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 cu
rare in the operating theatre transformed the prospects of survival of children dying from polio.
The development of IVF illustrates in a more complex form this interconnectedness, where four quite independent lines of research combined to culminate in the birth of the first test-tube baby: embryology, the study of human fertilisation in the early stages of foetal development; endocrinology, the elucidation of the mechanism of action of the female reproductive hormones; radioimmunoassay, the technique that allows minute quantities of hormones in the blood to be measured accurately; and optics, essential for the design of Patrick Steptoe’s laparoscope, through which he aspirated eggs from the ovary. When the definitive moments of post-war medicine are viewed separately they seem diverse and independent of each other, but their interconnectedness lies at the heart of the cumulative progressive nature of medical advance.
This Olympian view may seem to provide reason enough for the rise of medicine in the post-war years. But it is not, for as soon as one starts to scrutinise these events in greater detail, a whole new level of explanation becomes apparent. The first was the displacement of the traditional philosophy of medical practice with the revolutionary new creed of ‘clinical science’, where the best interests of the patient become – in the name of progress – secondary to the scientific scrutiny of his illness. The second, and without doubt much the most powerful single factor of all, was the stunning success of the exploitation by the pharmaceutical industry of medicinal chemistry, which increased within a few years the number of useful drugs from a handful to several thousand. The third, predictably enough, was the liberating power of technology – the pump, dialysis and endoscopy – in ‘opening up’ new territories to medical intervention. Finally, however, we are left with the curious phenomenon that the origins of several of the most significant achievements remain to this day inscrutable biological mysteries that lie beyond the range of rational explanation.
2
CLINICAL SCIENCE: A NEW
IDEOLOGY FOR MEDICINE
On 13 January 1935, King George V visited the Hammersmith Hospital in West London, formerly known as the Workhouse Infirmary, situated next door to one of Britain’s largest prisons, Wormwood Scrubs. This location had been chosen as the site for the British Postgraduate Medical School, the first institution in the country committed to ‘training specialists and the promotion of medical research in the advance of medical knowledge’. It was a ‘glittering gathering’. The King was met by the chairman of the board of governors, Austen Chamberlain, brother of the future Prime Minister, Neville, as well as ‘the most distinguished medical men of the day resplendent in their academic regalia’. The King expressed the wish ‘that the school with its happy union of ward and laboratory, joining students and teachers alike from all parts of our Empire . . . may prosper under God’s blessing’.1
But no sooner had the School become established than the outbreak of war threatened to close it. ‘The advance of medical knowledge’ had to give way to more urgent priorities. Most of the medical personnel of the School were seconded elsewhere, leaving behind a ‘skeleton staff’ to run the hospital, whose responsibilities now extended to looking after civilian casualties from the Blitz. And yet the research conducted in these straitened circumstances by the ‘skeleton staff’ that remained behind, John (later Sir John) McMichael, Sheila (later Dame Sheila) Sherlock and Eric (later Professor Eric) Bywaters, ensured the style of medicine epitomised by the School – ‘clinical science’ – would in the following twenty-five years revolutionise the practice and philosophy of medicine, for reasons that will be become clear enough.
Eric Bywaters, writing in the British Medical Journal in March 1941, described ‘a specific and hitherto unreported syndrome’ in civilian air-raid casualties who had been dug out of their homes with crush injuries to their limbs. He described this syndrome as follows:
The patient has been buried for several hours with pressure on a limb. On admission he was in good condition except for a swelling of the limbs and some local anaesthesia . . . a few hours later the blood pressure falls with pallor, coldness and sweating. The blood pressure can be restored by multiple transfusions of plasma and occasionally blood [but] anxiety now arises concerning the circulation of the injured limb which shows all the changes of incipient gangrene.
The patient’s urine output starts to fall, the kidneys fail resulting in coma and ‘death occurs suddenly usually within a week’. Bywaters suggested this ‘hitherto unreported syndrome’ be called ‘crush syndrome’, which he correctly inferred resulted from the crushed muscle clogging up the kidneys, and for which, as there was no treatment for kidney failure, there was nothing to be done. The most striking aspect of Bywaters’s paper is the manner in which this new syndrome is reported – the meticulous day-by-day recording of the patient’s steady deterioration in which the blood pressure, haemoglobin, urine volume, level of urea and other biochemical measurements are all noted. Indeed, Bywaters’s paper is the most detailed scientific monitoring of the biochemical changes prior to death from kidney failure ever to be reported.2
Sheila Sherlock’s research addressed another problem thrown up by the war: the difficulty in identifying the cause of jaundice in servicemen, and particularly distinguishing between the three main causes, infective hepatitis (now known to result from the hepatitis A virus), blood transfusion hepatitis (now known to be caused by the hepatitis B virus) and hepatitis arising as a complication of the treatment of venereal disease with arsenic. This too, as with Bywaters’s research, was in a sense ‘academic’ as there was no treatment for any form of hepatitis, but perhaps if specimens of liver were removed by a sharp needle through the abdominal wall (liver aspiration, now known as liver biopsy) and were examined under the microscope, this might reveal some valuable information? Sherlock performed liver aspiration on 126 patients, of whom two died following the procedure, including one who was ‘already moribund from subacute liver necrosis, general paralysis of the insane and rectal carcinoma’. She found three patterns of pathological change – ‘diffuse’ (generalised), ‘zonal’ (confined to one area) and ‘residual fibrosis’ (replacement of the liver with fibrous tissue), but there was no correlation between any of these specific patterns and the underlying cause of the hepatitis.3
Lastly, John McMichael investigated another military-related medical problem, the haemodynamic changes in the heart following severe blood loss. Here a group of volunteers agreed to have a catheter inserted into a vein in the arm and manoeuvred into the right side of the heart. They were then bled of 1 litre of blood, while the pressure within the heart was measured through the catheter.4
Through modern eyes these three research projects might seem straightforward, if of rather limited practical application. Their significance rather lies in the circumstances in which they were carried out. Research of any sort is never easy, but for these doctors to undertake these studies alongside their primary responsibility of looking after patients suggested a certain zeal and desire for knowledge. This zeal is the defining characteristic of the new ideology – clinical science – that was to transform medicine. It is difficult to describe how this philosophy of medicine differed from that of the pre-war years which it supplanted, but some idea can be gleaned from a comparison between two dominant medical figures of the pre-war years in Britain, Lord ‘Tommy’ Horder of London’s St Bartholomew’s Hospital and Sir Thomas Lewis of University College Hospital.
Lord Horder symbolised the pinnacle of achievement to which every consultant in London aspired. He was wealthy and stylish, arriving for his ward rounds at Bart’s in his Rolls-Royce and sporting a top hat. ‘Tommy [Horder] was certainly the greatest clinician of his day, based on vast experience and shrewd judgement. His short squat figure exuded wisdom and humanity.’5 Born the son of a Dorset draper, his reward for winning every prize at medical school was to be appointed for his first job as the house doctor to Samuel Gee, physician to the Royal Household, whose patronage rapidly propelled the young
Horder into the most influential circles.
Horder’s private practice read like a Who’s Who of the times. It included three prime ministers: Andrew Bonar Law, Ramsay MacDonald and Neville Chamberlain; writers: Sir James Barrie, Somerset Maugham, Rebecca West and H. G. Wells; and musicians: Sir Thomas Beecham, Sir Malcolm Sargeant, Sir Henry Wood. And in time he succeeded Samuel Gee as physician to the Royal Household, becoming medical adviser to first King Edward VII, then George V, Edward VIII, George VI and finally Queen Elizabeth II.6
Tommy Horder’s success was well deserved. He was very good at what he did, which, in the era before sophisticated medical investigations, was making an accurate diagnosis, relying almost exclusively on what are known as ‘clinical methods’, the ability to infer what is amiss from the patient’s history and physical signs elicited at examination. This was traditional doctoring, unencumbered by the trappings of technology, and its essential feature was the human relationship between doctor and patient.
While Lord Horder was attending to the rich and famous, Sir Thomas Lewis, the son of a Welsh mining engineer, was hard at work in the basement at University College Hospital investigating the many different types of irregularity of the heartbeat with the help of the newly invented electrocardiogram. This was extremely arduous and complex work, involving thousands of recordings of the heart, which Lewis then investigated further by conducting experiments on dogs, placing electrodes into their hearts to identify the precise manner in which the electrical impulses spread. The distinguished cardiologist Paul White subsequently recalled what it was like:
The Rise and Fall of Modern Medicine Page 21