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Chapter One The Body of Knowledge Most of the time we think we're sick, it's all in the mind. Thomas Wolfe, Look Homeward, Angel (1929) It is time to acknowledge that our belief in disease as a direct reflection of mental state is largely folklore. Editorial, New England Journal of Medicine (1985) Opening shots You, dear reader, are going to die. Not for a long time, I hope, and painlessly. But die you undoubtedly will. And unless you die in the near future, and from unnatural causes, you will be ill before you die -- probably several times. Some remarkable scientific discoveries have shown that your mind will affect your susceptibility to those illnesses and may have a substantial bearing on the nature and timing of your eventual death.     This book is about these scientific discoveries. It explores the ways in which your psychological and emotional state influence your physical health and how, in turn, your physical state affects your mind. It seeks to explain some of the extraordinary things that scientists have discovered in recent years about the interconnections between the brain, behaviour, immunity and health. By unravelling the biological mechanisms that underlie these phenomena, scientists can at last reconcile many commonplace notions about mental influences on health with a modern understanding of how the brain and behaviour affect the functioning of the body.     This is not intended to be a self-help book and I shall not be setting out detailed prescriptions for instant health or miracle cures for AIDS. The rapidly growing corpus of scientific knowledge about mind--body interactions has numerous potentially valuable applications in medicine, and I shall describe them. But practical action must be built on solid foundations of knowledge and understanding. As Sir Francis Bacon once remarked, `Knowledge itself is power.'     Bacon also remarked that `all knowledge and wonder (which is the seed of knowledge) is an impression of pleasure in itself.' I hope you will find the discoveries described here intriguing and worthwhile in their own right, regardless of their utilitarian value. We neglect the sheer wonder of scientific knowledge at our peril. Practical applications matter a great deal, but they are not the only fruits of science. Let us get down to business by conducting a simple thought experiment. When you have read this paragraph shut your eyes and cast your mind back to the most mortifyingly embarrassing moment in your life, the worst that you can dredge up from the dank recesses of your memory. Think hard and choose the most awful, squirm-inducing calamity. Be brutally honest. Perhaps you committed an appalling social blunder at an august gathering, or said exactly the wrong thing at the wrong time. Close your eyes and re-live the incident in all its ghastliness, focusing on your own humiliation.     Have you blushed? Are your cheeks burning with embarrassment? If so, you have just demonstrated a mundane example of an important biological principle: that mere thoughts and emotions can generate very real physical reactions.     If you would like to demonstrate the empirical truth of this principle again, but in a different and more recreational way, close your eyes and conjure up your most arousing and succulent sexual fantasy. You surely must have one. Sit back and let your mind savour the luscious details of whatever erotic images it has chosen. Let the moist, quivering images run rampant. The physical consequences of what is now going on in your mind should, with any luck, be more fun than a blush.     The mind's influence on the body is usually more serious than a blush or a sexual frisson , however. It can even determine when we die. As an appetizer we shall consider two examples. Iraqi SCUDs and Chinese grandmothers During the Gulf War of 1991 Iraq launched a series of missile attacks against Israel. Many Israeli civilians died as a result of these attacks. But the vast majority of them did not die from any direct physical effects of the missiles. They died from heart failure brought on by the fear, anxiety and stress associated with the bombardment. They died because of what was going on in their minds.     How do we know this? After the war was over Israeli scientists analysed the official mortality statistics and found something remarkable. There had been a large and anomalous jump in the death rate among Israeli citizens on one particular day: the day of the first Iraqi attacks.     In the early hours of 18 January 1991 Iraq launched the first of several SCUD missile attacks against Israeli cities. Measured in terms of physical destruction, the Iraqi weapons were surprisingly ineffective. There were no deaths through physical injuries in the first attack and only two people were killed by the direct physical effects of SCUD detonations during the subsequent sixteen days on which missiles fell. And yet, on the day of the first attack, the death rate in Israel leapt by 58 per cent. A total of 147 deaths were reported, 54 more than would have been expected on the basis of previous mortality figures for that time of year. In statistical terms this was a highly significant increase; the odds against it arising from random fluctuations alone were enormous. What happened?     The evidence consistently pointed towards one conclusion: the sharp rise in death rate on 18 January 1991 was primarily a consequence of severe emotional stress brought on by fear of the Iraqi bombardment. It was the psychological impact of the SCUD missiles, not their physical impact, that claimed the majority of the victims.     The reasoning behind this conclusion was straightforward. The unexpected `extra' deaths resulted in the main from heart failure or other forms of abrupt cardiovascular catastrophe. There was no increase in deaths from lingering diseases such as cancer, for example. As we shall see later, psychological stress can induce physiological changes which may prove fatal to someone who already has a diseased heart or clogged coronary arteries.     The `extra' deaths were concentrated in areas of Israel where the levels of fear and anxiety were highest: regions that were known to be threatened by Iraqi missiles. In parts of Israel where SCUDs were not expected to land the mortality rate remained much the same as usual. Psychological studies carried out during this period indicated that the most stressful time for Israeli citizens was the few days leading up to the outbreak of war on 17 January, peaking on the day of the first SCUD missile attacks. There was enormous and well-founded concern about possible Iraqi use of chemical and biological weapons. The entire Israeli population had been issued with gas masks and automatic atropine syringes in case of chemical attack, and every household had been told to prepare a sealed room.     After the first Iraqi strike had occurred, and turned out to be less cataclysmic than feared, there was a marked decline in levels of stress. As in other wars, the populace adapted to the situation with surprising speed. Then, as the fear and anxiety subsided, so the death rate also began to decline. There were seventeen further Iraqi missile attacks over the following weeks, but Israeli mortality figures over this period were no higher than average.     There is little doubt that many of the Israelis who died in the opening days of the war were killed by the Iraqi missiles. But there is equally little doubt that many of them died because of what was going on in their minds and not from physical injuries. Of course, their mental state was not the only thing that contributed to their deaths. Most, if not all, of those who died also had a pre-existing medical problem which made them especially vulnerable to the damaging effects of psychological stress. Many died because they had pre-existing coronary heart disease and their hearts gave out under the stress.     One of the recurring themes in this book is the simple point that disease and death seldom have single causes. The mind can help to precipitate illness or death, but this does not mean that bacteria, viruses, cancer cells, dogged arteries and other all-too-solid agents of disease are not also involved.     Mortality statistics have revealed another fascinating phenomenon. Psychological factors can not only hasten death, as happened during the Gulf War, they can also postpone it. There is less likelihood of a person dying on the eve of an occasion that has symbolic significance for them, such as an important religious festival or birthday. There is compelling evidence that individuals on the verge of death can postpone their death for a few days until the special occasion has passed.     A clear demonstration of this phenomenon came from some scrupulously designed research conducted by David Phillips and Daniel Smith of the University of California at San Diego. They analysed the mortality statistics for Chinese people living in California to see whether there were any fluctuations in the risk of dying at around the time of the Harvest Moon Festival -- an occasion which is of symbolic importance to Chinese people but not others.     Phillips and Smith found a large and statistically significant dip in the number of Chinese dying from natural causes just before the Harvest Moon Festival. This was followed by a corresponding and compensatory rise in mortality just after the festival was over. In the week preceding the festival the death rate among Chinese Californians was 35 per cent below the expected level, while in the week after the festival it was 35 per cent higher than expected. There was no overall change in the number of people dying, but some deaths that would otherwise have occurred just before the festival were somehow postponed until after it was over.     There is little doubt that this strange phenomenon of delayed death was specifically linked to the symbolic occasion of the Harvest Moon Festival. The dip and rise in the risk of dying was most evident among elderly Chinese women, who play a central role in the ceremonies. The Harvest Moon Festival is a movable feast -- the date varies somewhat from year to year -- so the fluctuation in mortality rate was definitely linked to the occasion itself, rather than to any specific calendar date. Furthermore, there were no comparable fluctuations in mortality among Jews and other non-Chinese Californians for whom the Harvest Moon Festival has no symbolic importance.     The analysis only looked at deaths from natural causes, so the phenomenon could not be explained by changes in people's propensity to commit suicide. Conceivably, some deaths might have been delayed because sick individuals took better care of themselves in the run-up to the festival, or because they received extra attention from their family and doctor. But the sheer scale of the phenomenon implied that something more profound was going on as well. In fact, the biggest fluctuations were in deaths caused by disorders of the heart and circulatory system, especially strokes and heart attacks. These are notoriously susceptible to psychological and emotional influences.     An almost identical dip and rise in mortality rate occurs among Jewish people around the festival of Passover. Like the Harvest Moon Festival, Passover is of cultural significance for one section of the community only and its dates vary from year to year.     The statistics reveal that the number of Jewish people dying from natural causes dips sharply just before Passover and bounces back with a compensatory increase immediately afterwards. Again, the fluctuation relates primarily to strokes and heart attacks and no such variation in mortality occurs among non-Jews for whom Passover has no personal significance.     Evidence like this strongly implies the existence of links between our mental or emotional state and our physical health. It is the scientific nature of these mind--body links, and their many ramifications, that we shall be exploring in this book. Roundheads and Cavaliers All scientists know of colleagues whose minds are so well equipped with the means of refutation that no new idea has the temerity to seek admittance. Their contribution to science is accordingly very small. Peter Medawar, A Note on `The Scientific Method ' (1949) I am too much of a sceptic to deny the possibility of anything. T. H. Huxley, letter to Herbert Spencer (1886) Contemporary attitudes towards the relationships between mind, body and disease are strangely confused. On the one hand we have the uncritical acceptance by the public, popular media and gurus of New Age medicine that the mind is both the source and the remedy for the majority of bodily ills. Set against these Cavaliers of mind--body interactions we have the Roundhead sceptics, who either dismiss the connections between psychological factors and physical disease as pseudo-scientific wishful thinking, or else simply ignore them altogether.     The tenet that psychological factors play a role in causing or curing bodily diseases is, of course, an ancient one -- far older than modern medicine. Throughout history people have held deep-seated beliefs in the power of the mind to influence physical health, and down the centuries (until the twentieth century, anyway) physicians have explicitly linked physical wellbeing with mental wellbeing. It therefore comes as no great surprise to us if a major emotional upset such as bereavement, depression, divorce or redundancy later manifests itself in physical form. Our everyday experience, let alone statistical data from the Gulf War, seems to support this view.     But is this age-old notion of the mind affecting physical health a self-evident truth or merely unsubstantiated pseudo-science? Is it true that we are more likely to fall ill when we are stressed, anxious or depressed? Are individuals with certain personality types more susceptible to colds, allergies, heart disease or cancer? These are questions of profound medical significance. They are also fascinating scientific puzzles.     In ancient times healers worked on the pragmatic basis that the mind and the body are intertwined. Physical disorders could stem from problems in the mind and mental disorders could be reflections of bodily disease. Accordingly, physicians were encouraged to treat the soul and not just the body, using soothing words to comfort the patient's mind.     Ancient Greek medicine placed great emphasis on the curative power of katharsis -- the purging and purification of the patient's soul. Plato and other great thinkers recognized that these psychological charms were remarkably effective in relieving physical ailments. They also recognized that these charms would not work properly unless both the patient and the physician believed in their curative powers.     Nowadays the supposedly damaging effects on health of anxiety, over-work, job insecurity and loneliness form a recurrent theme in the media, which preaches the message that stress makes us ill. The implicit connection between mental state and physical health seems to be uncritically accepted by an increasingly health-conscious public.     There has been an explosive growth in alternative and complementary forms of medicine, which tend to emphasize the underlying unity of mind and body. Around one third of the adult population has consulted a practitioner of the alternative medical arts at some time. Bookshop shelves groan under the weight of publications proclaiming the self-help gospel that health is all a matter of thinking the right thoughts and banishing negative emotions.     The self-help industry and New Age gurus offer us such tantalizing prospects as self-healing through love, thinking ourselves better from cancer, using the mind to heal all manner of dread diseases and, ultimately, reaching that holistic nirvana of health, happiness and self-fulfilment through the power of pure thought. It is easy to see why the sceptical Roundheads can be so dismissive of the mind--body Cavaliers.     A profound change in the pattern of diseases during the twentieth century may also have contributed to this trend. The infectious diseases that killed vast numbers until fifty years ago have almost disappeared from the wealthy industrialized nations -- though not from poorer parts of the world. Their place in the league table has been taken by chronic degenerative disorders such as coronary heart disease and cancer. Diseases of the heart and circulatory system, cancer and accidental injuries now account for more than three-quarters of all deaths. In contrast, infectious and parasitic diseases account for less than 0.5 per cent of all deaths.     The causal factors that contribute to these modern-day killers are much more complex than the relatively understandable causes of infectious diseases. We all recognize that tuberculosis is caused by bacteria, but cancer and heart disease are altogether more obscure. It is therefore easier to believe that the mind may play a role in their genesis. Factors as diverse as tobacco, red meat, slothfulness, insufficient fibre, childlessness, salt, pesticides, sunburn and radiation can cause serious diseases, so why not psychological stress or depression?     But is there any scientific basis for these beliefs? Just because people have always assumed something to be true does not make it so. After all, the earth was at one time assumed to be flat, stationary and at the centre of the universe. This belief appeared to be supported by everyday experience and was universally accepted as a self-evident truth. Yet it turned out to be completely wrong. Folklore, faith and dogma are not always reliable guides.     In stark contrast to the popular attitudes we have the inherent scepticism harboured by many scientists and doctors towards the notion that mere thoughts or emotions could possibly have an impact on such brutally physical processes as viral infections, coronary heart disease or cancer.     Scientific research in this field has often been tinged with a largely undeserved aura of crankiness. `Psychosomatic' phenomena carry with them a whiff of self-indulgent fantasy, along with the implication that they lack both substance and scientific respectability. The suggestion that psychological and emotional factors play a causal role in disease is often regarded as an admission that the real (i.e., physical) origins of the disease are not yet understood. As Susan Sontag put it in her 1978 book Illness as Metaphor : `Theories that diseases are caused by mental states and can be cured by will power are always an index of how much is not understood about the physical terrain of a disease.'     The belief in an intimate connection between mental state and physical health has had a decidedly rocky history in Western medicine, despite its promising beginnings in the civilizations of China and Greece more than two thousand years ago. By the end of the nineteenth century the overwhelmingly predominant approach to medicine was to focus exclusively on the disease and its identifiable physical causes, such as bacteria. Medical research could get to grips with bacteria, but thoughts and emotions were altogether too ethereal. The patient's mental state increasingly came to be seen as an embarrassing irrelevance -- the province of psychologists and other faintly disreputable types rather than a proper concern of scientific medicine. In later chapters we shall consider why the mind and body came to be separated in Western thought, and how this estrangement of psyche from soma has had such an all-pervasive influence on modern science and medicine.     Yet even in the late nineteenth century there were notable exceptions to this rule. For instance, in 1884 Daniel Hack Tuke, one of the pioneers of British psychiatry, published the second edition of a work entitled Illustrations of the Influence of the Mind Upon the Body in Health and Disease, Designed to Elucidate the Action of the Imagination . In it, Tuke argued that the mind and body are inextricably linked through physiological processes; and that our mental state consequently affects our physical health and vice versa. State-of-the art research in the closing years of the twentieth century has come to much the same conclusion -- and not before time.     History shows that important ideas can be ignored even if there is good evidence to support them. It is worth recalling the uncomfortable fact that compelling scientific evidence for the connection between smoking, disease and death was available for many years before it started to be taken seriously. Nowadays the link between smoking and all manner of dread diseases is almost universally accepted. Yet this was not always so. Scientists had suspected that smoking was bad for health long before the first solid evidence for a connection with lung cancer was published in 1950. During the 1950s and 1960s a succession of studies concluded that smoking increases the risks of lung cancer, heart disease and a host of other life-threatening conditions. Nevertheless, governments, the general public and even doctors remained sceptical of these links, and two decades passed before the research started to have an impact.     Contemporary physicians and scientists frequently dismiss the idea that the mind has a profound effect on physical health. To quote an editorial from a prestigious international medical journal: `we have been too ready to accept the venerable belief that mental state is an important factor in the cause and cure of disease.' Another sceptic, also writing in a leading medical publication, comments that `Mental stress is frequently blamed for the generation of organic disease, especially if it is of uncertain or complex aetiology, though without reliable or confirmatory argument ... The morbidity of mental stress is commonly widely exaggerated.' Or consider this trenchant counterblast from a third scientific sceptic: During the last quarter of the 19th century many medical men asserted confidently that the stress of `modern' life (i.e., all that gadding about in hansom cabs, paddle steamers, and railway trains) caused general paralysis of the insane [the final stages of syphilis]. Most of us now accept that this view was mistaken. I think that the notion that emotional factors have an important bearing on immunity, or on the cause or progress of cancer, comes into the same category.     In many respects the scientific evidence for connections between psychological factors and disease is stronger and more consistent than the evidence for certain other medical risk factors which are, nonetheless, regarded as less controversial. The putative links between dietary salt or cholesterol and heart disease are viewed with nothing like the same degree of suspicion and scepticism as psychological risk factors. Yet the scientific evidence that excessive salt or cholesterol in the diet actually cause heart disease in normal people is by no means conclusive. On the other hand, the evidence that psychological factors contribute to heart disease is wide-ranging and convincing, as we shall see later. There is a curious double standard at work here.     The fact is that most people, doctors and scientists included, find it inherently easier to believe in the reality of apparently simple physical causes of disease (such as cholesterol, salt, bacteria or viruses) than to accept that mere thoughts or emotions can affect our health. Partly as a result of such sceptical attitudes, research into the connections between the brain, behaviour, immunity and disease has, until recently, been remarkably neglected by mainstream medicine and seldom explained properly to the general public.     Can the starkly contrasting views of the uncritical Cavaliers and the sceptical Roundheads be reconciled? What are we to think when faced with conflicting claims about the mind's role in disease?     As we shall see, the scientific truth is subtler than either of these two extreme views. It is also far richer and more exciting. It turns out that the folklore was in certain respects right, while the sceptics were wrong in their sniffily dismissive attitude. Research has uncovered an array of solid, compelling evidence that the mind does indeed play a part in a multitude of disease processes, ranging from commonplace bacterial and viral infections to heart disease and even cancer. Some completely fictitious case histories Before delving into the science, let us turn our attention temporarily to storytelling. If it is true that our mental state influences our physical health then this fundamental aspect of human nature ought to have been noticed and reflected in literature throughout the ages. What can we see in the mirror that fiction holds up to the human condition?     The links between the mind, emotions, behaviour, disease and death have indeed been reflected in the lives of fictional characters over the centuries. The writers describing these mind--body phenomena obviously had no conception of their biological basis, but that did not stop them noticing and portraying the connections. Throughout this book I shall be referring to literary illustrations of the links between psychological factors and disease. But first, let me spell out what these fictional case histories are intended to convey and, perhaps more importantly, what they are not intended to convey.     I shall use literary allusions because they help to convey complex scientific ideas in a recognizable form. Well-turned examples drawn from literature are more cogent and ,more entertaining than any medical case history, no matter how supposedly authentic it may be. They also demonstrate the antiquity and universality of many of the concepts that underlie current theories. However, by citing fictional characters or situations to illustrate scientific theories I am certainly not implying that they constitute hard evidence in support of those theories. Fine words drawn from the imaginations of long-dead authors are clearly not the same as scientific data.     The idea that physical decline can stem directly from mental and emotional decline is a familiar theme in literature. Fictional characters often die from unrequited love, grief, shame or fury. Emily Bronte's Wuthering Heights , for example, is positively bulging with characters whose mental states lay waste their physical health. Death and disease run riot throughout the book. Let me remind you.     Believing his childhood sweetheart Catherine has spurned him, the tempestuous Heathcliff vanishes. Catherine, who does in fact love Heathcliff, is deeply upset and ridden with guilt. She consequently becomes mentally unstable and physically ill. Three years later Heathcliff returns. Catherine is torn between her love for Heathcliff and her love for Edgar Linton, whom she has meanwhile married. She breaks down under the mental pressure, shuts herself in her room and sinks into delirium. The vengeful Heathcliff subjects Catherine to an emotional battering which further weakens her health and she dies giving birth, a victim of psychological torment.     The bereaved Heathcliff determines to achieve his longed-for union with Catherine through his own death. He locks himself in a darkened room and wills himself to die. Four days later a servant enters the room to find his body. Heathcliff's mind has killed him, as surely as if he had been shot: Kenneth was perplexed to pronounce of what disorder the master had died. I concealed the fact of his having swallowed nothing for four days, fearing it might lead to trouble, and then, I am persuaded he did not abstain on purpose; it was the consequence of his strange illness, not the cause.     Death by shame is the tragic fate awaiting Madame de Tourvel in Choderlos de Laclos's Les Liaisons Dangereuses , that tale of sexual intrigue among the enormously rich, enormously idle and enormously depraved aristocrats of pre-Revolutionary eighteenth-century France.     The young, pious and austere Madame de Tourvel is a devoted wife. Nevertheless, she is ruthlessly seduced by a satanic libertine, the Vicomte de Valmont -- a man who `has spent his life bringing trouble, dishonour, and scandal into innocent families'. Valmont is egged on by the Marquise de Merteuil, his equally amoral former lover. Together they plot their seductions with the cold, unemotional precision of a military campaign.     Facing stiff resistance from the virtuous Madame de Tourvel, Valmont eventually breaks down her defences by convincing her that he will die from emotional torment unless she surrenders herself to him. Unable to resist his wiles any longer, Madame de Tourvel succumbs and Valmont has his wicked way with her.     The awful truth is then revealed -- Valmont has cruelly deceived Madame de Tourvel and does not love her at all. In a fit of anguish and shame she flees to a convent, locks herself away and announces that she will not leave until she is dead. Her health rapidly deteriorates: A burning fever, violent and almost continual delirium, an unquenchable thirst ... The doctors say they are as yet unable to diagnose ... As long as she is so deeply affected, I have scarcely any hope. The body is not easily restored to health when the spirit is so disturbed. The wretched Madame de Tourvel dies, destroyed by her grief and shame. No physical agent, other than Valmont, has intervened.     Fate, however, wreaks its just revenge on the perfidious Vicomte de Valmont and Madame de Merteuil. Valmont is fatally injured in a duel. Soon afterwards, the correspondence of Valmont and Merteuil, detailing their devilish seductions, is revealed and becomes the topic of widespread gossip. Madame de Merteuil is publicly humiliated, and one day later is afflicted by a virulent attack of smallpox which leaves her horribly disfigured and blind in one eye.     Another victim of physical decline brought on by seduction and shame is the eponymous heroine of Samuel Richardson's eighteenth-century blockbuster Clarissa . (At over a million words, it is also the longest novel in the English language.) Clarissa, a young lady of refined sensibilities, is seduced and raped by a superficially charming but unscrupulous bounder. Naturally -- for this is eighteenth-century England -- the dishonoured Clarissa is rejected and ostracized by her family and society. As her mental state declines, so does her physical health. Clarissa retreats into solitude and dies from grief and shame. Once again, a character's psychological and emotional state has been the prime cause of her death.     There are of course innumerable other examples, all making similar points about the impact of emotions on health. We shall encounter a number of these in later chapters, and I hope it will be apparent that the notions they portray do bear some relationship to the reality revealed by modern science. However, at the risk of repeating myself, let me repeat myself: the fantasies of novelists are not the same as hard scientific evidence. Fortunately, there is plenty of that as well. Invisible worms O Rose, thou art sick. The invisible worm That flies in the night In the howling storm, Has found out thy bed Of crimson joy, And his dark secret love Does thy life destroy. William Blake, `The Sick Rose', Songs of Experience (1794) The sharp divide between those who proffer psychological explanations for diseases and those who reject such theories in favour of purely physical causes is reflected in attitudes towards two particular disorders: tuberculosis and chronic fatigue syndrome.     Sir Peter Medawar, the Nobel Prize-winning immunologist and virtuoso science writer, once described tuberculosis as `an affliction in which a psychosomatic element is admitted even by those who contemptuously dismiss it in the context of any other ailment.' There is abundant evidence, dating back hundreds of years, that the course and progression of tuberculosis are influenced by the sufferer's mental state. The physical health of tuberculosis sufferers shows a tendency to deteriorate when they are subjected to severe stress or emotional upsets.     Someone who is infected with Mycobacterium tuberculosis , the bacterium that causes tuberculosis, develops a protective immune response which can hold the bacteria in check and prevent them from multiplying. The resulting stalemate between body and bacteria can mean that the disease will remain dormant for years. But if something happens to compromise or weaken the body's immune defences, the bacteria can run riot and cause a resurgence of disease.     The importance of psychological factors in tuberculosis was widely acknowledged until well into this century. As early as 1500 BC, Hindu scripts described a wasting disease -- almost certainly tuberculosis -- of which one of the main causes was said to be sadness. Hippocrates, Galen and other medical luminaries of ancient Greece taught that grief, anger and other strong emotions played a major role in tuberculosis.     Throughout the seventeenth, eighteenth and nineteenth centuries many eminent European physicians stated that the causes of tuberculosis (or phthisis , as it was then known) included mental states such as `a long and grievous passion of the mind', `a mournful disposition of the soul', `ungratified desires', `profound melancholy passions' or `disappointment in love'. During the eighteenth and nineteenth centuries, students of tuberculosis refined the theory of a link between the disease and a specific set of psychological characteristics. This was formalized in the concept of the tuberculosis-prone personality, or spes phthisica . As we shall see later, modern science has revived the concept of disease-prone personality types with the discovery of certain intriguing associations between personality traits, heart disease and cancer.     More familiarly, we have the romantic nineteenth-century notion that consumption (as tuberculosis was then known) is caused -- or, more accurately, exacerbated -- by an artistic temperament. Consumptive artists or writers were believed to be consumptive primarily because of their excessive artistic and aesthetic emotions, which literally consumed them. Consumption came to be something of a status symbol among the chattering classes.     Countless noted writers, artists and musicians of the nineteenth and early twentieth centuries did indeed suffer from consumption. Emily Bronte is but one example. She died of tuberculosis, a bitterly disappointed woman, within a year of Wuthering Heights being published to withering reviews. Other creative victims of tuberculosis included John Keats, Frederic Chopin, Robert Louis Stevenson, Stephen Crane, Katherine Mansfield, Robert Tressell, D. H. Lawrence, George Orwell and Franz Kafka. It is said that Kafka's health was weakened by his chronic unhappiness, his hypersensitive personality, his problematic relationship with his father and several unfortunate romantic tangles. He died in an Austrian sanatorium in 1924, aged forty-one.     On the other hand, tuberculosis accounted for more than one in five of all deaths in the nineteenth century and was still common in Europe until well into this century. On statistical grounds it is hardly surprising that at least some prominent names were included among its victims.     The fiction of the eighteenth and nineteenth centuries reflects this preoccupation with tuberculosis and the prevailing attitudes towards it. We can choose from a panoply of heroes and heroines who sink into tubercular decline in the aftermath of romantic tragedy. We have, for example, the ever popular tale of La Dame aux Camelias , Alexandre Dumas the younger's tear-jerker about the passionate but doomed love affair between Armand Duval and the enchanting courtesan Marguerite Gautier.     The young Duval meets Marguerite and is captivated by her. They become lovers. Marguerite is already consumptive, but under the healing influence of Armand's love she abandons her dissolute lifestyle and her health improves. Meanwhile, Armand's well-meaning father secretly persuades Marguerite that if she truly loves Armand she will leave him for his own good. Marguerite demonstrates her love for Armand by doing just that.     The cynical Armand thinks Marguerite has abandoned him out of boredom so that she can resume her former life of late nights, promiscuity and wild self-indulgence. He therefore sets out to punish her by humiliating her at every opportunity and revelling in the spectacle of her suffering: ... for the last three weeks or so, I had not missed an opportunity to hurt Marguerite. It was making her ill ... Marguerite had sent to ask for mercy, informing me that she no longer had either the emotional nor physical strength to endure what I was doing to her.     As a consequence of her deep unhappiness at their separation and the psychological battering she receives from Armand, the much-wronged Marguerite goes into terminal decline. Her consumption flares up and she expires. Armand realizes his error, but not until too late. As the narrator sagely concludes: `I have learned that one such woman, once in her life, experienced deep love, that she suffered for it and that she died of it.' Though Marguerite dies from tuberculosis, it is her emotions that have killed her. La Dame aux Camelias was, incidentally, modelled on Dumas' personal experience following his affair with the courtesan Marie Duplessis. Like the fictional Marguerite, Marie died of consumption not long after the affair ended.     Until the early part of the twentieth century, popular medical literature was largely in tune with fiction in the way it emphasized the importance of psychological and emotional factors in tuberculosis. To quote one everyman's guide to medicine from the 1930s: Happiness is a mighty important factor in the treatment of tuberculosis ... Mental brooding and loss of hope of recovery or of checking tuberculosis tends to drag the unfortunate individual into a deep chasm from which escape is rare. So, what happened and why have attitudes changed?     What happened was that in 1882 the German scientist Robert Koch announced to the world that he had discovered the real cause of tuberculosis -- the tubercle bacillus, Mycobacterium tuberculosis . Once it became known that tuberculosis was a bacterial infection, scientific interest in the role of psychological and emotional factors rapidly dwindled. The pendulum swung violently from the psychological to the physical. Open a contemporary medical text on tuberculosis and the chances are you will find little mention of psychology, emotions or the mind.     A lot of the old ideas about tuberculosis were plain wrong in their assumption that mental forces were sufficient to produce the symptoms by themselves; tuberculosis is undoubtedly a bacterial infection. Moreover, identifying a specific physical cause was immensely beneficial because it enabled medical science to find an effective remedy. Improvements in social conditions in the early twentieth century, followed by the introduction of effective antibiotics after the Second World War, led to an enormous decline in the incidence of tuberculosis in industrialized nations.     And yet it remains true that psychological and emotional factors do play a role in the disease. Later in this book we shall see how. It is not the nature of the tuberculosis that has changed, but the attitudes and interests of medical science. CHRONIC FATIGUE SYNDROME The misleading distinction between illnesses that are `physical' (in other words, real) and illnesses that are `psychological' (and therefore by implication not real) is starkly illuminated by the furore over chronic fatigue syndrome, otherwise known as myalgic encephalomyelitis (ME), post-viral fatigue syndrome or, if you read the tabloid press, yuppie 'flu.     It is with some trepidation that I thrust my head into the lion's den of controversy over the causes of chronic fatigue syndrome. Fierce arguments continue to rage and the medical establishment has yet to reach any consensus. In excess of eight hundred scientific publications have been devoted to the subject and the picture changes almost weekly. Those who suffer from the illness often have passionate views about its origins and anyone who gainsays them is asking for trouble.     The debate about chronic fatigue syndrome is relevant here because it exemplifies the false dichotomy between `psychological' and `physical' origins of illness. Throughout the controversy runs a seductively misleading vein: the implicit assumption that the illness must be either physical or psychological in origin. But first, what exactly is chronic fatigue syndrome?     Since 1988 the term chronic fatigue syndrome (CFS) has been used to describe a debilitating illness of unknown origin that has persisted for at least six months. As you probably know (for it is often in the news) CFS is characterized by a dreadful, disabling tiredness that is made worse by any physical exertion. This fatigue is accompanied by a motley assortment of other symptoms, including general malaise, intermittent fevers, pains in the joints, stiffness, night sweats, sore throats, poor co-ordination, visual problems, skin lesions and sleep disorders.     As if that were not enough, many CFS sufferers also experience psychological problems such as severe depression, forgetfulness, poor attention and lack of concentration. CFS can persist for years and it ruins the lives of those afflicted. Often they will be forced to give up work. Sufferers may show a measure of improvement over time, but the majority remain unwell for several years.     Cases of CFS have been reported in most industrialized nations including Britain, the USA, Canada, France, Spain, Israel and Australia. Sufferers tend to be young adults between twenty and fifty, though children can also be affected. According to the American Centers For Disease Control and Prevention, more than 80 per cent of CFS sufferers are women, most are white and their average age when the illness develops is thirty. Another common factor is that sufferers usually report having contracted some form of viral infection not long before the syndrome manifested itself.     As yet, no one has come up with a truly effective remedy for CFS. None of the drugs that have been used to treat the syndrome is of proven effectiveness and some may do more harm than good.     CFS, as currently defined, is a relatively recent phenomenon. (But then, so is AIDS; the fact that a disorder has only recently been recognized and defined does not detract from its reality.) Records of vaguely CFS-like syndromes, involving severe fatigue, muscle pains and other symptoms, date back at least two centuries. The medical history books, however, contain nothing that can be unequivocally compared with CFS before the second half of the nineteenth century, when neurasthenia became a common diagnosis. Incidentally, cultural stereotypes about the sort of person who was susceptible to neurasthenia were as strong in the nineteenth century as they are now about CFS. Neurasthenia was said to be a disease of affluent middle-class women, in much the same way that CFS has been inaccurately portrayed by the popular media as `yuppie `flu', a disease of affluent thirtysomething professionals.     It was not until the first half of the twentieth century that reports of a disorder corresponding to CFS started to accumulate. The first well-documented outbreak of a CFS-like disorder occurred in the 1930s in the USA and was attributed to a mystery virus. A similar mystery ailment afflicted the staff of a London hospital in 1955, in what became known as the Royal Free epidemic. The sufferers experienced persistent muscle pain and fatigue. To begin with the syndrome was referred to as benign myalgic encephalomyelitis. By 1956, however, it had proved to be anything but benign, and so it became known simply as myalgic encephalomyelitis, or ME.     Since they first appeared on the medical map, CFS-like illnesses have gone by a baffling variety of names including epidemic neuromyasthenia, neurasthenia, Iceland disease, Royal Free disease, atypical poliomyelitis, fibrositis, fibromyalgia, post-infectious neuromyasthenia, post-viral fatigue syndrome and myalgic encephalomyelitis. It is not certain that all these illnesses have been identical with what is now referred to as chronic fatigue syndrome. An analysis of twelve well-documented outbreaks of CFS-like disorders found they differed in various respects, notably with regard to neurological problems.     Now we come to the real meat of the problem. No one yet knows for certain what causes CFS. The arguments continue to rage and there are major divisions of opinion within the medical community. But what characterizes the whole debate -- especially as it is portrayed in the popular media -- is the implicit distinction between physical causes, which are held to be genuine, and psychological causes, which are held to be suspect.     With a few honourable exceptions, expert opinion on CFS divides neatly into two opposing camps. In one camp are those who maintain that CFS has a physical cause such as a virus or an immunological disorder. According to this view, the depression and other psychological symptoms that characterize CFS are consequences rather than causes of the underlying physical disorder.     In the opposing camp are those who argue instead that CFS is fundamentally a psychological disorder. According to this view, the physical symptoms such as exhaustion, muscle pains, fever and malaise, are manifestations of an underlying psychiatric problem.     Which view is correct? You may not be surprised to find that both are at least partially true. Many CFS sufferers have symptoms that match the diagnostic criteria for psychiatric disorders and organic disease. The evidence is undoubtedly complex and equivocal but it points towards one conclusion: that chronic fatigue syndrome has both physical and psychological components. Let us examine some of this evidence.     Most cases of CFS are preceded by a viral infection of one kind or another, and there have been repeated suggestions that a virus might lie at the root of the syndrome. For a long time the prime candidate was the Epstein-Barr virus, a member of the herpes virus family which is also responsible for glandular fever. During the 1980s chronic fatigue syndrome was widely referred to as `chronic Epstein-Barr virus infection', as though its viral origins had been firmly established. Other candidates have included retroviruses (of which HIV is an example) and polio-like viruses called enteroviruses.     There is as yet no conclusive evidence to support the viral theory and it has therefore fallen out of favour. But even if viruses are not the prime cause of CFS, it remains highly plausible that a viral infection might help to trigger or precipitate the syndrome when other causal factors are also present.     Several other physical causes besides viruses have been proposed. One theory maintains that the primary symptoms of CFS are produced by hyperventilation -- that is, abnormally rapid breathing. The evidence, however, is once again scant. Only a minority of CFS sufferers hyperventilate. On another tack, research at Johns Hopkins University in Baltimore has indicated that certain types of chronic fatigue (though not necessarily all cases of CFS) might result from abnormally low blood pressure. Yet another suggestion has been that CFS stems from a form of neurobiological disorder. One study revealed that more than a quarter of CFS patients had abnormal brain scans, and subtle changes have been found in the levels of neurotransmitter substances in the brain.     At present, the most favoured physical theories about the origins of CFS revolve around the immune system. There is growing support for the view that the symptoms of CFS result from a perturbation or abnormality in the sufferer's immune system. This immunological malfunction, it is argued, may be triggered by a viral infection which somehow throws the immune system out of kilter.     Evidence that CFS involves an immunological disorder is accumulating rapidly. Within the past few years various abnormalities have been found in the immune systems of CFS sufferers. These include alterations in the activity and surface structure of two important types of white blood cells: the natural killer cells and T-lymphocytes. (You will be hearing much more about these cells in later chapters.) It is becoming increasingly evident that CFS is associated with, if not directly caused by, a persistent, low-level activation of the immune system.     If CFS really is an immunological disorder then why do some perfectly sensible scientists and physicians persist in regarding it as primarily a psychological disorder? They persist because there is highly respectable evidence to support their viewpoint as well.     Several of the symptoms associated with CFS are also seen in psychiatric illnesses, notably depressive and anxiety disorders. A substantial proportion of those who seek medical help for chronic fatigue turn out to have a recognizable psychological problem. The authoritative Centers For Disease Control and Prevention in the USA has concluded that approximately 45 per cent of all CFS sufferers have some form of identifiable psychiatric disorder before the onset of CFS. Researchers at the University of Connecticut School of Medicine found that as many as three out of four of the chronic fatigue cases they examined could be more easily explained by psychiatric problems such as depression. To add to the picture that the mind plays a central role in the illness, Australian researchers have discovered that CFS patients exhibit significantly more signs of hypochondria than other medical patients.     Psychological theories of CFS have tended to focus on depression. Over half of all CFS sufferers exhibit clear signs of clinical depression. Often the depression appears to have preceded the chronic fatigue, suggesting that it might be a cause rather than a consequence of the syndrome. Severe depression is usually accompanied by prolonged reductions in physical activity which could, in turn, lead to a debilitating decline in muscle function. People who lie in bed for long periods become physically weak. The sleep disturbances that typify some depressive disorders might also exacerbate the sufferer's fatigue. Furthermore, it is known that severe depressive disorders are associated with changes in the immune system.     But hold fast. It is equally clear that many CFS sufferers become depressed as a consequence of their illness. It is hardly surprising that those suffering from a debilitating but unexplained illness should become depressed and abnormally preoccupied with their health. Although more women than men suffer from CFS this should not be interpreted as evidence that CFS is primarily a psychological disorder, as a few sexist pundits have implied. There are several perfectly respectable organic diseases, such as rheumatoid arthritis, which show a marked preference for one sex over the other.     At present it is probably safe to conclude that the case for CFS being primarily a psychological disorder remains unproven. The evidence for some sort of immunological malfunction is too good to dismiss. There is, however, no doubt that CFS sufferers' psychological reactions to their illness do have an important bearing on their wellbeing and recovery. Whether depression is a cause or an effect of the syndrome, it becomes a major problem in its own right and can seriously impede recovery.     The controversy over CFS is further complicated by the attitudes of those who suffer from it. People who are afflicted by a serious and debilitating disorder such as CFS want their illness to be publicly recognized as having a medically respectable cause. For most people this means a physical cause, such as a virus or an immunological disorder, rather than a psychological cause. Any suggestion that their symptoms might result from a psychiatric problem tends to provoke outrage.     This attitude is understandable. Talk of psychological causes often carries with it an unjustifiable connotation that the illness is not quite genuine. There is usually a strong whiff of `get a grip on yourself and snap out of it' in the air. Moreover, even in the late twentieth century there is still a wholly unreasonable stigma attached to mental illness. The average person would rather admit to having a physical illness, albeit a vague `mystery' virus or obscure immunological malfunction, for this absolves them of any accusations of malingering, neuroticism or weakness of character. One unfortunate outcome of this desire for a physical explanation is the tendency, in some countries at least, for CFS sufferers to shop around until they find a physician who will give them the diagnosis they want.     Ironically, it turns out that the CFS sufferers who believe most strongly in a purely physical explanation have greater difficulty in recovering from their illness. This may be because they fail to confront and deal with the psychological problems that invariably accompany the illness.     Evidence to support this conclusion has come from a study conducted by Michael Sharpe and colleagues in Oxford. They found that a form of cognitive behavioural therapy, in which CFS sufferers were helped to re-evaluate their attitudes towards their illness, was of major benefit. More than 70 per cent of CFS sufferers who received the behavioural therapy regained their ability to function normally, compared with a success rate of 27 per cent for sufferers who received only standard medical care.     The pressure to attribute CFS to purely physical causes has also had a substantial influence on how the popular media deal with the subject. Newspaper and magazine articles, TV features and self-help books tend to emphasize physical explanations for CFS and neglect its psychological aspects.     A survey by researchers at the University of London found that 69 per cent of all articles on CFS which had appeared in national newspapers and women's magazines since 1980 had favoured physical causes, compared to a mere 31 per cent of research papers in scientific and medical journals. There appeared to be a systematic bias in the popular media towards reporting physical as opposed to psychological explanations. Even the choice of name was affected. Whereas scientific papers typically used the neutral term chronic fatigue syndrome, the popular media instead favoured the more medical-sounding myalgic encephalomyelitis (ME).     Similar attitudes apply to other illnesses which, like CFS, have been tarred with the psychosomatic brush. Asthma and allergies are familiar examples. So too are inflammatory bowel disorders such as Crohn's disease and ulcerative colitis. The pendulum of opinion has swung violently back and forth over the years. Half a century ago asthma was widely regarded as an essentially psychological illness. Nowadays it is normal to play down the role of psychological and emotional factors and instead focus almost exclusively on its immunological mechanisms and physical triggers, ranging from fitted carpets to car exhaust fumes. In truth, there are good grounds for believing that both immunological and psychological factors play important roles in these diseases. Nevertheless, the overwhelming tendency is to opt for one explanation to the exclusion of the other.     As we shall see in subsequent chapters, this centuries-old opposition between mind and body, mental and physical, psychosomatic and organic, is a snare and a delusion. It has impeded scientific understanding and acceptance of some very important phenomena. There is nothing `alternative' or scientifically dubious about the fact that what goes on inside someone's brain influences their physical health.