Maybe. But it is Le Fanu’s notions of causation that are more at fault here. Epidemiology aims to uncover associations. Sometimes these associations, as Le Fanu has to admit, turn out to be true causes—as with smoking and lung cancer. But at other times, associations hide more subtle relationships. Perhaps red wine, let’s say, includes an as yet unidentified ingredient that explains why its consumption is linked to a particular outcome, such as a lower risk of heart disease. The idea that an association is equivalent to a cause is a fundamental error of epidemiological interpretation; but this does not mean it is futile to report associations. The conflicting reports of risk associations—for instance, that alcohol is or is not good for you—reflect the to and fro of scientific debate, not some essential flaw in the methods being used. What human science produces the entirely unequivocal and unchallengeable results that Le Fanu so yearns for?
He also expresses heartfelt discontent that the medical research industry, despite vast government and private investment, has so few certainties to show for its endeavors. But I think his conception of the research process is seriously mistaken. Clinical research never produces definitive conclusions for the simple reason that it depends on human beings, maddeningly variable and contrary subjects. Although medical science is reported as a series of discontinuous events—a new gene for this, a fresh cure for that—in truth it is nothing more than a continuous many-sided conversation whose progress is marked not by the discovery of a single correct answer but by the refinement of precision around a tendency, a trend, or a probability.
Advances in diagnosis and treatment depend on averaging the results from many thousands of people who take part in clinical trials. The paradoxical difficulty is that these averages, although valid statistically, tell us very little about what is likely to take place in a single person. Reading the findings of medical research and combining their deceptively exact numbers with the complexities of a patient’s circumstances is more of an interpretative than an evidence-based process. The aim is to shave off sharp corners of uncertainty, not to search for a perfect sphere of indisputable truth that does not and never could exist. In this way the process of research is often more important than the end result. It does not have the drama and heroism that Le Fanu dwells on in his ten definitive moments. But these moments are not typical of what most medical researchers do.
What should be clear is that Le Fanu is on shaky ground in rejecting the argument that changes in lifestyle have contributed to the rise and fall of heart disease in the US and Canada since the 1950s. He cites inconsistent findings that seem to prove a widespread confusion surrounding this orthodoxy. Superficially, his case is fair because risk factors related to lifestyles have usually been studied one at a time, providing a chaotic and conflicting picture overall. One recent study done at Harvard, however, has attempted to circumvent this problem by looking at the interplay of risk factors in a single large group of middle-aged women. The results will not please Le Fanu.
The small group who collectively did not smoke, remained reasonably thin, drank alcohol moderately, exercised regularly, and ate a diet rich in fiber and low in saturated fat reduced their risk of heart disease during a fourteen-year period by over 80 percent. Whichever way you interpret these data, how you live influences how you die. The Harvard epidemiologists conclude that their findings “support the hypothesis that adopting a more healthful lifestyle could prevent a substantial majority of coronary disease events in women.”14 The social theory of disease may not explain everything about life and death, but it would be wrong to cast epidemiology into oblivion just yet.
Le Fanu ends his review of medicine’s demise in typically unflinching style: “By the 1970s much of what was ‘do-able’ had been done.” His interpretation of the past fifty years is that medical science has reached its natural limit:
The main burden of disease had been squeezed towards the extremes of life. Infant mortality was heading towards its irreducible minimum, while the vast majority of the population was now living out its natural lifespan to become vulnerable to diseases strongly determined by ageing.
Any solution to the diseases that now affect human longevity
means discarding the intellectual falsehoods of The Social Theory and the intellectual pretensions of The New Genetics…. The simple expedient of closing down most university departments of epidemiology could both extinguish this endlessly fertile source of anxiety-mongering while simultaneously releasing funds for serious research.
Le Fanu misreads the ills of present-day medicine. But his approach to the discoveries of the past does bring into clear relief important social changes in the way medical research is done today, changes that should influence professional, public, and political attitudes to contemporary medicine.
Clinical research had become highly specialized, often eliminating the ordinary doctor from the process of day-to-day investigation. This upheaval in the way research was done accelerated during the 1970s, at the time Le Fanu identifies as being the start of medicine’s precipitous fall. There was a hiatus in dramatic discoveries, it is true, but that now seems to be coming to an end. As research moved from the bedside to the laboratory, doctors in clinics were left empty-handed, with little to contribute to the production of medical knowledge. But a far more important instrument was being given to them—the randomized controlled clinical trial.
The clinical trial is a human experiment, enabling physicians to study the safety and effectiveness of interventions, whether in the form of drugs, devices, or prescribed changes in behavior. According to the Declaration of Helsinki, in principle a trial must be sanctioned by an ethics committee and the patients involved must give informed consent to taking part in it. These conditions are not always met, particularly in the developing world, and a furious debate is currently taking place over whether the declaration should be revised. But still, the randomized trial has become the foundation of current clinical knowledge. Clinicians are increasingly being drawn into trial networks. Far from being divorced from medical research, doctors are now back at the center of its most powerful new means of discovery.
The centrality of clinical trials to twenty-first-century medicine means that further definitive moments, unlike those in earlier times, may not always be instances of positively beneficial discovery. “Negative” results—proving that a drug either does not work or causes more harm than good—can be equally if not more important in shaping medical knowledge. Trials allow scientific concepts to be tested experimentally and these theories can sometimes be proven embarrassingly mistaken.
For example, stroke is a leading cause of death and disability in the Western world. In the early 1990s animal experiments suggested that brain damage after a stroke occurred when chemicals released during an episode of oxygen starvation overstimulated surrounding neurons. A theory was developed and tested in the laboratory in which blocking the effects of these chemicals protected the brain from further harm. Recently reported trials have shown this carefully worked out theory to be either wrong or, at best, seriously oversimplified.15
The new genetics is likely to expand, not contract, the potential for drug discovery. Genes code for proteins. Now that most of the human genome sequence is available to us, the total protein complement of the human cell (the proteome) is within reach. Since proteins control most cell processes, they are important natural targets for drugs. Not only will the genome and proteome yield new sites for drug action, but finding the pattern for the ways genes and proteins are expressed in each disease state will enable much more precise classification of diseases. Subtle differences in diseases, notably cancers, which were previously thought to be homogenous pathological entities, are now being found, with significant implications for prognosis and treatment. Currently accepted disease classifications will soon be torn up. For example, one type of blood cancer that previously had an unpredictable outcome after treatment has recently been shown to consist of two separate categories of disease, categories that were distinguished from one another by their different molecular fingerprints. These two types of cancer had clearly distinct clinical outcomes. The confusion caused by lumping together two diseases as one was finally resolved.16
As these developments change the semantics of human disease, so they will reveal ever more clearly the vast inequalities in health between North and South. These differences have been with us for many years, but they have been all too openly emphasized by the excruciating brutality of the HIV/AIDS epidemic. The introduction of highly active antiretroviral treatment has cut the rate of illness by over 90 percent for the two million people living with AIDS in the developed world. But for the thirty-two million HIV-infected people living in poorer countries, access to these drugs is denied because of their high cost. According to a recent report from Médecins Sans Frontières, “In most poor countries the prices of HIV drugs condemn people with AIDS to premature death.”17 Contrary to Le Fanu, then, the major issue in medicine is not one of maintaining the past pace of discovery, but of making sure there is equitable access, throughout the world, to the discoveries we have already made.
There is one other aspect of medicine, hardly touched on by Le Fanu, which has probably caused deeper and more impassioned disagreement among today’s medical sects than any other issue during the past two decades. Screening for disease should bring about the successful convergence of epidemiology and clinical medicine. A group of people apparently free from disease is screened for a disorder that, once found, is treated. Since the condition is identified early, the chances of cure are high. Mammography, the Pap test, colonoscopy, prostate specific antigen—all of these investigations should throw up early warning signs of potentially fatal illnesses. Controversy is bound to arise over what to do when a result is positive. But these skirmishes are nothing compared with the terrifying choices that will be presented when genetic tests become more widely available.
Women with the gene mutations BRCA1 or BRCA2, which were first reported in 1994 and 1995, respectively, have a lifetime risk of breast cancer ranging up to 85 percent. If such a mutation is discovered in a woman, what should she do? She might have no identifiable disease at the time the mutation is found. Should she choose what may, for her, lead to peace of mind (prophylactic mastectomy) or should she choose regular surveillance? The little research that has been done suggests that about half of women with a risk mutation will choose prophylactic surgery, and that those who do so tend to be parents and of younger age.18 Genetic testing poses immensely difficult life choices for women at moments when the conflict between fear and apparent good health is unresolvable. Fear seems to drive the decision for surgery. As a leading team in genetic research on breast cancer recently wrote:
Prophylactic mastectomy is a mutilating and irreversible intervention, affecting body image and sexual relations. There is much concern about the potential psychological harm of DNA testing for BRCA1 and BRCA2 and prophylactic surgery, in particular mastectomy. However, in our experience and that of others, women who had mastectomy after adequate counselling rarely express regret, instead they are relieved from fear of cancer.
Finally, the separation of clinical medicine from public health seems as intractable as ever. And yet, oddly, it may be here that Le Fanu’s twin evils of genetics and social theory might find a useful meeting point. If one knows that a gene is in some way related to a disease, the study of those genes in populations can help one to plan the health services that will be needed to take care of those affected.
That is exactly what Shanthimala de Silva and her colleagues have done in Sri Lanka.19 They used chemical fingerprints for thalassemia, a genetically determined blood disorder causing severe anemia, to calculate that the island had over two thousand persons requiring treatment. To take appropriate care of these people would require about 5 percent of the country’s total health budget—$5 million, a large sum of money for a small nation. Yet it would be better to know what costs will be involved and to try to raise the money domestically and internationally than to ignore the disease. These findings have implications throughout the entire Indian subcontinent and Southeast Asia, where the gene frequencies for thalassemia are even higher than they are in Sri Lanka.
By improving the clarity of questions that medical practice poses and by diminishing the uncertainty of our answers to those questions, geneticists and social theorists have not damaged the “intellectual integrity” of medicine, as Le Fanu claims. They have simply blurred old and reassuring certainties. Le Fanu longs for the past authority enjoyed by doctors and for the deference that such authority demanded from patients. He berates these researchers for their erosion of medicine’s moral base. But just as scientists do not have ultimate control, despite their intense efforts to the contrary, over the interpretations others place on their work, so it seems ludicrous to impose a moral imperative on their motivations. Medical science is just as self-serving as any other branch of human inquiry. To claim a special moral purpose for medicine or even a beneficent altruism is simply delusional.
Many doctors do feel under pressure from the bureaucracy of managed care, the opportunism of zealous litigants, and the overwhelming weight of new knowledge that they are expected to assimilate. With all of these extraneous forces, is Le Fanu correct when he concludes that today “medicine is duller”? I doubt it. Medicine is as unpredictable, baffling, ambiguous, fallible, and absurd as it ever was.
Meir J. Stampfer et al., "Primary Prevention of Coronary Heart Disease in Women Through Diet and Lifestyle," The New England Journal of Medicine, July 6, 2000, p. 21.↩
See Kennedy R. Lees et al., "Glycine Antagonist in Neuroprotection in Patients with Acute Stroke," The Lancet, June 3, 2000, pp. 1949-1954.↩
See Ash A. Alizadeh et al., "Distinct Types of Diffuse Large B-Cell Lymphoma Identified by Gene Expression Profiling," Nature, February 3, 2000, pp. 503-511.↩
Carmen Perez-Casas, HIV/AIDS Medicines Pricing Report (Médecins Sans Frontières, 2000).↩
E.J. Meijers-Heijboer et al., "Presymptomatic DNA Testing and Prophylactic Surgery in Families with a BRCA1 or BRCA2 Mutation," The Lancet, June 10, 2000, p. 2019.↩
See Shanthimala de Silva et al., "Thalassaemia in Sri Lanka," The Lancet, March 4, 2000, pp. 786-791.↩
Meir J. Stampfer et al., “Primary Prevention of Coronary Heart Disease in Women Through Diet and Lifestyle,” The New England Journal of Medicine, July 6, 2000, p. 21.↩
See Kennedy R. Lees et al., “Glycine Antagonist in Neuroprotection in Patients with Acute Stroke,” The Lancet, June 3, 2000, pp. 1949-1954.↩
See Ash A. Alizadeh et al., “Distinct Types of Diffuse Large B-Cell Lymphoma Identified by Gene Expression Profiling,” Nature, February 3, 2000, pp. 503-511.↩
Carmen Perez-Casas, HIV/AIDS Medicines Pricing Report (Médecins Sans Frontières, 2000).↩
E.J. Meijers-Heijboer et al., “Presymptomatic DNA Testing and Prophylactic Surgery in Families with a BRCA1 or BRCA2 Mutation,” The Lancet, June 10, 2000, p. 2019.↩
See Shanthimala de Silva et al., “Thalassaemia in Sri Lanka,” The Lancet, March 4, 2000, pp. 786-791.↩