This little piggy went to market: The xenotransplantation and xenozoonose debate

Journal of Law, Medicine and Ethics

Volumn 27, Issue 2, 1999, Pages 137-152

  Clark, Margaret A ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

ANALYTICAL APPROACH; ANIMAL; ANIMAL RIGHTS; ART; ARTICLE; CHIMERA; COMMUNICABLE DISEASE; DECISION MAKING; DONOR; EMOTION; ETHICS; FACTUAL DATABASE; FAMILY; FOOD AND DRUG ADMINISTRATION; GOVERNMENT; GOVERNMENT REGULATION; HEALTH CARE AND PUBLIC HEALTH; HEALTH CARE ORGANIZATION; HUMAN; HUMAN EXPERIMENT; INFORMED CONSENT; INTERNATIONAL COOPERATION; INTERPERSONAL COMMUNICATION; LEGAL LIABILITY; ORGAN TRANSPLANTATION; PATENT; POLICY; PRACTICE GUIDELINE; PRIMATE; PROFESSIONAL STANDARD; PUBLIC HEALTH; PUBLIC HEALTH SERVICE; QUALITY OF LIFE; RESOURCE ALLOCATION; RISK; RISK ASSESSMENT; SOCIAL CHANGE; SOCIAL CONTROL; STANDARD; SWINE; TRANSGENIC ANIMAL; TRANSPLANTATION; UNITED STATES; XENOGRAFT;

ANALYTICAL APPROACH; HEALTH CARE AND PUBLIC HEALTH; PUBLIC HEALTH SERVICE;

ANIMAL RIGHTS; ANIMALS; ANIMALS, GENETICALLY MODIFIED; CHIMERA; COMMUNICABLE DISEASES; DATABASES, FACTUAL; DECISION MAKING; DISCLOSURE; EMOTIONS; ETHICS; ETHICS COMMITTEES; ETHICS COMMITTEES, RESEARCH; FAMILY; FEDERAL GOVERNMENT; GOVERNMENT; GOVERNMENT REGULATION; GUIDELINES; HEALTH CARE RATIONING; HUMAN BODY; HUMAN EXPERIMENTATION; HUMANS; INFORMED CONSENT; INTERNATIONAL COOPERATION; INTERNATIONALITY; LIABILITY, LEGAL; ORGAN TRANSPLANTATION; PATENTS; PRIMATES; PUBLIC HEALTH; PUBLIC POLICY; QUALITY OF LIFE; REFERENCE STANDARDS; RESOURCE ALLOCATION; RISK; RISK ASSESSMENT; SOCIAL CHANGE; SOCIAL CONTROL, FORMAL; SWINE; TISSUE AND ORGAN PROCUREMENT; TISSUE DONORS; TRANSPLANTATION; TRANSPLANTATION, HETEROLOGOUS; UNITED STATES; UNITED STATES FOOD AND DRUG ADMINISTRATION; UNITED STATES PUBLIC HEALTH SERVICE;

EID: 0033139872     PISSN: 10731105     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1748-720X.1999.tb01446.x     Document Type: Review

References (151)

1. A.S. Daar, Correspondence, "Xenotransplants: Proceed with Caution," Nature, 392 (1998): 11.
2. See R.E. Michler, "Xenotransplantation: Risks, Clinical Potentials, and Future Prospects," Emerging Infectious Disease, 2, no. 1 (1996) (visited June 14, 1999) 〈http://www.cdc.gov/ncidoc/ vol2no1/michler.html〉.
3. See Committee on Xenograft Transplantation Ethical Issues and Public Policy, Institute of Medicine, Xenotransplanlation: Science, Ethics and Public Policy (Washington, D.C.: National Academy Press, 1996): at 34 (discussing public education efforts after passage of the National Organ Transplant Act of 1984, 42 U.S.C. § 273) [hereinafter the Institute of Medicine].
4. See National Kidney Foundation, "Americans Recognize Organ Shortage," at 1 (Jan. 21, 1998), (visited June 14, 1999) 〈http://www.kidney.org/general/news/anima2man.cfm〉.
5. See Institute of Medicine, supra note 3, at 69.
6. See National Kidney Foundation, supra note 4, at 1.
7. See "Egypt Doctors Trying to End Sale of Kidneys, Group to Ban Transplants from Most Living Donors," San Francisco Chronicle, Jan. 24, 1992, at A16.
8. See S. Hazarika, "India Debates Ethics of Buying Transplant Kidneys," New York Times, Aug. 17, 1992, at A20.
9. See "Parts Needed for Transplants in Human Organs Stirs Global Attention," Los Angeles Times, July 16, 1989, at 6.
10. See "Turk Who Masterminded Trade in Human Kidneys Jailed for Two Years," The Independent, May 19, 1992, at 11 (discussing jailing of Turkish broker who brought poor Turks to England to donate organs).
11. See B. Edlune, "Courage Isn't Up to Bank Heists? Sell a Kidney, Cash Offered for Live Donors' Organs," Los Angeles Times, Nov. 13, 1988, at 12.
12. See H. O'Shaughnessy, "Murder and Mutilation Supply Human Organ Trade," The Observer, Mar. 27, 1994, at 27 (noting that doctors in Poland and Budapest are selling organs to the Swiss).
13. See S. Dillon, "Poor in Uruguay Sell Kidneys to Rich," Detroit Free Press, Dec. 9, 1991, at A3.
14. See W. Booth, "Witch Hunt," Washington Post, May 17, 1994, at C1-C2.
15. See Rights of the Child, Sale of Children: Report of Mr. Vitit Muntarbhorn, Special Rapporteur, U.N. Commission on Human Rights, 49th Sess., Agenda Item 24, at 22, 127, U.N. Doc. E/CN.4/67 (1993) and Summary Record, U.N. Commission on Human Rights, Subcomm. on Prevention of Discrimination and Protection of Minorities, 41st Sess., 39th mtg., at 21, 94, U.N. Doc. E/CN.4/Sub.2/SR (1989), cited in N. Morelli, "Organ Trafficking: Legislative Proposals to Protect Minors," American Journal of International Law and Policy, 10 (1995): 917-54.
16. See Rights of the Child, Sale of Children: Report of Mr. Vitit Muntarbhorn, Special Rapporteur, U.N. Commission on Human Rights, 49th Sess., Agenda Item 24, at 22, 127, U.N. Doc. E/CN.4/67 (1993) and Summary Record, U.N. Commission on Human Rights, Subcomm. on Prevention of Discrimination and Protection of Minorities, 41st Sess., 39th mtg., at 21, 94, U.N. Doc. E/CN.4/Sub.2/SR (1989), cited in N. Morelli, "Organ Trafficking: Legislative Proposals to Protect Minors," American Journal of International Law and Policy, 10 (1995): 917-54.
17. See Rights of the Child, Sale of Children: Report of Mr. Vitit Muntarbhorn, Special Rapporteur, U.N. Commission on Human Rights, 49th Sess., Agenda Item 24, at 22, 127, U.N. Doc. E/CN.4/67 (1993) and Summary Record, U.N. Commission on Human Rights, Subcomm. on Prevention of Discrimination and Protection of Minorities, 41st Sess., 39th mtg., at 21, 94, U.N. Doc. E/CN.4/Sub.2/SR (1989), cited in N. Morelli, "Organ Trafficking: Legislative Proposals to Protect Minors," American Journal of International Law and Policy, 10 (1995): 917-54.
18. See Morelli, supra note 15, at 917 n.5.
19. See id. at 917 n.11. The American letter to the European Parliamentary Assembly explains that the type of facilities and professional staff necessary for successful removal and transplant of organs are more elaborate than makeshift facilities available in developing countries. Facilities in the United States are government certified and inspected so to uncover any such irregularities in organ procurement.
20. See id. Letter from James Mason, Assistant Secretary of Health, and C. Everert Koop, Surgeon General, to Karel de Gucht, Chair, Human Rights Commission of the European Parliament (June 1989).
21. See id., citing A. McIntosh, "Regulating the 'Gift of Life': The 1987 Uniform Anatomical Gift Act," Washington Law Review, 65 (1990): 171-88, at 179.
22. See M. Engel, "Virginia Doctor Plans Company to Arrange Sale of Human Organ, Washington Post, Sept. 19, 1983, at A9.
23. C.D. Keyes, ed., New Harvest: Transplanting Body Parts and Reaping the Benefits (Clifton: Human Press, 1991): at 273-79.
24. Since at least 1906, pigs, goats, and primates have donated kidneys to humans. The longest "successful" (survival time) for such transplants is nine months. This involved a chimpanzee in 1963. See K. Reemstra, "Xenotransplantation: A Personal History," in M.A. Hardy, ed., Xenograft 25: Proceedings of the International Congress, 1988 (New York: Excerpta Medica, 1989): 7-16, at 10-16. In 1963, six baboons survived between ten and sixty days. See T.E. Staczl, "Baboon, Renal and Chimpanzee Liver Heterotransplantation," in Hardy, id., at 17-24.
25. Since at least 1906, pigs, goats, and primates have donated kidneys to humans. The longest "successful" (survival time) for such transplants is nine months. This involved a chimpanzee in 1963. See K. Reemstra, "Xenotransplantation: A Personal History," in M.A. Hardy, ed., Xenograft 25: Proceedings of the International Congress, 1988 (New York: Excerpta Medica, 1989): 7-16, at 10-16. In 1963, six baboons survived between ten and sixty days. See T.E. Staczl, "Baboon, Renal and Chimpanzee Liver Heterotransplantation," in Hardy, id., at 17-24.
26. See Institute of Medicine, supra note 3, at 6-7.
27. See id. at 13-14. See also O. Isacson and X.O. Breakefield, Commentary and Review, "Benefits and Risks of Hosting Animal Cells in the Human Brain," Nature Medicine, 3 (1997): 964-69.
28. See Institute of Medicine, supra note 3, at 14-15. The Food and Drug Administration approved this experiment, following approval from University of California's Institutional Review Board and Laboratory Animal Care Use Committee. Incorporating a number of risk-reduction and surveillance measures, the experiment is characterized as "proceed[ing] cautiously [with] evaluat[ion] along the way" by Louisa Chapman of the Centers for Disease Control and Prevention (CDC).
29. See R.S. Chari et al., Brief Report, "Treatment of Hepatic Failure with Ex Vivo Pig-Liver Perfusion Followed by Liver Transplantation," N. Engl. J. Med., 331 (1994): 234-37.
30. See Institute of Medicine, supra note 3, at 16.
31. See J.L. Platt, "New Directions for Organ Transplantation," Nature, 392, Supp. (1998): A11-A17.
32. See Institute of Medicine, supra note 3, at 26-38.
33. Enumerated in the Public Health Service (PHS) Guideline are the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome, Creutzfeldt-Jakob disease, rabies, and the hepatitis B and C viruses. See "Draft Public Health Service (PHS) Guideline on Infectious Disease Issues in Xenotransplantation," 61 Fed. Reg. 49,919-32, at 49,921-23 (Sept. 23, 1996).
34. See Institute of Medicine, supra note 3, at 41.
35. CDC's animal virus expert Chapman tells the following. In 1993, she was asked to consider the possibility of new germs passing into the human population through xenotransplants, and she thought the question silly, not deserving the expenditure of public dollars. But as she looked into xenotransplants, she changed her mind. She now spends most of her professional time on xenotransplant issues, because it is now known that a number of viruses, including some retroviruses (like HIV) and endogenous viruses can and do move between species.
36. Simian immune viruses (SIVs), which are present in any simian species, do not apparently affect their hosts. They are thought, however, to be the origin of HIV-1 (from chimpanzees), and HIV-2 (from sooty mangebey monkeys). SIV infection of humans has been documented in a person working in a primate lab. An outbreak in Germany in 1967 of Marburg virus (from lab monkeys) infected 31 people and was 23 percent fatal. Ebola, a filovirus, infected at least 220 people in Zaire in 1976, with an 88 percent fatality rate. A shepherd in Pakistan underwent surgery while infected with a type of hemorrhagic fever from domestic animals, thus exposing 17 people with a 24 percent fatality rate. See J.S. Allan, "Xenograft Transplantation and the Infectious Disease Conundrum," IALR Journal, 37 (1995): 37-48.
37. See L.C. Marcus and E. Marcus, Editorial, "Nosocomial Zoonoses," M. Engl. J. Med., 338 (1998): 757-59.
38. For sources, see Platt, supra note 28 (citing eight-six sources).
39. Known zoonoses detected by laboratory tests include salmonella, herpes B virus of monkeys, and toxoplasmosis. Other organisms to screen for are Brucella and Erysipelothrix from swine, T. gonii viruses, and mycobacterium species. Recommended test methods are species-specific screening methods and the use of DNA analysis (polymerase chain reaction). See Institute of Medicine, supra note 3, at 47.
40. See Institute of Medicine, supra note 3, at 13-14. See Isacson and Breakefield, supra note 24, at 964-69.
41. C. Clark, "Virology DNA from Different Retroviruses Exchange Genetic Information," AIDS Weekly Plus, Aug. 11, 1997, available in 1997 Westlaw IAC-NEWS-C 91AC.
42. See J. Ritter, "Pig Organs May Save Lives," Chicago Sun Times, Oct. 6, 1997, at 12.
43. See D.M. Smith, Letter, "Endogenous Retroviruses in Xenografts," N. Engl. J. Med., 328 (1993): 142-43.
44. See Isacson and Breakefield, supra note 24, at 964-69.
45. See R. Weiss, "Study Finds Danger from Pig Transplants," Houston Chronicle, Oct. 17, 1997, at 14; and P. Le Tissier et al., "Two Sets of Human-Tropic Pig Retrovirus," Nature, 389 (1997): 681-82.
46. See R. Weiss, "Study Finds Danger from Pig Transplants," Houston Chronicle, Oct. 17, 1997, at 14; and P. Le Tissier et al., "Two Sets of Human-Tropic Pig Retrovirus," Nature, 389 (1997): 681-82.
47. See Allan, supra note 33, at 37-48.
48. See Platt, supra note 28, at A12.
49. See C. Patience, Y. Takeuchi, and R.A. Weiss, "Infection of Human Cells by an Endogenous Retrovirus of Pigs," Nature Medicine, 3 (1997): 282-86.
50. See B. Nasto, "Xenotransplant Firms Get Xenophobic," Nature Biotechnology, 15 (1997): 1239.
51. See "FDA Proposes Precautionary Ban Against Ruminantto-Ruminant Feeding," FDA Press Office Release, Jan. 2, 1997, at 1-2.
52. See A.F. Hill et al., "The Same Prion Strain Causes CJD and USE," Nature, 389 (1997): 448-50, 498-501.
53. Early bone-marrow transplants had high mortality rates and serious immunological problems. Many patients died, but the net result is that the procedure is safer and more successful today.
54. See Institute of Medicine, supra note 3, at 46.
55. Fritz Bach is a prominent transplant researcher. His letter, calling for a moratorium on clinical trials, was recently published. See F.H. Bach et al., Correspondence, "Uncertainty in Xenotransplantation: Individual Benefit Versus Collective Risk," Nature Medicine, 4 (1998): 141-44.
56. See J. Chang et al., "An Epidemic ofMalassezia Pachydermitis in an Intensive Care Nursery Associated with Colonization of Health Care Workers' Dogs," N. Engl. J. Med., 338 (1998): 706-11, for an interesting account of an epidemic in a neonatal ward. The infectious organism, Malassezia pachydermatis, was apparently transmitted by health care workers who had dogs (12 of 39 dogs) that were infected.
57. See Platt, supra note 28, at A11-A17.
58. One commentator has suggested that the education of recipients' contacts be the responsibility of the institution or institutional regulatory board, not the patient. See J.K. Fredrickson, "He's All Heart ... and a Little Pig, Too: A Look at the FDA Draft Xenotransplant Guideline," Food and Drug Law Journal, 52 (1997): 429-51, at 445-46.
59. See id. at 450. The suggestion was made by the American Association of Transplant Surgeons.
60. See Institute of Medicine, supra note 3, at 16.
61. Without attempting a complete cataloguing of mythical half-beast half humans, one can easily mention the Minotaur of Crete, the cloven-footed god Pan, and mermaids as examples. A biotech company in Massachusetts working with pigs calls itself Circe, presumably after the sorceress who turned Odysseus' sailors into swine.
62. See Institute of Medicine, supra note 3, at 16.
63. Organ transplant patient Claire Sylvia feels presence of organ donor. See I. Weeks, "Transplant Recipient Tells Ghostly Tale," Tacoma News Tribune, Aug. 13, 1996, at SL4.
64. See J. Groopman, "The Sudden Epidemic," New Yorker, May 11, 1998, at 48-60. See also A. Weill, Health Newsletter, May 1998, at 1-2.
65. See J. Groopman, "The Sudden Epidemic," New Yorker, May 11, 1998, at 48-60. See also A. Weill, Health Newsletter, May 1998, at 1-2.
66. N. Goodman, Letter, "This is Where I Start to Draw the Line," British Medical Journal, 313 (1996): 696. Neville Goodman says this: shows how blinkered some human beings can be. The problem of viral infection was seen as a risk-which might be worth taking 'in the quest to end human suffering.' As if human suffering, in the global sense, has anything to do with a lack of organs. It makes me uneasy to think that many doctors do not seem to even think about these things. If they did, they might at least modify their rhetoric and stop inflating the importance of their interests. Id.
67. Note that the same sort of confusion and disagreement exists in later discussion of life patenting and xenotransplant, about which the commissioner of the Patent and Trademark Office has felt impelled to speak out on an application of chimera xenografting processes made by antibiotech activists, when technically and presumably morally equivalent patents have already been approved. These include technology to get cows to produce in their mammary glands the drug AAT (to treat cystic fibrosis); a xenograft process to move human immune complements into pigs, thereby making pigs' organs less "foreign" to human organ recipients' immune systems; a process to produce a blood-clot regulator in goats; and one to make a tissue plasminogen activator.
68. See J. Goodall, "Ethical Concerns in the Use of Animals as Donors," in Hardy, supra note 22, at 335-49.
69. See id. at 347.
70. See id.; and D.J. Rothman, "Xenograft: Social and Ethical Dimensions," in Hardy, supra note 22, 321-33, at 333.
71. See Institute of Medicine, supra note 3, at 16.
72. See id. at 77, quoting philosopher James Walters. Walters's idea is that "the highest moral status should be accorded those animals who are closest to qualities that most humans possess..." which enables man to "value beings in terms of their proximity or likeness to persons ... he thus holds that it may be more justifiable to use anencephalic infants as organ sources than to use chimpanzees." Id., citing James Walters, Remarks at Institute of Medicine Meeting "Xenograft Transplantation: Science, Ethics and Public Policy," Bethesda (June 25-27, 1995).
73. See id. at 74. An extension of the rights approach would be to invest other species with the same rights.
74. See Rothman, supra note 65, at 327-32. Daniel Rothman points out that Victorian antivivisectionists feared that callous treatment of animals would encourage inhuman treatment of the poor.
75. See G. Sessions and B. Devall, Deep Ecology (Salt Lake City: Gibbes-Smith, 1986); G. Snyder, The Practice of the Wild (San Francisco: North Point, 1990); R. Aitken, The Mind of Clover (San Francisco: North Point, 1984); and J. Seed et al., Thinking like a Mountain: Towards a Council of All Beings (Philadelphia: New Society, 1991).
76. See G. Sessions and B. Devall, Deep Ecology (Salt Lake City: Gibbes-Smith, 1986); G. Snyder, The Practice of the Wild (San Francisco: North Point, 1990); R. Aitken, The Mind of Clover (San Francisco: North Point, 1984); and J. Seed et al., Thinking like a Mountain: Towards a Council of All Beings (Philadelphia: New Society, 1991).
77. See G. Sessions and B. Devall, Deep Ecology (Salt Lake City: Gibbes-Smith, 1986); G. Snyder, The Practice of the Wild (San Francisco: North Point, 1990); R. Aitken, The Mind of Clover (San Francisco: North Point, 1984); and J. Seed et al., Thinking like a Mountain: Towards a Council of All Beings (Philadelphia: New Society, 1991).
78. See G. Sessions and B. Devall, Deep Ecology (Salt Lake City: Gibbes-Smith, 1986); G. Snyder, The Practice of the Wild (San Francisco: North Point, 1990); R. Aitken, The Mind of Clover (San Francisco: North Point, 1984); and J. Seed et al., Thinking like a Mountain: Towards a Council of All Beings (Philadelphia: New Society, 1991).
79. See J. Macy, World as Lover, World as Self (Berkeley: Parallax Press, 1991): at 53-64. Joanne Macy writes: The self is a metaphor. We can decide to limit it to our skin, our person, our family, our organization, our species.... The obvious choice then, is to extend our notions of self-interest. For example, it would not occur to me to say to you, "Oh, don't cut off your leg. That would be an act of violence." It wouldn't occur to me because your leg is part of your body. Well, so are the trees in the Amazon rain basin. They are our external lungs. And we are beginning to realize that the world is our body. Id. at 189-92. Arne Naess, the Norwegian philosopher who coined the term "deep ecology," puts it this way: The extensive moralizing within the ecological movement, the false impression that they are asked to make a sacrifice ... to show a nicer moral standard ... but all of that would flow easily if the self were widened and deepened so that the protection of nature was felt and perceived as protection of our very selves. Id. at 191. Thus, the Buddhist "Sangha," or fellowship, is extended into the "Council of All Beings," in which, as Lawrence Tribe would have it, trees have standing. Id. at 202.
80. See 61 Fed. Reg. 49,924-25 (Sept. 23, 1996). Section 3.2 of the Guideline specifies that animals should be raised in accordance with the Guide for the Care and Use of Laboratory Animals, which is a standard of the American Association for the Accreditation of Laboratory Animal Care. No specific mention is made about animal rights issues.
81. Human organs are not to be bought or sold. See National Organ Transplant Act, 42 U.S.C. § 273 (1984).
82. See Keyes, supra note 21, at 273-79. Don Keyes uses the retransplantation decision to illustrate this last point: If the first organ graft fails, should another scarce organ be used to replace it, or should another patient get a chance?
83. See Institute of Medicine, supra note 3, at 54.
84. See R.W. Evans, "Xenotransplantation: A Panel Discussion of Some Non-Clinical Issues," in Hardy, supra note 22, at 359-67.
85. See Institute of Medicine, supra note 3, at 81.
86. H.T. Engelhardt Jr., "Allocating Scarce Medical Resources and the Availability of Organ Transplantation: Some Moral Presuppositions," in D. Mathieu, ed., Organ Substitution Technology; Ethical, Legal and Public Policy Issues (Boulder: Westview Press, 1988): 221-31, at 221-22.
87. See id. at 224-26.
88. See N. Daniels, "Justice and Big Ticket Technologies," in Mathieu, supra note 78, at 211-220.
89. Transplant News, Feb. 13, 1998, available in 1998 Westlaw IAC-NEWS-C.
90. See D. Dickson, News, "Legal Fight Looms over Patent Bid on Human/Animal Chimaeras," Nature, 392 (1998): 423-24.
91. See "Part-Human Inventions May Not Meet 'Morality' Requirement for Patentability," Patent, Trademark and Copyright Law Daily (BNA), at d2 (Apr. 7, 1998).
92. Lowell v. Lewis, 15 F. Cas. 1018 (C.C.D. Mass. 1817) (No. 8568).
93. Id.
94. "'Morality' Aspect of Utility Requirement Can Bar Patent for Part-Human Inventions," Patent, Trademark and Copyright Journal News (BNA), at 555 (Apr. 9, 1998).
95. For a discussion about overcoming immune barriers, see Institute of Medicine, supra note 3, at 26-38.
96. See Dickson, supra note 82, at 423.
97. Id.
98. Id. at 434.
99. See "European Parliament Approves Draft Biotech Patent Directive," Patent, Trademark and Copyright Law Daily (BNA), at d3 (Aug. 28, 1997).
100. Fredrickson, supra note 54, at 429.
101. See "Investigational New Drug Application," 21 C.F.R. pt. 312, at 61-99 (1999).
102. See "Institutional Review Boards," 21 C.F.R. pt. 56, at 254-62 (1999).
103. See "Protection of Human Subjects, Subpart B, Informed Consent of Human Subjects," 21 C.F.R. pt. 50, at 246-51 (1999).
104. See "Draft Public Health Service (PHS) Guideline on Infectious Disease Issues in Xenotransplantation," 61 Fed. Reg. 49,920-30 (Sept. 23, 1996). For details on the transplant team's composition, see id. at 49,222, § 2.1. Besides the transplant surgeon, the team should include: (1) an infectious disease physician with experience in zoonoses, transplantation, and microbiology; (2) a veterinarian with specific expertise in the animal husbandry and infectious diseases of the animal species serving as the organ donor; (3) a transplant immunologist; (4) a hospital epidemiologist/infection control specialist; and (5) the director of the clinical microbiology laboratory. See id.
105. For details on health surveillance plans, see id. at 49,923, § 2.4.
106. For details on the Xenotransplantation site, see id. at 49,922, § 2.2.
107. For details on the clinical protocol review, see id. at 49922-23, § 2.3.
108. See id. at 49,922-23, §§ 2.1-.4; see also 61 Fed. Reg. at 49,923, § 2.5 and "Written Informed Consent and Recipient Education." Informed consent is to be obtained in accordance with 45 C.F.R. pt. 46 (1999) and 21 C.F.R. pt. 50 (1999) and the principles outlined in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects in Research. See 61 Fed. Reg. at 49,922-23.
109. See 61 Fed. Reg. 49,923-26. The Guideline contains detailed specifications for animal facilities used to raise animals for transplant organs. See 61 Fed. Reg. at 49,923-26, §§ 3-3.7. They must meet at minimum the recommendations in the FDA regulations on the care and uses of laboratory animals, the basis of animal lab accreditation. The Guideline prescribes measures to ensure animal health, safety of workers, screening, qualification, and pretransplant quarantine. It provides for the procurement and screening of xenografts, including detailed record keeping, rehearsal of procedures, transportation, and necropsy following animal death. The Guideline reads in quality control terms - it is objective and detached from any sentiment or acknowledgment of the sentience of the pharm's residents, except perhaps in reference to their deaths as "euthanizing." While most companies comply with requirements for specific-pathogen-free (SPF) environments to raise animals for xenotransplant, some have not. The animals are to be "closed herds," with new animals introduced only if necessary, after quarantine and careful screening. Reproduction by artificial insemination is recommended to reduce possible transmission of disease vectors. Any animal that becomes sick will necessitate testing of the whole herd. Animal colonies are developed for some species in two types of facilities: SPF facilities and gnotobiotic facilities, in which animals are raised as closely as possible to germ free. The costs of such facilities are tremendous, and the need to raise cesarean-born young in isolation creates ethical issues. Health problems are also associated with motherless young. See J. Randal, "Xenotransplants Moving Ahead Too Quickly for Some," Journal of the National Cancer Institute, 90 (1998): 348-50. The bibliography contained in the PHS Guideline is a good source for references on raising colonies of primates and swine, and the transmission of zoonoses. See 61 Fed. Reg. at 49,920.
110. See 61 Fed. Reg. 49,923, § 2.24; 49,927, § 4.1.14; 49,928, § 4.3.3.2; and 49,928, § 4.3.33.
111. See id. at 49,927, § 4.3.
112. See id. at 49,929, § 5.1; and 49,930, § 5.2.
113. The Guideline specifies that live animal cells, tissues, and organs intended for use in humans are subject to the Public Health and Services Act (PHSA), 42 U.S.C. § 262 (1994), IRB regulations, 21 C.F.R. pt. 56 (1999), and investigational new drug applications, 21 C.F.R. pt. 312 et seq. (1999). "Whole organs for transplant have not historically been regulated by FDA; rather, they fall under NOTA, which functions through a national clearinghouse. Xenografts will be regulated as biologicals by the PHSA and 21 C.F.R. pts. 50, 56, 312. While unmodified bone marrow is not regulated, FDA sees all "manipulated" cells and tissues as coming under this provision. In 1992, an updated rule was issued to advise on the regulation of these materials. Nonliving materials, such as pig heart valves, are regulated as medical devices. Premarket approval required for biologies involves an investigational new drug permit (IND) and three phases of clinical trials. At this time, the contents of INDs are considered proprietary information; hence, although some applications for xenograft products have been accepted, no public disclosure of their contents is required. Biologies, which are created with the assistance of genetic modification, are also subject to review by the National Institutes of Health's Recombinant DNA Advisory Committee, and therefore also to biosafety protocols at appropriate levels.
114. See R. Nowak, "FDA Puts Brakes on Xenotransplants," Science, 268 (1995): 630.
115. See M. Groves, "Transgenic Livestock May Become Biotech's Cash Cow," Los Angeles Times, May 1, 1997, at A1. Biotech companies PPL Therapeutics of Virginia, Nextran of New Jersey, and Alexion of Connecticut have been developing colonies of transgenic pigs for transplant. See also W.H. Allen, "Farming for Spare Body Parts," Bioscience, Feb. 1, 1995, at 73. Immutran of the United Kingdom has also been developing colonies of transgenic pigs for transplant.
116. See M. Groves, "Transgenic Livestock May Become Biotech's Cash Cow," Los Angeles Times, May 1, 1997, at A1. Biotech companies PPL Therapeutics of Virginia, Nextran of New Jersey, and Alexion of Connecticut have been developing colonies of transgenic pigs for transplant. See also W.H. Allen, "Farming for Spare Body Parts," Bioscience, Feb. 1, 1995, at 73. Immutran of the United Kingdom has also been developing colonies of transgenic pigs for transplant.
117. See 21 C.F.R. pt. 50, at 246-51 (1999). The informed consent recommended under the PHS Guideline goes beyond that required by 21 C.F.R. pt. 50, in that it covers: (1) disclosure of early stage of research; (2) mortality and morbidity information on previous recipients, including quality of life; (3) option of no transplant; (4) evaluation of relative risk and waiting time for availability of a human organ; (5) disclosure of probability of intense media attention; (6) potential risk for transmission of zoonotic agents known to be associated with donor species; (7) potential for transmission of unknown pathogenic agents: - uncertainty of these risks - possibility that infection might not be recognized for some time - that the nature of clinical diseases these agents may cause is unknown; (8) potential risk for transmission of xenogenic infectious agents to family, especially sexual contacts; (9) higher risk to immune-suppressed persons; (10) need for isolation procedures during hospitalization and special precautions following discharge; (11) need to comply with lifetime surveillance and monitoring, including: - physical exams, lab tests, archiving of tissue samples, reporting of any serious illnesses; (12) need to report any changes of address or telephone; (13) disclosure of need for complete autopsy on recipient's death, with the recipient's assent; (14) access by appropriate public health officials to all medical records, with confidentiality to be maintained as permitted by law (mandatory reporting of some communicable diseases); and (15) instructions and agreement never to donate tissue, blood, ova, sperm, and so forth, for use in humans.
118. See Institute of Medicine, supra note 3, at 62-63.
119. See 61 Fed. Reg. 49,920-30, at 49,924-26, §§ 3.Z-.7 (Sept. 23, 1996); see also id. at 49,923, § 2.4.
120. See Institute of Medicine, supra note 3, at 55.
121. The report was funded by the National Cancer Institute, CDC, FDA, Health Resources and Services Administration, the U.S. Navy, and several private organizations, including the Howard Hughes Medical Institute, the Greenwall Foundation, W.R. Grace, and Charles River Laboratories. See J. Bradbury, "Call for Xenotransplantation Moratorium," Lancet, 351 (1998): 271.
122. The Institute of Medicine report recommends the following. (1) Guidelines for human trials of Xenotransplantation addressing four major areas: (a) procedures to screen donor animals for infectious organisms, and development of SPF facilities to house them, (b) lifetime surveillance of xenotransplant recipients with periodic surveillance of their families and contacts, (c) establishment of tissue banks of samples from source animals and patients, and (d) establishment of local and national registries of xenotransplant recipients, with efforts to establish data banks with international coordination. (2) Required adherence to national guidelines with oversight by local IRBs and animal care committees, with expansion in their expertise. (3) Further investigation into new ethical and social issues raised by Xenotransplantation including expanded informed consent, fairness of organ allocation, and research into the psychological and social effects of xenotransplantation. (4) Coordinated cooperation between agencies and private industry under the Department of Health and Human Services. A broadly constituted advisory board should coordinate, not regulate, and suggest modifications to guidelines based on new data. (5) When the science base for specific types of xenotransplantation is judged sufficient and appropriate safeguards are in place, well-chosen human transplant trials using animal cells, tissues, and organs would be justified and could proceed. The panel also recommended allocating sufficient public and private funds to assure that risks of disease transmission can be controlled. See Institute of Medicine, supra note 3.
123. See Ritter, supra note 39, at 12.
124. See I. Kennedy, Letters, "Xenotransplantation Moratorium," Nature Biotechnology, 16 (1998): 120.
125. See D. Shapiro, Correspondence, "Xenotransplantation," Lancet, 349 (1997): 735-36.
126. See Editorial, "Have a Pig's Heart?," Lancet, 349 (1997): 219. The editorial asks whether It is a time-honored UK tradition that when a government is not sure which way to jump in tricky matters such as this, it sets up first an inquiry and then an interim regulator.... Why were the ethical and other aspects of xenotransplantation not explored earlier?... Is xenotransplantation a quantum leap towards a human cyborg warranting a high-profile moratorium? Yes, provided that productive discussion and not further dithering is the objective. Id.
127. Bach et al., supra note 51.
128. See Allan, supra note 33, at 37-48.
129. See C. Chastel, Letters, "The Dilemma of Xenotransplantation," Emerging Infectious Diseases, 2, no. 2 (1996): 10.
130. See L. Neergaard, "Scientists Want Use of Animal Organs in Humans Halted," Arizona Republic, Jan. 28, 1998, at A10; T. Siegfried, "Virus Fears Evoke Concerns about Transplants from Pigs," Dallas Morning News, Jan. 26, 1998, at 7D; R. Knox, "Caution Urged on Animal to Human Transplant," Boston Globe, Jan. 22, 1998, at A16; R. Know, "Crossing the Divide: Researchers Expand Testing of Animal to Human Transplants," Boston Globe, Feb. 2, 1998, at Cl; and R. Knox, "Animal-to-HumanTissue Transplants are Gaining Ground," Boston Globe, Feb. 8, 1998, at A9.
131. See L. Neergaard, "Scientists Want Use of Animal Organs in Humans Halted," Arizona Republic, Jan. 28, 1998, at A10; T. Siegfried, "Virus Fears Evoke Concerns about Transplants from Pigs," Dallas Morning News, Jan. 26, 1998, at 7D; R. Knox, "Caution Urged on Animal to Human Transplant," Boston Globe, Jan. 22, 1998, at A16; R. Know, "Crossing the Divide: Researchers Expand Testing of Animal to Human Transplants," Boston Globe, Feb. 2, 1998, at Cl; and R. Knox, "Animal-to-HumanTissue Transplants are Gaining Ground," Boston Globe, Feb. 8, 1998, at A9.
132. See L. Neergaard, "Scientists Want Use of Animal Organs in Humans Halted," Arizona Republic, Jan. 28, 1998, at A10; T. Siegfried, "Virus Fears Evoke Concerns about Transplants from Pigs," Dallas Morning News, Jan. 26, 1998, at 7D; R. Knox, "Caution Urged on Animal to Human Transplant," Boston Globe, Jan. 22, 1998, at A16; R. Know, "Crossing the Divide: Researchers Expand Testing of Animal to Human Transplants," Boston Globe, Feb. 2, 1998, at Cl; and R. Knox, "Animal-to-HumanTissue Transplants are Gaining Ground," Boston Globe, Feb. 8, 1998, at A9.
133. See L. Neergaard, "Scientists Want Use of Animal Organs in Humans Halted," Arizona Republic, Jan. 28, 1998, at A10; T. Siegfried, "Virus Fears Evoke Concerns about Transplants from Pigs," Dallas Morning News, Jan. 26, 1998, at 7D; R. Knox, "Caution Urged on Animal to Human Transplant," Boston Globe, Jan. 22, 1998, at A16; R. Know, "Crossing the Divide: Researchers Expand Testing of Animal to Human Transplants," Boston Globe, Feb. 2, 1998, at Cl; and R. Knox, "Animal-to-HumanTissue Transplants are Gaining Ground," Boston Globe, Feb. 8, 1998, at A9.
134. See L. Neergaard, "Scientists Want Use of Animal Organs in Humans Halted," Arizona Republic, Jan. 28, 1998, at A10; T. Siegfried, "Virus Fears Evoke Concerns about Transplants from Pigs," Dallas Morning News, Jan. 26, 1998, at 7D; R. Knox, "Caution Urged on Animal to Human Transplant," Boston Globe, Jan. 22, 1998, at A16; R. Know, "Crossing the Divide: Researchers Expand Testing of Animal to Human Transplants," Boston Globe, Feb. 2, 1998, at Cl; and R. Knox, "Animal-to-HumanTissue Transplants are Gaining Ground," Boston Globe, Feb. 8, 1998, at A9.
135. See M. Groves, "Transgenic Livestock May Become Biotech's Cash Cow," Los Angeles Times, May 1, 1997, at Al; and Allen, supra note 106.
136. See Allen, supra note 107, at 73 (listing seven companies, including Nextran and Immutran, doing similar work with pigs). See also J. Fox, "FDA Seeks 'Comfort Factors' Before Removing Hold on Porcine Xenotransplantation Trials," Nature Biotechnology, 16 (1998): 224.
137. "Leading Xenotransplant Researcher's Call for Moratorium on Human Clinical Trials Causes Furor," Transplant News, Feb. 13, 1998, available in 1998 Westlaw IAC-NEWS-C.
138. See D. Butler, "Last Chance to Stop and Think on Risks of Xenotransplants," Nature, 391 (1998): 320-24 (quoting Jonathan Allan as saying "Xenotransplant researchers haven't done their homework.")
139. See "Xenotransplantation: US FDA Plans to be Tough on Pig Transplants," Disease Weekly Plus, Jan. 5, 1998, available in 1998 Westlaw 904632.
140. See J. Wise, "Pig Virus Transfer Threatens Xenotransplantation," British Medical Journal, 314 (1997): 623.
141. See News in Brief, "Pig Virus Discovery Underlines Risks of Xenotransplants," Nature, 392 (1998): 10.
142. See "AIDS-Like Fear Warning Issued Against Use of Animal Organs in Humans," Chicago Tribune, Mar. 25, 1998, at 7.
143. A survey conducted by the National Kidney Foundation found that 75 percent of all respondents would consider a Xenotransplant for a loved one, if a human organ was not available. See National Kidney Foundation, supra note 4, at 1.
144. See Institute of Medicine, supra note 3, at 87.
145. See Daar, supra note 1, at 11.
146. See D. Bodansky, Remarks in Law A545 Lecture, University of Washington School of Law (Fall 1997) (on file with author).
147. Daar, supra note 1, at 11.
148. See 21 C.F.R. pt. 50, at 246-51 (1999).
149. R.W. Evans and D.L. Manninen, "US Public Opinion Concerning the Procurement and Distribution of Donor Organs," Transplantation Proceedings, 20 (1988): 781-85.
150. R.W. Evans and D.L. Manninen, Public Opinion Concerning Organ Donation, Procurement, and Distribution: Results of a National Probability Sample Survey (Seattle: Bauteile Human Affairs Research Centers, 1987): at 367.
151. Id.