Can Medicine Be Cured Page 2

  I asked my mother about her bout of pneumonia and the death of her brother. Billy’s death, she said, was a tragedy from which her parents never recovered. As I write, Ireland is in the throes of a medico-political crisis, because screening for cervical cancer by smear testing failed to detect pre-cancerous changes in some women. Although this type of screening has a recognized false negative, or ‘miss’, rate, the media and some opportunist politicians have created an atmosphere of popular outrage. ‘People say how bad the health service is now,’ my mother mused, ‘but they should go back to the 1940s and they would see what bad care was really like. All the problems we have are because people live so long now.’

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  The Greatest Breakthrough since Lunchtime

  Since the 1980s, medical research has become a global business and driver of economies; it is the intellectual motor of the medical–industrial complex. It is seen by the general public as a worthy philanthropic endeavour, carried out by altruists motivated only by a thirst for truth and a passion to cure disease and save lives. Many charities collect money to fund this noble activity, and these bodies have themselves become a substantial business sector. There is a broad societal consensus that medical research is a good thing, and the more money spent on it the better. The many people who give money to these charities might be surprised to learn that the great majority of medical research is a waste of time and money. There are two reasons for this waste: first, the vast majority of it is badly carried out, and second, research serves mainly the needs of the researchers and allied commercial interests.

  My experience of working for nearly three years as a research fellow taught me quite a lot about this strange subculture. Research fellows are junior doctors – usually with a few years of clinical experience – who step out of clinical employment for a period to work towards a doctoral-level degree, such as an MD or a PhD. My reason for doing it was the same as nearly all other doctors: career advancement. Hospital medicine in the 1980s was highly competitive. Consultant posts generally only became available because of retirement or death and many jobs attracted twenty or more highly qualified applicants. The training posts, such as registrar and senior registrar, were nearly as competitive, and the academic portion of one’s CV assumed great importance. Candidates were often judged more on their research record than their clinical skills. Ambitious trainee doctors were thus heavily incentivized to publish papers in the medical journals and to obtain doctoral degrees. After three years of house officer jobs at my local teaching hospital, I had drifted into a job as registrar in gastroenterology. This choice was dictated mainly by chance and expediency; I had no burning desire to pursue a career in this speciality, over, say, one in cardiology. It was simply the job I was offered. If I was to progress in this speciality, I would have to leave Ireland, as specialist training there was almost non-existent in the 1980s. I discussed the matter with one of the local consultants, who suggested that I try my luck in Edinburgh, for no better reason than he had himself trained there. He wrote on my behalf to the professor of gastroenterology, and I went over to meet him. I was offered a job on the spot as a research fellow, which would be funded by a drug company. At that time, the pharmaceutical industry spent a lot of money on such posts, particularly in gastroenterology. This financial support purchased goodwill with the medical academics, and was tax efficient. The professor explained that I would be required to do a small trial for this drug company, but that this work would occupy only a little of my time. The main focus of my research would be the immune system of the gut.

  When I started this post, I met the professor, expecting clear directions for my research. His advice, however, was vague: he suggested that I spend a few weeks in the library ‘reading the literature’ and learn some basic laboratory techniques. In the hospital library, I pored over papers on the intestinal immune system, a subject of indescribable dullness. I shared a laboratory bench with two shy Italians, who showed me how to ‘microdissect’ a biopsy from the small intestine, and stain it with various dyes, so that cell types could be counted. This counting was done by peering down a microscope at an intestinal biopsy, and clicking a manual counter every time a particular cell-type was seen. I spent many hours and days counting populations of a cell called the intra-epithelial lymphocyte. Although a helpful technician showed me the basic technique of measuring antibody levels, I soon learned that the laboratory staff resented the research fellows, quite correctly regarding them as careerist dilettantes. My professor was proud that his many research fellows came from all over the world, and the lab coffee room displayed a map of the world with a little flag on the country of origin of each lucky pilgrim.

  The study which paid my wages was a trial of a new drug for coeliac disease. It had been known since the late 1940s that coeliac disease can be treated very effectively by removing gluten from the diet. Why a drug should be mooted as a treatment for this disease is astonishing, but the idea is still seriously advocated, on the rather spurious grounds that some patients find the diet difficult to adhere to. The trial had been started by one of the Italians; I took it over, recruiting more patients. The patients had a pre-trial small intestinal biopsy, were told to continue on a normal diet, took this drug for three months, and then had another biopsy to see if there was any improvement. (The improvement with diet in coeliac disease can be seen in small intestinal biopsies.) The trial was ethically suspect, as there was no plausible biological basis why this drug, or indeed any drug, should be used as a treatment for a condition which already had a known dietary cause, and a known ‘cure’. Not surprisingly, the trial showed no benefit from this drug. One patient died shortly after the conclusion of the trial, of a rare intestinal cancer associated with coeliac disease. I do not think the drug was directly to blame, but the fact that she was advised to continue eating gluten for the duration of the trial while she took this ineffective agent surely did not help. I was of course keen to publish a paper on the trial, but we were contractually obliged by the drug company to show them any such paper before submission to a medical journal. Naturally, they were against publishing the findings, as it showed no benefit from their product. They needn’t have worried – the journal I sent it to rejected the paper without even sending it out for review. This was my first experience of the phenomenon of ‘negative publication bias’, i.e. rejection of papers describing trials with a ‘negative’ result.

  When I tried to get my professor to point me in the direction of a specific research project, he suggested that I should develop a technique of counting cells in intestinal biopsies automatically, using a computerized system called image analysis. We never discussed anything as scientifically hifalutin as a hypothesis, a question: the main concern was to develop a new technique to generate data. He arranged for me and a lab technician called Jim to work on this at another department at the university. Jim and I spent many fruitless hours on this image analysis, but the only images we could conjure looked like interference on a television set. After several frustrating weeks, we concluded that we couldn’t get any useful information using this technology. I reported back to my boss the lack of progress with the image analysis. The only option was to start again, with a new project. My professor had made his name in the 1970s with research conducted mainly on mice, and he had decided to shift the focus of his attention to humans. He was keen on adapting an animal technique called ‘whole gut lavage’ to humans, and I was given the task of developing this. I paid volunteers to drink four litres of an isotonic fluid called GoLytely, a laxative used to prepare patients for colonoscopy. When the volunteers were shitting clear, lager-coloured fluid, I collected this effluent, strained and filtered it, and added various chemicals to preserve the antibodies in this ‘lavage fluid’. I spent hours hanging around hospital toilets, peering into steel bedpans full of faecal fluid to see if it was ready for filtering. You can get used to anything. My paid volunteers were usually Dougie and Ewan, the foul-mouthed technicians from the animal unit, who were
always short of cash. A cynical contemporary of mine once defined a mouse as ‘an animal which if killed in sufficient numbers produces a PhD’; the Animal Unit housed all of these poor mice, as well as monkeys and – it was rumoured – goats. I managed to avoid killing any of these innocent animals, but I was taken one morning to the Animal Unit by one of the Italians, who expertly dispatched a mouse with a flick of his wrist, swinging it by the tail and smashing its head on the edge of the laboratory counter.

  The old cliché about all the world looking like a nail to a man with a hammer sums up much of medical research, and certainly mine. I was soon subjecting real patients to ‘whole gut lavage’ – most were preparing for colonoscopy anyway, but some weren’t. I used this gut lavage technique to measure antibodies to all sorts of things, and published on them all. I applied the technique (if you can call it a technique) to everything I could think of from Crohn’s disease to a type of arthritis called ankylosing spondylitis. Another more fastidious research fellow collected saliva – much less offensive to the eye and nose than my work – and he, too, looked at every possible comparison and combination of salivary antibodies. Instead of starting with a question, or a hypothesis, we began with a technique, and then produced as many data as possible. I spent two years collecting ‘whole gut lavage fluid’, intestinal juice, saliva and blood from various groups of patients and diseases. Over the next two years, I published several papers and wrote up my doctoral thesis. Flushed with this modest success, I foolishly formed the notion that I would make a career in research and was appointed to a more senior post in the same unit. This was a mistake, and I soon became disenchanted with academic life. After less than eighteen months in this post, I left to take up a job as senior registrar in Yorkshire. My research career, which petered out ignominiously, did, however, give me some very hard-won insight. I realized that I lacked the curiosity of the true scientist. I could have advanced as a medical academic by the conventional route, but had a low tolerance for boredom and, although cynical, I was not quite cynical enough. I was proud to have my paper in the Lancet and my MD degree, but that was enough, and I was relieved to move back into clinical work. The three years I spent as a research fellow were well spent from a purely utilitarian point of view: I achieved what I had set out to do, but it was a calculating, dispiriting business, and I produced little of lasting consequence.

  Although I didn’t add in any meaningful way to the body of scientific knowledge, I learned a lot about how medical research works. Few, if any, researchers were inspired by scientific curiosity; the senior academics I encountered were motivated mainly by things like promotion, grant money, publications and merit awards. A medical research laboratory is a factory, which produces the raw material of data. From these data, many things may be fashioned: presentations to conferences, publications in journals, doctoral degrees, successful grant applications, even air miles. What went on in the nearby wards seemed of little consequence, apart from being a source of the bodily fluids (‘clinical material’) from which the data emerged. The academic Brahminate – the professors, heads of departments and deans − held great power over appointments, even to posts with little or no academic component. They sat on committees. They doled out the grant money to each other. Their clinical commitment was very often a sinecure, as NHS teaching hospitals were largely run in those days by very experienced ‘junior’ doctors. Senior registrars, particularly in surgery, were often approaching forty by the time they were appointed as consultants. These senior registrars were commonly more clinically capable and astute than the consultants, particularly the academic ones. One academic consultant physician I knew conducted a ward round once a week. His decisions were so bizarre, dangerous and reliably wrong that the ward sister and senior registrar had to conduct a ‘real’ round after they had first guided this buffoon around all the patients in a kind of Potemkin charade. Another academic – a surgeon – was so dangerous in the operating theatre that he was promoted to a professorship with mainly teaching duties to keep him away from patients. The dependable presence of the senior registrars left the Brahmins free to pursue the research game. They generally recruited to their ranks people of similar outlook and temperament, so the system was self- perpetuating.

  I fell in with a gang of medical research fellows, and we met most lunchtimes in the doctors’ dining room (the hospital still had one in the late 1980s), and, on Fridays, at the pub. We anxiously compared our progress in presentations to conferences and papers accepted for publication. All of them are now professors of greater or lesser eminence; two have become deans of medical schools. I cannot recall a single conversation about science: all we talked about was our careers. Genetics was the fashionable way to go into medical research in the late 1980s, and the research fellows were much occupied by this. Those who got into genetics early were racing ahead and were awash with grant money. A venerable and eminent professor of medicine with whom I had worked was replaced by a geneticist with little in the way of clinical experience. This appointment was symbolic of the cultural shift in academic medicine. Up to that point, a professor of medicine was a sort of first among equals: he – it was usually he – had to command the respect of his colleagues as a clinician, was expected to take a lead in the teaching of medical students, and, if time permitted, to carry out research. By the late 1980s and early 1990s, this model was discarded, ushering in a new breed of senior academic, whose main role was the generation of grant money for laboratory research. They were invariably molecular biologists – geneticists or experts in some other aspect of basic cellular science, such as cytokine immunology. This new breed delegated teaching to more junior colleagues, and did little or no clinical work. The geneticist new-model professor of medicine of my acquaintance proudly abjured all clinical work, and his career peaked with a knighthood. David Sackett, founding father of evidence-based medicine, wrote in the British Medical Journal in 2004: ‘Basic medical scientists have hijacked the granting bodies and have erected research policies that place greater value in serving their own personal curiosities than in serving the sick.’ Nearly all senior academic appointments went to this new type of doctor, and the gulf between practising clinicians and researchers grew ever wider.

  I do not regret the time I spent as a researcher. I had the outsider’s perspective, but the insider’s access. I was sometimes so emotionally detached from the activity that I felt like an anthropologist, conducting field studies on the behaviour of medical academics. Harry Collins, a sociologist of science, and an expert on expertise, carried out such anthropological studies on gravitational-wave physicists, and liked them: ‘They’re my ideal kind of academic. They’re doing a slightly crazy, almost impossible project, and they’re doing it for purely academic reasons with no economic payoff.’ Collins’s tame physicists embodied the lofty ideals of science, such as honesty, integrity, universalism, a willingness to expose one’s ideas to the scrutiny of others and disinterestedness. I found little such idealism in my observations of medical researchers.

  Towards the end of my time as a research fellow, I had a strange, post-modern, Truman Show experience. I was browsing at a book fair when I came across a short novel called The Greatest Breakthrough since Lunchtime. The author – a doctor – wrote under the pen name Colin Douglas, and the book was first published in 1977. The inner flap of the dust jacket leaves us in no doubt as to the saucy 1970s tone of this slim volume, with a photograph of a bespectacled young woman opening her doctor’s white coat, to reveal that she is topless. The blurb promises ‘a novel about idleness, promiscuity, drunkenness, boredom, adultery and medical research’. The hero, David Campbell, is a young doctor working in the Edinburgh teaching hospitals, and clearly based on the author himself. The novel is a period piece, of interest only to doctors who have trained or worked in Edinburgh, but I bought it out of curiosity. As I read it, I felt an unsettling familiarity with the scenes that Douglas describes. After house jobs, the hero drifts into a research fellowship, funded by a drug
company, supervised by an academic physician called Rosamund Fyvie. Fyvie gives him the exact same pep talk as I received: ‘She had suggested a basic method for the colonic mucosa experiment and told him about the lab where it might be done. He should “just play around with it for a day or two” and “read himself into the field” over the first week.’ Many of the senior doctors in the book were clearly recognizable, even to an outsider like me. Campbell is set to work on ‘faecal vitamins’, not a million miles away from my whole gut lavage fluid antibodies. Douglas captures the boredom of this work well. As instructed, Campbell goes to the medical library to ‘read himself into the field’: ‘As a second-rate cathedral might be at a similar hour of the day, the library was thinly populated, similarly by a selection of the most faithful and the most idle in the community… There was a girl who produced endless publications on mouse prostaglandins as though by a strange compulsion…’

  Campbell seems to spend most of his time planning his next sexual conquest. Douglas describes Campbell’s encounters with a nurse (‘they liked each other, and sex together was marvellous’) and an obliging lab technician (‘“Christ, I needed that”, said Lorna’). He becomes very quickly disillusioned with life as a researcher; his boss Fyvie is ‘a raging psychopath on the make’, and her senior registrar Dempster ‘a dilettante con-man’. He muses on the motivation of his boss with his (married) colleague and love interest Jean:

  ‘We’re all in the business of helping to make her a professor. People and patients.’ Campbell smiled like a wicked uncle. ‘And that, my dear children, is the meaning of medical research.’

  Jean made a face and said, ‘And what are you doing in it? Do you want to be a professor in the nineteen nineties?’

  ‘I don’t think I do. I can’t make up my mind whether it’s because I’m not nasty enough or because I don’t care enough.’