Faculty Bibliography

The standard treatment for end-stage organ failure is transplantation, but demand for organs has always vastly outstripped supply. Discussions are ongoing about the feasibility of addressing the organ shortage through measures like increasing organ donations, improving post-transplant outcomes, and xenotransplantation. This paper examines the rationale, risks, and costs of xenotransplantation, such as xenozoonoses, creating a new form of industrialized animal farming, abandoning animal ethics principles, and the opportunity costs of investing finite research dollars in xenotransplantation instead of investing in more viable strategies. Alternative strategies that can ethically and effectively address the demand for heart, kidney, and other transplants are recommended: Improving disease prevention and management to reduce demand for transplant organs, improving transplantation methods, and systemic changes to donor policies and organ recovery methods to increase overall supply. Upon careful exploration of the full landscape of organ transplantation, it is considered whether these alternative strategies that do not impose the definite harms and significant risks of xenotransplantation are the most ethical and effective means to increase life-saving options and improve clinical outcomes for patients in organ failure.

Use of normothermic regional perfusion (NRP) to enable organ reconditioning and assessment in donation after circulatory determination of death (DCD) is controversial. We conducted a scoping review of peer-reviewed articles, news media, legal literature, and professional society position statements addressing ethical and/or legal issues in use of NRP in controlled DCD from January 1, 2005 to January 5, 2024. Thematic analysis, assessing the four principles of bioethics (autonomy, beneficence, non-maleficence, and justice) and sub-themes identified within each, was conducted for the 112 publications meeting inclusion criteria. More than 30 publications addressed the topic in each of 2022 and 2023, versus ≤6 per year previously. Non-maleficence was the most frequently addressed bioethical principle (111/112 publications), and most varied, with 14 subthemes. Attitudes towards NRP differed by type of NRP: Of 72 publications discussing thoracoabdominal NRP, 22 (30.6%) were 'In Favor', 39 (54.2%) 'Neutral', and 11 (15.3%) 'Against'; of 44 discussing abdominal NRP, 23 (52.3%) were 'In Favor', 20 (45.5%) 'Neutral', and 1 (2.3%) 'Against'. Attitudes differed by authors' country, degree, and affiliation, and by clinical focus of the publishing journal. Overall, our review shows the ethical and legal issues raised by NRP remain unresolved, and debate centered on non-maleficence.

BACKGROUND:Cardiac allotransplantation is the optimal treatment for end-stage heart failure. However, organ supply remains the principal issue impacting patients. Pediatric patients present unique challenges resulting in long wait-list times and increased mortality. Donation after circulatory death with normothermic regional perfusion represents a method to increase the number of available organs in this population. METHODS:Multi-institutional expert consultation was sought to outline extant technical, ethical, and logistical issues with regard to normothermic regional perfusion cardiac donation techniques. Specific advantages in the pediatric population are highlighted, as well as technical considerations resulting in successful organ procurement. RESULTS:Utilization of donation after circulatory death organs following normothermic regional perfusion in the United States is increasing and offers advantages to the pediatric heart failure population. Ethical reservations both nationally and abroad persist, namely pertaining to cerebral blood flow. This has led to variation in perception and utilization of normothermic regional perfusion, contributing to a discrepancy between donor and recipient locations. Procurement techniques and variations are described, with introduction into program planning and protocol development. Training in technical aspects of the procedure is paramount for both the surgeon and support staff to construct a successful program, along with transparent protocols to mitigate ethical concerns. CONCLUSIONS:Normothermic regional perfusion is relevant following donation after cardiac death in the pediatric population. Ethical and technical challenges remain in concert with substantial domestic and international variation. Standardization of technique may serve to increase future use and increase the number of available hearts for transplant, reducing pediatric mortality.

Xenotransplantation (XTx) presents a potential clinical alternative to the shortage of human organs for transplantation. Before clinical trials occur in the United States, public assessments are crucial to understand potential barriers to acceptance. The purpose of this study was to explore barriers and identify characteristics associated with attitudes toward XTx. A survey assessing demographic characteristics and attitudes toward XTx was distributed to a nationally representative sample of adults aged ≥18 years in the United States. Regression analysis was employed to identify characteristics associated with attitudes toward XTx. Between May 25 and June 14, 2023, 5008 respondents completed the survey. Importantly, half of the respondents expressed low or no knowledge of either transplantation or XTx. Approximately 40% expressed discomfort with receiving a pig organ for themselves or a loved one. Despite a lack of xenotransplant outcome data, 36% were open to experimental XTx if they needed a transplant. However, 57% rated lack of current evidence of success or fear of complications as top concerns. Regression models consistently associated being younger, female, not needing an organ, or being a member of a racial minority group with lower acceptance. This survey is the largest to date exploring public attitudes toward XTx. Despite overall acceptance, concerns persist. Increasing public acceptance is key as the field advances.

This manuscript reports on a landmark symposium on the ethical, legal and technical challenges of xenotransplantation in the UK. King's College London, with endorsement from the British Transplantation Society (BTS), and the European Society of Organ Transplantation (ESOT), brought together a group of experts in xenotransplantation science, ethics and law to discuss the ethical, regulatory and technical challenges surrounding translating xenotransplantation into the clinical setting. The symposium was the first of its kind in the UK for 20 years. This paper summarises the content of the expert lectures showcasing the progress which has been made in xenotransplantation including-the history of xenotransplantation, advances in gene edited animals and progress towards clinical xenotransplantation. We then set out the ethical and legal issues still to be resolved. Finally, we report the themes of the roundtable discussion highlighting areas of consensus and controversy. While the detail of the legal discussion was directed towards the UK, the principles and summary reported here are intended to be applicable to any jurisdiction seeking to implement clinical xenotransplantation.

Research involving recently deceased humans that are physiologically maintained following declaration of death by neurologic criteria-or 'research involving the recently deceased'-can fill a translational research gap while reducing harm to animals and living human subjects. It also creates new challenges for honouring the donor's legacy, respecting the rights of donor loved ones, resource allocation and public health. As this research model gains traction, new empirical ethics questions must be answered to preserve public trust in all forms of tissue donation and in the practice of medicine while respecting the legacy of the deceased and the rights of donor loved ones. This article suggests several topics for immediate investigation to understand the attitudes and experiences of researchers, clinical collaborators, donor loved ones and the public to ensure research involving the recently deceased advances ethically.