Public Attitudes to Xenotransplantation: A National Survey in the United States.

PURPOSE: Xenotransplantation 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 xenotransplantation. METHODS: A survey assessing demographic characteristics and attitudes toward xenotransplantation was distributed to a nationally representative sample of adults ≥ 18 years old in the United States. Regression analysis was employed to identify characteristics associated with attitudes toward xenotransplantation. FINDINGS: Between May 25 and June 14, 2023, 5008 respondents completed the survey. Importantly, half of respondents expressed low or no knowledge of either transplantation or xenotransplantation. 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 xenotransplantation if they needed a transplant. However, 57% rated lack of current evidence of success or fear complications as top concerns. Regression models consistently associated being younger, female, not needing an organ, or being member of a racially minority group with lower acceptance. CONCLUSION: This survey is the largest to date exploring public attitudes toward xenotransplantation. Despite overall acceptance, concerns persist. Increasing public acceptance is key as the field progresses advances.

Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

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 of 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 nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the 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 potentially 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.

Pressing ethical issues relating to clinical pig organ transplantation studies.

Clinical pig heart transplant experiments have been undertaken, and further clinical experiments and/or clinical trials of gene-edited pig organ xenotransplantation are anticipated. The ethical issues relating to xenotransplantation have been discussed for decades but with little resolution. Consideration of certain ethical issues is more urgent than others, and the need to attain consensus is important. These issues include: (i) patient selection criteria for expanded access and/or clinical trials; (ii) appropriate protection of the patient from xenozoonoses, that is, infections caused by pig microorganisms transferred with the organ graft, (iii) minimization of the risk of a xenozoonosis to bystanders, and (iv) the need for additional public perception studies. We discuss why it is important and urgent to achieve consensus on these ethical issues prior to carrying out further expanded access experiments or initiating formal clinical trials. The ways forward on each issue are proposed.

Close contacts of xenograft recipients: Ethical considerations due to risk of xenozoonosis.

With decades of pre-clinical studies culminating in the recent clinical application of xenotransplantation, it would appear timely to provide recommendations for operationalizing oversight of xenotransplantation clinical trials. Ethical issues with clinical xenotransplantation have been described for decades, largely centering on animal welfare, the risks posed to the recipient, and public health risks posed by potential spread of xenozoonosis. Much less attention has been given to considerations relating to potentially elevated risks faced by those who may care for or otherwise have close contact with xenograft recipients. This paper examines the ethical and logistical issues raised by the potential exposure to xenozoonotic disease faced by close contacts of xenotransplant recipients-defined herein as including but not limited to caregivers, household contacts, and sexual partners-which warrants special attention given their increased risk of exposure to infection compared to the general public. We discuss implications of assent or consent by these close contacts to potentially undergo, along with the recipient, procedures for infection screening and possible quarantine. We then propose several options and recommendations for operationalizing oversight of xenotransplantation clinical trials that could account for and address close contacts' education on and agency regarding the risk of xenozoonosis.

Genetic disenhancement and xenotransplantation: diminishing pigs' capacity to experience suffering through genetic engineering.

One objection to xenotransplantation is that it will require the large-scale breeding, raising and killing of genetically modified pigs. The pigs will need to be raised in designated pathogen-free facilities and undergo a range of medical tests before having their organs removed and being euthanised. As a result, they will have significantly shortened life expectancies, will experience pain and suffering and be subject to a degree of social and environmental deprivation. To minimise the impact of these factors, we propose the following option for consideration-ethically defensible xenotransplantation should entail the use of genetic disenhancement if it becomes possible to do so and if that pain and suffering cannot be eliminated by other means. Despite not being a morally ideal 'solution', it is morally better to prevent unavoidable pain until a viable non-animal alternative becomes available.

Xenograft recipients and the right to withdraw from a clinical trial.

Preclinical xenotransplantation research using genetically engineered pigs has begun to show some promising results and could one day offer a scalable means of addressing organ shortage. While it is a fundamental tenet of ethical human subject research that participants have a right to withdraw from research once enrolled, several scholars have argued that the right to withdraw from xenotransplant research should be suspended because of the public health risks posed by xenozoonotic transmission. Here, we present a comprehensive critical evaluation of the claim that xenotransplant recipients should be required to waive their right to withdraw from lifelong biosurveillance. We conclude that if xenotransplantation requires participants to waive their right to withdraw, then clinical trials may not be justifiable, given the ethical and legal obstacles involved with doing so. Consequently, if clinical trials are permitted with a right to withdraw, then they may pose a significant public health risk.

Out-of-Hospital Birth in Medical Education: A Thematic Analysis of Question Banks for Medical Licensing Examinations in the United States.

OBJECTIVES: This study assessed the content of US Medical Licensing Examination question banks with regard to out-of-hospital births and whether the questions aligned with current evidence. METHODS: Three question banks were searched for key words regarding out-of-hospital births. A thematic analysis was then utilized to analyze the results. RESULTS: Forty-seven questions were identified, and of these, 55% indicated a lack of inadequate, limited, or irregular prenatal care in the question stem. CONCLUSIONS: Systematic studies comparing prenatal care in out-of-hospital births versus hospital births are nonexistent, leading to the potential for bias and adverse outcomes. Adjustments to question stems that accurately portray current evidence are recommended.

Xenotransplantation: A historical-ethical account of viewpoints.

Formal clinical trials of pig-to-human organ transplant-known asxenotransplantation-may begin this decade, with the first trials likely to consist of either adult renal transplants or pediatric cardiac transplant patients. Xenotransplantation as a systematic scientific study only reaches back to the latter half of the 20th century, with episodic xenotransplantation events occurring prior to that. As the science of xenotransplantation has progressed in the 20th and 21st centuries, the public's knowledge of the potential therapy has also increased. With this, there have been shifting ethical stances toward xenotransplantation in key areas, such as religious and public viewpoints towards xenotransplantation, animal rights, and public health concerns. This review provides a historical-ethical account of xenotransplantation and details if or how viewpoints have shifted over time.

In defense of xenotransplantation research: Because of, not in spite of, animal welfare concerns.

It is envisioned that one day xenotransplantation will bring about a future where transplantable organs can be safely and efficiently grown in transgenic pigs to help meet the global organ shortage. While recent advances have brought this future closer, worries remain about whether it will be beneficial overall. The unique challenges and risks posed to humans that arise from transplanting across the species barrier, in addition to the costs borne by non-human animals, has led some to question the value of xenotransplantation altogether. In response, we defend the value of xenotransplantation research, because it can satisfy stringent welfare conditions on the permissibility of animal research and use. Along the way, we respond to the alleged concerns, and conclude that they do not currently warrant a cessation or a curtailing of xenotransplantation research.

Religion/Spirituality Curriculum in US Osteopathic Medical Schools: A Survey.

OBJECTIVE: Several articles have been published on the relationship between religion, spirituality, and health during the past 2 decades. Corresponding to this, professional medical organizations such as the Association of American Medical Colleges and the National Board of Osteopathic Medical Examiners have created competencies for medical students that include being able to understand how a patient's religious/spiritual beliefs may affect their health. It is not, however, certain how and to what extent medical schools implement religion/spirituality in medicine training into their curriculum. Our objective in this study was to quantify and assess the implementation of religion/spirituality in medicine curricula at US osteopathic medical schools. METHODS: In early 2021, an electronic survey was sent to individuals in curriculum positions at all US osteopathic medical school main and branch locations. The survey consisted of questions regarding the presence or absence of curriculum on religion/spirituality in medicine at their school, and, if it was present, what it consisted of. RESULTS: Ten institutions responded to the survey, with the majority (80%) stating they did not have religion/spirituality curriculum at their institution. CONCLUSIONS: Based on the current evidence, there may be a downward trend in osteopathic medical schools providing formal education on religion/spirituality in medicine.

Mathieu Jaboulay's (1860-1913) contribution to xenotransplantation.

Mathieu Jaboulay (1860-1913) was a professor of clinical surgery in Lyon, France who is best known for his development of vascular anastomosis and for conducting the first reported renal xenotransplantation experiments on humans, using pig and goat kidneys to treat end-stage renal failure in 1906. His insights and pioneering techniques contributed significantly to allotransplantation and contemporary attempts at xenotransplantation. He is also credited with inventing several surgical instruments and novel surgical techniques that continue to influence vascular, general, and urological surgery to this day. However, this article will focus specifically on his notable contributions to xenotransplantation research and surgery.

Scientific and psychosocial ethical considerations for initial clinical trials of kidney xenotransplantation.

The initial clinical trials of pig solid organ xenotransplantation (XTx) are drawing closer and could begin in the coming years. The first clinical trials may aim to transplant genetically-modified pig kidneys into adult humans. The impetus for beginning these first-in-human trials is the severe lack of deceased donor kidneys for transplantation and the number of patients with end-stage renal disease currently on transplant waitlists, which in the USA approaches 100 000. The majority of patients on the kidney transplant waitlist receive continuous renal replacement therapy. In the United States, for patients on the kidney waitlist, the median wait-time to receive a deceased human donor organ is approximately 4.5 years for patients aged 45-74, with a 5-year mortality (or removal from the waitlist because of deteriorating health) of approximately 40%. XTx has the potential to reduce the kidney waitlist morbidity and mortality while improving quality of life. By focusing on scientific and psychosocial criteria, we present ethical considerations of certain inclusion and exclusion criteria for these first-in-human clinical trials that we suggest have not yet been fully explored.

The attitudes of religious group leaders towards xenotransplantation: A focus group study.

Clinical trials of xenotransplantation (XTx) may start in coming years. Religious views have been mentioned as possible barriers to XTx acceptance. While there have been reports on perspectives of theologians in regard to XTx, no report has studied the perspectives of community religious leaders. A focus group was conducted with a sample of members of the following faith groups: Islam, Catholicism, and Protestantism. Qualitative content analysis was performed to identify interpretive themes. Four themes emerged. Participants were receptive to the idea of XTx and expressed no religious barriers to accepting a pig xenograft as a lifesaving therapy but did express certain concerns. Religious leaders accept the idea of XTx and do not see it as contradictory to their beliefs. However, some concerns were raised. Future studies addressing these concerns and exploring the potential role of religious leaders in educating the community on XTx are needed.

Organ transplant and Covid-19 vaccination: Considering the ethics of denying transplant to unvaccinated patients.

Recently, a number of organ transplant centers in the United States have proposed to only allow patients who have received the Covid-19 vaccination to be active on their transplant waiting list. This raises numerous ethical issues. This analysis utilizes current empirical data and the guidelines on the ethics of organ allocation published by the Organ Procurement and Transplant Network to guide our ethical reasoning. We conclude that it would be permissible to mandate Covid-19 vaccination as a condition of being listed for an organ transplant at a transplant center and offer recommendations for how to do so.

Factors influencing attitudes toward xenotransplantation clinical trials: A report of focus group studies.

BACKGROUND: Clinical trials of xenotransplantation (XTx, ie, cross-species transplantation, specifically the transplantation of genetically engineered pig organs into human recipients) are due to start within a few years. METHODS: Five focus groups were conducted in April-May 2019, among local religious leaders (N = 10), organ procurement staff/administrators (N = 5), patients and parents of patients who may need an organ transplant or are transplant recipients (N = 9), and local businesspersons in the community (N = 3). Groups were audio-recorded, transcribed, and analyzed with NVivo software to identify themes of participants' thoughts to XTx. RESULTS: An overall Cohen's kappa statistic of 0.71 was established. In general, there was wide agreement among participants that XTx is an exciting and acceptable option to explore as an organ alternative. Concerns were expressed primarily regarding issues of animal ethics, stigma regarding how pigs are viewed in society, organ allocation logistics, quality of life after receiving a xenograft, and how XTx would be accepted by certain theological traditions. CONCLUSION: Overall, various stakeholders accepted XTx as a clinical option. However, there were ethical, social, and physical concerns raised. Future studies exploring the development of education strategies that may help alleviate concerns related to XTx before it becomes a clinical alternative are needed among the general public, potential XTx candidates, and their family members.

Racial differences in attitudes to clinical pig organ Xenotransplantation.

INTRODUCTION: In addition to an organ donor shortage, racial disparities exist at different stages of the transplantation process. Xenotransplantation (XTx) could alleviate these issues. This study describes racial differences in attitudes to XTx among populations who may need a transplant or are transplant recipients. METHODS: A Likert-scale survey was distributed at outpatient clinics to parents of children with congenital heart disease (CHD) and kidney patients on their attitudes to pig organ XTx. Data from these two groups were stratified by race and compared. RESULTS: Ninety-seven parents of children with CHD (74.2% White and 25.8% Black) and 148 kidney patients (50% White and 50% Black) responded to our survey. Black kidney patients' acceptance of XTx although high (70%) was lower than White kidney patients (91%; P .003). White kidney patients were more likely to accept XTx if results are similar to allotransplantation (OR 4.14; 95% CI 4.51-11.41), and less likely to be concerned with psychosocial changes when compared to Black kidney patients (receiving a pig organ would change your personality OR 0.08; 95% CI 0.01-0.67 and would change social interaction OR 0.24; 95% CI 0.07-0.78). There were no racial differences in attitudes to XTx among parents of children with CHD. CONCLUSION: There are differences in attitudes to XTx particularly among Black kidney patients. Because kidneys may be the first organ for clinical trials of XTx, future studies that decrease scientific mistrust and XTx concerns among the Black community are needed to prevent disparities in uptake of possible future organ transplant alternatives.

Attitudes toward xenotransplantation: A survey of parents and pediatric cardiac providers.

BACKGROUND: Scientific advancements are occurring in cardiac xenotransplantation (XTx). However, there have been religious and social concerns surrounding this allotransplantation alternative. The purpose of this study was to explore the acceptance of XTx among stakeholders of the congenital heart disease (CHD) community. METHODS: A Likert-scale anonymous survey was distributed to physicians and nurses who care for children with CHD and parents of children with CHD. Psychosocial and clinical attitudes were compared across all groups to identify differences, and regression analysis was performed to identify factors associated with XTx acceptance. RESULTS: A total of 297 responded to the survey: 134 physicians, 62 nurses, and 101 parents. Potential acceptance of XTx if outcomes were similar to allotransplantation was high overall (75.3%), but different between the groups (physicians 86%; nurses 71%, parents 64%; P < .0001). Regression analysis showed respondents who reported religion would influence medical decision making (OR 0.48; 95%CI 0.24-0.97) and those who would not use a pig heart transplant as a bridge until a human heart became available were less likely to accept XTx (OR 0.09; 95%CI 0.04-0.21). Psychosocial concerns to XTx were minimal but were also associated with XTx acceptance particularly among parents (OR 0.17; 95%CI 0.03-0.80). CONCLUSIONS: Potential acceptance of XTx is high, assuming results are similar to allotransplantation. Religious beliefs and attitudes toward the use of XTx as a bridge to allotransplant may present barriers to XTx acceptance. Future research is needed to assess potential attitude differences in light of ethical, psychosocial, and religious objections to XTx.

Paediatric xenotransplantation clinical trials and the right to withdraw.

Clinical trials of xenotransplantation (XTx) may begin early in the next decade, with kidneys from genetically modified pigs transplanted into adult humans. If successful, transplanting pig hearts into children with advanced heart failure may be the next step. Typically, clinical trials have a specified end date, and participants are aware of the amount of time they will be in the study. This is not so with XTx. The current ethical consensus is that XTx recipients must consent to lifelong monitoring. While this presents challenges to the right to withdraw in the adult population, additional and unanswered questions also linger in the paediatric population. In paediatric XTx, parents or guardians consent not only to the initial treatment of the child but also to lifelong monitoring, thus making a decision whose consequences will remain present as the child develops the capacity for assent, and finally the capacity for informed consent or refusal. This article presents and evaluates unanswered paediatric ethical questions in regard to the right to withdraw from XTx follow-up in the paediatric population.