Stem cell

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
Category Questions
Replacement Can the research goals be met without destroying a human
embryo and with an alternative approach that raises less
severe ethical challenges?
Refinement If 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?
Reduction Can 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
Category Questions
Basic
research
Is the primary purpose of the study a better understanding of biology or
disease mechanisms?
Prevention Is the primary purpose of the study to develop treatments or devices that
will prevent the occurrence of illness or disease?
Cure Is the primary purpose of the study to develop treatments or devices that
will cure existing illness or disease?
Treatment Is the primary purpose of the study to develop treatments or devices that
will treat, but not necessarily cure, existing illness or disease?
Enhancement Is 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
Category Questions
Species Will this project involve human tissue? non-human
primates? Mixing of human and non-human species?
Oocytes Who will be the donors? Will the research require that
human oocytes, zygotes, or blastocysts be destroyed,
discarded, or damaged?
Zygotes
Blastocysts
Fetus Who will be the donors? How did the fetal tissue become
available?
Child or Adult Who 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
Category Questions
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 uses Are 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
Category Questions
Characterization Will the study consist only of genetic, biochemical, or morphological
characterizations of cells?
Differentiation Will the study consist of genetic or chemical manipulations to induce
differentiation or commitment to more specific lineages?
De-Differentiation Will 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 species Will 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
Category Questions
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?