The Rise and Fall of Modern Medicine (43 page)

The New Genetics begins to appear like a relentless catalogue of failed aspirations. This is profoundly shocking for, as already noted, virtually all doctors and to a greater or lesser degree the public perceive The New Genetics not only as the great scientific success story of the past fifteen years, but also as holding the key to a golden future when everything that is currently obscure will be revealed. This discrepancy between the perceived and the actual achievements of the New Genetics is pivotal to any analysis of the current state of medicine. It poses two related questions: ‘Why is there a pervasive belief in the
limitless possibilities of The New Genetics?' and its antithesis, ‘Why has the New Genetics failed to deliver?'

First, why the pervasive belief in ‘limitless possibilities'? The New Genetics emerged at precisely the right moment to fill the intellectual vacuum created by the End of the Age of Optimism of the late 1970s. Next, The New Genetics was serious science, apparently much more serious than the pot-luck empirical hit-or-miss medicinal chemistry that had generated so many new drugs in the 1950s and 1960s. And, being so serious, it was only natural to expect it would, by pinpointing the relevant genes, find ‘the ultimate cause' of common diseases. Then, the possibilities of The New Genetics were vigorously promoted in a way that had never happened before. Commercially, biotechnology pioneers like Robert Swanson were initially selling the
idea
that the technical complexity of making drugs by inserting genes into bacteria must mean they would be genuinely beneficial in previously untreatable diseases, like adult cancer and multiple sclerosis. And with billions of dollars of investors' money at stake, there was every incentive to talk up such possibilities.

This advocacy of the potential of The New Genetics has proved very persuasive with the result that, in the popular imagination, DNA has acquired the reputation of providing the key to understanding the whole of human biology. It is the Book of Man, a dictionary, a map or a blueprint determining who we are. Logically then, The New Genetics can, by offering an understanding of ‘the blueprint', improve our minds and bodies and make us better and healthier people. There is certainly every reason for molecular biologists to project this view of their task, as it is the ultimate guarantee of continuing funds for their research.
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But the chasm-like discrepancy between the promise and the
reality of The New Genetics poses a whole series of questions as to why it might have failed to ‘deliver'. The first and obvious constraint is quite simply that genetics is not a very significant factor in human disease. This is scarcely surprising, as man would not be as successful a species as he is (many would argue too successful) were it not that natural selection had over millions of years weeded out the unfit. Consequently there is only a handful of common gene disorders and they themselves are not very common. Further, the contribution of genetics to adult disease such as cancer is limited to a minority of cases and for everybody else it is almost invariably only one of several factors, of which the most important is ageing, an everyday fact of life about which there is not much that can be done.
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The second reason why The New Genetics might have failed to live up to expectations is that the genes themselves turn out to be infinitely more complex and elusive than could ever have been imagined. There was a charming and elegant simplicity revealed by the unravelling of the genetic basis for sickle cell anaemia – a defect in one triplet of nucleotides caused the insertion of the ‘wrong' amino acid in the haemoglobin protein, thus altering the red cells' physicochemical properties so that they ‘sickle'. It seemed, in the early 1980s, that genetics could be understood in terms of such well-defined rules and certainly, if all diseases had been similar to sickle cell anaemia, then everything would have been sorted out in no time. But now we know better. Sickle cell anaemia turns out to be virtually unique in the simple nature of its genetic defect. The behaviour of the genes turns out not to be determined by hard and fast rules, but rather is ambiguous, elusive, contradictory and unpredictable. The central concept that the gene, in the form of triplets of nucleotides, codes for an arrangement of amino acids that makes up a protein has turned out to be deficient in several ways. The
first is ‘linguistic': any triplet of nucleotides turns out to mean different things in different circumstances. Richard Lewontin, biologist at Harvard University, explains:

And just as one can never be sure what any triplet of nucleotides might mean, one can never be sure what the significance of a mutation in the nucleotides might be. Thus in sickle cell anaemia one defect in a sequence of nucleotides – GAG instead of GTG – leads to the insertion of the ‘wrong' amino acid (valine instead of glutamic acid) in the haemoglobin protein and thus causes the red blood cell to sickle. But in cystic fibrosis, 200 or more such mutations of nucleotides have been identified that can cause the disease, and a further 200 that make no difference. Nor can one be confident that the same mutation causes the same disease, as illustrated by two sisters who both
had the same mutation in the gene for the ‘light-sensitive' protein rhodopsin in the retina that results in blindness from retinitis pigmentosa (a gradual destruction of the retinal cells at the back of the eye). The younger sister was indeed blind but the visual acuity of her older sibling – whose rhodopsin gene contained exactly the same mutation – was excellent and did not prevent her from working as a night-time truck driver. So when, after prodigious efforts, the ‘ultimate genetic cause' of retinitis pigmentosa was finally pinned down to a specific defect in a specific gene, it then emerged that the ‘ultimate cause' was apparently quite compatible with not having the disease at all. Such perverse complexities, inexplicable in the conventional understanding of the mechanism of gene action, abound. They lead to a situation of incomprehensible complexity, where precisely the same genetic disease can be caused by different mutations in several genes, while several different diseases can stem from mutations in a single gene.
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It could, of course, be argued that The New Genetics is currently in the same situation as The Old Genetics was back in 1970 when, following the elucidation of the mechanism of gene action, most molecular biologists felt they had reached the limits of scientific understanding. Might it be that further technical innovations in the future may make genetic screening and gene therapy perfectly feasible? Perhaps, but the practical applications of The New Genetics rest on a concept of the nature of the gene – a unidirectional flow of information, ‘DNA makes RNA makes protein' – that is far too simplistic. Certainly the imagery of DNA as the ‘master molecule, the blueprint from which everything flows' is vivid enough, but genes by themselves can do nothing without interacting with other genes operating within the context of the whole cell within which they are located. In the words of Philip Gell FRS, Emeritus Professor of
Genetics at the University of Birmingham: ‘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 in which a perturbation at any point of the web changes the tension of every fibre right back to its anchorage in the blackberry bush. The gap in our knowledge is not merely unbridged, but in principle unbridgable and our ignorance will remain ineluctable.'
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T
here is, as has been suggested, a seductive familiarity in the symmetrical manner with which The New Genetics and The Social Theory sought to explain the causes of disease, evoking the separate contributions of nature (the gene) and nurture (upbringing) in human development.

The great appeal of The Social Theory is that it both provides an explanation for disease and opens the way to preventing it. The major significance of Bradford Hill's demonstration in 1950 of the causative role of smoking in lung cancer is that it held out the possibility of the dramatically different and potent alternative of ‘mass prevention' to the problem of illness. Self-evidently, public health campaigns to discourage people from smoking were likely to have a greater practical benefit, by orders of magnitude, by preventing lung cancer than seeking, not very successfully, to treat it with surgery or drugs. Prevention, as everyone knows, is better than cure. Indeed, the many great
achievements of the therapeutic revolution, the ‘cornucopia of new drugs' and the ‘triumphs of technology', could simply be dispensed with were it possible to identify modifiable causes of common diseases in people's everyday lives. The problem was that up until the mid-1970s the precise causes of these diseases remained quite unknown. And then, suddenly it seemed as if this ignorance was being swept away as, with increasing certainty, it was asserted that, in precisely the same way as abjuring smoking prevents lung cancer, so most cancers together with heart disease and strokes were similarly preventable were people to change their social habits. The rise in the scope and ambition of The Social Theory is really quite extraordinary. Thus a booklet published by the British Medical Association in the late 1960s with the old-fashioned title ‘Doctor's Orders' advised readers of the dangers of smoking, the merits of a ‘sensible balanced diet', and particularly to avoid becoming overweight. It warned that drinking more than a bottle of wine a day (or its equivalent) could damage the liver. But that was all. By the 1990s, this sensible – if rather obvious – advice had escalated to encompass every aspect of people's lives. The advice on a ‘sensible balanced diet' had metamorphosed into the claim that the serious diseases are quite simply the outcome of specific foods people consume: salt overloads the circulation, pushing up the blood pressure to cause paralysis or death from stroke; saturated fats in dairy foods and meat fur up the arteries to cause untimely death from a heart attack, as well as being ‘implicated' in causing many common cancers including those of the breast and bowel.

Meanwhile scientific investigations revealed that numerous other unsuspected hazards in people's lives, including the minuscule quantities of chemicals and pollutants in air and water, were similarly implicated in a whole range of serious illnesses such as leukaemia, stomach cancer, infertility and much else besides.
This was medicine on the grand scale of the great sanitary reforms of the nineteenth century when civil engineering, by providing a clean water supply, eradicated water-borne infectious diseases such as cholera. Now social engineering, by encouraging people to adopt healthy lifestyles, together with a serious assault on the environmental cause of disease, would have a comparably beneficial effect.

While it is very difficult to evaluate all the relevant evidence for such assertions, their origin undoubtedly can be traced to a powerful and persuasive critique by Professor Thomas McKeown in 1976 of the prevailing view that the progress of medical science could take the credit for the prodigious improvements in health over the preceding 100 years. On the contrary, he argued, doctors might pride themselves on the modern drugs and technology they deployed in their shiny new palaces of disease, but in reality they had played only a minor role in the precipitous fall in infant and maternal mortality and the substantial increase in life expectancy. These achievements could more readily be attributed to social changes: ‘Medical science and its services are misdirected,' he said, ‘because they rest on an indifference to the external influences and personal behaviour which are the predominant determinants of health.'

The essence of McKeown's argument is encompassed in a single graph (see page 354) showing the decline in mortality from tuberculosis of the lungs in England and Wales, from a peak of 4,000 per million of the population in 1838, down to 350 per million in 1945 when the drugs streptomycin and PAS were introduced, and then almost to zero by 1960. Thus 92 per cent of the decline in tuberculosis could be attributed to ‘social factors' and only 8 per cent to the great miracle of twentieth-century medicine, antibiotics. From this McKeown concluded
that ‘medical intervention can be expected to make a relatively small contribution to the prevention of sickness and health'. He conceded that there was ‘no direct evidence' that social factors were primarily responsible; nonetheless it seemed plausible enough that better nutrition, improved hygiene and housing (and particularly the decline in overcrowding) could account for this massive decline of tuberculosis.
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