Informing Ethical Translation of Xenotransplantation Clinical Trials

Xenotransplantation (XTx) is a novel intervention that involves transplanting organs, live cells, or tissues from nonhuman animals into humans. For years, XTx has been proposed as a strategy to alleviate the scarcity of organs for transplant patients, which is an ongoing public health problem that results in 8,000 people on the organ transplant waiting list dying each year. A first wave of experimental xenotransplants were performed in the U.S. from the 1960s to 1990s, involving a chimpanzee kidney, a baboon heart, and a baboon liver. Despite holding great promise, XTx experiments ended in the late 1990s due to a mix of scientific and ethical challenges. Today, XTx is undergoing a renaissance. Scientific advances in immunosuppression and genome editing techniques have minimized the risk of zoonotic disease transmission. The field is primed to translate findings to clinical care via clinical trials, starting first with transplanting pig kidneys into adult recipients. However, before clinical trials are conducted, XTx should address several key ethical, regulatory, and policy challenges. Existing guidelines for conducting clinical trials on XTx are over 20 years old and do not reflect changes in the science of XTx, changes in the organ transplant system, or up-to-date information about stakeholder perceptions. The overall objective of the proposed study is to develop ethics and policy recommendations and practical resource materials for patients, the transplant community, and IRBs to facilitate ethical translation of XTx clinical trials. Drawing on original in-depth interviews with relevant providers and regulators, and a survey of patients on kidney transplant waiting lists, our team of bioethicists and translational scientists working on XTx will: (1) identify and address gaps in and outdated aspects of existing guidelines and recommendations, regarding XTx clinical trials; (2) assess stakeholders’ perceptions and concerns about ethical, regulatory, and policy challenges for XTx clinical trials; and (3) develop and disseminate ethics and policy recommendations and practical resources on XTx clinical trials for patients, providers, IRBs, and the organizations that manage the U.S. organ transplant system. We will hold structured workshops with an Ethics & Policy Advisory Committee that includes experts in translational science and bioethics. The proposed study is highly innovative because it will generate missing and essential knowledge to facilitate ethical translational research on a novel biomedical intervention.