A Retrospective Overview of the Discussion of the Ethical Issues

by Margaret A. Somerville, AM, FRSC

[Dr. Somerville gave these closing remarks to Health Canada’s National Forum on Xenotransplantation, Clinical, Ethical and Regulatory Issues, November 7 & 8, 1997. Representatives of professional associations, transplant recipients, scientists, health professionals and specialists in the areas of transplantation, disease transmission, ethics, law, animal rights and veterinary medicine participated.   Reprinted with permission]

Some major conclusions and questions with respect to the ethical issues raised by xenotransplantation emerged from the Forum.

First, we recognized that xenotransplantation research on human subjects involves decision making in conditions of uncertainty with respect to risk. While this is true for all medical research on human subjects, the difference with xenotransplantation is that the risks not only are to the immediate subjects of the research, but also could be to the public at large. The transplantation of animal organs into humans involves crossing the species and immunological barriers, which carries the risk of transmitting to humans an infective agent that could, in turn, be passed on to others. This possibility of risk to the public in general from xenotransplantation, raises special ethical concerns.

One area of special ethical concern, was the use of animals as the source of organs. The ethical issues in this area involve, first, the ethics of the use, itself, of the animals and, second, the ethics of the way in which they would need to be treated in order to be an acceptable source of donor organs. The question which must be addressed is, is it inherently wrong to use animals for xenotransplantation or to treat them in the way that is necessary to make them suitable as organ donors? The majority of participants appeared to agree that this could be justified, provided certain ethical requirements were fulfilled. These included that everything reasonably possible was done to reduce the animals’ suffering; that the animals used were provided with as high a quality of life as possible; and the number of animals used was reduced to the minimum.

The issue of which animal species should be chosen as a source of organs was also a focus of discussion. Although primates were the closest genetic relatives of humans, they were rejected on several counts, including the following: in some instances, for instance, chimpanzees, the species is endangered; the suffering experienced by primates as a result of the living conditions required to make them suitable as organ donors was thought to be unacceptable (this same reasoning was not applied to pigs, but there was more an assumption that this differential treatment was justified, than an explanation of why this was the case); primates would be more difficult and much more costly to care for and manage than other animals that could be used, in particular pigs; the use of primates would be unacceptable to the general public; and the likelihood of the transfer of infective agents was more likely between more closely related species, that is between primates and humans than between pigs and humans. The sense of the meeting seemed to be that if it were ethically acceptable to use animals, then pigs (which were often referred to by the more derogatory term swine) were the animals of choice. There was little discussion of whether the choice in this respect reflected ethically relevant and justifiable differences between primates and pigs, or perhaps just greater personal identification with primates than pigs (the former look more like us), that is, a certain degree of anthropomorphism, and different cultural attitudes to primates as compared with pigs.

A second ethical aspect related to the use of animals involves the human-animal interface: the transfer of human genes into the animals in order to decrease the likelihood of organ rejection by the human recipient, and the transfer of animal organs into humans. Again, the participants did not seem to regard this as raising ethical difficulties that could not be overcome and that would require the prohibition of xenotransplantation. It was pointed out that the ethical questions surrounding the use of animals and the mixing of human and animal genes and organs, raise issues not just with respect to the physical realities they create, but also with respect to important societal values and, in particular, with respect to maintaining respect for both human and animal life. There was no dissent from the view that we have serious obligations to ensure that these values are not damaged.

The major ethical issue articulated at the forum, on which the participants were seriously divided in their views, was whether clinical trials of xenotransplantation in the human context should be allowed to commence. Leaving aside risks to transplant recipients, the central issue was expressed as whether, at this time, xenotransplantation can be regarded as sufficiently safe in terms of the risks of the transfer of an infective agent from an animal to a human that could put at risk the general public, for limited, carefully safeguarded, clinical trials to commence. The argument in favour of proceeding with a limited number of sentinel cases of xenotransplantation is that this is a life saving intervention for people with no other medical alternative and should be developed. This requires research on human subjects. The argument against this is that this could put the health and lives of others at risk.

In addressing this dilemma there was agreement, first, that the ethics of xenotransplantation must be embedded in the science - bad ethics is bad science and, in this area in particular, ethics cannot just be an add-on after the science has been carried out. Second, it was agreed that it is essential to proceeding with any human trials of xenotransplantation that there first be an informed public debate and that, ultimately, it is Canadian society which must decide whether xenotransplantation will proceed and, if so, under what general conditions. In short, these decisions must be taken by all stakeholders, not just the scientists or industries involved in xenotransplantation. It was acknowledged that we have insufficiently developed mechanisms for engaging in a broad, in-depth public debate, and it was recognised that there is an ethical requirement to establish the means through which this can be achieved, including possibly, setting up a National Advisory Committee.

It is relevant to note that most of the workshop reports which examined and articulated the ethical and scientific requirements for carrying out human trials on xenotransplantation, made these recommendations simply assuming, for the purposes of discussion, that it was ethically acceptable to proceed with xenotransplantation. In other words, they did not decide whether or not it was ethically acceptable to proceed. Rather if it were ethical, then the recommendations which they made were the ethical and scientific principles which should be applied. Some of the recommendations made in the workshops to govern xenotransplantation were it to proceed, would be unique to this form of research. For instance, recipients would be required to agree to long term - indeed lifetime - monitoring, informed consent would be required from the sexual partners of the recipients to the risks which these partners could run, etc. As well, of course, all the usual ethical and legal requirements governing medical research on human subjects would apply.

The crucial question, therefore, is are we ethically justified in creating unknown risks with xenotransplantation? In answering this question, as was discussed at the Forum, the allocation of the burden of proof will be crucial. It was my sense of the meeting that there was agreement that those who wish to undertake xenotransplantation, have the burden to show that this is both reasonably safe and ethical. This means that if there is equal doubt as to whether either of these requirements are fulfilled, xenotransplantation research on humans cannot proceed until this doubt has been resolved in favour of proceeding.

At a broader level, major insights that I saw the Forum as eliciting included that:

• The xenotransplantation debate is of great importance to society with respect to the ethics of protection of both human and animal life, and not simply in the present, but also with respect to future generations.
• We should take the ‘medical and scientific cloak’ off xenotransplantation. Xenotransplantation is a very important area of medical and scientific research, but it does not just involve medical and scientific decision making. Rather, it involves decision making in a medical and scientific context. This latter description should tell us that there is a much broader range of people and institutions, and considerations and concerns, that must be taken into account in deciding what we do about xenotransplantation, than simply the medical and scientific ones.
• The decision makers and the range of issues must definitely include the public and their concerns.
• We need credible, informed, wise and courageous discussion and decision making about xenotransplantation.

Organ transplantation has always been at the crossroads of new medical science and technology, on the one hand, and, the impact of these on individuals and society, including on our moral and ethical values, on the other hand. The birth of modern bioethics is often regarded as having taken place on the day on which Dr. Christian Barnard carried out the first human heart transplant in South Africa. We thought at that time, when we had dealt with the major ethical, legal and social issues that this raised, that we had solved most of the problems that the transplantation of organs would create for us. But we were surprised by the new issues that constantly arose in this context, and, interestingly, these were usually at the forefront of where we were pushing both our science and bioethics. Xenotransplantation is the latest situation in which transplantation science is challenging us to state where we stand on some very important and fundamental principles of human ethics. In a sense, transplantation is like the bioethics canary in the societal mine shaft. Therefore, how we handle the ethics of the science of xenotransplantation affects not only that area, but our society in general. Consequently, the xenotransplantation debate should be added to the other major societal debates in which we are engaging at the end of the twentieth century, many of which involve medicine or medical science (for instance, the debates surrounding genetics, human cloning, new reproductive technologies, euthanasia, allocation of and access to health care, etc.) which in combination will be a major force in determining the nature of the society that we will become.