Seeking consensus: A clarification and defense of altered nuclear transfer

Hastings Center Report

Volumn 36, Issue 5, 2006, Pages 42-50

  Hurlbut, William B ^a,b   George, Robert P ^b,c   Grompe, Markus ^d  

^a STANFORD UNIVERSITY MEDICAL CENTER   (United States)

^b President's Council on Bioethics   (United States)

^c PRINCETON UNIVERSITY   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33750939187     PISSN: 00930334     EISSN: None     Source Type: Journal    
DOI: 10.1353/hcr.2006.0079     Document Type: Review

References (32)

1. President's Council of Bioethics, White Paper: Alternative Sources of Human Pluripotent Stem Cells (Washington, DC: Presidents Council of Bioethics, 2005).
2. "Production of Pluripotent Stem Cells by Oocyte Assisted Reprogramming," at http://www.eppc.org/programs/bioethics/publications/ programID.35,pubID.2374/pub_detail.asp.
3. N. Gibbs, "Stem Cells: The Hope and the Hype," Time (August 7, 2006): 41-46.
4. In some techniques, the whole body cell is simply fused with the enucleated egg.
5. Studies of benign ovarian teratomas (dermoid cysts) have demonstrated that they most commonly arise after meiosis I and failure of meiosis II and are therefore diploid, containing a full complement of forty-six chromosomes. U. Surti et al., "Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin," American Journal of Human Genetics 47, no. 4 (1990): 635-43.
6. In this issue of the Hastings Center Report, Insoo Hyun and Kyu Won Jung similarly inaccurately characterize ANT as producing "entities engineered to develop like early embryos but lacking the biological capacity to implant and develop into human beings."
7. The trophectoderm is not simply the lineage of origin of the extra-embryonic membranes, it is an active participant in the comprehensive communication and cross-inductions that coordinate and control embryogenesis. The trophectoderm is the source of several chemical signals that are essential for development of the ICM to its next stage of differentiation. P.P. Tam and J. Rossant, "Mouse Embryo Chimeras: Tools for Studying Mammalian Development," Development 130 (2003): 6155-63.
8. A. Meissner and R. Jaenisch, "Generation of Nuclear-Transfer Derived Pluripotent ES Cells from Cloned Cdx2-Deficient Elastomeres," Nature 439 (2006): 212-21.
9. D. Kaushik et al., "Cdx2 Gene Expression and Trophectoderm Lineage Specification in Mouse Embryos," Science 311 (2006): 992 -96.
10. H. Niwa et al., "Interaction between Oct3/4 and Cdx2 Determines Trophectoderm Differentiation," Cell 123 (2005): 917-29.
11. The one remaining link with IVF, the procurement of oocytes, is a subject of intense scientific research and there appear to be several prospects for obtaining eggs without the expensive, morally dubious, and medically dangerous procedure of super-ovulation of female patients.
12. D.A. Melton, G.Q. Daley, and C.G. Jennings, "Altered Nuclear Transfer in Stem-Cell Research: A Flawed Proposal," New England Journal of Medicine 351 (2004): 2791-92;
13. and D. Solter, "Politically Correct Human Embryonic Stem Cells?" New England Journal of Medicine 353 (2005): 2321-23.
14. According to one recent poll, 56 percent of Americans express a distrust of science. "More Americans Than Ever Support Embryonic Stem-cell Research," Virginia Commonwealth University Life Sciences Poll, October, 24, 2005, at http://www.news.vcu.edu/news.aspx (last accessed September 14, 2006).
15. Depending on how the questions are asked, generally 35-50 percent of Americans object to research in which embryos are destroyed to obtain ES cells. That figure jumps to 60-80 percent when the research involves the intentional creation and destruction of cloned human embryos to get patient specific ES cell lines. See United States Conference of Catholic Bishops, "New Poll: Americans Continue To Oppose Funding Stem Cell Research That Destroys Human Embryos," http://www.usccb.org/comm/archives/2006/06-109.shtml;
16. "Split Remains," http://msnbc.msn.com/id/14527419/site/ newsweek/ (last accessed September 11, 2006).
17. L. Meng et al., "Rhesus Monkeys Produced by Nuclear Transfer," Biology of Reproduction 57 (1997): 454-59.
18. The term "embryo" is generally defined as the human organism from fertilization to the end of the eighth week. "Blastocyst" is a structural description designating a fluid filled spherical form, and is generally used in embryology to indicate the stage between morulation and gastrulation. Blastocyst-like stuctures, however, are common in a range of tissues during organismal development, and therefore this term can be used without implying the presence of a living organism.
19. By their argument it would be even more inappropriate to call the entity produced by ANT an embryo or even a disabled embryo, since not only is altered nuclear transfer a form of SCNT, but the ANT entity has by design even less potential to develop into a human being.
20. This is the distinction between embryo and embryogenesis, the process by which the embryo develops: the embryo undergoes embryogenesis. The single-celled human embryo already carries within itself the program essential to establish placental connection with the mother and to direct its own development. Even apart from the womb, placentation and gestation may proceed in any well-vascularizcd tissue within the abdominal cavity.
21. See the personal statements of Robert George (joined by Alfonso Gomez-Lobo) and William Hurlbut in President's Council on Bioethics, Human Cloning and Human Dignity: An Ethical Inquiry (Washington, D.C.: President's Council on Bioethics, July 2002).
22. On the question of what is the moral standing of a human being, and whether all or only some human beings have rights as persons, see P.L. and R.P. George, "The Wrong of Abortion," in Contemporary Debates in Applied Ethics, ed. A.I. Cohen and C. Wellman (New York: Blackwell Publishers, 2005), 13-26.
23. Nicanor Austriaco suggests that "Philosophically, an organism may be defined as a complete living substance that has its own internal principle of motion and change directed towards its natural perfection, and scientifically as a discrete unit of living matter that follows a self-driven, robust developmental pathway that manifests its species-specific self- organization"; N. Austriaco, "The Moral Case for ANT-Derived Pluripotent Stem Cell Lines," The National. Catholic Bioethics Quarterly, forthcoming.
24. A.J. Walker, "Altered Nuclear Transfer: A Philosophical Critique," Communio: International Catholic Review 31, no 4 (2005): 649-84.
25. For example, a complete hydatidiform mole may result when an egg without a nucleus is "fertilized" by two sperm. This pathological failure of fertilization will divide and form a blastocyst-like structure, but it produces only an overgrowth of placental tissue with little or no fetal parts at all. As with a teratoma, the structure possesses a full human genome but lacks the complementary epigenetic factors of the male and female gametes.
26. R. Jaenisch, "Human Cloning - The Science and Ethics of Nuclear Transplantation." New England Journal of Medicine 351 (2004): 2787-91.
27. Rightly understood, the entire interrelated network of molecular parts (nuclear and cytoplasmic) determine the identity of the cell, but here we use the term "epigenetic" (somewhat broadly) to emphasize the functional relationship between cytoplasm and genome.
28. Of course, it is not our intention to proclaim an "epigenetic essentialism."
29. In particular, 1542 mouse genes with well-matched human homologs that are preferentially expressed in early embryos have been identified by the Green laboratory at the University of Otago in New Zealand; J. L. Stanton and D.P. Green, "A Set of 1542 Mouse Blastocyst and Pre-blastocyst Genes with Well-Matched Human Homologues," Molecular Human Reproductin 8 (2002): 149-66.
30. This pattern of gene expression might provide a molecular signature of true embryos. Furthermore, 111 genes that are turned on and 95 genes that are turned off in human embryonic stem cells have been identified; M. Suarez-Farinas et al., "Comparing Independent Microarray Studies: The Case of Human Embryonic Stem Cells," BMC Genomics 6 (2005): 99. This pattern might provide a molecular signature of entities that would be uniquely classified as pluripotent stem cells. A comparison of these two gene patterns suggests that there is no overlap.
31. E. Christian Brugger, "ANT-OAR: A Morally Acceptable Means for Deriving Pluripotent Stem Cells. A Reply to Criticisms," Communio: International Catholic Review 32, no. 4 (2005): 753-69.
32. Personal communication.