Sir

The US Public Health Service (PHS) agencies have rejected recommendations for a moratorium on clinical trials of xenotransplants, and left the door open for nonhuman primates to be donors. Your Briefing on xenotransplantation1 summarizes the important elements of this subject, and captures perfectly the split between those who want to get it right and those who want to get it right now.

In the Briefing, Jonathan Allan, a virologist on the Food and Drug Administration (FDA)'s advisory subcommittee on xenotransplantation, points out the neglect of the precautionary principle in a situation where it is most needed, given the risk of public exposure to xenozoonoses. The United States is fortunate in having bodies such as the Centers for Disease Control and Prevention, the National Institutes of Health and the FDA, which give it the confidence to halt activities “should something happen” — but containment is the wrong strategy here, and any epidemic that starts may involve countries other than the United States.

Many countries, and not just those in the developed world, are likely to want to benefit from xenotransplantation. Given that nothing is to stop them from going ahead, apart from their national governments — if even that — the need for international cooperation in risk minimization and containment becomes obvious.

Recognizing and responding to this global dimension of the risk calls for interdisciplinary and international dialogue to harmonize guidelines, research, surveillance methods and the response in case of adverse outcomes. National registries will need to be compatible, and archived tissue perhaps accessible to scientists from other countries. Many of these issues were agreed upon at the World Health Organization consultation on xenotransplantation in Geneva last October.

With traditional research funding drying up in universities, biotechnology companies are increasingly involved in cutting-edge research. Transparency through peer-reviewed publication cannot be guaranteed and, although companies linked to major pharmaceutical companies will probably be guided by long-term interests, some venture-capital companies may seek short-term rewards. The long-term effects are unpredictable but, given that the public is being put at risk, an argument can be made for greater public debate, as suggested by Bach et al.2, and perhaps novel means of public supervision. A challenge in the days ahead is to define these means and to define what might constitute public or community consent.

Xenotransplants will almost certainly be too expensive in the early years to be the answer to the shortage of human cadaveric organs for transplantation. Furthermore, it is not yet known if xenogeneic organs will adequately replace the function of complex metabolic organs such as the liver. We must therefore continue to strive for other means of increasing donation of human organs and certainly ensure that xenotransplantation does not undermine allo-donation.

Xenotransplantation may also affect traditional transplant ethics3 by eroding the ‘gift’ metaphor and the confidentiality principle; through the complete reification and commodification of organs and the rewriting of the meaning of consent to include the community; and through erosion of the courtesy and cooperation between centres working with a very scarce resource.

Finally, no sensible person would want to hold back development of such a potentially useful technology were it not for the risk to public health. There may be reason to be confident that the risk of xenozoonoses is small, but the risk would be justified only if large numbers of patients could be saved in the very near future and we had no hope of improving our risk assessment capabilities quickly. This is not the case at present: xenotransplantation will have no immediate effect on overall transplant numbers; and risk assessment is improving.

We understand the similarity to the early days of genetic engineering and the call for an embargo then, which has proved unnecessary. However, one similarity should not constitute a cliché; the risk is serious enough and the immediate benefits are small enough to require this situation to be assessed in its own right. This is particularly true because, although most comments have been about clinical trials, the reality is that even minimal perception of success in trials will soon lead to xenotransplants as therapy and will encourage many unprepared units to ‘do’ xenotransplants. The immediate effect of the permissive US PHS guidelines will be that other countries will want to follow suit, so speeding further a process that the PHS itself felt obliged only a few weeks ago to halt as a result of new evidence on porcine endogenous retroviruses.

The PHS is listening and responding. Its guidelines are, fortunately, still evolving. Common sense would dictate caution even without a formal embargo. The guidelines are tougher than originally envisaged and may become tougher still. It would be a recognition of its global reach for the US PHS to acnowledge that it is here dealing with a global rather than a US issue and that there is no reason to hurry past prudence.