© Springer International Publishing Switzerland 2016
Ralf J. Jox, Galia Assadi and Georg Marckmann (eds.)Organ Transplantation in Times of Donor ShortageInternational Library of Ethics, Law, and the New Medicine5910.1007/978-3-319-16441-0_2121. Xenotransplantation and Tissue Engineering Technologies: Safeguarding Their Prospects sans Sacrificing our Future
(1)
Institute for Ethics, History and Theory of Medicine, University Münster, Münster, Germany
Jan-Ole Reichardt
is a lecturer and research associate in Ethics at the Institute for Medical Ethics, History and Philosophy of Medicine at the University of Münster and an associate member of its Centre for Advanced Study in Bioethics. Dr. Reichardt has degrees in philosophy, formal logics and theory of sciences from the University of Leipzig. His research interests lie at the intersection of ethics, moral and political theory, with a particular interest in topics related to normative concepts of living well, notions of human dignity, autonomy and institutional justice.
21.1 Introduction
The availability of comprehensive health care services is of paramount importance to all of us. Given this critical interest and our high willingness to pay for individual survival , large amounts of public and private resources are continuously invested into the advancement of our medical capabilities. Those investments bring technologies within our reach that may soon help us to overcome some major challenges of today’s regenerative medicine. At the same time, new capabilities produce new responsibilities and revolutionary breakthroughs enforce new dimensions of awareness, thoughtfulness, self-control and institutional guidance. For this reason, our bioscientific research is closely accompanied by medical ethicists who try to ensure a smooth transition of ideas into practice and try to safeguard our progression into a more capable and yet sustainable future.
This is particularly true for xenotransplantation research , where high hopes have been raised that the fatal resource gap of today’s transplant medicine might be bridged in the not too distant future. Regarding these hopes, most resources are currently bet on the genetical adaptation of swine to our human needs: sufficiently high performance levels with regard to the transplant recipients and sufficiently low risk levels with regard to those recipients and their respective environments. However, before translational success might be proclaimed here, some demanding challenges are to be met first:
(i)
Bioscientific challenges, related to the medical aspects of xenotransplantation,
(ii)
Economic challenges, related to the funding of the translational efforts and the prospects of return for the investing bodies, and
(iii)
Political challenges, related to the regulation of future xenotransplantation therapies and products.
The third set includes all legal, ethical, cultural and administrative aspects of the translational process. The present analysis is focused on the ethical challenges. It discusses a special form of externalities—some uncommon risks that are to be shouldered by uninvolved parties and the public. Its recommendations are given with the intent to eliminate unnecessary delays and to insure the protagonists’ motivation to invest adequate amounts into quality control and risk mitigation.
21.2 Who Would Benefit and Who Would Suffer if Xenotransplants Became Available?
Technological developments described as progress usually have a positive cost-benefit ratio for its end-users, but can also come with net costs to others. The following part provides an overview about the stakeholders of xenotransplant medicine. The following cost and benefit prospects are neither exclusive, nor are most of them specific to the deployment of xenotransplant therapies. They are brought together to provide a more complete understanding of the translational scenario and its presumably supporting and objecting stakeholders and thereby ease our judgment of this development’s legitimacy.
(A) It is undisputed that our medical system lacks the resources to treat all its patients with chronic organ failure and that we therefore are in need of additional organ substitutes with sufficient functional capabilities. The stem cell focused research in the field of regenerative medicine seems capable of closing these resource gaps over the next 20 years.1 But until these presumably less invasive treatments become available, genetically engineered xenotransplants could offer some interim solutions, if their own bioscientific challenges were solved prior to this.2 In that case, all patients with chronic organ failure (waiting for a respective transplant) would benefit: either directly, via xenotransplantation, or indirectly, via a reduced waiting time for the ordinary allograft.
(B) At the same time, not only current patients, but all those with financial access to the transplant system would statistically benefit from the availability of an additional transplant source, because it would raise their own prospects of survival should they suffer from chronic organ failure in the future.
(C) higher availability of transplants and a more controllable provision of those transplants would allow the organizations that provide the transplant services (hospitals, transportation and logistics) to maximise their efficiency by a reduction of idle time and a volume boost of scheduled transplantations. This would reduce their costs per patient and thereby allow them to bill less per case, cross-finance less profitable activities or distribute higher earnings to their shareholders if run on a for-profit basis.
(D) An increasing number of transplants would also benefit those individuals who are actively involved in the provision of transplant services: the so-called transplant community. It would increase the demand for their expertise, thereby enhancing job security, increasing their bargaining position in salary negotiations and their bonus payments in case of revenue-related salaries.
(E) Those who would produce the yet to become bedside-ready xenotransplants would also profit: the emergingbiotech industry that developed over the past 30 years in the field of regenerative medicine and that has to be differentiated from the medical device industry and the pharmaceutical industry (although not necessarily with regard to ownership and control).3
(F) As long as xenotransplants would require a complex regime of pharmaceutical immunosuppression , the pharmaceutical industry would also benefit from an increasing demand of new long-term customers. And as some insiders—on condition of anonymity—suggested in personal conversation, this group would financially profit the most from the availability of new xenotransplant therapies.
(G) The last group of beneficiaries would only benefit under very special circumstances: the for-profit health care insurance industry. They would profit from new therapies if they were cheaper than their current equivalents (like a kidney transplantation in comparison to a continuous dialysis treatment), but would suffer losses from medically preferable but more expensive therapies (like a heart or liver transplant in comparison to the patient’s sad but financially inexpensive death) . Non-profit oriented health insurance funds would neither benefit nor lose, but their two important tasks to keep health care services top-notch and as affordable as possible, could mislead their administrations to deploy rationing principles in addition to their actual task of rationalisation. Although the decisions about rationing in health care are tasks that are exclusive to the political representatives of the insured, the administrative body could be misled to weigh the potential benefits of some against the potential costs to the whole community of the insured and to judge the cost-benefit ratio of xenotransplants as imbalanced or economically unfavourable without any legitimization to do so. Neither would respective cost savings qualify as benefits, nor would respective payments qualify as losses.
(H) The first group of loss sufferers would consist of those animals that would function as transplant sources and from which the tissue parts, cells and organs would be harvested for transplantation purposes. This analysis doesn’t support an attitude of ignorance towards animals and their human-induced suffering. Instead, it argues that as long as a large majority accepts animal consumption not only for scientific experiments (and for the greater good), but also for culinary delights and the sheer joy of wearing leather clothes, as long as that doesn’t change, the legitimacy of animal consumption for the rescue of human lives should not be questioned. For that reason, the potential suffering of animals due to new techniques of xenotransplantation will not be taken into account in the following parts.
(I) The second group of net losers would consist of the large fraction of the community ofpeople who are insured who—from an ex-post perspective—will never need an organ transplant but will nevertheless have to pay for the costs of those who do. They might not qualify as loss sufferers in the proper sense, since this situation is exactly what insurance funds are invented for: to protect the insured against the financial fiasco of an improbable but expensive event’s actual occurrence. Some of the insured might nevertheless suffer statistical losses if an expensive treatment gets covered, but their individual risk level to develop a condition where they would finally profit from the availability of expensive treatments is much lower than those of other community members, and the associated savings are not deducted from their personal contribution to the insurance fund. On the other hand, a deliberate omission of risk-based cost adjustments can also be interpreted as a genuine act of solidarity —and to one-sidedly call these a personal loss or bad deal seems to imply a rejection of solidarity . However, some very healthy people could nevertheless regard the availability of (expensive) xenotransplant therapies as annoying.
(K) Then, there might be those who are insured, who will develop symptoms of chronic organ failure in the future, will get a xenotransplant in time but would have gotten an even better allotransplant, if xenotransplants were still unavailable then. But, since becoming worse off in that specific way would require a lot of genuine bad luck, this allocation issue is almost irrelevant. And bad luck in a fair lottery, where nobody knows one’s outcome in advance, provides no justification for those who become worse off later on to complain about specific measures that actually increase everyone’s expected utility prior to the draw. So the unlucky few, who would end up with a worse transplant in an era of xenotransplantation than they would today, aren’t an ethical hurdle to the progress of transplant medicine. And in most cases, they will not even know that they would be better off under counterfactual conditions.
(L) Those commercially involved in the provision of transplant services that become obsolete by the introduction of medical innovations also lose—namely the profitability of their existing investments (in expertise and technology): for example, those who deliver artificial heart assist or replacement devices, those who deliver or deploy haemodialysis devices, the pharmaceutical producers of insulin analogues and so on. But investments into treatment capabilities do not come with moral claim rights to an omission of progress beyond the status quo, while other people’s suffering might well impose some prima facie duties to allow and support relief promising changes. For that reason, economic losses of medical progress are in themselves morally irrelevant.
(M) The last group of negatively affected stakeholders suffers an increase in exposure-related risks. Although this group includes every human on this planet, some would be more exposed and some would be more vulnerable to the threat. These risks accrue to us from the possible existence, evolution and spread of xenozoonotic pathogens—a possible side effect, specific to the transplantation of animal cells, tissue parts and organs into human bodies. These side effects threaten the transplanted as well as their innocent bystanders (who have nothing to do with this particular transplantation and have not consented to any risk exposures in advance). For that reason, a patient’s informed consent to her xenotransplant therapy is not enough to justify her bystander’s risk increase and special attention to this problem is required to reach both: translational success and the moral legitimacy of this translation. The following parts of this analysis focus on these third person risks, which represent the by far most important (if not only relevant) ethical challenge to xenotransplantation’s translational success.
21.3 Third Person Risks—What do we Know?
To debate the acceptability of third person risks and the adequacy of risk-mitigating measures, a profound analysis of these risks is paramount. So what makes these risks so special? What do we know about such unintended side effects? As we will soon see, truthful answers to these questions might illuminate the topic at hand, but without a satisfactory disclosure of the facts we’re after. The reason for this dissatisfaction is that the risks at hand are of unknown probability and severity.4 On the other hand, we do know some aspects of those risks involved: The perceived dangers consist of the possibility that immunosuppressed patients with porcine organ transplants could function as bioreactors, breeding new cross-species pathogens, thus causing outbreaks of zoonotic diseases. This idea is based on the fact that xenotransplanted patients lose the repellent effects of two bodily barriers between their human tissue and the transplanted animal graft. Furthermore, the presumably necessary pharmaceutical suppression of their bodies’ graft rejection will simultaneously suppress their immune response capabilities, transforming a body ’s hostile environment for infectious agents into fertile soil for hazards. This is a rough sketch of the threats we might face, if the transplantation of xenografts becomes a widely used standard therapy in the not too distant future. But at the moment, this basic idea is just a hypothetical scenario without empirical plausibility and bears no moral weight when actual lives are at stake. To demonstrate that this idea is not an empty challenge, some evidence has to be given to support its plausibility and thereby its ethical relevance claim. And indeed, the perception of these dangers is neither rooted in mere paranoia, nor in technophobes’ apocalyptic fantasies. On the contrary: there is a well-documented history of species-crossing pathogens and their causation of zoonotic diseases. As Taylor et al. (2001, p. 983) demonstrated, a sometimes one- sometimes multidirectional pathogen transmission between humans and one or more animal species is quite common, since more than 60 % of all human diseases currently known to us are caused by species-crossing pathogens.5 And as Karesh et al. (2012) highlighted, their negative impact on human well-being can hardly be overestimated:
The greatest burden on human health and livelihoods, amounting to about 1 billion cases of illness and millions of deaths every year, is caused by endemic zoonosis that are persistent regional health problems around the world. Many of these infections are enzootic (i.e., stably established) in animal populations, and transmit from animals to people with little or no subsequent person-to-person transmission [.] Other zoonotic pathogens can spread efficiently between people once introduced from an animal reservoir, leading to localized outbreaks (e.g., Ebola virus) or global spread (e.g., pandemic influenza) (Karesh et al. 2012, p. 1936 f).
Although only a few of these (and some yet unknown) pathogens might be of relevance in xenotransplant cases, current research on the emergence of new diseases emphasizes the close connection between new infectious agents and changes in the relationship between humans and wildlife, mediated by livestock animals. As Pearce-Duvet (2006) puts it:
Agriculture may have changed the transmission ecology of pre-existing human pathogens, increased the success of pre-existing pathogen vectors, resulted in novel interactions between humans and wildlife, and, through the domestication of animals, provided a stable conduit for human infection by wildlife diseases (Pearce-Duvet 2006, p. 369).
The surveys of Jones et al. (2013) confirm this observation. They found several examples in which an increase in the intensity of our interaction with livestock and wildlife was associated with an increasing risk of zoonotic disease emergence. For this reason, they regard these intensifications as major factors with regard to the development of new diseases:
Expansion of agriculture promotes encroachment into wildlife habitats, leading to ecosystem changes and bringing humans and livestock into closer proximity to wildlife and vectors, and the sylvatic cycles of potential zoonotic pathogens. This greater intensity of interaction creates opportunities for spillover of previously unknown pathogens into livestock or humans and establishment of new transmission cycles (Jones et al. 2013, p. 8399).
Swine can be regarded as an archetypical livestock animal and the transplantation of porcine cells, tissue parts and organs into human bodies does indeed qualify as an intensification of our relationship with this species. Furthermore, swine—or swine cells, tissue parts and organs—are, with regard to some zoonotic pathogens, less resistant to an infection than humans. At the same time, infected swine are a known source of pathogen recombination, regularly giving rise to new breeds of influenza. For this reason, Ma et al. (2009) recommend a thorough prevention strategy regarding possible contact of swine with infectious agents:
Although HPAIV H5N1 viruses have been transmitted directly to man, it may be that some species of carnivores could act as an intermediate host as they are quite susceptible to infection with this subtype [.] In the case of swine, empirical and experimental evidence demonstrates swine can generate novel influenza A viruses that have the potential to infect humans and some avian species. At present, it is difficult to predict which virus, if any, might induce a human pandemic. History would suggest that the likelihood of such an event is low; however, it seems prudent to minimize the risk of transmission of swine viruses to people as well as minimize the risk of transmission of novel viruses to swine (Ma et al. 2009, p. 332).Related posts:
The Ethics of Organ Donation: Foundations and Challenges
Organ Donation and Transplantation in Germany
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