The Rise and Fall of Modern Medicine

by James Le Fanu

  It was at this crucial moment that Keys’s thesis emerged, now endorsed (thanks to his efforts) by the American Heart Association and without a serious challenger, to become the central explanation of the coronary epidemic. The epidemic was now so severe that virtually any explanation would have served as a way of making sense of why for over thirty years the toll of young men dying from coronaries had increased exponentially year by year, with absolutely no sign it was coming to an end. Like the AIDS epidemic of the 1980s, coronary disease became an absolute priority for those engaged in promoting the public health. By the early 1970s, the time had come to provide the incontrovertible proof that modifying these risk factors would prevent heart disease. To this end the protagonists in both the United States and Europe launched, in the early 1970s, the largest and most expensive scientific experiment ever conceived in the history of medicine, involving over 60,000 men and costing in excess of £100 million.

  In the United States 360,000 middle-aged men were interviewed to find the 12,000 at highest risk. Most were smokers, had been diagnosed as having raised blood pressure while still young and had markedly elevated cholesterol levels. They were then randomly allocated into either an ‘intervention’ or a ‘control’ group and the Multiple Risk Factor Intervention Trial (MRFIT) was launched. The complexity and expense of this study lay in the need to change people’s lives – to encourage them to give up one style of life and adopt another. There was little difficulty in ensuring that those with raised blood pressure were adequately treated, by giving appropriate medication. Discouraging smoking was, as always, more difficult, and every conceivable way was deployed to encourage the men to quit, including monetary rewards, hypnosis and aversion techniques. But such practicalities were nothing when compared to what was required to achieve the dietary modifications necessary to lower the cholesterol level. Nothing other than monumental changes would do, so the participants were showered with nutritional information, taught how to shop for groceries, what to order in restaurants, given advice on how to rewrite their favourite recipes, asked to record everything they ate and sign contracts pledging to abstain from various foods. They were told to eat only low-fat cheese, restricted to two eggs a week and instructed to avoid all cakes, puddings and pastries and to reduce markedly the amount of meat consumed. These prodigious efforts were rewarded – the average amount of saturated fat in their diet fell by about a quarter – but disappointingly their cholesterol level only fell by just over 5 per cent.

  The dedication and energy of those involved in MRFIT was admirable, but it would be quite unrealistic to expect that such prodigious efforts would be readily applicable in the real world. Hence the interest in the second of the two studies launched at the same time and organised by Geoffrey Rose, Professor of Epidemiology at the London School of Hygiene, the leading standard-bearer for Keys’s hypothesis in Europe. His project, co-ordinated under the auspices of the World Health Organisation and thus known as the ‘WHO Trial’, was much larger, involving almost 50,000 men in sixty-six factories in Britain, Belgium, Italy and Poland. The workers in the ‘intervention’ group were exposed to a blitzkrieg of health education to encourage them to change their lifestyle, backed up by evening meetings, floor shows, talks about heart disease and cookery demonstrations. Those in the ‘control’ factories were left in peace.

  It would seem unlikely on first principles, given that the rise in heart disease could not be explained by increasing amounts of saturated fat in the diet of Western nations, that these radical dietary changes to reduce fat consumption would be effective in preventing it. And so it turned out. Despite the prodigious efforts of the MRFIT trial to cajole so many men into changing their lives and giving up the pleasures of meat and eggs and cakes and pastries and much else besides, the results published in 1982 show they were no less likely to suffer from a heart attack than those in the ‘control’ group.18 Seven months later the WHO Trial delivered precisely the same verdict.19

  Nor was this the only problem for Keys’s thesis. There are only two ways in which it could be tested experimentally. The first, as represented by the trials, was to encourage people to change their diets and see the effect on heart disease. This, as has been noted, did not work. The alternative was to perform the experiment, as it were, the other way round and look to see whether the rising incidence of heart disease over several decades had been paralleled by major changes in what people ate. This, as has already been noted, was a central weakness of the thesis, as the twenty-fold rise in heart disease throughout the 1940s and 1950s had not been paralleled by increasing amounts of fat in the diet. By the early 1980s it was quite apparent that this original trend had been reversed and that the incidence of heart disease had gone into steep decline.20 The decline, it must be appreciated, was universal, across all ages, classes and ethnic groups, and international, occurring simultaneously in the United States, Canada, New Zealand and Australia. Thus if the ‘lifestyle’ theory of heart disease were correct, people would have had to have made substantial changes in their diet at least ten years earlier, not just in the United States but in all these other countries as well. Clearly this was impossible for, as shown in the graph on page 375, the precipitous rise and equally precipitous fall in heart disease occurs in different countries in parallel, while the proportion of fat in the diet hardly changes. Indeed, by the early 1980s, when this fall in heart disease was becoming ever more marked, the necessary dietary changes would have had to be monumental, much greater than those imposed on the ‘intervention’ group in the MRFIT trial. Rather, this pattern of ‘the rise and fall’ of heart disease resembled ‘the rise and fall’ of an infectious disease. It was not a ‘social’ but a ‘biological’ pattern, with the obvious implication that some unknown biological factor must be the culprit, either by influencing the severity of atheroma in the coronary arteries, or by precipitating the clot that causes the heart attack – or both.

  The seriousness of these developments for the proponents of The Social Theory is obvious enough. They were just getting into their stride with their ambitious programme to realign medicine towards preventing the Diseases of Affluence and now suddenly the scientific validity of its central pillar – the implication of the Western diet in the epidemic of heart disease – seemed highly questionable. There were two powerful interested parties in particular who could not acknowledge defeat. The first were those like Keys, Stamler, Rose and many others who had invested a lifetime’s work and hundreds of millions of pounds of research funds in trying to prove the thesis. The second were the drug companies who had made substantial capital investment in the development of cholesterol-lowering drugs, for which, naturally, they needed a market. Now cholesterol, as has been noted, is not entirely innocent, as, whatever might be the unknown ‘biological’ cause that explained the rise and fall of heart disease, it clearly was most likely to hit those with higher than average cholesterol levels and therefore more severe atheroma in their coronary arteries. Hence both the drug companies and the dietary protagonists had a mutual interest in salvaging Keys’s thesis. If the drug companies could show that their powerful cholesterol-lowering drugs reduced the chances of a heart attack in those with markedly raised cholesterol levels (which was probable), this would be evidence that the disease was indeed ‘preventable’, which would then shore up the position of the proponents of the dietary theory like Stamler and Keys. And if they could, in their turn, convince the public that too much fat caused heart disease, so everyone should lower their cholesterol levels, this would markedly increase the market for cholesterol-lowering drugs way beyond the minority ‘at high risk’. And that is precisely what happened.

  We start with the dietary protagonists. Clearly, for The Social Theory to survive despite the negative results of the trials, the focus would have to be shifted away from the scientific arena, where it could be debated, towards authoritative ex cathedra assertions that bacon and eggs (or their equivalent) really did cause heart attacks. The best way of ensuring this �
�fact management’ was through the medium of reports from ‘expert committees’ made up of the protagonists – the same ploy by which Keys first had his thesis officially endorsed by the American Heart Association back in 1961. From the early 1980s onwards, these expert committees multiplied like rabbits, each claiming to have examined the entrails of the scientific evidence to come to precisely the same verdict, that the Western diet caused heart disease (and strokes, diabetes, breast cancer and much else besides).

  The message of these reports was duly picked up by sympathetic journalists who passed it on to the wider public. Thus, in 1985, the readers of The Times were informed: ‘Western food is the main single underlying cause of Western disease which leaders of the medical profession [describe] in apocalyptic terms as a holocaust, which medicine can do nothing to check.’

  This very serious state of affairs naturally raised the important question of why so little was being done about it. Every good story requires a villain and, sure enough, the best intentions of the experts were being thwarted by powerful antagonistic forces in the form of the food industry and farmers – and their apologists, a small group of ‘corrupt’ scientists. ‘There are some who, from a position of authority, assert that fat and salt in the quantities consumed in Britain today are harmless to health. As far as I know they are all employed, paid by or associated with the food industry.’ The role of these scientific sceptics in condoning the food industry’s attempts to peddle lethal foodstuffs to the public was ‘the biggest scandal since the day 150 years ago when officials refused to act on the fact that cholera was caused by open sewers’.21

  As for the second interested party, the pharmaceutical industry, the prospects for the mass prescription of cholesterol-lowering drugs were much enhanced with the publication in 1984 of a clinical trial demonstrating that, for those at ‘high risk’, the drug cholestyramine reduced the chances of dying from a heart attack by 25 per cent. This result, according to the chief organiser, offered ‘conclusive proof’ that heart disease could be prevented. Admittedly the participants had all been at ‘very high risk’, but ‘the trial’s implications could and should be extended to all age groups and those with more modest elevations of cholesterol’.22

  The following week Time’s cover featured a plate of bacon and eggs arranged to resemble a doleful face with the headline ‘Cholesterol: And now the Bad News . . . ’. ‘Sorry, it’s true, cholesterol really is a killer,’ ran the story on the inside page. Newsweek pursued the same line, quoting an expert opinion that this was ‘a milestone, with implications for all Americans’.

  And how did the participants in this ‘landmark study’ fare? Cholestyramine must be sprinkled directly on to food, rendering meals unpalatable, with two-thirds of the participants reporting moderate to serious side-effects of constipation, gas, heartburn and bloating. After seven years of this regime thirty out of the 1,900 taking cholestyramine had had a fatal heart attack compared to thirty-eight out of the similar number in the control group. This indeed can be interpreted as ‘reducing the chances of dying from a heart attack by 25 per cent’ (8 divided by 38 and multiplied by 100 equals almost 25). But put another way, almost 2,000 men had to take cholestyramine for seven years to increase their chances of avoiding a heart attack by less than half of 1 per cent (8 divided by 2,000 multiplied by 100). This seems a modest enough achievement, except that overall cholestyramine made no difference at all, as the total number of deaths in the ‘intervention’ and ‘control’ groups were exactly the same, with the modest reduction in heart disease mortality in those taking cholestyramine being balanced by an increased risk of death ‘from other causes’.

  The gold mine of ‘cholesterol-lowering for all’ was much too enticing to be deflected by such considerations. After all, seven years’ worth of cholestyramine for 2,000 men added up to £9 million, which worked out at over £1 million for each of the eight fatal heart attacks prevented and (as there was no difference in overall mortality) an infinite sum for every life saved.

  Now for ‘the sting’. It is only natural to be suspicious when a drug company extols the benefits of drug X, but an entirely different matter when the desirability of taking such a drug is endorsed by apparently ‘independent’ experts as part of an ‘education’ programme. And sure enough, in December 1984, just a few months after the cholestyramine trial (and Time’s gloss upon it), the US National Institutes of Health launched the National Cholesterol Education Program with the double message: ‘The blood cholesterol level of most Americans is undesirably high’ and should be reduced because ‘it has been established beyond reasonable doubt’ that this would reduce the subsequent risk of a heart attack.23

  The strategy worked brilliantly. The fear of premature death from a coronary was quite sufficient to propel the health-conscious to their doctor’s surgery to have their cholesterol level measured; a quarter of whom would subsequently be started on drug therapy. Financially, everyone benefited: the drug companies; those involved in testing for cholesterol; and, in private health-care systems such as that of the United States, the doctors who charged their patients for check-ups on their cholesterol level. The total cost of this drug-company-inspired cholesterol obsession was phenomenal. By the mid-1990s hundreds of thousands of otherwise healthy men and women across the world were taking cholesterol-lowering drugs at a cost in excess of £3 billion a year.24

  Together the drug companies and Social Theorists had triumphed. Snatching victory from the jaws of defeat of the verdict of the trials, dozens of expert committee reports had persuaded most people that ‘Western food is the chief reason for our modern epidemic of heart disease’. This in turn had been the Trojan Horse by which millions had been prescribed cholesterol-lowering drugs. It is interesting to note how the ‘dietary and lifestyle’ explanation for heart disease had produced precisely the opposite effects to those anticipated. Its appeal lay in the promise of liberating people from their reliance on doctors, for by simply changing their diet they could reduce the risk of heart disease and thus the need for drugs and surgery. As it turned out the ‘lifestyle’ theory massively increased the influence of medicine, as medical experts now dictated what people should and should not eat. Further, it provided a context within which doctors could persuade otherwise healthy people that they needed to take drugs for life. And at the end of it all, Keys’s thesis was no ‘truer’ than it had been back in 1957, when the first of the American Heart Association committees had observed how it failed to account for the marked increase in heart disease.

  The two final events that would undermine the seamless litany of half-truths that sustained Keys’s thesis were, first, the ‘rediscovery’ that the clot or thrombus in the coronary arteries, not the levels of cholesterol in the blood, is the critical factor in causing a heart attack and, second, the circumstantial evidence for an infective cause for the rise and fall of heart disease over the past sixty years.

  The perception of the critical role of the thrombus, it will be recalled, was displaced in the mid-1960s when it emerged that blood-thinning drugs, though effective, had the regrettable consequence of increasing the risk of haemorrhage into the brain. This failure, however, did not mean that the thrombus was unimportant, just that better ways had to be found to prevent or dissolve it. Ideally, two types of drug are required, a simple compound that will prevent the platelets from sticking together to form a thrombus in the first place, but also a more potent ‘clot-busting’ drug that could be administered in the aftermath of a heart attack.

  Both types of drug had in fact already been around for a long time, in the case of the former – aspirin – for two hundred years. It is natural to presume that, given aspirin’s many therapeutic properties, there must be some common underlying physiological process with which it interferes – and so there is. In 1971 the British biochemist John Vane demonstrated that aspirin blocked the action of a family of closely related chemicals – the prostaglandins – produced fleetingly in minute quantities by many different tissues
in response to injury, one of which, thromboxane, encourages platelets to stick together to plug a bleeding artery or vein.25 So here was a very cheap drug that in small doses discouraged platelets from forming a clot thus preventing the two serious circulatory disorders of heart disease and stroke.26 For this most significant discovery John Vane would subsequently be awarded the Nobel Prize.

  Aspirin might prevent some, if not all, heart attacks but a complementary approach was needed that would dissolve the clot in the arteries after it has formed, thus restoring the blood flow to the heart muscle. In 1980 Dr Marcus de Wood of the University of Washington demonstrated that the drug streptokinase (originally derived from the streptococcus bacterium fifty years earlier) dissolved the acute blockage of one or other coronary arteries in 110 out of 126 patients.27 When combined together, aspirin and streptokinase, it emerged, have a truly astonishing effect, reducing by over half the numbers succumbing within the first four weeks following a heart attack.28

  The much neglected thrombus, marginalised by the baleful influence of the cholesterol obsession, may have turned out to be very important after all, but it still leaves unexplained the epidemic pattern of the rise and fall of heart disease which, as pointed out, is strongly suggestive of an underlying biological cause such as infection.

  It is significant here that the narrowing of the arteries by atherosclerosis, when examined under the microscope, is strongly suggestive of an inflammatory process. The specific agent involved would, however, remain elusive until 1992, when Dr Chochuo Kuo of the University of Washington, using a special staining technique, identified the bacterium chlamydia in the walls of the arteries of South African miners who had recently succumbed from a heart attack.29 This prompted a series of studies looking for evidence of chronic infection that would implicate, variously, the ‘atypical’ bacterium mycoplasma and several viruses including herpes and cytomegalovirus. Hence it would appear several interacting infectious agents might be involved: it is, observed Dr Stephen Epstein in the journal Circulation Research, ‘the aggregate number of pathogens with which an individual is infected that will determine the propensity to develop atherosclerosis and the . . . acute thrombotic arterial occlusion’.30