Dennis M. Sullivan, MD, MA (Ethics) Professor of Biology Director, Center for Bioethics Cedarville University

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Dennis M. Sullivan, MD, MA (Ethics) Professor of Biology Director, Center for Bioethics Cedarville University Center Web site: www.cedarville.edu/bioethics E-mail: sullivan@cedarville.edu

Cameron: The Biotech Century Signs of this modern era: ART techniques Excess frozen embryos Stem cell research Cloning

Pluripotent cells: not yet differentiated into mature cells Advantages of using stem cells: Can be programmed along one developmental pathway Not likely to be rejected immunologically (fewer surface markers) May perhaps grow into new nerve or muscle cells

Chronic diseases that might be helped: Diabetes mellitus Spinal cord or brain injury Replace neurons Replace glial cells Parkinson s disease Heart disease (heart muscle does not regenerate) Frozen embryos are available (though no proven benefit of this research yet) SCNT ( cloning techniques): may provide additional embryos to meet the demand

Sanctity of life concerns Utilitarian rationale Conception view of human personhood Objections similar to those regarding abortion Since frozen embryos are going to be destroyed anyway Assumes as given that which may not come true Concerns about moral complicity Frozen embryos will never meet the demand, must resort to cloning Somatic sources have demonstrated great benefit: Umbilical cord Bone marrow Epithelial cells Amniotic fluid 72+ somatic cell treatments now in clinical use Animal studies show great promise for the near future

Public Policy Initiatives: New Jersey: state budget includes $9.5 million for Stem Cell Institute California: Proposition 71sets aside $3 billion for embryonic stem-cell research over 10 years Illinois: Gov. Rod Blagojevich creates a stem-cell research institute by executive order Maryland: Stem Cell Research Act allocates $15 million for embryonic stem-cell research grants. Missouri voters back a constitutional amendment that safeguards embryonic stem-cell research in the state Iowa eases limits on some types of stem-cell research. June 20, 2007: President Bush vetoes legislation that would have eased federal restraints on stem-cell research.

The PGD Proposal The Non-Viable Embryo Proposal The Altered Nuclear Transfer Proposal

Context: PGD: an established method of genetically screening embryos during IVF attempts Samples a single blastomere of the 3-day morula Embryos with single gene defects discarded: Duchenne muscular dystrophy Hemophilia A Fragile X syndrome Retinitis pigmentosa Tay Sach's disease Others

Technique: Use PGD methods to remove a single blastomere Replicate this cell in culture to produce a stem cell line The embryo: Now minus one cell Can be implanted into a woman s uterus Such implanted embryos can develop normally

This may not be practical Normally, cells taken at a later (blastocyst) stage Stem cell lines may require 100s of cells Robt. Lanza (ACT) claims to have done this: Controversial paper in Nature Paper was proof of concept only Violates long-held traditions of human experimentation Embryo derives no benefit Informed consent not possible

Why not use non-viable embryos? Only destroy embryos whose further development has arrested Analogous with brain death criteria for organ transplantation

Could the derived cells be useful as stem cells? The cause of developmental arrest may be within the component cells This may make such cells inappropriate for stem cell cultures No real ethical warrant Are such embryos truly dead? Brain Death in adults well established No parallel criteria for embryos

http://www.bioethics.gov/background/hurlbut.html

The Hurlbut Proposal: SCNT technique Prior to transfer of diploid DNA into ooplast: RNA interference used to block expression of cdx2 protein Prevents development of trophoblast After nuclear transfer: Resulting entities incapable of implantation Called by Hurlbut biological artifacts Can be disaggregated after formation of inner cell mass Resulting cells can then be used for stem cell cultures Technical aspects already partially confirmed in a mouse model

Key question: Are such biological artifacts non-embryos or disabled embryos? There are natural biological precedents: Germ cell tumors (teratomas) Hydatidiform moles ANT-OAR: Variation of Hurlbut idea Direct creation of pluripotent stem cells Modification of epigenetic state so that no embryolike aggregation possible (no inner cell mass) Not yet tested in an animal model

For those who hold to personhood at conception: For the scientific community at large: These proposals may not pass ethical muster ANT-OAR still only theoretical The desire for destructive embryo research continues unabated Current stem cell researchers in the private sector will not bother with additional constraints On the other hand: Limited research has been performed based on ethical concerns alone Ethically, this is good news for everyone.

Brugger, E. C. (2006). Moral Stem Cells. First Things, May(163). Bush, G. W. (2001, August 9, 2001). Bush Announces Position on Stem Cell Research. Washington Post. Cheshire, W. P. (2002). Toward a Common Language of Human Dignity. Ethics and Medicine, 18(2), 7-10. Definition Of Embryo Death Criteria May Open Doors For Stem Cell Research. (2006). Medical News Today. Available at: http://www.medicalnewstoday.com/articles/44486.php Geisler, N. L. (1990). When Did I Begin? A Review Article. JETS, 33(4), 509-512. Harper, J., Delhanty, J., & Handyside, A. (Eds.). (2001). Preimploantation Genetic Dignosis. London: John Wiley. Hurlbut, W. B. (2004). Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells, President s Council on Bioethics. Available at: http://www.bioethics.gov/background/hurlbut.html Klimanskaya I, C. Y., Becker S, Lu S-J, Lanza R. (2006). Human embryonic stem cell lines derived from single blastomeres. Nature, 444, 481-485. McConchie, D. (2005). "Ethical" Embryonic Stem Cell Research? Center for Bioethics and Human Dignity. Available at: http://www.cbhd.org/resources/stemcells/mcconchie_2005-06-10.htm Sullivan, D. M. (2003). The Conception View of Personhood: A Review. Ethics and Medicine, 19(1), 11-33. Available at: http://www.cedarville.edu/centerforbioethics/resources/articles/conception.pdf

Dennis M. Sullivan, MD, MA (Ethics) Professor of Biology Director, Center for Bioethics Cedarville University Center Web site: www.cedarville.edu/bioethics E-mail: sullivan@cedarville.edu