XENOTRANSPLANTATION > INFORMATION > SHEET 5

Professor Albert Weale

Chairman of the Working Party on Xenotransplantation, Nuffield Council on Bioethics.

The overall message of the report can be summarised in the principle: "Proceed, but proceed with caution, always paying attention to the highest standards of patient care and animal welfare."

The Nuffield Working Party took as its major premise the view that transplantation is a successful and beneficial procedure for a wide range of conditions, delivering significant benefits to patients in terms of both quality and length of life. Anything that promised to alleviate the shortage of organs and other tissues available for transplantation should be looked at seriously.

At first sight xenotransplantation may not seem to raise ethical problems. Neither the US or UK enforces vegetarianism and if the eating of animals is allowed for the pleasure of the palate, it would seem only consistent to allow their use for the purposes of saving life through xenotransplantation. Indeed, pig heart valves have been widely used for some years without there being so much ethical controversy on the question.

Yet, this conclusion is rather too easy and as a working party we quickly identified six main questions to consider:

1. Is using animals to provide organs and tissue for transplantation into human beings acceptable? If so, are there special concerns about using higher primates or genetically modified animals?
2. If some use of animals for xenotransplantation is considered ethically acceptable, how can the welfare of the animals be adequately protected?
3. Since xenotransplantation raises the possibility that infectious diseases of animals will be transmitted into the human population, how can this risk be assessed and managed?
4. When should clinical trials start and how can the welfare and interests of early patients be protected?
5. How can the introduction and provision of xenotransplantation be managed? What are the implications for the financing of the health service if it is successful?
6. What attitudes will people have to xenotransplantation and how will individual recipients adjust to receiving a xenograft? What will be the effect of developments in xenotransplantation on the willingness of human beings to donate their organs?

These then were the questions. What conclusions did the Working Party come to?

Conclusions and recommendations
On the fundamental question of principle as to whether xenografting should take place at all, our view was that the benefits of transplantation are so considerable and the present organ shortage so serious that it would be ethically acceptable to develop xenotransplantation experimentally.

We found the specific and minor genetic modification in pigs currently undertaken to be ethically acceptable. We sought to identify ways, within the legal and institutional context of the UK, in which the welfare of all source animals was protected to a high standard.

We had some of our most interesting discussions on the extent to which we could recommend the prohibition of the use of certain species as potential source animals. All members of the Working Party agreed that arguments about endangered species ruled out the use of chimpanzees, but we were aware that the same argument could not be deployed directly in the case of baboons. For a variety of reasons, some scientific, to do with breeding rates and disease transmission and some ethical, to do with perceptions about the moral status of primates, we agreed that we could recommend the use of genetically modified pigs as a source of animals of choice over baboons. Only if a series of stringent conditions were met (no worries about conservation, adequate pathogen screening, alternative methods had been tried, and concerns about animal welfare could be put to rest) should the use of baboons be contemplated on a scale sufficient to meet the organ shortage.

We all agreed that the issue of disease transmission across species boundaries should be taken seriously. Indeed, we were influenced in this regard by the presentations at the Institute of Medicine conference, which our secretary attended. We recommend no source animal should be used unless it is identified as specified pathogen free according to criteria that are internationally recognised. Even so, there will be some residual risk from unknown disease causing organisms, but the mere suspicion that there might be a risk is not, in our view, sufficient to prohibit xenografting. However, adequate disease monitoring needs to be informed of the need for regular post-operative monitoring, and its implications.

As far as early patients are concerned, we suggest that the securing of consent should be the responsibility of trained personnel independent of the medical and surgical team undertaking the research. By this means, patients could consider the pros and cons of a xenograft with someone who had no professional interest in the development of the techniques. In addition, the research protocol needs to be of the highest standard, and they should always include provision for robust assessments of the post-operative quality of life of early recipients.
We were particularly concerned to protect the autonomy of those who, on conscientious or other grounds, refused the offer of a xenograft. We stipulated that, as a matter of principle, no one should be disadvantaged in the queue for a human organ on the grounds that they had refused an animal organ.

Given that the benefits of xenotransplantation would need to be demonstrated in clinical trials, we recommend that only adults capable of giving their consent to trials be recipients. Children and those adults who as a result of mental incapacity are incapable of giving consent with understanding should not be used as experimental subjects.

We were anxious to prevent the uncontrolled diffusion of xenotransplantation until it had proved its worth. Since there is a well developed machinery in the UK's National Health Service in the form of the Supra Regional Services Group we wished to assimilate xenotransplantation to the procedures that the Group covers, ensuring that it would only be carried out in designated specialist centres.

Issues of cost were difficult to make sense of at this early stage of development. We sensed, and this view seems to be shared by the Institute of Medicine Committee, that although cost per patient might not be much higher for xenografts than allografts, there would be a higher aggregate costs. However, in this regard, the problems of resource allocation are no different than for other potentially high cost innovative treatments or drugs.

Questions of wider social attitudes are also difficult to assess at this early stage, and we recommend that more research is needed in this difficult area. As part of our work we conducted an exercise in public interest in the issues that are raised, and we suspect that public attitudes will evolve quickly in the face of developments.We were especially anxious about the effects of xenotransplantation on the willingness of potential human donors to continue their gift of life. One issue that troubled us greatly was that xenotransplantation might work for some organs but not for others, making it difficult to convey the message that donors would still be needed for many years to come, and undermining the 'delicate web of solidarity' that links donors and recipients.

Concluding remarks
The overall message of the report can be summarised in the principle: "Proceed, but proceed with caution, always paying attention to the highest standards of patient care and animal welfare." Our report therefore has the tone of a permission rather than an endorsement.