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Stem Cell Research:

Status and Ethics


Stem Cell – Definition
 A cell that has the ability to
continuously divide and
differentiate (develop) into
various other kind(s) of
cells/tissues
Introduction
 Can we vs. should we
 Dramatic advances of modern
molecular genetics
 Should we ask the morality
questions before attempting the
“can we” questions?
Stem Cell/Cloning Topics
 What are stem cells?
 History of stem cell/cloning
research
 Possible uses of the technology
 Current status/knowledge
 Questions and known problems
 Legal considerations
 Politics
 Moral considerations
Kinds of Stem Cells
Stem cell
type Description Examples
Cells from early
Each cell can develop
Totipotent
Totipotent (1-3 days)
into a new individual
embryos
Some cells of
Cells can form any
Pluripotent
Pluripotent blastocyst (5 to
(over 200) cell types
14 days)
Cells differentiated, Fetal tissue, cord
Multipotent
Multipotent but can form a number blood, and adult
of other tissues stem cells
Stages of Embryogenesis

Day 2
2-cell embryo Day 3-4
Day 1
Multi-cell embryo
Fertilized egg

Day 5-6
Day 11-14 Blastocyst
Tissue Differentiation
Derivation and Use of
Embryonic Stem Cell Lines
Isolate inner cell mass
Outer cells (destroys embryo)
(forms placenta)
Inner cells
(forms fetus) Culture cells

Day 5-6
Blastocyst “Special sauce”
(largely unknown)

Liver
Heart
repaired
Kidney Heart muscle
History of Stem Cell/Cloning
Research
 Who invented cloning and when?
 Stem cell research – a new field of
study?
 History of human stem cell
research
 History of embryonic cell research
 History of cloning/human cloning
History of Human Stem Cell
Research
 In 1968, the first bone marrow
transplant was successfully used in
treatment of SCID
 Since the 1970’s, bone marrow
transplants have been used for
treatment of immunodeficiencies
and leukemias
Bone Marrow Stem Cells
History of Human Embryonic
Cell Research
 1954 – John Enders received a
Nobel prize in Medicine for growing
polio virus in human embryonic
kidney cells
History of Human Embryonic
Stem Cell Research
 In 1998, James Thomson (University of
Wisconsin-Madison) isolated cells from
the inner cell mass of the early embryo,
and developed the first human
embryonic stem cell lines.
 In 1998, John Gearhart (Johns Hopkins
University) derived human embryonic
germ cells from cells in fetal gonadal
tissue (primordial germ cells).
 Pluripotent stem cell “lines” were
developed from both sources
History of Somatic Cell
Nuclear Transfer (Cloning)
 1952 – Briggs and King cloned
tadpoles
 1996 – The first mammal cloned
from adult cells was Dolly, the
sheep.
 1998 – Mice cloned
 1998 – Cows cloned
 2000 – Pigs cloned
“CC” Carbon Copy

History of Cloning
 2001 – Cat cloned
 2002 – Rabbits cloned
 2003 – Mule cloned
 2004 – Bull serial-cloned
 2005 – Dog cloned
Possible Uses of Stem Cell
Technology
 Replaceable tissues/organs
 Repair of defective cell types
 Delivery of genetic therapies
 Delivery chemotherapeutic agents
Early Successes – Adult Stem
Cells
 Human mesenchymal stem cells
turned on genes found in bone,
cartilage, adipose, muscle,
hematopoiesis-supporting stromal,
endothelial, and neuronal cells.
 Multipotent adult progenitor cells
have been shown to differentiate
into functional, hepatocyte-like
cells.
Early Successes – Adult Stem
Cells
 Human neural stem cells can
migrate extensively in the brain
after injection.
 Adult stem cells have been
isolated from amniotic fluid,
peripheral blood, umbilical cord
blood, umbilical cord, brain tissue,
muscle, liver, pancreas, cornea,
salivary gland, skin, tendon, heart,
cartilage, thymus, dental pulp, and
adipose tissue.
Early Successes – Human
Cloning
 2001 – First cloned human
embryos (only to six cell stage)
created by Advanced Cell
Technology (USA)
 2004* – Claim of first human
cloned blastocyst created and a
cell line established (Korea) – later
proved to be fraudulent

*Hwang, W.S., et al. 2004. Evidence of a Pluripotent Human


Embryonic Stem Cell Line Derived from a Cloned
Blastocyst. Science 303: 1669-1674.
Cloned Human ESC
Differentiate Into Different
Tissue Types
Neural Retinal

Bone Cartilage Epithelial


Cloned Embryonic Stem Cells –
Advantages/Problems
 Advantages
 No rejection
 “Prefect match”
 Problems
 Only 10% of cloned oocytes became
embryos
 0% (0 out of 2061) survived to become a
cell line
 Genetic donor was same as egg donor
(i.e., won’t work for males!)
 Cost is high (health insurance probably
won't pay)
Unknowns in Stem
Cell/Cloning Research
 It is uncertain that human
embryonic stem cells in vitro can
give rise to all the different cell
types of the adult body.
 It is unknown if stem cells cultured
in vitro (apart from the embryo) will
function as the cells do when they
are part of the developing embryo
Challenges to Stem
Cell/Cloning Research
 Stem cells need to be
differentiated to the appropriate
cell type(s) before they can be
used clinically.
 Recently, abnormalities in
chromosome number and structure
were found in three human ESC
lines.
Challenges to Stem
Cell/Cloning Research
 Stem cell development or
proliferation must be controlled
once placed into patients.
 Possibility of rejection of stem cell
transplants as foreign tissues is
very high.
Challenges to Stem
Cell/Cloning Research
 Contamination by viruses, bacteria,
fungi, and Mycoplasma possible.
 The use of mouse “feeder” cells to
grow ESC could result in problems
due to xenotransplantation
(complicating FDA requirements
for clinical use).
Legal Considerations:
Embryonic Cell Research
 1973 – moratorium on government
financing for human embryo
research
 1988 – NIH Panel voted 19-2 in
favor of government funding
 1989 – DHHS Secretary Sullivan
extended the moratorium
Legal Considerations:
Embryonic Cell Research
 1990 – Congress voted to override
the moratorium, vetoed by
President Bush
 1993 – President Clinton lifted the
ban
 1994 – the Human Embryo
Research Panel favored research,
but Clinton overrode the panel
 1995 – Congress banned federal
funding
Legal Considerations:
Embryonic Cell Research
 August 25, 2000, President Clinton
allowed funding of research based
on cells from (aborted) human fetal
lines, but not embryonic cells
 On August 9, 2001, President
Bush announced his decision to
allow Federal funds to be used
only for research on existing
human embryonic stem cell lines
created prior to his announcement
Right to Life
The Declaration of Independence of the
United States guarantees “certain
unalienable Rights, that among those are
Life, Liberty and the pursuit of Happiness”
Laws Banning Reproductive Cloning
(as of 2004)
Laws Banning Research Cloning
(as of 2004)
Worldwide Stem Cell
Regulations
 2003 proposal to ban reproductive
and research cloning worldwide
was tabled by the United Nations
following objections by Great
Britain and other countries
 The proposal will be taken up
again in 2004, but dropped
Embryonic Reproductive
Cloning Laws Worldwide
Embryonic Research Cloning
Laws Worldwide
Stem Cells and Politics
 The California Stem Cell Research
and Cures Initiative
 Nancy Reagan
 Michael Reagan
 Congress
 John Kerry
The California Stem Cell
Research and Cures Initiative
 November, 2004 ballot initiative
 Established the California Institute
for Regenerative Medicine
 Run by an Independent Citizen's
Oversight Committee composed of
politicians, advocacy groups, and
“executive officers” of universities
 Indebted the state of California for
$3,000,000,000 in State General
Obligation Bonds
The California Stem Cell
Research and Cures Initiative
 ICOC requires grantees to
purchase goods and services from
California suppliers (> 50%)
 Established real estate
development and facilities
construction for research (up to
10% of total funding)
 3% for general administration, 3%
for grant administration
 Up to $6,000,000 per grantee/year
The California Stem Cell
Research and Cures Initiative
 Although the initiative purported to
fund all manner of stem cell
research, a clause prevents
funding of any stem cell research
other than embryonic stem cell
research:
“…other research categories funded
by the National Institute of Health
shall not be funded by the Institute”
 Passed by voters, November, 2004
Nancy Reagan and Embryonic
Stem Cell Research
 Nancy Reagan pushing embryonic
stem cell research as “cure” for
Alzheimer's disease.
 Alzheimer's disease is due to
pathology that spreads from
affected cells to healthy cells
 Stem cell treatments, if they
worked, would also become
abnormal shortly after treatment
Michael Reagan: My Father
Opposed Embryo Destruction
 “…my father, as I do, opposed the
creation of human embryos for the
sole purpose of using their stem
cells as possible medical cures.”
 Called media references to ESC
cures as “junk science.”
 Quoted ESC researchers who say
that ESC are unlikely to cure
Alzheimer’s Disease
Congress Calls for Review of
White House ESC Policy
 206 representatives said that the
current policy, instituted by Bush in
August 2001, have slowed
potentially lifesaving research
(4/30/04)
 58 Senators (including 14
Republicans) called for President
Bush to reverse his ESC policy
(6/4/04)
John Kerry Says Bush Has
“politicized science”
 “While the Bush administration has
politicized science, Kerry will put
America back on the path of
scientific excellence with a
commitment to scientific research
based on fact – not ideology.”
Moral and Ethical Considerations of
Stem Cell and Cloning Research
 Adult stem cells
 Embryonic stem cells
 Embryo must be destroyed
 When does human life/personhood
begin?
 Human cloning
 Embryos (see above)
 Reproductive cloning
When Does Human Life Begin?
Medical Embryology Textbooks
The Developing Human: Clinically
Oriented Embryology
“Zygote: this cell results from the
union of an oocyte and a sperm. A
zygote is the beginning of a new
human being (i.e., an embryo).
Human development begins at
fertilization… This highly
specialized, totipotent cell marks
the beginning of each of us as a
unique individual.”
When Does Human Life Begin?
Medical Embryology Textbooks
Essentials of Human Embryology
“In this text, we begin our
description of the developing
human with the formation and
differentiation of the male and
female sex cells or gametes, which
will unite at fertilization to initiate
the embryonic development of a
new individual.”
When Does Human Life Begin?
Medical Embryology Textbooks
Human Embryology & Teratology
“Fertilization is an important
landmark because, under ordinary
circumstances, a new, genetically
distinct human organism is thereby
formed…”
When Does Human Life Begin?
What Do Medical Doctors Say?
 Dr. Alfred Bongioanni (University of
Pennsylvania):
“I have learned from my earliest
medical education that human life
begins at the time of conception.”
 Dr. Jerome LeJeune (University of
Descartes):
“after fertilization has taken place a
new human being has come into
being.”
When Does Human Life Begin?
What Do Medical Doctors Say?
 Dr. Hymie Gordon (Mayo Clinic):
“By all criteria of modern molecular
biology, life is present from the
moment of conception.”
 Dr. Micheline Matthews-Roth
(Harvard University Medical
School):
“It is scientifically correct to say
that an individual human life
begins at conception”
Embryo Is Not a Person
“Persons . . . are members of a
social community that shapes and
values them, and personhood must
be defined in terms of interactions
and relationships with others.”

Susan Sherwin. 1999. Ethical Issues:


Perspectives for Canadians. Ed.
Soifer, Eldon. Peterborough, Ontario:
Broadview Press, p. 267
Embryo Is Not a Person –
Rebuttal
Personality definition problems
 Does a human non-person exist?
 What traits define personhood?
 Who makes the definition?
 Society has excluded certain
humans from personhood before
(e.g., African slaves, Chinese, etc.)
Should we make a new list of
human non-persons?
Embryo Is Not a Person –
Rebuttal
 The lack of certain personality traits
would remove from personhood:
 Those who are in a coma
 Elderly with degenerative disorders
(Alzheimer's, etc.)
 Mentally deficient
 Genetic
 Neurological disease
 Mental illness
 Is is okay to consider these human
beings as non-persons?
Definition of Personhood
 One who is consciously performing
personal acts
 eliminates those who are sleeping
 One with a present capacity to
perform personal acts
 eliminates those who are in a
coma
Definition of Personhood
 One who has a history of
performing personal acts
 eliminates one who was in a coma
from birth, but wakes up
 One with a future capacity for
performing personal acts
 makes those who are dying as
non-persons
Implications of Functionally-
Defined Personhood
 Newborns lack the ability to
perform personal functions – in
fact, newborn humans are less
capable physically and mentally
than virtually all other mammals
 Therefore, on the basis of
functionally-defined personhood,
newborns fail the test could be
killed on the basis of “non-
personhood”
At Conception, It Is Only a
Single Cell
Claim:
 Fertilized eggs are single cells, like
blood cells or other parts of the
body
Rebuttal:
 This single cell is unique from both
the father’s and mother’s cells and
is the beginning of every new
human being
Only a Small Percentage of
Embryos Implant
Claim:
 Embryos are only potential life. Most do
not result in births
Rebuttal:
 25-33% of women become pregnant in
the first month
 33% of implanted embryos die before
birth
 There are countries in which over 25% of
children die before age 5. Should we
allow killing of children?
Frozen Embryos Are Going to
Be Discarded Anyway
 Proponents of human embryonic
stem cell research say that
embryos from IVF are going to be
discarded and, so, should be used
for research
 Prisoners on death row are also
going to die, so why not do
research on them?
Devaluation of Human Life
 Right now it is only 5-12 day
embryos
 When science discovers it is
impossible to produce
organs/tissues in the absence of
surrounding developmental
processes, scientists will demand
the tissues be allowed to “mature”
prior to harvest
Christian Arguments and
Response
 We may not do evil so that good
will result (Romans 3:8)
 Humans are created in the image
of God before birth
 The human soul begins before
birth
Bible: Human Life Begins
Before Birth
 "Did not He who made me in the womb
make him, And the same one fashion us
in the womb? (Job 31:15)
 Yet Thou art He who didst bring me forth
from the womb… Thou hast been my
God from my mother's womb. (Psalms
22:9-10)
 For Thou didst form my inward parts;
Thou didst weave me in my mother's
womb. I will give thanks to Thee, for I am
fearfully and wonderfully made (Psalms
139:13-16)
 See also Isaiah 44:2, 24
When Does Ensoulment
Occur?
 John the Baptist: "For he will be great in the
sight of the Lord, and he will drink no wine
or liquor; and he will be filled with the Holy
Spirit, while yet in his mother's womb."
(Luke 1:15)
 Paul: But when He who had set me apart,
even from my mother's womb, and called
me through His grace… (Galatians 1:15)
 Jeremiah: "Before I formed you in the womb
I knew you, And before you were born I
consecrated you; I have appointed you a
prophet to the nations." (Jeremiah 1:5)
Murder Defined by the Bible
 People are not to be murdered
because they are created in the
image of God. (Genesis 9:6)
 Murder must be intentional, with
premeditation (Joshua 20:3)
 Killing of embryos is intentional,
and premeditated
Biblical Arguments: Summary
 The Bible indicates that God
recognizes human beings as
persons prior to development in
the womb
 Bible defines murder as being
intentional and premeditated
 ESC research destroys embryos
that are considered as ensouled
human beings
Morality of Human
Reproductive Cloning
 “Be fruitful and multiply” –
assumed to be natural, but IVF and
cloning not mentioned in the Bible
 Problems with cloned animals –
most suffer premature aging and
other genetic problems. Might be
avoidable with better techniques?
 Biblical basis to condemn human
reproductive cloning?

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