Exploring attitudes toward xenotransplantation: A scoping review of healthcare workers, healthcare students, and kidney patients.

BACKGROUND: Recent advances mean that formal clinical trials of solid organ xenotransplantation are increasingly likely to begin and patients requiring a kidney transplant could be the first participants. Healthcare workers and healthcare students constitute the current and future workforce that will influence public opinion of xenotransplantation. The attitudes of these populations are important to consider before recruitment for formal clinical trials begins. METHODS: This scoping review was reported according to the PRISMA extensions for scoping reviews checklist and the Joanna Briggs Institute methodology for scoping reviews. The Scopus, PubMed, and ScienceDirect databases were searched to identify articles that studied the attitudes of healthcare workers, healthcare students, or kidney patients toward xenotransplantation. RESULTS: The search generated 816 articles, of which 27 met the eligibility criteria. The studies were conducted in 14 different countries on five different continents. Participants from the 27 studies totaled 29,836-this was constituted of 6,223 (21%) healthcare workers, 21,067 (71%) healthcare students, and 2,546 (8%) kidney patients. All three groups had an overall positive attitude toward xenotransplantation. However, in studies where participants were asked to consider xenotransplantation when the risks and results were not equal to allotransplantation-the overall attitude switched from positive to negative. The results also found that Spanish-speaking populations expressed more favorable views toward xenotransplantation compared to English-speaking populations. CONCLUSION: The results of this review suggest that while attitudes of the three groups toward xenotransplantation are-on the face of it-positive, this positivity deteriorates when the risks and outcomes are framed in more clinically realistic terms. Only formal clinical trials can determine how the risks and outcomes of xenotransplantation compare to allotransplantation.

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.

No, pregnancy is not a disease.

Anna Smajdor and Joona Räsänen argue that we have good reason to classify pregnancy as a disease. They discuss five accounts of disease and argue that each account either implies that pregnancy is a disease or if it does not, it faces problems. This strategy allows Smajdor and Räsänen to avoid articulating their own account of disease. Consequently, they cannot establish that pregnancy is a disease, only that plausible accounts of disease suggest this. Some readers will dismiss Smajdor and Räsänen's claims as counterintuitive. By analogy, if a mathematical proof concludes '2+2=5', readers will know-without investigation-that an error occurred. Rather than dismiss Smajdor and Räsänen's work, however, the easiest way to undermine their argument is to describe at least one plausible account of disease that (1) excludes pregnancy and (2) avoids the problems they raise for it. This is our strategy. We focus on dysfunction accounts of disease. After outlining Smajdor and Räsänen's main arguments against dysfunction accounts, we explain why pregnancy is not a disease on these accounts. Next, we defend dysfunction accounts against the three problems that Smajdor and Räsänen raise. If successful, then contra Smajdor and Räsänen, at least one plausible account of disease does not imply that pregnancy is a disease. We suspect that defenders of other accounts can respond similarly. Yet, we note that insofar as dysfunction accounts align with the commonsense intuition that pregnancy is not a disease, this, all else being equal, seems like a point in their favour.

Disclosing the undisclosed: are radiographers and healthcare scientists required to communicate a provisional diagnosis when asked?

Patients need to be given the relevant information to be able to give informed consent, which might require the disclosure of a provisional diagnosis. Yet, there is no duty to give information to a patient if that patient is aware that this information exists but chooses not to request it. Diagnostic radiographers and healthcare scientists are often responsible for ensuring that patients have given informed consent for the investigations they undertake, but which were requested by other clinicians. Here we examine if they have a duty to disclose a patient's provisional diagnosis made by a referring clinician if the patient asks for this information as part of the informed consent process to a diagnostic investigation. We first consider aspects of UK law, professional guidance and salient ethical principles, emphasising that while professional codes of practice highlight the need to act in the patient's best interest, they do not require giving patients information they do not require for the examination or have not requested. We then propose that diagnostic radiographers and healthcare scientists placed in such a position use a 'minimally necessary disclosure' framework. This framework fulfils their commitment to their patient and the principle of veracity, while respecting the boundaries of their professional duties. The framework ensures that enough detail is given to the patient for them to be able to give informed consent, while shouldering the diagnostic professional from making a full disclosure, which is the duty of the referring clinician.

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.

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.

The Problem with 'Suction Only' Methods to Reduce Surgical Smoke Exposure.

Surgical staff and patients are frequently exposed to surgical smoke and there is mounting evidence that this may be harmful. Borsetti et al. have devised a novel approach to minimising intraoperative exposure to surgical smoke. Here, I briefly outline my concerns with the 'suction only' approach to addressing this problem. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Kidney xenotransplantation: Future clinical reality or science fiction?

There is a global shortage of organs for transplantation and despite many governments making significant changes to their organ donation systems, there are not enough kidneys available to meet the demand. This has led scientists and clinicians to explore alternative means of meeting this organ shortfall. One of the alternatives to human organ transplantation is xenotransplantation, which is the transplantation of organs, tissues, or cells between different species. The resurgence of interest in xenotransplantation and recent scientific breakthroughs suggest that genetically engineered pigs may soon present a realistic alternative as sources of kidneys for clinical transplantation. It is therefore important for healthcare professionals to understand what is involved in xenotransplantation and its future implications for their clinical practices. First, we explore the insufficiency of different organ donation systems to meet the kidney shortage. Second, we provide a background and a summary of the progress made so far in xenotransplantation research. Third, we discuss some of the scientific, technological, ethical, and public health issues associated with xenotransplantation. Finally, we summarize the literature on the attitudes of healthcare professionals toward xenotransplantation.

Xenotransplantation Clinical Trials and Equitable Patient Selection.

Xenotransplant patient selection recommendations restrict clinical trial participation to seriously ill patients for whom alternative therapies are unavailable or who will likely die while waiting for an allotransplant. Despite a scholarly consensus that this is advisable, we propose to examine this restriction. We offer three lines of criticism: (1) The risk-benefit calculation may well be unfavorable for seriously ill patients and society; (2) the guidelines conflict with criteria for equitable patient selection; and (3) the selection of seriously ill patients may compromise informed consent. We conclude by highlighting how the current guidance reveals a tension between the societal values of justice and beneficence.

A fair exchange: why living kidney donors in England should be financially compensated.

Every year, hundreds of patients in England die whilst waiting for a kidney transplant, and this is evidence that the current system of altruistic-based donation is not sufficient to address the shortage of kidneys available for transplant. To address this problem, we propose a monopsony system whereby kidney donors can opt-in to receive financial compensation, whilst still preserving the right of individuals to donate without receiving any compensation. A monopsony system describes a market structure where there is only one 'buyer'-in this case the National Health Service. By doing so, several hundred lives could be saved each year in England, wait times for a kidney transplant could be significantly reduced, and it would lessen the burden on dialysis services. Furthermore, compensation would help alleviate the common disincentives to living kidney donation, such as its potential associated health and psychological costs, and it would also help to increase awareness of living kidney donation. The proposed system would also result in significant cost savings that could then be redirected towards preventing kidney disease and reducing health disparities. While concerns about exploitation, coercion, and the 'crowding out' of altruistic donors exist, we believe that careful implementation can mitigate these issues. Therefore, we recommend piloting financial compensation for living kidney donors at a transplant centre in England.

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.

Inconsistency arguments still do not matter.

William Simkulet has recently criticised Colgrove et al's defence against what they have called inconsistency arguments-arguments that claim opponents of abortion (OAs) act in ways inconsistent with their underlying beliefs about human fetuses (eg, that human fetuses are persons at conception). Colgrove et al presented three objections to inconsistency arguments, which Simkulet argues are unconvincing. Further, he maintains that OAs who hold that the fetus is a person at conception fail to act on important issues such as the plight of frozen embryos, poverty and spontaneous abortion. Thus, they are morally negligent. In response, we argue that Simkulet has targeted a very narrow group of OAs, and so his criticisms are inapplicable to most OAs. We then explain why his responses to each of Colgrove et al's objections do not succeed, even for this restricted group. Finally, we note that Simkulet fails to provide evidence for his claims regarding OAs' supposed failures to act, and we show that OAs veritably do invest resources into these important issues. We conclude that Colgrove et al's reasons for rejecting inconsistency arguments (en masse) remain intact.

Why we should stop using animal-derived products on patients without their consent.

Medicines and medical devices containing animal-derived ingredients are frequently used on patients without their informed consent, despite a significant proportion of patients wanting to know if an animal-derived product is going to be used in their care. Here, I outline three arguments for why this practice is wrong. First, I argue that using animal-derived medical products on patients without their informed consent undermines respect for their autonomy. Second, it risks causing nontrivial psychological harm. Third, it is morally inconsistent to respect patients' dietary preferences and then use animal-derived medicines or medical devices on them without their informed consent. I then address several anticipated objections and conclude that the continued failure to address this issue is an ethical blind spot that warrants applying the principles of respect for autonomy and informed consent consistently.

Why we should not extend the 14-day rule.

The 14-day rule restricts the culturing of human embryos in vitro for the purposes of scientific research for no longer than 14 days. Since researchers recently developed the capability to exceed the 14-day limit, pressure to modify the rule has started to build. Sophia McCully argues that the limit should be extended to 28 days, listing numerous potential benefits of doing so. We contend that McCully has not engaged with the main reasons why the Warnock Committee set such a limit, and these still remain valid. As a result, her case for an extension of the 14-day rule is not persuasive.

If fetuses are persons, abortion is a public health crisis.

Pro-life advocates commonly argue that fetuses have the moral status of persons, and an accompanying right to life, a view most pro-choice advocates deny. A difficulty for this pro-life position has been Judith Jarvis Thomson's violinist analogy, in which she argues that even if the fetus is a person, abortion is often permissible because a pregnant woman is not obliged to continue to offer her body as life support. Here, we outline the moral theories underlying public health ethics, and examine the COVID-19 pandemic as an example of public health considerations overriding individual rights. We argue that if fetuses are regarded as persons, then abortion is of such prevalence in society that it also constitutes a significant public health crisis. We show that on public health considerations, we are justified in overriding individual rights to bodily autonomy by prohibiting abortion. We conclude that in a society that values public health, abortion can only be tolerated if fetuses are not regarded as persons.

Quotas: Enabling Conscientious Objection to Coexist with Abortion Access.

The debate regarding the role of conscientious objection in healthcare has been protracted, with increasing demands for curbs on conscientious objection. There is a growing body of evidence that indicates that in some cases, high rates of conscientious objection can affect access to legal medical services such as abortion-a major concern of critics of conscientious objection. Moreover, few solutions have been put forward that aim to satisfy both this concern and that of defenders of conscientious objection-being expected to participate in the provision of services that compromise their moral integrity. Here we attempt to bring some resolution to the debate by proposing a pragmatic, long-term solution offering what we believe to be an acceptable compromise-a quota system for medical trainees in specialties where a conscientious objection can be exercised, and is known to cause conflict. We envisage two main objectives of the quota system we propose. First, as a means to introduce conscientious objection into countries where this is not presently permitted. Second, to minimise or eliminate the effects of high rates of conscientious objection in countries such as Italy, where access to legal abortion provision can be negatively affected.

Questionable benefits and unavoidable personal beliefs: defending conscientious objection for abortion.

Conscientious objection in healthcare has come under heavy criticism on two grounds recently, particularly regarding abortion provision. First, critics claim conscientious objection involves a refusal to provide a legal and beneficial procedure requested by a patient, denying them access to healthcare. Second, they argue the exercise of conscientious objection is based on unverifiable personal beliefs. These characteristics, it is claimed, disqualify conscientious objection in healthcare. Here, we defend conscientious objection in the context of abortion provision. We show that abortion has a dubitable claim to be medically beneficial, is rarely clinically indicated, and that conscientious objections should be accepted in these circumstances. We also show that reliance on personal beliefs is difficult to avoid if any form of objection is to be permitted, even if it is based on criteria such as the principles and values of the profession or the scope of professional practice.

Parental responsibilities and moral status.

Prabhpal Singh has recently defended a relational account of the difference in moral status between fetuses and newborns as a way of explaining why abortion is permissible and infanticide is not. He claims that only a newborn can stand in a parent-child relation, not a fetus, and this relation has a moral dimension that bestows moral value. We challenge Singh's reasoning, arguing that the case he presents is unconvincing. We suggest that the parent-child relation is better understood as an extension of an existing relationship formed during the gestational period. The change in this relation at birth is not sufficient to justify the radical change in moral status required to rule out infanticide while accepting the permissibility of abortion. Given that the moral status of orphans is also problematic under Singh's account, we conclude that Singh has not shown that a newborn has greater moral worth than a fetus.