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Believe Your Doctor

UNTIL SCARCELY TWO hundred years ago, admirals conducting warfare on dis­tant seas were accustomed to losing more men to scurvy than to battle. After prolonged periods aboard ship, sailors would often begin to exhibit lassitude and depression, followed after a time by swollen gums and joints, frequent bruising and bleeding into the mouth. If the voyage was long enough, hemorrhages might occur into body cavities, and then heart failure would lead to death.

The disease was ascribed to various causes, ranging from the effect of climate or salt air to the existence of some deficiency in the diet. There was little agree­ment on therapies, although a few of those that included certain ingredients added to the daily rations seemed to have some degree of efficacy. In May 1747, James Lind, the ship's surgeon of HMS Salisbury, chose twelve sailors who were in sick bay with weakness and swollen gums, and divided them into six groups. His intent was to test the most commonly recommended dietary additives against one another.

For a trial period of fourteen days, each twosome received one of the six remedies that were thought to be most useful. They were, respectively, one quart of cider daily; twenty-five drops of elixir of vitriol three times a day; two spoonfuls of vinegar three times a day; one half-pint of seawater daily; two oranges and one lemon daily; and an elixer made of garlic, mustard seed, horseradish, Peruvian balsam, barley water, tamarinds and cream of tartar three times daily. Of the treatments, the citrus fruits gave by far the best results. One of the sailors who ingested them was fit for duty at the end of six days, and the other became well enough to help with the care of the rest of the sick. At the conclusion of the two weeks of trial, none of the remain­ing patients so much as approached such salubrious outcomes, and most of them had shown little or no improvement.

Even after Lind wrote a book on the subject in 1772, two decades more would pass before his recommendations to dis­pense citrus fruits and their juices to all sailors were heeded. It was not until 1795 that the practice was made universal on all British ships, with the result that scurvy was finally obliterated from the nation's navy and the citizens of the sceptered isle became forever after known as limeys. Lind bad conducted the first of a type of experiment that would two cen­turies later become known as a controlled clinical trial.

Under actual conditions of disease (and using real patients), Lind had tested sev­eral therapeutic methods and demon­strated that one of them was clearly superior to the rest. A few other clinical trials would be done before modern times—most notably the one reported by the French physician Pierre Louis in 1835, showing that bloodletting was ineffective against pneumonia. But the method did not come into general use until after the late 1940s, when it was successfully employed to evaluate the efficacy of the anti-tubercular drugs streptomycin and para-amino salicylic acid. Those trials established not only the remarkable use­fulness of the two pharmacologic agents, but also the concept that well-planned clinical studies involving large numbers of patients are critical to the understanding of disease and its treatment.

LOUIS, WHO CALLED his approach la methode numerique, is widely credited with bringing statistical techniques into the scientific investigation of disease. But it was the tuberculosis studies that ultimately convinced acade­mic physicians that a properly used con­trolled clinical trial was the indispensible way to make sense of the often conflicting mass of information to which doctors in practice are exposed. The word "random­ized" became associated with it, to indi­cate that no bias was to be used in the assignment of patients to one or another of the treatments being tested.

If, for example, one therapy is being compared with a second, patients are entered alternately into each group as they come for treatment. In evaluating drugs, it is often possible to conduct the experiment without the patient knowing to which arm of the project he is assigned. This is called a "blind" or "blinded" study. When neither patient nor analyzing researcher knows the arm, the term "dou­ble blind" is used. In theory at least, a dou­ble-blind randomized controlled trial should represent the sine qua non of sci­entific objectivity in the clinical assess­ment of pharmacological agents.

The uses of the randomized clinical trial are hardly restricted to the study of drug efficacy alone. In recent years, they—and the statistical methods upon which they are based—have become important tools to evaluate the role of certain environ­mental or biochemical factors in the health of large populations. At the same time, enormous progress has been made in the science of statistics, so that popula­tion studies can be utilized with ever-increasing reliability to reveal new infor­mation and determine the significance of observed trends, and indict factors that might otherwise escape detection.

Using such studies, the field of epidemi­ology has vastly expanded from a disci­pline devoted, as its name implies, to the study of epidemics and infectious disease patterns, into a wide panorama of investi­gations involving a multiplicity of the parameters of health and its maintenance. It is to the use of epidemiological tech­niques that we owe our recent awareness, for example, of the effect of personal habits—what we call lifestyle—on the con­dition of our bodies. Our relatively new knowledge ranges from such certainties as the positive correlation between smoking and lung cancer all along the spectrum toward factors whose effects are far less well documented, such as the decrease in the incidence of depression among those who take part in frequent physical exer­cise.

YET STATISTICAL METHODS are only as dependable as the re­searchers who use them. Flaws in the design of a study or in its analysis can lead to erroneous conclusions that then bear the imprimatur of seemingly objec­tive statistical proof. Thus, it has been "shown" that drinking coffee and Coke can lead to pancreatic and bladder cancer respectively, and that eating a diet high in animal fat will cause heart attacks.

Whoa, says the careful reader of each Tuesday's Science Times, or of the Har­vard Health Letter. How can discredited studies such as those involving coffee and Coke be mentioned in the same sentence as a well-documented statement like the one about fat and coronary heart disease? Surely, if we know anything about the causes of heart disease, it is that the inges­tion of high-fat foods results in an elevated level of cholesterol in the blood, which in turn is the cause of coronary attacks.

James Le Fanu is far less sure of such things than are the editors of the periodi­cals, the commentators on radio and tele­vision, and the authors of the books from which so much of the public gets its in­formation. He does not believe that eat­ing more fat causes more heart disease, nor does he trust doctors who say so, espe­cially those whose statistical research pur­ports to prove it. And he has no use for epidemiologists: "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:' Readers addicted to precise sentences may not forgive Le Fanu his use of "while" for "and," but they will have to put up with such minor annoyances if they are to fol­low his argument through its provocative 426 pages.

Unfortunately, they will also have to put up with much more that is aggravating, for this is a book filled with small factual errata, repeated misspellings, and other inaccuracies in the names of institutions and well-known people, and a fierce determination to make its point, even if some exaggeration is required to do it.

Add to the aggravations Le Fanu's mad­dening habit of spotlighting the statistics that support his case and ignoring those that do not. Despite his vitriolic attacks on the epidemiologists, he does not hesi­tate to quote their results when they come out his way.

And yet this book has been produced by a respected science writer with a profound insight into the history and conundrums of twentieth-century biomedicine. Le Fanu has a very important message for those who unthinkingly accept current dogma about the causes of disease and some of the ways in which individuals can influence them by how they live their lives. And the message should be heard also by everyone who believes that there is any real certainty in the practice of medicine.

IT IS IN recounting the history that Le Fanu is at his best. His thesis is that the great medical innovations of the twentieth century took place between the 1940s and the late 1970s, followed by a marked decline since then. Though the past two decades have been characterized by enormous strides in the laboratory and in statistical methods of studying disease, it is Le Fanu's assertion that little of thera­peutic value has yet emerged. The title of his book is based on his panoramic per­spective that medical researchers are lead­ing themselves and patients astray by focusing their efforts on areas that are unlikely to be productive or are deceptive in their appearance of validity.

Physicians have been seduced, in Le Fanu's view, by the siren calls of the research emanating from basic science laboratories. And they have also been seduced by a concept that he calls The Social Theory This latter is the notion that the most important reason why people become sick is that they indulge them­selves in unhealthy behaviors, such as smoking, eating an improper diet, not get­ting enough exercise, and making the mis­take of being poor. If they did not give in to such temptations, according to The Social Theory, the great majority of people would remain perfectly well right on into a vibrant old age. So it is nurture and not nature that is at fault; and self-nurture at that. Except for the proven relationship of cigarettes to lung cancer, Le Fanu rejects all of this, including the virtually self-evi­dent effect of poverty on health. He means to shock, and he succeeds.

Le Fanu has divided his book into two almost equal halves: the first in which he describes The Rise that ended around 1980, and the second in which he writes of The Fall. Those readers unfamiliar with the extraordinary development of clinical science after World War II will be engrossed by the story of The Rise for its well-crafted tales of medical accomplish­ment, and its character sketches of some of the leading figures in the effort. Those who know somewhat more about these things will find details with which they have probably not been familiar. This is no superficial run-through.

But Le Fanu’s account of The Fall is something else entirely. Here he takes on two of the most basic assumptions of the new medicine, and uses them to illustrate his iconoclastic thesis. One is the notion that the dogma he calls The New Genetics is the next frontier, destined to do for medical therapeutics what antibiotics did when they came upon the scene half a cen­tury ago. The other is the widespread belief that regulating the amount of fat in the diet will prevent coronary heart dis­ease. He trashes them both.

One cannot avoid the paradoxical impression that Le Fanu wrote his book in a great hurry, though he probably spent years earnestly studying his subject and forming his opinions. His is not a shallow understanding or a shallow mastery of a large amount of unrelated data. He is, in fact, a philosopher of a sort, but one in such a hot-tempered fervor to write it all down that he tramples on the details in order to paint the big picture. And even the big picture, as valid as much of it is, is distorted by the righteous indignation of its artist.

The American publication of The Rise and Fall of Modern Medicine will enrage some readers, astonish many more, and be greeted by a few with some such thought as, "It's about time someone said this." Le Fanu is well-known in England, where the book first appeared a year ago. He writes a weekly medical column for the Telegraph, and his articles have appeared in a variety of newspapers and magazines. He knows whereof he writes—up to a point.

LE FANU'S PRIMARY argument against the effects of a high fat diet is largely theoretical, and rests on the existence of a balancing mechanism within all multicellular organisms. Named the milieu interieur by Claude Bernard, the nineteenth-century physiologist who first described it, this consists of a ubiquitous chemical-rich fluid in which all the cells of the body are bathed. The fluid and its ingredients are so responsive to even minute changes from within (the cell) and without (the environment) that it immedi­ately acts to restore equilibrium when some new, noxious influence makes its appearance. By numerous feedback mechanisms, the milieu interieur maintains the steady state required for healthy cellular life. Le Fanu argues, and correctly, that only massive attacks on the integrity of this extracellular fluid can disrupt the harmo­nious balance that is thus maintained within the body. By his reasoning, raising the dietary intake of fat only mobilizes the milieu interieur to do what is necessary to keep the blood content of cholesterol at a steady level.

As one proof of the resistance of the body to external influences, and to sup­port his thesis that there is little cardiac significance in the amount of fat ingested, Le Fanu cites the massive multinational study—it involved more than 60,000 men—done in the 1970's and called the Multiple Risk Intervention Factor Trial (MRFIT). Great efforts were made to induce these men to reduce their intake of saturated fat, in order to lower cholesterol levels. The outcome was disappointing to the researchers, but it was apparently no surprise to Le Fanu, at least in retrospect: "These prodigious efforts were rewarded, the average amount of saturated fat in their diet fell by about a quarter, but dis­appointingly—if predictably because of the milieu interieur already alluded to—their cholesterol level only fell by just over 5 percent."

Although Le Fanu seems not to have noticed it, the very name of the MRFIT is a metaphor of sorts for a major theme of his book, and perhaps for its entire thesis. The proponents of The New Genetics believe that biomedical science stands on the verge of an era in which various forms of genetic manipulation will provide panaceas for a wide range of diseases; the proponents of The Social Theory believe that the paramount reason that people become ill is their style of life. Le Fanu summarizes the thinking that led to this latter conclusion, or at least his interpre­tation of it:

The great appeal of The Social Theory is not just that it provides an explanation for disease, but also opens the way to pre­venting them [sic].... [T]here would be no need for most drugs and treatments were it possible to identify why people became ill in the first place and prevent their diseases in a similar manner. The problem was that up until the mid-1970s no one seemed to know what these other causes of disease might be. And then sud­denly it seemed as if this ignorance was being swept away as, with increasing cer­tainty, it was claimed they lay simply in people's lives and that most cancers, not to mention strokes and heart attacks, could be prevented by people changing their social habits in precisely the same way that lung cancer could be prevented by stopping smoking.

In other words, if every man could be persuaded to change his habits in an appropriate manner, he would become Mr. Fit, and unlikely to fall victim to the many sicknesses that he incurs by his pre­sent way of living. This is, of course, a sig­nificant overstatement of the present viewpoint of most medical authorities, but it serves Le Fanu well in his attack on those who are committed to any part of it. In pursuing that attack, he provides important information that will probably be new to the general reader—and which has been overlooked or ignored by many physicians.

YET IT is in the analysis of that information that Le Fanu reveals his bias, and shows himself to be guilty of the sin of which he accuses oth­ers: forcing the evidence into conforma­tion with his predetermined conclusion. Sometimes this comes about because he deliberately misrepresents the claims of those he would bring down, as when he insists that they "argue that most common diseases are caused by an 'unhealthy' lifestyle" [italics mine]. But elsewhere it can be attributed to faulty comprehension of just what it is that the other side is talking about. There is a vast difference between asserting that lifestyle is a con­tributory factor—which is what most authorities claim—and calling it a cause.

Le Fanu's campaign against The New Genetics is based on a misunderstanding of the role of genes in disease. As evidence for his skepticism that genetic manipula­tion will ever be of much value in clinical medicine, he cites the fact that "there are approximately 4,000 diseases resulting from a defect in just one gene [elsewhere he gives the figure as 5,000] —the so-called single gene disorders. Luckily they are all very rare, except for a handful including Huntington's Chorea, cystic fibrosis and the congenital blood disorders such as sickle cell anemia." Moreover, "the genes themselves turn out to be infinitely more complex than could ever have been imagined... Sickle cell anemia turns out to be virtually unique in the simple nature of its genetic defect". And finally comes the ultimate summing up of his argument against the promise of The New Genetics:

Genetics is not a particularly significant factor in human disease. This is scarcely surprising, as man would not be as suc­cessful a species as he is (many would argue too successful), were it not that natural selection had over millions of years weeded out the unfit. Consequently there are only a handful of common gene disorders and they themselves are not very common. Further, the contribution of genetics to adult disease such as cancer is limited to a minority of cases and for everybody else it is almost invariably only one of several factors, of which the most important is ageing, an everyday fact of life about which there is not much that can be done.

Try telling such a thing to a 60-year-old diabetic with a strong family history of the disease, or to a 45-year-old man who has had, like his father and older brother be­fore him, a second coronary occlusion—or to me, among whose close relatives colon cancer keeps appearing, even without the presence of the specific gene that has been shown to be associated with the malig­nancy in a small minority of families. Le Fanu is simply, factually wrong: DNA is a contributor to many common pathologies other than those induced by a single gene, and in varying degrees can influence not only onset but also the course of a disease.

I AM NOT claiming that developing genetic therapies will be easy, or that they will necessarily revolutionize medicine in the next decade. The genetic contribution to disease is extraordinarily complex. To begin with, it comes not from one source but many. Genetically influ­enced diseases will probably all eventually be proven to be "oligogenic," which means that the hereditary component is medi­ated not by one but by many contributing bits of DNA at different sites on the chro­mosomes, all having differing degrees of effect on the eventual expression of the pathology and all interacting with numer­ous other factors. And so gene therapy may not revolutionize medicine at all.

Yet surely it will suffice if a significant improvement occurs in our ability to pre­vent only some of the common patholo­gies. Even if the percentage of patients involved is relatively low, the absolute number of people affected would be enor­mous. My confidence that solutions will be found comes from the history of late-twentieth-century science, which has again and again proven itself equal to tasks at first thought to be overwhelming and impossible to accomplish. Witness the Human Genome Project itself; witness the advances hailed by Le Fanu as "The Twelve Definitive Moments of Modern Medicine."

Pathologies such as diabetes, coronary arteriosclerosis, and colon cancer may not be "the so-called single-gene disorders," but without the input of the genetic pre­disposition, the other contributory factors would not add up to the full panorama of ingredients required to cause them. I hope Le Fanu endures to see the day when appropriate gene therapies are in regular use to decrease the likelihood that the potential diabetic, the young worrier over his father's early cardiac death, and my grandchildren will have to live under the sword of Damocles in their DNA. Perhaps he might then be embarrassed to be reminded that years earlier he instructed the readers of his book that gene therapy is "not only expensive but useless."

One need not necessarily agree—a least not yet—with one of gene therapy's pio­neers, W. French Anderson of the Univer­sity of California, that within the next few decades "virtually every disease will have gene therapy as one of its components," but the hiccoughs and tribulations of its begin­ning stages should not delude anyone into thinking that such research will lead to a clinical blind alley. Gene therapy and the development of stem cell techniques are among the avenues of research that hold the most promise of heralding yet another Rise of Modern Medicine, similar to the one that Le Fanu so accurately describes in the first part of his book. Were investiga­tors and clinicians as easily discouraged as he seems to be, we would never have had the benefits of open heart surgery, the cure of childhood cancer, and organ transplan­tation, three of the advances that he includes among those "Twelve Definitive Moments:' Each of them took decades to develop, and a long preliminary series of failures and aborted experimental meth­ods. Each of them was at first thought by many respected authorities to be impossi­ble to accomplish. Had he written his book during those intermediate years, Le Farm would have scoffed at every one of those efforts as "not only expensive but useless."

LE FANU SUFFERS from an out­moded notion of just why it is that people get sick. His eyes are fixed on a gonfalon that first began to inspire soldiers in the war on disease over a hun­dred years ago, but has more than outlived its usefulness: that standard, displaying the motto that each disease has a unitary etiology, is in fact a hindrance to contin­ued progress. Its hundred years of domi­nance since the late nineteenth century has long been over.

The introduction of the germ theory at that time transformed not only the under­standing of pathological processes, but the entire philosophy of disease causation. From vaguely expressed theories involving such uncertainties as humors, miasma, and constitutional weakness, physicians and scientists began to look for specific triggering agents, the concept being that for each disease there is only one instigat­ing factor. This formulation, sometimes called the theory of single causes, guided medical research for much of the next century, heightened in authority by its his­toric association with such monumental figures as Joseph Lister, Louis Pasteur, and Robert Koch.

The theory of single causes proved extremely useful in the elucidation of infectious disease. As one microbial source after another was discovered, researchers were stimulated to focus their efforts on finding the agent that was responsible for each particular sickness or syndrome. Yet it gradually became apparent that some pathologies, though they might have one major causative factor, would not produce sickness in any given individual unless an entire set of circumstances was just right for its development. If several, or some­times only one, of the contributory factors was absent, no illness occurred.

From this emerged the realization that disease is not an inevitable outcome of a single cause, but rather the result of many kinds of input, following a kind of proba­bilistic course from the molecular level all the way up to the environmental and per­haps even the psychological. Each of them sets off a chain of biological responses, and their sum total is what is recognized as an illness. And if there is even a rela­tively small genetic component of such a process, modifying it may abort the entire sequence. This is why it is not only the "single-gene" pathologies that may benefit from therapies directed toward their DNA, but also many, many others now known to be the outcome of such ele­ments—plus plenty more whose genetic interaction we have yet to learn about. The lesson is clear: if an entire sequence of events is required to set off an illness, suc­cessful treatment or removal of any one of the elements in that sequence will prevent the disease from occurring, whether the element is genetic or something else.

LE FANU'S HARSH criticism of what he calls The Social Theory suffers from something of the same disability as his attack on The New Genetics. After correctly pointing out major flaws in the research purporting to show that cer­tain aspects of lifestyle are determinants of health, he accuses the medical estab­lishment of maintaining that these are the single, or at least the major, etiologies of one or another pathological process. I do not know of any responsible physician who claims that the intake of fatty foods causes heart attacks. It contributes in varying measure to the probability that they will occur, and even this depends on multiple other factors, some of which are as yet unknown.

It is true that some of the leading pro­ponents of The Social Theory have long insisted that coronary heart disease is attributable primarily to the consumption of saturated fat, but a panel of the Ameri­can Heart Association (AHA) evaluated their evidence in 1957 and could not sub­stantiate the conclusions that they had drawn. Through a process of inside maneuvering by those with much to lose from such a decision, the relevant com­mittee in time came to include two of the most prominent of the researchers whose studies had been discounted, Ancel Keys of the University of Minnesota and Jere­miah Stamler of the University of Chicago (called by Le Fanu, in one of many such small errors that mar his book, Chicago University). The result was that the origi­nal committee's conclusion was reversed, and thereafter the American Heart Asso­ciation, calling the ingestion of saturated fat "the central explanation of the coro­nary epidemic," began to propagandize against it. The chicanery involved in this decision was soon forgotten.

LE FANU IS completely correct in his description of this course of events, and it brings no credit to the researchers or to the AHA. Unfortu­nately for their cause, MRFIT would throw a huge shadow over their theory, but its problems were compounded by the results of another study reported less than a year later, this one under the aus­pices of the World Health Organization, and involving some fifty thousand male factory workers in Britain, Belgium, Italy and Poland. The results were the same as had been reported following MRFIT. Keys, Stamler and the AHA were left without substantiation of their theory. There was no epidemiological evidence that reducing saturated fat in the diet would reduce the incidence of heart attacks.

Le Fanu, who is addicted to seeking causes that are inherent in independent human biology and therefore unaffected by individual habits, has convinced him­self that the increased incidence of coro­nary heart disease that was observed in the 1940s and 1950s, followed by its sub­sequent steep decline in the 1980s, can only be compared to the way in which the prevalence of certain infectious diseases has been known to rise and fall with seem­ing spontaneity.

This pattern of the 'rise and fall' of heart disease resembled 'the rise and fall' of an infectious disease. It was not a 'social' but a 'biological' pattern, with the obvious implication that some unknown biologi­cal factor must be the culprit, either by influencing the severity of atheroma in the coronary arteries, or by precipitating the clot that causes the heart attack—or both.

But though Le Fanu rejects The Social Theory, he is persuaded that cholesterol does play a role. And here he makes one of those insinuative statements that are likely to evoke that "it's about time some­one said this" comment:

Now, cholesterol, as has been noted, was not entirely innocent. Whatever might be the unknown 'biological' cause that explained the rise and fall of heart dis­ease, it clearly was most likely to hit those with higher than average cholesterol lev­els and therefore more severe atheroma in their coronary arteries. Hence, both the drug companies and the dietary pro­tagonists had a mutual interest in sal­vaging Keys's thesis. If the drug companies could show that their power­ful cholesterol-lowering drugs reduced the chances of a heart attack in those 'at high risk' (which was probable), this would be evidence the disease was indeed 'preventable' which would then shore up the position of the proponents of the dietary theory like Stamler and Keys. On the other hand, if the dietary protagonists could convince the public that too much fat caused heart disease and that every­one should lower their cholesterol levels, this would markedly increase the market for cholesterol-lowering drugs way beyond the minority 'at high risk'. And that is precisely what happened.

In addition, the dietary protagonists are accused of another motive for their unre­lenting campaign to perpetrate what Le Fanu calls "the great cholesterol de­ception": their reputations would be destroyed if they were proven wrong. And so everything was done to support the "false theory" whose acceptance was now seen as a means by which the profits of the pharmaceutical houses might be increased and the professional humiliation of Keys, Stamler, and the AHA avoided.

THIS IS ONE conspiracy theory to which there is good reason to sub­scribe, and it is worth taking seriously. Whatever may in the long run prove to be the truth about the effect of lifestyle changes in heart disease, there can be little doubt that the entire issue has been exploited by the pharmaceutical houses, into whose hands frightened patients and well-meaning doctors have fallen. After all, what is an individual physician to do with the large number of journal articles from respected research groups, appear­ing at least weekly or more, which, with seeming statistical significance, relate cholesterol levels, heart disease, and mor­tality to lifestyle? News of these articles does appear in highly respected periodi­cals and is repeated over the airwaves. In the average reader's mind, fat, cholesterol, and heart disease become blended into a single grim continuum, and the connec­tions are in time unquestioned.

During the very week I was reading Le Fanu's book, a significant paper appeared in The New England Journal of Medi­cine (no less) from the Harvard Medical School (no less) entitled "Primary Preven­tion of Coronary Heart Disease in Women Through Diet and Lifestyle." Its conclu­sion states that "among women, adher­ence to lifestyle guidelines involving diet, exercise, and abstinence from smoking is associated with a very low risk of coronary heart disease 84,129 women participated in the study. Such a report came as no news to the many subscribers to the Jour­nal, physicians and lay people alike, who have long been accustomed to reading of similar studies, even if the word "very" is not always associated with them.

THIS WOULD SEEM to give the lie to all that Le Fanu has told us, and yet it does not. As any long-time student of medical literature can attest, the past half century's reliance on large-scale statistical studies, whether or not they were randomized controlled clinical trials, has been a mixed blessing. As with MRFIT and the WHO study, the analysis of the data has not infrequently led to conclu­sions that would seem to fly in the face of the shared experience of clinicians treating patients in the course of everyday practice, and even to be counterintuitive to what any logical person might assume. Some­times the clinicians and the critically-minded lay people are eventually proven correct, and sometimes the epidemiolo­gists and statisticians are.

On a purely statistical or scientific basis it must be said that the jury is still out on the question of whether lifestyle changes, such as diet modification, really affect health. But it should also be pointed out that such studies as MRFIT and the WHO trial stand in direct contradiction to a great deal of evidence pointing in the opposite direction. More importantly, they stand in direct contradiction to what a widely experienced internist will de­scribe at the end of a long career during which he or she has followed thousands of patients over a period of decades. Though such a mature clinician has certainly observed that changing eating or other habits is very difficult to achieve, those patients who manage to do it are usually greatly benefitted in numerous ways, including those that Le Fanu says are a delusion.

And here we are faced with yet another paradox of this controversial brain-teaser of a book. At the end of a long bashing of the goals of the medicine of the past twenty years, Le Fanu sums up with a statement that is so undeniably correct that one can almost forgive him for the error-strewn, selective, and even mislead­ing path he has taken to get to this point. On his penultimate page, he presents his declaration of independence from molec­ular biology, genetics, the tyranny of epi­demiological studies, the application of ultra-sophisticated statistical methods to therapeutic intervention, and all of the other twenty-first century trappings that increase the distance between the patient and the personal physician who knows him as a distinct individual rather than as an enclosed chamber of biological phe­nomena and an object of modern versions of la methode numerique.

The solution, Le Fanu proclaims, is to be found in a return to the values inherent in the healing compact between two human beings, doctor and patient. It is in the study of individual men and women by caring and highly skilled healers that the promise of medicine has always been cen­tered and best fulfilled. And this is no dif­ferent than it has ever been.

The time has come to relocate medicine within that tradition so eloquently invoked by Sir William Osler. The time­less virtues ofjudgement and good sense might then triumph over the shallow restlessness of the present through a re­affirmation of the personal human rela­tionship between doctor and patient. The personal doctor listens carefully to what he is being told.

IRONICALLY, SOME OF those who might be expected to oppose such an apparently old-fashioned view of the art of healing stand shoulder to shoulder with Le Fanu in this, as should every doc­tor who has ever sat quietly and listened to a sick man or a sick woman tell a story of illness, or laid on hands during a thoughtful physical examination. In a wide-ranging critique of the usefulness of randomized trials, Alvan Feinstein, one of the world's leading clinical epidemiolo­gists, and himself a physician of wide experience, has this to say:

Although highly successful in investigat­ing remedial therapy, randomized clinical trials have sometimes created rather than clarified controversy when the treatments were for the complex problems involved in studying either the primary prevention of disease or the secondary prevention of adverse progression for an established disease.... Consequently, despite the magnificent scientific achievements of randomized clinical trials, the foundation of a basic science of patient care will also require major attention to the events and observations that occur in the ordinary circumstances of clinical practice.

And so the answer is finally not as simple as Le Fanu would have his readers believe.

LE FANU TELLS us on that same penultimate page that genuine progress is only to be made "by accepting at face value the version of events as revealed by this historical account," which is an intolerable burden for any critical reader, since his "historical account" is so skewed to his polemical intentions. And if that were not enough, it is dotted with those erroneous statements that make a reader wonder how they could be made by an author otherwise obviously so much in command of his material.

Some of Le Fanu's mistakes are small (he tells us that the word "cortisone" is synonymous with "steroids"), but others make one doubt his familiarity with the topic under discussion, and sometimes induce suspicion that he is distorting facts for the sake of strengthening his argu­ment. Le Fanu's wishful thinking to the contrary, insulin does not cure diabetes; neglecting the lethal microbe clostridium tetani, he writes that "none of the bacteria that cause disease in humans can be iso­lated from the soil"; bioengineers will be astounded to read that "it is only a matter of elementary mechanics to devise a machine that can do the work of human hands"; in a book that bases its arguments on "this historical account," it is disap­pointing to read that "in the early 1950s, patients who had been ventilated during major surgery such as open heart opera­tions would be sent back to the ward breathing spontaneously," in view of the fact that neither the surgeons at the Mayo Clinic nor those at the University of Min­nesota, where open heart surgery was introduced, had done more than a very few cases before the late summer and autumn of 1955; there is no such anatom­ical structure as "the main aorta"; there is surely not a neurologist alive who would agree that "drug treatment reduces the incidence of strokes almost to zero"; stom­ach ulcers are not synonymous with peptic ulcers (most peptic ulcers occur in the duodenum); the Freud-bashing of the day notwithstanding, it is silly and irresponsi­ble to remark that Freudian theory is "based on the perverse proposition that everything is the reverse of what it seems"; the demonstration of the structure of DNA by Watson and Crick hardly "un­locked the mysteries of the genetic code"— and there are plenty more misstatements like these.

In Le Fanu's book, the Nobel Prize winner Alexis Carrel is Carrell; Senator George McGovern is Senator Edward McGovern; the pioneer of cardiac transplantation Norman Shumway is Norman Shunway; the National Cancer Institute is the U.S. National Institute of Cancer; and so on. A few of Le Fanu's annoying little errors are repeated in several places in the text as well as in the index, and all are to be found in both the British and American editions of the book. These and certain inconsistencies in the bibliography add up to a sloppy book.And yet, reading between the lines, it is apparent that Le Fanu knows a great deal about his topic. The first half of The Rise and Fall of Modern Medicine, in spite of its sprinkling of factual errors, is never­theless generally quite accurate in its over­all presentation and is written in a rather personalized manner, so that some of the contributors come to life on the page. Even the contentious second half of the book demonstrates a wide knowledge of the subject matter, albeit one marred by certain misapprehensions and misinter­pretations, as noted above.

SO WHAT IS a reader left with, after studying this book, or perhaps only struggling through the obliquities of this attempt to analyze it? The first lesson is one that unswerving evangelists of the modern discipline that we call biomedi­cine ignore at their own peril, and at the peril of their patients. It is that medicine is not a science. It is an art, and an uncer­tain art at that. In recommending a return to the principles of William Osler, Le Fanu might have cited a specter that will always haunt the doctor taking care of the sick and advising the well, a specter of which Osler spoke before an audience of physicians almost a century ago: "this everlasting perhaps with which we have to preface so much connected with the practice of our art."

Inconsistencies abound, pendula swing, authorities differ, and medical certainties are ephemeral. No matter the brilliant efforts of the laboratory researchers, the statisticians and even the scientifically trained medical journalists, the perhaps will always be with us. There is no random­ized clinical trial, and there is no complex experiment in molecular biology, that will ever provide the answer to caring for the distinctive individual who has come for help, or at least not one that a wise clini­cian will not already have intuited through a combination of his or her training, ex­perience and empathy. About this at least, Le Fanu is right: "The timeless virtues of judgment and good sense" do indeed pro­vide the only real basis on which to fulfill the ancient Hippocratic compact between the healer and those who need healing.

Le Fanu may have failed to refute The Social Theory or The New Genetics, but his contribution is actually far greater than that. As wrong-headed as some of his notions may be, he has held up for inspection the frayed fabric of the tissue of certainty in which we clothe medical knowledge. He is a gadfly, a kind of agent provocateur who stirs up rebellion and afflicts the smug. He makes us think about our assumptions, though when we think critically enough we realize that his con­clusions are also incorrect. So at the end of his book we are still left with the need for counsel. How should a physician advise those who might question the effects of lifestyle on health, when it has now become clear that the science is not as strong as it has been made out to be?

Well, here is one old clinician who will tell anyone who asks that the evidence is quite strong enough for him. It is consis­tent with what he has observed in the lives of his patients and in his own life as well; it is consistent with his understanding of physiology and the pathology of disease; it is consistent with the opinions of col­leagues whom he respects; it is consistent with common sense. Long accustomed to making decisions in the face of the uncer­tainty inherent in the art of medicine, this grizzled surgeon advises every reader of Le Fanu's book or the present essay to eat less unsaturated fat, stop smoking, and get plenty of strenuous exercise. And one more thing: find yourself a better-paying job.