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The Eighth Asian Bioethics Conference
March 19-23, 2007, Bangkok, Thailand
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Bagher Larijani, MD
Professor of Tehran University
of Medical Sciences
Farzaneh Zahedi, MD
Researcher of Tehran University
of Medical Sciences
Medical Ethics and History of Medicine Research Centre,
& Endocrinology and Metabolism Research Centre,
Tehran University of Medical Sciences
INTRODUCTION
The discovery of Embryonic Stem
Cells (ESCs ) in the 1980s suggested
therapeutic approaches to chronic,
debilitating, and incurable diseases
such as Parkinson’s disease,
Alzheimer's, Diabetes Mellitus, and
brain and spinal injuries.
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Introduction (cont.)
Using ESCs are surrounded by a number
of ethical controversies, the extent of
which is partly dependent on their
source.
The debate over this subject became
further complicated in 1998 when
researchers were able to isolate human
Embryonic Stem Cells (hESCs).
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Introduction (cont.)
Many areas of stem cell research and
their potential clinical applications
are associated with controversy;
therefore there are varied sociocultural, ethical, political, and
religious viewpoints to be
considered in discussions about the
production and use of stem cells.
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POTENTIAL APPLICATIONS
The most important
application of hES cells is
clinically in
transplantation
and regenerative medicine.
7
POTENTIAL APPLICATIONS
Disorder
Cells transplanted
Disorder
Cells transplanted
Alzheimer's disease
Nerve cells
Kidney disease
Kidney cells
Atherosclerosis
Endothelial cells
leukemia
Hematopoietic cells
Liver disease
Hepatocytes
Macular degeneration
Retinal cells
Burns
Skin cells
Chronic pain
Chromaffin cells
Multiple sclerosis
Glial cells
Diabetes
Islet cells
Muscular dystrophy
Skeletal muscle cells
Epilepsy
Nerve cells
Osteoarthritis
Chrondrocytes
Heart disease
Cardiomyocytes
Parkinson's disease
Dopaminergic
neurons
Rheumatoid arthritis
Chrondrocytes
Strokes
Nerve cells
Spinal cord injuries
Nerve cells
Huntington's disease Nerve cells
Hypocalcemia
Parathyroid cells
Hypocholesterolemia Hepatocytes
NATURE BIOTECHNOLOGY 1999; 17: 1173
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APPLICATIONS IN RESEARCH
Models of human disease
The pharmaceutical research
Human developmental biology
Gene therapy
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Cell Characteristics in Stem Cell Biology
Term
Definition
Example
Totipotent
Able to Produce an entire being
Pluripotent
Able to produce all tissues and self- Embryonic
renew indefinitely
stem cell
Multipotent
Able to produce many cell types and Hematopoietic
self-renew over the lifetime of the stem cell
being and over many subsequent
generations if transplanted
Progenitor
Able to produce restricted number of Neural stem
cell types and with limited to no cell
capacity of self-renewal
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Blastomeres
STEM CELL SOURCES
There are various ways in which human
stem cells might be obtained:
•Adult Stem Cells
•Umbilical Cords
•Placenta
•Aborted Fetuses
•Spare Embryos from IVF Clinics
•Cloned Human Embryo
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EMBRYONIC STEM CELL
Embryonic stem (ES) cells are derived from
the inner cell mass of a blastocyst.
 The blastocyst forms at approximately 4 or 5
days after fertilization and contains from 64
to several hundred cells organized in an outer
shell, the trophectoderm, and a collection of
polarized inner cells termed the inner cell
mass (ICM).

J Clin Invest, Vol.114, No.9, 2004, pp. 1184-1186
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PLURIPOTENCY
Stem cells retain the ability to differentiate into
cells and tissues from all 3 germ layers
(endoderm, mesoderm, and ectoderm).
But, these cells cannot form the other
‘extra- embryonic’ tissues necessary for
complete development, such as placenta and
membranes, therefore
they cannot give rise to a complete new
individual.
•Human Reproduction, Vol.18, No.4, 2003, pp. 672-682
•The Journal of Urology, Vol.170, 2003, pp. 2453-2458
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hES cells are pluripotent
Source: NIH 2001: Stem Cells: Scientific Progress and Future Research Directions
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Disadvantages of ESCs
 Cancer
and Tumors : the potential of
introducing cancer into patients because
of rapid growth of embryonic stem cells
 Tissue Rejection
 Genetic Abnormalities
 Hundreds of thousands to millions of
stem cell lines would be required to treat
the majority of patients
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CLONING
An alternative method
of deriving human
ESCs is somatic cell
nuclear transfer
(SCNT), or cloning .
Dolly
1997-2003
SCNT across species is an
important challenge.
17
Removing the
maternal nucleus
before nuclear
transfer
Nuclear transfer
embryo about to be
activated
(Roslin Institute http://www.roslin.ac.uk)
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ADVANTAGES OF CLONING

No rejection, “Perfect match”
Stem cells produced by therapeutic
cloning are genetically similar to the
cells of the individual who donated the
nucleus, and thus avoid problems of
rejection.
•The Journal of Clinical Investing , Vol.14, No.10, 2004, pp. 1364-1370
•Journal of Medicine and philosophy, Vol.27, No.3, 2002. pp. 297-317
•The New England Journal of Medicine, Vol.346, No.20, 2002, pp. 1576-1579
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DISADVANTAGES OF CLONING
 Not Enough Human Eggs
 Cloning damages DNA
Further improvements in SCNT
protocols and in vitro culture systems
are needed before contemplating the
use of this technique for cell therapy.
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ADULT STEM CELLS
Stem cells have been identified in adult tissues.
Examples include the brain, skeletal muscle,
bone marrow and umbilical cord blood,
although the heart, by contrast, contains no stem
cells after birth.
 It is becoming increasingly evident that adult
stem cells can show considerably more
plasticity and could be more versatile than
previously believed.

• Cell prolif, Vol.37, 2004, pp. 23-34
• Proc Natl Acad Sci USA, Vol.100, 2003, pp. 1191-7
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Advantages/Disadvantages
Stem Cell
Cost
Human
Embryos
Low (?)
(IVF
leftovers)
Yes
Human
Clones
High
None
Tissue
rejection
Ethical
Problems
Unique
human
embryos
Cloned
human
embryos
Works for
genetic
diseases
Yes
No
Adult
Low
Autologous
None
None
No
Adult
Donated
Yes
None
Yes
Low
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KEY ETHICAL ISSUES
 Moral status of human embryo
 The creation of embryos only for research purposes
 Exploitation of women to obtain oocytes and
commercialization of human eggs
 Resource Allocation
 Justice: Equitable distribution of the benefits is also
important.
 Conflicts of Interests: financial interest of researchers
 Patenting of stem cell lines
 Animal/human hybrids
 …
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MAIN ETHICAL ISSUE

Moral status of human embryo:
The embryo is unavoidably destroyed
during the process of ESCs harvesting.
When does “human life” begin?
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Humanity of the Unborn
The Moral status of human embryo
is major ethical issue in conducting this
research. To create new cell lines, it is
necessary to destroy preimplantation
blastocysts.
The question is
whether the destruction of human embryos
amounts to the killing of human beings.
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The Status of the Embryo
 Does
the blastocyst have the same rights
(e.g., the right to life, to thrive, not to be
harmed, etc.) as human beings?
 If
the blastocyst has the same rights as a
human being, then to derive stem cells
from it means that a human being must be
killed.
Is it ethical to fertilize embryo merely for
stem cell harvesting?
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Views about the Moral Status of the Embryo



The Pro-Life View: An early embryo has the same
right to life as a normal adult human being. The
embryo is a ‘person’ and because of the potential
of the embryo to develop into a person, it ought
to be considered as a person.
The Pro-Choice View: An early embryo has no
moral status whatsoever.
The embryo (and even the fetus) as a ‘nonperson’ ought not to be attributed any moral
status at all.
There is a spectrum of opinions between these
extremes.
Human Reproduction, Vol.18, No.4, 2003,pp. 672-682
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The Status of the Embryo (cont.)
One moral argument is that human
‘personhood’ begins at conception,
or –as in cloning– at the genetic
beginning.
Based on this argument, the
destruction of embryos for research
cannot be justified.
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The Status of the Embryo (cont.)

It is necessary to consider that viewing the
embryo as a person rules out not only stem-cell
research, but all fertility treatments that
involve the creation and discarding of excess
embryos. However, defenders of in vitro
fertilization point out that embryo loss in
assisted reproduction is less frequent than in
natural pregnancy, in which more than half
of all fertilized eggs either fail to implant or are
otherwise lost.
New Engl J of Med, Vol.346, No.20, 2002, pp. 1579-82
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The Status of the Embryo (cont.)
A different moral argument underlines that
embryos do deserve protection and a certain
respect, but not to the same extent as fully
developed babies.
From this viewpoint, the moral status of
embryos gradually increases with their
development. Once they are born, they are
entitled to enjoy full rights as human beings.
Therefore, destruction of embryos can be
justified to provide a treatment for patients.
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The Status of the Embryo (cont.)
A third type of moral argument points out
that certain milestones exist in
embryonic development that change the
status of embryos.
 For example:
Ensoulment
 The primitive streak development at
day 14, before three germ layers
appear
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The sacred writings and teachings of
different religions contain
a wealth of teachings about the
key moments of life; its beginning
and its end.
Recent advances in scientific research and
technological sophistication have raised totally
new possibilities of deciding about birth and
death. Different religions, faiths, and customs
have different views on these issues
34
OVERALL CONSENSUS
All
religions believe that usage of
adult, placental, and umbilical
stem cells is acceptable.
Controversy lies with idea of
using embryonic stem cells
and where life begins.
35
Religious Questions
•What is an Embryo ?
•When does life begin ?
•At what point do rights apply?
•Is there any agreement on these
questions?
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Moral Status of Human Embryo
 There
is no consensus on the morality of
the embryo, even within particular
religious traditions.
 There is substantial debate regarding at
which specific stage dignity is conferred
in development (conception, primitive
streak development, implantation,
ensoulment or birth)
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CHRISTIANITY
Life
begins at conception
Killing embryo any time after
conception is equivalent to killing a
human being
38
Christianity (cont.)
Although Roman Catholicism officially
opposes human embryonic stem cell
research, some Roman catholic moral
theologians endorse it.
 Protestants have a wide range of views.
 Orthodox Church firmly reject any and all
manipulation of human embryos for research
purposes as inherently immoral and a
fundamental violation of human life.

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JUDAISM
A fetus is not seen as being an ensouled
person. Not only are the first forty days of
conception considered 'like water' but also
even in the last trimester, the fetus has a
lesser moral status.
 A number of Jewish thinkers hold that the
extracorporeal embryo, in the Petri dish or
cry preserved, does not have standing in
Jewish law and that it is justifiable to go
forward with embryonic stem cell
research.

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EASTERN RELIGIONS

Buddhism
Controversial on embryonic stem cell research
 Advocates:
- Central virtues of knowledge and compassion
- Want to alleviate human suffering
 Opponents:
- First precept of Buddhism: prohibits causing death
or injury to living creatures
- Ahimsa- non harming
- Life begins at conception; karmic identity of
recently deceased individual
- No enduring soul
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ISLAM
In opinion of most Muslim jurists,
stem cell and cloning research, as great
scientific events, would have advantages
and limitations.
 Due to majority of Muslim reference
decrees, according to inevitable
consequences of reproductive cloning, it
is prohibited.
Transplantation Proceedings, Vol.36, No.10, 2005, pp. 3188-3189
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ISLAM
According to Islamic beliefs, the fetus
undergoes a series of transformations
beginning as an organism and
becoming a human being. The fetus
culminates in becoming a full human
being when it is “ensouled” at 120 days
(the end of the fourth month) from the
moment of conception.
43
ISLAM
Holy Quran (chapter 23/verses 12-14)
describes the development of an embryo
into a full human person:
"We created Man of an extraction of clay, then
we set him, a drop in a safe lodging, then We
created of the drop a clot, then We created of the
clot a tissue, then We created of the tissue bones,
then we covered the bones in flesh; thereafter
We produced it as another creature. So blessed
be God, the Best of creators (khaliqin)!" 44
ISLAM
Nevertheless, the rights of the child begin
prior to her/his birth. Given the Islamic
teachings, the embryo, even in the first
days of its existence, has the right to live
and no one has the right to kill it; but the
punishment of fetus eradication in the
pre-ensoulment stages will be much less
than abortion after ensoulment.
45
ISLAM
It is obvious that because of the
potential therapeutic benefits of the
procedure of stem cell research and
cloning, destruction of the blastocyst
and research into human ESCs should
be justified according to the majority
of Muslim scholars.
46
The Islamic Fiqh Council (1997)
The conference was organized in Casablanca. A
consensus was reached that:
“Cloning does not bring into question any Islamic belief
in any way. Allah is the Creator of the universe but He has
established the system of cause-and-effect in this world.
Sowing a seed in the ground is the cause but only Allah
produces the effect from it in the form of a plant. Similarly
cloning is a cause and only through Allah's Will it can
produce the effect. Just as the person sowing the seed is
not the creator of the resulting plant, so the cloning
technician is not the creator of the resulting animal. Allah
alone is the Creator and all creation takes place solely
through His Will."
Human Cloning: comments by political groups, religious authorities.
http://www.religioustolerance.org/clo_reac.htm
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ISLAM
Most attendees concluded that
reproductive cloning is permissible
for plants and animals, but not
humans. "The extension of cloning
to human beings would create
extremely complex and intractable
social and moral problems."
Human Cloning: comments by political groups, religious authorities.
http://www.religioustolerance.org/clo_reac.htm
48
ISLAM
Currently, stem cell research and cloning
for therapeutic purposes is permissible
with full consideration and all possible
precautions in pre-ensoulment stages of
fetus development.
This is the consensus of Sunni and Shia
Muslims; but only a minority of Sunni
scholars are against it.
Transplantation Proceedings, Vol.36, No.10, 2004, pp. 3188-3189
Blood Cells, Molecules, and Diseases, Vol.32, 2004, pp. 100-105
49
A brief review of Islamic perspectives
about reproductive and therapeutic
cloning and stem cell research has been
published in 2004.
50
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NATIONAL LAW
Considerable differences exist
between countries in the
regulation of stem cell research
and nuclear transfer to produce
human embryo.
52
NATIONAL LAW
Reproductive cloning
is prohibited in Iran, however,
embryonic stem cell research
has been approved by the religious
authorities and some projects have
started.
Office of the Supreme Leader, Ref # M/8/239001, February 5, 2003
53
Stem Cell Research & Cloning

Iran was the 10th country in the world to
produce, culture and freeze hES cells (The
nine previous countries were Sweden, Japan,
the United States, Australia, Britain, India,
South Korea, and Singapore).
Iranian scientists have
established 6 human ESs lines
since 2004.
54
Stem Cell Research & Cloning

In addition, researchers at the Royan
Institute were witness to the birth of the
first cloned sheep born in Iran in 2006.
55
An emphasis on ethics has
been also voiced by medical
and religious authorities in Iran
in recent decade.
56
Compiling the Specific National Ethical
Guidelines for Biomedical Research
The Guidelines were compiled as a common project by
the “Medical Ethics Research Center” and the
“Endocrinology and metabolism research center” of
Tehran University of Medical sciences (2005-2006). This
project supported by “Deputy of research and
technology of the Ministry of Health ”.
The primary draft was reviewed by some law,
ethics, medical and religious experts.
57
Compiling the Specific National
Ethical Guidelines…(Cont.)
The Guidelines were
developed to observe ethical
rules in research and to
protect research participants
all over the country.
58
The Specific National Ethical Guidelines
for Biomedical Research
1.
2.
3.
4.
5.
6.
Ethical Guidelines for Clinical Trial
Ethical Guidelines for Research on Minors
Ethical Guidelines for Genetic Research
Ethical Guidelines for Gamete and Embryo
Research
Ethical Guidelines for Transplantation Research
Ethical Guidelines for Research on Animals
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CONCLUSION
Religion has an inevitable
influence on many medical
ethics decision-makings and
legislations.
61
Conclusion (cont.)
No consensus exists among religious
traditions (or secular moral traditions)
about the moral status of the embryo.
An ethical public policy in our
pluralistic world has to respect diverse
fundamental beliefs.
62
Conclusion (cont.)
Cooperation of scientists, ethicists,
jurisprudents and lawyers is essential
for establishing a well-controlled
system and appropriate ethical and
scientific supervision of the research
programs at national, regional and
international levels.
63
Conclusion (cont.)
Guidelines and protocols ought to be
established in order to allow
scientists to pursue new medical
advances while maintaining the
highest ethical standards in the use
of human embryos.
64
Conclusion (cont.)
Public education about the
ethical and policy issues
raised by stem cell research
and its application is
necessary.
65
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