by Sam Kean
Placebo-controlled trials are the gold standard in medicine: scientifically, they’re the best way to determine whether treatments work. But many doctors and activists were outraged at the use of placebos in Uganda. In North America, they pointed out, it’s considered unethical to withhold treatment from HIV patients, even during an experimental drug trial. Instead of comparing the short course with placebos, they wanted researchers to compare the short course with the long course that people in wealthy countries would have received. Anything less, they insisted, was a double standard, and was tantamount to condemning Black babies to death.
These accusations angered the scientists running the study, including many Ugandans. The long drug course would have been too expensive for their limited budgets, they argued, greatly lowering the number of people in the study and therefore its predictive power. Furthermore, they said their opponents—mostly rich white folks in developed countries—had no idea what running studies in Africa was like, and were guilty of “ethical imperialism” for applying first-world moral standards to complex third-world situations. If not for the trial, none of the Ugandan women would have received any treatment. Perhaps most importantly, they reiterated that a careful scientific study with proper placebo controls was the fastest and most effective way of determining whether a treatment worked. It would therefore save the most babies in the long run.
Neither side budged, and the arguments over what to do in times of medical crisis continue today. Most recently, during the early days of COVID-19, many people wanted to unleash doctors to try all sorts of experimental drugs—despite their often-harsh side effects, side effects that could (and did) kill people who would have survived otherwise. Then again, had some of those drugs worked, we might have been spared untold amounts of heartache and pain. As mentioned earlier, many ethicists consider poorly designed medical research ipso facto unethical. But in times of crisis, even the best designed trials can offend people’s morals. No one ever said ethics was easy.
The Nazi doctors who experimented on concentration-camp inmates remain the most reviled physicians of the twentieth century, if not all time. But if they have any competition, it’s an American neurologist named Walter Freeman. Unlike Josef Mengele, Freeman was no deviant, no sicko. If anything, he wanted to help people too badly—which was ultimately his undoing.
As we’ll see next chapter, Freeman developed what’s called the transorbital lobotomy—or, as his enemies styled it, the “icepick lobotomy.” Beyond the procedure itself, it was Freeman’s outsized ambition, and his forcing this “cure” on the masses, that made the lobotomy one of the most notorious medical procedures in history.
Footnotes
1 One horrific example of Nazi deviousness involved special desks that were equipped with X-ray tubes beneath the chairs. Women of “undesirable” classes would sit at the desks while they filled out some innocuous form. All the while they were secretly being bombarded with X-rays, part of a secret plot to render them sterile.
2 In fact, of all the rewarming methods tested, covering someone with blankets and relying on their own body heat proved the least effective. The light cradle with its sixteen intense bulbs was barely better. Vigorous rubbing of the limbs did help somewhat, but only in conjunction with hot baths. Booze turned out to be a terrible prophylactic against heat loss. It does produce a temporary feeling of warmth by sending blood rushing to the extremities, but it actually reduces the body’s ability to retain heat over the long run. That said, liquor does help restore body heat once people are in a bath, since its tendency to push blood to the extremities helps relieve the burden on the heart. So if you find someone in the wild with hypothermia, by all means call a doctor first. But in the absence of that, get them into a hot tub and get them something to drink.
Incidentally, most people don’t realize how shockingly close the Nazis came to covering up most of these atrocities. In fact, they might have gotten away with everything if not for the dogged efforts of one Jewish physician, Dr. Leo Alexander. For more on Dr. Alexander’s incredible work, see episode 5 at samkean .com/podcast.
3 To be fair, there’s anecdotal evidence that Rivers did protect at least one man enrolled in the study, a close friend of hers. She claimed he’d been lost to follow-up when in fact he lived just four blocks from the county health center. He also received a full dose of penicillin to deal with his syphilis in 1944, quite early. Furthermore, Rivers was not alone here. By 1969, the U.S. government was considering shutting the Tuskegee study down. But the Macon County Medical Society—which consisted almost entirely of Black doctors—voted to keep it going. In fact, the doctors promised that if they were supplied with a list of patients, they would withhold antibiotics from the men and refer them to Nurse Rivers instead.
Given how emotional this topic is, I’ll state again that this is not—not—an attempt to shift the blame for Tuskegee onto Rivers (or the Macon County doctors). The men and women at the PHS who designed the study deserve the shame here. But Rivers did take part and was culpable in her way. I bring up her case simply because her life presented the most compelling dilemma, given how she was caught between two worlds, the Black community she lived in and the white scientific community who controlled her professional fortunes.
4 Hunter injected his penis with venereal pus in order to determine whether gonorrhea and syphilis were the same disease or two separate ones, something that no one knew at the time. Alas, his experiment was doomed from the start, since the man he collected the pus from—unbeknown to Hunter—turned out to have both diseases. As a result, Hunter saw symptoms of each disease in himself, and erroneously concluded that syphilis and gonorrhea were in fact the same ailment. This mix-up caused all sorts of confusion until another doctor finally straightened the matter out in 1838. And while Hunter might seem heroic for experimenting on himself, he certainly didn’t sidestep all the ethical issues here. For one thing, it’s not clear what his then-fiancée and future wife thought of this all—or whether Hunter even told her what he was doing.
For more about self-experimentation in medicine—including some truly hair-raising tales of surgeons operating on themselves—see episode 20 at samkean.com/podcast.
5 I don’t have room to get into the whole saga here, but the story of Susan Reverby discovering Cutler’s long-suppressed work in an archive—a case that would eventually rocket all the way to the White House—is worth reading in full. Check out samkean.com/books/the-icepick-surgeon/extras/notes for the tale.
6 Even Susan Reverby, who first exposed him, has resisted the urge to call John Cutler a monster. While she certainly blames him for the horrors of Guatemala, as a feminist historian she also acknowledges the great amount of good he did later in developing countries.
8
AMBITION: SURGERY OF THE SOUL
The story stunned Egas Moniz. It was August 1935, a discouraging year for the neurologist, and he’d arrived at the conference in London a bitter man. As soon as he heard the story of the chimpanzees, however, all his frustrations vanished.
The chimps’ names were Becky and Lucy. Scientists at Yale University had been running them through some tests on memory and problem-solving. In one instance, the scientists placed a treat beneath one of two cups, then lowered a screen for a few minutes. Becky and Lucy had to remember which cup the treat was under or risk losing it. Another test involved using a short stick to drag a series of longer sticks within reach, then using the longest stick to secure another treat. Lucy aced both tasks, but Becky could never remember which cup the treat was under, and would throw epic tantrums if she missed out—hooting, slamming her fists, hurling feces, the works.
After training the chimps on these tasks, the scientists did something drastic. They surgically removed a huge chunk of the chimps’ brains—their entire frontal lobes—then reran the tests to see how well Becky and Lucy coped. The results were devastating. As the Yale team reported in London, the chimps couldn’t remember which cup the treat was under for more than
a few seconds now, and the dragging-the-sticks task was beyond them. Losing their frontal lobes had obliterated their working memories and destroyed their ability to solve problems.
All very interesting, if a bit sad. But the insights into memory and problem-solving weren’t what captivated Egas Moniz. As an aside, one Yale scientist mentioned that, after her surgery, Becky stopped throwing tantrums when she missed out on treats. She remained perfectly calm, he said, as if she’d joined a “happiness cult.” All in all, removing her frontal lobes had seemingly wiped out her neurosis.
Now, this wasn’t the whole story. If Becky went zen, the scientist also mentioned that Lucy went the opposite direction: After her surgery, she regressed from a calm and mature adult into a snarling, raving toddler. Removing her frontal lobes had introduced neurosis.
But Moniz, sitting in the audience, either missed the part about Lucy or ignored it. A vision of Becky—so calm, so serene—had seized hold of his own frontal lobes. During the Q&A afterward, he stood and asked whether brain surgery in humans might cure emotional disturbances in the same way.
The audience was shocked. Was Moniz really proposing to chop out someone’s frontal lobes?
No. But he had something equally dark in mind.
Moniz might never have gotten tangled up in lobotomies if not for his illustrious family. He grew up in Portugal in the 1870s, where an uncle had filled his head with tales about his ancestors—including the original Egas Moniz, a legendary soldier who’d helped repel the invading Moors in the 1100s. Such stories inflamed the boy, and stoked a strong desire to excel and become famous himself. As a young man he attended medical school in Portugal and did a residency in neurology in Paris. Shortly afterward, at age twenty-six, he was elected to the Portuguese parliament. By middle age, he was the ambassador to Spain, and he owned a palatial estate in Lisbon with a legendary wine cellar and scads of servants, whose livery he designed himself.
Dr. Egas Moniz, the glory-hungry neurologist who invented what would become known as the lobotomy. (Painting by José Malhoa.)
To his frustration, though, his eminence in politics far outpaced his eminence in medicine. In fact, when he won an appointment in neurology at a prestigious university in Lisbon, people sneered that he’d gotten the job because of his political connections, not his scientific acumen. Such talk stung him.
Then his health began sagging. Thanks to his sumptuous lifestyle, he’d long suffered from gout in his hands. This painful joint condition turned even handshakes into excruciating ordeals, and curbed his ability to work with patients. He also gained a substantial amount of weight in middle age, leaving him looking puffy and sad.
Unable to treat patients anymore, Moniz channeled his ambitions into developing new medical procedures instead. At that time, the 1920s, doctors could examine people’s bones using X-rays, but they had no good way to peer inside soft tissues. So a few scientists in France came up with what’s now called the angiograph. It involved injecting opaque liquids into people’s bloodstreams, liquids full of dissolved metal ions. A quick X-ray would bounce off the fluids, allowing doctors to see the contours of vessels and organs. Outside of gory accidents, this was the first-ever peek inside the guts of a living human being—a huge breakthrough.
Moniz threw himself into angiograph research, racing to secure the first pictures of the brain. He started with cadaver work. His assistant (who handled the instruments, given Moniz’s hands) would take a cadaver and pump opaque fluid into its brain. Next the assistant detached the head, probably with a saw, and jumped into Moniz’s chauffeured limousine with it; the limo then spirited the head across town to where the X-ray equipment awaited. For weeks, Moniz later recalled, he lived in dread of a car accident. He could practically see the severed head tumbling out onto the pavement, exposing his macabre experiments.
After the cadaver work, Moniz and his assistant graduated to live patients. But the fluids they injected (e.g., strontium bromide, sodium iodide) often leaked into the surrounding tissue, causing neurological problems like drooping eyes and seizures. One patient died. Shaken but undeterred, Moniz switched solutions and kept fiddling. In June 1927, he finally captured some gorgeous pictures of the arteries and veins that serve the brain. He even pinpointed a tumor near the pituitary gland of one patient based on the branching of vessels there.
These images were a big deal, and Moniz knew it. He worked hard to establish his priority, pumping out two dozen papers on angiographs in 1927 and 1928. Presumptuously, he also asked two colleagues to nominate him for the Nobel Prize, which they did—albeit grudgingly, apparently reluctant to refuse someone so connected.
The nominations weren’t enough. Because Moniz hadn’t invented angiographs, other scientists considered his work somewhat derivative, and as the 1920s passed into the 1930s, Moniz could see his share of the credit waning. There was no question that cerebral angiographs saved lives, and his colleagues now honored him as a legitimate scientist. But it was hardly enough to earn him a bust in the pantheon of his ancestors.
This was the state—sixty years old, crippled by gout, depressed over his legacy—in which Moniz arrived at the London conference in 1935. In a last-ditch effort to promote himself, he set up a booth there on angiography, but little came of the effort. Instead, Moniz spent most of his time chatting to the doctor in a neighboring booth, an ambitious young American neurologist named Walter Freeman, who also worked in brain visualization. Freeman proved a better showman than the aloof Moniz (colleagues remember Freeman at other conferences calling out like a carnival barker, rallying crowds of gawkers), but the two got along well enough, parlez-vousing in French about various aspects of their work. Pretty ho-hum.
At some point during the conference, however, Moniz attended the session on the chimpanzees Becky and Lucy—and felt the entire course of his life swerve. Few other people would have made the connection. But in the story of Becky, Moniz suddenly saw the solution to one of the most vexing problems of Western society—the shameful state of its insane asylums.
In ancient and medieval times, whenever somebody lost their wits, their families took them in and cared for them. But when industrialization fractured family life in the 1700s and 1800s, the burden for care shifted onto the government, which began herding its new wards into asylums. Every major city in the Western world had a lunatic asylum by 1900, and they were all depressingly similar: loud, filthy, overcrowded. “Patients were beaten, choked, and spat on by attendants,” one historian noted. “They were put in dark, damp, padded cells and often restrained in straitjackets.” (A woman at one asylum was even forced to give birth in a straitjacket, and do so in solitary confinement.) At best, asylums were warehouses for human beings. At worst, they drew comparisons to concentration camps.
Psychiatrists did try to help the insane, albeit without much success. The most common treatments involved rebooting people’s brains by inducing seizures and comas with drugs or electroshocks.1 Some patients did benefit from these measures (really), but only some. And the less said about other “treatments”—castration, injections of horse blood, refrigerated “mummy bags”—the better.
A scene from the famous Bethlem Royal Hospital in England, whose nickname— Bedlam—became synonymous with the wretched state of insane asylums. (From the Rake’s Progress series by William Hogarth.)
Indeed, the most depressing thing about asylums was their air of futility. Patients moaned and wept, rocked and howled, day after day, and nothing the doctors did ever made any difference. Even calling such people patients seems wrong, since that implies the prospect of a cure. Really, they were inmates. Some inmates couldn’t have beds, because they’d smash them and impale people with the pieces. Some couldn’t have clothing because they’d tear it off or soil themselves repeatedly. In some ways, these people were worse off than animals. At least animals are placidly content. These men and women were tormented by their own minds, hour after hour, decade after decade.
Suddenly, Moniz saw a way to sav
e them. If monkeying around inside Becky’s brain had ended her outbursts, then why couldn’t something similar help disturbed human beings? It was worth a shot. Except, instead of removing the frontal lobes, Moniz proposed something subtler: severing the connections between the frontal lobes and the limbic system.
In human beings, the frontal lobes allow for reflection, planning, and rational thought. The limbic system processes raw emotion. These two brain regions are connected by bundles of neurons that send signals back and forth. Moniz speculated that, in the brains of lunatics, their limbic systems had gone into overdrive, revving them up and overwhelming their frontal lobes with a barrage of signals.
Now, Moniz’s theory wasn’t complete bunk—disturbed emotions do overwhelm the brains of some people. But that theory was built on an outdated model of the brain as a sort of hardwired electrical switchboard, with the wires connecting different parts. To Moniz, insanity resulted from faulty wiring, full of shorts and bad connections. So by clipping those bad connections, he could return the brain to equilibrium—curing insanity with the flick of a knife.
Unfortunately, Moniz didn’t seem to realize that information flows both ways in the brain. Emotions can overwhelm the frontal lobes, no question. But the frontal lobes can also send signals back to the limbic system to tamp down on raw emotions and calm us. In fact, a loss of frontal-lobe control is probably what turned Lucy, the other chimp, into such a wreck after her surgery. Without feedback from the frontal lobes, her emotions ran amok.
