Claire Colby, MJLST Staffer
In early January, surgeons at the University of Maryland Medical Center made history by successfully transplanting a genetically altered pig heart to a human recipient, David Bennett. The achievement represents a major milestone in transplantation. The demand for transplantable organs far outpaces the supply, and xenotransplantation–the implantation of non-human tissue into human recipients–could help bridge this gap. In the U.S. alone, more than 106,000 people are on the waiting list for transplants. Legal and ethical questions remain open about the appropriateness of implementing xenotransplants on a large scale.
The FDA approved the January transplant through an emergency authorization compassionate use pathway because Bennett likely would have died without this intervention. Larger clinical trials will be needed to generate enough data to show that xenotransplants are safe and effective. The FDA will require these trials to show xenotransplantations are non-inferior to human organ transplants. IRB requirements bar interventions where risk outweighs benefits for patients, but accurately predicting and measuring risk is difficult.
If xenotransplantation becomes standard clinical practice, animal rights proponents may balk at the idea of raising pigs for organs. Far before that point, pre-clinical trials will make heavy use of animal models. Institutional Animal Care and Use Committees (IACUCs) which oversee animal research in universities and medical entities apply a “much lower ethical standard” for animals than human research subjects. Bioethicists apply a “3R” framework for animal subjects research that stresses replacing animal models, reducing animal testing, and refining their use. Because of the inherent nature of xenotransplantation, applying this framework may be near impossible. Ongoing discussions are needed with relevant stakeholders.
If both human and animal organs are approved for widespread transplant, but human organs prove superior, new allocation policies are needed to determine who gets what. Organ allocation policy is currently dictated by the Organ Procurement and Transplantation Network (OPTN). As it stands, organ transplantation shows inequality across racial groups and financial status. New allocation policies for organs must not reinforce or worsen these disparities.
Like all medical interventions, patients must be able to provide informed consent for xenotransplantation. The recipient of the altered pig heart had previously been deemed ineligible for a human heart transplant because his heart failure was poorly managed. Reserving experimental interventions, like xenotransplantations, for the sickest patients raises serious ethical concerns. Are these desperate patients truly able to give meaningful consent? If xenotransplantation becomes a common practice, the traditional model of institutional review boards may need updating. Currently, individual institutions maintain their own IRBs. Xenotransplantation of altered animal organs may involve several sites: procurement of the organ, genetic editing, and transplantation may all take place in different locations. A central IRB for xenotransplantation could standardize and streamline this process.
In all, xenotransplantation represents an exciting new frontier in transplant medicine. Responsibly implementing this innovation will require foresight and parallel innovation in ethics and public policy.
