Human research cloning, embryos, and embryo-like artifacts

Hastings Center Report

Volumn 36, Issue 5, 2006, Pages 34-41

  Hyun, Insoo ^a   Kyu, Won Jung ^b  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Hanyang University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33750966076     PISSN: 00930334     EISSN: None     Source Type: Journal    
DOI: 10.1353/hcr.2006.0080     Document Type: Review

References (45)

1. E. Weise, "Cloning Race Is On Again," USA Today (January 18, 2006);
2. C. Holden, "Harvard Cloners Get OK to Proceed with Caution," Science 312 (2006): 1584.
3. The Seoul National University Investigation Committee reported that Hwang and colleagues created seventy-one cloned human blastocysts from September 17, 2004 to November 8, 2005 with an efficiency rate of 9.99 percent. Seoul National University Investigation Committee, Final Report on Professor Woo Suk Hwang's Research Allegations, January 10, 2006, pp. 10-11 and 38-40.
4. The President's Council on Bioethics. Alternative Sources of Human Pluripotent Stem Cells (Washington, D.C: National Academies Press, 2005).
5. National Academy of Sciences, Stem Cells and the Future of Regenerative Medicine (Washington, D.C.: National Academies Press, 2002).
6. The President's Council on Bioethics, Monitoring Stem Cell Research: A Report of the President's Council on Bioethics (Washington, D.C.: National Academies Press, January 2004).
7. The President's Council's report came at a critical time in the political debate over embryonic stem cell research. On May 24, 2005, by a wide bipartisan margin, the House of Representatives passed a bill (HR810) that would allow scientists to use federal grant funds to conduct research on embryonic stem cell lines created after August 9, 2001. On June 30, Rep. Roscoe Bartlett of Maryland responded by introducing "The Respect for Life Pluripotent Stem Cell Act of 2005" (HR3144), which would provide $15 million a year in federal funds for the development of alternative sources of human pluripotent stem cells like those considered by the President's Council.
8. L. Chung et al., "Embryonic and Extraembryonic Stem Cell Lines Derived from Single Mouse Blastomeres," Nature 439 (2006): 216-19.
9. A. Meissner and R. Jaenisch, "Generation of Nuclear Transfer-Derived Pluripotent ES Cells from Cloned Cdx2-Deficient Blastocysts," Nature 439 (2006): 212-15.
10. K. Chawengsaksophak et al., "Cdx2 is Essential for Axial Elongation in Mouse Development," Proceedings of the National Academy of Sciences 101 (2004): 7641-45.
11. The President's Council on Bioethics, Alternative Sources, 36-50.
12. See also W.B. Hurlbur, "Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells," Perspectives in Biology and Medicine 48, no. 2 (2005): 211-28;
13. W.B. Hurlbut, "Altered Nuclear Transfer: A Way Forward for Embryonic Stem Cell Research," Stem Cell Reviews 1, no, 4 (2005): 293-300;
14. W.B. Hurlbut, "Framing the Future: Embryonic Stem Cells, Ethics and the Emerging Era of Developmental Biology," Pediatric Research 59, no. 4, Pt. 2 (2006): 4R-12R.
15. 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.
16. Meissner and Jaenisch, "Generation of Nuclear Transfer-Derived Pluripotent ES Cells."
17. Melton, Daley, and Jennings, "Altered Nuclear Transfer."
18. The Dickey Amendment to the Department of Health and Human Services appropriations act prohibits the use of funds appropriated to DHHS to support the creation of a human embryo for research purposes or research in which a human embryo is destroyed, discarded, or subjected to risk of injury or death greater than that allowed under federal requirements for fetuses in utero. See Battey's testimony during the Senate Subcommittee hearing on alternative sources of pluripotent stem cells: "Alternative Methods of Obtaining Embryonic Stem Cells," July 14, 2005, at http://appropriations.senate.gov/ hearmarkups/BatteyJuly121.htm.
19. "Testimony by George Q. Daley, MD, PhD," July 12, 2005, at http://appropriations.senate.gov/hearmarkups/DALEYTestimony.htm.
20. See Jaenisch's testimony before the President's Council, "Session 3: Stem Cell Research: Recent Scientific and Clinical Developments," July 24, 2003, at http://www.bioethics.gov/transcripts/july03/session3.html.
21. See also R. Jaenisch, "Human Cloning - The Science and Ethics of Nuclear Transplantation," New England Journal of Medicine 351 (2004): 2787-91.
22. P.R. McHugh, "Zygote and 'Clonote' - The Ethical Use of Embryonic Stem Cells," New England Journal of Medicine 351 (2004): 209-11.
23. C. Simerly et al., "Embryogenesis and Blastocyst Development after Somatic Cell Nuclear Transfer in Nonhuman Primates: Overcoming Defects Caused by Meiotic Spindle Extraction," Developmental Biology 276 (2004): 237-32. This study employed cloning technicians from Hwang's lab.
24. C. Simerly et al., "Embryogenesis and Blastocyst Development," 242.
25. C. Simerly, personal communication, August 5, 2005.
26. Simerly et al., "Embryogenesis and Blastocyst Development," 247-248. These proteins are NuMA, a spindle pole assembly protein, and HSET, the mitotic kinesin that traffics to the microtubule minus-ends in meiotic and mitotic spindles. While there may be inhibitory components present that would obviate the need for the spindle complex/centrosome, the current evidence suggests that is not the case.
27. Simerly Embryogenesis and Blastocyst Development," Ibid., 248.
28. M.R. Shin et al., "Nuclear and Microtubule Reorganization in Nuclear-Transferred Bovine Embryos," Molecular Reproduction and Development 62 (2002): 74-82.
29. C.S. Navara, N.L. First, and G. Schatten, "Microtubule Organization in the Cow During Fertilization, Polyspermy, Parthenogenesis, and Nuclear Transfer: The Role of the Sperm Aster," Developmental Biology 162 (1994): 29-40.
30. G. Schatten, "The Centrosome and Its Mode of Inheritance: The Reduction of the Centrosome during Gametogenesis and Its Restoration during Fertilization," Developmental Biology 165 (1994): 299-335.
31. Simerly et al., "Embryogenesis and Blastocyst Development," 248.
32. C. Simerly et al., "The Parental Inheritance of the Centrosome, the Cell's Microtubule-Organizing Center, in Humans, and the Implications for Infertility," Nature Medicine 1 (1995): 47-52.
33. G.J. Wu et al., "Microtubule and Chromatin Dynamics during Fertilization and Early Development in Rhesus Monkeys, and Regulation by Intercellular Calcium Ions," Biology of Reproduction 55 (1996): 260-70.
34. Simerly et al., "Embryogenesis and Blastocyst Development," 241-42.
35. Jaenisch, "Human Cloning," 2789-90.
36. According to Calvin Simerly, one possible way to investigate this question would be to examine cloned human blastocysts for protein and other deficiencies of the sort observed in cloned primate preimplantation embryos. C. Simerly, personal communication, August 5, 2005.
37. A new study has suggested yet another possible alternative source for pluripotent human stem cells. In a letter published in Nature, researchers claimed that some spermatogonial stem cells derived from adult mouse testis seem to behave like pluripotent mouse embryonic stem cells. However, it is unknown whether pluripotent human spermatogonial stem cells can be derived from adult human testicular biopsies; moreover, no cell culture system currently exists for establishing pluripotent human spermatogonial stem cells. K. Guan et al., "Pluripotency of Spermatogonial Stem Cells From Adult Mouse Testis," Nature 440 (2006): 1199-1203.
38. Meissner and Jaenisch, "Generation of Nuclear Transfer-Derived Pluripotent ES Cells."
39. Given our analysis in this article, the question arises whether the Dickey Amendment can be reasonably interpreted to prohibit human research cloning.
40. National Academy of Sciences, Guidelines for Human Embryonic Stem Cell Research (Washington, D.C.: National Academies Press, 2004).
41. International Society for Stem Cell Research, "ISSCR to Launch an International Embryonic Stem Cell Research Guidelines Task Force," http:/www.isscr.org/press_release/ethics_tf.h tm. Accessed on January 10, 2006.
42. Carina Dennis, "Cloning: Mining the Secrets of the Egg," Nature online news feature, February 8, 2006, at http://www.nature.com/news/2006/ 060206/full/439652a.html.
43. Paul McHugh advances a very similar argument; McHugh, "Zygote and 'Clonote,'" 210.
44. See Ronald Green's treatment in "Determining Moral Status," American Journal of Bioethics 1, no. 2, (2002): 20-30.
45. Eric Juengst suggested this point.