1. Stem Cell Research: Ethical Issues, ESCRO Committees, and Beyond Michael Kalichman Biomedical Ethics Seminar Series May 17, 2006

2. Status of research  Not forbidden in U.S.  Forbidden to use federal funds: any project in which a human embryo would be "destroyed, discarded, or knowingly subjected to risk of injury or death“ (Dickey. 1996)  Federal funds may be used for research on stem cell lines derived prior to August 9, 2001 (Bush)  With non-federal funds this research is still allowable

3. Stem Cell Sources  Adult, “tissue-specific” stem cells Bone marrow Umbilical cord blood Brain, heart  Human embryo IVF  Viable  Non-viable SCNT, Cloning

4. Hwang Woo Suk  Veterinary Researcher, Seoul National University, South Korea  Stem cell research funded extensively by Korean government and international community  Collaboration with U.S. scientist: Gerald Schatten  June 2005, Science: Nuclear transfer into 11 human eggs

5. Hwang Woo Suk What went wrong?  Standards of research  Falsification of data  Fabrication of data  And it was stem cell research…

6. “Being too focused on scientific development, I may not have seen all the ethical issues related to my research.” Hwang Woo Suk November 24, 2005

7. "The fraudulent stem-cell research reported by South Korean scientists suggests that American institutions are incapable of policing themselves to prevent similar scandals in this country, the chairman of a Congressional subcommittee said on Tuesday." Jeffrey Brainard, Wednesday, March 8, 2006 “Members of Congress Spar Over South Korean Cloning Scandal and Oversight of Stem-Cell Research in U.S.” Chronicle for Higher Education March 8, 2006

8. What are we doing?  RCR Courses  IRB and IACUC Reviews  NAS Guidelines  CIRM Guidelines

9. What is supposed to be reviewed?  Covered stem cell line means a culture-derived, human stem cell population that is capable of: 1) sustained propagation in culture; 2) differentiation along multiple cell lineages; and 3) self-renewing to produce daughter cells with equivalent developmental potential. This definition includes both embryonic and non-embryonic human stem cell lines regardless of the tissue of origin  CIRM Draft Guidelines: 2/10/06

10. What is supposed to be reviewed?  Covered stem cell line means a culture-derived, human pluripotent stem cell population that is capable of: 1) sustained propagation in culture; and (2) self- renewal to produce daughter cells with equivalent developmental potential. This definition includes both embryonic and non-embryonic human stem cell lines regardless of the tissue of origin. Pluripotent means capable of differentiation into mesoderm, ectoderm, and endoderm."  CIRM Draft Guidelines: 5/9/06

11. Why should we review this research?  We already have review committees  Is hESC research different?  What interests are we protecting with review of hESC research?

12. Special Respect "Persons holding the latter view-that the embryo itself lacks interests or rights because of its extremely rudimentary development--do not, however, necessarily view embryos as identical to any other human tissue. Indeed, many such persons would say that embryos, though lacking rights or interests in themselves, deserve "special respect" because of the embryo's potential, if placed in a uterus, to become a fetus and eventually to be born. Even embryos that will not be placed in the uterus have some meaning in this regard for they operate as a symbol of human life or constitute an arena for expressing one's commitment to human life.“ (Robertson, 1999)

13. Why should scientists insist on ethical review of hESC research?  Respect for life: developing embryo should be given closer scrutiny than adult cells  Ethical defensibility: strengthened by an independent ethical review  Public accountability: watched closely by the public especially by those who are morally opposed we need a proactive and serious role in addressing the ethical dimensions of our work

14. Goal for Discussion  Framework for review  Will not focus on: separation of funding sources apportioning intellectual property rights

15. Ethical Dimensions of Stem Cell Research  Should we use human embryos?  What questions should be studied?  How should research be conducted?  Who should benefit?  Who should bear the costs?  Who decides?

16. Ethical factors in hESC research 1. Special Respect 2. Why the study will be conducted 3. What will be studied 4. How the study will be conducted 5. Scientific merit

17. Special Respect CategoryQuestions ReplacementCan the research goals be met without destroying a human embryo and with an alternative approach that raises less severe ethical challenges? RefinementIf the research goals are best met by using human embryos, is it possible to do so without destroying the embryo or it is possible to do so by means that will not impair possible future development of the embryo? ReductionCan the research goals be met with the use of fewer human embryos? Russell and Burch, 1959

18. Ethical factors in hESC research 1. Special Respect 2. Why the study will be conducted 3. What will be studied 4. How the study will be conducted 5. Scientific merit

19. Why the study will be conducted CategoryQuestions Basic research Is the primary purpose of the study a better understanding of biology or disease mechanisms? PreventionIs the primary purpose of the study to develop treatments or devices that will prevent the occurrence of illness or disease? CureIs the primary purpose of the study to develop treatments or devices that will cure existing illness or disease? TreatmentIs the primary purpose of the study to develop treatments or devices that will treat, but not necessarily cure, existing illness or disease? EnhancementIs the primary purpose of the study to develop treatments or devices that are designed to enhance the human condition?

20. Ethical factors in hESC research 1. Special Respect 2. Why the study will be conducted 3. What will be studied 4. How the study will be conducted 5. Scientific merit

21. What will be studied CategoryQuestions SpeciesWill this project involve human tissue? non-human primates? Mixing of human and non-human species? OocytesWho will be the donors? Will the research require that human oocytes, zygotes, or blastocysts be destroyed, discarded, or damaged? Zygotes Blastocysts FetusWho will be the donors? How did the fetal tissue become available? Child or AdultWho will be the donors? What tissues will be donated?

22. Ethical factors in hESC research 1. Special Respect 2. Why the study will be conducted 3. What will be studied 4. How the study will be conducted 5. Scientific merit

23. How the study will be conducted CategoryQuestions Pain and suffering Will the study cause or risk injury of an organism that has sufficient neural organization to experience physical pain? self-awareness? memory? Informed and voluntary consent How will informed consent be obtained? What measures will be taken to ensure that the consent is voluntary, not coerced, and informed? Surrogate consent If the proposed donor lacks the capacity to provide informed and voluntary consent, will consent be provided by a surrogate who will adequately consider the interests of the donor? Alternative usesAre the cells or tissues generated for the purpose of the research project or were they spontaneously or intentionally generated for some other use?

24. How the study will be conducted CategoryQuestions CharacterizationWill the study consist only of genetic, biochemical, or morphological characterizations of cells? DifferentiationWill the study consist of genetic or chemical manipulations to induce differentiation or commitment to more specific lineages? De-DifferentiationWill the study consist of genetic or chemical manipulations to induce cells to revert to a less differentiated state? Somatic cell nuclear transfer Will nuclear material from diploid cells be inserted into oocytes? Mixing of speciesWill genetic material, cells or tissues of a non-human species be inserted into a human organism? Will genetic material, cells or tissues of human origin be inserted into a non-human species?

25. Ethical factors in hESC research 1. Special Respect 2. Why the study will be conducted 3. What will be studied 4. How the study will be conducted 5. Scientific merit

26. Scientific merit CategoryQuestions Clear hypothesis or question Is the proposed study designed to address a clearly stated hypothesis or question? Awareness of literature Is the design of the proposed study consistent with what has previously been published? Duplication of previous work Does the proposed study duplicate work that has already been done? If so, then is a rationale provided to adequately justify the need for the duplication? Qualifications of personnel Are the personnel who will perform the studies adequately trained in science and methodology? in the ethical, legal, and social implications of this line of research?