This article considers the claims (i) that saving human life through organ transplants from other species would be speciesist, (ii) that none the less it can be defended on grounds of loyalty to our species. I reject loyalty to one's species as a plausible extension of the virtue of loyalty, suggesting that solidarity with one's species is possible and may provide adequate grounds of defense of xenografting.

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)

This paper considers the ethical issues raised by xenotransplantation underfour headings: interfering with nature; effects on the recipient; effects on other humans; and effects on donor animals. The first two issues raise no insuperable problems: charges of unnaturalness are misguided, and the risks that xenotransplantation carries for the recipient are a matter for properly informed consent. The other two issues raise more serious problems, however, and it is argued that if we take seriously the risk of transferring new infectious agents (...) from animal to human populations and the interests of donor animals, then a moratorium on xenotransplantation is called for. The paperfinds that the recent Nuffield Council and Department of Health reports on xenotransplantation are insufficiently cautious in the conclusions that they draw from these considerations. (shrink)

I offer a critique of how we have gotten to the point of considering xenografts into humans through a kind of moral failure to generate an efficient system of organ harvesting from human cadavers. I consider several proposals for increasing the supply of transplantable human organs, including one recently proposed in detail by James Lindemann Nelson of the Hastings Center for routine retrieval with an opt-out option.

The current voluntary posthumous organ donation policy fails to provide sufficient organs to meet the demand. In these circumstances xenografts have been regarded as an expedient solution. The public perception seems to be that the only impediments to this technology are technical and biological. There are, however, important ethical issues raised by xenotransplantation that need to be considered as a matter of urgency. When the ethical issues raised by using non-human animals to provide replacement organs for human beings are considered (...) in a wider context and the possible alternatives to xenotransplantation are taken into account, a new dimension is added to the debate. In this broader context it is argued that a less ethically problematic solution is to adopt a presumed consent or opt-out organ procurement policy to regulate posthumous organ harvesting from humans. If there are still too few organs available, then the whole question of transplantation must be reassessed. (shrink)

Patient-derived xenografts are currently promoted as new translational models in precision oncology. PDXs are immunodeficient mice with human tumors that are used as surrogate models to represent specific types of cancer. By accounting for the genetic heterogeneity of cancer tumors, PDXs are hoped to provide more clinically relevant results in preclinical research. Further, in the function of so-called “mouse avatars”, PDXs are hoped to allow for patient-specific drug testing in real-time. This paper examines the circulation of knowledge and bodily material (...) across the species boundary of human and personalized mouse model, historically as well as in contemporary practices. PDXs raise interesting questions about the relation between animal model and human patient, and about the capacity of hybrid or interspecies models to close existing translational gaps. We highlight that the translational potential of PDXs not only depends on representational matching of model and target, but also on temporal alignment between model development and practical uses. Aside from the importance of ensuring temporal stability of human tumors in a murine body, the mouse avatar concept rests on the possibility of aligning the temporal horizons of the clinic and the lab. We examine strategies to address temporal challenges, including cryopreservation and biobanking, as well as attempts to speed up translation through modification and use of faster developing organisms. We discuss how featured model virtues change with precision oncology, and contend that temporality is a model feature that deserves more philosophical attention. (shrink)

The genetic modification of pigs as a source of transplantable organs is one of several possible solutions to the chronic organ shortage. This paper describes existing ethical tensions in xenotransplantation (XTx) that argue against pursuing it. Recommendations for lifelong infectious disease surveillance and notification of close contacts of recipients are in tension with the rights of human research subjects. Parental/guardian consent for pediatric xenograft recipients is in tension with a child’s right to an open future. Individual consent to transplant (...) is in tension with public health threats that include zoonotic diseases. XTx amplifies concerns about justice in organ transplantation and could exacerbate existing inequities. The prevention of infectious disease in source animals is in tension with the best practices of animal care and animal welfare, requiring isolation, ethologically inappropriate housing, and invasive reproductive procedures that would severely impact the well-being of intelligent social creatures like pigs. (shrink)

Allograft shortage is a formidable obstacle in organ transplantation. Xenotransplantation, the interspecies transplantation of cells, tissues, and organs, or ex vivo interspecies exchange between cells, tissues, and organs is a frequently suggested alternative to this allograft shortage. As xenotransplantation steadily improves into a viable allotransplantation alternative, several bioethical considerations coalesce. Such considerations include the Helsinki declaration’s guarantee of patients’ rights to privacy; political red tape that may select for undermined socioeconomic groups as the first recipients of xenografts; industry incentives in (...) xenotransplantation investments; conflicts of interest when a clinician supervises a patient as a research subject; the psychosocial impact of transplantation on the xenograft recipient, and the rights of animals. This review illuminates these issues through a conglomeration of expert opinion and relevant experimental studies. (shrink)

Three experiments on neural grafting with adult rat hosts are described. Working memory impairments were produced by lesioning the hippocampus or severing its connections with the septum by ablating the fimbria-fornix. The results suggest that the survival and growth of a neural graft, whether an autograft or a xenograft, is not a necessary condition for functional recovery on a task tapping working memory.

BackgroundMany procedures currently require the use of bone grafts to replace or recover bone volume that has been resorbed. However, the patient’s opinion and preferences must be taken into account before implementing any treatment. Researchers have focused primarily on assessing the effectiveness of bone grafts rather than on patients' perceptions. Thus, the aim of this study was to explore patients' opinions regarding the different types of bone grafts used in dental treatments.MethodsOne hundred patients were randomly chosen participated in the study. (...) A standardized survey of 10 questions was used to investigate their opinions regarding the different types of bone grafts used in dental treatments. Descriptive statistics were calculated for the different variables, and absolute frequencies and percentages were used as summary measures. A value of p <0.05 was selected as the threshold for statistical significance.ResultsThe highest rate of refusal was observed for allografts and xenografts. The grafts with the lowest rates of refusal were autologous grafts and alloplastics. No significant differences were found between the various types of bone grafts in the sociodemographic variables or the refusal/acceptance variable. Similarly, no significant relations were observed between a specific religious affiliation and the acceptance/refusal rates of the various types of graft.ConclusionsAllografts and xenografts elicited the highest refusal rates among the surveyed patients, and autologous bone and alloplastics were the most accepted bone grafts. Moreover, no differences were found in the sociodemographic variables or religious affiliations in terms of the acceptance/refusal rates of the different bone grafts. (shrink)

We live in an age of great scientific and technological innovation, and what seemed out of the question or at least very doubtful only a few years ago, today lies almost within our grasp. In no area is this more true than that of human health care, where lifesaving and life-enhancing technologies have given, or have the enormous potential in the not so distant future to give, relief from some of the most terrible human illnesses. On two fronts in particular, (...) xenograft or cross-species transplantation and genetic engineering of animals on behalf of gene therapy in humans, such relief appears very promising, if not actually on the horizon. Certainly, extensive research work on both fronts is underway both in the United States and abroad. (shrink)

The growth factor progranulin (PGRN) regulates cell division, survival, and migration. PGRN is an extracellular glycoprotein bearing multiple copies of the cysteine‐rich granulin motif. With PGRN family members in plants and slime mold, it represents one of the most ancient of the extracellular regulatory proteins still extant in modern animals. PRGN has multiple biological roles. It contributes to the regulation of early embryogenesis, to adult tissue repair and inflammation. Elevated PGRN levels often occur in cancers, and PGRN immunotherapy inhibits the (...) growth of hepatic cancer xenografts in mice. Recent studies have demonstrated roles for PGRN in neurobiology. An autosomal dominant mutation in GRN, the gene for PGRN, leads to neuronal atrophy in the frontal and temporal lobes, resulting in the disease frontotemporal lobar dementia. In this review we will discuss current knowledge of the multifaceted biology of PGRN. (shrink)

New technologies are changing our lives radically and quickly. New biotechnologies are moving to commercial uses faster than government regulators or private citizens can monitor. This tension manifests itself in the current debates over xenotransplantation technologies in medicine. The possibility of removing cells, tissues, and organs from animals and transplanting them into human beings is startling and unnerving. Natural immunesystem barriers between species, and even between individuals within a species, are formidable. Typically, transplantation results in violent rejection and death of (...) the grafted organ. But despite the natural barriers to transplantation, xenotransplantation aims specifically to overcome them.In this paper, I will discuss applications of xenograft technology, which raises clinical risks, ethical concerns, and policy issues. I conclude with a set of specific recommendations. As a recent letter to the journal Nature puts it, there is a “split between those who want to get it right, and those who want to get it right now.” No one knows what all the risks, benefits, and unintended consequences of xenotransplantation will be. (shrink)

New technologies are changing our lives radically and quickly. New biotechnologies are moving to commercial uses faster than government regulators or private citizens can monitor. This tension manifests itself in the current debates over xenotransplantation technologies in medicine. The possibility of removing cells, tissues, and organs from animals and transplanting them into human beings is startling and unnerving. Natural immunesystem barriers between species, and even between individuals within a species, are formidable. Typically, transplantation results in violent rejection and death of (...) the grafted organ. But despite the natural barriers to transplantation, xenotransplantation aims specifically to overcome them.In this paper, I will discuss applications of xenograft technology, which raises clinical risks, ethical concerns, and policy issues. I conclude with a set of specific recommendations. As a recent letter to the journal Nature puts it, there is a “split between those who want to get it right, and those who want to get it right now.” No one knows what all the risks, benefits, and unintended consequences of xenotransplantation will be. (shrink)

Topic Read 01. Jan 09 Introduction/Pretest/Critical Thinking 02. Jan 11 Ethical Theory Homepage 03. Jan 16 More about Ethical Theory 04. Jan 18 Euthanasia CC-2 05. Jan 23 More about Euthanasia CC-4 06. Jan 25 Birth Defects CC-9 07. Jan 30 Euthanasia/Birth Defects Symposium 08. Feb 01 Animals as Research Subjects CC-10 09. Feb 06 More about Animals as Research Subjects 10. Feb 08 Humans as Research Subjects CC-11 11. Feb 13 Organ/Tissue Donation & Xenografts CC-13/14 12. Feb 15 Research (...) Symposium 13. Feb 20 MID-TERM EXAM 14. Feb 22 Sexual Orientation/Discrimination 15. Feb 27 Human Sexuality/Sexual Ethics Homepage 16. Mar 01 Human Sexuality Symposium 17. Mar 06 Pharmaceuticals & Empiricism 18. Mar 08 Recreational Drugs 19. Mar 20 HIV/AIDS CC-17 20. Mar 22 Contraception 21. Mar 27 Drugs/AIDS Symposium 22. Mar 29 Abortion CC-5 23. Apr 03 More about Abortion 24. Apr 05 Abortion Symposium 25. Apr 10 Assisted Reproduction CC-6 26. Apr 12 Cloning and Stem Cell Research CC-7/8 27. Apr 17 Cloning and Stem Cell Research Symposium 28. Apr 19 LATE-TERM EXAM 29. Apr 24 Medicare/HMO CC-18 30. Apr 26 Medicare/HMO Symposium.. (shrink)

On October 26, 1984, Dr. Leonard Bailey and the transplant team of Loma Linda University Medical Center in California operated on a five-pound baby girl born a few weeks earlier with hypoplastic left heart syndrome. In babies born with this defect the left side of the heart is much smaller than the right and is unable to pump sufficient blood to sustain life for more than a few weeks. This rare defect occurs about once in every 12,000 live births; it (...) accounts for about a quarter of all cardiac deaths of newborns. In an operation known as a xenograft, involving cross-species transplantation of an organ, Dr. Bailey removed the defective heart from the baby and replaced it with the heart of a baboon. (shrink)

An increasing shortage of transplant donor organs currently results in an escalating number of preventable human deaths. Xenotransplantation. the use of animal organs for transplantation into humans, is now heralded as medicine's most viable answer to the urgent and insurmountable human organ scarcity. Although claimed to be a biomedical prerogative, xenotransplantation is a cultural phenomenon - a procedure engaging both the physical and symbolic manipulation of human and nonhuman bodies, thereby transforming corporeality, identity, and culture. Biomedical and scientific discourses about (...) xenografts have obscured issues related to nonhuman animals and also could be distressful to human organ recipients, revealing that the xenograft may not be widely embraced. (shrink)

Depuis le début du siècle, des chercheurs ont expérimenté, mais sans succès, des greffes d’organes animaux. Pourtant, la xénogreffe puise de certaines réflexions antiques. La xénotransplantation est une alternative médicale futuriste au cours de laquelle on passe de la greffe d’organes humains à celle d’organes animaux. Ce dilemme nécessite une réflexion bioéthique. L’éthique distincte de la morale requiert un champ beaucoup plus ouvert qui met en tension différentes disciplines. C’est de cette tension que naît un questionnement qui suscite une réflexion (...) et une démarche spécifique. Pour ce faire, 42 étudiants tunisiens en 2e année de licence en biotechnologie sont invités à prendre une décision argumentée entre le fait d’accepter ou de refuser, en cas de nécessité absolue, une transplantation d’un cœur porcin. Nous constatons que l’approche adoptée par ces étudiants est plutôt déductive et les processus d’argumentations restreints mobilisés ne reflètent pas la tension qui caractérise le raisonnement dans ce genre de dilemme : la mort ou le fait d’accepter dans son corps un cœur porcin, d’autant plus que pour certaines religions, même la consommation de la viande de porc est un péché. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:A New Look at Animal-to-Human Organ TransplantationCharles R. McCarthy (bio)The acute shortage of organs available for transplantation into human beings combined with a new scientific understanding of the immune systems of both humans and animals make it probable that animal-to-human solid organ transplants (xenografts) may soon be attempted at a frequency rate unknown in the past. 1 Optimism about successful animal-to-human organ transplantation is greater than at any previous (...) time. The creation of a reliable supply of animal organs appears to be technically feasible. At least five major transplant centers in the United States are currently considering plans to pursue xenotransplantation. Although, at the time of this writing, no federal guidelines prohibit animal-to-human organ transplantation, the institutions considering such programs are awaiting deliberations on the subject by the Institute of Medicine (IOM), the Food and Drug Administration (FDA), and the Department of Health and Human Services (DHHS).The demand for organs suitable for transplantation into human beings greatly exceeds the supply. According to the United Network for Organ Sharing (UNOS 1996a), approximately 44,000 patients in the United states awaited organ transplantation at the end of 1995. In 1994, more than 3,000 patients died while on the transplant waiting list, and the demand for transplantable organs increases annually (UNOS 1996b). The figures do not include the hundreds or perhaps thousands of patients who could profit from a transplant, but who do not meet the requirements of the UNOS waiting list. Even if efforts to persuade persons to donate organs are redoubled, and even if the consent to donate organs should become a legal presumption, there is little prospect of developing a sufficient supply of transplantable human organs to meet the growing demand.As technical and biological barriers to successful animal-to-human xenografts are lowered, the prospect of raising dedicated colonies of animals, genetically altered to reduce the chances that human hosts will reject organs derived from them, is being seriously discussed. 2 Such colonies do not exist at the present time. [End Page 183] However, if new techniques for animal-to-human transplantation prove successful, it is likely that animal colonies will be established to provide a ready and predictable supply of organs for transplantation to humans. Some believe that commercial investment in colonies of purpose-bred animals to serve as a source of transplantable organs is close at hand (Leventhal 1994).New drugs and new combinations of existing drugs have improved the chances of successful medical outcomes for patients who receive solid organ transplants. It is now recognized that serial application of immunosuppressive drugs can reduce the likelihood of both short- and long-term organ rejection (Makowka 1994). Improved understanding of both human and animal immune systems, insights into histocompatibility, new agents to control graft-versus-host disease, animal breeding programs for the production of transgenic animals, and improved surgical techniques have opened, as never before, the possibility of successful transfer of organs from animals to humans. Some rate the chances of good patient outcomes (usually measured in terms of time of patient survival) as high, others make more conservative predictions, but virtually all experts believe that the chances for successful human patient outcomes resulting from xenotransplantation are improved. Because many patients face immanent death unless their organs can be replaced, there can be little doubt that many humans will readily consent to xenotransplantation.History Suggests CautionDespite the advances in immunosuppression, the frequency of failure in past animal-to-human xenograft attempts should temper the optimism of the transplant community. To date, all efforts to prolong human life by implanting solid organs from animals into human recipients have failed. The first attempts at animal-to-human xenotransplantation early in the twentieth century resulted in the early death of all recipients (Neuhof 1923). More sophisticated efforts at xenotransplantation occurred in the late 1960s and early 1970s, a period when anti-rejection drugs began to make allografts more feasible. Although one human recipient of a xenograft survived for nine months (with poor quality of life), most patients died within a matter of minutes, hours, or a few days following the transplantation of organs from chimpanzees or baboons (Starzl... (shrink)