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Existing Ethical Tensions in Xenotransplantation

Published online by Cambridge University Press:  06 June 2022

L. Syd M Johnson
L. Syd M Johnson*
Affiliation:
Center for Bioethics and Humanities, SUNY Upstate Medical University, Syracuse, New York, USA
*
Corresponding author. Email: johnsols@upstate.edu
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Abstract

The genetic modification of pigs as a source of transplantable organs is one of several possible solutions to the chronic organ shortage. This paper describes existing ethical tensions in xenotransplantation (XTx) that argue against pursuing it. Recommendations for lifelong infectious disease surveillance and notification of close contacts of recipients are in tension with the rights of human research subjects. Parental/guardian consent for pediatric xenograft recipients is in tension with a child’s right to an open future. Individual consent to transplant is in tension with public health threats that include zoonotic diseases. XTx amplifies concerns about justice in organ transplantation and could exacerbate existing inequities. The prevention of infectious disease in source animals is in tension with the best practices of animal care and animal welfare, requiring isolation, ethologically inappropriate housing, and invasive reproductive procedures that would severely impact the well-being of intelligent social creatures like pigs.

Keywords

xenotransplantationzoonotic diseaseCOVID-19research ethicsanimal well-being
Type
Research Article
Information
Cambridge Quarterly of Healthcare Ethics , Volume 31 , Issue 3 , July 2022 , pp. 355 - 367
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Notes

1. Ahmad, MU, Hanna, A, Mohamed, A-Z, Schlindwein, A, Pley, C, Bahner, I, et al. A systematic review of opt-out versus opt-in consent on deceased organ donation and transplantation (2006–2016). World Journal of Surgery 2019;43:3161–71CrossRefGoogle ScholarPubMed.

2. Hardy, JD, Chavez, CM, Kurrus, FD, Neely, W, Eraslan, S, Turner, MD, et al. Heart transplantation in man: Developmental studies and report of a case. JAMA 1964;188:1132–40CrossRefGoogle ScholarPubMed.

3. Barnard, C, Wolpowitz, A, Losman, J. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. South African Medical Journal 1977;52:1035–8Google ScholarPubMed.

4. Bailey, LL, Nehlsen-Cannarella, SL, Concepcion, W, Jolley, W, et al. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 1985;254:3321–9.CrossRefGoogle ScholarPubMed

5. Starzl, TE, Marchioro, , Peters, G, Kirkpatrick, CH, Wilson, WEC, Porter, KA, et al. Renal heterotransplantation from baboon to man: Experience with 6 cases. Transplantation 1964;2:752 CrossRefGoogle Scholar.

6. Starzl, TE, Fung, J, Tzakis, A, Todo, S, Demetris, AJ, Marino, IR, et al. Baboon-to-human liver transplantation. The Lancet 1993;341:65–71 CrossRefGoogle ScholarPubMed.

7. Rabin RC. In a first, surgeons attached a pig kidney to a human, and it worked. The New York Times; 2021 October 19.

8. Pentz, RD, Cohen, CB, Wicclair, M, DeVita, M, Flamm, AL, Youngner, SL, et al. Ethics guidelines for research with the recently dead. Nature Medicine 2005;11:1145–9Google ScholarPubMed.

9. Food and Drug Administration. Guidance for industry: Public health issues posed by the use of nonhuman primate xenografts in humans. Rockville, MD: U.S. Dept. of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research; 1999.

10. Cooper, DK, Gollackner, B and Sachs, DH. Will the pig solve the transplantation backlog? Annual Review Of Medicine 2002;53:133–47CrossRefGoogle ScholarPubMed.

11. Hammer, C. Zu den Möglichkeiten der Xenotransplantation. Bundesgesundheitsblatt—Gesundheitsforschung—Gesundheitsschutz 2002;45:801–6CrossRefGoogle Scholar.

12. Fishman, JA. Infectious disease risks in xenotransplantation. American Journal of Transplantation 2018;18:1857–64CrossRefGoogle ScholarPubMed.

13. Johnson LSM. Pigs as spare (human) parts. Impact Ethics. Halifax, Nova Scotia: Impact Ethics; 2015; available at https://impactethics.ca/2015/10/26/pigs-as-spare-human-parts/ (last accessed 29 October 2021).

14. Rollin, B. Ethics, science, and antimicrobial resistance. Journal of Agricultural and Environmental Ethics 2001;14:29–37 CrossRefGoogle Scholar.

15. See note 12, Fishman 2018, at 1857–64.

16. Niu, D, Wei, H-J, Lin, L, George, H, Wang, T, Lee, I-H, et al. Inactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9. Science 2017;357(6357):1303–7.CrossRefGoogle ScholarPubMed

17. Denner, J, Scobie, L and Schuurman, HJ. Is it currently possible to evaluate the risk posed by PERVs for clinical xenotransplantation? Xenotransplantation 2018;25:e12403 CrossRefGoogle ScholarPubMed.

18. See note 9, Food and Drug Administration 1999.

19. Nuffield Council on Bioethics. Animal-to-Human Transplants: The Ethics of Xenotransplantation. London: Nuffield Council on Bioethics; 1996.

20. Sykes, M, D’Apice, A, Sandrin, M. Position paper of the Ethics Committee of the International Xenotransplantation Association. Xenotransplantation 2003;10:194–203.CrossRefGoogle ScholarPubMed

21. Public Health Service. PHS Guideline on Infectious Disease Issues in Xenotransplantation. Rockville, MD: Food and Drug Administration; 2001.

22. Belmont Commission. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC: United States Department of Health Education, and Welfare; 1979.

23. World Medical Association. Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310:2191 CrossRefGoogle Scholar.

24. Council for International Organizations of Medical Sciences. International Guiding Principles for Biomedical Research Involving Animals. Geneva: Council for International Organizations of Medical Sciences; 2012.

25. Health and Human Services. 45CFR46 Protection of Human Subjects (The Common Rule). Washington DC: United States Government; 2009.

26. See note 20, Sykes et al. 2003, at 194–203.

27. Hurst, DJ, Padilla, LA, Walters, W, Hunter, J, Cooper, DKC, Eckhoff, DM, et al. Paediatric xenotransplantation clinical trials and the right to withdraw. Journal of Medical Ethics 2020;46:311–5CrossRefGoogle ScholarPubMed.

28. See note 12, Fishman 2018, at 1857–64

29. Organ Procurement and Transplantation Network. Guidance for Donor and Recipient Information Sharing; 2012; available at https://optn.transplant.hrsa.gov/resources/guidance/guidance-for-donor-and-recipient-information-sharing/ (last accessed 27 Oct 2021).

30. See note 26, Hurst et al. 2020, at 311–5.

31. Rousseau, J-J. On the social contract. In: Cress, DA, ed. The Basic Politic Writings. Indianapolis, IN: Hackett; 2011:155–252 Google Scholar.

32. See note 9, Food and Drug Administration 1999.

33. Opriessnig, T, Huang, YW. Third update on possible animal sources for human COVID-19. Xenotransplantation 2021;28(1):e12671 CrossRefGoogle ScholarPubMed.

34. Centers for Disease Control and Prevention. Animals and COVID-19, 2021; available at https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html (last accessed 22 Oct 2021).

35. Chandler JC, Bevins SN, Ellis JW, Linder T, Tell RM, Jenkins-Moore M, et al. SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus). bioRxiv 2021; available at https://www.biorxiv.org/content/10.1101/2021.07.29.454326v1.full (last accessed 29 Oct 2021).

36. See note 33, Opriessnig, Huang 2021, at e12671.

37. Bermejo, M, Rodríguez-Teijeiro, JD, Illera, G, Barroso, A, Vilà, C, Walsh, PD. Ebola outbreak killed 5000 gorillas. Science 2006;314:1564.CrossRefGoogle ScholarPubMed

38. Centers for Disease Control and Prevention. Hendra Virus Disease (HeV); 2021; available at https://www.cdc.gov/vhf/hendra/ (last accessed 22 Oct 2021).

39. Chua, K, Bellini, W, Rota, P, Harcourt, BH, Tamin, A, Lam, SK, et al. Nipah virus: a recently emergent deadly paramyxovirus. Science 2000;288:1432–5.CrossRefGoogle ScholarPubMed

40. Sparrow, R. Xenotransplantation, consent and international justice. Developing World Bioethics 2009;9:119–27CrossRefGoogle ScholarPubMed.

41. See note 40, Sparrow 2009, at 119–27.

42. See note 19, Nuffield Council on Bioethics 1996.

43. Gonzalez, J, Garijo, I, Sanchez, A. Organ trafficking and migration: A bibliometric analysis of an untold story. International Journal of Environmental Research and Public Health 2020;17:3204. doi:10.3390/ijerph17093204.CrossRefGoogle ScholarPubMed

44. See note 20, Sykes et al. 2003, at 194–203

45. See note 19, Nuffield Council on Bioethics 1996.

46. See note 10, Cooper et al. 2002, at 133–47.

47. See note 20, Sykes et al. 2003, at 194–203.

48. McGlone, JJ. Comparison of sow welfare in the Swedish deep-bedded system and the US crated-sow system. Journal of the American Veterinary Medical Association 2006;229:1377–80.CrossRefGoogle ScholarPubMed

49. Velarde, A, Dalmau, A. Slaughter of pigs. In: Špinka, M, ed. Advances in Pig Welfare. Sawston: Woodhead Publishing; 2018:295–322.CrossRefGoogle Scholar

50. Pedersen, LJ. Overview of commercial pig production systems and their main welfare challenges. In: Špinka, M, ed. Advances in Pig Welfare. Sawston: Woodhead Publishing; 2018:3–25.CrossRefGoogle Scholar

51. Hryhorowicz, M, Lipiński, D, Hryhorowicz, S, Nowak-Terpiłowska, A, Ryczek, N, Zeyland, J. Application of genetically engineered pigs in biomedical research. Genes 2020;11:670.CrossRefGoogle ScholarPubMed

52. See note 21, Public Health Service 2001.

53. Kamm, FM. Failures of just war theory: Terror, harm, and justice. Ethics 2004;114:650–92CrossRefGoogle Scholar.

54. International Committee of the Red Cross. Geneva Convention Relative to the Treatment of Prisoners of War. (Third Geneva Convention), Article 13; 1949.

55. Nuremberg Tribunals. The Nuremberg Code; 1949.

56. Benz-Schwarzburg, J, Ferrari, A. Super-muscly pigs: Trading ethics for efficiency. Issues in Science and Technology 2016;32:29 Google Scholar.

57. Norcross, A. Puppies, pigs, and people: Eating meat and marginal cases. Philosophical Perspectives 2004;18:229–45CrossRefGoogle Scholar.

58. Reichart, B, Längin, M, Radan, J, Mokelke, M, Buttgereit, I, Ying, J, et al. Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation? The Journal of Heart and Lung Transplantation 2020;39:751–7CrossRefGoogle ScholarPubMed.

59. Pound, P, Nicol, CJ. Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions. PloS One 2018;13(3):e0193758CrossRefGoogle ScholarPubMed.

60. Russell, WMS, Burch, RL. The Principles of Humane Experimental Technique. London: Methuen & Co; 1959 Google Scholar.

61. Johnson, LSM. The road not mapped: The neuroethics roadmap on research with nonhuman primates. AJOB Neuroscience 2020;11:176–83CrossRefGoogle Scholar.

62. See note 19, Nuffield Council on Bioethics 1996.

63. Marino, L, Colvin, CM. Thinking pigs: A comparative review of cognition, emotion, and personality in Sus domesticus. International Journal of Comparative Psychology 2015;28(1): 1–27 CrossRefGoogle Scholar.

64. See note 19, Nuffield Council on Bioethics 1996.

65. See note 21, Public Health Service 2001.

66. Horback, K. Nosing around: Play in pigs. Animal Behavior and Cognition 2014;2:186–96.CrossRefGoogle Scholar

67. Bekoff, M. Animal emotions: Exploring passionate natures: Current interdisciplinary research provides compelling evidence that many animals experience such emotions as joy, fear, love, despair, and grief—We are not alone. BioScience 2000;50:861–70.CrossRefGoogle Scholar

68. De Waal F. Mama’s Last Hug: Animal Emotions and What They Tell Us about Ourselves. New York: WW Norton & Company; 2019.

69. See note 19, Nuffield Council on Bioethics 1996.

70. See note 59, Pound, Nicol 2018, at e0193758.

71. Pound, P, Ebrahim, S, Sandercock, P, Bracken, MB, Roberts, I, Reviewing Animal Trials Systematically (RATS) Group. Where is the evidence that animal research benefits humans? British Medical Journal 2004;328:514–7CrossRefGoogle ScholarPubMed.

72. Wu, Y, Ravnic, DJ, Ozbolat, IT. Intraoperative bioprinting: Repairing tissues and organs in a surgical setting. Trends in Biotechnology 2020;38:594–605 CrossRefGoogle Scholar.

73. Vijayavenkataraman, S, Yan, W-C, Lu, WF, Wang, C-H, Fuh, J. 3D bioprinting of tissues and organs for regenerative medicine. Advanced Drug Delivery Reviews 2018;132:296–332.CrossRefGoogle ScholarPubMed

74. Willemse, J, Lieshout, R, van der Laan, LJW, Verstegen, M. From organoids to organs: Bioengineering liver grafts from hepatic stem cells and matrix. Best Practice & Research Clinical Gastroenterology 2017;31:151–9CrossRefGoogle ScholarPubMed.

75. Hariharan K, Kurtz A, Schmidt-Ott KM. Assembling kidney tissues from cells: The long road from organoids to organs. Frontiers in Cell and Developmental Biology 2015;3: 1-9.

76. Patel, MS, Zatarain, J, De La Cruz, S, Sally, MB, Ewing, T, Crutchfield, M, et al. The impact of meeting donor management goals on the number of organs transplanted per expanded criteria donor: A prospective study from the UNOS Region 5 Donor Management Goals Workgroup. JAMA Surgery 2014;149:969–75CrossRefGoogle ScholarPubMed.

77. See note 13, Johnson 2015.

78. See note 1, Ahmad et al. 2019, at 3161–71.

79. Siminoff, LA, Traino, HM, Genderson, MW. Communicating effectively about organ donation: A randomized trial of a behavioral communication intervention to improve discussions about donation. Transplant Direct 2015;1:e5CrossRefGoogle ScholarPubMed.