Shrinks

by Jeffrey A. Lieberman

  In 1960, Life magazine called Kline “a pioneer of the new drug therapies for mental illness.” He was celebrated throughout medicine and elected to the most elite scientific societies. Perhaps more than any other single person, Nathan Kline was also responsible for the deinstitutionalization of patients from mental hospitals in New York State: Buoyed by the dramatic results of his ongoing psychopharmacologic research, Kline supplied Governor Nelson Rockefeller with a vision of medication-driven community mental health care, an effort that dovetailed with President Kennedy’s introduction of the Community Mental Health Act in 1963. Kline was sought out by celebrities and politicians for treatment and frequently lauded in the press. His meteoric rise demonstrated the transformative effects that drugs were having on psychiatry and mental health care—but it would also reveal the hazards that accompanied the rapid pharmaceuticalization of psychiatry.

  Nathan Kline was at the height of his career when I first met him in 1977 at a psychopharmacology meeting sponsored by the National Institute of Mental Health in Florida. I was in my second year of residency training in psychiatry and had been dispatched to the Sonesta Hotel on Key Biscayne by my mentor to present the results of our investigation of a new antipsychotic drug.

  The roughly three hundred attendees were a mix of academic researchers and National Institute of Health scientists, along with representatives from pharmaceutical companies. On the evening of the first day’s sessions, a cocktail reception was held on the terrace adjacent to the pool overlooking the beach. I approached the crowd and was struck by a memorable sight. On one side of the terrace was a rowdy group of conference-goers gabbling away in shorts, bathing suits, and T-shirts. On the other side, reclining on a chaise longue overlooking the ocean, was Nathan Kline, looking regal in an immaculate white tropical leisure suit, and surrounded by a coterie of attendants. He held a tropical drink in one hand as he directed his minions with the other, like a monarch granting an audience to his subjects.

  Shortly before the conference I had read a report in the Archives of General Psychiatry about Kline’s research with a new compound called beta-endorphin, which he had administered to schizophrenia patients with dramatic results. This was an astonishing finding, as the only known antipsychotics were all chemical variants of chlorpromazine, whereas beta-endorphin was a naturally occurring peptide that was produced by the body, a completely different kind of compound. After discovering an entirely new class of antidepressants (the MAO-inhibitors), it appeared that Kline had now discovered an entirely new class of antipsychotics.

  I nervously walked over and introduced myself. I asked him several questions about his study, as much to impress him with my knowledge as to deepen my understanding of his. At first he greeted me warily, but after realizing that I was a genuine admirer he warmed up and responded enthusiastically. He concluded by thanking me magisterially for my questions.

  Only later did I learn that despite his fame, Kline had become something of a pariah in scientific circles. In modern parlance, he had “jumped the shark.” It should have been apparent to me at the Florida conference that his pompous behavior would be alienating to his colleagues, but as a young resident I was naïve and starstruck. I would soon learn firsthand his sins against the medical codes of conduct.

  As I continued my residency at St. Vincent’s Hospital in Manhattan, I began to encounter what many psychiatrists in New York dubbed the “Kline experience.” Patients of Dr. Kline began to drift into the emergency room and the outpatient clinic, and as new admissions to the psychiatric inpatient unit. All were victims of Kline’s risky and sometimes heedless practice. They suffered from severe adverse reactions caused by elaborate cocktails of psychotropic medications—or from the effects of their abrupt withdrawal. Whereas most psychiatrists treated depression, bipolar disorder, schizophrenia, or anxiety disorders by prescribing one or two medications, possibly three on a rare occasion, Dr. Kline frequently prescribed extravagant combinations of five or more medications in their most potent forms, often at high doses. It got to the point where I was able to guess whether a patient was one of Kline’s simply by glancing at the list of medications on his chart. No one else had the confidence—or recklessness—to prescribe such witches’ brews of mind-altering cocktails.

  Nathan Kline (1916–83), a flamboyant pioneer of psychopharmacology. (Portrait of Dr. Kline by David Laska, courtesy of Dr. Eugene Laska and the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY; photograph courtesy of Koon-Sea Hui, MPhil, PhD)

  In the end, it was not the death of a patient or a massive malpractice suit that prompted Kline’s downfall, though that was surely a possibility. It was the very study that had inspired me to timidly seek an audience with him in Florida. Kline had failed to submit the protocol for his study to an Institutional Review Board for approval, an ethical and legal requirement when conducting medical research on human subjects. Not only that, he hadn’t bothered to get the proper informed consent from the patients to whom he was administering experimental psychoactive compounds. Apparently, in his eagerness to achieve another stunning scientific success (and perhaps win a Nobel), he had rushed to be the very first researcher to publish on a potential new class of psychopharmaceutical.

  The FDA investigated Kline, and in 1982 he was compelled to sign a federal consent decree swearing to never conduct research on drugs again. Psychoactive drugs had launched Kline’s career—and they ended it in ignominy. A year later, he died on an operating table from complications arising from an aortic aneurysm.

  Despite Kline’s excesses, the advent of psychopharmacology had irrevocably changed the field of psychiatry for the better. Those suffering from severe mental illness now could hope for relief and genuine recovery. But it also created tensions in a field struggling to redefine itself. This quandary was not lost on the media, which laid bare the emerging ideological fault lines. In 1955, in the wake of chlorpromazine’s redesign of the mental health landscape, Time magazine reported, “The ivory-tower critics (mainly psychoanalysts) argue that the red-brick pragmatists—state hospitals—are not getting to the patients’ ‘underlying psychopathology’ and so there can be no cure. These doctors want to know whether he withdrew from the world because of unconscious conflict over incestuous urges or stealing from his brother’s piggy bank at the age of five. In the world of red-bricks, this is like arguing about the number of angels on the point of a pin.”

  But before the psychopharmacologists could permanently tip the balance away from the ivory-tower psychoanalysts, one final revolution was still necessary.

  Part III

  Psychiatry Reborn

  If there is one central intellectual reality at the end of the twentieth century, it is that the biological approach to psychiatry—treating mental illness as a genetically influenced disorder of brain chemistry—has been a smashing success. Freud’s ideas, which dominated the history of psychiatry for much of the past century, are now vanishing like the last snows of winter.

  —EDWARD SHORTER

  Chapter 7

  Out of the Wilderness: The Brain Revolution

  Here is this three-pound mass of jelly you can hold in the palm of your hand, and it can contemplate the vastness of interstellar space. It can contemplate the meaning of infinity and it can contemplate itself contemplating on the meaning of infinity.

  —VILAYANUR RAMACHANDRAN

  Every pusillanimous creature that crawls on the earth or slinks through slimy seas has a brain!

  —THE WIZARD OF OZ

  If I Only Had a Brain

  In The Wizard of Oz, the Scarecrow yearns for a brain. To his surprise, the Wizard informs him that he already possesses one—he just doesn’t know it. For most of the twentieth century, the same might have been said about psychiatry—it was brainless. Though ostensibly a medical specialty devoted to abnormalities of thought and emotion, psychiatry did not turn its attention to the organ of thought and emotion until the 1980s.

  Psychiatrists were not alon
e in ignoring the brain—the level of interest in the pinkish stuffing inside our heads has long been woefully disproportionate to its importance, especially when compared to its main rival for anatomical preeminence: the heart. When we marry or fall in love, we give our heart to another, but never our brain. When someone leaves us we feel heartbroken, not brainbroken. Generous people are said to have big hearts or be good-hearted or have hearts of gold rather than brains of gold. Even the Bible invests the heart with psychic properties: “And you shall love the Lord your God with all your heart.”

  But the heart is nothing more than a glorified pump. Its sole function is to contract and expand, over and over, two billion times over the average lifespan, pushing blood through the body. In contrast, the human brain is an unfathomable supercomputer that exceeds every other organ in complexity by many orders of magnitude. Starting as an unimaginably tiny neural tube forming three weeks after conception, the brain grows at an astonishingly rapid pace to become a three-pound corrugated doughlike lump—comprising a hundred billion neurons communicating through thirty trillion connections—that somehow regulates our heart rate, body temperature, and appetite while simultaneously driving us to sing melodies, sculpt statues, code software… and pen lengthy treatises about itself. Comparing the heart to the brain is like comparing a child’s dollhouse to New York City.

  One thing that has always confounded any researcher wishing to scrutinize the brain is the fact that this arcane supermachine is encased within an impenetrable vessel: the skull. Until very recently, the only way to actually examine a thinking, feeling brain was through extremely invasive procedures or by carving up a lifeless brain at autopsy. It’s not very surprising that the first science-tinged theory of the brain was founded on a rather ingenious (if completely misguided) method of circumventing the need to directly access the brain: phrenology.

  Developed by the German physician Franz Joseph Gall in 1809, phrenology took as its starting point the assumption that different parts of the brain controlled specific functions. One region controlled hunger, another controlled lust, another anger. As neuroscientists would later confirm, this assumption turned out to be largely correct: specific mental functions are indeed localized in specific brain regions. Gall’s next two hypotheses were not so lucky, though. He believed that if a person exhibited disproportionate activity issuing from a particular mental function—excessive lust, for instance—then (1) the part of his brain that governed lust would be enlarged, and (2) the skull above this enlarged part of his brain would also be enlarged. Thus, Gall claimed it was possible to discern a person’s true psychological constitution by measuring the relative size of the various bumps and indentations on his head. You might say that phrenology was the world’s first crude attempt at brain mapping.

  Gall diligently appraised the skull geometries of prisoners, hospital patients, and asylum lunatics, and reported many sensational “findings.” The heads of the stark raving mad featured a depression toward the back of their skull, which Gall interpreted as indicating a diminishment of their faculty of self-control. Young thieves possessed bumps just above their ears. All of these purported correlations between skull geometries and behavior turned out to be completely groundless. We now know there is no connection between a person’s personality and the shape of his head.

  Unable to provide any useful predictions about human behavior, phrenology had completely fallen out of favor by the middle of the nineteenth century, about the same time that Wilhelm Griesinger declared that mental illnesses were “illnesses of the nerves and brain.”

  A century later, in the late 1940s and ’50s, the first cohort of brain-focused psychiatrists began to emerge in American psychiatry. Though they were far outnumbered by the Freudians, members of organizations like the Society of Biological Psychiatry revived the brain-focused studies of their German forebears. But they did not limit themselves to the examination of postmortem specimens; they also trolled for clues in the bodily fluids of living patients—the blood, cerebral spinal fluid, and urine. The new generation of biological psychiatrists believed that somewhere in this organic soup they would find their Holy Grail: a biological marker for mental illness.

  Just as John Cade believed that mania was produced by a metabolic toxin, the biological psychiatrists hypothesized that mental illness might be caused by some pathogenic organic compound aberrantly produced by the body—a compound presumably detectable through laboratory tests. The inspiration for this hypothesis was a metabolic disorder known as phenylketonuria (PKU), a condition caused by a genetic mutation that prevents the liver from metabolizing phenylalanine, an essential amino acid. The faulty metabolism in individuals with PKU produces an accumulation of a substance known as phenylketone. Too much phenylketone interferes with the brain’s development and leads to intellectual disability and behavioral problems. Thus, phenylketone serves as a biomarker for PKU: If physicians detect the compound in a patient’s blood or urine, it indicates he probably has the disorder, since people without this condition have extremely low levels of phenylketone.

  In the mid-1960s, biological psychiatrists began searching for a biomarker by comparing the urine of mentally ill patients and healthy individuals with a new technique called chromatography. Chromatography uses a special chemical-sensitive paper that turns a different color for each distinct compound it comes into contact with. If you place a drop of urine from a healthy person onto one strip of paper and a drop of urine from an ill person onto another and then compare the colors on each strip, you can identify differences in the types and amounts of the urine’s chemical constituents—and these differences might reflect the biochemical by-products of the illness.

  In 1968, the biological psychiatrists’ chromatographic efforts paid off with a sensational breakthrough. Researchers at the University of California at San Francisco discovered that the urine of schizophrenia patients produced a color that did not appear in the urine of healthy individuals—a “mauve spot.” Enthusiasm among biological psychiatrists only increased when another group of researchers discovered in the urine of schizophrenics the existence of a separate “pink spot.” Many believed that psychiatry was on the verge of a new era, when psychiatrists could discern the entire rainbow of mental illnesses merely by instructing patients to pee on a scrap of paper.

  Unfortunately, this urine-fueled optimism was short-lived. When other scientists attempted to replicate these wondrous findings, they uncovered a rather mundane explanation for the mauve and pink spots. It seemed that the putative biomarkers were not by-products of the schizophrenia itself, but by-products of antipsychotic drugs and caffeine. The schizophrenic patients who participated in the chromatography studies were (quite sensibly) being treated with antipsychotic medications and—since there was not much else to do in a mental ward—they tended to drink a lot of coffee and tea. In other words, the urine tests detected schizophrenia by identifying individuals taking schizophrenia drugs and consuming caffeinated beverages.

  While the search for biomarkers in the 1960s and ’70s ultimately failed to produce anything useful, at least it was driven by hypotheses that posited physiological dysfunction as the source of mental illness, rather than sexual conflicts or “refrigerator mothers.” Eventually biological psychiatrists broadened their search for the diagnostic Holy Grail beyond the bodily fluids. They turned instead to the substance of the brain itself. But since the organ was encased within impenetrable bone and sheathed in layers of membranes, and couldn’t be studied without risking damage, how could they hope to peer into the mystifying dynamics of the living brain?

  Throwing Open the Doorways to the Mind

  Since so little was learned about mental illness from the visual inspection of cadaver brains in the nineteenth and early twentieth centuries, psychiatrists suspected that any neural signatures associated with mental disorders must be much more subtle than the readily identifiable abnormalities resulting from strokes, age-related dementias, tumors, and traumatic brain injuries. What
was needed was some way to peer inside the head to see the brain’s structure, composition, and function.

  The invention of X-rays by Wilhelm Roentgen in 1895 seemed, at first, the longed-for technological breakthrough. X-rays aided the diagnosis of cancer, pneumonia, and broken bones… but when early radiographs were taken of the head, all they showed was the vague outline of the skull and brain. Roentgen’s rays could detect skull fractures, penetrating brain injuries, or large brain tumors, but not much else of use to biologically minded psychiatrists.

  If psychiatrists were to have any hope of detecting physical evidence of mental illness in the living brain, they would need an imaging technology that revealed the fine architecture of the brain in discernible detail or, even better, somehow disclosed the actual activity of the brain. In the 1960s, this seemed an impossible dream. When the breakthrough finally came, the funding that enabled it came from a most surprising source: the Beatles.

  In the early 1970s, the EMI corporation was primarily a record company, but they did have a small electronics division, as reflected in their unabbreviated name: Electric and Musical Industries. EMI’s music division was raking in enormous profits from the phenomenal success of the Beatles, the world’s most popular band. Flush with cash, EMI decided to take a chance on a highly risky and expensive project in its electronics division. The EMI engineers were trying to combine X-rays from multiple angles in order to produce three-dimensional images of objects. Surmounting technical obstacles using profits from “I Want to Hold Your Hand” and “With a Little Help from My Friends,” EMI engineers created a radiographic technology that obtained images of the body that were far more comprehensive and detailed than anything in medical imaging. Even better, the resulting procedure was not invasive and elicited no physical discomfort in the patients. EMI’s new technology became known as computed axial tomography—more commonly referred to as the CAT scan.