[IN-PERSON/LIVESTREAMED] Plenary Session: The New Age of Gene Edited Xenotransplantation

This plenary session will be held in-person, livestreamed for the Virtual Meeting, and recorded for on-demand access by attendees registered for PRIMR23 on this day.

The use of animal organs, or xenografts, has long been viewed as a promising solution to the insufficient supply of human organs to meet the needs of an ever-growing list of individuals who could benefit from lifesaving transplants. Historically, xenotransplantation has been unsuccessful due to transplant rejection from a cycle of immune reactions to the foreign graft. Advances in gene editing have now allowed genetic engineering of animals to improve human compatibility. Combined with advances in immunosuppressive therapy and techniques for prolonged xenograft survival time, we have now seen recent groundbreaking cases of successful xenotransplantation, such as the first genetically modified pig heart transplanted into a living human in 2022 at the University of Maryland. To further understand the mechanical, molecular, and immunologic aspects of xenotransplantation, several research centers are currently performing research involving heart, kidney, and liver xenotransplantation to recently deceased donors maintained on ventilator support. The advancing progress of gene edited xenotransplantation raises ethical and regulatory concerns of relevance to HRPP, IRB, and IACUC members. Considerations for human recipients include fair and just allocation of this research and ensuring appropriate informed consent for xenotransplantation research, including the risk/benefit conundrum presented by this cutting-edge research for "desperate" patients and the potential public perceptions related to the research and recipient. Considerations for animals include revisiting the ethical dilemmas of sacrificing animals for the benefit of extending human life, with the added challenge of using gene editing in large and highly sentient animal models (e.g., pigs and baboons), who are raised specifically as donors for human recipients and research. For research on recent human decedents, institutional questions arise with regard to what oversight of this work is needed and to which regulatory body it falls, along with ethical concerns related to next-of-kin consent, substituted judgment, and the questionable role for advanced directives. Further, we might ask if improvements in the United Network for Organ sharing would invalidate the ethical basis on which the need for xenotransplantation is grounded.