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Society, Religion and Technology Project Church of Scotland Looking at the ethics of technology for a New Millennium

The Ethics of Xenotransplantation

The Nuffield report "Animal-to-Human Transplants - the Ethics of Xenotransplanation", is available from the Nuffield Council on Bioethics, 28 Bedford Square, London WC1B 3EG, Tel. 0207-631 0566, Fax 0207 323 4877ISBN 0-9522701-2-9, UKP10.00 in UK, UKP12.00 overseas.
The UK Department of Health report "Animal Tissue into Humans - A Report by the Advisory Group on the Ethics of Xenotransplanation" , ISBN 0-11-321866-4., UKP25.00 is available from HMSO, PO BOX 276, London SW8 5DT, Tel 0207-873 0011, Fax 0207 873 9090.
In the US, the Institute of Medicine made a report in 1996 "Xenotransplanation - Science, Ethics and Public Policy", published by National Academy Press in Washington DC. ISBN 0-309-05549-0.

Contents of SRT Submission : The Ethics of Xenotransplantation

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The issues under discussion by our working group cover a very wide range. In some we are responding to an existing technology where there is already a commercial product (e.g. the "FlavrSavr" tomato). In others we are assessing a promising technology which is still under development (PPL's transgenic sheep producing alpha-1-antitripsin). In a few cases, we are looking at the potential implications of what is still at the level of more speculative research. The Cambridge xenografting1 research on genetically modified pig's hearts for transplants represents an example of the latter. We have prepared a case study on this issue, even though strictly there is as yet no "case", in the sense of a proven technology. We considered it important to study precisely because of the need to be pro-active on the ethics of new technological developments, especially those with important implications and wide potential application. It has also already excited media and public attention and controversy, which therefore in that sense "makes it" an issue.
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Summary of the Genetically Modified Pig Heart Technology

Genetic manipulation has become involved as a possible way of preventing the hyperacute response whereby human antibodies act rapidly to reject the transplanted tissue as though responding to an infection. The Cambridge research is attempting to transfer the gene which directs the production of regulatory factors for human "complement" into pigs, so that the heart is no longer recognised as foreign. Conventional drug therapy is, however, still required to prevent rejection by response to the histocompatibility antigens, which react to the different tissue surface chemicals of an organ transplanted even within the same species.

The actual technique being used involves a single gene (it is presumed without a regulator). There appear to be several groups of people working on the technique and different groups appear to have chosen different genes to work with. The Cambridge group was still some way from applying the technology to human recipients. In early 1995, they were only at the stage of producing homozygous lines of transgenic pigs. Groups overseas have gone further in the genetic engineering aspects, but none are at a clinical trial stage.

Some believe that even if the hyperacute rejection problem could be solved in xenografting through one or other of these genetic manipulations, other problems may need to be solved which could mean that clinical application was still some years away. This in itself poses the problem, to which we shall return, that incautious reporting, publicity and media coverage can prematurely raise expectations of a "cure" amongst sufferers and those who care for them.

The most pragmatic question is whether the treatment would actually work. This is not in itself an ethical issue, but as we will see, its implications do raise some issues. It would seem that several formidable obstacles must all be overcome, including the effectiveness of the animal donor heart as a heart, matching the specific donor pig heart to a specific host human physiology, freedom of donor heart from carrying an animal-originated disease into the human being, the surgery and its aftermath, hyperacute rejection, and histocompatibility rejection.

One of the dangers which is inherent in this type of research is that it is not possible to predict the outcome of organ transplantation from such pigs. The first patients would face a very uncertain future. However, as they were already facing a high likelihood of death from their existing grave clinical condition, they might be content to gamble. The research so far has concentrated on overcoming the immunological difficulties. It might be asked if we would do better using preliminary stages such as transplanting veins from pigs as a less drastic way of assessing the rejection. Against this it could be argued that this would be creating an unnecessary new risk to a very sick person without treating their actual condition.

Problems may arise because of differences in physiology between humans and pigs. There are differences in life-span, heart rate blood pressure, and the structure of the regulatory hormones which maintain the basic physiological stability of the animal. It is not clear how an organ from one species would perform in another. It would be essential that the organ did not carry any infective agent able to harm a human. Hence it would be necessary to use animals from specialist disease free facilities, which raises some animal welfare questions.
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• Unnaturalness
• Theological and Other Underlying Issues
• Genetic Modification as a Principle
• Is the heart special?
• Intuitive Repulsion - the "Yuk Factor"
• Wrong Use of Animals in Principle
• Conclusion on Issues of Principle
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Unnaturalness

But what it is that is seen as "unnatural"? Several possibilities might include :

• Any sort of transplant, including a human to human transplant,
• The transplant of even a "normal" animal organ into a human being,
• The genetic engineering of an animal to produce an organ suitable for transplanting,
• The crossing of particular species boundaries - e.g. pig - human rather than another animal,
• Transplants involving certain organs, rather than others.

Some already object on principle to human-human transplants, but the particular significance of xenografting is the transfer of organs between different species. Does this represent breaking a barrier between the various natural species, and especially between human beings and animals? The issue is complicated by the possibility of an objection in principle to genetic modification of animals. Because of the problems of hyperacute rejection of organs or tissue from a different species, it seems likely that xenografting would always entail genetic modification on the part of the donor animal. Conceivably, it might also require some measure of genetic therapy on the human recipient as well. To unravel this complication, we would first pose the question of how people would react to the idea of a xenograft if the heart was from a normal pig rather than a transgenic one (supposing for a moment that the suppressors for the acute immune reaction could be supplied in some other way than genetic modification of the pig or human).

We would conclude that, whether or not one associates it with the sense of unnaturalness or a violation of the natural order, there is clearly something artificial about putting a pig's heart into a man or woman. The point is: does that matter?
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Theological and Other Underlying Issues

Others argue that none of these prohibitions exactly meets the case in point, since the intent of xenografting is not to interbreed humans and animals, and that the divine prohibition could not be against the exchange of genetic material as such, since at least at the level of micro-organisms, such exchange occurs routinely in nature. Moreover the normal Christian understanding is that human beings have been reconciled to God through the death and resurrection of Jesus Christ, fulfilling and superceding the numerous ceremonial regulations in the Old Testament, such as which animals may be eaten, and the way in which animals are slaughtered. It is a moot point whether the regulation against crossing animal or plant kinds falls into this category, or whether it reflects a wider moral teaching which would still be relevant.

It might be argued that there are many cases in nature where one living organism makes use of the metabolism of another by parasitic action on a host, or by co-operative (symbiotic) co-existence. These would seem, however, to be of a different order from physically cutting out an organ and implanting it in another organism.

The very concept of "species" is an attempt to rationalise and classify the biological diversity of the natural world, in ways that take due recognition of the similarities and differences that genuinely exist. The classification may be a human construct, but it is not without justification. The questions of whether this implies barriers between species is another matter, however. In terms of evolutionary biology, some might argue that, since the evolutionary grouping of a potential continuum of genetic possibilities into discrete nodes is in a state of continual, if slow, variation, then barriers are not relevant. This is especially true in the case of mammals, because so much of our genetic material is common.

Others, however, would point out that pigs and humans have nonetheless developed down different "branches" of the genetic tree, and are patently different, however much DNA they actually have in common. A pig's heart is ordered for a pig to live. The Old Testament distinction of "kinds", whether or not this should be linked to the biological notion of species, may be said to reflect the goodness and purposiveness of the Creator who had caused a cosmos to be generated so well suited to human life. For some this order represents a wisdom which humans are certainly invited and called on to use, but which they should not seek to alter radically, in the sense of altering aspects which are seen as inherent in the order itself. This is in part a matter of respect for the Creator, and part a reflection of the feeling of risk involved in fundamental changes to God's order by "mere" human beings, and proud human beings at that. Because human beings cannot know the full extent of the consequences of interventions at this level, we should not attempt to do so. Some argue that perhaps the Old Testament prohibition reflects divine knowledge of the risk to human health that would result from crossing living biological material from another kind. They ask how can we be sure that intermingling pig and human genes, say, will not give rise to new diseases which cannot be put back into the test-tube. This, however, leads the discussion into consequential issues, which we address later.

From the clear cultural distinction between humans and non-humans flow vital features of human moral and social life. Human life is uniquely valued, and the killing of humans is forbidden in ethical systems except as punishment or in time of war. If human life and animal life become intermingled, it might be argued that there is a danger of the distinctive moral claims ascribed to human life being undermined. It has been observed by some that the closer one moves animals, in concept, towards humans (so increasing one's duty of care to animals), the more ready is the danger of treating some humans merely "like animals". There are grounds for some caution on this point.

In summary, a case can be advanced for religious prohibition of intervention across the "kinds", on the basis of natural order of God's creation, and elements of this view could also be argued from some non-religious perspectives. Most of our group would not take this position. For many Christians (and others), it remains to be justified why a line should be drawn at this particular point rather than any other human intervention into nature or to God's created order, and why the Old Testament proscription should be read as universal and therefore valid in a Christian understanding.
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Genetic Modification as a Principle

We have mentioned the possibility of an objection in principle to genetic modification of animals or (if it ever became appropriate in the treatment) humans. We would not object in principle on either of these, but, bearing in mind that a specific alteration to the fundamental genetic makeup of an animal is involved, we would need to consider the justification for this in the light of the consequences, both advantages and disadvantages.
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Is the heart special?

Researchers are working on the possibility of using donor kidneys from pigs; would this be less controversial? For some it might be. In many cultures, the heart has a special resonance. In the English language, it is the seat of emotions (especially love), courage, enthusiasm and innermost thoughts. In many cultures the heart is similarly accorded a special place in human identity. Obviously this is culturally driven, and subject to change. [Oliver Cromwell used the metaphor the "bowels of Christ", which would seem strange today.] For some people, perhaps, the heart is seen as too vital to what it is to be human to allow substitution by an animal's heart, but this would not seem to be an overwhelming objection. From a biblical standpoint especially, we would not relate essential humanness to any one part of the body. Rather the human being is seen as a whole. One would require a very good reason to have a non-human heart, but it would not a priori violate one's humanness.

To put the xenografting case in the extreme, one might ask the theoretical question of how much of a person would have to be made up of animal organs, blood and tissues before that person would cease to be "human"? Pragmatically, one might answer that long before a stage had been reached where this question had much reality, the life would probably be non-viable. But on the underlying point, from a Christian perspective (and in most traditional societies), the person is indivisibly mind and body, and does not cease to be that, notwithstanding a wide range of physiological changes, disabilities and injuries.
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Intuitive Repulsion - the "Yuk Factor"

Much can depend on how the question is presented - say in the media, or by proponents or opponents of the technology. It can be presented in terms of here is a "miracle" that someone who has suffered a major trauma is now able to walk around because of this wonderful technological innovation. It might, on the other hand, be presented as yet another example of natural boundaries being abused by technology driven blindly, without sufficient care for the consequences to you and me, or to the rights and feelings of animals. The sense of suggestion, either way, is very powerful.

Some argue that this is primarily a case of unfamiliarity. On thinking through the issues, they conclude that there is little difference between killing an animal specifically to obtain one of its organs and killing it to eat it, but we are more familiar with one than the other. With many technological developments, unfamiliarity has been a barrier to the society to whom the it was first announced. The next generation often grows up better informed and used to the idea, and often tends to look back on earlier attitudes with surprise or even condescension. Indeed, heart transplants are themselves an example of this effect. The sense of "yuk" has in this case been largely dispelled by familiarity. But education and familiarity are not always the answer to overcoming these intuitions; the case of nuclear power has to some extent worked the other way.

Issues of public perception in biotechnology are important and should be treated with respect, and not simply be dismissed because they may contain elements of ignorance, emotion and cultural conditioning. We are all members of the public.
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Wrong Use of Animals in Principle

Conclusion on Issues of Principle

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