Faculty Bibliography

Religious viewpoints have been shown to influence the ways in which many persons approach medical decision-making and have been noted as a potential barrier to xenotransplantation acceptance. This study sought to explore how attitudes toward xenotransplantation differ among various religious beliefs. A national Likert-scale survey was conducted in 2023 with a representative sample in the United States. Religious belief was self-reported. Regression analysis was used to identify associations with religious belief and hesitations about xenotransplantation. Five thousand and eight individuals across the United States responded to the survey. The two biggest concerns about xenotransplantation across religious groups were the current lack of evidence about success and the risk of xenozoonosis. Although they still expressed concerns about certain issues, Catholic and Muslim respondents were most comfortable with xenotransplantation for all. On average, the risk of xenozoonosis was a concern among 25% across all religious beliefs (p <0.0001). Orthodox Christians expressed the highest rate of negative feelings toward the recent xenotransplantation experiments on brain dead and living individuals. Those who reported no religion were most likely to have negative feelings about killing pigs for human organ transplant (OR 1.26; 95% CI: 1.08-1.46). As xenotransplantation progresses from pre-clinical studies to clinical trials, and potentially to clinical therapy, hesitations among religious groups exist. Specific studies should be designed to investigate how religious viewpoints can affect xenotransplantation acceptance.

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.

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.

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.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including non-human primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potential novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions, and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.