Modern medicine can be seen as a quest to understand pathogenesis, the biological cause of an illness. Once pathogenesis—the word comes from the Greek pathos (suffering) and genesis (origin)—has been established by scientific experiment, accurate diagnoses can be made, and targeted therapies developed. In the early years of the AIDS epidemic, there were all kinds of theories about what was causing it: toxicity from drug use during sex, allergic reactions to semen, and so on. Only after the discovery of the human immunodeficiency virus helped lay such conjectures to rest did it become possible to use specific blood tests for diagnosis and, eventually, to provide antiviral drugs to improve immune defenses.

Sometimes a disease’s pathogenesis is surprising. As a medical student, I was taught that peptic ulcers were often caused by stress; treatments included bed rest and a soothing diet rich in milk. Anyone who had suggested that ulcers were the result of bacterial infection would have been thought crazy. The prevailing view was that no bacterium could thrive in the acidic environment of the stomach. But in 1982 two Australian researchers (who later won a Nobel Prize for their work) proposed that a bacterium called Helicobacter pylori was crucial to the onset of many peptic ulcers. Although the hypothesis was met with widespread scorn, experimental evidence gradually became conclusive. Now ulcers are routinely healed with antibiotics.

But what can medicine do when pathogenesis remains elusive? That’s a question that has bedevilled the field of psychiatry for nearly a century and a half. In “Mind Fixers” (Norton), Anne Harrington, a history-of-science professor at Harvard, follows “psychiatry’s troubled search for the biology of mental illness,” deftly tracing a progression of paradigms adopted by neurologists, psychiatrists, and psychologists, as well as patients and their advocates.

Her narrative begins in the late nineteenth century, when researchers explored the brain’s anatomy in an attempt to identify the origins of mental disorders. The studies ultimately proved fruitless, and their failure produced a split in the field. Some psychiatrists sought nonbiological causes, including psychoanalytic ones, for mental disorders. Others doubled down on the biological approach and, as she writes, “increasingly pursued a hodgepodge of theories and projects, many of which, in hindsight, look both ill-considered and incautious.” The split is still evident today.

The history that Harrington relays is a series of pendulum swings. For much of the book, touted breakthroughs disappoint, discredited dogmas give rise to counter-dogmas, treatments are influenced by the financial interests of the pharmaceutical industry, and real harm is done to patients and their loved ones. One thing that becomes apparent is that, when pathogenesis is absent, historical events and cultural shifts have an outsized influence on prevailing views on causes and treatments. By charting our fluctuating beliefs about our own minds, Harrington effectively tells a story about the twentieth century itself.

In 1885, the Boston Medical and Surgical Journal noted, “The increase in the number of the insane has been exceptionally rapid in the last decade.” Mental asylums built earlier in the century were overflowing with patients. Harrington points out that the asylum may have “created its own expanding clientele,” but it’s possible that insanity really was on the rise, in part because of the rapid spread of syphilis. What we now know to be a late stage of the disease was at the time termed “general paralysis of the insane.” Patients were afflicted by dementia and grandiose delusions and developed a wobbly gait. Toward the end of the century, as many as one in five people entering asylums had general paralysis of the insane.

Proof of a causal relationship between the condition and syphilis came in 1897, and marked the first time, Harrington writes, that “psychiatry had discovered a specific biological cause for a common mental illness.” The discovery was made by the neurologist Richard von Krafft-Ebing (today best known for “Psychopathia Sexualis,” his study of sexual “perversion”) and his assistant Josef Adolf Hirschl. They devised an experiment that made use of a fact that was already known: syphilis could be contracted only once. The pair took pus from the sores of syphilitics and injected it into patients suffering from general paralysis of the insane. Then they watched to see if the test subjects became infected. Any patient who did could be said with certainty not to have had the disease before. As it turned out, though, none of the subjects became infected, leading the researchers to conclude that the condition arose from previous infection with syphilis.

This apparent validation of the biological approach was influential. “If it could be done once,” Harrington writes, “maybe it could be done again.” But the work on syphilis proved to be something of a dead end. Neurologists of the time, knowing nothing of brain chemistry, were heavily focussed on what could be observed at autopsy, but there were many mental illnesses that left no trace in the solid tissue of the brain. Harrington frames this outcome in the Cartesian terms of a mind-body dualism: “Brain anatomists had failed so miserably because they focused on the brain at the expense of the mind.”

Meanwhile, two neurologists, Pierre Janet and Sigmund Freud, had been exploring a condition that affected both mind and body and that left no detectable trace in brain tissue: hysteria. The symptoms included wild swings of emotion, tremors, catatonia, and convulsions. Both men had studied under Jean-Martin Charcot, who believed that hysteria could arise from traumatic events as well as from physiological causes. Janet contended that patients “split off” memories of traumatic events and manifested them in an array of physical symptoms. He advocated hypnosis as a means of accessing these memories and discovering the causes of a patient’s malady. Freud believed that traumatic memories were repressed and consigned to the unconscious. He developed an interview method to bring them to consciousness, interpreted dreams, and argued that nearly all neuroses arose from repressed “sexual impressions.”

Freud acknowledged the fact “that the case histories I write should read like short stories and that, as one might say, they lack the serious stamp of science.” He justified the approach by pointing to the inefficacy of other methods and asserting that there was “an intimate connection between the story of the patient’s sufferings and the symptoms of his illness.” Many neurologists, responding to the demand for confessional healing, gave up on anatomy and adopted psychotherapeutics.

Soon, however, the limits of this approach, too, were exposed. During the First World War, men who returned from the trenches apparently uninjured displayed physical symptoms associated with hysteria. Clearly, they couldn’t all be manifesting neuroses caused by repressed sexual fantasies. The English physician Charles Myers coined the term “shell shock,” proposing a physiological cause: damage to the nervous system from the shock waves of artillery explosions. Yet that explanation wasn’t entirely satisfactory, either. Sufferers included soldiers who had not been in the trenches or exposed to bombing.

Harrington commends physicians who charted a middle course. Adolf Meyer, a Swiss-born physician who, in 1910, became the first director of the psychiatry clinic at the Johns Hopkins Hospital, advocated an approach he called, variously, “psychobiology” and “common sense” psychiatry—the gathering of data without a guiding dogma. Meanwhile, in Europe, Eugen Bleuler, credited with coining the term “schizophrenia,” took a view somewhat similar to Meyer’s and incurred the wrath of Freud. In 1911, Bleuler left the International Psychoanalytical Association. “Saying ‘he who is not with us is against us’ or ‘all or nothing’ is necessary for religious communities and useful for political parties,” he wrote in his resignation letter. “All the same I find that it is harmful for science.”