The Ethics of Regulating Reproductive Technologies

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In the Name of God
Cloning And Stem Cell Research Issues Religious
Viewpoints on Value Of Life
The Eighth Asian Bioethics Conference March
19-23, 2007, Bangkok, Thailand
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Farzaneh Zahedi, MD Researcher of Tehran
University of Medical Sciences

• Bagher Larijani, MD
• Professor of Tehran University
• of Medical Sciences

Medical Ethics and History of Medicine Research
Centre, Endocrinology and Metabolism Research
Centre, Tehran University of Medical Sciences
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INTRODUCTION

• The discovery of Embryonic Stem Cells (ESCs ) in
  the 1980s suggested therapeutic approaches to
  chronic, debilitating, and incurable diseases
  such as Parkinsons 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 socio-cultural,
  ethical, political, and religious viewpoints to
  be considered in discussions about the production
  and use of stem cells.

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Scientific Facts and Promises
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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
Alzheimer's disease Nerve cells
Atherosclerosis Endothelial cells
Burns Skin cells
Chronic pain Chromaffin cells
Diabetes Islet cells
Epilepsy Nerve cells
Heart disease Cardiomyocytes
Huntington's disease Nerve cells
Hypocalcemia Parathyroid cells
Hypocholesterolemia Hepatocytes
Disorder Cells transplanted
Kidney disease Kidney cells
leukemia Hematopoietic cells
Liver disease Hepatocytes
Macular degeneration Retinal cells
Multiple sclerosis Glial cells
Muscular dystrophy Skeletal muscle cells
Osteoarthritis Chrondrocytes
Parkinson's disease Dopaminergic neurons
Rheumatoid arthritis Chrondrocytes
Strokes Nerve cells
Spinal cord injuries Nerve cells
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 Blastomeres
Pluripotent Able to produce all tissues and self-renew indefinitely Embryonic stem cell
Multipotent Able to produce many cell types and self-renew over the lifetime of the being and over many subsequent generations if transplanted Hematopoietic stem cell
Progenitor Able to produce restricted number of cell types and with limited to no capacity of self-renewal Neural stem cell
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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.
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Removing the maternal nucleus before nuclear
transfer
Nuclear transfer embryo about to be
activated (Roslin Institute http//www.roslin.ac.u
k)
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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 Tissue rejection Ethical Problems Works for genetic diseases
Human Embryos Low (?)(IVF leftovers) Yes Unique human embryos Yes
Human Clones High None Cloned human embryos No
AdultAutologous Low None None No
AdultDonated Low Yes None Yes
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Ethical challenges
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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 non-person 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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Religious Perspective
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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

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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.

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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

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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
• 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.

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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)!"

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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.

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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.

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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 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.religioustoleran
ce.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.religioustoleran
ce.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.

Transplantation Proceedings, Vol.36, No.10, 2004,
pp. 3188-3189 Blood Cells, Molecules, and
Diseases, Vol.32, 2004, pp. 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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Stem Cell Research and Cloning in Iran
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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.

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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
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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.

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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.

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• An emphasis on ethics has been also voiced by
  medical and religious authorities in Iran in
  recent decade.

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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.

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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.

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The Specific National Ethical Guidelines for
Biomedical Research

1. Ethical Guidelines for Clinical Trial
2. Ethical Guidelines for Research on Minors
3. Ethical Guidelines for Genetic Research
4. Ethical Guidelines for Gamete and Embryo Research
5. Ethical Guidelines for Transplantation Research
6. Ethical Guidelines for Research on Animals

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Conclusion
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CONCLUSION

• Religion has an inevitable influence on many
  medical ethics decision-makings and legislations.

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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.

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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.

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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.

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Conclusion (cont.)

• Public education about the ethical and policy
  issues raised by stem cell research and its
  application is necessary.

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Thanks for your time