Research opportunities and ethical considerations for heart and lung xenotransplantation research: A report from the National Heart, Lung, and Blood Institute workshop.

Xenotransplantation offers the potential to meet the critical need for heart and lung transplantation presently constrained by the current human donor organ supply. Much was learned over the past decades regarding gene editing to prevent the immune activation and inflammation that cause early organ injury, and strategies for maintenance of immunosuppression to promote longer-term xenograft survival. However, many scientific questions remain regarding further requirements for genetic modification of donor organs, appropriate contexts for xenotransplantation research (including nonhuman primates, recently deceased humans, and living human recipients), and risk of xenozoonotic disease transmission. Related ethical questions include the appropriate selection of clinical trial participants, challenges with obtaining informed consent, animal rights and welfare considerations, and cost. Research involving recently deceased humans has also emerged as a potentially novel way to understand how xeno-organs will impact the human body. Clinical xenotransplantation and research involving decedents also raise ethical questions and will require consensus regarding regulatory oversight and protocol review. These considerations and the related opportunities for xenotransplantation research were discussed in a workshop sponsored by the National Heart, Lung, and Blood Institute, and are summarized in this meeting report.

Perception of Polish patients with cancer of the ethical and legal issues related to biobank research.

BACKGROUND: Although biobanks have become fundamental to many research centers and contribute to medical development, they generate many ethical and legal issues that may discourage patients from donating. MATERIALS AND METHODS: To understand patients' perception of ethical and legal issues related to biobanks we conducted a survey among 548 Polish patients with cancer. RESULTS: While 93.1% of patients with cancer declared themselves willing to donate biospecimens left over after a medical procedure to a biobank, most opted for one-time consent or study-specific consent, blanket consent being less frequently preferred. Many patients believed that future use of previously collected tissues require second contact. Most patients preferred pseudonymization over anonymization of the data, and supported donors' right to withdraw informed consent at any given moment. Finally, while personal health information was the most expected form of compensation for donation, most patients suggested that all parties, including the biobank concerned, the sponsors of the research, and the donors, should own the rights to cancer tissues donated and profit from the biobank research. Patients' opinions on the ethical and legal issues related to biobank research were associated with age, sex, religiosity, education level, and place of residence. CONCLUSIONS: Since biobanks generate ethical and legal issues related to informed consent, data protection and storage, as well as the sharing of biosamples, tissue ownership, and profit sharing, that may discourage patients from donation, when asking a patient for a donation, healthcare professionals should communicate in a donor-centered manner and address patients' ethical and moral concerns related to donation and offer resources to help manage these concerns.

Ethical and Equity Guidance for Transplant Programs Considering Thoracoabdominal Normothermic Regional Perfusion (TA-NRP) for Procurement of Hearts.

Donation after circulatory determination of death (DCDD) is an accepted practice in the United States, but heart procurement under these circumstances has been debated. Although the practice is experiencing a resurgence due to the recently completed trials using ex vivo perfusion systems, interest in thoracoabdominal normothermic regional perfusion (TA-NRP), wherein the organs are reanimated in situ prior to procurement, has raised many ethical questions. We outline practical, ethical, and equity considerations to ensure transplant programs make well-informed decisions about TA-NRP. We present a multidisciplinary analysis of the relevant ethical issues arising from DCDD-NRP heart procurement, including application of the Dead Donor Rule and the Uniform Definition of Death Act, and provide recommendations to facilitate ethical analysis and input from all interested parties. We also recommend informed consent, as distinct from typical "authorization," for cadaveric organ donation using TA-NRP.

Restoring the Organism as a Whole: Does NRP Resurrect the Dead?

The introduction of normothermic regional perfusion (NRP) in controlled donation after circulatory determination of death (cDCDD) protocols is by some regarded as controversial and ethically troublesome. One of the main concerns that opponents have about introducing NRP in cDCDD protocols is that reestablishing circulation will negate the determination of death by circulatory criteria, potentially resuscitating the donor. In this article, I argue that this is not the case. If we take a closer look at the concept of death underlying the circulatory criterion for determination of death, we find that the purpose of the criterion is to show whether the organism as a whole has died. I argue that this purpose is fulfilled by the circulatory criterion in cDCDD protocols, and that applying NRP does not negate the determination of death or resuscitate the donor.

An Ethics Committee's Evaluation of Normothermic Regional Perfusion (NRP) in 2018-Unsatisfactory Answers Then-and Now.

An adult university hospital ethics committee evaluated a proposed TA-NRP protocol in the fall of 2018. The protocol raised ethical concerns about violation of the Uniform Determination of Death Act and the prohibition known as the Dead Donor Rule, with potential resultant legal consequences. An additional concern was the potential for increased mistrust by the community of organ donation and transplantation. The ethics committee evaluated the responses to these concerns as unable to surmount the ethical and legal boundaries and the ethics committee declined to endorse the procedure. These concerns endure.

Squaring the Circle. Brain death and organ transplantation.

PURPOSE OF REVIEW: The adoption of brain death played a crucial role in the development of organ transplantation, but the concept has become increasingly controversial. This essay will explore the current state of the controversy and its implications for the field. RECENT DEVELOPMENTS: The brain death debate, long limited to the bioethics community, has in recent years burst into the public consciousness following several high-profile cases. This has culminated in the reevaluation of the Uniform Determination of Death Act (UDDA), which is in the process of being updated. Any change to the UDDA has the potential to significantly impact the availability of organs. SUMMARY: The current update to the UDDA introduces an element of uncertainty, one the brain death debate had not previously had.

Ethical Solutions to the Problem of Organ Shortage.

Organ shortage is a major survival issue for millions of people worldwide. Globally 1.2 million people die each year from kidney failure. In this paper, we critically examine and find lacking extant proposals for increasing organ supply, such as opting in and opt out for deceased donor organs, and parochial altruism and paired kidney exchange for live organs. We defend two ethical solutions to the problem of organ shortage. One is to make deceased donor organs automatically available for transplant without requiring consent from the donor or their relatives. The other is for society to buy nonvital organs in a strictly regulated market and provide them to people in need for free.

The unique moral permissibility of uncontrolled lung donation after circulatory death.

Implementing uncontrolled donation after circulatory determination of death (uDCDD) in the United States could markedly improve supply of donor lungs for patients in need of transplants. Evidence from US pilot programs suggests families support uDCDD, but only if they are asked permission for using invasive organ preservation procedures prior to initiation. However, non-invasive strategies that confine oxygenation to lungs may be applicable to the overwhelming majority of potential uDCDD donors that have airway devices in place as part of standard resuscitation. We propose an ethical framework for lung uDCDD by: (a) initiating post mortem preservation without requiring prior permission to protect the opportunity for donation until an authorized party can be found; (b) using non-invasive strategies that confine oxygenation to lungs; and (c) maintaining strict separation between the healthcare team and the organ preservation team. Attempting uDCDD in this way has great potential to obtain more transplantable lungs while respecting donor autonomy and family wishes, securing public support, and enabling authorized persons to affirm or cease preservation decisions without requiring evidence of prior organ donation intent. It ensures prioritization of life-saving, the opportunity to allow willing donors to donate, and respect for bodily integrity while adhering to current ethical norms.

Thewithdrawal of consent to haematopoietic stem cells (HSC) donation: The complicated balance between donor's rights and patient's protection.

Hematopoietic stem cells donation is an essential prerequisite of allogeneic transplantation. Both family donors and matched unrelated donors should have a conscious involvement in every phase of the overall path, from selection to HSC collection. Donors also should be informed about the right to withdraw at any time as well as the extreme risk for recipient's life coming from the decision of interrupting, if the donation is not carried out once the patient's preparative regimen has commenced. We report our challenging experience about a donor who withdraws her consent to HSC donation after 3 days of mobilization with G-CSF. The possibility of withdrawal protects the donor but it also puts at risk both a chance for a transplant and the patient's life if preparative regimen has started. Can the donor really be free to withdraw the consent to HSC donation at any time even when this endangers the life of a recipient? Is this ethical? However, if the donor decides to withdraw, would we really be ready to manage promptly all the consequences coming from the consent revocation? At the moment there is not a well-defined "plan B" in case of impossibility to proceed with the transplant when conditioning has already started or has even been completed. In our opinion, because of this hard balance and such a high risk, it would be necessary to plan every time an alternative strategy which may be different according to different circumstances.

Examining consent for interventional research in potential deceased organ donors: a narrative review.

In the last decade, research in transplant medicine has focused on developing interventions in the management of the deceased organ donor to improve the quality and quantity of transplantable organs. Despite the promise of interventional donor research, there remain debates about the ethics of this research, specifically regarding gaining research consent. Here, we examine the concerns and ambiguities around consent for interventional donor research, which incorporate questions about who should consent for interventional donor research and what people are being asked to consent for. We highlight the US and UK policy responses to these concerns and argue that, whereas guidance in this area has done much to clarify these ambiguities, there is little consideration of the nature, practicalities and context around consent in this area, particularly regarding organ donors and their families. We review wider studies of consent in critical care research and social science studies of consent in medical research, to gain a broader view of consent in this area as a relational and contextual process. We contend a lack of consideration has been given to: what it might mean to consent to interventional donor research; how families, patients and health professionals might experience providing and seeking this consent; who is best placed to have these discussions; and the socio-institutional contexts affecting these processes. Further, empirical research is required to establish an ethical and sensitive model for consent in interventional donor research, ensuring the principles enshrined in research ethics are met and public trust in organ donation is maintained.

Decisional authority of gamete donors over embryos created with their gametes.

In the ongoing discussion on the rights and obligations of gamete donors, scant attention has been paid to the decisional authority of gamete donors over the disposition of the embryos created with their gametes. This paper analyses four different positions: three cases relate to the disposition options for surplus or unused embryos by the first recipients, and one case relates to the use of the embryos stored by the first recipients for procreation.We conclude that the gamete donor causally contributes to the creation of the embryos and thus becomes indirectly responsible. To avoid that donors would become accomplices to an activity to which they morally object, a qualified generic consent mentioning types of research should be obtained. No consent from the donor is required for the destruction of the embryos.The cancellation of the agreement by anonymous or identifiable gamete donors should not be possible for embryos in storage for reproduction by the recipients. The interests in not becoming a genetic parent against one's wishes do not outweigh the damage done to recipients who would no longer be able to use their embryos. Known donors, on the contrary, should be able to withdraw their consent up to the moment of transfer of the embryos based on the greater harm caused to them as a consequence of attributional parenthood. They should also be able to veto transfer of the embryos to other people than the original recipients.

Where do these cadavers come from?

Cadaveric surgical courses are highly useful in developing operative skills, however, the provenance of the cadavers themselves remains opaque. Trade in cadaveric parts is an important source of material for courses, and this has spawned the unique service of body brokerage. Body brokers, however, operate in an unregulated market and obtain bodies by exploiting family members' altruistic instincts and financial concerns. Unethical and illegal sale of body parts has been well-documented, while the use of cadavers for uses other than that consented by donors is also a key concern. Undoubtedly, cadaveric surgical courses would have used bodies sourced from brokers, and questions remain about the moral and ethical implications of this. We discuss this issue using an ethical and historical context as well as offering solutions to ensure the ethical sourcing of cadavers for surgical training.

The ethical obligation of the dead donor rule.

The dead donor rule (DDR) originally stated that organ donors must not be killed by and for organ donation. Scholars later added the requirement that vital organs should not be procured before death. Some now argue that the DDR is breached in donation after circulatory determination of death (DCDD) programs. DCDD programs do not breach the original version of the DDR because vital organs are procured only after circulation has ceased permanently as a consequence of withdrawal of life-sustaining therapy. We hold that the original rendition of the DDR banning killing by and for organ donation is the fundamental norm that should be maintained in transplantation ethics. We propose separating the DDR from two other fundamental normative rules: the duties to prevent harm and to obtain informed consent.

Remapping the organ donation ethical climate: a care ethics consideration.

Organ donation has gained much attention as the need for transplant exceeds the supply of organs. Various proposals have been put forward to address the organ shortage challenge, ranging from offering incentives to donors, addressing family refusals to donations and instituting presumed consent laws. Presumed consent as the favoured approach has not been universally effective in increasing actual transplants despite its appeal. Few considerations have been given to the broader ethical climate influencing the organ donation debate. This paper examines the ethical climate surrounding organ donation and identifies the challenges existing within such environments. It explores care ethics and its application to the donation system, demonstrating how it can influence the organ donation phases. The conclusion drawn from the analysis is that a caring ethical climate in the pre, during and post-transplant system respects donor autonomy, addresses family reluctance to agree to donation, facilitates the needs of the donee and creates an environment that promotes non-maleficence for all stakeholders.

Assessment of Somatic Support Process for Pregnant Brain Death Patients Occurring in a Transition Country Between Asia and Europe from Medical, Ethical, Legal and Religious Aspects.

In spite of the fact that brain death during pregnancy is not a common occurrence, it is an important ethical problem for all cultures and religions can have a significant influence on the donation decision after brain death. Therefore, this study aimed to present the case of a pregnant patient developing brain death which occurred in our intensive care unit and to compare the medical, ethical and legal problems relating to pregnant cases developing brain death with 24 cases in the literature. A 21-year-old 19-week pregnant case with gestational diabetes was monitored in the anesthesia intensive care unit and developed brain death due to intracranial mass and intraventricular hemorrhage. Though brain death is a situation well understood by organ transplant professionals, brain death developing in pregnant patients still involves many medical, ethical and legal problems.

[An ethical evaluation of presumed consent for organ donation in Switzerland]. / Une évaluation éthique du consentement présumé pour le don d'organes en Suisse.

Following a current trend in European countries, Switzerland is about to decide to adopt (or reject) a presumed consent legislation for organ donation. In such a system, every citizen is considered as a potential organ donor except in case of expressed refusal during lifetime. The presumed consent system raises ethical and practical issues that need to be carefully understood and weighed before deciding on its fate. This article reviews the most pressing ethical issues and provides the empirical data necessary for assessing the presumed consent legislation in Switzerland. At the end of the analysis, the reader will be able to form her own informed opinion on the issue.

A l'image d'autres pays européens, la Suisse est sur le point de décider d'adopter (ou de rejeter) une législation du consentement présumé pour le don d'organes. Dans un tel système, tout citoyen est considéré comme donneur potentiel, sauf en cas de refus exprimé de son vivant. Le consentement présumé soulève des enjeux éthiques et pratiques qu'il importe de comprendre et pondérer soigneusement avant de statuer sur son sort. Cet article fournit les principales clefs d'analyse ainsi que les données empiriques nécessaires à cet exercice. Au terme de l'analyse, le lecteur pourra se forger une opinion informée et réfléchie sur le sujet.

Genetic databases and the future of donor anonymity.

Anonymity is a multifaceted term. Anonymity is rarely eternal or absolute. The use of genetic databases increases the risk of identification of previously anonymous donors. Searches through genetic databases jeopardize the privacy of people who did and did not register on them. Three types of searches can be distinguished in the context of gamete donation: offspring looking for their donor, offspring looking for donor siblings and donors looking for their donor offspring. All three types of searches violate the rights of recipients and donors. It is argued that despite the existence of genetic databases, anonymity maintains the same function as it had before: it expresses a wish for distance and privacy by both donors and recipients and, even if not enforceable, should be respected by all parties in good faith.

Utilisation of small paediatric donor kidneys for transplantation.

With the increasing need for kidney transplantation in the paediatric population and changing donor demographics, children without a living donor option will potentially be offered an adult deceased donor transplant of marginal quality. Given the importance of long-term graft survival for paediatric recipients, consideration is now being given to kidneys from small paediatric donors (SPDs). There exist a lack of consensus and a reluctance amongst some centres in transplanting SPDs due to high surgical complication rates, graft loss and concerns regarding low nephron mass and long-term function. The aim of this review is to examine and present the evidence base regarding the transplantation of these organs. The literature in both the paediatric and adult renal transplant fields, as well as recent relevant conference proceedings, is reviewed. We discuss the surgical techniques, long-term graft function and rates of complications following transplantation of SPDs. We compare graft survival of SPDs to adult deceased donors and consider the use of small paediatric donors after circulatory death (DCD) organs. In conclusion, evidence is presented that may refute historically held paradigms regarding the transplantation of SPDs in paediatric recipients, thereby potentially allowing significant expansion of the donor pool.

Is it acceptable to contact an anonymous egg donor to facilitate diagnostic genetic testing for the donor-conceived child?

We discuss a case where medically optimal investigations of health problems in a donor-conceived child would require their egg donor to participate in genetic testing. We argue that it would be justified to contact the egg donor to ask whether she would consider this, despite her indicating on a historical consent form that she did not wish to take part in future research and that she did not wish to be informed if she was found to be a carrier of a 'harmful inherited condition'. We suggest that we cannot conjecture what her current answer might be if, by participating in clinical genetic testing, she might help reach a diagnosis for the donor-conceived child. At the point that she made choices regarding future contact, it was not yet evident that the interests of the donor-conceived child might be compromised by her answers, as it was not foreseen that the egg donor's genome might one day have the potential to enable diagnosis for this child. Fertility consent forms tend to be conceptualised as representing incontrovertible historical boundaries, but we argue that rapid evolution in genomic practice means that consent in such cases is better seen as an ongoing and dynamic process. It cannot be possible to compel the donor to aid in the diagnosis of the donor-conceived child, but she should be given the opportunity to do so.