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The Eighth Asian Bioethics Conference March 19-23, 2007, Bangkok, Thailand

Bagher Larijani, Bagher Larijani, MDMDProfessor of Tehran University Professor of Tehran University

of Medical Sciencesof Medical Sciences

Farzaneh Zahedi, MDFarzaneh Zahedi, MD Researcher of Researcher of Tehran University Tehran University

of Medical Sciencesof Medical Sciences

Medical Ethics and History of Medicine Research Centre,Medical Ethics and History of Medicine Research Centre,& Endocrinology and Metabolism Research Centre,& Endocrinology and Metabolism Research Centre,

Tehran University of Medical SciencesTehran University of Medical Sciences

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The discovery of Embryonic Stem The discovery of Embryonic Stem Cells (ESCs) in the Cells (ESCs) in the 1980s1980s suggested suggested therapeutic therapeutic approachesapproaches to chronic and to chronic and incurable diseases.incurable diseases.

Using ESCs are surrounded by a Using ESCs are surrounded by a number of number of ethical ethical controversies.controversies.

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POTENTIAL APPLICATIONS

The most important The most important application of hES cells is application of hES cells is

clinically in clinically in

transplantation transplantation

and regenerative and regenerative medicine.medicine.

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POTENTIAL APPLICATIONSDisorderDisorder Cells transplantedCells 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

DisorderDisorder Cells transplantedCells 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 diseases Models of human diseases The pharmaceutical researchThe pharmaceutical researchHuman developmental biologyHuman developmental biologyGene therapyGene therapy

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EMBRYONIC STEM CELL Embryonic stem (ES) cells are derived from Embryonic stem (ES) cells are derived from

the inner cell mass of a the inner cell mass of a blastocystblastocyst. . The blastocyst forms at approximately 4 or 5 The blastocyst forms at approximately 4 or 5

days after fertilization and contains from 64 days after fertilization and contains from 64 to several hundred cells organized in an to several hundred cells organized in an outer shell, the trophectoderm, and a outer shell, the trophectoderm, and a collection of polarized inner cells termed the collection of polarized inner cells termed the inner cell massinner cell mass (ICM). (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 Stem cells retain the ability to differentiate into cells and tissues from all cells and tissues from all 3 germ layers3 germ layers

(endoderm, mesoderm, and ectoderm). (endoderm, mesoderm, and ectoderm).

But, these cells But, these cells cannot form the othercannot form the other

‘ ‘extra- embryonic’ tissuesextra- embryonic’ tissues necessary for necessary for complete development, complete development, such as such as placentaplacenta and and

membranesmembranes, therefore , therefore

they cannot give rise to a complete new they cannot give rise to a complete new individualindividual..

•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 TumorsCancer and Tumors : the potential : the potential of introducing cancer into patients of introducing cancer into patients because of rapid growth of because of rapid growth of embryonic stem cells embryonic stem cells

Tissue Tissue RejectionRejection Genetic AbnormalitiesGenetic Abnormalities High Failure Rate & CostHigh Failure Rate & Cost: Hundreds : Hundreds

of thousands to millions of stem cell of thousands to millions of stem cell lines would be required to treat the lines would be required to treat the majority of patients.majority of patients.

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CLONING

An alternative method An alternative method of deriving human of deriving human

ESCs is ESCs is somatic cell somatic cell nuclear transfernuclear transfer

(SCNT), or (SCNT), or cloningcloning . .

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”No rejection, “Perfect match”Stem cells produced by Stem cells produced by therapeutic cloningtherapeutic cloning are are genetically similargenetically similar to the cells of the to the cells of the individual who donated the nucleus, and thus individual who donated the nucleus, and thus avoid problems of rejectionavoid 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

DISADVANTAGES OF CLONING Not Enough Human Eggs Not Enough Human Eggs Cloning damages DNA Cloning damages DNA

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Advantages/Disadvantages

Stem CellStem Cell CostCost Tissue Tissue rejectionrejection

Main Main Ethical Ethical ProblemProblem

Human Human EmbryosEmbryos

LowLow ( (??))(excess (excess embryos embryos of IVF)of IVF)

YesYesDestruction Destruction of human of human embryosembryos

Human Human ClonesClones HighHigh NoneNone

Destruction Destruction of cloned of cloned human human embryosembryos

AdultAdultStem CellsStem Cells LowLow

None None (Autologous)(Autologous)Yes Yes ((Donated)Donated)

NoneNone

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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 embryoMoral status of human embryo: : The embryo is unavoidably destroyed The embryo is unavoidably destroyed during the process of ESCs harvesting.during the process of ESCs harvesting.

The question is The question is

whether the destruction of human embryos whether the destruction of human embryos amounts to the amounts to the killing of human beingskilling of human beings..

When does “human life” begin?When does “human life” begin?

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The Status of the Embryo (cont.)

One moral argument is that human One moral argument is that human ‘‘personhoodpersonhood’ begins at ’ begins at conceptionconception, ,

or –as in cloning– at the genetic or –as in cloning– at the genetic beginning.beginning.

Based on this argument, the Based on this argument, the destruction of embryos for research destruction of embryos for research

cannot be justified.cannot be justified.

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The Status of the Embryo (cont.)

A different moral argument underlines thatA different moral argument underlines that

the moral status of embryos the moral status of embryos gradually gradually increasesincreases with their development. Once they with their development. Once they are born, they are entitled to enjoy full rights are born, they are entitled to enjoy full rights

as human beings.as human beings.

Therefore, destruction of embryos can be Therefore, destruction of embryos can be justified to provide a treatment for patientsjustified to provide a treatment for patients..

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The Status of the Embryo (cont.)

A third type of moral argument points A third type of moral argument points out that out that certain milestonescertain milestones exist exist

in embryonic development that in embryonic development that change the status of embryos. change the status of embryos.

For example:For example: Ensoulment Ensoulment The primitive streak The primitive streak

development at day 14, before development at day 14, before three germ layers appear 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 All religions believe that usage of adultadult, , placentalplacental, and , and umbilicalumbilical stem cells is stem cells is acceptableacceptable..

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Controversy lies with idea of Controversy lies with idea of using using embryonic stem embryonic stem cellscells and and where life where life

beginsbegins..There is substantial debate regarding There is substantial debate regarding at at which specific stage dignity is conferredwhich specific stage dignity is conferred in in development (conception, primitive streak development (conception, primitive streak development, implantation, ensoulment or development, implantation, ensoulment or birth).birth).

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CHRISTIANITY

Life begins at Life begins at conceptionconceptionKilling embryo any time after Killing embryo any time after

conception is conception is equivalent to killingequivalent to killing a a human beinghuman being

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Christianity (cont.) Although RomanAlthough Roman CatholicismCatholicism officially officially

opposes human embryonic stem cell opposes human embryonic stem cell researchresearch, some Roman catholic moral , some Roman catholic moral theologians endorse it. theologians endorse it.

ProtestantsProtestants have a wide range of views. have a wide range of views. OrthodoxOrthodox Church firmly reject any and all Church firmly reject any and all

manipulation of human embryos for research manipulation of human embryos for research purposes as inherently immoral and a purposes as inherently immoral and a fundamental violation of human life.fundamental violation of human life.

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JUDAISM A A fetus is not seen as being an ensouled fetus is not seen as being an ensouled

personperson. Not only are the first forty days of . Not only are the first forty days of conception considered 'like water' but also conception considered 'like water' but also even in the last trimestereven in the last trimester, the fetus has a , the fetus has a lesser moral status.lesser moral status.

A number of Jewish thinkers hold that the A number of Jewish thinkers hold that the extracorporeal embryo, in the Petri dish or extracorporeal embryo, in the Petri dish or cry preserved, does not have standing in cry preserved, does not have standing in Jewish law and that it is Jewish law and that it is justifiable to go justifiable to go forward with embryonic stem cell forward with embryonic stem cell researchresearch..

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EASTERN RELIGIONS BuddhismBuddhism

There is a notable diversity of views by Buddhists on There is a notable diversity of views by Buddhists on cloning.cloning.

AdvocatesAdvocates: Cloning might be permissible under : Cloning might be permissible under some understandings of Buddhism such as:some understandings of Buddhism such as:

-- Central virtues of Central virtues of knowledge and compassionknowledge and compassion

-- Alleviate human suffering Alleviate human suffering OpponentsOpponents: Some primacy teachings of Buddhism : Some primacy teachings of Buddhism

can restrict such research; for instance:can restrict such research; for instance:

- - Buddha Buddha prohibits infliction of violence or harmprohibits infliction of violence or harm on on sentient beings.sentient beings.

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ISLAMISLAM

In opinion of most Muslim jurists, In opinion of most Muslim jurists,

stem cell and cloning research, as great stem cell and cloning research, as great scientific events, would have scientific events, would have advantages advantages

andand limitations limitations. . Due to majority of Muslim reference Due to majority of Muslim reference

decrees, according to decrees, according to inevitable inevitable consequencesconsequences of of reproductive cloningreproductive cloning, it is , it is prohibitedprohibited. .

Larijani B, Zahedi F. Transplantation Proceedings 2004;36(10): 3188-3189.

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According to Islamic beliefs, the fetus According to Islamic beliefs, the fetus undergoes a undergoes a series of transformationsseries of transformations

beginning as an organism and beginning as an organism and becoming a human being. The fetus becoming a human being. The fetus

culminates in becoming a full human culminates in becoming a full human being when being when it is “ensouled” at 120 daysit is “ensouled” at 120 days (the end of the fourth month) from the (the end of the fourth month) from the

moment of conception.moment of conception.

ISLAMISLAM

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Given the Islamic teachings, the embryo, Given the Islamic teachings, the embryo, even even in the first days of its existencein the first days of its existence, has the right to , has the right to live and no one has the right to kill it; but the live and no one has the right to kill it; but the

punishment of fetus eradication in the pre-punishment of fetus eradication in the pre-ensoulment stages will be much less than ensoulment stages will be much less than

abortion after ensoulment.abortion after ensoulment.

ISLAMISLAM

However, considering the However, considering the potential therapeutic potential therapeutic

benefitsbenefits of the procedure of stem cell research of the procedure of stem cell research

and cloning, destruction of the blastocyst and and cloning, destruction of the blastocyst and

research into human ESCs could be research into human ESCs could be justifiedjustified. .

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The conference was organized in CasablancaThe conference was organized in Casablanca . .

A consensus was reached that: A consensus was reached that: Cloning does not bring into question anyCloning does not bring into question any

Islamic beliefIslamic belief in any wayin any way. . Allah has established the Allah has established the system of system of

cause-and-effectcause-and-effect in the world. in the world. Cloning is Cloning is a causea cause and only through Allah's Will it and only through Allah's Will it can produce the effect. can produce the effect.

The Islamic Fiqh Council (1997)The Islamic Fiqh Council (1997)

Human Cloning: comments by political groups, religious authorities.http://www.religioustolerance.org/clo_reac.htm

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ISLAMISLAM

Currently, stem cell research and cloning Currently, stem cell research and cloning for for therapeutic purposestherapeutic purposes is is permissiblepermissible with full consideration and all possible with full consideration and all possible

precautions precautions in pre-ensoulment stagesin pre-ensoulment stages of of fetus development. fetus development.

This is the consensus of Sunni and Shia This is the consensus of Sunni and Shia Muslims; but only a minority of Sunni Muslims; but only a minority of Sunni

scholars are against it.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 A brief review of Islamic perspectivesIslamic perspectives about reproductive and therapeutic about reproductive and therapeutic

cloning and stem cell research has been cloning and stem cell research has been published in 2004.published in 2004.

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Reproductive cloningReproductive cloning

is is prohibitedprohibited in in IranIran, however, , however,

embryonic stem cell researchembryonic stem cell research

has been has been approvedapproved by the by the religious authorities and some religious authorities and some

projects have started.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

SCR and Cloning in Iran

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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.

SCR and Cloning in Iran (cont.)

Researchers at the Royan Institute were witness to the birth of the first cloned sheepfirst cloned sheep born in Iran in 2006.

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An An emphasis on ethicsemphasis on ethics has been voiced by has been voiced by

medical and religious authorities in Iran in medical and religious authorities in Iran in

different decades.different decades.

SCR and Cloning in Iran (cont.)

The The Specific National Ethical Specific National Ethical Guidelines for Biomedical ResearchGuidelines for Biomedical Research

were compiled in were compiled in 2005 and 2005 and communicated to medical universities communicated to medical universities

and research centers in and research centers in 20062006..

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

1.1. Ethical Guidelines for Clinical TrialEthical Guidelines for Clinical Trial

2.2. Ethical Guidelines for Research on MinorsEthical Guidelines for Research on Minors

3.3. Ethical Guidelines for Genetic ResearchEthical Guidelines for Genetic Research

4.4. Ethical Guidelines for Gamete and Embryo Ethical Guidelines for Gamete and Embryo ResearchResearch

5.5. Ethical Guidelines for Transplantation ResearchEthical Guidelines for Transplantation Research

6.6. Ethical Guidelines for Research on AnimalsEthical Guidelines for Research on Animals

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Cooperation of scientists, ethicists, Cooperation of scientists, ethicists,

jurisprudents and lawyers is essential jurisprudents and lawyers is essential

for establishingfor establishing wellwell--controlled, controlled,

culturally-adaptedculturally-adapted systems in systems in

different countries.different countries.

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Conclusion (cont.)

AnAn ethical public policyethical public policy in ourin our pluralistic world has topluralistic world has to respect respect diverse religious and cultural diverse religious and cultural beliefsbeliefs..

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

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