A cautionary tale

Could the reaction against GM crops damage the future of human genetics? asks John Gillott

In January the US Federal Drugs Administration (FDA) suspended all gene therapy trials at the institute, pending further investigation of what it considers to be the centre's inadequate adherence to regulations. Gelsinger's father, who continued to praise the work of the institute immediately after his son's death, is now contemplating legal action.

Gelsinger's death, and the FDA's action, have shaken the gene therapy community. But the case has also led to renewed expressions of support for the principle behind the work. Patients and researchers in the field have stressed that, while every effort must be made to control the risks through proper scrutiny of the trials, 'like most medical interventions, gene therapy is potentially dangerous', and that some level of risk is justified because such work offers the hope of cures for currently incurable disorders (editorial comment, Nature Medicine, January 2000). This was in sharp contrast to the reaction of Britain's Lord Alton. Echoing the language used to condemn non-human applications of genetic engineering, the veteran moral crusader and anti-abortion campaigner told the Mail on Sunday, 'I take a cautious position on research like this....The science is unproven. Safety and ethical considerations are unresolved. These factors are enough to require a moratorium to allow us to stop and consider' (23 January 2000).

Was this merely a predictable response from a conservative figure of the past - or a warning of trouble to come? In recent years genetically modified (GM) crops have become the focus of massive concern and calls for caution and restraint. Now some in the field of human genetics are worried that human genetic engineering and other therapeutic applications of related technologies - currently fields in their infancy, but experiencing rapid growth - may provoke the same reaction.

There is an argument for not being too concerned. Opinion surveys show that genetics as applied to medicine currently enjoys a much higher level of public support than does GM food. A MORI poll, conducted in 1999 as part of the government's review of the regulation of the biosciences, reported that advances in human health are seen as the biggest benefit to arise from scientific developments. The percentage of people giving the thumbs up, minus the percentage giving the thumbs down, was +56 for new medicines. For the development of cures and/or the eradication of disease it was +42. By contrast, GM food scored -44. The report also noted that 'the main issues which the public would take into account in determining whether a biological development is right or wrong are whether people would benefit from it and whether it would be safe to use'. Similar results were recorded across Europe in The Europeans and Modern Biotechnology, a major survey published by the European Commission in 1996 - genetic testing and medicines received an overall positive evaluation; GM foods a small net negative.

But it would be complacent to think that the reaction against GM foods witnessed over the past two or three years will pass human genetics by - it is already crossing over. Nor can a general public support for medicine be relied upon to carry the day.

Lord Alton may be out on a limb in his reaction against human genetics, but he does connect with something. Alan Irwin, who monitored some of the pilot workshops for the government's biosciences review of last year, reports that 'there was a sense that these areas of science were slow to deliver tangible benefits (for example, compared to rapid progress in information technology). At the same time, the biosciences seemed to generate unexpected outcomes and findings (Dolly was often quoted) that set new problems for society'.

While medical applications of human genetics are supported in the abstract, some of the very measures that might bring these about and speed up the delivery of 'tangible benefits' are also the 'unexpected outcomes' that so concern people. The ends are popular; the likely means less so. In the study commissioned to accompany the biosciences review, MORI reported a net score of -55 percent for cloning technologies - an even lower score than that for GM foods. In another MORI poll for Novartis, 74 percent opposed the cloning of animals and 60 percent opposed the cloning and development of human cell lines.

The rapidity with which negative attitudes towards GM crops sharpened, and the reasons for this, suggest that unease with medical applications could develop into a more focused critical response. Reflecting on the 1996 study The Europeans and Modern Biotechnology, Martin Bauer and colleagues detected an underlying unease: 'When thinking about biotechnology in general terms, the public expresses a sense of unease. This is based on concerns about gene transfers across species boundaries, together with feelings that government spokespersons and regulators are biased towards an industry driven by commercial interests, and a certain amount of scepticism that the longer-term safety issues are given insufficient attention.' But back then, they did not notice a widespread strong opposition to any form of biotechnology: 'in 1996 biotechnology was not a particularly salient subject with the general public. Although there was an attentive minority whose attitudes towards biotechnology tended to be relatively polarised, a considerable proportion of the UK public appeared both untouched and untroubled by the subject.'

What has happened over the past three years? The public clearly has become more sceptical of GM foods, but the strength of reaction against this technology has not come from there. Campaigners strongly opposed to GM foods have played upon a general public anxiety about science, risk and new technological developments to create a platform for their own views, assisted by sympathetic sections of the media and academia. The government's inability to hold its nerve in discussions of these controversial new technologies has made it more and more likely to cave in under pressure. Scientists, placed on the defensive, have often failed to mount a strong defence of their work and the principles behind it. The consequence of all this has been that the terms of the debate are now reposed.

A striking example is given by a recent report from the ESRC Global Environment Change Programme, The Politics of GM Food: risk, science and public trust. Based heavily upon the work of the Centre for the Study of Environmental Change at Lancaster University, it seeks to replace 'sound science' with other measures as the basis for regulating the field. So according to the ESRC report, 'if anything, the public are ahead of many scientists and policy advisers in their instinctive feeling for a need to act in a precautionary way'. When critics of mainstream science have attempted to point up specific faults in the risk assessment process, they have usually been convincingly rebuffed. The get-out clause is to play upon uncertainty. This is how the notion that the public is ahead of scientists is justified - they, unlike the men in white coats funded by industry, do not have a vested interest in pretending we know more than we do.

This is the approach promoted in the ESRC report. A chief failing of the regulatory process, its authors argue, lies in its treatment of 'deep uncertainties and "ignorance" about the possibility of entirely unforeseen events'. What they are really calling for is not so much regulation as restraint on science and technological applications. After all, what else could regulation based on dealing with 'entirely unforeseen events' mean? Scientists who might chafe against this idea are warned that the only way to regain trust is to become more humble. Along with government they must 'maintain a culture of humility and pluralism in the face of the many sources of uncertainty and ignorance in the appraisal of GM foods and other agricultural strategies'. Unsurprisingly, the authors of the ESRC report call not only for no commercial planting of GM crops, but also for a halt to the trials.

The fact that such views are now being taken seriously by government is the greatest cause for concern. Many of the arguments advanced have the potential to restrict developments in areas such as xenotransplantation, the therapeutic application of cloning technologies, the use of transgenic animals in medical research and applications and gene therapy. Consider the third of Tim O'Riordan's 'six rules for a precautionary world': 'where there is the possibility of irreversible damage to natural life support functions, precautionary action should be taken irrespective of foregone benefits.' We might think it farfetched to imagine that irreversible damage on such a scale could possibly result from the areas of research mentioned: but the precautionary principle also asks us to give weight to 'deep uncertainties and "ignorance" about the possibility of entirely unforeseen effects'. In America, bioethicists are already challenging areas of research on grounds similar to this, and a leading player in the field, George Annas, wants a new Federal Human Experimentation Agency to be created, guided by the spirit of the precautionary principle.

The promise of direct benefit to patients does strike a chord with the public. In the poll for Novartis, when it was suggested that procedures such as cloning might be needed to fight disease, support for them went up. And for the moment at least there isn't a vociferous well-organised campaign to restrict human genetics. But popular attitudes and the focuses of campaigning activity are in flux, while therapeutic applications of human genetics are still some way off. Outright bans are unlikely in all but a few areas, but more subtle restrictions, such as excessive delays in decision-making, high regulatory hurdles and a cautious attitude among investors, could well end up becoming the norm if supporters of human genetics accept the new received wisdom on how to regulate the field, and rely on public support for medical applications of science to protect the field from its critics.

In the USA, the Turning Point Project, a coalition including well-known anti-biotech activists such as Jeremy Rifkin, has taken out a series of full-page advertisements in the New York Times (at $40 000 a throw), accusing scientists of 'creating genetic pollution'. In case we are in any doubt, board member Andrew Kimbrell made plain in an interview with BioCentury that this includes all aspects of genetics: 'the biological pollution issue cuts across sectors and applies to agriculture, medicine and military uses of biotechnology.' If those interested in medical application of genetics need a wake-up call, that should do it.