Respect for persons,informed consent andthe assessment of infectious disease risks in xenotransplantation

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.This revised version was published online in October 2005 with corrections to the Cover Date.     

Immunology in clinical practice. XXIII. Xenotransplantation]

Currently xenotransplantation is being discussed on national and international levels as a possible solution to tranplantation waiting lists, in view of the lack of alternative therapies. In recent years, enormous progress has been made in the area of immunology, especially concerning hyperacute rejection. However, long-term survival is still fiction due to relatively unknown, sequential rejection processes. Moreover, it remains questionable if xenogeneic organs will function physiologically, especially if they are metabolically complex. A third problem is the possible infectious risk of xenotransplantation to the patient and the population. Regarding this hazard, various committees and policy reports demand clarity first before the initial clinical transplantations become fact. In the Netherlands, the government largely adopted an identical advice by the Health Council. Artificial organs and cloning developments indicate that xenotransplantation might merely be an intermediate station in the route to develop adequate treatment for patients with organ failure.     

Expanding the conceptual toolkit of organ gifting

In jurisdictions where the sale of body tissue and organs is illegal, organ transplantation is often spoken of as a gift of life. In the social sciences and bioethics this concept has been subject to critique over the course of the last two decades for failing to reflect the complexities of organ and tissue exchange. I suggest that a new ethical model of organ donation and transplantation is needed to capture the range of experiences in this domain. The proposed model is both analytical and empirically oriented, and draws on research findings linking a series of qualitative sociological studies undertaken in New Zealand between 2007 and 2013. The studies were based on document analysis, field notes and 127 semi‐structured in‐depth interviews with people from different cultural and constituent groups directly involved in organ transfer processes. The aim of the article is to contribute to sociological knowledge about organ exchange and to expand the conceptual toolkit of organ donation to include the unconditional gift, the gift relation, gift exchange, body project, and body work. The rationale for the proposed model is to provide an explanatory framework for organ donors and transplant recipients and to assist the development of ethical guidelines and health policy discourse.     

The ethics debate in relation to xenotransplantation

Xenotransplantation is the transplantation of organs and cells from one species to another: it has enormous potential to increase the supply of organs and tissues to alleviate human disease. Recent scientific progress has eliminated the obstacle of hyperacute rejection, which is the massive destruction of the transplanted organ within 24 h. Despite this progress and the tremendous clinical potential, a number of ethical issues require careful consideration. These issues involve the human recipients, source animals, biotechnology companies and ultimately, the general public. One of the greatest concerns is the potential risk that an infectious agent will be transferred with the organ to the recipient, from whom it may spread, leading to a possible epidemic. However, there is no current evidence that porcine endogenous retrovirus, which is the agent of greatest concern, will be pathogenic. Using modern biotechnology, it may be possible to generate pigs that are free of this virus in the near future. Addressing these issues deliberately and in a scientific manner, with public involvement and education, will result in a greater understanding of the risks and benefits of xenotransplantation. This knowledge can then be utilised to fulfil the increasing demand for transplantable organs, with minimal risk.     

Problematising the ethics of organ donation after circulatory death in the UK

This commentary addresses the ethics of controlled organ donation after circulatory death (DCD) in the UK, a practice which has recently been revived as part of attempts to increase rates of organ donation. Despite being linked to growth in donor rates, bioethics and clinical scholars have drawn attention to the ethical issues which DCD poses for health professionals, particularly around the requirement to alter the end-of-life care of potential donors. In this commentary, the UK policy response to the ethics of DCD is examined by drawing on Foucault’s problematisation approach. This analyses the broader contexts within which the policy version of ethics for DCD has been created, and examines the potential implications of this form of ethics for the work of health professionals. It is argued that the policy version of ethics for DCD has a specific normalising role, which acts as an integral part of the efficiency drive by transplant medicine to optimise the potential for donation. In turn, this form of ethics is premised upon providing the right tools for health professionals to make ethical decisions around DCD. In so doing, it fails to account for the everyday practices of health professionals involved in end-of-life care. In conclusion, the commentary advocates bringing the social science perspective into debates on DCD, to ensure that the terms and practice of this technology, and its policies, are adequately problematised.     

In defense of the reverence of all life: Heideggerean dissolution of the ethical challenges of organ donation after circulatory determination of death

During the past 50 years since the first successful organ transplant, waiting lists of potential organ recipients have expanded exponentially as supply and demand have been on a collision course. The recovery of organs from patients with circulatory determination of death is one of several effective alternative approaches recommended to reduce the supply-and-demand gap. However, renewed debate ensues regarding the ethical management of the overarching risks, pressures, challenges and conflicts of interest inherent in organ retrieval after circulatory determination of death. In this article, the author claims that through the engagement of a Heideggerean existential phenomenological and hermeneutic framework what are perceived as ethical problems dissolve, including collapse of commitment to the dead donor rule. The author argues for a revisioned socially constructed conceptual and philosophical responsibility of humankind to recognize the limits of bodily finitude, to responsibly use the capacity of the transplantable organs, and to grant enhanced or renewed existence to one with diminished or life-limited capacity; thereby making the locus of ethical concern the donor–recipient as unitary ‘‘life.’’ What ethically matters in the life-cycle (life-world) of donor–recipient is the viability of the organs transplanted; thereby granting reverence to all life.     

Patients,Families, and Organ Donation: Who Should Decide?

Although 69 to 75 percent of U.S. adults say they would be willing to become organ donors, half of the families that are asked to consider donating the organs of a deceased family member refuse to consent. This discrepancy is most noticeable when the refusal of a family conflicts with the known wishes of a patient. It is the practice of nearly all organ procurement organizations in the United States not to procure organs or tissue when families refuse, even if the patient's wishes have been documented. Recently, the Center for Organ Recovery and Education (CORE) adopted a controversial policy of acting on the documented wishes of individuals to donate, independent of family consent. An examination of the moral and political issues raised by this policy lead to the conclusion that the CORE policy is not only justified, but morally required.     

Gamete retrieval in terminal conditions: is it practical? What are the consequences?

There is an increasing interest in, and request for, gamete retrieval from recently deceased or near-dead subjects for the purpose of posthumous procreation. This usually arises in an emergency situation with little time for physicians to consider ethical ramifications. Advance planning is needed to help these physicians make thoughtful decisions. After considering the complexity of the issues involved, the Ethics Consult Service and the Ethics Committee at the University of Virginia requested that we develop a policy on gamete retrieval for subjects in terminal conditions, which would govern and guide involved providers should this process be requested. Our team consisted of members of the Ethics Consult Service and Ethics Committee, as well as personnel who might be intimately involved in the gamete retrieval process, including the director of the Human Gamete and Embryo Laboratory, a urologist, and a reproductive endocrinologist. In addition to reviewing the current literature describing the actual processes involved, we explored the ethical implications of gamete retrieval in these situations. A policy was developed and approved by the Ethics Committee at our institution, and is included in this article.     

Nanomedicine–emerging or re-emerging ethical issues? A discussion of four ethical themes

Nanomedicine plays a prominent role among emerging technologies. The spectrum of potential applications is as broad as it is promising. It includes the use of nanoparticles and nanodevices for diagnostics, targeted drug delivery in the human body, the production of new therapeutic materials as well as nanorobots or nanoprotheses. Funding agencies are investing large sums in the development of this area, among them the European Commission, which has launched a large network for life-sciences related nanotechnology. At the same time government agencies as well as the private sector are putting forward reports of working groups that have looked into the promises and risks of these developments. This paper will begin with an introduction to the central ethical themes as identified by selected reports from Europe and beyond. In a next step, it will analyse the most frequently invoked ethical concerns–risk assessment and management, the issues of human identity and enhancement, possible implications for civil liberties (e.g. nanodevices that might be used for covert surveillance), and concerns about equity and fair access. Although it seems that the main ethical issues are not unique to nanotechnologies, the conclusion will argue against shrugging them off as non-specific items that have been considered before in the context of other biomedical technologies, such as gene therapy or xenotransplantation. Rather, the paper will call on ethicists to help foster a rational, fair and participatory discourse on the different potential applications of nanotechnologies in medicine, which can form the basis for informed and responsible societal and political decisions.     

Neither property right nor heroic gift,neither sacrifice nor aporia: the benefit of the theoretical lens of sharing in donation ethics

Two ethical frameworks have dominated the discussion of organ donation for long: that of property rights and that of gift-giving. However, recent years have seen a drastic rise in the number of philosophical analyses of the meaning of giving and generosity, which has been mirrored in ethical debates on organ donation and in critical sociological, anthropological and ethnological work on the gift metaphor in this context. In order to capture the flourishing of this field, this article distinguishes between four frameworks for thinking about bodily exchanges in medicine: those of property rights, heroic gift-giving, sacrifice, and gift-giving as aporia. These frameworks represent four different ways of making sense of donation of organs as well as tissue, gametes and blood, draw on different conceptions of the relations between the self and the other, and bring out different ethical issues as core ones. The article presents these frameworks, argues that all of them run into difficulties when trying to make sense of reciprocity and relational interdependence in donation, and shows how the three gift-giving frameworks (of heroism, sacrifice and aporia) hang together in a critical discussion about what is at stake in organ donation. It also presents and argues in favour of an alternative intercorporeal framework of giving-through-sharing that more thoroughly explicates the gift metaphor in the context of donation, and offers tools for making sense of relational dimensions of live and post mortem donations.     

Social consensus on medical technology policy: ethical issues and citizen participation

Social consensus is considered to be a necessary condition for a policy to be introduced and implemented effectively. This is the case with the approval, regulation and prohibition of certain advanced medical research and technology, especially when they could invoke moral disputes in society. Public policies on organ transplantation, definition of death, euthanasia, genetic screening and diagnosis, and human stem cell research are recent examples. The concept of consensus, however, is elusive, along with the measures to secure it. Technocratic decision making, as a paternalistic activity frequently led by experts, sometimes poses a challenge to democratic decision making, supposedly based on a well-informed and rational public. It also remains to be proved whether public involvement in policymaking can be a solution to ethical value conflicts in society. From the perspective of policy sciences, this paper first introduces the concept of consensus, especially consensus on moral issues in pluralistic societies, and its implications to public policy, including citizen participation in decision making. Then, it briefly explains the historical background with which social consensus and public involvement have increasingly flourished in the field of technology assessments and technology policy making, including biomedical technology. Next, major institutions, governmental and nongovernmental, involved in the ethical aspects of medical research and technology, are presented along with their efforts for citizen participation. Finally, the paper discusses some of the future agendas on this issue.     

Organ donation after assisted death: Is it more or less ethically-problematic than donation after circulatory death?

A provocative question has emerged since the Supreme Court of Canada’s decision on assisted dying: Should Canadians who request, and are granted, an assisted death be considered a legitimate source of transplantable organs? A related question is addressed in this paper: is controlled organ donation after assisted death (cDAD) more or less ethically-problematic than standard, controlled organ donation after circulatory determination of death (cDCDD)? Controversial, ethics-related dimensions of cDCD that are of relevance to this research question are explored, and morally-relevant distinctions between cDAD and cDCD are identified. In addition, a set of morally-relevant advantages of one practice over the other is uncovered, and a few potential, theoretical issues specifically related to cDAD practice are articulated. Despite these concerns, the analysis suggests a counterintuitive conclusion: cDAD is, overall, less ethically-problematic than cDCDD. The former practice better respects the autonomy interests of the potential donor, and a claim regarding irreversibility of cessation of the donor’s circulatory function in the cDAD context can be supported. Further, with cDAD, there is no possibility that the donor will have negative sensory experiences during organ procurement surgery. Although the development of appropriate policy-decision and regulatory approaches in this domain will be complex and challenging, the comparative ethical analysis of these two organ donation practices has the potential to constructively inform the deliberations of relevant stakeholders, resource persons and decision makers.     

Incentivizing Organ Donor Registrations with Organ Allocation Priority

How donor organs are allocated for transplant can affect their scarcity. In 2008, Israel's Parliament passed an Organ Transplantation Law granting priority on organ donor waiting lists to individuals who had previously registered as organ donors. Beginning in November 2010, public awareness campaigns advertised the priority policy to the public. Since April 2012, priority has been added to the routine medical criteria in organ allocation decisions. We evaluate the introduction of priority for registered organ donors using Israeli data on organ donor registration from 1992 to 2013. We find that registrations increased when information about the priority law was made widely available. We find an even larger increase in registration rates in the 2 months leading up to a program deadline, after which priority would only be granted with a 3‐year delay. We also find that the registration rate responds positively to public awareness campaigns, to the ease of registration (i.e. allowing for registering online and by phone) and to an election drive that included placing registration opportunities in central voting locations. Copyright © 2016 John Wiley & Sons, Ltd.     

The ethical implications and religious significance of organ transplantation payment systems

One of the more polarizing policies proposed to alleviate the organ shortage is financial payment of donors in return for organs. A priori and empirical investigation concludes that such systems are ethically inadequate. A new methodological approach towards policy formation and implementation is proposed which places ethical concerns at its core. From a hypothetical secular origin, the optimal ethical policy structure concerning organ donation is derived. However, when applied universally, it does not yield ideal results for every culture and society due to region-specific variation. Since religion holds significant influence in the organ donation debate, three religions—Catholicism, Islam, and Shinto—were examined in order to illustrate this variation. Although secular ethical concerns should rest at the core of policy construction, certain region-specific contexts require cultural and religious competence and necessitate the adjustment of the optimal template policy accordingly to yield the best moral and practical results.     

Some ethical aspects of donation and transplantation

Ethical and legal consensus in our country bases the practice of donations and transplants on different ethical principles, which are contained in the legislation, closely conforming to the four principles of principialist bioethics: autonomy, beneficence, non-maleficence, and justice. The level of donations achieved in our milieu might, in fact, be related to a strict respect for these principles by the health professionals, as well as to the excellent organisation of the transplant world. Many scientific, technical and ethical challenges have had to be met to reach the present state of the transplant. And there are many current challenges. The article only analyses some of these due to their technical, ethical and social repercussions: organ transplants involving a live donor, the public request for organs, the organ market, the transplant of non-vital organs (basically the face transplant), the use of stem cells and the banks of umbilical cord cells. The aim of the article is to state the ethical problems raised by these new practices, in order to lay the foundations for a moral deliberation that must necessarily involve the whole of society.     

International perspectives on the ethics and regulation of human cell and tissue transplantation

The transplantation of human cells and tissues has become a global enterprise for both life-saving and life-enhancing purposes. Yet current practices raise numerous ethical and policy issues relating to informed consent for donation, profit-making, and quality and safety in the procurement, processing, distribution, and international circulation of human cells and tissues. This paper reports on recent developments in the international debate surrounding these issues, and in particular on the attention cell and tissue transplantation has received in WHO's ongoing process of updating its 1991 Guiding principles on human organ transplantation. Several of the organizers of an international working group of stakeholders from a wide range of backgrounds that convened in Zurich in July 2006 summarize the areas of normative agreement and disagreement, and identify open questions regarding facts and fundamental concepts of potential normative significance. These issues must be addressed through development of common medical, scientific, legal and ethical requirements for human cell and tissue transplantation on a global basis. While guidance must accommodate the distinct ethical issues raised by activities involving human cells and tissues, consistency with normative frameworks for organ transplantation remains a prime objective.     

Using practice guidelines to allocate medical technologies. An ethics framework

Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.     

Xenotransplantation: utopia or clinical reality?

Xenotransplantation, i.e. the transplantation of organs (tissues, cells) from animals into humans has been a major question in medicine for many years. Based on the ever increasing shortage of suitable donor organs, the research of xenotransplantation grew more intensive than ever before. The problems associated with xenotransplantation can be divided into four categories: i./ immunological, ii./ physiological, iii./ infectious-microbiological, iv./ ethical. In this study the author attempts to summarize the possibilities of xenotransplantation, the problems associated with it, and their possible solutions.     

猪内源性逆转录病毒及其敲除抑制方法

猪内源性逆转录病毒（porcine endogenous retrovirus,PERV）是一种以前病毒DNA形式整合入猪基因组中的逆转录病毒,它可随细胞基因组的复制而复制。部分猪源细胞可释放PERV病毒颗粒,并能感染多种体外培养的人源细胞。由于猪器官大小和解剖生理与人体器官相似,被认为是异种器官移植的最佳供体。但猪基因组内的 PERV 存在跨物种间感染风险,以猪源器官作为器官供体移植人体后可能导致 PERV 感染人体。PERV 感染是异种器官移植的一大障碍,从生物安全性考虑,需要去除或抑制猪基因组内PERV,以降低其物种间传播风险。因此,本文对PERV的生物学特征及近年来PERV的去除和抑制方法等方面的研究进展进行了综述。