Science

In the days of old, propagandists for science would make a mantra of Hume's principle that there is no relation between statements of fact and of value. But nowadays, you can't tell where the science stops and the ethics begin. On the slippery slope are risks: scientific uncertainty and potential harm. When these are extreme, science becomes too important to be left to the scientists (and their sponsors). The latest example of this is xenotransplantation, the use of animal organs and tissues as spare parts for humans.

Up until quite recently, the formidable problems of cross-species rejection made xenotransplants generally impractical. But that is being overcome, and many scientists believe that we are on the verge of an explosion of xenotransplants. The benefits will be enormous. Patients will not have to wait endlessly for suitable donors. And apart from solid organs - heart, liver and kidney - implants of animal cells and tissues will bring benefits to much greater numbers of patients. Xeno cells and tissues could be used to cure diabetes and treat Parkinson's and Huntington's disease, multiple sclerosis and the effects of strokes.

But the other side of the equation is equally awesome. There is a small but real risk of xenozoonosis, the transmission of animal diseases to humans via organ transplants or blood. So the advantages of xenotransplants have to be weighed against the possibility that animal viruses might jump to humans and cause disease or even pandemics.

There is considerable evidence for xenozoonosis. We know, for example, that Ebola and Marburg monkey viruses have caused large disease outbreaks in humans. There is also strong evidence to suggest that the HIV virus originated from monkeys. In the 1950s, millions of people were accidentally contaminated with simian virus 40 (SV40) through contaminated polio vaccines made in a broth of monkey kidneys. Last year, millions of chickens and ducks had to be slaughtered in Hong Kong because of an outbreak of H5N1, a fatal flu virus. Normally, the H5N1 virus infected only chickens and ducks. But this time it had jumped species, infecting people who had come into direct contact with diseased fowl.

When viruses jump species their character can change unpredictably. Viruses lying dormant in animals can become activated and deadly in humans. Such transformations would be favoured by xenotransplants. Viruses that do not normally infect humans through normal pathways would enjoy close cell-to-cell contact. They could recombine with human viruses, and through a well-known mechanism even generate pandemics. There is another, more subtle danger. Xenozoonoses could behave like the HIV virus. One could lie dormant and spread quietly for decades before it is detected, by which time it would have taken its toll and could have even contaminated the blood supply.

One way to avoid these dangers is to breed disease-free animals specifically designed for xenotransplants. The favourite donor here is the pig. But this option has been dealt a serious blow. Earlier this year, scientists discovered that while they can clean the pigs of most viruses, there are four known variants of a pig virus (the porcine endogenous retrovirus, or PERV), found in the chromosomes of pigs, that cannot be eliminated. Two of these variants are able to cross the species barrier and infect humans. There is also a third virus, not found in all pigs, which has been found to infect human cells under laboratory conditions. It seems that multiple copies of PERV are integrated in the pig genome, suggesting that breeding "clean" pigs is not that easy, if not quite impossible.

So what should we do? Proceed with xenotransplants? Pause and think and declare a moratorium? Or, given the risks, abandon that whole mode of biomedical engineering? And how, and by whom, should such policy issues be debated and negotiated?

Earlier this year, a group of scientists, led by Fritz Bach, a xenotransplant scientist at Harvard Medical School, called for a moratorium on clinical trials of xenotransplantation. Bach argued that we did not really know much about the risks involved, and much more time was needed to explore fully all the different varieties of risk. He suggested that a national committee of "broadly concerned citizens from many walks of life" should be set up to grapple with the risk issues. But the US Food and Drug Administration (FDA) rejected the call and opted, as regulatory agencies usually do, for a "responsible framework" for conducting research.

As part of this framework, the FDA wants all future recipients of xenotransplants to be monitored for infectious diseases throughout the rest of their lives. The recipients, and their close contacts, will also be prohibited from donating blood. Such a monitoring regime, critics of the FDA have argued, would be too burdensome and restrictive. Patients who would traditionally have the right to withdraw from experimental trials would be forced to accept a lifetime of monitoring. They would also face quarantine and be forced to live in isolation for months, if not years. Moreover, monitoring itself is not a fail-safe exercise. It does not provide an absolute guarantee against infections escaping into the wider population.

The British government has issued its own guidelines on regulating xenotransplantation. Here, the wise and well-informed Secretary of State for Health will sit in judgement on each application requesting a xenotransplant. He will receive advice from the UK Xenotransplantation Interim Regulatory Authority (UKXIRA); the authority, in turn, will rely on a number of expert assessors.

But can we trust the Secretary of State for Health and a small number of "experts" - scientists, functionaries of regulatory agencies, executives of pharmaceutical comp-anies - to make such vital decisions? The ministers and experts now have little credibility for the handling of complex ethical problems where the risks seem small but the public health consequences extremely serious. Are we to overlook how badly the ministers and experts in question handled the issue of HIV-contaminated blood in the 1980s and the BSE crisis in the 1990s?

Both the scientists and the capital-hungry biotechnology companies, who dominate research in the field, have a vested interest in promoting the xenotransplant boom. The biggest corporate player in xenotransplantation, the Swiss company Novartis, is investing US$1 billion in the technology. At least three other companies are currently working on designer pigs: Protein Pharmaceuticals, Alexion of New Haven, Connecticut (which is linked to the US Surgical Corporation), and Nextran of Princeton, New Jersey. Xenotransplants spell big bucks; it has been estimated that by 2010 the market will be worth $6 billion.

There is already an excessive hype about the potential benefits of xenotransplants. Unrealistic expectations among desperate patients will doubtless fuel pressure to proceed with clinical trials. They have little to fear personally from xenozoonosis, and will naturally discount such uncertain risks. However, we should keep in mind the principle that, however risky or grotesque an innovation in biomedical engineering, there will always be someone with the hope of finding happiness in it. Even elementary double-blind testing of drugs involves denying someone the chance of benefit. Just as hard cases make bad law, heartbreaking medical cases can justify policies that are disastrous for public welfare.

I am almost inclined to say that we need a public debate on such inherently contentious issues of science policy. But "debate" is now rapidly becoming one of those cliched words whose real meaning is mainly ironic. Just as "community" is the place where the vulnerable are dumped for "care" on the cheap, public debate is now an exercise indulged in by those without the clout or connections to tell the government what to do. Only when there is a prospect of political pressure being exerted when a consensus emerges is debate a genuine option.

Without a clear focus on practical policy issues, any debate can become windy and tedious for participants and audiences alike. For an effective public debate on issues like xenotransplantation, we need a list of "what if?" questions about the various pathways, both to benefit and to disaster. Uncertainties, be they quantitative, qualitative or ethical, must be stated clearly. If there is to be regulation, then the question "who guards the guardians?" is legitimate and urgent. We have had enough of ministries and regulators playing three monkeys in the face of the open flouting of their regulations, as in the case of the abattoirs and potentially BSE-infected tissue.

Non-technical people can be quite competent at debating such issues; indeed, it could well be that with less personal investment in the supposed perfections of the scientific and regulatory systems, citizens can have something to teach scientists about these matters. This has been the experience of participatory groups here and abroad. So, I say that xenotransplants is an issue that can be settled only with the full involvement of citizens. It is high time that we got the politics of science in order.

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