James Le Fanu

‘For every problem there is a solution: neat, plausible and wrong’. H.L.Mencken

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Geneticists are not gods

The news this week that cloning techniques are to be allowed in Britain for therapeutic purposes has encouraged the perception that science fiction isbecoming fact. But a writer and doctor thinks it is time for a dose of scepticism. The momentum of modern genetics looks to many people unstoppable. There simply is no other field of medical research that has anything like the same promise, observes one of Britain?s leading geneticists, Sir Walter Bodmer, adding: There can be no doubt of its enormous benefit to mankind. This week, authoritative government advisers endorsed proposals for cloning human embryos as a source of spare parts tissues and who knows where it will end. It is presumably only a matter of time before scientists will be able to grow whole human organs and create perfect babies by screening out those with unhealthy genes or selecting those that have any particular talent their parents might desire.

We may not like the sound of it, Catholic theologians like Gino Concetti may protest that people have the right to be born in a human way and not in a laboratory, but this, it seems, is the future and we have to accommodate ourselves to it. To be sure, there is and will continue to be ethical controversy but, as ever, science will win the day ? for no other reason than that its critics can so readily be portrayed as being indifferent to human suffering for opposing, on moral grounds, this vital new field of medical research.

But is this really the future? The dramatic promises of scientists to control nature and conquer disease may seem impressive but it is only natural that they should seek to draw attention to their work and perhaps even enhance their self- importance, secure in the knowledge that the complexity of genetics effectively precludes others from coming to an independent judgement about the valid-ity of their claims.

Several recent developments would suggest that, behind the facile talk of the benefits of cloning and genetic manipulation, the prospects for genetic research are turning out to be much less hopeful than they have been portrayed. It is always useful to have a historical perspective on these matters and it is striking how current controversies have a direct parallel in the original argument, back in the 1980s, over the legalisation of experiments on human embryos. At that time, the proponents argued that banning such experi-ments would condemn future generations to 4,000 inherited genetic illnesses that could be prevented. This is obviously a difficult claim to counter, but it was not at all obvious that human embryos were necessary for such investigations. Indeed, as the former editor of the authoritative science journal Nature, John Maddox, observed in 1985: There seems something of a dearth of serious proposals for human embryo experiments that would make sense. His invitation to scientists to submit suggestions that could be published as part of a campaign in favour of legislation elicited none of sufficient merit. Ten years on, not one of the many touted benefits of human embryo research has materialised.

Now the focus has shifted to genetic screening, gene therapy and the cloning of human embryos, but again there appears to be a discrepancy between the putative and realistic expectations from such procedures. There are two important reasons why this might be so.

The first, perhaps surprisingly, is that the genes are not actually a very important factor in human illness, as natural selection ensures that those with genetic diseases are unlikely to have many offspring. Certainly, there are 4,000 recognised diseases caused by a defect in a single gene, but individually they are, for the most part, very rare and, importantly, unpredictable and thus difficult to prevent. Certainly, there may be a genetic component to many diseases, from schizophrenia through to cancer, but only infrequently is the susceptibility a determining factor. So genetic manipulation, leaving aside the enormous technical problems involved, is unlikely to be an effective form of treatment.

The second reason for the discrepancy between the hype and reality of genetic research is that the workings of the human genome now appear to be more inscrutable than had originally been anticipated. Perversely, the more that is known, the less comprehensible it becomes. Consider the following. When the 3 billion molecules of DNA that make up the human genome are finally spelt out, they will fill the equivalent of 48 volumes of the Encyclopaedia Britannica. But these 48 volumes have to be compressed within the nucleus of the cell and in doing so the human genome packs over 100 trillion times as much information as the most sophisticated computer which human intelligence has so far been able to devise.

This 100-trillion-times miniaturised information system present in the single-celled conceptus immediately after fertilisation will, over the following months and years, reproduce itself billions of times. Somehow, the genes within it know how to instruct the foetal cells to form, first the basic structure of the embryo with a back and front, head and limbs, and then know how to instruct them to acquire the specialised functions of nerves, muscle fibres or liver cells, and then know how to instruct them to grow through childhood and adolescence to adulthood, and in the process link up and interact with each other to form functioning organs within the totality of the human body.

Now, the scientific community can only have the vaguest understanding of the details of how this comes about. Indeed, it would not be unreasonable to conceive of the extraordinary potential of the biological information located within the nucleus of every cell as the mirror image of the infinite size and grandeur of the universe.

Taken together, this ineffable complexity of the human genome and the marginal contribution of genes to human disease point to the same conclusion ? the brave new world promised by the geneticists is likely to be illusory. This emerges quite clearly from recent developments in the two fields where genetics might most obviously be expected to deliver on its promises ? genetic screening and gene therapy.

The discovery in the late 1980s of the gene for cystic fibrosis raised the hope that this, the commonest life-threatening inherited disease in Western societies (though it is still not very common, with only 300 cases a year in Britain), could be prevented by antenatal diagnosis and selective abortion of those foetuses found to carry the abnormal gene.

Theoretically this is certainly possible, but the logistical problems involved have proved almost insuperable, as illustrated by the experience of a screening programme in Edinburgh. Over a period of five years, 25,000 couples were tested to find 22 who were both carriers of the abnormal gene and thus at risk of having a child with cystic fibrosis. The diagnosis was confirmed by antenatal testing in eight of these pregnancies and the foetus subsequently aborted. This type of genetic screening is a massive undertaking. It is highly debatable whether it is worthwhile to generate so much parental anxiety just to terminate 0.03 per cent of pregnancies, especially as the cost of each case of cystic fibrosis prevented was in excess of ?100,000. Or, as an editorial in the Lancet cautiously expressed it, we still have to think whether such a screening programme is what we want. It is a fair bet it will not happen. And if this is the verdict for cystic fibrosis screening, then the prevention of genetic disease by prenatal testing is scarcely an option for all the other, much rarer, inherited disorders.

The experience with gene therapy, the attempt to replace a dud gene with a normal one, has proved even more disappointing as it simply does not work at all. Two hundred trials of gene therapy over the last decade have, according to the United States National Institute of Health, which sponsored them to the tune of hundreds of millions of pounds, resulted in no evidence of therapeutic benefit to patients ? or even animal models; and, just as scientists have so conspicuously failed to deliver on their promises about genetic screening and gene therapy, so there is no reason to believe their forecast this week that nervous tissue from cloned human embryos will cure Parkinson?s Disease or Alzheimer?s.

Indeed, genetic researchers have already responded to these setbacks by postponing into the distant future the time when they expect their endeavours to be of enormous benefit to mankind. There is every reason to be sceptical, because the most important insight of recent years has been that the conception of the gene, on which the hopes of genetic manipulation rest, has proved to be far too simplistic. The genes are not, as commonly portrayed, master molecules, the blueprint from which everything flows, because individually they can do nothing without interacting with and being controlled by other genes whose function is in turn controlled by the cell within which they are located. The heart of the problem lies in the fact that we are dealing not with a chain of causation, but with a network; that is, a system like a spider?s web, writes a former professor emeritus at Birmingham University, Philip Gell. A perturbation at any point changes the tension of every fibre right back to its anchorage in the blackberry bush. The gaps in our knowledge are therefore not merely unbridged, but unbridgeable.

Probably the most conspicuous effect of the false promises of genetic research has been to persuade the public that we are moving into an era where man can control his destiny and thus traditional moral perspectives are no longer relevant. It would, however, be not unreasonable to draw the opposite conclusion and perceive in the infinite complexity of the human genome as now revealed, an ineffable mystery that requires our respect.

Copyright: Telegraph Group Ltd