Published on October 23, 2007
Slide1: The Eighth Asian Bioethics Conference March 19-23, 2007, Bangkok, Thailand Farzaneh Zahedi, MD Researcher of Tehran University of Medical Sciences : 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: 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. 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). Introduction (cont.) Introduction (cont.): 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. POTENTIAL APPLICATIONS: POTENTIAL APPLICATIONS The most important application of hES cells is clinically in transplantation and regenerative medicine. POTENTIAL APPLICATIONS: POTENTIAL APPLICATIONS NATURE BIOTECHNOLOGY 1999; 17: 1173 APPLICATIONS IN RESEARCH: APPLICATIONS IN RESEARCH Models of human disease The pharmaceutical research Human developmental biology Gene therapy Cell Characteristics in Stem Cell Biology : Cell Characteristics in Stem Cell Biology STEM CELL SOURCES: 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 EMBRYONIC STEM CELL: 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 PLURIPOTENCY: 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 Slide15: hES cells are pluripotent Source: NIH 2001: Stem Cells: Scientific Progress and Future Research Directions Disadvantages of ESCs: 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 CLONING: 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. Slide18: Removing the maternal nucleus before nuclear transfer Nuclear transfer embryo about to be activated (Roslin Institute http://www.roslin.ac.uk) ADVANTAGES OF CLONING: 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 DISADVANTAGES OF CLONING: 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. ADULT STEM CELLS: 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 Advantages/Disadvantages: Advantages/Disadvantages KEY ETHICAL ISSUES: 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 … MAIN ETHICAL ISSUE: MAIN ETHICAL ISSUE Moral status of human embryo: The embryo is unavoidably destroyed during the process of ESCs harvesting. When does “human life” begin? Humanity of the Unborn: 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. The Status of the Embryo: 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? Views about the Moral Status of the Embryo: 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 The Status of the Embryo (cont.): 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. The Status of the Embryo (cont.): 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 The Status of the Embryo (cont.): 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. The Status of the Embryo (cont.): 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 Slide34: 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 The sacred writings and teachings of different religions contain a wealth of teachings about the key moments of life; its beginning and its end. OVERALL CONSENSUS: 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. Slide36: What is an Embryo ? When does life begin ? At what point do rights apply? Is there any agreement on these questions? Religious Questions Moral Status of Human Embryo: 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) CHRISTIANITY: CHRISTIANITY Life begins at conception Killing embryo any time after conception is equivalent to killing a human being Christianity (cont.): 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. JUDAISM: 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. EASTERN RELIGIONS: 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 ISLAM: 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 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. ISLAM 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)!" ISLAM 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. ISLAM Slide46: 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. ISLAM 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." The Islamic Fiqh Council (1997) Human Cloning: comments by political groups, religious authorities. http://www.religioustolerance.org/clo_reac.htm 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." ISLAM Human Cloning: comments by political groups, religious authorities. http://www.religioustolerance.org/clo_reac.htm ISLAM: 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 Slide50: A brief review of Islamic perspectives about reproductive and therapeutic cloning and stem cell research has been published in 2004. NATIONAL LAW: NATIONAL LAW Considerable differences exist between countries in the regulation of stem cell research and nuclear transfer to produce human embryo. 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 NATIONAL LAW 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). Stem Cell Research & Cloning Iranian scientists have established 6 human ESs lines since 2004. Slide55: In addition, researchers at the Royan Institute were witness to the birth of the first cloned sheep born in Iran in 2006. Stem Cell Research & Cloning Slide56: An emphasis on ethics has been also voiced by medical and religious authorities in Iran in recent decade. Compiling the Specific National Ethical Guidelines for Biomedical Research: 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. Compiling the Specific National Ethical Guidelines…(Cont.): 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. The Specific National Ethical Guidelines for Biomedical Research: The Specific National Ethical Guidelines for Biomedical Research 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 CONCLUSION: Religion has an inevitable influence on many medical ethics decision-makings and legislations. CONCLUSION Conclusion (cont.): 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. Conclusion (cont.): 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. Conclusion (cont.): 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. Conclusion (cont.): Conclusion (cont.) Public education about the ethical and policy issues raised by stem cell research and its application is necessary.