Transcript Larijani_stemcell_AB.. - Center for Ethics of Science and Technology

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
The discovery of Embryonic Stem
Cells (ESCs) in the 1980s suggested
therapeutic approaches to chronic
and incurable diseases.
Using ESCs are surrounded by a
number of ethical controversies.
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POTENTIAL APPLICATIONS
The most important
application of hES cells is
clinically in
transplantation
and regenerative medicine.
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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 diseases
The pharmaceutical research
Human developmental biology
Gene therapy
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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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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
 High Failure Rate & Cost: 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.
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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.
DISADVANTAGES OF CLONING
 Not Enough Human Eggs
 Cloning damages DNA
•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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Advantages/Disadvantages
Stem Cell
Cost
Human
Embryos
Low (?)
(excess
Yes
embryos of
IVF)
Destruction
of human
embryos
High
None
Destruction
of cloned
human
embryos
Low
None
(Autologous)
Yes (Donated)
None
Human
Clones
Adult
Stem Cells
Tissue rejection
Main Ethical
Problem
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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.
The question is
whether the destruction of human embryos
amounts to the killing of human beings.
When does “human life” begin?
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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.)
A different moral argument underlines that
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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Recent advances in scientific research
and technological sophistication have
raised totally new possibilities of
defining birth and death; as key
moments of life.
All religions believe that usage of
adult, placental, and umbilical stem
cells is acceptable.
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Controversy lies with idea of
using embryonic stem cells
and where life begins.
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
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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
There is a notable diversity of views by Buddhists on
cloning.
 Advocates: Cloning might be permissible under
some understandings of Buddhism such as:
- Central virtues of knowledge and compassion
- Alleviate human suffering
 Opponents: Some primacy teachings of Buddhism
can restrict such research; for instance:
- Buddha prohibits infliction of violence or harm on
sentient beings.
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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.
Larijani B, Zahedi F. Transplantation Proceedings 2004;36(10): 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.
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ISLAM
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 preensoulment stages will be much less than
abortion after ensoulment.
However, considering the potential therapeutic
benefits of the procedure of stem cell research and
cloning, destruction of the blastocyst and research
into human ESCs could be justified.
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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 has established the system of
cause-and-effect in the world. Cloning is
a cause and only through Allah's Will it
can produce the effect.
Human Cloning: comments by political groups, religious authorities.
http://www.religioustolerance.org/clo_reac.htm
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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.
- Larijani B, Zahedi F. Transplantation Proceedings 2004;36(10): 3188-3189.
- Blood Cells, Molecules, and Diseases 2004; 32: 100-105.
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A brief review of Islamic perspectives
about reproductive and therapeutic
cloning and stem cell research has been
published in 2004.
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SCR and Cloning in Iran
Reproductive cloning
is prohibited in Iran, however,
embryonic stem cell research
has been approved by the religious
authorities and some projects have
started.
- Larijani B, Zahedi F. Transplantation Proceedings 2004;36(10): 3188-3189.
- Office of the Supreme Leader, Ref # M/8/239001, February 5, 2003
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SCR and Cloning in Iran (cont.)


Iran was the 10th country in the
world to produce, culture and freeze
hES cells.
Iranian scientists have established 6
human ESs lines since 2004.
 Researchers at the
Royan Institute were
witness to the birth of
the first cloned sheep
born in Iran in 2006.
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SCR and Cloning in Iran (cont.)
An emphasis on ethics has been voiced by
medical and religious authorities in Iran in
different decades.
 The Specific National Ethical
Guidelines for Biomedical Research were
compiled in 2005 and communicated to
medical universities and research centers
in 2006.
Larijani B, et al. Developing World Bioethics 2006; 6(2): 106–110.
Larijani B, et al. Eastern Mediterranean Health Journal 2005; 11(5/6), 1061-1072.
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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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 Cooperation of scientists, ethicists,
jurisprudents and lawyers is essential
for
establishing
culturally-adapted
well-controlled,
systems
in
different countries.
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Conclusion (cont.)
 An ethical public policy in our
pluralistic world has to respect
diverse religious and cultural
beliefs.
 Public education about the ethical
and policy issues raised by stem cell
research and its application is
necessary.
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