The Rise and Fall of Modern Medicine (28 page)

Nor indeed was that the end of the story. It soon became clear that helicobacter was not only implicated in gastritis and peptic ulcer but also some cases of stomach cancer.
¹⁴
Soon after, every gut specialist in the world was looking for and finding helicobacter in their patients' stomachs and curing their ulcers with antibiotics. There was now no escaping the scale of their earlier collective self-deception, for not only had they failed to see these bacteria – even though they were present in virtually all their patients – they had systematically misinterpreted the many clues pointing to the fact that peptic ulcers must be caused by an infectious organism.

So how did the helicobacter protect itself against the corrosive effect of hydrochloric acid in the stomach? It turned out to be a very unusual organism, with a streamlined spiral shape propelled by a tail moving it very rapidly through the acidic secretions to find sanctuary in the mucus layer of the stomach wall. Though it does not directly penetrate the cells of the stomach wall to cause an ulcer, it does produce a range of toxins that, by causing inflammation, generate the fluids and debris that are believed to be its main source of nutrition. Helicobacter is thus perfectly adapted to its unusual environment and, once installed, persists probably for life.
¹⁵

The elucidation of helicobacter's role in so many diseases of the stomach has provoked another of those ‘paradigm shifts' in changing scientific understanding, not only of the diseases with which it is directly associated, but of all diseases. Prior to the discovery of helicobacter the three main stomach diseases – gastritis, peptic ulcer and stomach cancer – were believed to be separate entities, each with its own plausible explanations, so stress-induced excess acid led to peptic ulcers, or pickled foods or salt or nitrate fertilisers in some way damaged the lining of
the stomach wall to cause cancer.
^16
,
17
But these theories were essentially a ‘façade of knowledge', providing little insight as to how these illnesses might be prevented or cured. And then along comes Marshall, for whom the reverse of the standard cliché applies: chance favoured his unprepared mind. It was precisely because he was young and inexperienced that he was able to think the ‘unthinkable', that peptic ulcer might be an infectious disease. And in the aftermath of his self-experiment everything fell into place. Helicobacter offered both a unifying biological explanation for all the important diseases of the stomach, while simultaneously making treatment and prevention a practical proposition. There could be no more striking instance of the contrast between a coherent biological explanation that opens up the possibility of genuinely effective treatment and pseudo-explanations – whether psychological or dietary – that blame patients for their disease and leave them impotent to do anything about it.

Nor indeed do the implications of helicobacter stop here. Its discovery necessarily raises the question how many of the other diseases of unknown causation, such as multiple sclerosis or rheumatoid arthritis or diabetes, might also have a biological cause that will make them amenable to curative treatment in a similar way. This issue will be returned to.

PART I

The Rise

I
n an influential essay, ‘Science: the Endless Frontier', published in 1946, the American physicist Vannevar Bush described science as ‘a largely unexplored hinterland' that would provide the ‘essential key' to the economic prosperity of the post-war years. He himself had participated in ‘the greatest mobilisation of scientific power in the history of the world', the Manhattan Project, which at a cost of $2 billion had built from scratch in under five years the first atomic bombs, which had been dropped with such devastating effect on the Japanese cities of Hiroshima and Nagasaki. This awesome power unleashed by atomic fission would, predicted Bush, soon cease to be a ‘jealously guarded military secret', becoming instead ‘a source limitless energy' in the service of peace and industrial progress.

Vannevar Bush's optimistic anticipation of science's ‘endless frontier' was to be repeatedly vindicated over the following twenty years. In 1948 the invention of the transistor increased the calculating power of computers a million-fold, to usher in the Electronic Age. Five years later in 1953 Francis Crick and
James Watson's identification of the structure of DNA unlocked the mysteries of the genetic code. In 1961 Yuri Gagarin's orbit of Earth launched the Space Race that would culminate eight years later in the first Moon landing. Even when compared to such momentous events, the Big Bang of the post-war therapeutic revolution was the most momentous of all, a multitude of discoveries in diverse scientific disciplines stretching over a period of three decades. And its ‘definitive moments', already described, were only the headlines. For a proper sense of the scientific ferment that underpinned these achievements, it is necessary to imagine the thousands of chemists in their laboratories synthesising and testing millions of chemical compounds, or to reflect on the time and energy expended by similar numbers of physiologists, endocrinologists and neurochemists in making sense of, for example, the subtle hormonal regulation of the pituitary gland, or the mode of action of neurotransmitters in the brain.

The phenomenal scale of the post-war medical achievement calls out for explanation. What inspired it? And sustained it? What can it teach us in general about the nature of scientific solutions and the origins of scientific innovation?

The most striking impression of the twelve definitive moments is how little they have in common. The paths to scientific discovery are so diverse and depend so much on luck and serendipity that any generalisation necessarily appears suspect. The relative ease with which Howard Florey rediscovered the therapeutic potential of penicillin could not be more different from Philip Hench's twenty years' relentless failure in pursuit of Substance X, which quite fortuitously turned out to be cortisone. Nor again is there much in common between the two ‘definitive' surgical moments – open-heart surgery and transplantation. Open-heart surgery is technically very difficult
and would never have happened without the innovation of the pump. Transplantation, by contrast, is technically quite simple, but would have been inconceivable without the fortuitous discovery of azathioprine's capacity to induce immunological tolerance. This diversity of discovery is perhaps best illustrated by the contrast between the experiences of Bob Edwards and Barry Marshall. Bob Edwards first had to demonstrate that not one but two accepted truths about human fertilisation were in error before even starting on the major project of in vitro fertilisation, which then frustratingly took seven years to be realised. By comparison, Barry Marshall had it easy. His discovery of the significance of helicobacter in peptic ulcer depended on his complete lack of any experience of medical research, which allowed him to think the unthinkable – that it might be an infectious disease.

Nonetheless, diverse as these paths of innovation might appear, they are clearly ‘of a piece', carried along by a strong undercurrent of ideas and events, among the most important of which was the war. It is a truism that the urgency of conflict accelerates the pace of innovation, and four – at least – of the definitive moments were forged by the necessities of war time.

The search for an antidote to chemical weapons led Alfred Gilman and Louis Goodman to inject nitrogen mustard into a mouse with a lymphoma and observe that the tumour ‘regressed to such an extent it could no longer be palpated'. Again, military intelligence reports of rumours that Luftwaffe pilots boosted by injections of adrenal hormones were able to fly at heights of over 40,000 feet stimulated the US National Defense Research Council to initiate the arduous research programme that culminated in the synthesis of cortisone.

The war also had a major influence on the development of heart surgery, in particular the demonstration by the American
surgeon Dwight Harken, operating on casualties from the D-Day invasion of Normandy, that bullets and shrapnel could be removed from the heart without killing the patient. This, in turn, encouraged surgeons – including Harken himself – to start performing operations on the heart, such as dilating narrowed valves. Then there was penicillin. Howard Florey would probably never have made his brave decision in 1941 to turn the Department of Pathology at Oxford into a chemical factory to make penicillin had it not been for the Dunkirk spirit that prevailed at that time.

The influence of the war can be detected in two other ways closely related to Vannevar Bush's concept of the ‘endless frontiers' of science. Bush, as a major participant in the Manhattan Project, had seen at close hand what state funding and the central direction of research could achieve. The lesson was not lost and the notion of massive state investment in research as a basis of future prosperity was readily extrapolated to health, which led in time to the vast billion-dollar-funded organisations such as the National Institutes of Health and the National Cancer Institute.

But, more important still, the Allied victory in 1945 released a surge of pent-up utopian energies. The limitless possibilities of science would build ‘a better world', whose form, according to Vannevar Bush, ‘is predestined by the laws of logic and the nature of human reasoning'. The builders of this new world would include ‘men of vision who can grasp in advance just what is needed for rapid progress, who can tell by some subtle sense where it will be found and have an uncanny skill in bringing it into the light'. Nowadays such unbridled optimism seems naive, even embarrassing. But it alone can explain why, during this period, doctors and scientists seemed prepared to take on what at the time appeared quite insoluble problems. If the
possibilities of science truly were limitless then everything was possible, including the cure of childhood cancer, transplanting organs and open-heart surgery.

Taken together, these war-related therapeutic innovations contributed to the creation of a ‘critical mass', when a high level of activity in many fields of medical research sparked off a chain reaction of further developments. This internal dynamic can be conveniently divided into six separate themes. The first two, and the concern of the rest of this chapter, were the coincidental discovery of antibiotics and steroids and the ‘inter connectedness' of medical research. The remaining four, examined in the remaining chapters of this section, are: the rise of ‘clinical science' in the 1940s as the dominant ideology of medicine; the fusion of chemistry with capitalism to give rise to the pharmaceutical revolution; the contribution of technology; and ‘the mysteries of biology'.

It is obvious now that the post-war medical achievement was built on the twin pillars of antibiotics and steroids or, to revert to the earlier metaphor, they were the fuse that lit the chain reaction of post-war medical innovation. There is no difficulty in recognising the crucial role of antibiotics, but the claim that cortisone was equally important might be considered more contentious. Certainly, the therapeutic effects of antibiotics and steroids were very different but crucially they were also complementary: antibiotics in their assault on infections, the commonest known cause of disease; steroids by proving so useful in many diseases whose causes were and remain unknown. They were both effective in specific diseases – penicillin against pneumonia, steroids in the treatment of rheumatoid arthritis – but they also transformed whole categories of illness. Antibiotics effectively eliminated the vast burden of misery caused by
chronic infections – of the bones and joints that so preoccupied orthopaedic surgeons, or of the ear, sinuses and upper airways that had kept ENT surgeons so busy, or of the female reproductive organs that had been such an important cause of infertility and maternal mortality. As for steroids, they established in a way that had never been clear before that apparently quite distinct diseases – asthma, eczema, chronic active hepatitis, myasthenia gravis, polyarteritis, optic neuritis – nonetheless shared the common feature of arising from uncontrolled and excessive inflammation.

Nor was that all. Antibiotics and steroids changed the everyday practice of medicine, but they also offered positive proof of the notion, already alluded to, that ‘the possibilities of science' were limitless and that one day apparently insoluble problems would be overcome. And indeed they were instrumental in bringing this about: steroids provided the crucial breakthrough – along with azathioprine – in overcoming the immunological rejection of transplanted organs in 1963, and they were also one of the four drugs of the protocol with which Dr Donald Pinkel achieved his 50 per cent cure rate of leukaemia in 1971. Antibiotics provided a source of several important anti-cancer drugs and also made transplantation possible by protecting immunocompromised patients against the threat of overwhelming infection.

This contribution of antibiotics and steroids to the success of transplantation and cancer therapy illustrates the second feature of the ‘internal dynamic' of the post-war medical achievement, which for want of a better term might be described as the ‘interconnectedness' of medical research, the way in which developments in different scientific disciplines came together at particular moments to propel the therapeutic revolution onwards. Thus, Henri Laborit's observation of the ‘euphoric
quietude' in his surgical patients became – in the form of chlorpromazine – the cornerstone of the psychopharmacological revolution in psychiatry, while Bjorn Ibsen's experience of the use of curare in the operating theatre transformed the prospects of survival of children dying from polio.