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May 23, 2005
What are some of the moral and ethical dimensions of the debate over xenotransplantation? This article discusses many of the issues at stake.
The term 'xenotransplantation' derives from the Greek word xenos, meaning foreign, and all the issues surrounding this procedure spring from the notion of associating something 'foreign' with a human body.
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In recent years the transplantation of human cells, tissues and organs (allotransplantation) has dramatically improved the survival and health prospects for people suffering from life-threatening illnesses. Xenotransplantation involves transplanting living cells, tissues or organs between species, and in particular, from animals to humans. It is being considered because worldwide the demand for human cell, tissue and organ donation far exceeds the supply. This would be true even if everyone agreed to donate their cells, tissues or organs when they die. Furthermore, the world's population is ageing, which will place increasing demand on donation as more people suffer from chronic degenerative diseases. Currently there just are not enough human donors to go round, and as a result people on waiting lists are dying.
The body's immune response is serious enough with donated human organs and tissues, but it is so severe with animal organs and tissues that xenotransplantation has not been seen as a viable option. However, interest in xenotransplantation has been rekindled as a result of recent advances in the genetic modification of animals to make their tissues less likely to be rejected. The development of increasingly sophisticated anti-immune drugs and the accelerating need for cells, tissues and organs have also contributed to an intensification of research into the possibilities of xenotransplantation.
Along with the promise of a potentially unlimited supply of organs and tissues there are risks in xenotransplantation, especially from the transfer of diseases across species - as is thought to have happened with HIV. There are also questions as to whether we should be performing these procedures on animals and humans, with respect to the effects on animals' lives and the 'mixing' of different species.
One objection to xenotransplantation is that it contravenes the appropriate relationship between humans and nature, or between humans and God. Beliefs about these relationships may come from a cultural background, involvement in a particular religion, or from a spirituality that is not derived from a particular culture or religion.
For many people human need is the factor that most incisively challenges cultural or spiritual beliefs that might otherwise prevent the use of a particular biotechnology. A life-threatening condition, whether in oneself or a loved one, may see some cultural or spiritual beliefs give way to the need to preserve life or improve health. The preservation of life may itself be the spiritual or cultural value that carries the greatest weight. The intersection of cultural and spiritual beliefs with human need is always an area where complex issues arise, not only for individuals but for society as a whole.
As an indication of religious viewpoints, the Australian public consultation on xenotransplantation received submissions from representatives of the Christian, Jewish and Islamic religions, who agreed that xenotransplantation does not contravene the order of creation, and that the use of animals for human benefit is acceptable. A review of world religions found that xenotransplantation is acceptable in most of the major religions. Both Islam and Judaism forbid the eating of pork, but accept xenotransplantation on the basis that humans have a higher place in the world and therefore have the right to use animals for their welfare, as long as the animals are treated with respect. A number of religions that do object to transplantation, such as the Hindu or Buddhist faiths, still allow the individual to make a choice.
Many people who feel that xenotransplantation is 'unnatural' will not be thinking from within a religious framework. Some believe that species have an integrity that should not be transgressed by mixing parts of one species with another. Species have evolved to occupy their own ecological niches, to be functioning parts of a whole, and therefore there is something fundamentally wrong with xenotransplantation. The idea that species have value in themselves as they are, quite apart from their usefulness to humans, is a strong theme in the conservation movement. This can give rise to strong clashes of belief systems, as when a proposal to develop an area could endanger the survival of a species valued by conservationists but not valued by developers.
Certainly feeling part of an overall system of being, life or nature is an important part of the ethical and spiritual beliefs of many people, which often carries with it responsibilities for caring for other parts of that system - a concept often referred to as 'stewardship'. We will be looking further at this stewardship relationship in the next section when considering the interests of animals.
We do, however, need to be careful when rejecting something purely on the basis that it is 'unnatural'. On the face of it, the term 'unnatural' could be seen to cover any medical intervention, or the selective breeding of animals and plants, or for that matter wearing clothes, driving cars and flying in aeroplanes. Also, the objection in terms of unnaturalness can merge imperceptibly with what has been called the 'yuck factor' - an intuitive reaction that something is disgusting and therefore wrong. Such a reaction is perfectly valid but in the context of xenotransplantation it could be accommodated, by individuals having the right to refuse their personal consent for a xenograft. If someone feels strongly that they could not tolerate having parts of another species in their own body, this would be seen by many to be a justifiable response. Denying a medical procedure to others purely on the basis that one finds it personally distasteful may be much harder to justify.
When we were discussing the different types of xenotransplantation, we noted that some organs (especially) and tissues are more related to an individual's sense of personal identity than others. Would - or in fact should - the particular tissue, cells or organ involved alter our thinking about xenotransplantation? Consider the transfer of a number of pig pancreas cells to a person suffering from diabetes. Compare this to a person who has been given a pig's heart, or perhaps even a pig's eyes. Is there a point at which the person receiving the transplant, or other people, would feel that he or she was now less human? That somehow their personal identity had been compromised?
Some tissues and organs appear to be more integrally related to the sense we have of ourselves as human beings. These are likely to be tissues and organs that are most readily visible, are related to reproduction and the continuance of our lineage, or that we traditionally associate with our thoughts and social interaction. For example, according to the Catholic Church, "the implantation of a foreign organ into a human body finds an ethical limit in the degree of change that it may entail in the identity of the person who receives it." Both Pius XII and John Paul II have clearly upheld the moral legitimacy of the therapeutic use of xenotransplantation, as long as "the transplanted organ does not affect the psychological or genetic identity of the person who receives it", and the procedure balances benefits over risks. In particular, the Church refers to the head and sexual organs as "indissolubly linked with the personal identity of the subject".
Some may argue that concerns about identity are simply another version of the 'yuck factor'. Just as, for cultural and historical reasons, it may seem more unethical to use dogs or chimpanzees rather than pigs for medical procedures, it may seem more unethical to use eyes rather than a kidney. This is a complex area, and for many people issues of personal identity and mixing the identities of different species will be significant when weighed against the potential medical benefits.
For some, the arguments about nature and identity are beside the point when set against the needs of potential recipients. The most obvious reason for xenotransplantation research is that it offers the prospect of treating people in serious need. If xenotransplantation were actually to work, it would be used for people who would otherwise die or else suffer from less effective treatments for serious conditions. For some, the chance of meeting these health needs is sufficient reason to go ahead with such research. Meeting needs - saving life especially - is considered by some to be a basic principle of humanity. It might also be a requirement of a just society that it do its best to help its members when they are severely ill and can be helped. Some believe it would be a dereliction of duty to fail to exercise our ingenuity as humans to solve or at least ameliorate such central problems of the human condition as disease and premature death.
An argument that sometimes accompanies the ethical plea to help people suffering from disease is that those who object to xenotransplantation are free to reject a xenograft in their own case, but they should not be able to impose their views on others, and in particular not those who desperately need treatment. What's more, it is sometimes said, when people are touched by real cases - and especially when they need treatment for themselves, or a loved one, - cultural or spiritual concerns about nature or identity will seem irrelevant abstractions.
Responding to serious needs, particularly saving lives, matters for many people. For others it must be balanced against or limited by other factors. Later sections discuss how xenotransplantation affects the interests of animals and how it poses a potential risk to public health. But even setting those topics aside, some people believe that we can go too far in trying to defeat death and disease, and for them xenotransplantation might be going too far. Death, it is said, is a fact of life: humans have a natural life cycle, but modern humans have a tendency to ignore death or refuse to face up to it.
Researchers, research sponsors and the wider community generally agree that non-human primates (such as baboons and other monkeys) are not a suitable source for any of the proposed animal therapies (external therapies, cell therapies or organ transplants) because of the risk of infections to the recipient and the wider community. The US Food and Drug Administration has effectively prohibited the use of non-human primates in animal-to-human xenotransplantation since 1999.
The use of non-human primates in medical research also raises serious ethical issues. Non-human primates are highly intelligent animals with complex behavioural and social needs that are difficult to meet in a medical research environment. However, baboons are considered the most suitable species for animal-to-animal studies (such as pig to baboon) to obtain important information on the effectiveness of a procedure before it can be tested in an animal-to-human trial.
At present, pigs are considered to be the most likely and appropriate non-human source of organs and tissues. The anatomy and functioning of pigs are very similar to those of humans. Pigs are domesticated animals that are easy to breed, and, importantly, pigs are suitable for genetic modification.
Animal-to-animal transplantation studies would use a variety of animal species in the early stages of the research (such as mice, rats and rabbits). If these studies show promising results, researchers will need to trial the procedure in an animal study that is as much like the future clinical use of the therapy as possible. This will usually involve the use of non-human primates (specifically baboons) as transplant recipients, as noted above, but fish and cattle might also be used for some procedures, such as helping to grow skin. Researchers are also considering the use of other species (such as cattle, fish and mice) for cellular transplants.
Researchers predict that immune rejection of animal-to-human transplants may be avoided by genetically modifying the source animals, as well as by treating the human recipient with drugs to suppress their immune response (immunosuppressant drugs). Genetic modification of source animals involves inserting some human genes into the animals to make their cells, tissues and organs behave more like human-to-human transplants.
This raises some difficult ethical issues about the rights and welfare of the animals, such as whether the insertion of human genes may make the animal in some way 'human', or whether inserted genes cause unexpected side-effects in the animals. One view may be that these issues need to be considered case by case to ensure that the proposed modification does not alter the animal in any other significant way. The aim would be to ensure that the animals retain the essential characteristics of their species.
Virtually everyone believes that mammals, at least, have some ethical significance, in that it is wrong to hurt or kill them, especially if this has no benefit to humans. People who believe that human benefits outweigh the harm caused to animals often argue that these benefits are potentially very large, in terms of lives saved and suffering alleviated. This argument is often based on the belief that humans in some sense have a moral status superior to that of animals, and that therefore the needs of humans outweigh the rights of animals.
Some think it is wrong to cause suffering to or kill animals even if this has major benefits. Such an argument might be based on the belief that humans and animals have the same moral status, but it is not necessary to take this position to argue against the exploitation of animals. Some opposing the exploitation of animals maintain that the benefits to humans of xenotransplantation are often overstated and the suffering of animals understated. In this view, many animals will have to die or suffer in research for gains that are purely speculative.
It is a matter of controversy how much suffering xenotransplantation experiments and rearing would cause. For example, some types of xenotransplantation involve killing young pigs under anaesthesia, whereas others involve the destruction of a chimpanzee's immune system through chemotherapy and radiation. To minimise the risk of cross-species infection, source animals for xenotransplantation would probably need to be bred and raised in monitored, biosecure facilities. The adverse effects on animals could give rise to particular concern, especially since these source animals would need to be raised in isolation.
The primary question seems to be how we ought to weigh the interests of animals against those of humans. The answer to this could depend on the animal in question - whether apes, pigs or mice - and how much the animal suffers in rearing and experimentation. It may also depend on the benefits to humans, in terms of exactly how safe and effective xenotransplantation will be.
One of the reasons there has been renewed scientific interest in xenotransplantation is the possibility that genetic modification will greatly reduce the immune response that is currently a major barrier to the use of animal-to-human transplants.
Pigs have a molecule on the surface of their cells called the Gal antigen, which triggers an acute immune response in humans. Genetic modification has made it possible to 'knock out' the Gal gene that produces this molecule in pig cells. Cloned piglets have now been born with the Gal gene deleted, which removes the molecule that causes the human immune system to reject pig cells, tissues and organs. Research is still being carried out on this and other aspects of the human immune response to pigs to see to what extent genetic modification can solve the problem of rejection. While immunosuppressant drugs may still be needed, the genetic modification of pigs to deactivate or delete molecules that trigger human immune reactions significantly improves the chances of successful xenotransplantation.
People with strong objections to genetic modification may accept the transfer of an animal organ or animal tissue if it has not been genetically modified, but oppose the use of xenotransplantation if it involves genetic modification of the source animal.
This article is adapted from The Cultural, Spiritual and Ethical Aspects of Xenotransplantation: Animal-to-Human Transplantation, a publication of Toi te Taiao: New Zealand's Bioethics Council.
Copyright © 2005 Science & Theology News.
This article posted July 3, 2005.