Many Ethical Questions Still Unresolved with Xenotransplantation

By Stacey Kusterbeck

Although human clinical trials in xenotransplantation (cross-species organ transplantation) have not yet taken place, scientific advancements continue to bring this possibility closer to reality.¹ Yet many important ethical issues still are unresolved.

“There is a need to understand how best to proceed with a potentially revolutionary advancement in transplantation science that comes with serious risks,” according to Brendan Parent, JD, director of Transplant Ethics and Policy Research at NYU Grossman School of Medicine. A group of experts, including Parent, recently convened to explore ethical and legal issues involved with xenotransplantation and attempted to delineate areas of consensus and areas where there is still controversy.² “Some groups think there is consensus on some of these issues. But whose consensus should matter for deciding whether or how to proceed?” asks Parent. Below are some central unresolved ethical questions:

• Who should be the first trial participants? For whom can the risks be justified?

• What will be the definition of success for the first clinical trials?

• How do researchers get informed consent from those seeking to participate in the first trials?

• How can researchers justify the risks of xenozoonotic viral transmission to the recipient, their contacts, and the community? Who gets to decide when these risks are justified?

• If xenotransplantation moves beyond clinical trials, how do clinicians decide how to allocate xeno organs vs. human organs?

• Is it possible to ethically justify raising and slaughtering cognitively complex nonhuman animals with moral interests for the sake of saving human lives or to justify killing thousands of pigs and baboons during preclinical research? “Instead of pointing to the meat industry to justify xenotransplantation, perhaps we should use xenotransplantation to question the meat industry,” offers Parent.

It is important for ethicists to be involved for each complex xenotransplant decision, asserts Parent. Ethicists can help in these specific ways, Parent suggests:

• Design informed consent documents and processes for potential recipients.

“Ethicists can do their own empirical research, speaking with transplant candidates, their families, and the public in order to make recommendations to, and collaborate with, researchers in designing the actual informed consent process,” advises Parent.

• Ensure that each candidate has a patient advocate (a social worker, chaplain, ethicist, or nurse unaffiliated with the research team) helping them make decisions about participation.

• Help define the criteria that are considered by institutional review boards (IRBs) and regulatory bodies when researchers seek xenotransplant trial approval.

“There should be significant community outreach and education to ensure that the public understands and accepts the risks,” adds Parent.

Daniel J. Hurst, PhD, ThM, MSc, sees these as pressing ethical issues with xenotransplantation:

• patient selection criteria for expanded access and/or clinical trials;

• how to appropriately protect the xenograft recipient and bystanders from xenozoonoses;

• the need for additional public viewpoint studies.³

“Ethicists at centers preparing for xenotransplantation should undoubtedly be involved,” urges Hurst, director of medical professionalism, ethics, & humanities at Rowan University School of Osteopathic Medicine in Stratford, NJ.

Clinical trial applications of investigational new devices (which is how the U.S. Food and Drug Administration [FDA] classifies xenotransplantation) need to be approved by the FDA and, also, by the IRB at the local level. “IRBs must ensure they have the expertise to handle such studies and are knowledgeable about the risk-benefit profile,” cautions Hurst. Centers also need to give thoughtful consideration to the informed consent process. The informed consent process will need to make clear any post-transplant monitoring requirements for infectious disease, which is a contested area in xenotransplantation.⁴

“Ethicists can help xenotransplantation researchers think through these issues and potential courses of action to address each,” asserts Hurst.

REFERENCES

1. Jones-Carr ME, Fatima H, Kumar V, et al. C5 inhibition with eculizumab prevents thrombotic microangiopathy in a case series of pig-to-human kidney xenotransplantation. J Clin Invest 2024 Jan 25:e175996. doi: 10.1172/JCI175996. [Online ahead of print.]
2. Thom R, Ayares D, Cooper DKC, et al. Update on the ethical, legal and technical challenges of translating xenotransplantation. J Med Ethics 2023 Nov 10:jme-2023-109298. doi: 10.1136/jme-2023-109298. [Online ahead of print.]
3. Hurst DJ, Cooper DKC. Pressing ethical issues relating to clinical pig organ transplantation studies. Xenotransplantation [In press.]
4. Padilla LA, Hurst D, Maxwell K, et al. Informed consent for potential recipients of pig kidney xenotransplantation in the United States. Transplantation 2022;106:1754-1762.