Clinical Trials of Xenotransplantation and Brain-Computer Interfaces: Commonalities and Cautions in Ethics Policy
Main Article Content
Abstract
The quest of medicine to restore function to diseased or damaged human organs has journeyed from human-to-human transplantation to animal-to-human xenotransplantation and now to brain-computer interface implantation. Despite the disparate nature of the latter two technologies, similar ethical questions arise. We explore the history and ethics of xenotransplantation, some of the current technologies supporting the procedure, and current policy guidelines pertaining to clinical xenotransplantation. We then examine the emerging field of brain-computer interfaces. We highlight common ethical issues, including the vulnerability of potential subjects, infection risks, ownership considerations, explanation mandates, and the uncertainty of financial underwriting of technology. We discuss the concept of Ulysses contracts as a method of resolving the conflict between the interests of clinical trial sponsors and technology companies and the subjects and recipients of the permanently implanted technology. Finally, we propose considerations for the explicit delineation in clinical trials of permanently implanted technologies including xenotransplantation and brain-computer interface technologies.
Article Details
How to Cite
SPILLMAN, Monique A.; SADE, Robert M..
Clinical Trials of Xenotransplantation and Brain-Computer Interfaces: Commonalities and Cautions in Ethics Policy.
Medical Research Archives, [S.l.], v. 13, n. 4, apr. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6445>. Date accessed: 15 may 2025.
doi: https://doi.org/10.18103/mra.v13i4.6445.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Blackstock MJ, Ray DC. Organ donation after circulatory death: an update. Eur J Emerg Med. Oct 2014;21(5):324-9. doi:10.1097/MEJ.0000000000000082
3. Harrison JH, Merrill JP, Murray JE. Renal homotransplantation in identical twins. Surg Forum. 1956;6:432-6.
4. Furukawa H, Todo S. Evolution of immunosuppression in liver transplantation: contribution of cyclosporine. Transplant Proc. Mar 2004;36(2 Suppl):274S-284S. doi:10.1016/j.transproceed.2004.01.023
5. Pasrija C, Tipograf Y, Shah AS, Trahanas JM. Normothermic regional perfusion for donation after circulatory death donors. Curr Opin Organ Transplant. Apr 1 2023;28(2):71-75. doi:10.1097/MOT.0000 000000001038
6. Entwistle JW, Drake DH, Fenton KN, Smith MA, Sade RM, Cardiothoracic Ethics F. Normothermic Regional Perfusion: Ethical Issues in Thoracic Organ Donation. Ann Thorac Surg. Jul 2022;114(1):44-51. doi:10.1016/j.athoracsur.2022.01.058
7. Sade RM, Carpenter AJ, D'Amico TA, et al. Unethical Studies on Transplantation in Cardiothoracic Surgery Journals. Ann Thorac Surg. Dec 2021;112(6):1746-1752. doi:10.1016/j.athoracsur.2021.07.070
8. Chen S, Sade RM, Entwistle JW. Organ Donation by the Imminently Dead: Addressing the Organ Shortage and the Dead Donor Rule. J Med Philos. Sep 3 2024;49(5):458-469. doi:10.1093/jmp/jhae028
9. Shah SK, Truog RD, Miller FG. Death and legal fictions. J Med Ethics. Dec 2011;37(12):719-22. doi:10.1136/jme.2011.045385
10. Deschamps JY, Roux FA, Sai P, Gouin E. History of xenotransplantation. Xenotransplantation. Mar 2005;12(2):91-109. doi:10.1111/j.1399-3089.2004.00199.x
11. Guideline on Infectious Disease Issues in Xenotransplantation (United States Public Health Service) (2001).
12. Malouin R. Surgeons' quest for life: the history and the future of xenotransplantation. Perspect Biol Med. Spring 1994;37(3):416-28. doi:10.1353/pbm.1994.0001
13. Good AH, Cooper DK, Malcolm AJ, et al. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant Proc. Apr 1992;24(2):559-62.
14. Sykes M. Developing pig-to-human organ transplants. Science. Oct 14 2022;378(6616):135-136. doi:10.1126/science.abo7935
15. AP. Alabama woman becomes longest living recipient of pig organ transplant. NBC News. January 25, 2025. https://www.nbcnews.com/science/science-news/alabama-woman-becomes-longest-living-recipient-pig-organ-transplant-rcna189303
16. Gene-edited pig kidney gives living donor new lease on life. December 17, 2024, 2024. https://nyulangone.org/news/gene-edited-pig-kidney-gives-living-donor-new-lease-life
17. Zhao W. Pig organs in humans: a forum on xenotransplantation. Natl Sci Rev. Oct 2024;11(10):nwae208. doi:10.1093/nsr/nwae208
18. Cooper DKC, Pierson RN, 3rd, Hering BJ, et al. Regulation of Clinical Xenotransplantation-Time for a Reappraisal. Transplantation. Aug 2017;101(8): 1766-1769. doi:10.1097/TP.0000000000001683
19. Schwarz NA. Farm Animal to Animal Farm: The Legal Implications to Human-Pig Chimeras and Xenotransplantation. Health Law Outlook. 2024;14(1):4.
20. Wang J, Xie W, Li N, et al. Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation. Cell Stem Cell. Sep 7 2023;30(9):1235-1245 e6. doi:10.1016/j.stem.2023.08.003
21. Reardon S. US agency to lift ban on funding human-animal hybrids. Nature. Aug 11 2016;536(7615): 135. doi:10.1038/nature.2016.20379
22. Koplin JJ, Savulescu J. Time to rethink the law on part-human chimeras. J Law Biosci. Oct 2019;6(1):37-50. doi:10.1093/jlb/lsz005
23. Goerlich CE, Chan JL, Mohiuddin MM. Regulatory barriers to xenotransplantation. Curr Opin Organ Transplant. Oct 2019;24(5):522-526. doi:10.1097/MOT.0000000000000678
24. Rabin RC. F.D.A. Approves Studies of Pig Organ Transplants for Kidney Patients. New York Times. 02/23/25, 2025. https://www.nytimes.com/2025/02/03/health/pig-kidney-transplants-clinical-trials.html
25. Entwistle JW, Sade RM, Drake DH. Clinical xenotransplantation seems close: Ethical issues persist. Artif Organs. Jun 2022;46(6):987-994. doi:10.1111/aor.14255
26. Source animal, product, preclinical, and clinical issues concerning the use of xenotransplantation products in humans: Guidance for industry (Food and Drug Administration) (2016).
27. Spillman MA, Sade RM. Clinical trials of xenotransplantation: waiver of the right to withdraw from a clinical trial should be required. J Law Med Ethics. Summer 2007;35(2):265-72. doi:10.1111/j.1748-720X.2007.00135.x
28. Nuremberg Military T. The Nuremberg Code. JAMA. Nov 27 1996;276(20):1691.
29. Padilla LA, Hurst D, Maxwell K, et al. Informed Consent for Potential Recipients of Pig Kidney Xenotransplantation in the United States. Transplantation. Sep 1 2022;106(9):1754-1762. doi:10.1097/TP.0000000000004144
30. Brawley OW. The study of untreated syphilis in the negro male. Int J Radiat Oncol Biol Phys. Jan 1 1998;40(1):5-8. doi:10.1016/s0360-3016(97)00 835-3
31. Drew L. The brain-reading devices helping paralysed people to move, talk and touch. Nature. Apr 2022;604(7906):416-419. doi:10.1038/d41586-022-01047-w
32. Silva AB, Liu JR, Metzger SL, et al. A bilingual speech neuroprosthesis driven by cortical articulatory representations shared between languages. Nat Biomed Eng. Aug 2024;8(8):977-991. doi:10.1038/ s41551-024-01207-5
33. Li Q, Ding D, Conti M. Brain-computer interface applications: Security and privacy challenges. 2015:
34. Patrick-Krueger KM, Burkhart I, Contreras-Vidal JL. The state of clinical trials of implantable brain-computer interfaces. Nature Reviews Bioengineering. 2025;3:50-67.
35. Gordon EC, Seth AK. Ethical considerations for the use of brain-computer interfaces for cognitive enhancement. PLoS Biol. Oct 2024;22(10): e3002899. doi:10.1371/journal.pbio.3002899
36. Neuralink. Patient Registry. Accessed 021825, 2025. https://neuralink.com/
37. Burwell S, Sample M, Racine E. Ethical aspects of brain computer interfaces: a scoping review. BMC Med Ethics. Nov 9 2017;18(1):60. doi:10.1186/s12910-017-0220-y
38. Ienca M, Haselager P. Hacking the brain: brain-computer interfacing technology and the ethics of neurosecurity. Ethics Inf Technol. 2016;18:117-129.
39. Davidoff EJ. Agency and Accountability: Ethical Considerations for Brain-Computer Interfaces. Rutgers J Bioeth. Spring 2020;11:9-20.
40. Garbe T. The Presentation of Brain-computer Interfaces As Autonomy-enhancing Therapy Products: A Mechanism to Promote Societal Acceptance of Implant Technologies. NanoEthics. 2024;18(3):13.
41. Clarke A. 2001 A space odyssey. 1st ed. New American Library (US); 1968.
42. Dynamics D. DCD Zero Downtime. Episode 18-The origin of the Internet of Things with Peter Lewis. October 13,2022. https://www.datacenterdynamics.com/en/podcasts/zero-downtime/episode-18-the-origin-of-the-internet-of-things-with-peter-lewis/
43. Tubig P, Gilbert F. "The trauma of losing your own identity again: the ethics of explantation of brain-comptuer interfaces. In: Dubljevic V, Coin A, eds. Policy, Identity, and Neurotechnology, Advances in Neuroethics. Springer Nature; 2023:27-41.
44. Cassinadri G, Ienca M. Non-voluntary BCI explantation: assessing possible neurorights violations in light of contrasting mental ontologies. J Med Ethics. Aug 8 2024;doi:10.1136/jme-2023-109830
45. Walker T. Ulysses contracts in medicine. Law and Philosophy. 2012;31:77-98.
46. Bublitz JC, Gilbert F. Legal aspects of unwanted device explantations: A comment on the patient R case. Brain Stimul. Sep-Oct 2023;16(5):1425-1429. doi:10.1016/j.brs.2023.09.008
47. Dictionary Ws. Privacy. Accessed 021825, 2025. https://www.merriam-webster.com/dictionary/privacy
48. Brain Computer Interfaces: Applications, Challenges and Policy Options (Government Accountability Office) (2024).
49. Kurth HA. Colorado Amends Privacy Act with H.B. 1058, Adding New Protections for Biological and Neural Data. Privacy and Information Security Law Blog. 2025;XV(49)
50. Marks P, Solomon S. Clarifying US regulations on xenotransplantation. Nat Biotechnol. Dec 2021;39(12):1500-1501. doi:10.1038/s41587-021-01144-7