Stand: Mai 2023
Ansprechpartner: Marius Bartmann

Autorennachweis

The history of transplantation medicine

 There are indications in some ancient myths that man may have attempted to perform transplantations in historic times, but the origins of scientifically sound transplantation practice can be traced back to the early twentieth century when improvements in vascular surgery and operation techniques provided practitioners with the necessary technological basis. The first successful kidney transplantation was performed between identical twins in the USA in 1954. 1963 saw the first successful liver and also the first lung transplantation. In 1965, the pioneers managed to transplant a pancreas successfully. The first heart transplantation, carried out by Christiaan Barnard in South Africa in December 1967, caught the attention of people throughout the world. The first successful multi-organ transplantation took place in 1989. The problems which became evident during the initial stages, such as the difficulties encountered in preserving organs after removal or in dealing with the recipients' immunological response, could be addressed and at least to some extent solved through the experience gained and the development of immunosuppressive drugs.

The present state of research

 Transplantation medicine today is recognized as being part of standard professional practice in many countries. Especially in the case of end-stage failure of organs which is called terminal organ failure, organ transplantation is mostly the only treatment option. There is a long list of different cell and tissue types, organs or indeed entire organ systems for which the medical basis for transplantation is now secured.

 Transplantation can only succeed when the transplanted material is not rejected by the receiving organism. Transplantation of foreign organs may trigger an immunological defence reaction, with the result that the transplanted organ cannot fulfil its proper function. One differentiates between acute rejection and chronic rejection. Acute rejection refers to the period immediately following transplantation, and it may occur in varying degrees of severity. The chronic form of rejection is characterised by a long-term process in which the organ gradually fails. The defence mechanisms of the patient's own body must be kept permanently suppressed with the help of immunosuppressive medication, and this requires a high degree of cooperation on the part of the patient.

In addition to the phenomenon of failure or rejection of the transplanted organ or tissue, transplantations can also lead to a so-called graft-versus-host reaction in which the immune system cells which are transferred with the transplant recognise the recipient's body as being "foreign" and attack it.

With xenotransplantations, as is the case in general, the biggest obstacle to a successful, long-term transplant is immune responses against the donor organ. Modern techniques of genome editing, particularly the gene scissors CRISPR/Cas9, contributed substantially to engineering pig hearts in such a way as to minimize the risk of the organism's organ rejection (see also the entry on genome editing in human medicine).

In early 2022, a significant advance in the field of xenotransplantation was achieved. For the first time, the heart of a genetically modified pig was transplanted into a patient. Genes were deactivated which can cause rejection reactions of the human immune system. Furthermore, human genes were added to increase the acceptance of the foreign organ. Finally, genetic modifications were made to prevent the porcine organ from responding to growth hormones and increasing in size beyond what is normal in humans. The patient survived for 2 months. The exact cause of death is not yet fully determined, but one factor was probably a viral infection of the pig's heart that initially went undetected. Nevertheless, the procedure is considered a milestone in xenotransplantation.

Organ demand and shortage

 There is a great disparity between organ demand and organ donations. In Germany, according to the German Foundation for Organ Transplantation (DSO), a total of 2,905 organs were donated post-mortem in 2021, but 8,730 organs were needed for patients on the transplant list.

According to the DSO's assessment, the violations of guidelines for organ allocation that became known in 2012 have led to a loss of public confidence in the transplantation system: Audits had shown that data had been manipulated in individual transplant clinics to help patients obtain a donor organ more quickly. On the other hand, the increasing importance of advance decisions is also seen as a possible cause for declining donor numbers, as conflicts can arise between living wills and organ donation declarations. This is when a patient documents a basic willingness to donate organs but simultaneously objects to the performance of life-sustaining measures in an advance directive. The conflict arises because organ transplantation requires life-sustaining measures, from brain death diagnosis to potential donation.

According to a representative survey by the Federal Center for Health Education (BZgA), 84% of respondents in 2022 had a positive attitude toward organ and tissue donation, but only 31% had documented their decision in an organ donor card. Policymakers are therefore focusing on broad-based education of the population about the importance of and options for organ donation. One key measure was the introduction of the so-called decision solution in 2012, which stipulates that all health insurance policyholders over the age of 16 are regularly asked about their willingness to donate organs. However, in the aforementioned BZgA survey, only 54% stated that they were sufficiently informed on the subject.

Because the demand for organs would probably not be met in full even if the willingness to donate organs were considerably greater, it is also important to use and further develop alternative forms of transplant recovery. For some organs, such as the kidneys and liver, the option of living donation can be used. Other alternatives to post-mortem organ donation include the development of artificial organs (alloplastic transplantation), the use of animal organs (xenotransplantation), or the generation of organs from stem cells. Because these possibilities of organ procurement are still under development and are in part ethically controversial, there are also repeated attempts to commercialize organ donation. Models for commercialization apply to both living donation and post-mortem organ donation. In the United Kingdom, a model proposed by the Nuffield Council on Bioethics caused a stir in 2011: For organ donors, the government health care system should cover funeral costs. However, such proposals are largely viewed critically. The United Nations (UN) and the World Health Organization (WHO), for example, reject any commercialization of organ donation, citing human rights – even though the shortage of organs is increasingly leading to illegal organ trafficking.

Organ donation in Germany

In Germany, the transplantation of human organs is regulated by the "Gesetz zur Spende, Entnahme und Übertragung von Organen und Geweben" (German Transplantation Act). This was passed by the German Bundestag on 05 November 1997, came into force on 01 December 1997, was published in a new version on 04 September 2007 and reformed on 01 August 2012. Depending on whether the organs are removed post-mortem or from a living donor, it imposes different regulations.

In general, in Germany the so-called decision solution is in place, i.e. the organs of a deceased person may only be retrieved if the person in question permitted organ donation (§ 3 para. 1 no. 1 TPG), e.g. in the form of an organ donor card, or if the next of kin consent to the donation (§ 4 TPG). After years of discussion about the introduction of a dissent solution to address the low number of organ donations, the decision solution that had already been in place was essentially confirmed by the Bundestag on January 16, 2020. The corresponding "Act to Strengthen Decision-Making in Organ Donation" (Gesetz zur Stärkung der Entscheidungsbereitschaft bei der Organspende) came into force on March 1, 2022. The previously applicable decision solution is retained, according to which organ donation must be a conscious and voluntary decision. To strengthen the willingness to make a decision, the law provides for the introduction of an online register in which citizens can record their decision. In addition, primary care professionals should regularly encourage the people they treat to document their decision in this online register, which will additionally be possible in ID centres in the future.  The Second Act Amending the Transplantation Act (GZSO) was already passed in April 2019.

The procedure of a post-mortem organ donation in Germany

The Transplantation Act stipulates that three parties, in particular, must be significantly involved in the organization of a post-mortem organ donation: firstly, the collection hospitals and transplant centres, secondly, the coordinating unit German Foundation for Organ Transplantation (DSO), and thirdly, the international allocation agency Eurotransplant.

It is the task of the hospital staff to diagnose brain death in accordance with the guidelines of the German Medical Association (Bundesärztekammer) to communicate with the next of kin and to inform the nearest operative centre of the DSO if approval for an organ donation has been obtained – either in the form of an organ donor card or in that the next of kin have confirmed the will of the person who has died. It then devolves upon the DSO to coordinate the removal of the organ. For the protection of the organ recipient, the first step is to conduct appropriate laboratory investigations. If there are no signs of infections or tumour disease which could endanger the recipient, the DSO transmits all relevant data to Eurotransplant, which performs the selection of the recipient with the help of computer analysis.

As soon as the recipient has been selected, Eurotransplant prepares the organ removal together with the DSO and the regional coordination staff of the donor hospital. At the same time, the (international) transport of the organ from the donor hospital to the respective transplantation clinic for the recipient is set in motion. The DSO reimburses the personnel and material costs which arise in the course of an organ donation. The costs incurred for the actual transplantation of the donated organ are carried by the recipient's health insurance. The name of the donor is never communicated to the recipient, and also the next of kin of the donor are not informed as to the identity of the donor. However, the transplantation centre will disclose whether it was possible to transplant the organ or organs successfully, if the next of kin wishes to find out.

The procedure for living-donor organ transplantation in Germany

A living donor transplantation represents a possible alternative to post-mortal donation. According to German Transplantation Act, a living-donor transplantation involving a kidney, parts of a liver or any other organ which cannot regenerate is only allowed between close relatives and persons with very close personal ties. In order to ensure that a donation of this kind takes place on a voluntary basis and that medical risks for the donor are minimised as far as possible, and also to preclude any possibility of abuse or organ trafficking, every potential case must be thoroughly investigated by an expert commission beforehand.

Apart from comprehensive laboratory tests to determine the respective blood groups and other medical factors such as HLA compatibility, cardiopulmonary exercise tests and organ-specific function tests are to be carried out. Finally, investigations in the form of psychological interviews must be conducted with the aim of shedding light on the relationship between the donor and the recipient, the donor's motivation and the extent to which he or she is aware of the possible consequences of losing the organ in question.

As it is possible to effectively coordinate the transplantation involving donor and recipient, the prospects of success for transplantation from a living donor are generally significantly better than is the case with post-mortal organ donations. By amendments of the German Transplantation Act on the one hand and of the Social Insurance Code (SGB V) on the other hand, pending legal uncertainties regarding treatment and aftercare of the donor have been eliminated: The graft recipient's health insurance has to reimburse all costs incurred to the donor, i.e. expenses for pre-and post-operative care, rehabilitation and continued payment of wages during periods of disability.

Ethical issues in the procurement of post-mortem donated organs

In the case of post-mortem donation, the main question from an ethical perspective is when interventions in the human body for the purpose of organ removal are ethically justifiable.

The reliable determination of death

With regard to post-mortem organ donation, there is a debate about when a person is dead, whereby the question of the concept of death as such is not a purely scientific (medical) question, but always also a normative (ethical-philosophical) question. In addition to final cardiac and circulatory arrest (cardiac death), irreversible cessation of brain function (brain death) is considered a certain criterion of death in Germany – and also in most other countries. The guidelines of the German Medical Association (Bundesärztekammer) define precisely the procedure and process of brain death diagnosis. The debate about the brain death criterion reached its climax in several drafts of the Transplantation Act and in the passing of the law in June 1997, but even at present the brain death criterion is again the subject of controversial discussion. In favour of brain death as a definite criterion for determining death, it is argued that with the loss of brain functions, the physical-spiritual unit constituting a person is destroyed forever. As soon as brain death occurs, a person can no longer think, recognize, decide, experience, plan, feel and perceive. A person can no longer have consciousness or self-awareness.

Those who oppose the use of brain death as a general criterion for death consider brain death as merely a stage encountered on the path leading to death, a phase which must still be associated with the life which is in the process of being extinguished. As many patients for whom brain death has been diagnosed still display physiological reactions – from bodily warmth and skin hue through spontaneous embraces up to erections and ejaculations and even the continuation of a pregnancy for a certain time in a brain-dead person – they maintain that those affected cannot be regarded as completely dead. A report published in 2008 by the US President's Council on Bioethics provides support for the opponents of the brain death criterion. The President's Council concludes that the equation of death and brain death can no longer be scientifically justified. Current research would show that the integration of the organism is an accomplishment brought about by the organism as a whole and not, as previously assumed, by the brain alone. Since the President's Council wants to hold on to the equation of death and brain death, it proposes an alternative justification – a natural-philosophical one instead of a scientific one. According to this new conception, what is decisive is not when a person is biologically dead, but what constitutes her or his life. The President's Council focuses on active human abilities, such as the ability to receive stimuli from the environment and to interact with it. This ability manifests itself, among other things, in spontaneous breathing. Critics, however, consider such a natural-philosophical justification of the brain death criterion problematic because it was unfalsifiable.

The report published by the US President's Council rekindled the ethical debate about the brain death criterion in Germany as well because not equating death with brain death would have serious ethical and legal consequences. In Germany, as in other countries, the removal of organs for organ donation is allowed only if the donor is dead (with the exception of living donor transplantation) – this is the so-called "Dead Donor Rule", which is enshrined in the German Transplantation Act (§ 3 TPG).

Organ removal from brain-dead people would therefore have to be regarded as a form of killing if death and brain death are not considered identical. However, if one still wants to adhere to transplantation medicine without organ removal becoming a form of killing, then according to the President's Council there would only be the following two alternatives:

1. Abandoning the "Dead Donor Rule".
2. Organ removal after cardiac death (organ removal from "non-heart-beating donors" only).

However, both alternatives are ethically and legally problematic. Abandoning the "Dead Donor Rule" would mean abandoning the unconditional validity of the ban on killing as well. Restricting organ removal exclusively to "non-heart-beating donors" would have the consequence that far fewer organs were transplanted. This dilemma is also the motive and the reason why the President's Council chose a new justification of the equation of death and brain death as a way out.

In February 2015, the German Ethics Council published an opinion on the debate about brain death. The German Ethics Council unanimously considers it acceptable to conform to a person's consent to organ donation after a correct diagnosis of brain death, thus confirming the basic idea of the prevailing German Transplant Act. The majority of the Council's members regard brain death as a sufficient criterion for ascertaining the death of a human being. A minority, however, objects to equating the irreversible failure of all brain functions with human death. Similarly to the US President's Council, this minority considers the Dead Donor Rule dispensable. The removal of organs represents an acceptable form of letting a human being die in an autonomous way rather than a wrongful killing. Since the German Ethics Council did not reach a unanimous vote on the equation of brain death and death, its opinion consequently demands a transparent exposition of the conflicting views on the criterion of brain death for the public debate.

Consent for post-mortem organ donation

At issue is whether medical professionals are authorized to remove tissue or organs from a corpse for the purpose of curing a sick person without consent given by the dead person during his or her lifetime or without the consent of his or her relatives. If the deceased person has given written or verbal consent to organ removal during his or her lifetime, medical professionals are required to determine the medical feasibility of the willingness to donate and, if possible, to carry it out. There is disagreement about how to deal with cases in which a deceased person has left neither consent nor objection. In the tension between the public interests in increasing organ donation and the interests of the deceased or the relatives in preserving the integrity of the corpse, advocates of the dissent solution seek a balance: Organ transplantation should not be mandatory, but they place the burden of decision on the potential donor.

In order to increase the number of organ donations in Germany, many experts believe that an amendment to the Transplantation Act is necessary. As early as 2011, the Bundestag's Health Committee held a public hearing on the question of whether the consent solution for organ donation, according to which organs may only be removed from people if they themselves have recorded their consent in an organ donor card before their death or if their relatives agree to an organ removal after their death, is still up to date. The decision solution in Germany also stipulates that all citizens should be regularly asked whether they are willing to donate their organs post-mortem. The above-mentioned dissent solution was also brought up. However, the dissent solution is still extremely controversial.

Questions of fair allocation of organs when supply is limited

A further ethical problem in current transplantation medicine can be seen in the equitable distribution of post-mortally donated organs. The shortage of organs available for transplantation calls for a fair system of organ allocation. The question becomes acute in cases where two or more patients meet the medical criteria for one and the same donor organ. According to the German Transplantation Act, the allocation of organs is to be based on the criteria of  “success and urgency” (§ 12 TPG). However, these two principles may come into conflict. The likelihood of success of a transplant would be greatest in younger and comparatively healthy persons, but this would systematically disadvantage older and more severely ill persons. Conversely, a one-sided orientation to the criterion of urgency would result in a prioritization of emergencies. Balancing these two principles cannot therefore be clearly defined from an ethical point of view, but must be negotiated in a transparent public debate.

In Germany, the organs subject to allocation (heart, lungs, liver, kidney, pancreas and intestines) are distributed by the allocation Eurotransplant and according to the guidelines of the German Medical Association. In view of the difficulties inherent in allocating organs, suggestions have been put forward to limit the distribution of donor organs to people who themselves have agreed to allow their organs to be used in the event of their death. Critics of this model point out that its practical implementation could lead to undesired discrimination. There is broad consensus that social criteria such as a person's socio-economic status should not play a role in the distribution of organs.

Ethical questions concerning organ donation by living donors

The progress being made in transplantation medicine, together with the present shortage of organs, adds fuel to the discussion concerning the legitimacy of donation by living donors. Where an organ donor is still living, the ethical issues revolve around the donor and the recipient, as well as the physician in his or her role as mediator between them.

Free-will decision on the part of a living donor

The donation of an organ by a living donor presupposes his or her informed consent. According to the stipulations of the German Transplantation Act, it is permissible only between first and second-degree relatives or between people who have a "close personal relationship". The aim of this ruling is to prevent the possibility of trade in organs, to ensure that the donation is, indeed, voluntary, and also to protect donors against making over-hasty decisions which they may regret later if complications arise. In view of the fact that in such cases a healthy person undergoes an operation which does not directly benefit himself or herself and which involves a health risk which could even result in the donor's death, most countries require that the number of such donations be limited to what is absolutely necessary in order to supply the demand for transplants. In Germany, this requirement is implemented by means of the "principle of subsidiarity of post-mortal donation against donation by living persons". This means that a donation from a living donor is only permissible when no suitable organ from a dead person is available at the time of organ extraction. A surgeon may only remove organs from living donors when these criteria of urgency and lack of alternatives are fulfilled. Further, physiological tests must be performed to confirm that the operation will not endanger the potential donor more than is normally to be expected. Finally, psychological tests must be carried out in order to establish whether the donor's decision is truly made of his or her own free will and that he or she is adequately informed. As far as responsible medical practitioners are concerned, the ethical discussion focuses on the extent to which an operation which does not benefit the person being operated on can be reconciled with the classical principle of medical ethics known as 'nihil nocere' – 'do no harm'.

A particularly ethically controversial case is the so-called saviour siblings. Savior siblings are children conceived through artificial insemination and genetic selection using preimplantation genetic diagnosis (PGD) to help their older sick siblings with blood, tissue or organ donations (see also the entry on preimplantation genetic diagnosis). In Germany, the creation of a saviour sibling is prohibited, but permitted in some countries (e.g. Great Britain or Sweden). The creation of so-called saviour siblings is subject to strong criticism and is seen by many as the first step on the way to so-called "designer babies". In some countries, so-called cross-over transplantation is permitted, in which suitable couples donate organs to each other if transplantation within the partnership is impossible due to a lack of compatibility. In Germany, too, crossover transplantation was declared permissible in a specific case, since in the opinion of the Federal Social Court it could be assumed that there was a personal relationship of proximity between the donor and the recipient.

Extension of the group of potential donors

It is a matter of debate as to whether those people who donate organs or parts of organs while they are still living should receive remuneration in order to increase the number of people willing to donate. There is a body of opinion which regards such 'acknowledgement payments' as being appropriate in view of the considerable risks and disadvantages which the donor takes upon himself or herself. As they are prepared to make a positive contribution towards reducing the shortage of organs for donation, this deserves recompense. Further, it may be psychological aid for the recipient if they know that the donor at least receives some sort of financial compensation. Feelings of guilt are common, and could in this way be somewhat relieved. However, many experts from the fields of medicine, law and ethics reject any form of organ sale out of hand. In their view, the donation of organs against payment of money is not compatible with human dignity and the constitutionally defined code of ethics, and therefore unacceptable There is grave concern that such a practice would lead to the exploitation of poorer members of society because such people would be more likely to agree to organ removal while they are still living.

In addition to the idea of providing financial incentives to encourage more people to become living donors, there are several other possibilities which have been put forward with the aim of increasing the donor pool. For instance, the discussion of cross-over donation has increased in recent years. This could prove to be a life-saving solution for patients who cannot benefit from a donation from close relatives on account of blood group and HLA incompatibility.

Another way of increasing the number of donors would be to introduce a so-called pooling system of anonymous living donors. These donors provide organs for persons whom they have not themselves designated and who remain unknown to them. According to the model presently under discussion, the organs donated in this way are to be 'pooled' so as to ensure that mutual anonymity is maintained and the possibility of organ trade is excluded. The pooled organs are then to be allocated according to criteria similar to those which are applied to post-mortal donation.

Ethical implications of xenotransplantation for animals

The ethical implications of xenotransplantation strongly depend on the underlying ethical theory. The most important theories are anthropocentrism, according to which only human beings possess an inherent moral value, pathocentrism, which defines sentient beings as morally relevant, biocentrism, which assigns moral value to all living beings, and finally holism, a theory that claims that moral significance is not something an individual has but rather the whole system of nature. Within these theories, there are further internal differentiations such as the difference between a strong and a weak anthropocentrism. According to strong anthropocentrism, no non-human entity has an intrinsic moral value, while in weak anthropocentrism non-human beings do have a moral status which is derived from humans, yet they do not possess an internal value of their own.

The assessment of xenotransplantation depends on which of these theories is considered correct. The strong anthropocentrism sees no ethically questionable aspect in transplanting an animal organ into a human, as long as there is a benefit for human beings to be found. Since only human beings are given a moral value, animals can be used for the good of mankind in any conceivable way, including xenotransplantation. For a weak anthropocentrism, there is a limit to the way animals should be treated, as they do have a moral significance derived from the moral value of a human being. In Kant's theory, animal abuse harms the abuser, as it reduces her ability to empathize. The abuser is brutalized by her action and therefore the action is not permitted. Accordingly, xenotransplantation is morally justified as long as the animal doesn't have to suffer unnecessarily.

According to pathocentrism, the preference of "not wanting to suffer" is a necessary ability for an entity to be understood as having a moral value. Some pathocentrists argue that the gradation of moral value does not depend on a particular species membership – theories of that sort are referred to as "speciesist" – but rather on the degree to which an entity has distinctive preferences. What follows from this thought is a symmetry thesis, according to which beings with equally distinctive preferences should be treated equally. A baboon for instance might have equally distinctive preferences as an anencephalic infant. Anencephalia is a disease that prevents the child's brain from fully developing and causes the death of the child within a few days. If the preferences of a baboon and an anencephalic infant are indeed equally distinct and will never develop beyond this level, then we are either morally justified in taking organs from both or we are not justified to take organs from either of them.

Critics object that this approach neglects that "harm" is always experienced by an individual and this fact is overseen by advocates of utilitaristic theories such as pathocentrism. Therefore there is no justification for xenotransplantation as long as a sentient being is harmed, for every living being that can experience the sensation of being harmed has an absolute moral value. Here, harm refers to more than just physical pain. Rather it describes a more encompassing concept of which well-being is the opposite.

Finally, biocentrism ascribes a moral value to all living beings. Nevertheless, a gradation of the moral value of different beings is possible within this theory. A human being might be more valuable than a plant. In opposition to pathocentrism though, it is not the ability to have preferences, for instance, the preference to avoid harm, but rather the fact that an entity is alive, that makes the living being morally valuable. What follows from biocentrism, therefore, is the call for treating animals and plants more carefully, not necessarily the claim that all living beings are absolutely equal when it comes to moral value.

In Germany predominates a conception that incorporates anthropocentric and biocentric elements. In practice, this means that animals are accorded certain rights, but they do not have the same moral status as humans. Consequently, supporters of this view are in favour of xenotransplantation if it enables the preservation, saving, promotion or protection of human life.

However, the animals’ well being during the procedure also needs to be taken into account. The German animal welfare act requires to minimise the animal pain to an "indispensable" amount (sect. 7 para. 1 TierSchG). Experiments involving animals are only to be conducted if the pain that will be inflicted upon the animal is "ethically justifiable" (sect. 7 para. 2 TierSchG).

Ethical implications of xenotransplantation concerning human beings

Another aspect of xenotransplantation which provokes discussion concerns the assessment of its risks and benefits. The allocation of available organs raises the question, of whether economically and logistically extensive research can be justified in the face of the fact that it will only help a relatively small group of people, namely people who need an organ. The question is whether the effort could be spent in a way that helps more people in the outcome. In addition, xenotransplantation is still a highly experimental procedure that requires extensive research including experiments on human beings in order to achieve any progress at all.

Its advocates stress its value, for instance in helping a seriously ill patient. The critics point out that the risks involved in using transplants of animal origin remain obscure. In the main, these risks concern the rejection reactions, which so far remain beyond satisfactory medical control, and the possibility of transferring infectious pathogens to the transplant recipient and other persons. Risks of a possible infection and a repulsion of animal organs due to the genetic differences between animals and human beings are even higher. The problem does not only involve the possibility of transmission of already known human pathogenic infections but also the risk of infections that formerly were not human pathogenic evolving into human pathogenic infections. There is a disagreement though concerning the likelihood of this case. Moreover, in order to meet the ethical requirements of informing the patient of possible risks, there is a claim for public notification of the risk of infections that could evolve into human pathogenic infections. Furthermore, there is a discussion concerning the effects of the availability of animal organs on the willingness for organ donation resulting in a possible shortage of "higher quality" human organs.