3. Life, Death, and Stem Cell Research Richard L. Elliott, MD, PhD, FAPA Director, Medical Ethics Professor, Internal Medicine Mercer University School of Medicine Adjunct Professor Mercer University School of Law

4. Goals l Background –Timeline –Principles of medical ethics l Sources and fate of stem cells l Potential therapeutic uses and abuses l Access to results l Ethics and IVF –Preimplantation Genetic Determination –IVF, RU486, IUDs l Cloning

5. Recent Timeline l 1978 Louise Brown IVF l 1996 Dolly the sheep l 1998 First human embryonic stem cells l 2001 Federal funding for stem cell research limited to existing stem cell lines l 2004 South Korean researchers claim first human cloned to generate stem cells l 2007 Reprogramming of fibroblasts into stem cells l 2009 Executive order reversed previous ban on federal funding for new embryonic stem cell lines

6. Principles of Medical Ethics l Autonomy –Informed consent of gamete donors, parents around fate of embryos l Beneficence –Potential therapeutic uses of hESC cell research l Non-maleficence –Harm to embryos l Social justice –Who will benefit? Will all have access to uses?

7. Sources of Stem Cells l Existing stem cell lines –Pre-2009 18 hESC lines approved for study using federal funding l Unused embryos from IVF –2010 43 approved hESC lines, 115 submitted for review. But only one line from pre-2009 lines approved thus far l Programmed adult skin cells (iPSC) l Umbilical cord blood l Amniotic fluid cells l Bone marrow l Fetal tissue l Somatic cell nuclear transfer

8. In Vitro Fertilization

9. IVF – In Vitro Fertilization

10. Ethical Issues and IVF-Derived hESCs l Weighing harm to embryos vs potential benefits l Informed consent l hESCs and personhood l Federal funding for hESC research

11. Beneficence and Therapeutic Potential

13. First FDA-approved Clinical Trial Using hESCs l January 2009 l Geron l Spinal cord injury

14. Autonomy, NIH, Informed Consent, and hESCs l hESC derived from IVF for reproductive purposes l Available alternative uses explained l No payments for embryos l Care provided independent of decision l Should avoid clinician/researcher same l Donors gave voluntary written consent to use embryos for research

15. NIH, Informed Consent, and hESCs l Must provide information on: –Fate of embryos –Embryos may be kept for years –Research not intended as treatment for donor –What personal, potentially identifying information would be available to researchers –That research might result in financial gain for researchers, not donors

16. Non-maleficence and The Moral Status of the Embryo

17. When Does Life Begin?: Biological Landmarks l Day 1 Fertilization l Day 4-5Cells used for hESC l Day 7-10Implantation l Day 14 Primitive streak l Weeks 18-20Quickening l Month 9Delivery

18. The Moral Status of the Embryo: When is the early embryo fully human? l Aristotle and Aquinas: ensoulment with quickening l Catholic Church through 1591 – abortion before quickening not punishable l 1869 - Pius IX - Excommunication for abortion at any stage of pregnancy l Multiple ethics panels concluded the embryo is a developing human deserving respect but not full rights and protections

19. Faith and Embryonic Stem Cell Research l Harris Poll 2005 –70% Americans favor, 19% oppose –70% Catholics, 38% born-again Evangelicals favor l 57% who oppose abortion favor embryonic stem cell research – “not in womb, not abortion” l O. Hatch – opposes abortion, favors hESC research l Islam - no prohibition l Judaism – no prohibition l Hindus – unclear l MUSM research – IVF acceptable across faiths

20. Embryos and the Law l Georgia Criminal Law: “unborn child” means a member of the species homo sapiens at any stage of development who is carried in the womb. l Roe v. Wade: "We need not resolve the difficult question of when life begins. When those trained in the respective disciplines of medicine, philosophy, and theology are unable to arrive at any consensus, the judiciary, at this point in the development of man's knowledge, is not in a position to speculate as to the answer.“ May abort up to time of fetal “viability”

21. Ethics, IVF, and Stem Cells l Does use of hESCs from IVF for procreation restrict research on cells from the poor? l Is it morally acceptable to use existing stem cell lines created from embryos? l Should gamete donors and potential parents have equal rights? –Who should determine fate? l Should Federal funds be used to derive new hESC lines for research?

22. What to do with leftover embryos? l Over 500,000 embryos in storage l $100-150/year l What if donors don’t pay for storage?

23. Access to Stem Cell Benefits

24. Stem Cell Fraud, Scams and non-FDA Approved Treatments Cloned human Offshore clinics Non-FDA approved

25. Resources l Elliott_rl@mercer.edu l This presentation –Medicine.mercer.edu – search medical ethics –“resources” l NIH resources on stem cell ethics –http://bioethics.od.nih.gov/stemcell.htmlhttp://bioethics.od.nih.gov/stemcell.html l International Society for Stem Cell Research –http://www.isscr.org/public/ethics.htm

27. Supplemental Slides for Dr. Elliott

28. More Complete Timeline l 1974 Congress bans all federally funded fetal tissue research l Ethics Advisory Board established to set guidelines for research on fetal tissue research on tissue derived from abortions. EAB recommends federally funded research into IVF l 1981 EAB disbanded, effectively ends federal funding into research on embryonic stem cells l DHHS continues moratorium on federal funding despite 18-3 recommendation for federal funding by b Human Fetal Tissue Transplantation Research Panel l 1993 Moratorium on federal funding lifted l 1994 Moratorium reinstated

29. Preimplantation Genetic Testing l Sex selection l Genetic “defects” –Physical characteristics

30. Stem Cells and PEDs l Should results from stem cell research be used to enhance performance? –Human Growth hormone –Anabolic steroids –EPO

31. IVF, RU486, IUDs l RU486 as an emergency contraceptive and IUDs prevent implantation l Contraception vs abortion in preventing implantation l Compare unused (non-implanted) embryos from IVF with RU486 and IUDs ethically

32. Terminology l IVF l Embryonic stem cells l Totipotency, pluripotency l Cloning

34. Cloning

35. Somatic Cell Nuclear transfer

36. Somatic Cell Nuclear Transfer l Generate stem cells with defective gene for research on disease, e.g., Parkinson’s l Use patient’s cells to generate stem cells to create tissue for transplantation that has similar immunological characteristics as patient l Hybrids l Human cloning

37. Induced Pluripotent Stem cells

39. What are areas of ethical concern? l Source and fate of stem cells l Potential therapeutic uses and abuses l Access to results l Ethics and IVF –Preimplantation Genetic Determination –IVF, RU486, IUDs l Cloning

40. NIH Guidelines for Stem Cell Lines l Pre-2009 18 hESC lines approved for study using federal funding l 2010 43 approved hESC lines, 115 submitted for review. But only one line from pre-2009 lines approved thus far