Infectious Madness: The Surprising Science of How We "Catch" Mental Illness


Germ Theory Redux: The Acquisition of Mental Illness

A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it.


“When I was a student in the 1960s, I once saw a man in the final stage of syphilis,” recalls English writer John Cornwell. “He was a patient on a psychiatric ward in London where I was working. White-haired, olive-skinned, emaciated, without a name or known country of origin, he had been picked up from a gutter in the London docks.”

The man lived in a state hospital for the mentally ill, where he was cared for by a kind but resigned staff. “He stood all day in the corridor leaning against the wall, doing a slow-motion foot shuffle.” The man, Cornwell tells us, was more than psychologically impaired. He could not hear or speak and seemed oblivious to his surroundings. “The ward charge nurse assured me that he was ‘unlucky, the last of his kind.’ He had not been given treatment in time to halt the final devastation of the disease.”1

Cornwell’s account reminded me of a patient I had encountered while working in an upstate New York county hospital in the 1960s. He was probably in his early sixties, but he looked younger, thanks to his vacant gaze and unfurrowed brow. Dressed in khaki pants and a T-shirt,2 he was gently propped in front of a peeling greenish wall every day, and he remained there, a slight smile playing about his lips, his equanimity undisturbed by the chaos and noise of the behavioral renegades with whom he shared the dayroom. Once, he was placed too close to the naked bulb of a torchère lamp whose shade had been lost in some forgotten drama, but when a staff member moved it to a safe distance, he neither averted his eyes nor tracked the aggressive glare. He was blind. He was also deaf, unable to speak or communicate, and he showed no signs of being able to reason or remember. He was reduced to someone who ate and defecated, who was bathed and dressed and shuffled along to nowhere with utter indifference. No one ever visited him.

What had happened to this man? The aide shepherding him to dinner whispered, “He’s got paresis, and it has destroyed his brain. It’s an old disease, you never see it now. He was treated with penicillin, but they can’t bring back the lost function.”

Lost. I hung on the adjective, which seemed to capture his condition so perfectly. Then I did a double take. “Penicillin? An antibiotic? For a severe mental disorder?” The aide shrugged as she and her charge moved on.

The antibiotic was in order because general paresis, a form of neurosyphilis, is seen in the late stages of syphilis and can emerge twenty to thirty years after the initial infection. Because it attacks in a very nonspecific manner, the neurosyphilis infection can appear in many different ways and damage many different areas of the brain. Whatever region comes under fire by the bacteria and their antibodies determines the disease’s signs and symptoms, which are legion. In both Cornwell’s patient and in the upstate New York man I observed, aural and visual systems had been destroyed and motor functions reduced to stereotyped residual movements. This damage can cause delusions, hallucinations, a diminished ability to think or speak, personality changes, impaired judgment, anger, irritability, and a sad or depressed mood. Both short-term and long-term memory may eventually disappear. There are physical consequences too, including changes in the pupil of the eye, overactive reflexes, sharp pains, a slow degeneration of the neurons’ ability to transmit messages (somewhat like that seen in multiple sclerosis), and profound muscle weakness, all of which eventually relegate paresis sufferers to bed.

The New York man was treated in a general hospital, but the man with paresis whom Cornwell encountered in England was being treated by psychiatrists in a mental institution, as befitted his profound dementia and psychological and mental losses.3 If one had to choose between the two labels, this clearly was mental illness. Or was it? Given that a paresis patient is dogged by the loss of control over his movements, loss of vision, and other physical problems, and given that all this carnage resulted from a bacterial infection, was this not a physical disorder? For that matter, does one have to choose?

“There may be said to be two classes of people in the world,” mused Algonquin Round Table habitué Robert Benchley in 1920, “those who constantly divide the people of the world into two classes, and those who do not.”4Physicians belong to the first group. They embrace the long-standing mind-body dualism that insists that mental disorders solely affect the mind, and physical disorders are the product of distorted physiology.

The fact that psychiatric diseases are now routinely located in brain dysfunction doesn’t resolve the issue, because this acknowledgment doesn’t necessarily represent a dissolution of the imaginary boundary between the physical and the mental. Instead, this stance often entails a belief in two distinct species of “mind.” In one, consciousness and mental disorders are created by and dependent on the functioning of the brain, a sort of ghostly extension of the brain into psychic space. The other mind is viewed as completely separate from the brain. But without a specific indication of precisely which mind is meant, the scientific literature is often maddeningly fuzzy and unhelpful.

To what extent is automatically ascribing mental disease to psychological trauma and genetic determinism and physical disease to tangible environmental causes just a lazy habit of thought?

For ancient Greeks, the distinction between psychological and medical illness was not the most salient or definitive characteristic of disorders. In Hippocrates’s disease taxonomy, mania, melancholia, and hysteria were treated with the same humoral-imbalance corrections that he prescribed for physical illnesses.

At the other extreme, there’s a long history of attributing psychosis to moral failure. In Deuteronomy 28:27–29, rebellious Israelites were threatened with insanity. “The Lord will smite you with madness, blindness and with bewilderment of heart,” it promises. Medieval scholars and theologians believed madness was spiritually induced, either by a failure of faith or by a punishment from the gods, a theory that died hard and that, arguably, persists in pockets of fundamentalism and faith healers.

However, by the time of the Renaissance, physicians and other Western medical experts placed mental diseases firmly in the fold of physical ailments and treated them as such.5 This view persisted for centuries. “From the Renaissance until the second half of the 18th century,” wrote R. E. Kendell in the British Journal of Psychiatry, “melancholia and other forms of insanity were generally regarded as bodily illnesses not differing in any fundamental ways from other diseases.” Even the famous psychiatrist Karl Menninger hypothesized in 1922 that schizophrenia was “in most instances the byproduct of viral encephalitis.” And although it seems counterintuitive to suggest that humans can catch depression or schizophrenia in the same way we catch the flu, this hypothesis springs from germ theory, developed by Louis Pasteur in the 1860s and Robert Koch in the 1870s, which posits that specific microbes such as bacteria, viruses, and prions (infectious proteins) cause illness.6

Although most people think only of physical illness, not mental disease, when they think of germ theory, pioneering psychiatrists like E. Fuller Torrey, the executive director of the Stanley Medical Research Institute (SMRI), have sought to change this. Torrey has long rejected the relegation of mental disease to psychological causes alone and has spent the last half a century tracing the relationship between infection and mental illness.

In the 1990s, Torrey observed that in the late nineteenth century, schizophrenia and bipolar disorder went from being rare diseases to relatively common ones. During the same period he noticed that owning cats as pets replaced regarding them as Satan’s minions, relegating them to barns for rodent control, and burning them to celebrate important holidays.

Around the time that England’s first cat show was held at the Crystal Palace, in 1871, cat ownership became popular in America. That same year brought a sharp rise in U.S. schizophrenia rates7 (except among rural Hutterites, who “almost never” keep cats as pets). Cats carry a zoonotic infection (a disease humans acquire from animals) that causes schizophrenia.

In this case, Torrey suspected Toxoplasma gondii, an infectious single-celled organism discovered in 1908 by Charles Nicolle and Louis Manceaux of Paris’s Institut Pasteur. The parasite lives in the tissues of many warm-blooded animals, but it can reproduce only within the stomachs of felids (domestic cats and other members of the family Felidae), making its survival dependent on access to cats. Most healthy adults are unaffected or only mildly sickened by a T. gondii infection, but it produces a variety of serious ailments, including toxoplasmosis, in those with compromised immune systems and in young children with immature immune defenses.


Successful Victorian English artist Louis Wain (1860–1939) was best known for his drawings, which featured large-eyed anthropomorphized cats. Wain spent his last years in a mental hospital where he had been diagnosed with schizophrenia and his images have been used in psychiatric textbooks to document the supposed deterioration of his art as his mental health worsened.

Torrey and his frequent research partner Robert Yolken of Johns Hopkins University have investigated the roles of influenza, T. gondii, and other pathogens in mental disorders. They undertook this research nearly a half century ago, when Freudian and psychosocial paradigms defined mental illness. As the next chapter explains, their efforts helped to shift this paradigm.

A microbial revolution

In his landmark book The Structure of Scientific Revolutions, Thomas Kuhn explains that those in the humanities—people who study, for example, eighteenth-century English literature, African American history, or German existentialism—are free to select the most convincing perspectives, assumptions, and causal frameworks within which to interpret their facts, but scientists are bound by a shared overarching theory. Kuhn defines that worldview, or Weltanschauung, as “what members of a scientific community, and they alone, share.”

A paradigm shift is a revolution, for it seeks to overturn the prevailing worldview. But such an overturning is not to be undertaken lightly, because the scientific community’s work, careers, and economies rest on the existing paradigm, and to nullify it is to cross the Rubicon, forever abandoning the rules that had previously defined scientific thought. Having embraced the theory of evolution, scientists cannot return to creationist myths to explain the variety of animal life. Having embraced germ theory, scientists cannot revert to believing that sin, demons, or wandering wombs cause madness or that malarious airs increase one’s risk of contracting malaria. We are stuck, as it were, with what we know.

So we must choose our revolutions carefully. Yet the one this book describes—the recognition of infection as an important cause of mental illness—may have already begun; most of us just haven’t realized it yet.

I say this because revolution takes place when anomalies arise that the existing worldview cannot explain. For example, it is hard to think of schizophrenia as a genetic disease when genetically identical twins are discordant—that is, when only one of the duo becomes schizophrenic. Such an anomaly doesn’t immediately trigger researchers to discard the theory; in fact, many such anomalies are tolerated (or ignored) until a sort of critical mass accumulates that throws the field into “a state of crisis,” according to Kuhn. New theories are then proposed, although sometimes they are not really new but ideas that have periodically resurfaced, been marginalized, decried as heresy, and forgotten. The hypothesis that infection causes or encourages common mental illnesses—and some uncommon ones—is an example, because as potential paradigm shifts go, it is a perennial. As I noted above, the theory has been with us since ancient times and reappears intermittently as part of the Western medical paradigm.

No one is suggesting that infection should completely replace stress, genetics, and psychological trauma as an explanation for mental illness, just that infection complements them and joins them as an important causative factor. And it is sometimes the primary factor.

The idea that a case of the flu might consign one to madness sounds fanciful. But consider that we are just now discerning the infectious roots of old familiar physical illnesses, many of which had been supposed to have psychological or behavioral triggers.

Cervical cancer, for example, was long ascribed to sexual immoderation in women and poor hygiene in their male partners, but it is now known to be the legacy of infection by strains of the human papillomavirus, HPV. Ninety percent of ulcers, which were once blamed on a spicy diet and uncontrolled stress, are now known to be caused by Helicobacter pylori. Contrary to the theory that held sway as late as the 1990s, heart disease is not a product of having a tense, hostile, angry type A personality but, often, of infection by bacteria including Streptococcus tigurinus and Chlamydophila pneumoniae.

Bacteria, viruses, parasites, fungi, and the infectious proteins called prions are surfacing as possible causes of mental illness as well, a theory that explains many previously mysterious anomalies. Schizophrenia, for example, has been traced to waves of influenza epidemics as well as to infections with bornavirus; species of adolescent anorexia and Tourette’s syndrome have been connected to streptococcal infections that affect the basal ganglia; and autism is linked to marauding infections from children’s own guts. This book explores the evidence for all of these and more.

Cartesian skirmishes

In the seventeenth century, René Descartes posited the existence of two fundamental kinds of substance: mental and material.8 According to this Cartesian dualism, the mental has no spatial existence, and the material cannot think. Substance dualism became popular among scientists and clerics alike, perhaps because it does not preclude the religious belief that immortal souls occupy an independent realm of existence distinct from that of the physical world.9

But dualism is far more than a philosophy in medicine; it has long been a political stance as well, adopted as the default position that legitimized and laid a scientific veneer over the struggle of physicians to dominate medical care. Based in part on this theory of dualism, physicians were able to gradually appropriate the care of the physically ill from the clergy, who had established the religious hospitals that had originally assumed the care of the sick.

Still, although the law often required at least one resident physician in a psychiatric hospital or asylum, during the centuries before the discovery of effective medication, doctors were content to leave the care of the mentally ill to the clergy and nuns. However, the majority of the mentally ill were not confined to institutions. Michel Foucault has observed that madmen were allowed to roam freely in medieval Europe and temporarily confined only when their behavior became extreme enough to pose a threat. Moreover, such confinement was long the prerogative of the family, not the doctor. “From the seventeenth century to the nineteenth century, the right to demand the confinement of a madman belonged to the family: it was the family, first of all, that excluded madmen.”10

But with the eighteenth-century advent of the industrial age, tolerance of the freewheeling idleness of the mad ceased. In 1800, there were only three thousand insane people confined in state-run and religious institutions in all of England. By the end of the century, that number had ballooned to a hundred thousand, and psychiatrists, after gaining experience in the insane asylums, could claim to be experts on madness. In his book Mind-Forg’d Manacles, medical historian Roy Porter describes the events leading up to this critical transitional period and, in particular, the changes in the way insanity was perceived.11

In France and England, the mad were now incarcerated, but not without company. “They shared their confinement with the unemployed, sick people, old people, all those who were unable to work,”12observed Foucault. Later, Freud seemed to reinforce the notion of idleness as a key component of madness when he described the mentally ill patient as “a person who could neither work nor love.”13 The fight for dominance between religious orders and physicians now had an objective: control of the asylums. Physicians vied for the “ownership” of madness, the last major province of health care where treatment was still in the hands of nonphysicians—notably the clergy, whose acknowledged realm was the care of the soul.

The very fact that separate facilities were controlled by separate professions went a long way toward convincing people that the care of the mentally ill was fundamentally different from that of the physically sick. Physicians reinforced this dualism by their insistence on “scientific” causes and models for physical illness. But they had only the naked eye and simple tools like microscopes to rely on—none of the blood assays, electron microscopes, MRIs, or CT scans that reveal pathology to us today. As a result, myopia reigned, as anyone could plainly see that autopsies of the mentally ill did not reveal the trademark anatomical findings, deterioration, or injury that one saw in physical illnesses. Moreover, the heroics of eighteenth-century medicine against physical illness—cupping, bleeding, and purging—had no discernible effect on madness.

By the late eighteenth century, insanity, or “wrongheadedness,” was regarded by physicians, clergy, and laypersons alike as fundamentally different from corporeal diseases. This schism owed much to Cartesian dualism, but it was heavily reinforced by political events that dealt the prestige of physicians a series of high-profile blows, raising questions about their ability to treat, or even recognize, mental illness.

The mad king

Chief among these events was the madness of King George, against which conventional medical practitioners seemed powerless. In 1765, George III of England, twenty-five, began to complain of an intolerable burning in his limbs and joints. His courtiers had complaints too; they found that he had suddenly become a crashing bore, collaring and speaking without pause or discernible point about hunting, his horses, and the minutiae of English government to anyone he could find. One could not exactly walk out on a garrulous king of England, no matter how narcotic his monologues, so his physicians listened. One of them actually began counting the words in the king’s long, meandering sentences, perhaps to ease the ennui. He found that each contained as many as four hundred words, rapidly spoken and tumbling together in the kind of pressured speech that usually signals urgency. The king, however, was in no hurry. He rambled repetitiously for hours on end before becoming agitated and confused, sometimes foaming at the mouth or going into convulsions. His alarmed physicians regularly huddled around him to study the royal signs and symptoms—profuse sweating, intermittent nausea, and a fast pulse—but they were clearly at sea and arrived at no diagnosis. The puzzling speech changes were similar to those of people with mania and malignant euphoria, but his physicians failed to recognize this. They resorted to commonly used measures like blistering George’s skin and dosing him with arsenic, a poisonous metalloid so toxic that it remains a commonplace device in murder mysteries. Some now think it worsened George’s state. Even after the king’s urine turned blue, the court physicians proved unable to render a diagnosis, to say nothing of a cure.

It fell to a clergyman named Francis Willis to heal him. After undergraduate studies at Oxford, Willis was ordained an Anglican priest and given a fellowship at his alma mater in 1740. In 1776 he moved to Greatford Hall in Lincolnshire and transformed it into a unique private sanatorium. In contrast to the prisonlike asylums of his day, Willis’s treatment facility went beyond restraints and straitjackets and focused on compassion, cheerfulness, industry, fresh air, and exercise. His prime tenet was respect for individual dignity; he ignored class distinctions and insisted on neatness of dress. Strangers were often astonished by the sight of humble Greatford residents—mentally ill gardeners, plowmen, and other laborers—strolling the grounds dressed like the London gentlemen among them, in silk waistcoats and breeches, powdered wigs and white stockings. Willis’s success in curing titled Englishmen caught the attention of George’s deeply concerned wife, Queen Charlotte, who brought Willis to court in 1788.

Francis Willis arrived at court, seemingly the perfect man for the job. Not only could he boast a dramatic string of successes in treating the mentally ill, but he also possessed an unusual attribute for a minister—a medical degree, if not membership in the medical fraternity.

King George’s doctors refused to accept him as a professional peer and referred to him as “nothing more than a mountebank.” Nor did English medical society in general respect his credentials; for example, he was never admitted to the Royal College of Physicians.

There may have been good reason. Early in his career, as he pursued his unusual mental-health treatments, Willis had represented himself as a physician and practiced medicine without a degree. In 1759, concerned about possible legal consequences, he induced friends at Oxford to grant him a medical degree after the fact and without the usual training—a physician in name only.14

Court physicians were inclined to forgive none of this—the specious medical degree, the iconoclastic methods, and, perhaps worst of all, Willis’s success. They clamored against Willis’s appointment, but Queen Charlotte and the English government were desperate for a cure and held firm because the king’s illness was proving disastrous. Some blamed it for the poor political judgment the king was exercising, including the vengeful iron hand he took with the American colonies that resulted in England’s humiliating defeat in the 1776 War of Independence.

Unlike the court physicians, who had offered jargon-laden explanations to the queen as they tried one unsuccessful remedy after another, Willis explained his methods in simple, accessible terms and with a warm, respectful manner. Under Willis’s care, the king was made to take fresh air and regular exercise and to pay careful attention to his grooming. Willis spoke with and sometimes lectured the king with compassion and consideration. But Willis was practical as well. He was not above restraining the king and locking him in a room in Greatford when he thought it necessary to avoid flight or self-harm.

I cannot find evidence that Willis made a definitive diagnosis, but on February 26, 1789, Willis’s bulletin described the “entire cessation of his Majesty’s illness.” George was cured, to the nation’s relief, and the Reverend Francis Willis was rewarded with an annuity of one thousand pounds, state portraits, and a special commemoration medal. He also earned national fame and became so successful that he opened a second asylum at Shillingthorpe Hall. Willis’s religious and moral methods of treating mental illness had triumphed where conventional medicine had failed.

However, the still-unnamed disease flared up occasionally, and the king gradually worsened; he spent his final decade straitjacketed and hidden away in Windsor Castle, blind, his insanity interspersed with tragic periods of lucidity. He finally died, in 1802, to be remembered as the mad king who lost America.

Postmortem diagnosis is a popular hobby, and most think that George III suffered from the genetic disease porphyria, whose name comes from the Greek word porphyrus, meaning “purple,” because royally hued excreta are hallmarks of the disease. Porphyria is often inherited, which bolsters the belief that it was George’s ailment, because it afflicted his son George IV; his granddaughter Princess Charlotte, who died during childbirth of complications of the disease;15 and other relatives of his, including Mary, Queen of Scots, and her son, King James I of England.

It wasn’t until 1871, more than a century after King George fell ill, that Felix Hoppe-Seyler determined the mechanism by which porphyria develops. Various signs and symptoms accompany the eight known types of porphyria,16 but they all involve the abnormal accumulation of porphyrins or their precursors. These compounds are required for heme production, an essential component of blood and cellular metabolism, but porphyrins are toxic when they accumulate, causing symptoms where they build up.17

The most common physical signs and symptoms include severe, burning abdominal pain, bluish to reddish urine, leg and arm paralysis or weakness, a rapid pulse, and hypertension. But they also include psychological changes such as anxiety, irritability, and confusion that can progress to depression or delirium if porphyrins hamper neural transmission.

The inability of King George’s physicians, presumably the best in the nation, to diagnose and treat the king’s lunacy dealt a staggering blow to the profession, undermining faith in medical doctors’ fitness to care for the mentally ill. And the success of the Reverend Willis seemed to validate the clergy’s primacy in dealing with emotional woes. The madness of King George also contributed to the schism between physical and mental illness by supporting the assumption that if physicians couldn’t effectively treat mental illness, it must not be physical.

Even today, the case of King George remains controversial, and doctors fail to agree on his diagnosis. Some theorize that George’s blue urine was a red herring, a side effect of the deep blue gentian flowers with which his doctors dosed him. Some are convinced that his madness was iatrogenic—that is, that he was poisoned by the arsenic used to treat him. Writing in the journal History of Psychiatry, Timothy J. Peters and Allan Beveridge make a strong case for bipolar disorder.18

But whether porphyria was the right diagnosis or not, most pertinent to this discussion is the fact that the ailment is neither strictly a mental disorder nor strictly a physical one; it is both. George’s physicians erred when they focused on the physical signs and symptoms of his illness and refused to see that any treatment must also address the disease’s heavy psychological freight, from anxiety to confusion and delirium. This myopia persists today. Given the tools and medications doctors had at the time, understanding the psychological component of George’s illness might not have helped physicians treat the king, but insisting on viewing a disease as mental or physical when indeed it was both obscured its true nature and may have obscured potential treatments as well.

The false dichotomy of mental versus physical disease was further reinforced by infamous cases of medical abuse and neglect that were addressed by clergy and social workers. For example, in 1790, Quaker Hannah Mills, a melancholic widow from Leeds, England, was brought to the York lunatic asylum. The institution prohibited all visits from her family and friends, and although Hannah was young and physically healthy, she died there just six weeks after arriving, under suspicious circumstances. Fellow Quaker William Tuke of York was appalled to hear of her fate, and he later learned that the asylum’s inmates were restrained inhumanely and warehoused in squalid conditions. The “therapeutic” emphasis of the lunatic asylum seemed to fall on controlling and quieting the human mass. Tuke was determined to create a humane treatment center utilizing Christian precepts and ethics, a facility where he could employ psychologically based approaches that came to be known as moral treatment. He raised funds and consulted his religious brethren before building the York Retreat, which proved instrumental in the development of more humane methods in the custody and care of people with mental disorders.

Tuke’s clean, attractive, dignified facilities and caring staff helped the patients weather psychological issues. So did the retreat’s welcoming of visits from family, and the Tuke center became a world-famous institution, heading a successful revolution in the care and treatment of the mentally ill.19

The York Retreat’s philosophy, like that of Francis Willis, focused on the psychological rather than the physical cause of mental illness. It helped establish madness as distinct from the body and best treated by the religious orders. In this era, when medicine could offer little for serious physical illnesses besides supportive care or ill-advised heroics, hospitals in general were unpopular destinations. Invidious comparisons between the supportive treatment offered by the Quakers and the medical hellholes where patients rarely improved further undermined faith in medical doctors’ ability to understand and care for the mentally ill.

Who would rule the asylum—doctors or religious orders?

Rush to medical judgment

Doctors like Benjamin Rush20 sought to appropriate the care of mentally ill patients by ascribing their illnesses to purely physical causes, such as infection.

Benjamin Rush, revered as the “father of American psychiatry,” knew that doctors and clergy were in contention for the control of mental-health care. And Rush, a signer of the Declaration of Independence, was a fighter; he was a surgeon with the Philadelphia militia when they battled the British, and he won appointment as surgeon general of the middle department of the Continental army.

Admittedly, the battles he chose to fight could be quixotic or downright reckless and reactionary, as when he insisted on practicing bloodletting years after it had been proven not only useless but dangerous.21He also freely administered mercury even though its toxic effects were well known. Rush was a vocal and militant abolitionist and one of the few white doctors of the era who championed black medical aspirants, but he sabotaged his fine antislavery sentiments and writings when he purchased a slave, William Grubber, in 1776, whom he retained even after joining the Pennsylvania Abolition Society in 1784.

In his fight for the prestige and primacy of American physicians, Rush insisted that the fundamental pathology of diseases of the mind was wholly somatic, lying within “the blood vessels of the brain.” In his 1812 psychiatry text Medical Inquiries and Observations upon the Diseases of the Mind, Rush included the first detailed taxonomy of mental disorders, each with its own physical cause. He cited disruptions of blood circulation and sensory overload as the basis of mental illness, and he treated his patients with devices meant to improve circulation to the brain, including such Rube Goldberg designs as a centrifugal spinning board and a restraining chair with a head enclosure.

Rush, whose image adorns the seal of the American Psychiatric Association today, tended to find physical causes, including infectious ones, for many human conditions. For example, in 1792 he theorized that the dark skin of African Americans was caused by a form of leprosy, predicting that with proper treatment, blacks could be “cured” and become white.22


Dr. Benjamin Rush designed two mechanical contrivances to aid in the treatment of the insane. The belief at the time was that “madness” was an arterial disease, an inflammation of the brain. Pictured here is the “tranquilizing chair” in which patients were confined. The chair was supposed to control the flow of blood toward the brain and, by lessening muscular action or reducing motor activity, reduce the force and frequency of the pulse. Both of Rush’s devices were supposed to exert an influence in some way on circulation, which was believed to be essential to the successful treatment of the insane. In actuality, they did neither harm nor good.

Photo: © 2008 Hoag Levins

In 1812, the politically powerful Rush led the successful charge to establish doctors’ primacy over the asylum. He did so in part by ascribing physical causes to mental illnesses, and over the next few decades, new research supported his claims. Wilhelm Griesinger’s 1845 book Psychische Krankheiten sind Erkrankungen des Gehirns (Mental Diseases Are Diseases of the Brain) convinced German physicians, generally acknowledged to be the world’s best, that mental diseases had physical origins. Still, some physicians remained skeptical. After all, changes in the “sick” brain could not be seen with the naked eye or a microscope. The evidence was thin.

Until one disorder changed everything.

Unmasking a familiar madness

Paresis is a forgotten word, but it was once a familiar species of madness. The diagnosis was given to one of every five inmates of New York City’s mental asylums by the 1920s23 and it was twice as common in Europe; Robert Schumann, Guy de Maupassant, Gaetano Donizetti, and Friedrich Nietzsche number among its victims.24 Some speculate, with less compelling data, that it also killed Hitler and Christopher Columbus.25 Also known as dementia paralytica and as general paresis of the insane, the condition was first described in 1822 by physician Antoine-Laurent Bayle. He noted that paretics, as they were called, experienced a coarsening of the personality followed by mania, vivid delusions, and dementia. After a period of months to years, this psychological deterioration culminated in a “rapid and complete mental decay” that included frequent seizures, paralysis, incontinence, psychosis, severe visual disturbances, and death.

For seventy years after Bayle described the disorder, doctors attributed this common mental malady to the usual suspects—trauma, overwork, anxiety, and even intemperance—because paresis, like many a mental disorder before it, was viewed as a punishment for depravity.

In 1857, Drs. Johannes Friedrich Esmark and W. Jessen suggested a biological cause for paresis: syphilis. To bolster their case they compiled copious statistics on paresis patients who also suffered from syphilis, and they reported their findings widely. Intrigued, other researchers began to correlate paresis with patients’ medical histories and found that a history of syphilis was extremely common. Moreover, Wassermann tests later developed to detect syphilis quantified the high correlation of syphilis in paretics by confirming that the spirochete bacteria Treponema pallidum lurked within their brains. Many researchers started to view paresis as the tertiary stage of syphilis, which often attacked the brain indiscriminately, and they began referring to it as neurosyphilis. This theory held out hope that if syphilis was ever cured, paresis could be too.

Nineteenth-century asylum keepers, however, persisted in viewing paresis as wholly mental in character. The long-standing insistence on divorcing physical illnesses from mental ones had to do with religious philosophy and culture but also with the politics of the asylum, which remained a battleground between physicians and religious and philosophical healers.26

Matters were complicated by the fact that most physicians, despite the evidence that paresis was the mental manifestation of a physical disease, continued to treat paretics with the same ineffectual therapeutics given other mentally ill patients. Traditional treatments such as “douches, cold packs, mercury, blistering of the scalp, venesection, leeching, sexual abstinence, and holes drilled into the skull [trephination]” continued—without positive results. Even when toxic mercury-based treatments for syphilis were replaced by Paul Ehrlich’s safer, more effective arsenic-based Salvarsan (also called arsphenamine and compound 606), it was not used against paresis.

But in June 1917, Professor Julius Wagner-Jauregg of the University of Vienna Hospital for Nervous and Mental Diseases undertook a radical approach. He had noticed that some paretic patients improved markedly after contracting an infectious illness that gave them fevers. He decided to fight fire with fire by turning one disease against another: he sought to suppress the symptoms of paresis by infecting its sufferers with malaria.

Wagner-Jauregg reasoned that the infamous high fevers of malaria might kill the syphilis spirochetes, or at least inactivate them, because many bacteria can operate only within a very narrow temperature range. This is why our bodies respond to many infectious diseases with fever. Wagner-Jauregg hoped that malarial fevers would raise the paretics’ body heat above the spirochetes’ survival zone, rendering them unable to do further harm.

He inoculated Austrian subjects with malaria-infected blood and was rewarded with fevers that soared to 106 degrees F. In the end, Wagner-Jauregg recorded dramatic clinical improvements, if no cures.27 The world was so gratified by the apparent success of malaria therapy that Wagner-Jauregg won the Nobel Prize in Physiology or Medicine in 1927.28 This despite the fact that the treatment proved dangerous—as many as 15 percent of the subjects died—and that his studies did not use any modern techniques for minimizing bias.29 As a result, his skewed conclusions reflected what he wished to see—that malaria therapy helped paresis patients. Wagner-Jauregg offered evidence, rather than proof, to substantiate the theory that infection causes paresis, and that evidence was not free of bias. But it—and the Nobel Prize—made powerful arguments for infection.

One might think that Wagner-Jauregg’s Nobel Prize–winning studies of this common mental disease would help elevate biological psychiatry. But by the 1930s, Wagner-Jauregg’s work was eclipsed by his compatriot and fellow neurologist Sigmund Freud.

Freud, the founder of psychoanalysis, began his career studying microscopic neuroanatomy at Vienna General Hospital, dissecting the nerves of crayfish and investigating cerebral palsy. But brain science was so primitive in the late nineteenth century that the basic workings of the neuron were a mystery, and Freud left objective physiologic science behind, choosing instead to study the mind’s role in repressing drives that are “powerful enough to evoke madness” when neglected.30 To combat such repression, Freud refined the “talking cure,” or the practice of psychoanalysis, in which doctors perceive and interpret the unconscious struggles of patients as a means of helping them to achieve greater self-awareness.

Freud’s conception of mental illness as arising from psychic conflicts resonated with mental-health providers and their patients, much more so than the biophysiological, infection-related model did, and the psychoanalytical approach transformed twentieth-century psychiatry. Upstaging the infectious nature of paresis, Freudian psychoanalysis swept aside the startling role of infection in mental illness31 and reinforced the divide between mental and physical illness.

Under the auspices of the Rockefeller Foundation, Mark Boyd became one of many researchers who sought to reproduce Wagner-Jauregg’s celebrated successes. But this research also lacked some of today’s controls against researcher bias. Double-blind studies and other techniques that we currently rely on to reduce bias in study interpretation were not in common use in that era, and these experiments were repeated throughout the first half of the twentieth century with the same lack of rigor. So once again, it was all too easy for researchers to see what they wished to see—that their paresis patients were being helped by infection with a chronic, debilitating disease.

But there still was no cure for syphilis—which meant there was none for paresis. Because demonstrating the infectious nature of paresis did not appreciably change the way doctors treated it, the discovery did not improve the clinical course of the disease. What’s more, associating paresis with syphilis added the stigma of venereal disease to that of insanity. As historian Allan M. Brandt noted in his masterly No Magic Bullet, “Venereal disease remained a symptom of social decay and sexual evil,” and psychiatrist Joel T. Braslow observed that “newspaper and magazine articles in periodicals such as the New York Times, Good Housekeeping, Scientific American, Hygeia, Reader’s Digest, Newsweek, and Popular Mechanics depicted neurosyphilitics in highly value-laden, moralistic terms,” using phrases such as “‘wretched maniacs,’ ‘those whose sins it rewarded,’ and ‘doomed human derelicts.’”32

Inspired by Wagner-Jauregg’s Nobel and buoyed by the clinical benefits touted in parallel studies, researchers continued with malaria-therapy experiments until 1943, the year when a portentous paper by John F. Mahoney33demonstrated that penicillin cured syphilis. The antibiotic arrested paresis too, proving that the mental illness was indeed a late stage of syphilis infection. As physicians wielded penicillin against paresis, it all but vanished from the United States, and today, you’d have to visit a developing nation with poor health care to find a case.

The question of malaria therapy’s effectiveness became clinically moot, at least against paresis in the West, but the enigmatic prospect of using one disease to fight another lingers as an unanswered question of medical history.

Germ theory: a paradigm shift

Before Wagner-Jauregg won the Nobel and Freud forged the future of psychiatry, a paradigm shift had already taken place that transformed science’s approach to the nature of disease. It is the very framework that supports the role of infection in mental illness—germ theory. Developed by Louis Pasteur and Robert Koch, germ theory posits that specific microbes such as bacteria, viruses, and prions (infectious proteins) cause illness.34

Although nineteenth-century German bacteriologists Robert Koch and Friedrich Loeffler were the first to provide evidence that infinitesimally small life-forms called microbes caused disease, scientists as early as the seventeenth century had suggested that tiny beings might be the source of illness. They could produce no credible proof, however, and it was not until 1883 that the microscope revealed the pathogens, disproving theories that illness was caused by sinful behaviors or poisonous vapors.

Germ theory—the discovery of these tiny agents of infection—accelerated treatment and prevention. Pasteur saved the lives of millions of women35 when he discovered the cause of childbed fever. Germ theory also revealed to him that bacteria were the source of wine spoilage and he figured out how to prevent it through a process we still call pasteurization—heating the libations to kill bacteria, a deeply appreciated feat in oenophile France. For his part, Koch discovered that the airborne Mycobacterium tuberculosis caused the dreaded tuberculosis and that Bacillus anthracis caused anthrax. As a result of these findings, infectious agents were widely acknowledged as a cause of disease that had previously been ascribed to vague “miasmas” and “air.”

By the twentieth century the paradigm shift to germ theory had changed the face of medicine. The most common, terrifying killers, including tuberculosis, smallpox, influenza, diphtheria, yellow fever, bubonic plague, and whooping cough, were now known to result from infection by pathogens. Accordingly, scientists turned their attention to devising vaccines, antibiotics, and public-health measures to stem their spread. The smallpox virus was eradicated, except for some samples preserved in Western laboratories. As medical innovations tamed these illnesses, Americans began living longer and eventually dying of other illnesses like cancers and heart disease (although we now recognize many of these diseases as infectious in origin as well).

But the germ-theory paradigm shift bypassed mental illness. Paresis was recognized as infectious and then rooted out of the asylum by penicillin, but diseases like schizophrenia, depression, bipolar disorder, and obsessive-compulsive disorder remained the province of mental health, with its emphasis on talk therapy, behavioral conditioning, cognitive therapy, and other manipulations of the mind. By the 1980s new medications based on altering brain chemistry tacitly acknowledged the physical nature of much mental illness, but the supposed dichotomy between physical and mental illness stubbornly remained and still does to this day. Thus it is that even in our time, when most psychiatrists treat only with medication, the growing evidence that infection makes a strong contribution to mental illness is studiously avoided.

This book makes the case for ending that avoidance. In the chapters that follow, I will discuss the evidence that influenza as well as the parasite Toxoplasma gondii are implicated in schizophrenia and von Economo’s encephalitis. I’ll talk about how Group A streptococci can cause anorexia, obsessive-compulsive disorder, and Tourette’s syndrome and how microbes residing in our guts cause some cases of autism as well as various autoimmune diseases with psychiatric components. I’ll look at how prions, or infectious proteins, cause Creutzfeldt-Jakob disease, or CJD, the human version of mad cow disease, which is marked by personality changes, depression, memory loss, and impaired thinking as well as movement disorders.36 I’ll explore how rare complications of measles and some forms of food poisoning engender mental derangement serious enough to require institutionalization. Certainly infection is unlikely to stand alone as a cause in many ailments, as it does for paresis; the traditional risk factors of genetics, stress, and other environmental pressures are sure to apply as well. Yet most researchers into the infection connection estimate that known pathogens account for 10 to 20 percent of cases of mental illness.

Paresis is not the only precedent. Belief in the infectious roots of madness is not an exclusively postmodern view; in fact, a few mental illnesses have long been recognized as infectious. Rabies immediately comes to mind. Caused by one of the lyssaviruses, named after Lyssa, the Greek goddess of madness and rage, the disease is a ferociously aggressive mental state caused by the bite of an infected animal—or human. Ergotism is another example: ergot, fungi that infect rye, produces the alkaloid ergotamine, which causes burning sensations, tissue loss, psychosis, hallucinations, irrational behavior, seizures, convulsions, and even death. Eating bread or other foods made with tainted rye has been recognized as a cause of dramatic syndromes such as St. Anthony’s fire during the medieval period and the Great Fear in France.37 Some have ascribed the mass hysteria of the Salem witch trials to ergotism, although others dispute that theory.38

Despite this, our authoritative references still maintain the ironclad distinction between mental and physical disease. Editors of the Diagnostic and Statistical Manual of Mental Disorders, known as the DSM,admit that the text has reinforced the strict but often imaginary dichotomy between mental and physical disease. “The term ‘mental disorder’ unfortunately implies a distinction between ‘mental disorders’ and ‘physical disorders’ that is a reductionist anachronism of mind/body dualism,” the (now superseded) DSM-IV website notes, adding that “the term persists… because we have not found an appropriate substitute.”39

Still, the very word mental in mental disorders seems to contradict the idea of a biomedical basis for these conditions, even though some consciousness research in neuroscience has emerged with evidence for just such biological underpinnings. Writing in Neuroscience, Chun Siong Soon and his team found that “in some contexts, the decisions that a person makes can be detected up to 10 seconds in advance by means of scanning their brain activity.”40Furthermore, subjective experiences and covert attitudes are observable, providing41 “strong empirical evidence that cognitive processes have physical basis in the brain,42 although it does not completely dispel the possibility of mind-body distinction.”

The price of revolution

Maybe it shouldn’t surprise us that mental-health professionals continue to behave as though the mind/body divide were real. One survey found that physicians think of mental illness as a continuum, from the physiological disorders, such as autism, to the nonbiological disorders, such as adjustment disorder.43 Respondents said they believed medication was the best treatment for the more biological diseases and talk therapy was best for the nonbiological disorders.

The problem lies in whether these same doctors actually understand which mental disorders are biological and which are not. Writing in the Wilson Quarterly, psychological anthropologist Tanya Luhrmann of Stanford describes the Research Domain Criteria, a project that proposes to dispense with the diagnoses enshrined in the Diagnostic and Statistical Manual of Mental Disorders and elsewhere. It instead seeks to address the specific challenges and issues facing individual patients, from sadness to phobias to memory loss. But, she writes, there is too much at stake economically for this plan to go into effect, because the payment system depends on “the fiction of clear-cut, biologically distinct diseases.”44

She’s right. Economics is an important factor in any element of U.S. medicine. But there’s even more at stake here, because, as Thomas Kuhn reminds us, scientists’ bodies of work, careers, livelihoods, and prestige rest on the existing paradigm, so toppling it can be a very risky and difficult enterprise. Resistance is natural, making revolution painful and costly in terms of far more than money.

Yet, as research gains in sophistication and medical knowledge increases, so do examples of how permeable the diaphanous membrane is between sickness of the mind and ailments of the body.

We know, for example, that infection profoundly changes a sick person’s behavior in a predictable manner. We can see this very easily in the elderly whose immune systems have lost their vigor. When my mother was confined to a nursing home with dementia, she had lost the ability to walk, initiate speech, or do any but the simplest tasks, but she smiled alertly, nodded meaningfully, and understood much of what was said to her. We had many conversations without her saying a word other than good or yes. But whenever she became listless, unengaged, and uncommunicative, failing to eat and interact with others, I would suspect an infection, and I soon learned that other families in her nursing home saw the same dynamic with their loved ones.

The nurses tended to validate our hunches. In fact, the positive screens sometimes seemed a formality, verifying the infection that everyone already suspected based on the elder’s sick behavior. Of course, many factors can be involved, but behavioral changes in response to an infection are not confined to people with paresis or the elderly. Whether you tend to be reclusive, gregarious, or somewhere in between, your behavior hews closely to a new norm when you are stricken with, say, the flu, as Martin H. Fischer, MD, hinted when he quipped, “When a man lacks mental balance in pneumonia he is said to be delirious. When he lacks mental balance without the pneumonia, he is pronounced insane by all smart doctors.”

We see the same overlapping of the physical and the mental in established mental diseases caused by physical infections, like paresis and rabies, but also in novel infections that lead to more familiar diseases, like depression and schizophrenia.

The threat may begin in the womb, as the next chapter reveals.

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