By Jerome Groopman
May 20, 2019
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 wason 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.”
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 wason 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.”
It was a pragmatic, empirical approach, trying to find what worked for each patient. I admired his humility and reflected that his field was not so unlike my own, where, despite a growing knowledge of the pathogenesis of cancer, one could not precisely predict whether a patient would benefit from a treatment or suffer pointlessly from its side effects. In some sense, everything my colleague and I did for the patient was in the end biological. Words can alter, for better or worse, the chemical transmitters and circuits of our brain, just as drugs or electroconvulsive therapy can. We still don’t fully understand how this occurs. But we do know that all these treatments are given with a common purpose based on hope, a feeling that surely has its own therapeutic biology. ♦
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