The Tale of the Dueling Neurosurgeons

by Sam Kean

  To maintain his connection to New Guinea in between trips there, Gajdusek also began “adopting” Papuan youths, starting with a brash and lively lad named Mbaginta’o in 1963. Among other things, Mbaginta’o had to learn how to use a toilet, wear shoes, and eat with utensils before immigrating to Maryland. Gajdusek nevertheless enrolled him, as “Ivan” Gajdusek, in Georgetown Prep, an elite local high school. Ivan adjusted well, and eventually Gajdusek brought over a “brother” for him. He too thrived, so another brother appeared. Then another. Pretty soon—story of his life—Gajdusek went overboard, and dozens of teens from other tribes followed over the next few decades, some initially against their will. Gajdusek paid to feed and clothe all of them and sent them to good schools. Rather than focus on academics, however, many of his “sons” preferred boozing, racing cars, seducing the daughters of local Rotarians, and generally, as Gajdusek fumed, “fucking around.” In short, they behaved like teenagers. Gajdusek did invoke some discipline—his boys did laundry, mowed, cooked, and cleaned their rooms. But it didn’t help them adjust when “dad” would jet off for months at a time to track down some exotic disease and occasionally leave them unsupervised.

  The breakthrough came in 1966. After years of tedium—and no results—Daisey the chimp developed a drooping lip and a shuffling, stuttering gait, signs of cerebellum damage. Georgette came down with symptoms shortly afterward. After drawing blood and ruling out every disease and nutritional deficiency and poison they could think of, colleagues summoned Gajdusek back from Guam. Gajdusek arrived grumpy—he hated having his trips cut short—but grew excited when he saw the chimps. The researchers euthanized them and performed autopsies, then sent some brain tissue to a pathologist. She found plaques and spongy holes. Gajdusek’s team ripped off a paper for Nature in one day, and it appeared in print two weeks later, exploding like a grenade. Not only had they killed the genetic theory of kuru, they’d proved that a degenerative brain disease was contagious in primates, an unheard-of result. Furthermore, they dared speculate on the broader implications of their work for medicine. They proposed that kuru, scrapie, and Creutzfeldt-Jakob—which all cause “spongiform” brain damage and can all lie dormant for long periods before roaring awake—were caused by a new class of microbes, which they dubbed “slow viruses.”

  The epidemiology of kuru also became clearer in the 1960s. Gajdusek had always balked at linking kuru and cannibalism, since doing so reinforced barbaric “bushman” stereotypes.* Besides, the cannibalism connection had always foundered on a few facts. For one, only women ate the brains at funeral feasts, but children still got kuru, children of both sexes. What’s more, Christian missionaries—despite insisting that the Fore eat the body and blood of Christ—had all but eradicated cannibalism by the mid-1950s, while kuru itself had not ceased.

  To some people, though, cannibalism still made a lot of sense. The Fore had adopted cannibalism only in the 1890s, when the fad of funeral feasts had diffused down from the north. Intriguingly, the first kuru cases appeared a decade later. And kuru flared up hottest among the tribes most enthusiastic about the feasts. More important, dogged anthropologists determined that the Fore had been lying a little about who ate what. Gooey gray and white matter were supposed to be verboten for the young’uns, but Fore mothers, being mothers, had often indulged them anyway, providing a plausible vector for the infection. And while cannibalism did cease in the 1950s, the chimp experiments explained the lag, since kuru could take years to emerge even when injected directly into the brain. With all these facts laid in front of them, scientists realized that cannibalism explained everything.

  These were the first bits of good news, ever, in kuru research. Thankfully, they weren’t the last. By the late 1960s the demographics of kuru had shifted and it was becoming rarer. With no more funeral feasts, the average age of victims in The Book was increasing year by year, as fewer and fewer young people contracted it. Kuru never quite disappeared, but by 1975, when Papua New Guinea gained independence from Australia, the highlanders could finally feel they were putting an awful three-quarters of a century behind them.

  What’s more, in 1976, their champion, Gajdusek, won a Nobel Prize for his discovery of slow viruses. Gajdusek led an American sweep in the sciences that year, and Milton Friedman and Saul Bellow won as well. Gajdusek got characteristically pissy about all the fuss and formality of the prize. (Friends speculated he’d probably never worn a tie before the ceremony.) But the Nobel affirmed kuru as a disease of major importance. Besides, Gajdusek got a kick out of taking eight of his adopted boys to Sweden. They slept in one of Stockholm’s fanciest hotels—on the floor, in sleeping bags.

  Even with the imprimatur of a Nobel, however, one question kept nagging scientists: what exactly were the slow viruses that caused kuru, scrapie, and Creutzfeldt-Jakob?

  One problem with the slow virus theory was the presence of the blood-brain barrier. Scientists have known since 1885 that if you inject, say, blue dye into the bloodstream, the heart, lungs, liver, and pretty much every other organ will turn blue. The brain won’t, because the BBB allows only certain preapproved molecules across. (Unfortunately, it also bars most pharmaceuticals we swallow or inject, making common brain diseases like Alzheimer’s and Parkinson’s difficult to treat.) Microbes have an even harder time crossing the barrier: aside from some exceptions, like the corkscrew-shaped syphilis bacteria that plagued Charles Guiteau, most bugs cannot penetrate the neurosanctum neurosanctorum.

  Furthermore, kuru brains never got inflamed, a fact impossible to square with any known microbe. The purported viruses proved alarmingly resistant to sterilization, too. Tissue infected with kuru remained contagious even after it was roasted in ovens, soaked in caustic chemicals, fried with UV light, dehydrated like jerky, or exposed to nuclear radiation. No living thing could survive such abuse. This led a few scientists to suggest that the infectious agents might not technically be alive; perhaps they were mere scraps of life, like rogue proteins. But this idea ran so counter to everything biologists knew that getting them even to consider it took someone every bit as tenacious and stubborn as Carleton Gajdusek.

  That someone was Stanley Prusiner, who initiated the next great phase of kuru research. Not that his career had gotten off to a great start. Prusiner, a neurologist, pretty much flunked out when he first visited the highlands in 1978. Native bois practically had to push him up the mountains with two hands on his backside, and not long after seeing his first patients, some intestinal distress waylaid him and villagers had to lug him back down. Nevertheless, Prusiner returned to his lab in San Francisco full of grand plans. In particular he bet big on rogue proteins as the biological vector for both kuru and Creutzfeldt-Jakob. Unlike cells, proteins aren’t alive; in fact, most proteins are helpless outside the cell. But maybe, just maybe, Prusiner argued, some proteins could survive independently and even reproduce in some manner. Because they’re simpler, proteins should also survive sterilization better, should have an easier time crossing the BBB, and should avoid triggering inflammation in the brain, since they lack the proper markers for our immune cells to recognize.

  Somewhat rashly, Prusiner decided—even before he had any evidence that they existed—to name these rogue proteins, calling them prions (pree-ons), a portmanteau of protein and infection. (This fudged the order of the i and o, of course, but Prusiner felt the ends justified the spelling peccadillo. “It’s a terrific word,” he once gushed. “It’s snappy.” Certainly snappier than proins.)

  Most scientists disparaged the prion as a vague, fictitious construct—the “p-word,” they called it. And in parallel with their dislike of prions, many colleagues developed a pretty healthy aversion to Prusiner himself. In some circles the p-word came to stand for pushy and publicity, since Prusiner preened and promoted himself and even hired a PR agent. To be fair, Prusiner repeatedly offered to collaborate with colleagues, but most spurned him, including Gajdusek’s group. Another time, when Prusiner named Gajdusek as a coauthor on a paper, as
a courtesy, Gajdusek hijacked the writing process and refused to allow Prusiner to publish it until he’d deleted all mention of the word “prion.” To his credit, Prusiner shrugged these insults off. And after years of laborious work, his team finally isolated a prion in 1982.

  The discovery almost ruined him. During follow-up work, his lab determined that normal brain cells manufactured a protein with the exact same amino acid sequence as the prion protein. (Amino acids are the building blocks of proteins.) In other words the healthy brain, as a matter of course, produced something pretty much identical to prions all the time. But if that was true, why didn’t we all have kuru or Creutzfeldt-Jakob? Prusiner didn’t know, and he brooded over this reversal for months.

  Never one to get too discouraged, he soon realized that, far from invalidating his theory of infectious proteins, this new result made it all the more interesting. The key point is that, while the amino acid sequence does help define a protein’s identity, proteins are also defined by their 3-D shape. And just as you can rearrange the same sequence of fifty Legos into different structures by snapping the pieces together at different angles, the same sequence of amino acids can be twisted into different proteins with different shapes and different properties. In this case, Prusiner’s team determined that a crucial corkscrew-shaped stretch on the normal prions—the ones healthy cells made—got mangled and refolded in the deadly prions, like an untwisted coat hanger. Clearly, there was a “good” prion and a “bad” prion, and kuru and Creutzfeldt-Jakob seemed to involve the conversion of the former to the latter.

  So what causes the conversion? Oddly, the catalyst turns out to be the bad prion itself. That is, the bad prion has the ability to lock onto copies of the normal prion that float by and mangle them, changing their shape until they’re clones of the bad one. These bad clones then clump together, forming minuscule protein plaques that harm neurons. That’s bad enough, but every so often the clump grows too large and breaks in two. And when it does—here’s the key—the rate of converting good prions into bad prions doubles, since each half can now drift off and corrupt others independently. Even worse, those two clumps will both grow too large in turn and split, producing four bad prion clumps. After another round of growth and breakage, those four will become eight, and so on. In other words, prions are a slow chain reaction. The end result is an exponentially growing number of prion vampires—and plenty of dead neurons and spongy holes.*

  This prion theory also helped explain where kuru came from. Unlike kuru, Creutzfeldt-Jakob appears in ethnic groups worldwide. It usually starts when a gene mutates in some unlucky person’s brain, and he begins to produce bad prion proteins spontaneously. Around 1900 some eastern highlander almost certainly came down with a form of Creutzfeldt-Jakob that attacked the cerebellum, and his equally unlucky loved ones consumed the brain. Prions are indeed immune to cooking and digestion, unfortunately, and can cross the BBB. As a result, the loved ones’ brains got infected, and they died. The loved ones were in turn consumed, infecting still more people—who themselves died and were themselves consumed, and so on. Eventually, they started calling the killer kuru. Notice that it wasn’t cannibalism per se that caused the outbreak; eating brains isn’t inherently deadly. It was the bad luck of eating patient zero. Sadly, then, the very proteins that Fore women had so craved at the funeral feasts ended up killing them.

  Since the 1980s prion research has swelled in importance. The outbreak of mad cow disease in the 1990s was basically a case of bovine kuru. British farmers were feeding the ground-up brains of cattle that had a prion disease to other cattle, who in turn infected the humans who ate them. (Not coincidentally, Prusiner won a Nobel Prize for prion research just after the mad cow scare, in 1997.) Disturbingly, some people might still have deadly bovine prions lying dormant inside them.

  More recently, prion research has crossed over into mainstream neuroscience. The snarly protein plaques in kuru brains seem to grow and spread in much the same way as the snarly protein plaques that ravage the brains of people with Alzheimer’s, Parkinson’s, and other neurodegenerative diseases—first turning innocent proteins rogue, then clumping together into plaques that poison neurons and interfere with synapses. (There’s even evidence that Alzheimer’s plaques in particular require the presence of the normal prion proteins to do damage.) Thankfully, you can’t “catch” diseases like Alzheimer’s and Parkinson’s. But if other scientists can build on this prion work and slow down or even cure these ailments—which affect more than six million people in the United States alone and will grow increasingly common as our population ages—more Nobels will surely follow.

  Gajdusek himself had first suggested the kuru–Alzheimer link decades ago but didn’t really pursue it. After winning the Nobel, in fact, he got more and more lethargic. There were still plenty of lectures worldwide as well as occasional jaunts to study diseases in places like Siberia. But having gained back the weight (and then some) he’d shed in New Guinea long before, he slowed down a lot, and spent more and more time at home with his adopted children.

  Or rather, his adopted sons, since the vast majority of youths he’d surrounded himself with were male. A few colleagues, having noticed the pattern here—All strapping lads, eh?—began snickering about this and winking at each other whenever Gajdusek prattled on about “my boys.” The FBI found the situation less funny.

  As early as 1989, Maryland police had started investigating Gajdusek on charges of sexual molestation. The FBI got involved in 1995, when agents began scouring his published journals and field notes. A number of passages made them cringe. Passages describing various boys’ pubic hair; passages about boys who, “with the slightest encouragement to their fondling, [go] searching in my pockets”; passages about him waking up on Christmas morning having “slept well again, like a bitch with her half-dozen pups lying and crawling over her”; passages about fathers who “smile and… indicate that I should let the boys play sexually with me.” All of this was vague or ambiguous, though, and it all took place in New Guinea anyway. So the FBI began questioning his adopted sons, and finally found one who claimed that Gajdusek had had relations with him as a teenager in Maryland. (Other victims came forward later.) The young man agreed to call the seventy-two-year-old scientist, and during their conversation he asked him, “Do you know what a pedophile is?” Gajdusek allegedly answered, “I am one,” then admitted to having sex with other boys. Gajdusek begged him to keep quiet, but the phone call was being recorded. Just before Easter in 1996, as a pudgy, jet-lagged Gajdusek pulled into his driveway one morning, returning from a conference in Slovakia on mad cow disease, a half dozen police cars whipped out of hiding, their red and blue lights screaming. Arrested and jailed on charges of “perverted practices,” Gajdusek ranted from his cell, vowing to “pray to my pantheon of gods” for deliverance and attacking his accusers as “jealous, vindictive… probably psychotic.” Eventually, though, he pleaded guilty and served eight months.

  In subsequent interviews* Gajdusek more or less admitted everything: “all boys want a lover,” he claimed, later adding, “and if I find them playing with my cock, I say good on you, and I play with theirs.” He further defended himself by saying that the boys always approached him for sex, not vice versa, and that they came from a culture where sex between men and boys was appropriate, so no harm done. (An intellectual, he also invoked the widespread pederasty of classical Greece.) In truth, the highlanders weren’t the sexual libertines he claimed: they knew full well about other pedophiles who’d settled in their land and taken advantage of their culture, and they despised these men as perverts. Gajdusek also seemed willfully blind to the power he’d held over his boys in America as their guardian and master. Regardless, he never apologized, and fled to Europe after his jail term. He summered in Paris and Amsterdam, and wintered in northern Norway, enjoying the never-ending nights of winter solitude. He died, defiant and alone, in a hotel room in Tromsø, Norway, in 2008.

  It’s a complex legacy. Gajdusek
was one of the outstanding neuroscientists of his era: he alerted the world to a brand-new brain disease, and his experiments on the brains of apes (along with Prusiner’s crucial research) opened up a whole new realm of not-quite-living “biology.” He also proved that infectious agents can crouch inside the brain for years before springing—a baffling notion then, yet one that foreshadowed the long latency of HIV. Moreover Gajdusek fought harder than anyone to help the victims of this cruel disorder, and it remains the only human disease besides smallpox ever eradicated: since 1977, 2,500 people have died of kuru, but none since 2005. The Book has probably had its last entry. Yet even as he fought to save Fore society, Gajdusek was apparently preying on its most vulnerable members. What’s more, for all his sweat and blood, his work on the brain saved exactly no one; missionaries and patrols had largely stopped the cannibalism before he arrived, and every last person who caught kuru died. In the end, neuroscience proved impotent—and even today most Fore people remain convinced that sorcerers caused kuru.

  But perhaps that’s too bleak a view: the victims of kuru didn’t die in vain. Basic biological research serves as the foundation for more and better work, and because of those victims’ sacrifices we now know that kuru ravages the brain in ways tantalizingly similar to Alzheimer’s, Parkinson’s, and other plagues of old age. So perhaps the “world’s rarest disease” holds the insight to preventing brain decay in human beings everywhere. If that proves to be so, the Fore will have gotten inside our brains as surely as they got inside the brains of so many scientists. And as neuroscience continues to expand its scope and map out how the tiny circuits in our brains give rise to higher-level drives and emotions, perhaps even the self-delusions and contradictory desires of someone like D. Carleton Gajdusek will start to make a little more sense.

  CHAPTER SEVEN