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. (shrink)

Xenotransplantation is defined as “any procedure that involves the transplantation, implantation, or infusion into a human recipient of either live cells, tissues, or organs from a nonhuman animal source, or human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs.” Xenotransplantation has been viewed by desperate patients and their surgeons as a solution to the problem of the paucity of human organs available for transplantation. Foes of xenotransplantation argue that (...) the use of animal organs degrades the human race and should be avoided.In this paper, we briefly review the cultural context of xenotransplantation and explore the infectious disease risk of xenotransplantation. The United States Code of Federal Regulations requires life-long surveillance of a xenotransplantation recipient due to the largely unknown risk of novel infectious disease transmitted across species, known as xenogeneic infectious disease. We argue that despite being in the interest of protecting the public health, the imposition of lifelong surveillance requirements on xenotransplant recipients effectively abrogates the right to withdraw from a clinical trial after the transplantation has taken place. Moreover, we argue that a waiver of the right to withdraw should be made explicit in the interest of full disclosure, out of respect for the research subject’s right of self-determination. (shrink)

What Ivan Illich regarded in his Medical Nemesis as the ‘expropriation of health’ takes place on the surfaces and in the spaces of the screens all around us, including our cell phones but also the patient monitors and (increasingly) the iPads that intervene between nurse and patient. To explore what Illich called the ‘age of the show’, this essay uses film examples, like Creed and the controversial documentary Vaxxed, and the television series Nurse Jackie. Rocky’s cancer in his last film (...) (submitting to chemo to ‘fight’ cancer) highlights what Illich along with Petr Skrabanek called the ‘expropriation of death’. In contrast to what Illich denotes as ‘Umsonstigkeit’ – i.e., a free gift, given undeservedly, i.e., gratuitously – medical science tends to be tempted by what Illich terms scientistic ‘black magic’, taking over (expropriating) the life and the death of the patient in increasingly technological ways, a point underscored in the concluding section on the commercial prospects of xenotransplants using factory farm or mass-produced (and already for some time) human-pig mosaics or chimeras. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

Ravelingien et al1 argue that, given the restrictions that must be imposed on recipients of xenotransplanted organs, we should conduct clinical trials of xenotransplantation only on patients in a persistent vegetative state. I argue that there is no ethical barrier to using terminally ill patients instead. Such patients can choose to waive their rights to the liberties that xenotransplantation would probably restrict; it is surely rational to prefer to waive your rights rather than to die, and permissible to allow patients (...) to make this choice.Perhaps the single most important advance in the history of moral thought occurred when it came to be generally recognised that all people are protected by rights that are inviolable, at least without their consent. The precise nature and content of these rights is controversial, but there is a consensus among reasonable people over their core. We all have a right to life, to liberty, to security of person and to equality before the law. Other rights—so-called positive rights, such as the right to economic security, or cultural rights, for instance—may be controversial, but we all agree at least on these.Ravelingien et al1 therefore seem to be on solid ground when they conclude that it would not be permissible to use living persons as subjects in clinical trials of xenotransplantation, as such trials, potentially or actually, result in the violation of the core human rights of the subjects. Their argument is as follows:" Xenotransplantation carries with it a currently unquantifiable risk of the transmission of viruses, from the animal that is the source of the organ transplanted, to the human recipient. Such viruses could have potentially catastrophic consequences, up to and including triggering a global and devastating pandemic. Therefore, it would be necessary to monitor the health status of recipients of … ". (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

Although it is commonly believed that the concept of brain death was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile’s definition of (...) death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord’s statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation. (shrink)

To most people outside the relevant laboratories and operating rooms, xenotransplants and artificial organ transplants are bizarre. While the bizarre scares many away and angers others, Lesley A. Sharp approached it and asked, What behooves medical research to take organs out of pigs and primates and design organs out of metal and plastic and use them to replace failing organs in humans? Sharp attended years of conferences, visited countless hospitals and laboratories, and interviewed engineers, scientists, and surgeons to explore the (...) choices and implicit values of decision‐makers in alternative transplantation. The Transplant Imaginary: Mechanical Hearts, Animal Parts, and Moral Thinking in Highly Experimental Science is a rich resource for philosophers who wish to expound on the morality of implanting nonhuman animal and mechanical organs into humans. The author's thorough ethnographic survey of xeno‐ and biomechanical transplant research leads well into two lines of questioning. First, how ethical is the pursuit of alternative transplant? Second, what is essential for transplant researchers to do their jobs ethically? (shrink)

When surgeons transplant animal organs into humans, people who did not receive the organs incur risks. These third parties may stand near or far in time or space. No one knows the likelihood, breadth, or nature of the risks in question. The common wisdom among infectious-disease specialists is that in the best of xenotransplant conditions, such third-party risk may be minimized but not eliminated.

The Journal of Medical Ethics can sometimes read part Men Like Gods and part A Brave New World. At times, we learn how all controversies can resolved with reference to four principles. At other times, we learn how “every discovery in pure science is potentially subversive”.1 This issue is no exception. Here, we can read about the utopia of gene editing, manufactured organs, and machine learnt algorithmic decision-making. We can also read about the dystopia of inherited disorders from edited germlines, (...) the testing of xenotransplants on braindead patients, and misdiagnosis by artificial intelligence. What we see in the three papers that I will foreground here is the application of medical ethics to avoid the dystopia while preserving the promises of medical science. But as I seek to explain here, our ability to address the controversies that we anticipate in medical science depend on our ability to refine our understanding of what medical ethics requires of us now. From the diagnosis of eye diseases from fungus images to predicting the risk of imminent risk of suicide attempts, machine learnt medical decision making has, in some high profile instances, outperformed clinicians in medical diagnosis and treatment recommendations. While clinician and machine learnt diagnoses will both involve degrees of uncertainty and fallibility, Thomas Grote2 asks us to consider is how much weight a clinician ought to give an algorithmic diagnosis which she disagreements with. Since a clinician is held to account for …. (shrink)

Given the increasing need for solid organ and tissue transplants and the decreasing supply of suitable allographic organs and tissue to meet this need, it is understandable that the hope for successful xenotransplantation has resurfaced in recent years. The biomedical obstacles to xenotransplantation encountered in previous attempts could be mitigated or overcome by developments in immunosuppression and especially by genetic manipulation of organ source animals. In this essay we consider the history of xenotransplantation, discuss the biomedical obstacles to success, explore (...) recent developments in transgenic sourcing of organs and tissues, and analyze the problem of infectious disease resulting from xenotransplantation (xenosis). We then apply a model of risk analysis to these risks. The conclusions of this risk analysis are used in an ethical evaluation of informed consent in xenotransplantation, with an ethical foundation in Kantian autonomy and Levinasian heteronomic alterity. Our conclusion is that individual and collective informed consent to the infectious disease risks of xenotransplantation requires an open, participatory and dialogical public policy process not yet seen in the United States and Europe. Until that process is created, we propose caution in xenotransplantation in general and a postponement of solid organ xenotransplants in particular. (shrink)

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. (shrink)

In this article, we provide an ethical analysis of the first porcine cardiac xenotransplant, performed in Maryland, USA in early 2022. David Bennett was offered the experimental procedure after he was deemed ineligible for human heart transplantation and mechanical circulatory support, based on a history of non-compliance. It was reported that Mr Bennett’s previous instances of non-compliance were for medically non-life-threatening conditions years earlier, where the risks of non-compliance were not as high. We argue that, in Mr Bennett’s case, (...) a history of non-compliance in a different context, should not necessarily rule him ineligible for a potentially life-saving treatment now. Furthermore, using previous non-compliance to exclude individuals from donor organs may have the unintended effect of placing the burden of testing xenotransplantation on those who are already disadvantaged. We then argue that it is not enough to rely on patient consent to ethically justify xenotransplantation research. Taking a broad ethical perspective is crucial when mapping a clinical pathway for xenotransplantation. (shrink)

In the fall of 2021 a news story reported of a successful experimental xenotransplant of a genetically engineered pig kidney in to the circulatory system of a research subject who was dead by neurological criteria. Although not a first of its kind, this case raises the issue of the ethics of research on those declared brain dead. Such possibilities have been discussed in the published literature since 1974, when Willard Gaylin expressed concern over human dignity when he imagined hospital (...) wards filled with “neomorts” used for education, teaching, research, and manufacturing. In this essay, the author explores the nuances of whether such subjects are considered alive, dead, or something in between. Notions of consent/ permission and risk/benefit are determined by this categorization. After discussing the 2005 Consensus Panel Guidelines on Research with the Recently Dead, the essay concludes with the need for a liminal state between living and dead that respects human dignity but also recognizes the utilitarian value of such experiments to protect fully alive humans. Having not just guidelines but oversight structures such as the University of Pittsburgh’s Committee for Oversight of Research Involving the Dead (CORID) and regulations are necessary if such work is to become more common. (shrink)