by Sam Kean
Sex and Punishment
In addition to nerves and neurons, the brain also sends out signals via hormones. Hormones play an especially important role in regulating emotions, which provide a crucial bridge between brain and body.
Neurosurgeon Harvey Cushing made quite a first impression. At 8 a.m. on New Year’s Day 1911, a surgical resident named William Sharpe reported to Cushing’s hospital in Baltimore for his first day of duty. If Sharpe expected an easy day—a tour, some chitchat, reviewing a few charts—Cushing had other ideas. Sharpe walked in to find Cushing wrist-deep inside a dog’s skull, digging out the poor mutt’s pituitary gland. Without preamble or introduction, Cushing handed Sharpe fifty dollars to bribe a priest and ordered him to rush to a Washington, D.C., funeral parlor. There, Sharpe was to remove all the endocrine glands—plus the brain, heart, lungs, pancreas, and testicles—of one of Cushing’s patients, a giant. And since the funeral would start at 2 p.m., Sharpe had better scoot.
Neurosurgeon Harvey Cushing. (National Library of Medicine)
At the funeral home the priest on duty collected his take and led Sharpe to the back room where the giant, John Turner, lay in a custom-built coffin. An illiterate brick-wagon driver, Turner had endured an excruciating growth spurt starting at age fifteen; he’d ended life, at thirty-eight, a seven-foot-three-inch Goliath barely able to walk. Sharpe asked the priest to help him lift Turner out of the casket, but the priest threw up his hands: it turned out that, contra Cushing, no one had permission to perform an autopsy. In fact, Turner’s family opposed it. With no hope of moving the 343-pound giant, Sharpe had to flay him right there in the coffin. He undid the spinnaker-sized tuxedo jacket, and made the first incision around 11 a.m. Soon lost in his work, he barely heard the mourners gathering in the front parlor.
Around 1:00 p.m., Sharpe realized he’d made a tactical mistake: he should have started with the head. Of all the glands he had to secure, the pituitary—a small hormone factory, and Cushing’s darling gland—was the most important. But it resided deep within the skull, so excavating it would require sawing through the skullcase, a noisy process. And by now, Sharpe could hear Turner’s family getting restless in the other room—the priest had no good answer for why they couldn’t see the body just yet. Sharpe sawed quickly, but Turner’s overgrown skull turned out to be an inch thick in places. Sharpe soon heard fists pounding on the door, demanding to know what that noise was.
After popping the skull open, Sharpe peeled back the cobwebs of connective tissue around the brain and exposed the pituitary. The pituitary gland dangles beneath the brain like a dollop of tissue about to drip off. It’s normally pea-sized but often swells grotesquely inside giants, due to tumors. Sharpe didn’t have much time to examine Turner’s gland, though, since the occupants of the front room had outright revolted by then.
Sharpe scrambled to stitch Turner up and gather his organs, and just as he finished, the dam burst. Luckily the priest (not wanting two dead bodies on his hands) had already called a cab for Sharpe. And as Turner’s family spilled into the room, Sharpe dashed out the back door, hopped into his taxi, and yelled go. As the car sped away, a rock hurled in fury smashed against the trunk.
Back in Baltimore, Sharpe deposited the glistening viscera in a refrigeration unit. He called Cushing and retired early that night in a resident dorm, satisfied and proud. But just before dawn a hand shook him awake. Cushing stood over him, volcanic. “You missed the left parathyroid body!” he screamed. Sharpe tried to explain about the priest and the tuxedo and the rock—not to mention the fact that he’d never heard of the parathyroid body. Cushing cut him short and fired him.
Although inconsolable, Sharpe let two fellow residents treat him to breakfast in the hospital cafeteria. They explained that Cushing erupted like this all the time—he had poor emotional control. Halfway through their meal, the PA system crackled: Paging William Sharpe. William Sharpe to Dr. Cushing’s office. Sharpe must have trembled as he approached the door—had he missed something else? But he found Cushing calm and levelheaded. He showed Sharpe a parathyroid gland and explained its function. Turning back to his work, he wished Sharpe a good day and never mentioned the incident again. (Sharpe, of course, remembered it for the rest of his life.)
Those twenty-four hours were classic Cushing. There was a legitimate medical question at stake; he sought out the answer ruthlessly; and somewhere along the way he lost his head. Even during his childhood in Cleveland, his family had called him Pepper Pot for his tantrums, and as an adult he blew up at nurses and residents almost daily. But Cushing’s rage was easy-come, easy-go, and even those who got scorched couldn’t deny his brilliance.
After attending Yale University—where he’d fallen out with his father because he insisted on playing baseball for the Bulldogs instead of focusing solely on academics—Cushing sailed through Harvard Medical School and secured a job at The Johns Hopkins Hospital in Baltimore. He promptly derided Baltimore as dull, with row houses “as alike as streptococci” bacteria. But he found it convenient that his superior at Hopkins was a morphine addict,* since this left him unsupervised and free to experiment with new technologies. He used electricity to stimulate the brains of epileptic patients and built a device that displayed a patient’s blood pressure and pulse automatically, so surgeons could tell at a glance if there was trouble. Cushing also started using X-rays in 1896, just a year after their discovery, to hunt for brain tumors and for bullets lodged in people’s bodies. (Fortunately for him, he had too many other obligations to experiment much with X-rays; a less busy colleague died of radiation poisoning.)
Cushing eventually devoted himself to brain surgery, especially brain tumors. And although his exact and demanding temperament didn’t endear him to his staff, those qualities did make him an excellent surgeon. Unusually for the time, he bothered distinguishing between different species of brain tumors and adjusted his approach accordingly. His ritualistic devotion to cleanliness reduced mortality rates for brain surgery from around 90 percent to 10 percent. And when a patient did die, he used the autopsy to check what he’d done wrong, which was almost unheard of. Finally, he had superhuman concentration. Brain surgeries can take ten hours or more—surgeons sometimes joke about the tumor growing back before they can sew the patient up. But Cushing could work on his feet indefinitely without flagging, and if he caught an assistant daydreaming, he’d snap—a flashback to Yale—“Eyes on the ball!”
By age thirty-two he’d built a comfortable practice, and could have cruised for the next few decades. But a devastating mistake changed the course of his career. In December 1901 he met a fourteen-year-old girl who was chubby, nearly blind, and sexually immature (no breast buds, no menarche). Cushing diagnosed excessive pressure inside her skull and opened her up to drain the excess fluid. She didn’t improve, and soon died. The autopsy, to Cushing’s chagrin, revealed a cyst pressing on her pituitary gland, a possibility he’d overlooked.
To be fair, most surgeons of that era would have overlooked it. Although not technically part of the brain, the pituitary sits on the brain’s south pole, the neurological equivalent of Antarctica, so reaching it required a long, invasive surgery. Even when surgeons did reach it, they hesitated to touch it, since it nestles right near the optic nerves (hence the girl’s near blindness). And no one knew what good touching it would do anyway, since its function remained a mystery. Some called it an evolutionary relic, like an appendix, while others linked it to a baffling array of diseases: face and hand deformities, obesity, skin problems, even (contradictorily) both gigantism and dwarfism. Given its obscurity and inaccessibility, most surgeons preferred to pretend it didn’t exist. Cushing was not most surgeons, and determined to get to the bottom of it.
However puzzled, the more Cushing read about the gland, the more it intrigued him—especially its association with growth disorders. As a lad, whenever the circus had swung through Cleveland, Cushing had raced to see the sideshows, gaping for hours at the giants, dwarfs, fat ladies,
and other “prodigies.” Pituitary work rekindled this illicit fascination, and in the early 1900s—under the guise of research—he started visiting giants and dwarfs up and down the East Coast, as well as freaks in traveling circuses, and taking detailed medical histories.
A few, like John Turner, bristled at this intrusion. But most remembered their slight, dapper doctor fondly and even let him visit their homes. Cushing’s most memorable consultation took place late one night in Boston, when he rendezvoused with the World’s Ugliest Lady in her private boxcar outside a train station. Because the train yard was a labyrinth, Cushing requested a guide, and his Virgil turned out to be a three-foot dwarf brandishing a lantern. The flickering oil light made for some eerie visual effects on their journey, and Cushing later remembered that once or twice as they wandered, the dwarf seemed to transform into “a hobgoblin” before his eyes. At the Ugly Lady’s boxcar, a giant lifted the dwarf onto the platform, then helped lift the five-foot-seven-inch Cushing. Inside he found the circus’s menagerie of freaks splayed about on couches, including a “half-lady” with no legs. Cushing remembered thinking he’d stumbled into a fairy tale, and throughout his interview he felt a smile twitching his lips, even as their tales of suffering stung his eyes with tears.
After studying dozens of freakish medical histories, Cushing determined that the pituitary gland’s primary job was communication. We normally think of the brain communicating with the body through nerve impulses; that’s how the brain creates movement, for instance. But the brain has other ways of issuing commands, through chemicals such as hormones. It’s just that instead of secreting hormones directly, the brain sometimes outsources that job to glands. And there’s no more important gland for hormone regulation, Cushing declared, than the pituitary “master gland.” It’s a veritable hormone factory, with half a dozen different types of cells, each of which secrete distinct hormones. And the over- or underproduction of any one hormone can cause a distinct disease, which explains why the pituitary was linked to so many different ailments.
Thanks to his obsession with giants and dwarfs, Cushing zeroed in on one hormone in particular, growth hormone. If a child gets a pituitary tumor, the cells that secrete growth hormone often start to proliferate. The gland then pumps out too much growth hormone, and the child shoots up into a giant. In contrast, if a nearby cyst crushes these cells, the gland produces too little growth hormone and renders the child a dwarf. It turns out, then, that there was no “contradiction” with the pituitary: problems with it could indeed produce both dwarfs and giants.
Cushing also determined that pituitary disturbances after childhood caused different ailments. People who reach an adult height obviously won’t shrink back into dwarfs if their hormone-producing cells die. But they can regress sexually, becoming apathetic about sex and packing baby fat onto their faces and bellies. Men’s genitals might retract, too; females might stop menstruating. Similarly, a revved-up pituitary gland won’t make adults taller, since the growth plates in their arms and legs have fused. But a flood of growth hormone in particular can cause acromegaly, a condition where people’s hands, feet, and facial bones thicken* and their eyes bulge out as if they’re being strangled. Cushing’s “ugly lady” in the boxcar had this unsightly disorder.
John Hemens, a farmer from South Dakota who suffered from acromegaly, before developing symptoms.
Hemens just before Harvey Cushing operated on him.
Excited by his discoveries and eager to expand his neurosurgical repertoire, Cushing began operating on pituitary cases in 1909. His first patient was John Hemens, a farmer from South Dakota whose hands and feet had grown several sizes in adulthood. (Many people with pituitary trouble have to buy bigger gloves and boots every few years.) Hemens’s face had swelled grotesquely, too: his tongue and lips grew so thick he could barely speak, and gaps had opened up between his teeth where his jawbone had expanded. Head to toe, it looked like classic acromegaly, and Cushing decided to remove part of the pituitary. He knocked Hemens out with ether, then entered his skull through an omega-shaped incision (Ω) just above the nose; after wriggling his instruments into the brainpan, Cushing lopped off a good third of the gland. Hemens woke up minus his sense of smell, but his long-standing headache and eye pains had disappeared, and the swelling in his face and hands soon subsided. Cushing declared him cured.
The relief didn’t last, unfortunately; many of Hemens’s symptoms returned within a year. But the result nevertheless encouraged Cushing: no one had ever alleviated a pituitary disorder before, even slightly. So Cushing kept pushing forward, doing bolder operations. In 1912 he even dared transplant a pituitary gland from a dead infant into a comatose Cincinnati man whose pituitary had been destroyed by a cyst, in a last-ditch effort to save the man’s life. The patient died without regaining consciousness, and the case caused a scandal when a newspaper reported, in a howler, that Cushing had actually transplanted the baby’s entire brain. Even this setback couldn’t deter Cushing, and he kept developing new treatments.
Soon enough, a colleague putting together a new book asked Cushing to submit an eighty-page chapter on the master gland. Cushing submitted eight hundred pages. He later condensed that into his own book, The Pituitary Body and Its Disorders. Frankly, the book had some shortcomings. Always obsessive, Cushing had started attributing any and all disorders of unknown origin to this “potent mischief-maker,” and had therefore included some dubious cases. Nevertheless, the book deserved its fame. Before it, doctors mostly ignored giants, dwarfs, and fat ladies as inexplicable “prodigies.” And if doctors did dare to treat a hormone imbalance, they usually (especially with women) simply tore out the sex organs and hoped for the best. Cushing provided a more rational, more humane alternative, and provided the first real relief that most victims had known.
Beyond its medical merits, the book became famous for another reason—its haunting photographs. Thanks to his love of technology, Cushing had long ago started “kodaking” his patients to document their deterioration. Indeed, he was an early proponent of “before” and “after” comparison shots—except that he inverted the modern gimmick, since his patients always looked worse in the second picture. Dandies in three-piece suits suddenly had shrunken genitals and so much belly fat they looked pregnant; elegant mademoiselles suddenly sported humpbacks and mustaches. Perhaps the saddest photo showed the giant John Turner propping himself up on two chairs, his face alarmingly ruddy and his legs looking rickety enough to collapse beneath him. (A five-foot-eight-inch assistant of Cushing’s, who happened to be standing next to Turner in this picture, often got stopped at medical conferences even decades later because people still recognized him from that photo.)
Pituitary giant John Turner. Even decades later, Cushing’s assistant, right, still got stopped by people at medical conferences who recognized him from this photo.
In some ways the book combined the artistic innovations of Vesalius with Velázquez’s interest in human deformity. But whereas Velázquez lent his subjects dignity, Cushing’s photographs make for uncomfortable viewing today. There’s something almost ruthless about them. Turner and most other patients were stripped naked; none had black bars over their faces or genitals, and most didn’t even try to smile. They call to mind that old superstition about cameras stealing people’s souls. Certainly, Cushing cared for his patients as people. He kept up correspondence with hundreds of them, and excoriated Time magazine once when it mocked some circus freaks (including Cushing’s “ugly lady”) in a column. At the same time, Cushing wasn’t above making a crack himself in private, and he certainly capitalized on the public fascination with freaks to cement his own fame.
Already by 1913 Cushing had parlayed his book into an appointment at Harvard, and despite his punishing schedule he took on even more work throughout the 1910s and 1920s. He wrote a biography of his mentor, which won a Pulitzer Prize in 1926. Meanwhile he began a massive project—whole tables in his house were covered in paraphernalia—to hunt down every su
rviving manuscript and original likeness of Vesalius, whom Cushing considered his spiritual forefather. (Cushing even tracked down some rare first editions of Fabrica—one, oddly, found in a Roman blacksmith’s shop.) He got so wrapped up in this and other work that he didn’t notice the stock market crash of 1929 until months later, when patients stopped trickling in. He nevertheless celebrated removing his two thousandth brain tumor* in 1931. Along the way—always confident in his own abilities—he also operated on his family members a few times, removing two of his children’s appendixes and a tubercular growth from a daughter’s neck.
Decades of nonstop work finally wore Cushing down, and his health deteriorated further after he himself was diagnosed with a small brain tumor in the late 1930s; he eventually died of complications from a heart attack in 1939. Again, not all of Cushing’s early work has held up. But more than anyone else of his era, he illuminated how the brain’s glands work (or fail to), and he laid crucial groundwork for understanding how the brain influences the body. Even as Cushing lay dying, in fact, other scientists were expanding on his insights and linking his master gland to another major brain-body system, the system that produces human emotions.
Appropriately enough, the modern study of emotions began with one man’s rage. In 1937 Cornell neuroscientist James Wenceslaus Papez (rhymes with “drapes”) got wind of a new research grant being offered; the money would help scientists study how emotions work inside the brain. Papez thought the underlying implication of the grant—that scientists knew nothing about the neuroscience of emotions—insulted some colleagues of his who’d already illuminated key aspects of the field. So in what he later described as “a fit of spleen,” Papez wrote a paper outlining the current state of knowledge. But the whole of his paper far exceeded the sum of its parts.