G. Semenza and R. Jaenicke (Eds.

)
Selected Topics in the History of Biochemistry: Personal Recollections VI
(Comprehensive Biochemistry Vol. 41) © 2000 Elsevier Science B . g 363

Chapter 7

Erik Jorpes - a pragmatic physiological

chemist

VIKTOR MUTT a' t, MARGARETA BLOMBACKb

aDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet,

Stockholm, Sweden
bCoagulation Research, Department of Surgical Sciences, Karolinska Institutet,
Stockholm, Sweden

Erik Jorpes' childhood and youth

On 15 J u l y 1894, a son, t h e i r first child, w a s born to f i s h e r m a n

J o h a n E m i l P e t t e r s s o n a n d his wife on t h e small i s l a n d of
KSkar in t h e ~ a n d archipelago b e t w e e n F i n l a n d a n d
Sweden. 1 T h e boy w a s given t h e C h r i s t i a n n a m e s J o h a n
E r i k a n d t h e family n a m e J o h a n s s o n , son of J o h a n , in accor-
dance w i t h a w i d e - s p r e a d c u s t o m in S c a n d i n a v i a at t h a t time,
of u s i n g t h e C h r i s t i a n n a m e of t h e f a t h e r as t h e family n a m e .
Erik, as h e w a s u s u a l l y called, g r e w u p on t h e island, learn-

t Deceased in September, 1998.

1The/~land Islands originally belonged to Sweden. They were occupied by
Russian and also by French soldiers for about 200 years, but after World War
I the United League of Nations in 1918 decided, against the wish of the
population, that they should belong to Finland. However, the native
language of the people in Aland is still Swedish.
364 V. MUTT, M. BLOMBACK

Erik Jorpes at work.

ERIK JORPES 365

ing the names of the various sea-birds, their patterns of flying

and their calls. He also learned where to find fish and seals
and, when sailing, to avoid reefs. He early became interested
in wild flowers and, while going to the village school, collected
an excellent herbarium. He seemed to be predestined to
continue in his father's trade as a fisherman and small-scale
farmer. However, as described by clergyman Runar Backman
in his biography of Erik Jorpes [1], there was intense cultural
activity in Finland, among both the Finnish-speaking and
Swedish-speaking parts of the population, at the end of the
nineteenth and the beginning of the twentieth centuries.
Students from the universities in Helsinki and Abo went to
remote areas in the countryside to help to educate the people.
For this reason, a newly graduated woman school teacher from
o

Abo went to K5kar, where she became acquainted with Erik

and his parents and was so struck by the boy's intellectual
capacity that, after prolonged efforts, she succeeded in
persuading his parents not to let his school education end
with primary school. This seemed to present insurmountable
financial obstacles: However, the teacher helped Erik obtain a
stipend, exempting him from tuition fees, and she also
arranged for him to live with her family in Abo.
It thus became possible for him to continue his education at
the Classical Swedish Lyceum in Abo. This was something of a
'gentleman's school'. Most pupils had well-to-do parents and
no idea of what it meant to live under very limited financial
conditions.
Erik with his homespun clothes, island accent, and books
borrowed from the school library, instead of bought by himself,
at first did not quite fit in. This was largely compensated by
the fact that for 5 years he was the best pupil in his class and -
on the suggestion of his teachers - by his skipping the sixth
grade. In the seventh grade, 1912-1913, he met Arvid Ahlroth,
the son of a worker, who had been the best pupil in his class
each year. Erik and Arvid remained lifelong friends. In connec-
tion with his graduation in the spring of 1914, Erik changed
366 v. MUTT, M. BLOMBACK

his family n a m e from Johansson to Jorpes, which was the

name of his parents' homestead in KSkar. o

Erik Jorpes began his medical studies in Abo and continued

them at the University of Helsinki. He passed the Bachelor of
Medicine examination in J a n u a r y 1918, with high marks in
anatomy and physiology and the highest possible mark,
eximia cum laude approbatur, in medical chemistry.

Jorpes treating sick and wounded soldiers

At this time, the vicious civil war broke out between the
'Whites' and 'Reds' in Finland which, in December 1917, had
declared its independence from Russia. Erik Jorpes, instead of
continuing his medical studies, began, consistent with a work-
ers' uprising, despite his lack of clinical experience, to treat the
wounded and sick on the 'Red' side as the only 'doctor' in the
field hospital. When the 'Whites', with the help of German
volunteers, were victorious some months later, the 'Reds',
together with Russian soldiers, fled into Russia, and Erik
Jorpes went with them in a medical capacity. The fugitives
were quartered in barracks in the town of Buij, some 400 km
north-east of Moscow. The conditions at the barracks were
deplorable. Typhus fever was rampant. Erik almost
succumbed, but recovered. During this time, he was among
those in Moscow who started the first Finnish Communist
Party. He r e t u r n e d secretly in September 1919 to Finland,
and then went to his parents' home in KSkar. Although on
the 'Red' side he ha d only worked in medicine, his friends
believed that he might be arrested and tried for treason in
Finland. This was because during the civil w ar he h ad worked
for some time as a j o u r n a l i s t o n a newspaper published by the
losing side. He therefore came to Sweden as a political refugee
in October 1919. From KSkar, he was smuggled to the island of
Waxholm, near Stockholm, by two fishermen, who were later
fined for helping him, a fugitive, to escape. 2
ERIK JORPES 367

Erik Jorpes' start in Sweden

In Stockholm, E r i k Jorpes applied for admission to K a r o l i n s k a

Institutet, i.e. t h e Medical School in Stockholm, to continue his
medical studies. The t e a c h e r s at t h e I n s t i t u t e supported his
application. However, a n y person who was not a Swedish citi-
zen h a d to obtain permission to s t u d y medicine from the Chan-
cellor of the Universities, i.e. from t h e g o v e r n m e n t . E.J. was
o

aided by a vicar, originally from Aland, who contacted H j a l m a r

Branting, the leader of the Social Democrats a n d Minister of
F i n a n c e in a coalition g o v e r n m e n t of liberals a n d social demo-
crats. The vicar told h i m t h a t E.J. was a knowledgeable medi-
cal s t u d e n t who, d u r i n g t h e r e c e n t war, h a d not killed people,
but r a t h e r c u r e d t h e m . B r a n t i n g passed on this information to
the proper people, and E.J. obtained t h e n e c e s s a r y permission
and was a d m i t t e d to Karolinska I n s t i t u t e in 1920. He became
a Swedish citizen in 1923 and, by presidential decree, was
relieved of his F i n n i s h citizenship in t h e s a m e year. It was
said t h a t E r i k h a d to promise B r a n t i n g n e v e r to w o r k w i t h
politics in S w e d e n - w h i c h was probably true.
With this, E.J. was free from the chaotic a f t e r m a t h of World
War I, but he could not overlook t h e problem of m o n e y for t h e
necessities of e v e r y d a y life. H e r e his eximia c u m l a u d e appro-
b a t u r in medical c h e m i s t r y was of some help. He contacted
E i n a r H a m m a r s t e n , who was Laborator (roughly Associate
Professor) of C h e m i s t r y a n d P h a r m a c y in t h e D e p a r t m e n t of
C h e m i s t r y at Karolinska Institute. The h e a d professor, J o h n
SjSqvist, was t h e n deeply involved in a d m i n i s t r a t i o n a n d
teaching, so t h a t r e s e a r c h was h a n d l e d m a i n l y by E i n a r

2Rumours or facts: some people have said that Jorpes was Minister of
Finance for 1 day in Finland. According to another rumour, heofledwith a
bowler hat, usually worn only by a 'gentleman'. The people in Aland could
not quite forgive Erik Jorpes for working with the Reds: when a taxi driver
drove me (M.B.) around Aland in 1958 he said 'So you are visiting with Erik
Jorpes who joined the Reds in 1917'.
368 v. MUTT, M. BLOMBACK

H a m m a r s t e n . This was the nephew of Olof H a m m a r s t e n who

in 1894 had found that a preparation of 'nucleoproteid' from
beef pancreas gave a colour reaction for pentoses which was
then thought to be present only in plants. Thereafter, his co-
worker, Ivar Bang, in 1898, had isolated a 'nucleic acid' from
pancreas composed of adenine, a pentose and phosphoric acid.
Einar H a m m a r s t e n had begun his studies of nucleic acids in
the early 1920s, which were to become a central theme of his
scientific career and, especially if seen together with the work
of his pupils and other collaborators, was to leave an indelible
imprint on this field. Erik Jorpes' first scientific paper,
published in 1922 with Einar Hammarsten, dealt with nucleic
acids of beef pancreas [2]. By the time he became a Bachelor of
Medicine, he had already published five papers on nucleic
acids. An extensive analysis of the nucleic acids from the
pancreas was presented 1928 in his doctoral thesis, '[)-ber
Pentosenucleins~iuren in Tierorganismus u n ter besonderer
Berficksichtigung der Pankreasnucleins/iuren' [3]. He showed
that they were composed of three purine nucleotides and two
pyrimidine nucleotides, something which was totally incompa-
tible with the current theories that nucleic acid bases exist in
even ratios. His work was later extended by Loring, Chargaff
and Kerr. During this time, he also collaborated with
H a m m a r s t e n in his physical chemistry work. It is difficult to
imagine today the amount of work that was necessary for a
thesis of this type in the pre-chromatographic era, when it
took 1 day to measure the pH of a solution and the separation
of the various purine and pyrimidine bases had to be done on
the basis of differences in the solubilities of their various salts!
Seen in retrospect, this thesis was an early sign of the downfall
of the then prevalent tetranucleotide theory on the structure
of nucleic acids.
In 1925, E.J. had completed his medical education at Karo-
linska Institute. However, he never worked as a physician. In
1924, he was appointed assistant in the Department of Chem-
istry, i.e. to one of the six salaried positions: professor, associ-
ERIK JORPES 369

ate professor (laborator), assistant teacher, two assistants

(amanuens), and janitor.
When John SjSqvist retired in the spring of 1928, he was
succeeded by Einar Hammarsten and Erik Jorpes was
appointed pro tempore Laborator after Hammarsten, and in
the following year, permanent Laborator. During SjSqvist's
time in office, the Chemistry Department regarded the teach-
ing of medical students as its main responsibility. Hammar-
sten, however, changed this and tried to bring the
department back to what it originally had been, a centre for
basic research. This was noted by the Rockefeller Foundation
from whence support in various ways was obtained for the
department over many years. E.J. received a fellowship
which enabled him to work in the USA for a whole year,
1928-1929.

J o r p e s as a g r a n t e e i n A m e r i c a : n u c l e i c a c i d s ,
endocrine secretion of pancreas, secretin, insulin, and
heparin

E.J. spent most of the time in New York at the Rockefeller

Institute for Medical Research in the laboratory of P.A.
Levene, working on nucleic acids and carbohydrates, which
resulted in publications in the Journal of Biological Chemistry
[4,5]. However, Erik Jorpes also had other interests. His work
on nucleic acids of the pancreas led to investigations, together
with Hammarsten, of the possibility that they might be
involved in the secretion of bicarbonate by the pancreas. In
this connection, E.J. spent some time during the summer of
1929 at the Marine Biological Laboratory at Woods Hole,
where he carried out a comparative study of the nucleic acid
composition of the islets of Langerhans and the exocrine
pancreas in those fish in which they occur separately.
These studies led to his interest in the way in which secre-
tion of the exocrine pancreas was regulated, eventually lead-
ing to Work which resulted in the isolation of secretin. His
370 V. MUTT, M. BLOMBACK

interest in the secretion of the pancreas seems to have had an

independent origin. In addition to his work in the department,
SjSqvist had also maintained a clinical practice and had seen
the utter hopelessness of treating patients with diabetes melli-
tus. When, in 1922, reports from Toronto disclosed that the
group of Banting, Best, Collip and Macleod had succeeded in
obtaining therapeutically useful preparations of insulin [6]
(see also Ref. [7]), SjSqvist suggested to E.J. that he devise a
method for the preparation of insulin in Sweden.
On his r e t u r n from the USA in 1929, Jorpes attempted to
interest various Swedish pharmaceutical companies in the
production of insulin. This was first done in collaboration
with the well-known pharmaceutical company, Astra, and
thereafter with the much smaller Vitrum Pharmaceutical
Company, owned by the pharmacist Otto Bjurling and ru n
by his son GSsta, also a pharmacist.3 Together with G. Bjur-
ling, E.J. visited the insulin group in Toronto in the summer
1929. They were well received and learned much about insu-
lin. In 1930, Vitrum launched an insulin preparation on the
market on the lines of Jorpes' method of production. This
proved to be of great importance during World War II, when
Sweden was isolated and had to rely on its own production of
insulin. This preparation was comparable to the best. During
the 1950s, Jorpes, Mutt and Rastgeldi [8] improved the
production method further.

Heparin
In 1916, in the Department of Physiology at Johns Hopkins
University, Baltimore, the second year medical student J.
McLean, w h e n he was purifying blood coagulation, accelerat-

3Vitrum Pharmaceutical Company was later bought by Kabi, which later

joined Pharmacia. Pharmacia has recently joined Upjohn (1998) to form a
world-wide companyPharmacia & Upjohn.
ERIK JORPES 371

ing phospholipids from dog liver (on the instigation of Profes-

sor W.H. Howell), observed that certain fractions retarded,
rather than accelerated, blood coagulation [9,10]. Two years
later, Howell and Holt named the coagulation-inhibiting
substance heparin [11]. Howell developed a method for its
purification and found that it gave a colour reaction for uronic
acids [12]. From 1922 onwards, a preparation of partially puri-
fied heparin had become commercially available for experi-
mental purposes from a Baltimore company and later also
from another foreign company. Following his successful work
on insulin, Best had started to try to prepare heparin on a
large scale at the University of Toronto. An improved method
for obtaining it from beef liver was devised by Charles and
Scott [13,14]. Erik Jorpes, in collaboration with Vitrum, used
their method for the preparation of heparin from beef and
horse livers. Work on heparin was also being done at the Carls-
berg Foundation in Copenhagen, where Fischer and Schmitz
in 1933 thought that they had isolated the pure substance [15].

Erik Jorpes' w o r k on h e p a r i n

Why did Erik Jorpes start to work on heparin? Crafoord

describes, in 1940, how he, in 1929, had just read the newly
published paper by Howell [12] in which he described the
effects of heparin. Crafoord was struck by a new idea that
heparin, apart from its value as treatment for venous throm-
bosis, might also be a valuable prophylactic agent against
postoperative thrombo-embolism. He discussed this with
Erik Jorpes, who pointed out that a negative phase occurred
after the anticoagulant effect had worn off and that the
preparation had toxic effects and therefore he thought it
impossible to avoid such effects and to prepare heparin o n a
large scale. Crafoord was therefore very pleased when Jorpes
told him in 1935 that he had solved the problem of the chem-
istry of heparin and that chemically pure heparin could be
prepared. Both negative effects had been shown to be due to
372 V. MUTT, M. BLOMB_~CK

contaminants. In August 1935, Crafoord started to treat his

patients prophylactically with heparin [16-19].
E.J. found that the descriptions of the chemical properties of
heparin, reported by various groups, were contradictory,
except on one point - everyone stated that heparin contained
carbohydrate. Jorpes used as his starting point Howell's find-
ing of uronic acid in heparin. However, instead of determining
it qualitatively by a colour reaction, he estimated it quantita-
tively, with Tollens and Lef~vre's method, by determining the
amount of carbon dioxide released on its decarboxylation,
when heparin was hydrolyzed by a strong mineral acid. Jorpes
then showed that the amount ofuronic acid increased in paral-
lel with the increase in purity of the heparin, when the
preparations were fractionated on the basis of activity
increase with decreasing water solubility of the brucine or
barium salts of heparin [20,21]. E.J. had earlier worked not
only with nucleic acids but also with another acidic substance
of high molecular weight, chondroitin sulphuric acid 4 [22]. It
therefore seems likely that, having convinced himself of the
occurrence of uronic acid in heparin, he also started to look for
the other two typical components of chondroitin sulphuric
acid, i.e. galactosamine and ester sulphate. He found both,
sulphuric acid and hexosamine, determined by the quantita-
tive colour reaction of Elson and Morgan. Sulphuric acid
occurred in a much higher amount than chondroitin sulphuric
acid and E.J. thought heparin was a chondroitin polysulphuric
acid. When, together with Sune BergstrSm, he found that the
hexosamine was not galactosamine, as in chondroitin polysul-
phuric acid, but glucosamine, heparin was characterized as a
mucoitin polysulphuric acid 4 instead [23-25]. Although much
important knowledge h a s been added to the chemistry of
heparin by later work in many laboratories and, indeed,

4Chondroitinsulphuric acid correspondsto what is nowadays called chon-

droitin sulphate + dermatan sulphate.
ERIK JORPES 373

continues to be done, the fundamental observations on

heparin by E.J. in the mid-1930s, i.e. its content of uronic
acid, glucosamine and high degree of esterification with
sulphuric acid, have withstood the test of time [26].
E.J. and his co-workers at Karolinska Institute in the late
1930s provided further evidence about the high molecular
nature of heparin [26] and also about its biosynthesis in the
mast cells of Ehrlich having discovered that heparin gave a
metachromatic reaction with Toluidine Blue [27]. Jorpes and
his young collaborators BostrSm and Mutt in the 1950s
showed that one of the three sulphate groups in heparin
must be linked to the amino group [28,29].

Erik Jorpes and other studies by his colleagues in

clinical medicine

Unlike many other scientists in basic research, Erik Jorpes

felt impelled to make his findings of practical use in medicine.
In the same year (1937), when Crafoord wrote his first paper
on prophylactic treatment with heparin, Murray, Jaques,
Perrett and Best reported their findings on the same subject
[30], using heparin prepared in Toronto. Not only Crafoord but
many other colleagues of Jorpes in various clinical disciplines
were studying the treatment and prophylaxis of thrombosis
and pulmonary embolism with heparin. E.J. summarized
some of the early results in Sweden in a book entitled Heparin
in the Treatment of Thrombosis (1st edn. 1939; 2nd edn. 1946
[31]) and in a symposium on heparin and thrombosis, held in
Stockholm in 1940 [32]. In the heparin book [31], Erik Jorpes
reported everything he knew about heparin's history, chemis-
try, mode of action, synthesis and standardization, etc. He
described its clinical advantages and a few drawbacks. He
even discussed the possibility of using heparin to treat diabetic
gangrene, which has recently been adopted in Sweden, using
low molecular mass heparin. He compared the death rates
from thrombo-embolism to those from traffic accidents and
374 v. MUTT, M. BLOMBJkCK

described the social consequences of the sequelae of deep

venous thrombosis. He pointed out the importance of
physiotherapy and early mobilization. The book of the sympo-
sium [32,33] is a fascinating account of the first steps using
heparin treatment and prophylaxis at a time when, for
instance, many women were confined to bed-rest for a fort-
night after childbirth. One paper on postoperative prophylaxis
by Crafoord describes the co-operation with Jorpes [18]. The
paper by Bauer on diagnosis of venous thrombosis by venogra-
phy and treatment with heparin is indeed impressive [34].
Bauer's experience of treatment with heparin from 1940 to
1945 is described in the heparin book (the mortality rates
and hospital stay were cut to one-tenth and the sequelae
were greatly reduced) [31]. Bauer stressed that thrombosis
must be diagnosed early in order to avoid the sequelae and,
if the thrombosis had spread to the thigh, sequelae would be
common.
Zilliacus, in 1946 [35], did a follow-up study of the sequelae
of thrombosis in patients given conservative or heparin treat-
ment. He found that among 132 patients who had been conser-
vatively treated, only a few had no sequelae, while of 130 cases
treated with heparin, more than half were completely asymp-
tomatic.
Not only heparin, but also other glycosaminoglycans (muco-
polysaccharides) were investigated. Particularly during the
1950s preparations and methods for analyzing various glyco-
saminoglycans and studying their metabolism were worked
out. Sven Gardell and E.J. early isolated and purified heparan
sulphate (heparin monosulphuric acid) by a unique technique
[36]. The discovery of heparan sulphate has during the last
decade been shown to be of great importance. Electrophoresis
was then used to separate glycosaminoglycans, hyaluronan
(hyaluronic acid), chondroitin sulphate ÷ dermatan sulphate
(chondroitin sulphuric acid) and heparin in a buffered slab of
Hydro Super Gel [37,38]. Later on, Gardell separated the indi-
vidual glycosaminoglycans, chondroitin-sulphate + dermatan-
ERIK JORPES 375

sulphate (chondroitin sulphuric acid) and keratan sulphate

(keratosulphate) of the nucleus pulposus and the cornea [39].
Together with John Scott, a guest researcher, Gardell in
Jorpes' laboratory successfully evaluated the principle of
using quaternary ammonium salts to fractionate polysacchar-
ides. They also developed a column technique in which the
polysaccharides were precipitated on top of a cellulose column,
saturated with 1% cetyl pyridium chloride (CPC) in water and
keratan sulphate was then eluted with the same CPC. Hyalur-
onan, chondroitin sulphate + dermatan sulphate and heparin
were then separated using a gradient of magnesium chloride
in CPC [40,41].
Gardell also introduced a micro method for the qualitative
and quantitative determinations of small amounts of glucosa-
mine and galactosamine and made a valuable contribution to
the quantitative and qualitative determinations on a micro-
scale of neutral sugars [39,42,43].
Later on, Gardell and his many co-workers continued the
research on the chemistry of animal glycosaminoglycans in an
outstanding way at the University ofLund, where he was Profes-
sor of Medical Chemistry for many years. He died in 1998.
Harry Bostr5m determined the uptake of radioactive
sulphate in studies on the turnover rates of chondroitin
sulphates in the cartilage of rats and in skin (together with
Gardell) [44,45]. An in vitro technique was also developed and
used to study various factors that inhibited or stimulated the
incorporation of sulphate in cartilage. This reaction was inhib-
ited by cortisone and certain salicylates [46,47].
He and collaborators also described the presence of a
'sulphate exchange stimulating factor' in the serum of various
animals, probably synthesized in the liver [48,49]. This was
the first observation of the growth factor later called 'sulfation
factor', and insulin-like growth factor, type I. By using the
same in vitro system, BostrSm et al. [50] showed the effect of
glutamine as a precursor in the synthesis of chondroitin
sulphates.
376 v. MUTT, M. BLOMBACK

BostrSm (who later became Professor of Internal Medicine

at the University of Uppsala) and Odeblad studied the uptake
of radioactive sulphate in various tissues in the rat and found
a very high uptake of sulphate in mast cells [44]. In collabora-
tion with others, BostrSm studied the in vitro survival of arter-
ial grafts and the synthesis of sulphated glycosaminoglycans
in the cornea and sclera [51,52].

Other important research in the department

Edman and protein characterization

In the beginning of the 1940s, Pehr Edman was purifying

hypertensin-angiotensin from horse blood. He developed one
of the earliest chromatographic methods for its purification,
followed by electrodialysis. He determined the amino acid
composition, but could not correlate it with the biological
activity. In the hope of one day being able to discover the
relation between structure and biological activity, he later,
when Associate Professor at the University of Lund, worked
out his phenylisothiocyanate method for determining amino
acid sequences in proteins and peptides which ever since has
been used world-wide to determine countless sequences [53-
55].

Viktor Mutt's isolation of gastrointestinal h o r m o n e s

(secretin and cholecystokinin-pancreozymin) and
related research

Jorpes' earlier studies on secretin and access to newer meth-

ods of separation stimulated further research on secretin and
on the purification and structure of other gastrointestinal
hormones. Although, in the beginning, Jorpes was in charge
of these studies, Viktor Mutt, who showed exceptional ability
in this field, gradually took over and continued with this field
all his life. Secretin was purified in 1953 and later also chole-
ERIK JORPES 377

cystokinin-pancreozymin [56-59]. Mutt brought pioneering

contributions to peptide research with his method of establish-
ing the C-terminal amide structures, which are unique chemi-
cal features of certain peptide hormones and neuropeptides
[60]. He continued to work at the Institute until his death in
1998. Birgitta Werner, later Viktor Mutt's wife, studied certain
gastrointestinal enzymes in new-born prematures in the
lowest weight groups [61].
During the middle of the 1950s, enterokinase was purified
and characterized by the Japanese guest researcher, Ikuo
Yamashina [62,63].

Research on coagulation and fibrinolysis proteins

Due to his interest in heparin, Jorpes also initiated and

supported work on blood coagulation proteins. The report
below belongs to the period before Jorpes became a pensioner
and the references are mostly only to theses by different
researchers. In each of them a summary of the published
papers can be found along with the pertinent literature.
Jorpes was responsible for the standardization of heparin
due to his commitments to the Vitrum firm. Stable fibrinogen
preparations were needed for a satisfactory standardization of
heparin and Birger and Margareta Blomb~ck therefore devel-
oped a method for the production of pure fibrinogen starting
from Cohn's fraction I [64]. Its chemical structure was studied
together with Pehr Edman, Ikuo Yamashina, Torvard Laur-
ent, Birgit Hessel and Agnes Henschen (later Pehr Edman's
wife) (see Refs. [65-67]). An intermediate fraction in the
process of purification, fraction I-0, contained high amounts
of factor VIII activity (lacking in haemophilia A and von Will-
ebrand's disease). Birger Blomb~ck, Margareta Blomb~ck and
Birgit Hessel and other collaborators started to produce this
fraction in the cellar of the department. Patients with these
diseases could then be successfully treated for spontaneous
bleeding and given prophylaxis during operations to prevent
378 v. MUTT, M. BLOMBACK

invalidating joint bleeds. In this context, Jorpes' collaboration

with Erik SkSld, head of the Blood Centre and a specialist in
haemophilia, and especially with Crafoord, was of great value,
because we sometimes used large amounts of the blood
collected in Stockholm, saying only that we needed it for
work with Crafoord. The method for preparation of fraction
I-0 has been used in many countries for many years. Much
of the clinical work was done in collaboration with Inga
Marie Nilsson, MalmS. Birger and Margareta Blomb~ick are
still working at the Karolinska Institute, Birger mostly on
fibrinogen, whereas Margareta is more clinically oriented.
In the same cellar of Jorpes' laboratory, plasminogen, uroki-
nase and prothrombin were purified. Per Wall~n, later joined
by Kurt BergstrSm [68,69] worked out a method for preparing
pure plasminogen, which was based on the interaction with
lysine or s-aminocaproic acid. The properties of purified
bovine plasminogen and of h u m a n urokinase and the activa-
tion of the former to plasmin were studied. The properties of
purified tissue plasminogen activator were investigated by Per
Wall~n (who died in 1999) in Ume~, where he worked together
with BjSrn Wiman. Staffan Magnusson purified prothrombin
and thrombin and studied the conversion of the proenzyme to
the enzyme and their chemical properties [70]. He continued
this work in Aarhus, where also many other proteins, espe-
cially of hemostasis, were purified and chemically character-
ized. Magnusson died in 1990.

V i k t o r Mutt's r e c o l l e c t i o n s o f E r i k J o r p e s i n t h e
r e s e a r c h e n v i r o n m e n t i n 1944

I started to work in Erik Jorpes' laboratory in the autumn of

1944. The Department of Chemistry at the Karolinska Insti-
tute was not situated where it is today in the municipality of
Solna on the western outskirts of Stockholm, but instead at
Hantverkargatan near Stockholm's Town Hall, on the shores
of lake M~ilaren, separated by a bay from the island of Riddar-
ERIK JORPES 379

holmen, where the Institute had first been located at the turn
of the nineteenth century. Serafimer Hospital, which had
opened in 1752, was on the other side of H a n t v e r k a r g a t a n
and, in 1944, was the teaching hospital in internal medicine
and surgery for the Karolinska Institute.
On the lake shore, just outside the Institute, there were
always creaking barges with quick-lime for construction
firms around Stockholm. At odd intervals we went there to
buy quick-lime for a crown or two to prepare 'absolute' dry
alcohol in a huge all-glass distillation apparatus in the base-
ment of the Chemistry Building. There were also special appa-
ratuses for drying ether and preparing distilled water. One
room in the basement was at everybody's disposal and was
to be used for large-scale extractions of tissues and centrifuga-
tions. Several rooms were used by TorbjSrn Caspersson, a co-
worker of Einar H a m m a r s t e n who, in 1944, had been
appointed Personal Research Professor in Medical Cell
Research and Genetics at the Institute, and Director of one
of the newly established Medical Nobel Institutes. Another
Nobel Institute used several other rooms. The Director was
another co-worker of Einar Hammarsten, Hugo Theorell,
who had been appointed Professor of Biochemistry at the
Institute, and Director of the Biochemical Nobel Institute in
1937 - he later received the Nobel prize. Thus in 1944, four
groups, which formed r a t h e r closed societies, directed by
Einar Hammarsten, Erik Jorpes, Hugo Theorell and TorbjSrn
Caspersson, were working in the building of the Chemistry
Department [71]. H a m m a r s t e n and Jorpes belonged to the
department proper.
In E.J.'s unit, work on heparin and insulin was still going on
in the a u t u m n of 1944. This was reflected by the type of equip-
ment in use, such as a Kjeldahl apparatus for the determina-
tion of nitrogen, a van Slyke apparatus specifically for amino-
nitrogen, and a polarimeter with tubes of various lengths for
determination of the optical rotation of carbohydrate solu-
tions. Because of his collaboration with Vitrum, at that time
380 V. MUTT, M. BLOMBACK

the manufacturing firm of heparin and insulin for clinical use

in Sweden, E.J. was responsible for testing the strength of
both these products. Insulin activity was determined by
recording a fall in blood sugar in rabbits in response to the
administration of insulin, and for determining the activity of
heparin, E.J. had devised a method which was reliable,
although unpleasant. A wooden rack was used that had
holes for ten glass tubes, each with a glass bead in it. A dilution
series of a solution of standard heparin was pipetted into the
first five tubes while a dilution series of the heparin solution to
be tested was pipetted into the other tubes. One had to go to
the slaughterhouse with a number of such racks and immedi-
ately after the cow had been killed collect the blood gushing
forth from its severed neck vessels into a crystallization bowl
and from this quickly empty it into the tubes. These were then
covered with a tightly fitting lid and the rack was brought back
to the laboratory. On inverting the rack, the beads fell so long
as coagulation had not occurred.

Recollections of Margareta Blomb~ck on the working

e n v i r o n m e n t i n t h e 1950s a n d t h e e a r l y 1960s

When Birger Blomb~ick and I started in Jorpes' department in

1950, it was still situated at the lake shore but in 1951 it
moved to the area where it is now located, in Solna. All sorts
of preparations, centrifugations and purification of different
proteins took place in the cellar. Large amounts of pancreas,
intestines and blood were brought there from the slaughter-
house to prepare insulin, gastrointestinal hormones and fibri-
nogen; later, fibrinogen and .fraction I-0 were prepared from
h u m a n blood in the same cellar. The latter, of course, had to be
prepared under sterile conditions, since it was to be used in
patients.
On the first floor, H a m m a r s t e n and his pupils, among others
Peter Reichard, Ulf Lagerkvist and Torvard Laurent, had their
writing desks and laboratories. Jorpes and his pupils had their
ERIK JORPES 381

desks and analytical laboratories mostly on the second floor but

also in other parts of the building. Among the pupils were
Viktor Mutt, Harry BostrSm, Sven Gardell, Selahaddin Rast-
geldi, Per Wall~n, Birger Blomb~ick and myself. We were later
joined by Lennart Rodin, Kurt BergstrSm, Staffan Magnusson,
Agnes Henschen and Birgit Hessel.
Jorpes had wisely chosen an efficient secretary and an excel-
lent librarian. In the 1950s, we were very spoiled by having
help from a glass blower, a workshop for necessary construc-
tions (on the initiative of Hammarsten), and personnel who
helped us wash glassware, etc. and prepare blood fractions
and secretin, etc. The salaries of many of these engineers
and technicians were paid by Erik Jorpes personally.

E r i k J o r p e s as h i s t o r i a n a n d t e a c h e r

Erik Jorpes was a great admirer of Berzelius. He was a

member of the Swedish Academy of Sciences, and Berzelius
had been its permanent secretary from 1818 to 1848. In 1960,
Jorpes wrote a book in Swedish, and in 1966, an expanded
version in English on the life of Berzelius [72,73]. In the
early 1970s he enthusiastically took part in the reorganization
of the Berzelius museum created in 1898 by the Academy.
He wrote many essays on the history of several researchers
and of Nobel. In addition, he wrote many reviews in the fields
which interested him particularly, such as blood coagulation,
heparin [74-78], insulin and together with Viktor Mutt on
gastrointestinal hormones [59]. He was also very proud of
his pupils' findings and happily and quickly described them
at the congresses in which he participated. At the time of his
death, he was working on the literature concerning heparin.
The first part, with the literature up to July 1958, was
published [79]. The second part has not been published yet.
A heavy teaching burden fell on Erik Jorpes' shoulders. As a
teacher, Erik Jorpes was strict and as an examiner, he was
feared. He painstakingly prepared his lectures, which were
382 v. MUTT, M. BLOMBJkCK

n o t only a c c u r a t e a n d i n f o r m a t i v e b u t also i n t e r e s t i n g . He
always k e p t t h e m up-to-date, at t h e s a m e t i m e p r e s e n t i n g a
fair historical b a c k g r o u n d . 5 It w a s a joy a n d a s t i m u l u s as a
s t u d e n t to h a v e t h e privilege of l i s t e n i n g to him. He t a u g h t n o t
only m e d i c a l s t u d e n t s b u t also t o g e t h e r w i t h Gardell s t a r t e d
t h e t r a i n i n g of l a b o r a t o r y n u r s e s a n d a s s i s t a n t s in Sweden.

Jorpes and the international research community

E r i k J o r p e s ' good i n s i g h t into t h e h i s t o r y of m e d i c i n e m a d e

h i m actively i n t e r e s t e d in h o w m e d i c a l r e s e a r c h w a s funded.
T o g e t h e r w i t h George Kahlson, Professor of Physiology at t h e
U n i v e r s i t y of L u n d , a n d s o m e colleagues at K a r o l i n s k a Insti-
tute, like E i n a r H a m m a r s t e n a n d R a g n a r Granit, Professor of
Neurophysiology, h e c o n t r i b u t e d v e r y actively to t h e establish-
m e n t of t h e S w e d i s h Medical R e s e a r c h Council in 1947, w h i c h
h a s b e e n of g r e a t i m p o r t a n c e for t h e d e v e l o p m e n t of m e d i c a l
r e s e a r c h in S w e d e n ever since.
He w a n t e d to i n c r e a s e collaboration b e t w e e n r e s e a r c h work-
ers, a n d always w e l c o m e d r e s e a r c h w o r k e r s from o t h e r coun-
tries. As m e n t i o n e d , h e p a r t i c i p a t e d in m a n y congresses w h e r e
h e enjoyed t h e c o m p a n y of his m a n y foreign friends. O n e of his
p a r t i c u l a r i n t e r e s t s w a s 'The I n t e r n a t i o n a l C o m m i t t e e on
H a e m o s t a s i s a n d T h r o m b o s i s ' in t h e creation of w h i c h h e
p l a y e d an active p a r t in 1954. E.J. w a s also deeply involved
in s t a r t i n g congresses on g a s t r o i n t e s t i n a l h o r m o n e s .

J o r p e s as a p e r s o n

E r i k J o r p e s often spoke of t h e diseases s u c h as tuberculosis,

5Jorpes used a number of methods to help students remember important

dates in the history of medicine. For example, he would ask if any student
could tell what happened in the year 1628. Several students would reply at
once: 'The Vasa ship sank in Stockholm harbour', whereupon E.J. would
comment 'That is correct, but William Harvey also discovered the circulation
of the blood.'
ERIK JORPES 383

pneumonia and pulmonary embolism which, during his youth

and early manhood, led to the death of many young people.
Perhaps it was this - and his experience during the war years
- that always made him work hard to try to transfer quickly
into practical medicine the knowledge gained in biochemistry.
Collaboration with doctors in the clinical disciplines was
necessary to this end, but above all with the pharmaceutical
industries. Erik Jorpes had an amazing capacity for work to
which his prolific writing in varying spheres bears witness.
Even in old age he still worked late into the night.
As an individual, he was reserved, and lived simply, accord-
ing to strict principles. He was always punctilious and very
courteous in his manner. He was a teetotaller because, as he
pointed out, he had learned on/~land how an overindulgence
in spirits could lead to personal tragedy.
As has been previously mentioned, Erik Jorpes had good
contacts with the pharmaceutical industry, particularly with
the Vitrum company. The royalties he received for his work
reached high figures and, during certain periods, he was
regarded as belonging to Sweden's highest income bracket.
The high royalties probably arose because he was not keen
on patenting. What he sold was his knowledge. However,
most of the money went straight to his research activities in
the department, including remuneration of foreign and some-
times Swedish research workers. Nor did he eVeroforget his
native village, and he very willingly subsidized the Aland fish-
ery and agriculture industries.
In 1921, Erik had started a regular correspondence with a
very capable woman, a domestic science teacher from the
south of Sweden, whom he married in 1930, when his income
was assured. She cherished and spoiled him although he was
always at work. She arranged very enjoyable dinners and
evenings in their home. In 1933, a daughter was born and in
1935, a son. When Erik was asked whether he was going to
visit his son in the hospital, he answered, 'sons you can have
more of but the structure of heparin is unique' [20,21].
384 V. MUTT, M. BLOMBACK

The best time to reach him during work was between 9 and
10 p.m. in the evening, w h e n coffee or tea was served in the
Department of Chemistry. However, personal contact was
greatest w h e n invited, perhaps in the company of some foreign
research worker, to his s u m m e r house on RunmarS, an island
in the Stockholm archipelago. Not only did we participate in
expeditions to the outermost islands, but also absorbed his
knowledge of flowers, birds and fish, including the art of fish-
ing. The days spent with Erik Jorpes, who was then comple-
tely relaxed in the surroundings he loved, are unforgettable.
Erik Jorpes died in 1973 and is buried on RunmarS.

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[27] Holmgren, H. and Wilander, O. (1937) Beitrag zur Kenntnis der
Chemie und Funktion der Ehrlichschen Mastzellen. Zeitschrift ffir
mikroskopisch-anatomische Forschung. 42, 242-287.
[28] Jorpes, J.E., BostrSm, H. and Mutt, V. (1950) The linkage of the amino
group in heparin. Alleged acetyl content ofheparin. J. Biol. Chem. 183,
607-615.
[29] Jorpes, E., BostrSm, H. and M~nsson, B. (1952) On the linkage of the
amino group in heparin. Acta Chem. Scand. 6, 797-798.
[30] Murray, D.W.G., Jaques, L.B., Perrett, T.S. and Best, C.H. (1937)
Heparin and thrombosis of veins following injury. Surgery 2, 163-187.
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[31] Jorpes, J.E. (1946) Heparin in the Treatment of Thrombosis. An

Account of its Chemistry, Physiology, and Application in Medicine,
2nd edn., pp. 1-260. London, Oxford Medical Publications, Oxford
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[32] Symposium on heparin and thrombosis (1941) Acta Med. Scand.
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[33] Jorpes, E. (1941) Pure heparin for the prevention and treatment of
thrombosis. Acta Med. Scand. 107(fasc II), 107-115.
[34] Bauer, G. (1941) Early diagnosis of venous thrombosis by means of
venography and abortive treatment with heparin. Acta Med. Scand.
107(fasc II), 136-147.
[35] Zilliacus, H. (1946) On specific treatment of thrombosis and pulmonary
embolism with anticoagulants; with particular reference to post-
thrombotic sequelae; results of 5 years' treatment of thrombosis and
pulmonary embolism at series of Swedish Hospitals during years
1940-45. Acta Med. Seand. Suppl. 171.
[36] Jorpes, J.E. and Gardell, S. (1948) On heparin monosulfuric acid. J.
Biol. Chem. 176, 267-276.
[37] Gardell, S., Gordon, A.H. and Aqvist, S. (1950) Electrophoresis of
mucopolysaccharides in a slab of Hyflo Super-cel. Acta Chem. Scand.
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[38] Gardell, S. (1952) Some contributions to the technique of analyzing
polysaccharides with particular reference to animal mucopolysacchar-
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[39] Gardell, S. (1956) The mucopolysaccharides of nucleus pulposus. Acta
Chem. Scand. 9, 1035.
[40] Scott, J.E., Gardell, S. and Nflsson, I.M. (1957) The use of long-chain
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column. Acta Chem. Scand. 11, 668-675.
[42] Gardell, S. (1958) Determination of hexosamines. In Methods in
Biochemical Analysis, Vol. 6, pp. 289-317. New York, Interscience.
[43] Gardell, S. (1953) Separation on Dowex 50 ion exchange resin ofgluco-
samine and galactosamine and their quantitative determination. Acta
Chem. Scand. 7, 207-215.
[44] BostrSm, H. (1953) ChemicM and autoradiographic studies on the
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Chem. 196, 483-487.
ERIK JORPES 387

[46] BostrSm, H. and Odeblad, E. (1953) The influence of cortisone upon

the sulphate exchange of chondroitin sulphuric acid. Ark. Kemi. 6,
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[47] BostrSm, H. and M~nsson, B. (1955) The action of salicylates and
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[48] BostrSm, H. and M~nsson, B. (1953) The demonstration of a liver factor
stimulating the sulphate exchange of chondroitin sulphuric acid. Acta
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[49] BostrSm, H., Jorpes, E., M~nsson, B., Rod6n, L. and Vestermark, A.
(1955) On the partial purification of a liver factor stimulating the
sulphate exchange of chondroitin sulphuric acid. Ark. Kemi. 8, 469-
480.
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[51] Bellman, S., BostrSm, H., GSthman, B. and Rod6n, L. (1956) On the
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[52] BostrSm, H. and Dohlman, C.-H. (1955) Uptake of sulphate by muco-
polysaccharides in the rat cornea and sclera. Acta Ophtalmol. 33,455-
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[53] Edman, P. (1949) A method for the determination of the amino acid
sequences in peptides. Arch. Biochem. 22, 475-476.
[54] Edman, P. (1950) Preparation of phenyl thiohydantoin from some
natural amino acids. Acta Chem. Scand. 4, 277-282.
[55] Edman, P. (1950) Method for determination of the amino acid sequence
in peptides. Acta Chem. Scand. 4, 283-293.
[56] Jorpes, J.E. and Mutt, V. (1953) A new method for the preparation of
secretin. Ark. Kemi. 6, 273-276.
[57] Jorpes, J.E. and Mutt, V. (1954) On the action of highly purified
preparations of secretin and of pancreozymin. Ark. Kemi. 7, 553-559.
[58] Jorpes, J.E. and Mutt, V. (1961) The gastrointestinal hormones,
secretin and cholecystokinin-pancreozymin. Ann. Intern. Med. 55,
395-405.
[59] Jorpes, J.E. and Mutt, V. (1973) Secretin and cholecystokinin (CCK). In
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ed.). Berlin, Springer-Verlag.
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York, Raven Press.
388 V. MUTT, M. BLOMBACK

[61] Werner, B. and Mutt, V. (1954) The pancreatic response in man to the
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[62] Yamashina, I. (1954) Studies on enterokinase. I. The purification and
general properties. Ark. Kemi. 7, 539-543.
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tion. Ark. Kemi. 9, 225-229.
[64] Blomb~ick, B. and Blomb~ick, M. (1956) Purification of h u m a n and
bovine fibrinogen. Ark. Kemi. 10, 415-443.
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Scand. 47(Suppl. 114), 1-32.
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Toxicol. 11, 367-376.
ERIK JORPES 389

[77] Jorpes, J.E. (1956) The pharmacy of blood, its products and substi-
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[78] Jorpes, J.E. (1958) Research Work Performed at Chemistry Department
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A Review. Uppsala, Almqvist & Wiksells Boktryckeri AB.
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