Can Medicine Be Cured Read online

  The book ends with the death of a young girl with Down’s syndrome (called a ‘mongol’ in the novel). She had been recruited, without her consent, by Dempster and Fyvie to a trial of an experimental drug for peptic ulcer, and dies as a result of bone-marrow failure caused by this agent. As I read this scene, I thought of my coeliac patient who had died after being recruited to the fatuous and futile drug trial which paid my wages. At the end of The Greatest Breakthrough since Lunchtime, Campbell abandons his research post and returns to clinical work.

  How could this would-be titillating, trashy book, published more than ten years before, capture, with some accuracy, the flavour of my life as a research fellow? The novel – a bizarre hybrid of Confessions of a House Officer and sub-Illichian critique of medical research – crystallized some of my hard-earned lessons. Medical research was a Byzantine game played by cynical careerists; data were more important than ideas; professorships were more important than patients.

  3

  Fifty Golden Years

  During the three years I spent as a research fellow, I presented my work to medical conferences, usually at the annual meeting of the British Society of Gastroenterology (BSG). Britain then led the world in this field, and the BSG was at the zenith of its influence, attracting thousands of delegates from all over the world to its meetings. If your paper was accepted, it would be either as a ‘poster’ or an ‘oral’ presentation. A poster presentation was less prestigious: all you had to do was stand, for a few hours, next to a board with your research findings pinned to it, and answer questions from anybody who happened to pass by and show an interest. Sometimes, nobody even looked at your poster, much less engaged you in scientific disputation. The oral presentations were a different event. These sessions were gladiatorial affairs, where the society’s grandees attempted to outdo each other in rudeness towards the terrified presenters. (These grandees all looked like the more aristocratic members of Margaret Thatcher’s cabinet, men like Lord Carrington and Douglas Hurd.) Such bullying was never questioned or challenged. It was taken for granted that one would be savaged by the big beasts at these presentations, particularly if one of them held a personal grudge against your boss. All of this was accepted as part of the rough and tumble of medical research, and was thought to toughen up the young. The ‘plenary’ or ‘keynote’ lectures were often given by basic scientists who delivered long and mainly incomprehensible talks on their subject to an audience composed mainly of clinical backwoodsmen who had little interest in such matters and who, after a boozy few days, returned no wiser or better informed to their district general hospitals and to the mundane business of treating the sick.

  In September 1987, shortly after I moved to Edinburgh, the BSG held its golden jubilee meeting in London, marking fifty years since its foundation. A paper I submitted had been accepted as a poster presentation, so I travelled south to stand by my presentation in a vast hall in the University of London. This poster described some rather pedestrian research on coeliac disease I had conducted back in Ireland, and attracted little attention, except for a dismissive scowl from a senior academic I recognized as a leader in the field. The BSG was founded in 1937 by Sir Arthur Hurst (who had been knighted earlier that year) and was initially called the Gastroenterological Club. Two of the society’s senior members, John Alexander-Williams and Hugh Baron, wrote:

  The society, as we know it today, began its life essentially as a club for physicians and gentlemen. Members maintained exclusive standards by selecting only those of like mind and manners. ‘Bounders’ were denied membership by ‘black-balling’. They embraced gastronomy as well as gastroenterology and the early meetings were characterized by their indulgence in good food and wine. As gentlemen, they championed modesty and eschewed publicity; their proceedings and papers were not published.

  Had he been a gastroenterologist, Evelyn Waugh might have applied for membership of this club, which devoted much discussion to matters such as the wearing of formal dress at its dinners. The barbarians, however, were at the gates. During the 1950s and 1960s, the club became a society and admitted anyone keen to join, including foreign trainees and non-medical scientists: ‘the British Society of Gastroenterology had become a society of scientists rather than a club for gentlemen’, lamented Baron and Alexander Williams. Membership grew from 40 to 1,500. Two large meetings were needed every year to accommodate the number of scientific papers submitted. The pharmaceutical and medical devices industries partly funded these conferences, with huge exhibitions to promote their wares.

  Thousands of delegates attended the golden jubilee meeting of 1987, and a huge hall accommodated the Trade Exhibition. Although the grandees didn’t realize it, this meeting coincided with the end of British medicine’s golden age. In the fifty years since Sir Arthur Hurst and his chums had gathered for a congenial dinner at the Langham Hotel in London, medicine had been transformed, and Britain was at the heart of this revolution. Sir Francis Avery Jones, grandest of the grandees, and, by common consent, the ‘Father’ of British Gastroenterology, had attended the first meeting in 1937, and was guest of honour in 1987. In those fifty years, Sir Francis had witnessed the arrival of penicillin, effective drug therapy for tuberculosis, kidney dialysis, organ transplantation, endoscopy, CT and MRI scanning, in vitro fertilization, the eradication of smallpox and the discovery of the double helix of DNA. Every delegate at the golden jubilee meeting was given a copy of a book (paid for and published by the drug company Smith, Kline & French) containing a selection of the most influential gastroenterology papers published in the previous half-century. The book’s introduction was written, naturally, by Sir Francis, whose career had spanned this golden age.

  This book tells the story of how medical research in Britain evolved over those fifty years, from curiosity-driven inquiry by passionate individuals to an industrialized, institutionalized activity. Many of the early papers from the 1940s and 1950s were written by single authors – single authorship of ‘original’ research papers is now almost unheard of, most being attributed to a committee of a dozen or more contributors. Most of these craggy individualists were full-time clinicians, not laboratory researchers, amateurs in the true sense of the word. Many of the publications in the collection evince a warm glow of nostalgia, a longing for simpler times. A paper by Sir Francis Avery Jones (single author), published in the British Medical Journal in 1943, describes the contemporary treatment of bleeding peptic (gastric and duodenal) ulcers. The main treatment in Sir Francis’s day was diet: ‘The patients received two-hourly purée feeds.’ The contents, and sequence, of this diet are described in some detail: ‘Cup of milky tea; three slices of thin bread-and-butter; bramble jelly; sponge cake.’ His patients must have felt entirely safe in his patrician hands. The collection included the famous paper on Munchausen’s syndrome by Sir Francis’s old friend Richard Asher, his colleague at the Central Middlesex Hospital. Asher was a general physician who achieved some fame for his elegant, often contrary, essays. The type of glutinous prose found in medical journals has been labelled by Michael O’Donnell, the writer, doctor and broadcaster, as ‘decorated municipal gothic’, but in those innocent days of the early 1950s, journals like the Lancet published prose stylists like Asher. Munchausen’s syndrome is a factitious disorder: those affected feign illness to gain attention. Asher named it after the fictional German nobleman: ‘Like the famous Baron von Munchausen, the persons affected have always travelled widely; and their stories, like those attributed to him, are both dramatic and untruthful.’ I find his assumption that the readers of the Lancet would be familiar with R. E. Raspe’s Singular Travels, Campaigns and Adventures of Baron Munchausen strangely touching.

  British science has a reputation for being at the forefront of innovation, but of failing to put in the boring work of practical application and commercial development. Such was the history of endoscopy. Harold Hopkins was a physicist based at Imperial College in London who discovered how to convey optical images along flexible glass
fibres. He had been prompted to work on this after a chance meeting in 1951, at a dinner party, with Hugh Gainsborough, a physician at St George’s Hospital. Gainsborough knew that Hopkins specialized in optics – he had invented the zoom lens – and suggested to him that he should try to develop a flexible endoscope. At that time, endoscopes were rigid instruments, with very limited views; ‘intubation’ – passing the instrument down the patient’s throat – was both dangerous (the pharynx or oesophagus might be perforated) and extremely uncomfortable. Hopkins wrote a paper for Nature (the most prestigious of all science journals) in 1954, which is included in the BSG’s jubilee collection. He described a unit consisting of ‘a bundle of fibres of glass, or other transparent material, and it therefore appears appropriate to introduce the term “fibrescope” to denote it’. Hopkins tried, and failed, to interest an industrial partner. An enterprising South African gastroenterologist called Basil Hirschowitz, who had trained with Sir Francis Avery Jones, picked up on Hopkins’s idea, and along with two physicists at the University of Michigan, and with the financial support of the giant American Cystoscope Makers Inc (ACMI), developed the first commercial fibreoptic endoscope in 1960. Hirschowitz somehow managed to pass the endoscope down his own throat, before trying it out on a patient. The BSG awards an annual prize for innovation in endoscopy, named after Hopkins.

  Although the British ceded commercial development of endoscopy to the Americans and the Japanese, they continued to come up with innovative applications of the new technology. In 1972, Peter Cotton, then a senior registrar at St Thomas’ Hospital in London, wrote a paper for the Lancet describing how the common bile duct (which drains bile from the liver into the intestine) could be cannulated with an endoscope, and X-rays of this duct obtained by injecting dye. Bile duct obstruction due to gallstones and cancer is common, causing pain and jaundice. The procedure is called ‘Endoscopic Retrograde Cholangio-Pancreatography’ (ERCP) and is now routine. I have performed thousands. As well as identifying the cause of bile duct obstruction, it is used to relieve this obstruction by removing gallstones and inserting stents through blockages caused by cancers. Before ERCP, patients with bile duct obstruction had to undergo a major operation. Cotton was not the first to describe this technique; he went to Japan in 1971, where he spent three weeks with the gastroenterologist Kazuei Ogoshi, and brought the procedure back to Britain. He singlehandedly established ERCP in Britain, and trained the first generation of specialists who spread the procedure throughout Britain and North America. All British users of this procedure can trace their training, in a form of apostolic succession, back to Cotton. Despite this achievement, he failed to be appointed to a consultant post at St Thomas’, an example, surely, of the British medical establishment’s distrust of show-offs. He was later successful in his application for a post at the Middlesex Hospital, following which he was taken in hand by Sir Francis Avery Jones, an episode which he describes in his memoir The Tunnel at the End of the Light: ‘Avery was kind to me when I was appointed to The Middlesex. He took me to lunch at the Athenaeum, the quintessential private London club, and explained some of the facts of private practice to me over roast pheasant and a frisky claret.’

  Peptic ulceration is the theme of more than a quarter of all the papers in the jubilee collection. In the early decades of the twentieth century, up to 10 per cent of the adult male population in Britain were afflicted with chronic peptic ulcer. The disease was then commonly attributed to stress, a notion mocked by Richard Asher: ‘One might just as well argue that the use of wrist watches was becoming increasingly common compared with Victorian times, and that therefore the increasing incidence of peptic ulcer was attributable to the wearing of wrist watches.’ Many patients with peptic ulcer underwent major surgery. The work of the great Viennese surgeon Theodor Billroth (1829–94) began the development of a variety of operations for ulcer disease, and this type of surgery made up most of the workload of abdominal surgeons in the first half of the twentieth century. Some of these operations were so ‘radical’ that the treatment was often worse than the disease, creating a whole population of patients known as ‘gastric cripples’ who suffered ever after from emaciation and malabsorption.

  By the early 1970s, the pharmaceutical industry was becoming increasingly influential in medical research. James (later Sir James) Black of Smith, Kline & French’s Research Institute described the histamine H2-receptor in the stomach in a paper published in Nature in 1972 and included in the collection. This receptor controls acid secretion in the stomach. Black developed a drug to block the receptor, thus reducing acid secretion. Cimetidine (branded as ‘Tagamet’ by Smith, Kline & French) was the first effective drug treatment for peptic ulcer, and the first so-called ‘blockbuster’ drug. This success was the model for later, even more profitable, blockbusters, the spectacular profits from which created the global giant which is now Big Pharma. Although cimetidine did heal ulcers, patients invariably relapsed once the course of treatment was completed, so most continued taking the drug indefinitely. Cimetidine was certainly an advance, but not a cure. Paradoxically, this limitation was the key to its commercial success, and the reason why it became the first blockbuster drug: because so many patients took the drug for years – rather than weeks – sales were huge. Smith, Kline & French made a fortune, and Sir James Black won the Nobel Prize for Medicine in 1988.

  Sir Francis Avery Jones celebrated the great progress made in the half-century of the speciality, but lamented the failures in other areas:

  Although remarkable progress has been achieved in these fifty years, there are still many unsolved problems. The clinical study of diseases, their diagnosis and treatment has made giant strides forward, but unfortunately the causes of major illnesses, including peptic ulcer, ulcerative colitis and Crohn’s disease, still remain to be discovered.

  Sir Francis was seventy-seven when he wrote his introduction to this selection of papers, so perhaps cannot be blamed for not keeping a close eye on the medical literature. Had he done so, he might have spotted that for five years running up to the jubilee meeting in 1987, Robin Warren (a pathologist) and Barry Marshall (a trainee gastroenterologist) from Perth, Australia, had produced several papers strongly suggesting that peptic ulcer and gastritis were caused by a bacterium called Helicobacter pylori. Less than two months after the jubilee meeting, the Lancet published a paper by a Dublin group led by Colm O’Morain, which showed that eradication of Helicobacter not only healed duodenal ulcers, but crucially – and unlike cimetidine – kept them healed. Marshall and Warren published a paper a year later, also in the Lancet, with the same conclusion. A combination of antibiotics taken for a week was shown to cure a condition which up to then very often required a mutilating surgical procedure. It is not difficult to understand, therefore, why the global gastroenterology community might have felt a collective cognitive dissonance. Many initially ignored it, but by the early 1990s, most were convinced. The whole clinical and academic infrastructure which had grown around the surgical treatment of peptic ulcer simply disappeared, and the surgeons found other things to do.

  Arthur Hedley Visick, surgeon at York County Hospital, might also have experienced severe cognitive dissonance had he survived into the late 1980s. He wrote a paper for the Lancet in 1948 on ‘Measured Radical Gastrectomy’, a procedure he performed on 500 patients between 1936 and 1947: the operation removed between one-half and two-thirds of the stomach in patients with chronic peptic ulcer. Surgeons travelled to York from all over Britain and abroad to watch Visick operate. He died of a stroke in 1949 at the age of fifty-one, having collapsed in the surgical outpatients. Visick did not survive long enough to be told that all of those 500 patients could have been cured with a course of antibiotics. The Helicobacter story, however, is not a simple narrative of the plucky Australian outsiders taking on a monolithic medical establishment. Helicobacter became the centre of a new medical industry, just as gastric acid secretion was the obsession of a previous generation. Helicobacter got its
own conferences and journals; Marshall and Warren won the Nobel Prize for Medicine in 2005, and many others further down the food chain got chairs and large research grants. The Gadarene researchers who once followed the dogma of gastric acid secretion now switched allegiance to Helicobacter. Few admitted that peptic ulcers were already in steep decline by the time Helicobacter was discovered, and that most such ulcers were by then caused by anti-inflammatory painkillers (including aspirin), not Helicobacter. The great majority of people infected with Helicobacter never develop a peptic ulcer; eradicating the organism in those without ulcer is of questionable benefit. In developing countries such as India, the vast majority of the population is infected with Helicobacter, yet peptic ulcer is rare. No matter. The Helicobacter bandwagon drove on regardless, with the new dogma proclaimed by consensus conferences, and, when I checked on PubMed this morning, 40,580 publications. I am a co-author of one of these 40,580 papers. An enterprising researcher from an institution in another city invited me to collaborate on a study of the prevalence of Helicobacter infection in patients with coeliac disease, for no other reason than he had a blood test for Helicobacter and I had a large bank of stored blood from coeliac patients. There was no interesting question to answer, and I don’t think we found very much, but we did get a publication out of it. This paper is a good example of the man-with-a-hammer scientific opportunism. There was no plausible biological reason why Helicobacter and coeliac disease should have any connection, and the question was of little interest either clinically or scientifically. And yet: a paper was published.

  Many of the papers in the BSG collection describe work and ideas which are now discredited. Medical research is a conformist activity, driven largely by received opinion. The collective obsession with the physiology of gastric acid secretion is now perplexing, particularly when the (admittedly counter-intuitive) answer (Helicobacter) was knocking loudly at the door. Long before Marshall and Warren discovered Helicobacter, papers had appeared intermittently in the journals describing bacteria in the stomach, but were dismissed on the grounds that bacteria could not possibly survive in the acid environment of the stomach. Alan Bennett once wrote about his uncle Norris, who was obsessed by his firm conviction that arthritis could be cured by the simple expedient of cutting off the feet of one’s socks. Perhaps the medical establishment thought that the idea of curing peptic ulcer with a course of antibiotics was about as biologically plausible as Uncle Norris’s cure for arthritis. Many of these important discoveries – again, Helicobacter – were often serendipitous findings by enthusiasts with prepared minds, rather than the result of planned, lavishly funded institutional research. Diseases come and go, and effective treatments often arise when the disease was declining anyway (peptic ulcer, tuberculosis). Today’s exciting innovation is tomorrow’s stifling consensus, while other once-exciting innovations will tomorrow be as forgotten as Ozymandias, King of Kings. Since 1987, Big Science has taken over, and the jubilee papers now seem quaint and almost innocent.