd generation had objectively been in-
volved in crime and what was the new generation doing? The
very low esteem of the general public f o r genetic engeneering in
all its forms results f r o m this.

Lessons from the Past

The present situation differs f r o m the past in essential points:

• In the past only phenotypes w e r e available f o r evaluation. N o w

genotypes will be unambiguously determined.

• In the past the state and its agencies enforced sterilization,

abortion and death. N o w these decisions are left t o the indi-
vidual citizen.

• In the past knowledge about the presumed genotypes was

freely circulated among the interested state agencies. N o w state
agencies are under control. But what about Insurance compa-
nies and prívate business?

In the best of all possible worlds, which does not exist, where
everybody finds employment, housing and health Insurance, the
Human Cenóme Project poses no threat. But in the US where
about one percent of the population belongs t o the homeless,
w h e r e 37 million people have no health Insurance, w h e r e the
crowds of the p o o r and the jobless are growing, the Human Ce-
nóme Project does pose problems. Here the economic pressure
in immense that the insurance company may know the genotype
t o determine the insurance rate and that the company may know
the genotype of its potential employee. I am afraid that such a si-
tuation where all is decided by consenting individuáis under eco-
nomic pressure, will push the US in the next half century in a si-
tuation resembling the science fiction novéis of Philipp K. Dick.
Social injustice will become first justified and later amplified by
genetic injustice. The discovery that some unfavourable genotype
are frequently found in certain ethnic groups will make racism
again respectable. The end of this development can only result in
violent social upheavals t o end o r cement this state of scientific 363
racism. This will also mean the end of respectable genetics be-
cause the geneticists will be unable t o hide like their Germán col-
leagues did a century ago.

Since I find this development utterly undesirable I propose here

again what I proposed in vain here and elsewhere l2.

1. Every person has the right t o know his genotype in full, in

part or, if he wishes, not at all.

2. The genotype of a person should not be determined unless

the person has specifically asked f o r this. It should be a crim-
inal offense t o determine the genotype of a person w i t h o u t
being authorized by this person. Exceptions as genetic finger-
printing should be carefully qualified.

3. Parents have the right t o ask, o r not t o ask, f o r particular

genotypes of their children, when the onset of the sickness
brought about by the particular genotype is below the age of
eighteen. They have not the right t o ask f o r genotypes of
their children if their genetic condition will not disable them
before the age of eighteen.

4. Every pregnant mother has the right t o ask, o r not t o ask,

f o r the genotypes of the unborn. The genotypes of the un-
born should not be determined unless after specific authori-
zation of the pregnant woman. Insurance companies should
n o t have the right t o ask f o r the genotype of an unborn.
A b o r t i o n should be decided by the pregnant w o m e n and not
by another persons.

5. N o t h i r d person, Insurance company, employer and the like

has the right t o ask f o r the genotype of a particular person
o r t o determine it. Breach of this should be made a criminal
offense.
364

REFERENCES

1. Lifton, R. J . 1986. The Nazi Doctors. Medical Killing and the Psy-
chology of genocide. N e w Y o r k : Basic Books, Inc., Publishers.

2. M ü l l e r - H i l l , B . 1988. Murderous Science. Elimination by Selection of

Jews, Gypsies and Others, Germany 1933-1945. O x f o r d : O x f o r d U n i -
versity Press.

3. P r o c t o r , N . 1989. Racial Hygiene. Medicine under the Nazis. Cam-

bridge, Mass. USA: Harvard University Press.

4. W e í n d l í n g , P. 1989. Health, Race and Germán Politícs between Na-

tion Unification and Nazism 1870-1945. Cambridge, N e w Y o r k ,
Melbourne: Cambridge University Press.

5. K e w i e s , D. J. 1985. In the Ñame ofEugenics. Genetics and the Uses

of Human Heredity. N e w Y o r k : A l f r e d A . Knopf. Publishers.

6. T h e W e l l b o r n S c i e n c e . £ugen/gs in Germany, franee, Brazil, and

Russia, 1990. Ed. by M.B. Adams. O x f o r d : O x f o r d University Press.

7. T e i c h , M. 1990. The Unmastered Past of Human Genetics. In: Fin de

Siécle and its Legacy. Ed. by M. Teich & R. Portar. Cambridge: Cam-
bridge University Press.

8. K e l l o g , V . 1917. Headquarters Nights. A Record of Conversations

and Experiences oí the Headquarters of the Germán Army in France,
Belgium, Boston.

9. M ü l l e r - H i l l , B . 1991. Selektion. Die Wissenschafi von der biologis-

chen Auslese des Menschen durch den Menschen. In: Medizin und Ge-
sundheitswesen in der NS-Zeit Ed. by N. Frei, pp. 137-155. München:
Oldenbourg.

10. S a l l a r , K. 1961. Die Rassenlehre der Nationalsozialismus in Wissen-

schafi und Propaganda. Darmstadt: Progress-Verlag.

I I. K o c h , G . 1985. Die Gesellschafi für Konstitutionsforschung. Anfang

und Ende 1942-1965. Erlangen: Verlag Palm und Enke.
 365

THE INFLUENCE OF
EUGENIOS ON HUMAN
GENETICS

Daniel ¡. Kevles

Institute of Technology of California,

Pasadena, California (USA)

ABSTRACT

As from 1900, eugenics became institutionalized in

severo/ European countries a n d in the United States,
However, thirty years later, it began to be criticized
as a science because o f its scant scientifíc consis-
tency and due to social prejudices, although it con-
tinued to influence h u m a n genetics, particularly in
the United States.
W i t h time, biochemistry síowly gained ground within
genetics, contributing scientifíc rigour to research;
thalasemia a n d falciform anemia are two examples
o f this genetic research. Consequently, scientifíc
rigor gradually s u p p l a n t e d eugenics, in any case,
ethics must always be present a n d not only when
applying a certain research b u t o/so when ques-
tion'mg the aims o f research.
Human beings - s l o w and uncontrollable b r e e d e r s - have never 367
been as advantageous for genetic research as, say, poultry, rodents,
and fruit flies. Nevertheless, almost immediately after the redis-
covery of Mendel's laws, in 1900, biologists began t o apply them
t o the study of heredity in man -because he was man. In 1902,
the British physicial Archibald Garrod convincingly showed that
certain ¡nborn errors of metabolism- notably alcaptonuria - w e r e
caused by a Mendelian recessive gene. In 1907, the Mendelian
inheritance of human eye color was demonstrated in Britain by
C.C. Hurst, a flower breeder. Clearly, early research in human
genetics comprised the study of purely physical traits and diseases
for their own sake However, through the first third of the twentieth
century, human genetics was enormously influenced by eugenics
- t h a t is, by the cluster of ideas and activities centered on the aim
of improving the quality of mankind through the manipulation of
its biological heredity.

Invented as a self-conscious doctrine in the late nineteenth cen-

tury, eugenics became a popular social movements after 1900,
developing a large following in the United States, Britain, Ger-
many, and many o t h e r countries. The backbone of the move-
ment was formed of people drawn f r o m the white middle and
upper middle classes, especially professional groups. Its support-
ers included prominent laymen and scientists, particularly genet-
icists, for w h o m the science of human biological improvement
offered an avenue t o public standing and usefulness. Eugenicists
declared themselves t o be concerned w i t h preventing social de-
generaron. They found signs of such degeneration in the social
and behavioral discordances of urban industrial society - f o r
example, crime, slums, and rampant disease; t o o k these as symp-
toms of social pathologies; and attributed them phmarly t o bio-
logical causes- t o " b l o o d , " t o use the t e r m of inheritable essence
common at the t u r n of the century.

T o eugenically-minded biologists, the causes of social degen-

eration had t o be understood t o be r o o t e d o u t - w h i c h made
the study of human heredity essential t o the eugenic program.
Such biologists u n d e r s t o o d eugenics t o be the application of
human genetic knowledge t o social problems and the develop-
m e n t of t h a t k n o w l e d g e t o be t h e basic branch of eugenic
"science". As a result, the human genetics program included the
study of medical disorders - f o r example, diabetes and epilepsy-
not only f o r t h e i r intrinsic interest but because of t h e i r social
costs. A still m o r e substantial part of the program consisted
of t h e analysis o f t r a i t s alleged t o make f o r social b u r d e n -
straits involving qualities of t e m p e r a m e n t and behavior t h a t
might lie at the b o t t o m of, f o r example, alcoholism, p r o s t i t u -
t i o n , criminality, and poverty. A major object of scrutiny was
mental deficieney - t h e n commonly t e r m e d "feeblemindedness"
which was often identified by intelligence tests and was widely
interpreted t o be at the r o o t of many varieties of socially dele-
terious behavior.
368 A large fraction -perhaps m o s t - of research in human heredity
was pursued in laboratories established t o develop eugenically
useful knowledge.The most prominent of these institutions, both
of which w e r e ceated early in t h e century, w e r e the Galton
Laboratory for National Eugenios, at University College London,
under the directorship of the statistcian and population biologist
Karl Pearson; and the Eugenios Record Office of the Carnegie
Institution of Washington's Department of Genetics, located at
Cold Spring Harbor, on Long Island, N e w York, and headed by
the biologist Charles B. Davenport. Eugenic science was institu-
tionalized in Germany beginning in 1918, with the establishment
ofwhat became the Kaiser W i l h e l m Institute f o r Research in Psy-
chiatry. The institutionalization continued w i t h the creation, in
1923, of a chair f o r race hygiene at Munich, t o which the biolo-
gist Fritz Lenz was appointed; and with the founding, in 1927, of
the Kaiser W i l h e l m Institute f o r Anthropology, Human Heredity,
A n d Eugenics in Berlin, which was directed by the anthropolo-
gist Eugen Fischer, a conservative nationalist Catholic w h o then
headed the Society f o r Radial Hygiene.

Staff at o r affiliated w i t h these laboratories gathered Information

bearing on human heredity by examining medical records of con-
ducting extended family studies often relying upon fieid workers
t o construct t r a i t pedigrees in selected populations -say, the
residents of a rural c o m m u n i t y - on t h basis of interviews and the
examination of genealogical records. A n i m p o r t a n t feature of
Germán eugenic science was t w i n studies. By 1926, as a result of
its various surveys and studies, the Eugenics Record Office had
accumulated about 65,000 sheets of manuscript field reports,
30,000 sheets of special traits records, 8,500 family trait sched-
ules, 1900 printed genealogies, t o w n histories, and biographies.

Karl Pearson, an adamant anti-Mendelian, sought t o determine

heritabilities by calculating correlations among relatives o r be-
t w e e n generations f o r different diseases disorders, and traits.
Studies emanating f r o m his laboratories typically explored the
relationship of physique t o intelligence; the resemblance of first
cousins; the effect of parental occupation upon children's welfare
of the birthate; and the role of heredity in alcoholism, tuberculo-
sis, anad defective sight. However, the approach that dominated
eugenic science in most laboratories was not correlational but
Mendelian analyses attempts t o use phenotypical and family data
t o account f o r the inheritance of a variety of medical afflictions
and social behaviors in genetic terms.

Typical of Mendelian w o r k in eugenic science w e r e the studies of

Charles B. Davenport and his associates, which appeared in his
comprehensive 1 9 I I book, Heredity in Relation to Eugenics and in
later publications. W h e r e v e r family pedigrees seemed t o show a
high incidence of a given character. Davenport concluded that
the trait must be inheritable and attempted t o fit the pattern of
inheritance into a Mendelian frame. Although he noted that single
genes did not seem t o determine important mental and behavioral 369
characteristics, he did argüe that patterns of inheritance w e r e
evident in insanity, epilepsy, alcoholism, "pauperism", and crimi-
nality. The mental and behavioral characteristics of different races
w e r e a mayor concern of Davenport's, w h o , like eugenic scien-
tists elsewhere, held different national groups and " H e b r e w s " t o
represent biologically different races and express different racial
traits. However, although he declared himself frequently on the
subject, he actually did little research in It, particularly of a
Mendelian type, except f o r an inquiry into "race-crossing" be-
tween blacks and whites in Jamaica, the effects of which, he con-
cluded, w e r e biologically and socially deleterious.

Davenport helped introduce Mendelism into the studies of "fee-

blemindedness" conducted by Henry H. Goddard, the psycholo-
gist w h o intoduced intelligence testing into the United States.
Davenport provided field w o r k e r s f o r Goddard's surveys of the
mental characteristics of a local population in N e w Jersey and ad-
vice on genetic i n t e r p r e t a r o n of the data.The surveys contrib-
uted essential material t o t w o highly influential books by Goddard
-The Kallikak Family: A Study in the Heredity of Feeblemindedness
and Feeble-mindedness: ¡ts Causes and Consequences, published res-
pectively in 1912 and 1914. Goddard speculated that the feeble-
minded w e r e a f o r m of undeveloped humanity: "a vigorous ani-
mal organism of l o w intellect but strong physique - t h e wild man
of today." He argued that they lacked "one o r the other of the
factors essential t o a moral life an understanding of right and
w r o n g , and the p o w e r of c o n t r o l " , and that these weaknesses
made them strongly susceptible t o becoming crimináis, paupers,
and prostitutes.

Goddard was unsure w h e t h e r mental deficiency resulted f r o m

the presence in the brain of something that inhibited normal de-
velopment o r f r o m the absence of something that stimulated it.
But whatever the cause, of one thing he had become virtually
certain: it behaved like Mendelian character. Feeblemindedness
was "a condition of mind o r brain which is transmitted as regu-
larly and surely as c o l o r of haír o r eyes." A c c o r d i n g t o later
studies by Goddard and others, it also occurred w i t h dispropor-
tionately high frequency among lower - i n c o m e and minoritaty
g r o u p s - notably recent immigrants in the United States f r o m
Eastern and Southern Europe.

Eugenic research in Germany before the Nazi period was similar

t o that in the United States and Britain, and much of it remained
similar after Hitler came t o power. The Institute f o r A n t h r o p o l -
ogy, Human Heredity, and Eugenics, f o r example, continued t o
press investigations into subjects such as the genetics of diabetes,
tuberculosis, and brain disease; the heritability of criminality; the
effects of race crossing (with no particular emphasis on Jews o r
Aryans). However, during the Hitler years. Nazi bureaucrats pro-
vided eugenic research institutions w i t h handsome support and
370 t h e i r research programs w e r e expanded t o c o m p l e m e n t the
goals of Nazi biological policy, exploiting ongoing investigations
into the inheritance of disease, intelligence, and behavior t o advise
the government on its sterilization policy. Fischer's Institute, the
staff o f w h i c h i n c l u d e d t h e p r o m i n e n t g e n e t i c i s t O t m a r
von Verschuer, trained doctors for the SS in the intricacies of
racial hygiene and analyzed data and specimens obtained in the
c o n c e n t r a r o n camps. Some of the material - f o r example, the
internal organs of dead children and the skeletons of t w o murdered
J e w s - carne f r o m Josef Mengele, w h o had been a gradúate
student of Verschuer's and was his assistant at the Institute. In
1942, Verschuer succeeded Fischer as head of the Institute (and
would serve postwar Germany as professor of human genetics at
the University of Muenster).

Davenport, Lenz, and eugenic scientists in other countries manag-

ed, in the end, t o expose genuinely Mendelian patterns in the in-
heritance of traits that could be well specified - c o l o r blindness,
f o r e x a m p l e - and w e r e entirely physical. Their w o r k s showed
that single genes might account f o r such abnormalities as brachy-
dactyly, polydactyly, and albinism, and f o r such diseases as he-
mophilia, otosclerosis, and Huntington's chorea. Lenz, in parti-
cular, also d e v e l o p e d i m p o r t a n t mathematical m e t h o d s f o r
overcoming ascertainment bias - t h e tendency in human genetic
field surveys t o find a higher frequency f o r a given trait among
siblings than its t r u e probability of occurrence. Some fraction of
their w o r k thus contributed usefully t o the early study of human
genetics.

However, the fraction was rather small. Combining Mendelian

theory w i t h incautions speculation, they often neglected polygen-
ic complexities in favor of single-gene explanations. They also
paid far t o tittle attention t o cultural, economic, and other envi-
ronmental influences in their accounts of mental abilities such as
low scores on IQ tests and social behaviors such as prostitution.
Some of Davenport's trait categories w e r e ludicrous, particularly
in studies on the inheritance of w h a t he called " n o r m a d i s m " ,
"shiftlessness", and "thalassophilia" - t h e love of the sea that he
discerned in naval officers and concluded must be a sex-linked
recessive trait because, like color blindness, it was almost always
expressed in males.

Class and race prejudice w e r e pervasive in eugenic science. In

northern Europe and the United States, eugenics expressed stand-
ards of fitñess and social valué that w e r e predominantly white,
middle class, Protestant - a n d indentified with "Aryans". In the as-
sumptive reasoning of eugenicists, lower-income groups w e r e
not poor because they had inadequate educational and economic
opportunity but because their moral and educational capacities,
rooted in their biology, w e r e inadequate. W h e n eugenicists cele-
brated Aryans they demonstrated nothing more than their o w n
racial biases. Davenport, indulging in unsupportable anthropology,
found the Poles "independent and selfreliant though clannish"; 371
the Italians tending t o "crimes of personal violence"; and the He-
brews " i n t e r m e d i a t e b e t w e e n t h e slovenly Servians and t h e
Greeks and the tldy Swedes, Germán, and Bohemlans" and givlng
t o "thleving" though rarely t o "personal violence". He expected
that the "great influx of blood f r o m Southeastern Europe" would
rapidly make the American population "darker in pigmentation,
smaller in stature, more mercurial... more given t o crimes of lar-
ceny, kidnapping, assault, murder, rape, and sex-immorality".

In the I930s, in the United States and Britain at least, eugenic

science -eugenically colored theories of human heredity- was in-
creasingly criticized for its scientific shoddiness and social preju-
dice. It was charged with vagueness in Identification of putatively
heritable traits and w i t h uncritical acceptance of hearsay evi-
dence gathered in the field surveys. A n assessment of the Eugenics
Record Office pointed out, for example, that its vast body of re-
cords were worthless f o r the study of human genetics, not least
because they fastened upon traits such as personality, character,
sense of humor, self-respect, loyalty, holding a grudge, and the
like, all of which could seídom be measured o r honestly recorded
if they were. Eugenic science was also indicted f o r its distortions
of race and class bias and for its neglect of h o w social and cul-
tural environment might shape soca! behavior, not t o mention
performance on intelligence tests.

In the I930s and I940s, eugenics influenced the field of human

genetics in the United States and Britain partly by making it unat-
tractive t o most of the new generation of geneticists. T o be sure,
the field was unappealing partly because the techniques and skills
of plant and animal genetics, in which most geneticists w e r e train-
ed, did n o t readily transfer t o t h e study of human heredity,
which depended upon at least some medical knowledge as well
as special mathematical methods. However, in the United States,
where eugenic doctrine had been virulently deployed against mi-
nority groups, plant and animal geneticists were also discouraged
f r o m having anything t o do w i t h human genetics because of its
associations w i t h the racism, sterilizations, and scientific poppy-
cock. One American geneticists recalled having been warned that
it was just t o o difficult t o get the necessary reliable Information
on human heredity. " T h e r e c o r d s are p o o r ; classification is
poor... Let's w o r k w i t h experimental organisms. The only thing
you can do with human genetics is develop prejudices. A n d anyone
w h o w e n t into human genetics was immediately classified as a
person of prejudice".

However, the eugenic idea remained tantalizing t o some scien-

tists and drew an exceptionally talented cadre into human genet-
ics. The group included Ronald A. Fisher, J.B.S. Haldane, Lance-
lot Hogben, Julián Huzley, and Hermann J. Muller. One might cali
t h e m " r e f o r t n eugenicists" because, unlike t h e i r predecessors,
they held that any eugenics must be free of racial and class bias
372 and must also be made consistent with what was known about
the laws of heredity. In this latter regard, they had important
allies among physicians like the British authority in mental defi-
ciency Lionel Penrose, an anti-eugenicists, w h o thought that ge-
netics might be advantageously deployed in preventive o r thera-
peutic medicine. W h a t bound Penrose t o g e t h e r w i t h r e f o r m
eugenicists like Haldane was a deep-seated belief in the need t o
develop a sound science of human genetics.

Partly t o emancípate the field f r o m a prejudicial eugenics, the

new students of human heredity preferred t o search f o r well-
defined, sharply segregating traits as immune as possible both t o
uncertainty in Identification and t o environmental influence. They
thus welcomed with particular enthusiasm the rapidly increasing
knowledge of t h e human b l o o d groups, seven of w i c h w e r e
known by the early I930s, which displayed patterns of inherit-
ance that seemed t o conform t o Mendel's laws. The blook groups
promised t o open the d o o r t o the genetic mapping, via linkages,
of the human chromosomes. Hogben, in his influential Genetical
Principies in Medicine and Social Science, published in 1931, called
attention t o the recent development of mathematical methods
for transforming data into tests of linkage, adding that if unambi-
guous markers like t o blood groups could be found f o r every
c h r o m o s o m e , then t h e r e w o u l d be a set of socially unbiased
benchmarks in connection w i t h which the human genome could
be catalogued.

T o Hogben and others, linkage studies w e r e also promising f o r

eugenic prognosis. Eugenicists had long been stymied by the prob-
lem of tagging the heterozygous carriers of genes f o r recessive
traits, which w e r e not expressed until - t o o late f r o m a eugenic
point of v i e w - they joined homozygously in offspring. Linkage
studies might revea! that a deleterious recessive gene occurred
on the same chromosome as did one of the blood groups; anyone
found t o have that blood group w o u l d be spotlighted as a prob-
able carrier of the recessive. Similarly, if the gene was a dominant,
the Identification of an infant's blood group w o u l d enable one t o
predict the probability - i t w o u l d depend upon the degree of link-
age- that the disease resulting f r o m the dominant w o u l d be ex-
pressed in the child. Appropriate steps might then be taken t o
prevent the expression - o r at least t o mitígate the effects- of the
disease itself. If the disease came on late in the child-bearing
years, people fated t o contract it could be adised before they had
children of the chance of transmitting it t o their offspring and
they might then refrain f r o m reproduction.

A good deal of effort was expended, especially in England, on the

search f o r linkages, and also on surveys for consanguinity in the
families of hospital patients suspected of suffering from recessive
diseases. However, no linkages w e r e found between, on the one
side, the blood groups o r any o t h e r universal, non-sex-linked
character and, on the other, any type of genetic disease o r disor-
der. Hogben's team was similarly unsuccessful, and so was every 373
laboratory in the United States and Britain that attempted the
task. Almost as disappointing was the search f o r consanguinity.
Nevertheless, the research program of the thirties produced
powerful mathematical methods of linkage analysis and, for the
most part, a large amount of reliable data, particularly measures
in Britain of the national incidence of consanguinity as well as of
the incidence of numerous rare diseases. It was also advanta-
geous, Haldane noted, t o k n o w that single recessive genes did
not seem t o account f o r goitre, pyloric stenosis, harelip, o r spina
bifida, among other maladies.

A f t e r W o r l d W a r II, biologists i n t e r e s t e d inhuman genetics

sought t o emancípate the field entirely f r o m its eugenic associa-
tions and research ambitions. Lionel Penrose, appointed Galton
Professor and head of the eugenics laboratory at University C o l -
lege London, managed t o have his chair renamed the Galton
Professorship of Human Genetics, the title of the laboratory's
journal changed f r o m Annals of Eugenics t o Annals of Human Ge-
netics, and focus its w o r k on human and medical genetics as such,
particularly on the study of hereditary phenomena that could be
objectified quantitatively o r otherwise. Penrose's most important
ally was J.B.S. Haldane, the W e l d o n Professor of Biometry at
University College, w h o , although still eugenically inclined, back-
ed Penrose's scientific program, stressing in particular the essen-
tial importance t o human genetics of biochemistry.

In the United States during the postwar years, a key figure in liber-
ating human genetics f r o m its eugenic attachments was James V.
Neel, w h o had started o u t in fruit-fly genetics under C u r t Stern,
taken an M.D., and in 1948 assumed a joint faculty appointment
in the Medical School and the Laboratory of Vertébrate Biology
of the University of Michigan. Initiative f o r the creation of the
post seems t o have coe f r o m the head of the laboratory. Lee R.
Dice, a eugenically inclined ecologist w h o had persuaded the uni-
versity t o establish a small outpatient heredity clinic t o help peo-
pie learn whether they might have " b a d " genes. Neel assumed
responsibility f o r the clinic, and he spent part of his time ex-
ploring how the carriers of genetic disorders might be detected.
However, he recalled, " W h e n I came into human genetics, I had
one, I guess absolute, guiding principie: T r y t o be as rigorous as I
would have been had I remained w i t h Drosophila. That meant pick-
ing p r o b l e m s carefully, p r o b l e m s w h e r e w e c o u l d get solid
scientific evidence about inheritance in man". Neel's search f o r
solid scientific evidence - a n d f o r indicators of deleteriours ge-
netic c a r r i e r s - focused his attention on human blood. " Y o u can
spread it out, you can look at it, you can treat it objectively", he
remarked, and by the late 1940s he had w o r k e d o u t the genetics
of thalassemia and sickle-cell anemia.

During the I950s and I960s, human geneticists inb both the United
States, Britain, and elsewhere advanced the objectification of
374 human genetics considerably through biochemical and chromo-
somal research, further removing the field f r o m its eugenic past.
However that past remains alive in memory and an awareness of
it can assist us in thinking ethically about human genetics n o w
and in the future.

In this connection, several points might be kept in mind. Eugenics

was not an aberration, the commitment merely of a few oddballs
and mean-spirited social theorists. It was embraced by leading
biologists and it was integral t o the research programs of promi-
nent, powerful institutions devoted t o the study of human hered-
ity. The lure of alleged biological imperatives, having tantalized
capable scientists in the past, could equally seduce them in the
future, even though the expression of the imperatives may differ
in language and s o p h i s t i c a t i o n . Indeed, eugenics remained a
powerfully attractive idea even after the social prejudice of its
early f o r m was recognized and exposed. Objective, socially un-
prejudiced knowledge - t h e type sought by Haldane, Hogben, and
their like-minded colleagues- is not ipso fado inconsistent w i t h
eugenic goals of some type. Such knowledge may, indeed, assist
in seeking them. The enrichment of human genetics by molecular
biology has in fact prompted some leading contemporary biolo-
gists t o raise w i t h enthusiasm the possibility of a " n e w eugenics"
- a eugenics that, in the vein of the reform eugenic program of the
1930s, cold be free of social bias and, as a result of D N A engineer-
ing, could be scientifically achievable. The more that is learned
in the f u t u r e about human genetics, the m o r e might it edge
towards a reunión with eugenic goals - w i t h all the hazards that
such a reunión w o u l d entail.

Nevertheless, I doubt that a new eugenics will soon arise - a t

least not an overt eugenics. The social and ethical challenges of
the Human Genome Initiative lie in the detailed issues on which
this conference has focused, notably the use of genetic information
in genetic counseling, diagnostic testing, insurance, and employ-
ment. The issues will t u r n on economic costs - w h o pays for what
and how m u c h - rather than on the quality of the gene pool as
such. However, it is w o r t h remembering that the pursuit of hu-
man genetic knowledge was intimately a part of t h e eugenics
movement and that the results of this research - t h e claims of
what human qualities, especially behavioral ones, w e r e genetic-
established part of what we deplore about the eugenics move-
ment. A n d one hears echóse of eugenic discourse in some of the
claims -well-intentioned though they may b e - by contemporary
practitioners of behavioral genetics.

Many early eugenicists w e r e scientifically and socially wellinten-

tioned, t o o . Indeed, politically, a number w e r e progressives o r
advocates of the socialist left. Goddard argued that, since certain
anti-social deviates w e r e feebleminded and that since their flee-
blemindedness resulted f r o m their genes, they w e r e n o t truly
responsible for their behavior. He suggested that they should not
be imprisoned but should be placed in therapeutic institutions, 375
where educations and training might make up f o r their genetic
inadequacies. Yet however well-intentioned, their research yield-
ed claims about the genetics of intellectual capacity and moral
behavior that w e r e stlgmatizlng t o the so-called feelbeminded
and members of various mlnority groups - a n d that w e r e f o r the
most part utterly w r o n g .

N o doubt similar good intentions lie behind contemporary claims

made about the genetics of behavior and mental disorder. H o w -
ever, there is reason t o suspect that result concerning the genet-
ics of, f o r example, alcoholism, manic depression, and the like
may also be w r o n g and may also be socially stigmatizing as well
as hurtful t o families. The categories of behavior that one finds
specified in some of this resarch are, in the vein of the early eu-
genic studies, of decidedly dubious merit. Declarations that a
propensity f o r "traditionalism" is genetically based frankly cali t o
mind Davenport's analysis of thalassophilia. The inferences about
genetics drawn from these studies raise doubts in the mind of any-
one familiar w i t h the early eugenic literature. Just because ge-
netic conclusions are couched in the language of RFLPs does not
make the behavior categories about which the conclusions are
reached any m o r e reliable o r persuasive.

Perhaps a code of ethics is needed for how genomic analyses of

behavior should be handled. Perhaps, because of their stigma-
tizing potential, they should be published in a journal unabashedly
entitled, " T h e Journal of Results that May Be W r o n g " . Perhaps
they should n o t be announced in press conferences. M o r e se-
riously, perhaps the genomic community should establish stand-
ards for h o w t o deal with socially charged Information. The great-
er the social explosiveness, the m o r e rigorous should be the
requirements of rigor and reliability for its publication. Whatever
the case, the influence of eugenics on the history of human genet-
ics suggests that it is not only h o w the results of research are
applied that merits ethical scrutiny. It is also what questions are
asked about human behavior, including racial and sexual differ-
ences - a n d h o w the results are handled.
376

REFERENCES

A d a m s , M a r k B., e d . The Wellborn Science: Eugenics in Germany, franee,

Brazil, and Russia. N e w Y o r k , 1990.

A l i e n , G a r l a n d E . " T h e Eugenics Record Office at C o l d Spring Harbor,

1910-1940". Osiris, 2d ser., 2 (1986), 225-64.

C r a v e n s , H a m i l t o n , The Triumph of Evolution: American Scientists and

the Heredity-Environment Controversy, 1900-1940. Philadelphia, 1978.

G r a h a m , L o r e n R. Beíween Science and Valúes. N e w Y o r k , 1981.

H a l l a r , M a r k , Eugenics: Hereditarian Attitudes in American Thought N e w

Brunswick, 1963.

K e v i e s , D a n i e l J . , In the Nome of Eugenics: Genetics and the Uses of Hu-

man Heredity. N e w Y o r k , 1985; Berkeley, 1986.

M ü l l e r - H I I I , B e n n o . Murderous Science: Elimination by Scientific Selection

ofjews, Gypsies, and Others, Germany, 1933-1945. O x f o r d , 1988.

P r o c t o r , R o b e r t N . Racial Hygiene: Medicine Under the Nazis. Cam-

bridge, 1988.

W e i s s , S h e l l a F a i t h . Roce Hygiene and National Efficiency: The Eugenics

ofWilhelm Schallmayer. Berkeley, 1987.
 377

LESSONS FROM T H E PAST:

PROJECTS F O R T H E FUTURE.
THE HUMAN CENOME
PROJECT AND T H E SOCIAL
CONTRACT: AN APPROACH
OF LECAL POLICY

Christian Byk

Member of the Bioethical C o m m i t t e e of the Council of Europe,

Secretar/ General t o the Milazzo Group. París (France)

ABSTRACT

Science and ¡aw co-exist, although they are confront-

ed in certain instances. The H u m a n Genome Project
wil give a unique character to each h u m a n being,
and it is only logical to think o f the impücations to be
derived f r o m this fact, implications on which Law
musí give its opinión. This project must count upon
internationaí iaws for the respect for law a n d profes-
sionai ethics on the one hand, a n d for human rights
on the other.
H o w could the Human Genome Project and its applications in 379
medicine benefits f r o m the lessons of the past in matter of law?
Is t h e influence of Law so p o w e r f u l t h a t it could have some
influence upon the development of Science? D o n ' t you believe it
would be merely presumptuos t o think we could draw f r o m the
Law some useful lessons which could be used t o define w h a t
should be the Human Genome analysis?

The only lesson f r o m the past I have in mind is Galilee's story.

Thus I could conclude here this speech telling you that the best
thing we could imagine f o r the Genome Project is that it should
not become a matter of law w i t h perhaps one exception about
which I will tell you n o w a few words. In Galilee's story, Science
and Law come into conflict because the concept of Science im-
plied by the theory of Galilee and the concept of Law used by his
opponents and judges opposed t w o worlds. Galilee's w o r l d was
announcing a new period in human development in which Science
will obey its o w n rules while the w o r l d of his judges was large
ly based on religious principies which w e r e supposed t o apply
t o all human activities. As far as the Law in no more considered
as a part of a global and unique view of h o w universe is con-
ceived, the danger has disappeared. However, if the Law is not a
way t o enforce the idea we have about how our w o r l d should
be, what should the Law do?

Let me imagine that the Law is useless and that the p o w e r of

Science is sufficient enough t o organize our life. But does Science
say anything about justice, human rights o r m o r e simply about
the way t o divorce and t o pay alimony t o your wife?

W e could then conclude that Science and Law, although they have
their o w n autonomy, belong t o the same w o r l d . In this w o r l d
no one of them could dominate the other. Both are necessary t o
organize and even p r o m o t e our every day life. Then, I come t o
my exception which I consider myself as the main role of the
Law. The Law, I mean the legal approach, should not be regarded
as an independant system of control and sanctions but as a realis-
tic t o o l t o maintain a cióse relationship between Science and So-
ciety, t o make aware all those concerned by these t w o elements
that the context in which Science is developing supposes a per-
manent interaction between Society and the scientific activities.

As far as w e agree on this process, the problems are simple. Law

does not intend t o stop the development of sciences and we be-
lieve Science will not transform o u r w o r l d into a big laboratory.
So the problematic is only t o find a way in which Science and
Law could opérate all together. Unfortunately, this is where our
difficulties begin.

As regard t o the Human Genome analysis which aims t o bring us

a better knowledge of o u r genetic individuality, we have t o con-
380 sider how far this project could affect our society, which evolu-
tion w e could admit and which w e should not.

For the first time in human history, the knowledge in genetics

will enable science t o completely identify and differentiate each
human as genetically unique '. W i l l the possibility which are then
opened t o individual differentiation affect the Social C o n t r a c t
which govern Society? W i l l it reinforce the trend for more indi-
vidual liberties? O r will it créate a "brave new w o r l d " in which in-
dividual differences will be the basis of social inequality? In her ad-
dress t o the Fifth Economic Summit Conference held in 1988 in
Roma, Prof. B.M. Knoppers expressed the view that the develop-
ment of genetics implies the renegotiation of the Social Contract
and suggested t w o founding principies: reciprocity which means
exchange of Information and mutuality which means civic respon-
sibility 2.

I can neither assure you that the genetics technologies will lead
t o the renegotiation of the Social C o n t r a c t ñ o r that the Law
could solve all the questions raised by the genetics technologies.

However, I would like t o show that a legal approach is necessary

t o offer t o o u r Society a way t o deal democratically w i t h the so-
cietal cholees related t o the use of Genetics.

The simple reference t o the scientific means and the tremendous

amount of money which will be devoted in the Human Genome
analysis w o u l d have been sufficient enough t o demónstrate " h o w
big and how fast" public authorities and the community in general
are concerned with Genome Projects3.

But other reasons justify a public policy approach of this ques-

tion: the fears and anxiety raised in the population by the biologi-
cal revolution 4 but also the interrogations of scientists t h e m -
selves about what they should do with the new biological power 5.

If w e consider institutionnal issues are legal issues, the analysis of

the role played by our democratic institutions in the Human Ge-
nome debate reveáis a complete failure.

W i t h the exception of the USA6, Germany7 and Sweden 7'1, no

official assessment has been realized on the implications of the
human genome analysis. Some countries addressed specific issues
such as prenatal diagnosis, gene therapy o r the use of D N A fin-
gerprints. But neither the executive of the legislative branches
which are supposed t o represent the citizens did tackle w i t h
such a question.

The factual reason is probably that apart Japan 8 and the U.S.A.9
no other country in W e s t e r n Europe launched its o w n program
in o r d e r t o map and sequence the Human Genome. Countries
are either associated in the Humane Genome Organization 10 or.
as member of the EEC, they are part in the European C o m m u - 381
nity project on genome analysis 1'.

The conceptual reason is that traditional public mechanisms have

n o t till n o w been equal t o the task of debating the questions
raised by the new biology.

Governments which function often as leaders of many legislative

initiatives have been very reluctant t o address such issues. In
France, f o r example, the Government asked f o r severa! reports
in the field of bioethics 12 and even f o r a draft bilí l3, but always
refused t o go f u r t h e r in the legislative process. In the United
Kingdom, where the Government presented a bilí on embryo re-
search in Parliamentl4, the proposed t e x t left fuil cholee t o M.P's
between the prohibition of research and its regulation.

Legislative bodies have not better succeeded in this way. So far

as I know, there has been little significant legislative activity of a
traditional sort on the subject of the new biology - t h a t is, by a
committee made up solely of members of the legislation consider-
ing a bilí, through hearings and committee deliberation, leading
t o a debate on the floor of the legislature and eventually t o the
adoption of a status. A . M . Capron, w h o directed the U.S. Presi-
dent's Commission f o r the Study of Ethical Problems in Medicine
and Biomedical and Behavioral Research (1979-1983), explained
that "legislators w a n t probably t o stay at some distance f r o m
controversia! issues in particular when a topic seems t o implícate
the issue of abortion. But they also realize that these issues re-
quire more sustained analysis than the legislative committee pro-
cess w o u l d allow" l5. Federal systems are also concerned w i t h
the specific problem t o know at what leve! of government the
question should be addressed. Judicial cases constitute another
c u s t o m a r y f o r u m f o r law-making, especially in c o m m o n law
countries.

There has been some significant decisions by courts in the field

of the new biology such as the N e w Jersey Supreme C o u r t deci-
sión on surrogate m o t h e r h o o d in the Baby M case in 1988 l6.

As regard t o genetics, courts have also dealt with cases in pre-

natal diagnosis 17 o r the possibility t o patent living organisms l8.
The disclosure t o third parties (employers, insurance companies)
of Information obtained by genetic testing of adults is also an im-
portant matter f o r litigation l9.

Yet the courts are ill-suited t o resolve all the questions in the
context of existing law and the control of research experimenta-
r o n can not be accomplished by courts w i t h o u t any specific legal
references.

In matter of very difficult legal issues, case law does not also per-
mit t o know a priori what will be the legal solution adopted.
382 lf existing institutional mechanisms have not yet been able t o play
their role in setting up a democratic debate in the fleld of ge-
netics, w h o should do?

As other fields related t o the new biology, genetics led t o the de-
velopment of new institutions.

T w o categories of institutions are concerned.

The mándate f o r most of the groups in the first category is di-

rectly related t o public policy and the law.

W h a t solution should the government bring t o a particular acti-

vity?

Some of these institutions have been mandated t o give their o w n

views on such an issue and t o propose guidelines f o r a coming
legislation.

This was the case in Germany w i t h the Benda report on genome

analysis20.

O t h e r groups are only requested t o address the state of the art

and t o present the different alternatives offered t o the legislator.

This is mainly the task of O T A in the United States w i t h its ma-

j o r reports on Gene Therapy, Genetic Testing in Occupational
Disease and Mapping o u r Genes 2I).

A second characteristic of the groups in this first category is

autonomy.

Although they usually r e p o r t t o the government o r t o the legisla-

t o r , these groups are independant from the existing administra-
tive framework.

Sometimes, they are just ad hoc commissions outside the admi-

nistration but relying on the administrative s u p p o r t of some
ministries.

In other cases they are permanent autonomous institutitons al-

ready existing t o help public authorities in defining new policies.
The best examples is provided by the Law Reform commissions
in several provinces of Canadá and States in Australia 22. It is also
the case o f t h e ethical Commission of the Medical Research
Council in Canadá, Australia, N o r d i c countries and in the United
Kingdom 23.

Finally, new institutions have been created in some countries t o

deal specifically w i t h bioethics issues. Such is the task in France
of the C o m i t é consultatif national d'ethique 24 o r in the United
States of the Congressional Biomedical Ethics Advisory C o m -
mittee25. National committees also exist in Australia26, D e n - 383
mark27, Italy28, L u x e m b o u r g , Malta, Portugal 29 and Sweden.
Spain is planning t o have its o w n very soon.

The issue of membership is very important t o look at the demo-

cratic aspects of these institutions. W i t h the exception of the
Law R e f o r m C o m m i s s i o n s , biomedical scientists and p r a c t i -
tioners domínate the groups. This fact does not in itself seem a
ground f o r criticizing a committee but it shows the limits of en-
larging the bioethical debate t o other professional groups.

However, lawyers, ethical and religious experts, as well as so-

cial scientists and m e m b e r s o f t h e general public are often
represented.

The second category of institutions concerned is formed by the

increasing number of institutional review boards which are in the
different countries in charge t o review research protocols.

O f course, their major task is scientific review but they also con-
tribute t o the diffusion of ethics in research and practise.

The institutions, not all completely novel, that I have just described
have played till n o w a major role in the development of bio-
ethics. The w o r k they have accomplished multidisciplinar/, asses-
sing and proposing bodies is great and their will probably extend
their jurisdictions in the coming months t o other áreas covered
by genetics 30.

However t w o lessons can probably be drawn f r o m the present

experience.

First, this is the importance of methodology in the legal approach

of ethical issues.

Is the group empaneled t o address a single issue o r an ongoing

set of issues? A group w i t h a broad mándate has certainly the ad-
vantage t o give a more coherent view on matter of law but a t o o
broad mándate risks creating an ethics "bureaucracy".

Then comes the need f o r this new institutions t o justify that the
w o r k accomplished, especially w h e n it includes guidelines o r
draft legislation, takes into account the different opinions existing
in the community. In o r d e r t o satisfy w i t h such an objective, spe-
cific methodology should be set up.

I will say t h a t objective and impartial r e p o r t i n g is insufficient.

Public opinión should n o t get the feeling that the new institu-
tions are w o r k i n g on an insularity basis. Therefore a major effort
t o communicate should be done by institutions in carge w i t h
studying the legal and ethical questions raised by genetics.
384 Large symposiums should be organized t o make the public aware
of the importance and o p p o r t u n i t y t o deal w i t h such issue 3I.
Pre-reports should also be published and public hearings held in
different localitles.

The aim is not t o built a false consensus but t o créate interaction

between the proposals of the commission and the comments of
the public.

The methodology adopted by Law Reform commissions in Austra-

lia and Canadá constitutes a good example of what could be done.

The impact of the Human Genome analysis will probably impose

the setting up of amplified and permanent means t o fulfil w i t h this
task.

A second issue of great importance is t o k n o w h o w a further

step could be accomplished in t e r m of legislative process?

Except if al! those groups come t o the conclusión than there is

absolutely no need f o r legislation, we have t o think about this
question: h o w should a decisión be taken?

W e observed that in many issues the executive and legislative

branches have been reluctant t o take the initiative of Law Reform.

Does it mean that the oniy possible reform is, as it was realized
in Switzerland, t o mention in the law that the principies elabo-
rated by one of those new institutions should apply t o the mat-
t e r concerned?32.

Couldn't w e do an effort on this point and imagine an Interactive

approach that could contribute t o p r o m o t e a democratic pro-
cess of decisión?

Public votes are already used in societal issues. If it consists in

letting a group of citizens drafting a bilí and collecting signatures
t o submit this bilí t o a ballot such a procedure could be risky be-
cause it will exacérbate particular interests and controversial de-
bate 33. But if it obliges the government t o propose its o w n bilí
o r counter-project either t o Parliament o r t o the vote of the
citizens, it could sometimes stimulate in a good manner the p r o -
cess of law.

A popular initiative of Swiss citizens on reproductive medicine is

under way t o be transformed by the Swiss Federal Council in a
governmental counter-project largely based on the proposals of
the federal commission on reproductive medicine34.

My remarks concerning the institutional approach w o u l d have

not been complete w i t h o u t saying a few w o r d s about Interna-
tional cooperation.
It is obvious that scientific cooperation is a professional necessity 385
f r o m those involved in the ambituous program of genome analy-
sis. The Human Genome Project has already been conceived on
the basis of international cooperation 35, Therefore, the question
of international legal cooperation is already posed in t w o ways.

First w e should consider h o w t h e ethical and legal guidelines

which w o u l d apply t o the coming common research realized on
the ground of such a cooperation will be elaborated?

W h o is going t o do it? H o w could it be enforce? Could some na-

tional authorities prevent scientists in their juridictions t o particí-
pate in the Human Genome Project? For example, you k n o w
that the European Commission has not yet accepted t o particí-
pate in H U G O 3 6 .

Secondly, w h a t will be the appropriate international f o r u m f o r le-

gal cooperation?

The Council of Europe has since many years adopted a method-

ology and a program in bioethics and genetics but it is only a re-
gional organization 37. O n the International level, w h o has no in-
ternational program of cooperation except t h e publication of
national legislations.

So, do we need a specific organization linked t o H U G O as w e

n o w have an international ethics c o m m i t t e e on AIDS o r is it
possible, as the Secretary General of the Council of Europe sug-
gested, t o develop an international cooperation f r o m a regional
one 38.

Unesco which since 1990 has established a t w o year program on

Science and Ethics could also bring its contribution t o the rela-
tionship between Science, Ethics and Culture39.

I k n o w that many of the international projects concerning the

Human Genome analysis such as H U G O o r the EEC program
have now substantial money t o fund ethical and legal studies.

I have no idea of what was the mind of those w h o decided t o in-

clude this legal studies in their programs but I guess that they
merely wanted t o prove that these programs will be realized in
respect w i t h the law and professional ethics.

However, this p r o p o r t i o n of legal and ethical w o r k will appear

quite illusory if, prior t o any study, some principies are not inter-
nationally recognized t o be used as references. A m o n g these
principies comes first the respect of the rights of individuáis such
as informed consent, confidentiality and access t o genetic data.
But equitable diffusion of genetic Information f o r scientific and
therapeutic purposes, prohibition of any military use of genetic
Information as well as the prohibition of compulsory state policy
386 which could affect the individual genetic inheritage should also be
considered.

T h e r e f o r e , legal and ethical studies at t h e international leve!

should also be coordinated t o facilítate the assessment of inter-
national programs and approphate decisions.

It is then rather difficult t o reach t o any other conclusión than

the following!

Mapping and sequencing the Human Genome supposes first map-

ping and sequencing the legal approach t o the Human Genome
Project.
 387

REFERENCES

1. J o r d á n , B e r t r a n d . 1989. Les cantes du génome humain, in La

Recherche. Vol. 20, n0 216. Dec. 1989, p. 1487.

2. K n o p p e r s , B . M . 1988. Human Genetics, Predisposition and t h e

N e w Social C o n t r a c t , Fifh Economic Summit Conference o n Bio-
ethics, Sequencing t h e Human Genome, Ethical and Social Issues.
Roma. A p r i l 10-15, 1988, Class International, 1989, p. 168.

3. N a s h , J . M a d e l e i n e a n d T h o m p s o n , D. 1989. T h e Gene
Hunt. Time magazine. March 20, 1989, p. 58.

4. C o u n c í l f o r Responsíble G e n e t i c s . Position Paper o n Humane

Genome Initiative. Genewoích, vol. 6, n0 4-5, p. 3.

5. R e n é , L . , D r . 1989. Chairman o f t h e O r d r e des Médecins, t h e

French Medical Association, Agir sur le Génome, Bulletin de /'Ordre.
Sept. 1989, p. I.

6. O f f i c e o f T e c h n o l o g y A s s e s s m e n t 1988. Mapping o u r Genes.

Washington D.C. A p r i l 1988.

7-1 S e n d a C o m m i s s i o n 1985. In-Vitro-Fertilization, Genomanalyse

und Gentherapie. J. Schweitzer Verlag, 1985.

7. I. C o m m i t t e o f G e n e t i c s 1984. Genetic Integrity, Ministry o f

Social Affairs, 1984.

8. O T A , 1988. Mapping our genes. Washington, april 1988, p. 136.

9. H u m a n G e n o m e Initiative 1989. Human Genome Quarterly.

Vol. I, n0 I. Spring 1989, p. I.

10. H u m a n e G e n o m e I, held O c t 2-4, 1989 in San Diego (USA)

described status o f gene research cooperation.

11. O T A . Id., p. 139.

12. A l n o t , M . O . a n d o t h e r s . Les procréations artifícielles. La Docu-

mentation Frangaise, 1986 and Counseil d'Etat, D e l'Ethique au
D r o i t , La D o c u m e n t a r o n Fran^aise, 1988.

13. A v a n t - p r o j e c t d e loi relatif aux droits de l'homme e t aux sci-

ences de la vie, r e p o r t t o t h e French Prime Minister, 1989.
388 i 4. H u m a n F e r t i l i z a t i o n a n d E m b r y o l o g y Bill 1989.

15. C a p r o n , A . M. 1990. T h e N e w Ethical Institutions. International

Journal of Bioethics. Vol. I, n0 I, 1990, p. 43.

16. In t h e matter o f Baby M, Supreme C o u r t o f N e w Jersey, Feb. 3,

1988.

17. K n o p p e r s , B . M. 1986. Conception artificielle et responsabilíté

médicale. Ed. Y. Blais Inc, Cowansville, 1986, p. 82.

18. B e i e r , F . K.; C r e s p i , R. S . a n d S t r a u s s , J . , Biotechnologie e t

p r o t e c t i o n par bravet, une analyse Internationale, O C D E , París,
1985; O T A , N e w developments in Bioetechnology, I O w n e r s h i p
of Human Tissues and Cells, Washington D C 1987, 5 Patenting
Life, W a s h . D C , 1989.

19. O T A 1983. The Role of Genet/c Testing in the Preventíon of Occupa-

tional Disease. W a s h . D C . 1983; p. I I I , N e l k l n , D . a n d T a n c r e -
dl, L., Dongerous Diagnosis: The Social Power of Biological Information.
N e w Y o r k , Basic Books, 1989.

20. See n o t e (7).

21. O T A . The Role of Genet/c Testing in the Preventíon of Occupatíonal

Disease. W a s h . D C . 1983; G e n e T h e r a p y , 1984; Mapping o u r
Genes, 1988.

22. See t h e w o r k i n g document issued by t h e Law Reform C o m m i s -

sion o f Canadá o n biomedical research (1989), that 1985 O n t a r i o
Law R e f o r m C o m m i s s i o n r e p o r t o n r e p r o d u c t i v e technologies
and t h e n u m e r o u s r e p o r t s published by t h e N e w South W a l e s
Law Reform Commission (organ transplants. Artificial Insemina-
t i o n , IVF, surrogate m o t h e r h o o d ) .

23. In Canadá, t h e Medical Research Council played an i m p o r t a n t role

in t h e elaboration o f guidelines concerning research o n human
beings; in Australia, t h e first national guidelines concerning r e p r o -
ductive technologies w e r e elaborated by t h e National Health and
Medical Research Council Ethics C o m m i t t e e .

24. Presidential decree o f Feb. 23, 1983 instauring t h e C o m i t é consul-

tatif national d'éthique p o u r le sciences de la vie e t de la santé.

25. Established by statute (P.L 99-158), t h e Biomedical Ethics A d v i -

s o r y C o m m i t t e e is c o m p o s e d o f 14 m e m b e r s distinguished in
fields relating t o biomedical ethics.

26. T h e N a t i o n a l B i o e t h i c s C o n s u l t a t i v e C o m m i t t e e has been

set up in 1989 by t h e Federal G o v e r n m e n t .

27. T h e D a n i s h C o u n c i l o f E t h i c s has been established by law

n.0 353 o f June 3, 1987.

28. T h e ¡ t a l l a n C o m m i t t e e has been set up in March 1990 and

consists in 40 members.

29. T h e P o r t u g u e s e c o m m i t t e e created in June 1990 is very simi-

lar t o t h e French C o m m i t t e e .
30. For a comparative overview o f National Ethics C o m m i t t e e s , see 389
B y k , C . Les instances d'étique en droit comparé in Cahiers Interna-
tionaux de Sociologie, V o l . L X X X V I I I , 1990, p. 215.

31. See T h e International Symposium titled "Procreation Genetics and

the L a w " organised by t h e French G o v e r n m e n t in January 1985,
proceedings published by Actes Sud, 1985.

32. See A r t i c l e 13 o f t h e Legge sanitaria of A p r i l 18, 1989 of t h e can-

t ó n o f Ticino which explicitly says that physicians have t o apply
the guidelines o n reproductive medicine of t h e Swiss Academy o f
Medical Sciences.

33. See t h e 1988 Californian ballot initiative t o legalize voluntary e u -

thanasia. T h e initiative has in fact failed because t h e required n u m -
ber o f signatures has n o t been collected.

34. T h e initial project concerned t h e amendment o f article 121 o f t h e

federal constitution t o prohibit t h e potential abuses o f reproduc-
tive technologies and genetic engineering; see also t h e r e p o r t o f
the Commission d'experts p o u r la génétique humaine e t la méde-
cine de la r e p r o d u c t i o n , Berne, 1988.

35. T h e initial p r o j e c t w h i c h goes under t h e ñame H U G O (Human

G e n o m e Organization) was initiated by some 32 scientists f r o m
the participating countries.

36. This is largely due t o t h e action of European MP's w h o have c r i -

tized o n ethics grounds t h e proposed program o f t h e Commission
on predictive medicine. The adopted proposal which has been r e -
named genome analysis will last t w o years instead o f a previous
t h r e e years period.

37. T h e Parliamentary Assembly adopted several resolutions on genet-

ics and e m b r y o research (1982, 1986, 1989) while t h e C o m m i t t e e
of experts o n Bioethics ( C A H B I ) prepared since 1983 harmonized
guidelines in t h e different fields covered by bioethics.

38. See t h e declaration o f Mrs. C. Lalumiére, Secretary General, t o

the European Conference of Ministries of Justice held in Istanbul
(June 4-8, 1990).

39. U N E S C O , 1 9 9 0 - 1 9 9 1 . Program o n t h e ethical consequences

raised by Science and m o d e r n technologies, división o f science and
technology policies.
 39

DIAGNOSTIC PROOF AND

GENETIC TESTING

Alexander M , Capron

The Law Center, University of Southern California,

Los Angeles, California (USA)

ABSTRACT

Genetic testing a n d diagnostic p r o o f pose ethical

a n d legislative problems. The development a n d car-
rying out o f tests such as the detection o f phenylce-
tonuria in new-born infants or the detection o f Tay-
Sachs disease have shown the need for norms o f
application. The same may be said with regard to
genetic therapy. It is obvious that biomedicine is ad-
vancing rapidly a n d that the scientific aspects on the
one h a n d a n d the ethicai ones on the other, reiative
to the same research project, are not considered by
the same peopíe. This fact shows the need to revise
the personal perspectives o f experts in ethics a n d o f
legislators, to the extent that scientifíc-technical ad-
vances with social implications are made.
Introduction 393

A t a meeting devoted t o the future of a field as dynamic and

scientifically exciting as molecular genetics - a future tied today t o
the modern mantra, "mapping the Human G e n o m e " - it Is perhaps
n o t surprising (albeit somewhat dlsappointing) that only on the
last day does o u r attention t u r n t o history, t o draw "lessons
f r o m the past". Some of those lessons, as we have already heard,
are dramatic, Indeed horrlfying. It would, for example, be difflcult
(and very wrong) t o overlook the role that a perverted genetics
played in the Nazi policy of "racial hygiene". Ñ o r can w e ignore
the lingering effects of this eugenic heritage on clinical genetics in
the post-War era.

The Seemíng Innocence of Screening

and Testíng

In linking these "lessons f r o m the past" t o "prospects f o r the fu-

t u r e " , as the title for this session does, I am sure that the meet-
ing's organizers did n o t intend t o imply that w e are bound t o re-
peat t h e past, much less t h a t learning f r o m t h e past means
emulating it. Yet I suspect that were it possible t o put aside the
history of eugenics discussed by Professors Müller-Hill and Kevles,
the topic of my talk - " T e s t i n g and Screening"- w o u l d be less
likely t o raise concerns about the dangers of emulating the past.
That is, despite the attention and concern that has focused on
certain aspects of human genetics, such as genome mapping and
gene therapy, genetic testing and screening today provokes little
excitement.

Nevertheless, I will t r y t o show that screening and testing should

be topics of central concern t o anyone considering the ethical
issues raised by modern genetics. Furthermore, experiences w i t h
testing and screening have a great deal t o teach us about the
potential uses (and misuses) of the knowledge garnered through
mapping the Human Genome and about the potential f o r public
enthusiasm t o outrun medical knowledge.

The Focus of the Paper

W h i l e science is universal, ethics and public policy are very p r o -

vincial. For better o r w o r s e , this insularity (or, less pejoratively,
this particularity) is an inevitable aspect of my presentation,
which describes the development of screening and testing in
the United States, looking back t o n e w b o r n screening and pre-
394 natal testing, and t h e n f o r w a r d t o susceptibility and c a r r i e r
screening.

The rapid increase in the number and technical capacity of screen-

ing methods for ¡nherited conditions that can be expected over
the next decade will affect many relationships. Plainly, some spe-
cific legal responses t o this Increase in genetlc capabilities are
possible, such as the passage of legislation t o protect the confi-
dentiality of genetlc Information and t o prevent dlscrlmlnatlon
agalnst those w h o have - o r w h o are belleved t o be at hlgh risk of
developlng- a genetlc disablllty.

Yet such responses, valuable as they may be, only address symp-
toms and do not respond t o the underlylng problems that the
genetlc technlques uncover. If w e are t o address the fundamen-
tal issues, w e need t o elévate t h e m t o a level of much greater
publlc vlslblllty, f o r if deeper problems are going t o be over-
eóme, some collective redefinitlons in concepts and standards
will be required.

The history of screening and testing

Before w e can look t o these baslc Issues and attempt t o under-

stand their Implications f o r the future, we have t o look back t o
experiences with genetlc screening and testing. These t w o terms
are sometimes used interchangeably while other times they are
used, as I do here, t o refer t o sepárate though related activitles.
W h e n the difference Is drawn, screening connotes the initial ac-
tion and testing encompasses diagnostic follow-up.

Screening may be undertaken f o r several reasons. In the w o r d s

of a National Research Council study:

Genetlc screening may be defined as a search In a populatlon

of persons possessing certain genotypes that I) are already
assoclated w i t h disease o r predispose t o disease, 2) may lead
t o disease In their descendants, o r 3) produce other varla-
tions not known t o be assoclated with disease '.

The three types of screening -medical management, reproduc-

tive and research- mentioned in this deflnitlon can be further
differentiated in a n u m b e r of o t h e r ways. For example, one
might focus on whether the screening method Is well valldated
o r Is still experimental, o r w h e t h e r It Involves a biochemical test
f o r a gene p r o d u c t , a d i r e c t enzyme assay, o r an analysis of
varlations in D N A base-pairs withln in a kindred. Based upon the
results of a screen, further diagnostic testing may then be under-
taken t o confirm o r rule o u t the existence of the genetic condi- 395
tion in question.

Screening f o r T r e a t m e n t : The P K U Story

The earliest mass genetic screening p r o g r a m in t h e U n i t e d

States is n o w almost three decades oíd: newborn screening f o r
PKU (phenylketonruia). Looking back at this program - w h i c h is
so r o u t i n e today t h a t it hardly ever excites any professional
much less public a t t e n t i o n - reveáis a history that may be very in-
fomative f o r those engaged in genome research today. As w e
will see, the lessons concerns scientific naTvete, medical mis-
takes, public overconfidence, premature action, and a willingness
t o use coerción t o achive collective goals. Furthermore, it may
be that some of the concepts absorbed f r o m screening f o r in-
born errors of metabolism (such as PKU) are misleading as w e
move into an era when genetic screening may aim at conditions
that are at once m o r e complex and less obvious than the single-
gene defects that have been the major focus of medical genetics
until now.

In PKU, defects in the metabolic process in which phenylalanine

is catalyzed t o tyrosine creates an amino acid imbalance that pro-
duces harmful changes in the central nervous system. It had been
known since the I930s that an elevated level of phenylalanine is
associated w i t h mental retardation 2. A n d by the mid-1950s it
had been shown that lowering dietary phenylalanine could re-
verse PKU's major biochemical abnormalities. Y e t by the time
the condition is clinically detectable, it is t o o late t o institute die-
tary t r e a t m e n t because severe and irreversible mental damage
has already occurred.

Thus, effective t r e a t m e n t of PKU became possible only when, in

1961, Dr. Robert Guthrie developed a bacterial inhibition assay
that could be applied t o tiny blood specimens collected on filter
paper f r o m a heel prick of new bables right before discharge
f r o m the hispital. Field testing of the Guthrie method began in
1962 and showed that when the test was used w i t h infants w h o
had had adequate exposure t o proteins, the blood screening
method let few false negatives slip by. In o r d e r t o avoid missing
cases, the presumptive level of serum phenylalanine was set
fairly low, which produces a high rate of false positives (over
90%). Thus, diagnosis depends upon f o l l o w - u p testing, ideally
during the flrst month of life. Children found t o have PKU can
then be placed on a commercially available diet that has a very
low level of phenylalanine (while also supplying other essential
396 amino acids); it is recommended that they remain on the diet in-
t o late childhood.

Although at the time, the inicial triáis of the Guthrie assay left
many questions unanswered - b o t h about the testing methods and
about the disease itself- the prospect that a cause of retardation
could be eliminated soon generated enthusiasm among the natio-
nal and state mental retardation associations f o r routine screen-
ing of all newborns. In Massachusetts, the state healt department
promoted a large-scale trial (with the state lab being responsible
f o r r u n n i n g t h e assays o n t h e s e r u m specimens) t h a t was
successful in screening most infants. This trial program operated
w i t h o u t legal compulsión, yet in 1963 the state became the first
t o adopt a mandatory genetic screening statute - s p u r r e d by the
health department director (who also chaired the public health
services committee of what is n o w known as N A R C , the National
Association f o r Retarded Citizens).

A t the time, the N A R C committee merely urged states t o adopt

laws directing each state health board " t o make recommenda-
tions for approphate screening tests as they are developed and
accepted". The following October, however, N A R C adopted the
committee's conclusión that states be recommended t o adopt
laws requiring PKU screening f o r all newborns. By the end of
1965, a majority of states in the USA had such laws. Althogh a
few have since repealed t h e m , 45 states still have mandatory
statutes.

The adoption of such laws seems puzzling, not the least because
the voluntary programs seemed t o have been reaching most in-
fants. Moreover, the rush t o legislate occurred well before an-
swers w e r e available t o several important biomedical questions,
as the Nationl Research Council committee observed a decade
later. In particular, the signiflcance of elevated phenylalanine was
n o t well understood at the time, ñor had the variations f r o m
"classical P K U " been differentiated. For example, the fact that
some degree of hyperphenylalanemia does not necessarily cause
retardation was n o t fully established; yet this meant that a large
number of the children placed on a low phenylalanine diet w e r e
n o t at risk f o r retardation in the first place, which confounded in-
t e r p r e t a t i o n of the studies t h a t aimed t o determine w h e t h e r
adopting the diet could ensure normal inteiligence in children
w i t h PKU.

Likewise, the adoption of widespread screening occurred before

sufficient time had elapsed even t o measure the regime's impact
on inteiligence, which requires the testing of capacities that are
not reliably measaured until later in childhood. And the proper
level of phenylalanine - t o avoid the detrimental effects of too Hule 397
of this essential amino acid (as well as inadequate t y r o s i n e ) - had
n o t been w o r k e d out, ñor had physicians decided when it was
safe for children t o go off the special diet (age 2, 6, 10, o r never?).

The history of screening for PKU in the USA (which has been fol-
lowed in a number of states by the addition t o the screening stat-
utes of o t h e r rare inborn errors of metabolism such as Maple
Syrup Uriñe disease) is interesting but the details are less impor-
tant for our present discussion than the implications of the whole
experience f o r potential uses of the data n o w being produced
by the genomic cartographers. Before we further explore those
implications for gene mapping, w e should look briefly at another
área of "testing and screening", namely experiences w i t h repro-
ductive screening.

Screening f o r R e p r o d u c t i v e Purposes:
Tay-Sachs a n d Sickle Ce//

Given the way the public and its elected representatives w e r e

convinced t o support mandatory PKU screening - t h a t is, as a
means of preventing mental retardation- it seems hardly surprising
that the programs w e r e generally not perceived as "genetic" at
all. Instead, in the USA the public's recognition of the potential
impact of truly genetic testing came a decade later w i t h the com-
mencement of a number of efforts t o screen carriers of auto-
somal recessive disorders. Such screening produces information
that typically has no necessary implication f o r the health of the
person screened but that indicates a risk (usually 25% in each
pregnancy) f o r offspring if one's mate also carries the same (or a
similar) abnormal gene.

Screening f o r t w o diseases in the early t o m i d - l 9 7 0 s provide

illustrative examples, b o t h involving diseases t h a t o c c u r at a
much higher than average rate in a minority population in the
United States. The first is largely a success story: beginning in
the Baltimore-Washington área in the early I970s, community
based screening programs for Tay-Sachs disease (a progressive
neurological disorder that is typically fatal between the second
and fifth year of life) w e r e offered t o Jews of Eastern European
extraction. Success is measured not in the large percentage of
the at-risk population of child-bearing age w h o participated but
rather in such facts as: I) a good educational effort, resulting in
only a small percentage of the nonparticipants having not heard
of the program, 2) enrollment having been based on informed,
v o l u n t a r y consent of adults ( m o s t programs w o u l d n o t t e s t
398 children), and 3) confidentiality of test result having been main-
tained.3

Several factors w e r e probably crucial t o the success of those

programs that w o r k e d . First, the programs w e r e mounted by
university researchers w h o -having no propietary interest In the
t e s t i n g - w e r e willing, indeed eager, t o have the ethlcal design of
their programs widely discussed both among colleagues and con-
sultants and w i t h the communities affected. Second, the p r o -
grams w e r e almed at a communlty with a sense of self-ldentity
and institutions (synagogues and communlty centers) where In-
formation about Tay-Sachs and the screening program could be
spread and particlpatlon could be endorsed by respected leaders.
T h i r d , the members of these communities w e r e usually well edu-
cated and sophlsticated users of the health care system. Fourth,
most children b o r n In these communities result f r o m marital
unions, so that both partners have a stake in knowing whether
they w e r e carriers and making reproductive decislons In light of
that knowledge. Fifth, and perhaps most Important, Tay-Sachs of-
fered something of real utility because it was linked w i t h the abil-
Ity t o perform a prenatal test f o r any pregnancy that resulted
f r o m the unión of t w o carriers; if the results showed the fetus t o
be homozygous for the Tay-Sachs gene, the parents could choose
t o termínate the pregnancy and t o conceive again, with 3:1 odds
favoring the next fetus n o t being affected. Although selectlve
abortion understandably excites concerns about genocide among
many ethnic and racial minorities, in the c o n t e x t of a severe
autosomal recessive c o n d i t l o n , t h e results o f screening and
prenatal diagnosis actually improve reproductive prospects withln
families in which the disease had previously occurred. W h e n a dis-
ease is devastating enough, many pregnant w o m e n will a b o r t
rather than run the risk (even if only 25%) of bearing (another)
affected child.

Despite the predicates of success, not all community-based Tay-

Sachs programs achieved a hlgh rate of screening; the program In
Montreal was one such example. And when higher rates opf screen-
ing w e r e obtaln, questions sometimes aróse about t h e i r ethl-
cality. As Holtzman observes, the more than seven-fold increase
in the rate of screening In the Montreal Jewish when a program
was introduced into the hlgh schools may well be attributed not
only t o the greater ease of obtaining specimens in that setting
but also t o external pressure4.

The risks of coerción and of adverse consequences t o persons

screened can be seen even more starkly In the experlence in the
USA w i t h screening in African-American communities f o r sickle
cell anemia carriers, which also began In the early I970s. A t this
time, no means of prenatal diagnosis existed, so that carrier-car- 399
her couples were faced w i t h the choice of not reproducing o r
of doing so with the knowledge of a 25% risk. A person identified
as a carrier might even not want prospective mates t o know this
information, f o r fear of being ostracized. Furthermore, some em-
ployers and insurers, acting f r o m ignorance o r malice, treated
heterozygotes f o r the sickle cell gene as though they had the di-
sease and attempted t o place limits on, o r even t o exelude, them.
Before these problems w i t h sickle cell carrier screening w e r e
perceived, screening programs w e r e launched by c o m m u n i t y
groups, m i n o r i t y politicians s u p p o r t e d governmental funding
(sometimes merely as a means t o get their constituents access t o
some portion of governmental health funds and t o draw the atten-
tion of researchers t o the disease), and seventeen states passed
laws mandating screening in a variety of settings, f r o m schools t o
marriage license bureaus t o custodial institutions. W i t h greater
clarity about the program's problems and the misuse of results,
Congress adopted t h e National Sickle Cell Anemia, Cooley's
Anemia, Tay-Sachs and Genetic Diseases A c t of 1976 under
which programs supported with federal funds have t o be "wholly
voluntar/'5.

Commenting on this episode, physician-lawyer Philip Reilley has

pointed t o the "glaring errors, including egregious drafting mis-
takes that hopelessly muddled the scientific faets about sickle
cell anemia" as demonstrating " t h e abyss that separates lawmak-
ers f r o m thechnical experts"6. Like the PKU experience, the
experience w i t h sickle-cell screening also sounds a cautionary
note as we contémplate the uses that my be made of the results
of genome mapping, namely the risk that programs will move
t o o quickly t o de f a d o and even de jure compulsión, while ig-
noring the risks of discrimination and the potential difference in
diagnosing " i n - b o r n " as opposed t o "acquired" diseases o r dis-
orders.

What líes ahead for genome mapping?

I hope that what I have said so far demonstrates t w o things: first,

that even a topic as unglamorous and as apparently w i t h o u t non-
controversy as genetic screening and testing actually raises many
genuine ethical and public policy issues, and second, that gene
mappers would do well t o learn from our experience with screen-
ing and testing. Lessons can also be garnered f r o m other áreas of
the new genetics which are thought of as m o r e controversia!,
like gene therapy. Since other speakers have not pointed t o these
lessons, I will describe them briefly.
400 The D i f f i c u l t y o f K n o w i n g W h a t Problems
Will Materialize

First, I want t o emphasize the risk that we in ethics and policy

face of addressing t h e w r o n g issue, often because scientists
themselves mispredict the future. Let me ¡Ilústrate thls w i t h an
e x a m p l e d r a w n n o t f r o m genetlc screenlng b u t f r o m gene
therapy (another área on which the genome project will have
great Impact.)

In the 1970s and early 'SOs, the general expectatlon was that the
first attempts at gene therapy w o u l d be for the hemogloblnopa-
thles. As it t u r n e d o u t , t h a t expectatlon was b o t h right and
wrong. It was right in that the first attempt t o use recombinant
technology in gene therapy was Kline's unauthorized and unsuc-
cessful attempt t o treat several thalassemia patients. But it was
w r o n g because the reason others did not perform o r support
such experiments was that modification of hemoglobin function
turned o u t t o require a level of genetic regulation that gene ther-
apy techniques are still not able t o achieve. So the target diseases
became those -like A D A deficiency- where such regulation of the
inserted genetic message does n o t seem t o be necessary f o r
therapeutic efficacy.

This change in technique was n o t necessarily of ethical i m p o r t .

Likewise, a f u r t h e r change f r o m expectations - t h e switch f r o m
a t t e m p t i n g t o modify hematopoietic stem cells t o modifying
circulating l y m p h o c y t e s - was n o t in itself ethically significant.
But the f u r t h e r change ofattempting t o t r e a t a genetic disease
t o treating cáncer w i t h genetically modified cells does seem t o
me significant f o r ethical and legal analysis. The first e x p e r i -
ment w i t h human subjects involving gene transfer approved by
the RAC (Recombinant D N A A d v i s o r y C o m m i t t e e ) at N I H in-
volved the use of t u m o r - i n f i l t r a t i n g lymphocytes (so-called TIL
cells), tagged w i t h a genetic marker t h r o u g h gene transfer, in
t r e a t m e n t of malignant melanoma. T h e second e x p e r i m e n t ,
approved just this fall, involves inserting and active gene f o r
t u m o r necrosis f a c t o r i n t o t h e T I L cells. These approvals
w e r e given before the first a t t e m p t t o use gene therapy f o r a
genetic disease, namely A D A deficiency. As French A n d e r s o n
notes in an editorial in the latest issue of Human Gene Ther-
apy, besides t r e a t i n g cáncer, gene t h e r a p y may also p r o v e
useful in t r e a t i n g cardiovascular disease ( b o t h as an aid t o
healing a f t e r s u r g e r y and by d e c r e a s i n g a r t h e r o s c l e r o s i s
t h r o u g h increasing L D L r e c e p t o r s ) , infectious diseases like
AIDS, and as a "sophisticated drug delivery system" applicable
in general t o all diseases. 7
I point t o this history t o draw t w o very basic and perhaps o b - 401
vious lessons: first, that biomedical science develops in unpre-
dictable ways, and second, thát when those developments de-
p a r t s u f f i c i e n t l y f r o m w h a t b i o m e d i c a l s c i e n t i s t s have
p r e d i c t e d , ethicists and p o l i c y m a k e r s m u s t also reevaiuate
t h e i r perspectiva and perhaps r e w r i t e t h e l r prescriptions. In
the case of gene therapy, the shift f r o m the hemoglobinopa-
thies t o ADA-deficiency and even the shift f r o m the " p e r m a -
nent" changes expected f r o m stem-cell alterations t o the t e m -
p o r a r y ones c r e a t e d by r e c o m b i n a n t lymphocytes may n o t
have been ethically significant, but the shift f r o m treating ge-
netic diseases t o being merely a means f o r targeted drug de-
livery seems t o me t o cali f o r ethical and legal reexamination.
A t the very least, it should make us ask again a basic question:
n o t just " W h a t is disease?" but m o r e particularly " W h a t is a
genetic disease?".

N o r m a l i t y a n d A b n o r m a l i t y : O p e n f o r a N e w Look?

The need t o reexamine our ideas about genetic disease is likely

t o arise not only f r o m gene therapy research but also very ur-
gently f r o m the results of the G e n o m e Mapping Project. For
example, what consequence will there be f o r concepts of " n o r -
mal" and "abnormal" when molecular genetics demonstrates that
the line of difference between the "disease" and "nondisease" is
nothing more than the rearrangement of a single D N A base-pair
(out of the billions in every cell).

Questions like this can seem very philosophical (in the perhaps
pejorative sense of being merely of intellectual interest), but I am
convinced that they can have profound practical implications as
well. In terms of my assigned topic of "testing and screening",
consider what happens when a test shows an individual t o be
"abnormal". Certainly, part of the result is t o sepárate that per-
son f r o m others, t o genérate the sense of the person being very
different. T o the exent that the difference is understood t o be as
minor as a single D N A base-pair - a n d henee perceived as basi-
cally random, the sort of chance event that could easaily happen
t o anyone, rather than as the more major change that marks a
person as "diseased"- then the perception of distance between
affected and unaffected persons may disminish. 8 This would have
obvious (and beneficial) implications regarding a major concern
arising f r o m genome mapping, namely, the risk that the ability t o
detect more genetic differences will créate more instances of dis-
crimination against those marked as "abnormal".
402 Implications for Insurance a n d E m p l o y m e n t

T w o áreas in which the issue of discrimination are frequently

cited are employment and insurance (especially ¡n countries, such
as the USA, in which w o r k and insurance are tied t o a competi-
tive market place rather than being derived as a matter of social
entitlement). The potential that Information derived f r o m ge-
nome mapping will greatly enhance the ability of genetic testing t o
" s o r t " people into different groups based on genetic differences
raises an interesting challenge. It is usual t o reflect that challenge
back onto the genetic enterprise itself: t o say, in other w o r d s ,
that the genome project creates a risk that "genetic predictions"
(i.e., predictiions about the future occurrence of illness in an indi-
vidual w h o carries a gene associated with greater than average
susceptibility t o a particular illness) will be used by employers
and insurers as screening devices. This way of viewing the chal-
lenge is legitímate but I w o u l d like t o t u r n the challenge around
and ask instead: what are the Implications of any new genetic
predictive capabilities f o r our notions of insurance and employ-
ment? For example, in the fleld of health insurance in the USA,
we have seen a movement f r o m a risk-sharing model t o a group-
narrowing model - i n o t h e r w o r d s , f o m seeing ourselves as all
being in roughly the same situatjpn (thereby making it morally
desirable t o spread hsks as broadly as possible) t o seeking our
individual advantage in placing ourselves in a group f r o m which
we have excluded people w h o are at higher risk than ourselves.
W h e n the exclusions are based on voluntarily acquired risks
(such as f r o m smoking), they have gained general public support.
Such exclusions do not seem ethically objectionable, so long as
we apply a fairly strict understanding of the t e r m "voluntary". But
exclusions grounded in genetic differences are less benign.

Nonetheless, it would be a mistake t o conclude that genetic test-

ing has no place in insurance. W h e t h e r it is acceptable depends
not on abstract ethical principies but on o u r conception of the
purpose of insurance.

Thus, the outcome of the Genome Project could be t o forcé us

t o reevaluate the principies underlying insurance. Likewise f o r
employment, wheter w e regard everyone as entitled t o compete
for any job or belive that limits can be placed based on the costs
(of illness, etc.) when a particular person w o r k s in a setting that
exposes him o r her t o risks t o which the person in unusually sus-
ceptible. Does "voluntary assumption of risk" resolve the prob-
lem o r are there o t h e r desiderata regarding employment that
may override individual willingness t o assume a health risk? If a
person is excluded f r o m a workplace, what guarantees of compa-
rable w o r k must be available? Does it make a difference if the ge-
netic susceptibility is linked w i t h a particular ethnic o r racial 403
group - s o that a policy of exclusión might remove an entire ra-
cial o r ethnic group f r o m a particular type of employment? W h a t
if the potentially dangerous condition (such as toxic fumes) only
affects a small number of people rather than affecting all people
and simply harming those w i t h peculiar susceptibility more rap-
idly o r more severely? Such questions involve a reevaluation of
the employee-workplace relationship generally; they are provoked
by the potential use of genome mapping results in genetic testing
programs but they are questions of broader interest than just t o
people concerned about genome mapping policies.

Mondotoriness

I have already argued that the history of genetic testing and screen-
ing shows the risk that they will be made mandatory innappro-
priately o r at the least prematurely. I also mentioned in passing
that there was quite a backlash against such developments and a
renewed emphasis on the requirements of voluntariness. The ge-
nome mappers may provoke a challenge here as well -indeed, I
believe that they already have. For example, in light of the impor-
tance of linkage analysis t o mapping and diagnosis, we may need
t o rethink the concepts by which we describe our relationships
and duties. In light of the genetic connections that bind people t o
one another, in terms not only of inheritance but also of molecu-
lar diagnostics, what are the proper meanings of "autonomy" and
"privacy"? D o n ' t I have some obligation t o allow myself t o be
tested if that is the only (or by far the best o r easiest?) way t o
map a gene that is of potential importance t o the health of other
members of my family? W h a t if the knowledge has no immediate
potential t o benefit my family but is scientifically important? O r
might aid in the detection of disease in other families sometime
in the future?

Even m o r e difficult questions will arise as genetic screening and

testing gain the ability t o predict more and more conditions (in-
cluding those that w o u l d not today be labeled a "disease") in the
fetus. It is t o o son t o predict what consequences might all this
have f o r our predisposition t o protect free choice in prívate mat-
ters generally and in medical care in particular. But it is clear that
more than a reexaminaron of voluntariness and mandatoriness
will be needed: along the way, w e will need t o examine what w e
mean by such concepts as "responsible parenthood". Such a no-
t i o n already exists in the context of behavior t o w a r d born child-
ren and may be extended t o reproductive cholees as well - i n -
deed, this can already be seen in a number of unfortunate judicial
decisions upholding forced cesearen sections. In light of such
404 cases, the intrusions inherent in involuntary genetic testing could
actually be regarded as less onerous, particularly if those doing
the tests did n o t plan t o forcé an intervention afterwards but
planned t o rely on the person's conscience (and other pressures)
t o coerce "responsible" behavior once the results of the genetic
test w e r e known.

Conclusíons

In this essay I have attempted t o do several things: t o sketch the

history of genetic testing and screening and draw implications f o r
genome mapping, and t o speculate about a broad range of conse-
quences in the testing-screening arena as the findings of the map-
ping project begin t o be applied. Let me cióse, then, by summa-
rizing a few of the basic lessons that w e might draw f r o m o u r
experiences thus far w i t h genetics in the public arena.

First, not only lay society but the health professions have been ill-
prepared f o r new genetic knowledge and technologies. As a re-
sult, health professionals often have not played an effective role
either witch individual patients o r in the process by wich public
policy was formulated. Further, we have seen that genetic tech-
nologies may be put into use in nonhealth-care settings by people
w h o have little connection w i t h science o r medicine.

Second, although w e tend today t o regard the public as fearful of

genetic developments, history also shows that the enthusiasm of
the public (or at least of its elected representatives) f o r a new
technology may rapidly outstrip knowledge of how t o use it wise-
ly. Programs have even be adopted that relate t o genetic diseases
w i t h o u t any real appreciation of what difference, if any, attaches
t o the disease of interest being "genetic". Instead, the program
may be justified t o policymakers on economic o r other grounds.

Third, despite ritual affirmation of the valué of personal self-de-

termination, it w o u l d be naíve t o think that when policymakers
become convinced of the valué of genetic screening o r testing
they will refrain f r o m mandatory measures, especially if the health
of children appears t o be involved. Furthermore, if services do
become routine, then failure t o use them may open a person t o
accusations of behaving irresponsibly. "Responsible" behavior
may also be encouraged by the economic incentives offered by
employers and insurers, not solely through mandatory legislation.

Finally, history shows us the ways in which the exceptional be-

comes the routine. A n d when something becomes routine, in-
cremental changes may occur in our moral attitudes, whether it
is about o u r mutual obligations t o one another (can I exelude 405
you f r o m my Insurance base because you're at risk of getting
sick?), about w h o qualifies as a member of the moral community
(are the unborn included?), o r about parents' rights t o make
cholees about their chlldren's health care (does that extend t o
newborn tests for in-born metabolic problems?). N o t all changes
are bad, and many are beyond the ability of anyone t o prevent,
especially when they arise f r o m new knowledge which is there
whether one likes it o r not. But w e ought still t r y t o anticípate
the probable o r even possible consequences of the genome map-
ping project and t o avoid harmful ones if we can, a prospect that
is improved if we will learn f r o m our experiences this far w i t h
genetic testing and screening.
406

REFERENCES

1. C o m m í t t e e f o r t h e S t u d y o f I n b o r n E r r o r s of M e t a b o l í s m .
National Research C o u n c i l , Genetic Screening: Programs, Principies,
and Research 9 (1975).

2. N o r m a l serum phenylalanine is about 2 mg%; modérate elevations

(between 6 and 20 mg%) créate a risk o f retardation; and phenylke-
tonuria, which is diagnosed when blood levéis reach 20 mg% (and
tyrosine is below 5 mg%), seldom exists w i t h o u t producing retarda-
t i o n , although hyperphenylalaninemia "is n o t synonymous w i t h r e -
t a r d a t i o n " . Id at 24.

3. H o l t z m a n , N e i l A . Proceed with Caution: Predicting Genetic R/sk in

the Recombinant DNA Era, B a l t i m o r e : Johns H o p k i n s U n i v e r s i t y
Press (1989), p. 167.

4. id. at 217.

5. P u b . L a w 9 4 - 2 7 8 . Nonetheless, while t h e probiem of involuntary

carrier screening may have been eliminated, Holtzman notes that
although t h e operative section (Sec. I 103) of t h e act survived t h e
repeal o f t h e authorizing sections by t h e Maternal and Child Health
Services Block G r a n t A c t o f 1981.
The number o f states using federal funds under t h e block grant t o
s u p p o r t m a n d a t o r y n e w b o r n s c r e e n i n g p r o g r a m s exceeds t h e
number o f states offering screening o n a voluntary basis.
Holtzman at p. 223.

6. Reílly, P h i l i p . Genetics, Law, and Social Policy, Cambridge: Harvard

University Press (1977), pp. 67-68.

7. A n d e r s o n , W . F . " W h i t h e r Goest T h o u , Gene Therapy?" Human

Gene Therapy 1:227-228 (1990).

8. If such a change in perception o c c u r r e d , it w o u l d likely then extend

t o o t h e r genetic differences of a m o r e major sort, as f o r example,
the rearrangement o r deletion o f large pieces o f a c h r o m o s o m e .
CLOSING
SESSION
 409

CLOSING REMARKS

Santiago Gñsolía

Institute of Cytological Research, Valencia (Spain).

Y o u r Majesty, 41 I

In the ñame of the distinguised group of personalities f r o m the

basic, medical and social sciences, etc., w h o have taken part in
this workshop, and on my o w n behalf, I should like t o thank you
f o r your generosity and f o r honouring this Congress w i t h y o u r
presence today.

Y o u r presence clearly shows the deep concern of the C r o w n f o r

science and its effects on society. I should also like t o mention
the support and p r o t e c t i o n Y o u r Majesty has given f o r many
years t o those less fortúnate ones w h o suffer physical and psy-
chic disabilities.

It Is therefore quite logical and fitting that Y o u r Majesty should

take part in and preside the Closing Session of this II W o r k s h o p
on International Cooperation f o r the Human Genome Project,
wich has been devoted t o the ethics of the matter. In this w o r k -
shop, problems have been discussed that may affect new groups
alienated on account of genetic causes w i t h regard t o employ-
ment, Identification, Insurance, etc.

W e are on the threshold of a huge t r a n s f o r m a r o n in society that

will t o a great extent be due t o the rapid pace of development
and progress in scientific knowledge. As His Royal Highness, the
Prince of Asturias quite rightly said a few weeks ago in Valencia
" t h e development of a country depends m o r e on its creative ca-
pacity than on its natural resources".

W e may perhaps n o t realize what a powerful factor f o r the devel-

o p m e n t o f a n a t i o n s c i e n t i f i c g r o w t h means, o r t h e social
changes it implies, obviously, genetics is today unrivalled among
the sciences in this respect. Genetics is n o w about t o take a
gigantic step forward: t o attempt t o k n o w the Human Genome,
which has been compared t o the A p o l l o Project on account of its
dimensions and novelty. Yet I believe it is even m o r e than this,
f o r this project does not end w i t h the drawing o u t of a map that
locates each and every one of the 50.000 t o 100.000 genes that
represent the Human Genome, ñ o r w i t h t h e identification of
each one of its components.

Apart from the immediate advantages that this entails for medicine
and the new technology it brings, t o possess the " d i c t i o n a r y "
will enable us in future years —perhaps in the new century— t o
come t o k n o w ourselves better.

Like all advances, the Human Genome Project gives rise t o new
problems. In this sense, this is why this Congress is historically
important, f o r participants in same have shown, f r o m an interdis-
ciplinary approach, their concern and fulfilment as members of
the scientific c o m m u n i t y by publicly and clearly discussing t h e
ethical problems posed and t o be posed by the new knowledge.
41 2 W h e n i was w o r k i n g at the University of Chicago in the building
next t o Stagg Field, I can remember the photographs taken of the
occasion of the first chain reaction carried o u t on December
the 2nd, 1942. In these photographs, everybody was smiling;
however, the chain reaction finally killed 40,000 people in Nagaski
alone. Thus, scientists do not wish the same thing t o happen now
as happened t o those w h o t o o k part in the development of the
atomic bomb. These scientists later regretted not only their parti-
cipation, but also the iron censorship that prevented any clear
discussion of the possible ethical implications of their research.

From the social point of view, the dilemma is obvious; t o protect

both the individual and society, t o o . T o this end, clear discussion
is required and one cannot wait until their is suitable legislation.
For example, in th United States there is the so-called "Human
Genome Privacy A c t " -although it is currently being p o s t p o n e d -
which is a draft of a law with the aim of giving the individual the
right t o disclose of otherwise his o r her genetic identification.
Thus discrimination as t o employment, Insurance and education
will be forbidden, f o r it seems there have already been cases of
discrimination on grounds of genetic evidence. It is thought that
similar laws will be suggested in other countries. But jurists and
politicians need time t o think and act. It is therefore an urgent
need for the scientists themselves t o act through prívate means
such as foundations which, even though they have n o t the eco-
nomic capacity of state entities, do have the agility that official
organisms lack and cannot have. For this reason, I should like t o
publicly mention and thank the generosity of the BBV Foundation,
which has begun its activities w i t h a meeting as important as this,
a meeting of such vast universal projection as the II W o r k s h o p
on International Cooperation f o r the Human Genome Project:
Ethics".

Finally, I should like t o thank all participants w h o have made this

meeting possible, and particularly Her Majesty the Queen f o r her
special sensitivity t o these problems.
 413

Lu/s Oro

General Secretar/ t o the National Planof the I + D.

interministerial Committee f o r Science and Technology
O n behalf of the Interministerial C o m m i t t e e f o r Science and 415
Technology, I should like t o express my thanks for the invitation
t o take part in this act, in which w e have had the occasion t o
listen t o important conclusions on the Human Genome Project,
a project that is inserted within the growing f r a m e w o r k of scien-
tific internationalization, and has the oustanding merit of posing
its possible repercussions at t h e same t i m e as w o r k is being
carried o u t on it.

The Interministerial C o m m i t t e e f o r Science and Technology, in

which all Ministerial Departments take part in Research and De-
velopment planning, w o r k e d out a National Health Programme
within the f r a m e w o r k of the National Plan, in which the Human
Genome is considered a specific objective.The Interministerial
Committee has also strongly supported the creation and launch-
ing of the corresponding programme of the European Economic
Community. All this will undoubtedly contribute t o the integration,
subsidizing and c o o p e r a t i o n of research, which by t h e i r very
nature, is of utmost importance t o projects such as the once w e
have discussed today.

T h e Spanish A d m i n i s t r a t i o n is making great efforts t o attain

greater participation day by day in the International scientific field.
These efforts are not isolated ones f o r the Autonomous C o m -
munities also devote important funds t o scientific research. All
this, together w i t h the initiative of foundations such as the one
t h a t has received us today, is enabling t h e Spanish system of
science and technology t o g r o w in importance on a w o r l d - w i d e
scale.

The creation of trained human resources is the most important

wager f o r the development of science and technology. W i t h this
in mind, the National Plan f o r the Training of Research Personnel
is enabling a great number of young scientists t o be trained both
in our country and abroad. T o this end, I should like t o thank the
laboratories of the International community f o r their help and
support by having opened their doors t o our researchers.

All this is bringing about a new situation in the w o r l d of science

and technology in Spain. During the hard times, our researchers,
some of w h o m are present here, kept alight the t o r c h that has
today made Spanish science and technology important on the In-
ternational scene. This is n o t a mere personal opinión: on the
strength of bibliometric studies carried out, our advance in the
w o r l d of science is quite clear.

T o return t o the Human Genome, I should not like t o leave o u t

the importance of this project and promise that we shall, within
o u r limited resources, contribute t o its development t o some
extent. W i t h i n this development, independently of the benefits it
may bring t o knowledge and its application t o medicine and
other sciences, theré is its valué and importance in contributing
416 t o set up an ever-increasing internationalized system of science
and technology.

Finally, I wish t o congratúlate all of you f o r having reserved an

important space and time for the study of ethical and social as-
pects, as likewise f o r the importance of your concluslons.

Thanking you all very much.

 417

josé Angel Sánchez Asiaín

President of the Banco Bilbao Vizcaya Foundation

Y o u r Majesty, 419

It is a great privilege f o r me t o thank you today f o r having hon-

o u r e d us by accepting t o preside this Closing Session of the
W o r k s h o p on International Cooperation f o r the Human Genome
Project, of which o u r King is the H o n o r a r y President. O n ac-
count of the ambitiousness of its scientific objectives, this project
has aroused great enthusiasm, and at the same time profound in-
terrogations on the social consequences t o be derived f r o m the
broadening of our knowledge that the development of this p r o -
jects offers.

For, t o a t t e m p t ourselves t o e n c o u n t e r t h e keys t o u n d e r -

standing why w e are what we are f r o m the biological point of
view, why o u r organism behaves as it behaves, also arouses great
fascinatlon, numerous and even controversia! philosophical and
ethical questions. This w o r k s h o p has consequently been focused
on confronting some of them on the basis of the excellent inter-
ventions of those taking part.

I wish t o express my sincere admiration, respect and gratitude t o

Professor W a t s o n , Professors Gilbert and Dausset, co-partici-
pants, in the development of certain essential aspects of this
great project on the genome, all of w h o m w e r e awarded the
máximum distinction of the Swedish Academy of Sciences.

I should also like t o express my admiration for Professor Santia-

go Grisolía, an outstanding biologist, winner of the Prince of As-
turias Prize, and alma mater of this i m p o r t a n t encounter; my
thanks t o o , t o the Valencian Foundation f o r Advanced Studies
and t o all those w h o agreed t o think together over the past few
days on the ethical implications of this great project.

T o attempt t o understand the genetic basis of the human species

is a thrilling prospect, n o t only f o r those w h o actively and di-
rectly take part in it, but also f o r the great majority of people
w h o follow its development in admiration, albeit an admiration
not free of concern. A concern that is of course reasonable. For
this century has shown us that tools based on scientific know-
ledge can be used f o r alternative, and often counterposed, ends,
because our w o r l d has also at times shown that it has attained an
amazing capacity and perfection of means and tools at its dis-
posal, although it has at times been misguided as t o t h e end
and aims that should be pursued. As Einstein said what charac-
terizes our century is perfection of means and confusión of aims.

This does not prevent society f r o m highly valuing science and

technology, knowledge and research, as important enterprises in
themselves, independently of their applications, on account of
their valué in improving our knowledge of the universe and o u r
place in it. Society is also aware that many of the problems w e
face up t o over the w o r l d can only be solved by means of a wise
420 applying of science and technology, nevertheless, this wise ap-
plying must be founded on an ethics of responsability, that is, in
the conviction that w e are responsible f o r t h e consequences,
whether foreseeable o r otherwise, t o be derived f r o m o u r acts
and not merely f r o m o u r good o r bad intentions. This wisdom
will also enable us t o analyse and anticipate as far as possible the
side-effects t o be derived f r o m applications considered at the
outset as w o r t h y of development.

A n d these dilemmas take on a singular forcé and relevance when

w e deal w i t h disciplines such as biology, particularly the molecu-
lar biology entailed in the Human Genome Project. In the last
years of this century they make up one of the fields of knowledge
that are on the frontiers of scientific knowledge. This is because
their discoveries can directly affect the human being's o w n phy-
siobiological identity. A n d because any manipulation, intervention
o r i n f o r m a t i o n on this identitymay bring far-reaching conse-
quences f o r the individual that may even affect both his o r her
o w n individuality and the esemble of links and relationships he o r
she has w i t h society.

"The prospect of a genetic map, of a complete biological book of

humanity, at one and the same time arouses enthusiasm and con-
cern, giving rise t o questions of an ethical and philosophical na-
t u r e " . This is textually stated in one of the central reports f o r
setting up the Human Genome Project in the United States. And
this concern for the ethical aspects of the project on the genome
should oblige us t o question ourselves on the direction and ob-
jectives t o which o u r o w n research is channelled, questions t o
which certain answers have been proffered here over the past
few days. In any case, I think that the dignity of the human being is a
mission and that respect for same must be an essential part of any re-
search activity.

For this reason, one should welcome the rise of a growing sensi-
tivity t o the ethical and social problems which scientific develop-
ment brings. And particularly in the Human Genome Project, in
which reflection on the ethical dimensión runs parallel t o devel-
opment of research itself, and can therefore influence the later
course of same instead of w a i t i n g f o r t h e f i r s t n o n - d e s i r e d
impacts t o occur.

In any case, whenever new cognitive categories emerge, new

perceptive approaches, new tools f o r the analysis of vital phenom-
ena, that is, whenever the human being resorts t o innovation as
a driving mechanism, there occurs a double phenomenon of con-
t e s t a r o n on the one hand and practical application on the other,
which notably affects a great deal of the structural resources of
o u r society, w h e t h e r these be scientific, political, socio-eco-
nomic, legal o r of any other kind. I also think that whenever these
convulsions occur, the urgencies t o innóvate and the inertias t o
preserve are usually rare in c o m m o n forums of encounter, in 42
time of joint reflection and compatible codes of communication.

A n d it is precisely this truly key function of providing environ-

ments of convergence, of supplying spaces for reflection, of of-
fering the means for new horizons of reference t o be explored and
common compatibilities and languages t o be sought, that is the
t r u e vocation of o u r Foundation, the BBV Foundation. For t o
créate suitable frameworks t o reflect at liberty on the great chal-
lenges of the end of this century, t o interpret emergent situations
through a new prism, and t o achieve renewed systems of refer-
ence that allow f o r innovating voyages is w i t h o u t doubt the jus-
tification for all o u r efforts.

Therefore, our Foundation, either alone o r in collaboration w i t h

other institutions, as in the case of this W o r k s h o p with the Va-
lencian Foundation f o r Advanced Studies, will continué in its ef-
forts t o encourage, support and stimulate new pluh-disciplinary
spaces for encounter and reflection. This, in o r d e r t o offer the
results t o all strata of society as cultural paradigms, as elements
of the new education society demands if it is t o solve w i t h o u t
violence its serious problems of identity and survival. For this In-
formation is an unrenounceable right of society, and it is one of
the most important means t o a person's beign able at each m o -
ment t o make free decisions as t o the direction and f o r m t o be
taken by development and the technological applications of basic
knowledge.

Madam: I should like t o end by saying that it is of extraordinary

valué f o r science and culture, as f o r all of us, that the C r o w n
should offer such exemplary understanding and support f o r the
efforts of all those w h o , at different levéis of science, w o r k and
strive t o attain thresholds of knowledge t o be shared w i t h o t h -
ers, knowledge that leads t o attemps at improving - f r o m the in-
novation that co-exists w i t h t r a d i t i o n - the conditions o develop-
ments of human dignity w i t h the desire t o attain a freer, m o r e
cultured society. My sincere thaks f o r this.

Many thanks t o you all.

 423

Julián García Vargas

Minister of Health and Consumer Affáirs (Spain)

Your Majesty, 425
Ladies and Gentlemen:

O n behalf of the Government of Spain, I should like t o thank all

scientists and experts w h o have intervened for their participation
in this International W o r k s h o p , as llkewlse the support of the
BBV Foundation and the hard w o r k of its President, Professor
Grisolía.

The highest praise is due t o all of those w h o have made it pos-

sible f o r this W o r k s h o p t o be held in Spain on the ethical aspects
of one of the most wide-ranging ever scientific projects which
even has the backing of UNESCO and the ECC.

I should also like t o congratúlate you f o r the approach that is

being given t o this ambitious task of analysing the human genome
by carrying out the purely scientific w o r k alongside reflection on
its possible social and ethical consequences at one and the same
time. Had this always been done in all fields of science, mankind
could have been spared an era of fear and uncertainty which has
today fortunately been overeóme.

The scientific community and society have much t o learn f r o m

this approach, which is based on inter-disciplinary dialogue, in or-
der t o solve the conflicts that arise between biomedical advances
and ethics, w i t h the fundamental participation of the citizens
themselves. T o be more precise, this dialogue must lead us t o
w o r k o u t norms of behaviour in genetic research and its applica-
tions.

These norms can no longer be based on the ideal portrayed in

Plato's Republic, which allowed the intellectual leader, the philos-
opher, t o discern between the true and the false, good and evil,
the just and the unjust.

The great revolutions of the modern era, the English, the A m e r i -

can and later the French revolutions, suggested another, m o r e
democratic and symmetrical type of human relationships. These
ideas are crystallized in the spirit of the Enlightenment, the de-
fensor of the autonomous nature of the human individual, of the
individual as subject w h o as such should be respected by all those
w h o hold different moral stances, w h o must take an active part
in the decisions o r reflections that affect him o r her. A modern
philosopher and sociologist, Habermas, has updated this spirit by
speaking of "communicative action", of this very participative ra-
tionality which is characteristic of our time.

In societies such as ours, w i t h their f r a m e w o r k of co-existence

drawn o u t in the modern Constitutions that support ideological
and social pluralism and the respect f o r human right, the rela-
tionship t o be established between scientists, the individual and
426 society has become autonomous, plural, desacralized and con-
flictlve.

O r this reason, In texts such as the recent Law of Assisted H u -

man Reproductlon of 1988, It is stated that there Is no doubt
that scientific research must continué its course and that It should
not be limited unless thls be on firmly based crlterla that prevent
It clashlng wlth human rlghts and the Individual^ dlgnity, and that
t o thls end an open, rlgours and dispassionate collaboration Is
required between society and sclence.

This is the gist of the speech glven t o this workshop by Professor

Jean Dausset, Nobel prize winner, Presldent of the Universal Move-
ment f o r Scientific Responsibility, w h o proposed t o the Orga-
nizaron of the United Natlons that an International Commission
should be created t o control manipulation of the map of the hu-
man genome.

As was t o be expected, w e are in Spain advanclng In the same di-

rection and consequently, w l t h the State in the role of the in-
spirer of social articulation, w e are working on the constitution
of the National Commission of Bio-ethics, In which scientific,
professional and social personalices connected wlth the sclences
of health and blology are t o particípate.

The Commission will be responsible f o r Informing and advising

the Health Administrations as t o security, efflclency, plausibility
and ethical aspects related t o the technologies relevant t o health
and medical assistance, as likewise w l t h regard t o the criteria as
t o limiting their applications.

The project of the Royal Decree thls Commission has created Is

already w r i t t e n o u t and will soon be examined by a great number
of public and prívate institutlons f o r them t o offer suggestlons
and Ideas.

Y o u r Majesty, genetics Is a science of the future that can explain

and solve many aspects of the blological process and alteratlons
in people's state of health, but It also poses important questions.

Finally, therefore, I encourage you t o continué t o reflect on the

questions which are still w i t h o u t an answer, so that all together
thls research will n o t only be of a very high scientific quality, but
will also have the relevance f o r the human collective w e all hope
for.

T h a n k y o u all very much.

 427

Joon Lerma

President of the Valencian Community

Y o u r Majesty, 429
Mr. Minister,
Ladies and gentlemen:

As representative of the Government of the Valencian C o m m u -

nity, I am honoured t o be here today with you, f o r the Closing
Session of this II W o r k s h o p on International Cooperation f o r the
Human Genome Project, which has dealt w i t h ethical aspects of
same.

In the first place, on behalf of the Valencia Community, I should

like t o thank Her Majesty, Queen Sofia f o r being here w i t h us t o -
day, Her presence certainly honours this workshop and sets it at
the level fitting t o it, once more displaying the interest of o u r
Monarchy f o r science and culture, an interest that both stimu-
lates and encourages us as w e had the occasion t o see recently
when His Highness, t h e Prince of Asturias visited us f o r the
awarding of the Jaime I Prize. I should also like t o thank the Min-
ister of Health and Consumer Affairs f o r attending today, and
mention the distinguished scientists among us.

This is not the first time that Valencia has been the vénue f o r an
encounter of this nature. In O c t o b e r 1988, the I W o r k s h o p on
the Human Genome was held here. These internationally impor-
tant events have made o u r city and Community a scientific f o r u m
and act as a measure of h o w important w e consider the develop-
ment of knowledge in all fields and the advantages of a modernity
invariably t o be understood as at the service of society and its
members.

The conclusions of this meeting have once more shown the qual-
ity of contemporary science, f o r which scientific knowledge must
only be used in the service of the dignity, integrity and the future
of human beings, Spain is fully immersed in the European and
world-wide tendency t o use technology rationally as a factor of
progress i m p r o v e m e n t and the attainment of higher levéis of
equality and welfare, and the people of Valencia feel identified
with this project. W e therefore feel that it is important not t o be
left on the margin of the Human Genome Project, on which a
competent research group of ours is working.

W e believe that it is legitímate t o t r y t o make medicine advance

by using genetic mapping, which opens up the way t o knowledge
and enables scientists t o design and apply new therapies t o
diseases that had so far been resistant t o the advances of medi-
cine, such as cáncer.

This must of course be achieved on the strength of presupposi-

tions of a severely humanistic and social ethics, so that scientific
discoveries do not get o u t of hand -as has unfortunately so often
occurred in other fields. Self-awareness and self-limitation must
govern science itself so that the inertia of its discoveries may not
430 'ose sight of its objectives, which are none other than those of
helping life t o develop m o r e fully.

Science does not possess the keys t o human nature, neither do

w e believe that genetic mapping will reveal its secrets t o us. The
essence of human nature does not lie in genes but in language,
f o r man is a fundamentally social being endowed w i t h speech,
that is, w i t h thought, and is conditioned by his environment. O n e
should n o t let oneself be led away by fantasy when dealing w i t h
these matters that are so often trivialized and subject t o a banali-
zation that magnifies them, t o the detriment of their t r u e role
and dimensión.

W h e n this w o r k s h o p was inaugurated, I said something I should

like t o repeat here. Ethics is an extremely flexible sphere; if it is
individual, it may be subjective and henee arbitrary. Therefore, the
only valid frame of reference in this field is the law. But the politi-
cian and legislator need the scientist t o supply the Information on
the profound consequences of his discoveries before debating on
their limits and establishing universally valid rules.

This makes meetings such as the one we are now closing have
such extraordinary importance, f o r they take knowledge out of
the laboratory into the grounds of debate, and because it is no
longer the grounds of debate, and because it is no longer the mi-
croscope o r the computer that is used in them, but speech, re-
flection and criticism.

My warmest congratulations t o those whose efforts have made it

possible f o r this t o take place once m o r e amongst us. W e shall
always be happy t o welcome such distinguished visitors and hope
that they t o o , you, have spent these days with us full of positive
experiences.

Many thanks t o you all.

 431

INDEX

Presentatlon 7

Introduction ' '

General Remarks 23
Genetic Polymorphism and the Surrounding Environ-
ment (James Watson) 25
The Human Genome Project and Public Opinión (Jack
McConnell) 29
Scíentific Revisión 33
The C u r r e n t State and Future Prospects of the Physi-
cal Mapping of the Human Genome (David Scheles-
singer) 35
Sequencing the Human Genome: Current State (Walter
Gilbert) 45

N a t i o n a l Policies 53
The Human Genome Project: The French View (Jean
Frangois Girard) 55
A Germán Point of View (Hans-Martin Sass) 61
A British Approach (Tony Vickers) 75
Scientific and Ethical Aspects of the Human Genome
Project in Italy (Paolo Vezzoni) 83
Policy in Relation t o the Human Genome Project. The
View f r o m the USSR (Alexander Bayev) 89
T h e Human G e n o m e P r o j e c t in t h e U n i t e d States
( N o r t o n D. Zinder) 97
W h y Isolate the Third W o r l d ? W h a t Part does UNES-
C O have t o Play? (Claude Rosenfeld) 105

Religous C o n s i d e r a t i o n s I 19
The Catholic Point of View and its Ethical Implications
(Angelo Serra) 121
A r t i f i c i a l R e p r o d u c t i o n : an Islamic P o i n t o f V i e w
(Azeddine Guessous) 129
Ethical Attitudes of a Jewish Scientific w i t h Regard t o
Genetic Intervention (Haim Aviv) 137
Protestantism and the Human Genome Project (Jack L.
Stotts) 145
432 T h e C o n c e p t of t h e " I " 155

Biological Determinism and the Concept of Social Res-

ponsibility. T h e Lesson of C a r r i e Buck (J. David
Smith) 157
T h e H u m a n : a P r o t e s t a n t C h r i s t i a n V i e w (Jack L.
Stotts) 167
Mankind in Search of Meaning (James S. Grisolía) 183

T h e I m p a c t of t h e H u m a n G e n o m e P r o j e c t on
Medicine 201

Genetic Therapy (Theodore Friedmann) 203

The Impact of Human Genome Mapping on the Doc-
tor-Patient Relationship (Albert R. Jonsen) 2! I
The Impact of Human Genome Studies on Clinical Ge-
netics (Michele D'Urso) 22!

T h e I m p a c t of t h e H u m a n G e n o m e P r o j e c t on
Biology 229

T h e H u m a n G e n o m e P r o j e c t : in Defence of Basic
Science (Giorgio Bernardi) 231
N o Time for Knitting: The Genetic Quest of the A r -
gentinian Grandmothers (Mary-Claire King) 247
Participation in and Access t o the Data of the Human
Genome Project (Elke Jordán) 257

Identification a n d D i a g n o s i s 263

Ethics and Human Genetics once the Human Genome

has been Mapped (John Fletcher) .' 265
Diagnostic Testing of Genetic Disorders in the Early
Stages of Pregnancy: Social and Ethical Implications
(Bruno Brambati) 275

Professional S e c r e c y and Confidentiality 285

Confidentiality (José Elizalde) 287

Genetic Technology, Insurance and the Future ( G . W .
de W i t ) 297
The Human G e n o m e Project and Labour Relations
(Tomás Sala) 315

Ethical Aspects Derived from C o m m e r c i a l

Applications 321

The Commercial Aspect of Diagnostic Testing (Helen

Donis-Keller) 323
Biotechnology (Eladio Montoya) 333

Diagnostic Population 339

Diagnostic Population Testing of Gene CF ( N o r m a n

Fost) 34!

L e s s o n s f r o m t h e P a s t : P r o s p e c t s for t h e F u t u r e . 347
 " B e y o n d D e c l a r a t i o n s : Is it Possible t o Fit Ethics 433
i n t o t h e H u m a n G e n o m e P r o j e c t ? " ( W i l l i a m G.
Bartholome) 349
Genetic Inequality and Social Injustice: A Lesson f r o m
History (Benno Müller-Hill) 357
The Influente of Eugenios on Human Genetics (Daniel
J. Kewles) 365
Lessons f r o m the Past: Projects f o r the Future. The
Human G e n o m e Project and Social C o n t r a c t : A n
Approach of Legal Policy (Cristhian Byk) 377
Diagnostic Proof and Genetic Testing (Alexander M.
Capron) 39!
C l o s i n g Sessíon 407
Santiago Grisolía 409
Luis O r o 413
José Angel Sánchez Asiaín 417
Julián García Vargas 423
Joan Lerma 427
Index 431
Design: A l b e r t o Corazón.
FUNDACION DDV
Alcalá, 16-planta quinta
28014 Madrid
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