The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code

by Sam Kean

  What’s more, studying Jewish DNA has helped confirm a once scarcely credible legend among the Lemba tribesmen in Africa. The Lemba had always maintained that they had Jewish roots—that ages and ages ago, a man named Buba led them out of Israel to southern Africa, where they continue today to spurn pork, circumcise boys, wear yarmulke-like hats, and decorate their homes with emblems of elephants surrounded by six-sided Stars of David. The Buba tale sounded awfully tall to archaeologists, who explained these “Black Hebrews” as a case of cultural transmission, not human emigration. But Lemba DNA ratifies their Jewish roots: 10 percent of Lemba men overall, and half the males in the oldest, most revered families—the priestly caste—have none other than the signature Cohanim Y.

  While studying DNA can be helpful in answering some questions, you can’t always tell if a famous someone suffered from a genetic disorder just by testing his or her descendants. That’s because even if scientists find a clean genetic signal for a syndrome, there’s no guarantee the descendants acquired the defective DNA from their celebrated great-great-whatever. That fact, along with the reluctance of most caretakers to disinter ancient bones for testing, leaves many medical historians doing old-fashioned genetic analysis—charting diseases in family trees and piecing together diagnoses from a constellation of symptoms. Perhaps the most intriguing and vexing patient undergoing analysis today is Charles Darwin, because of both the elusive nature of his illness and the possibility that he passed it to his children by marrying a close relative—a potentially heartbreaking example of natural selection in action.

  After enrolling in medical school in Edinburgh at age sixteen, Darwin dropped out two years later, when surgery lessons began. In his autobiography Darwin tersely recounted the scenes he endured, but he did describe watching an operation on a sick boy, and you can just imagine the thrashing and screaming in those days before anesthesia. The moment both changed and presaged Darwin’s life. Changed, because it convinced him to drop out and do something else for a living. Presaged, because the surgery roiled Darwin’s stomach, a premonition of the ill health that dogged him ever after.

  His health started to fall apart aboard HMS Beagle. Darwin had skipped a prevoyage physical in 1831, convinced he would fail it, and once asea he proved an inveterate landlubber, constantly laid low by seasickness. His stomach could handle only raisins for many meals, and he wrote woeful letters seeking advice from his father, a physician. Darwin did prove himself fit during the Beagle’s layovers, taking thirty-mile hikes in South America and collecting loads of samples. But after returning to England in 1836 and marrying, he deteriorated into a honest-to-gosh invalid, a wheezing wreck who often disgusted even himself.

  It would take the genius of Akhenaten’s greatest court caricaturist to capture how cramped and queasy and out-of-sorts Darwin usually felt. He suffered from boils, fainting fits, heart flutters, numb fingers, insomnia, migraines, dizziness, eczema, and “fiery spokes and dark clouds” that hovered before his eyes. The strangest symptom was a ringing in his ears, after which—as thunder follows lightning—he’d always pass horrendous gas. But above all, Darwin barfed. He barfed after breakfast, after lunch, after dinner, brunch, teatime—whenever—and kept going until he was dry heaving. In peak form he vomited twenty times an hour, and once vomited twenty-seven days running. Mental exertion invariably made his stomach worse, and even Darwin, the most intellectually fecund biologist ever, could make no sense of this. “What thought has to do with digesting roast beef,” he once sighed, “I cannot say.”

  The illness upended Darwin’s whole existence. For healthier air, he retreated to Down House, sixteen miles from London, and his intestinal distress kept him from visiting other people’s homes, for fear of fouling up their privies. He then invented rambling, unconvincing excuses to forbid friends from calling on him in turn: “I suffer from ill-health of a very peculiar kind,” he wrote to one, “which prevents me from all mental excitement, which is always followed by spasmodic sickness, and I do not think I could stand conversation with you, which to me would be so full of enjoyment.” Not that isolation cured him. Darwin never wrote for more than twenty minutes without stabbing pain somewhere, and he cumulatively missed years of work with various aches. He eventually had a makeshift privy installed behind a half-wall, half-screen in his study, for privacy’s sake—and even grew out his famous beard largely to soothe the eczema always scratching at his face.

  That said, Darwin’s sickness did have its advantages. He never had to lecture or teach, and he could let T. H. Huxley, his bulldog, do the dirty work of sparring with Bishop Wilberforce and other opponents while he lay about the house and refined his work. Uninterrupted months at home also let Darwin keep up his correspondence, through which he gathered invaluable evidence of evolution. He dispatched many an unwary naturalist on some ridiculous errand to, say, count pigeon tail feathers, or search for greyhounds with tan spots near their eyes. These requests seem strangely particular, but they revealed intermediate evolutionary forms, and in sum they reassured Darwin that natural selection took place. In one sense, then, being an invalid might have been as important to On the Origin of Species as visiting the Galápagos.

  Darwin understandably had a harder time seeing the benefits of migraines and dry heaving, and he spent years searching for relief. He swallowed much of the periodic table in various medicinal forms. He dabbled in opium, sucked lemons, and took “prescriptions” of ale. He tried early electroshock therapy—a battery-charged “galvanization belt” that zapped his abdomen. The most eccentric cure was the “water cure,” administered by a former classmate from medical school. Dr. James Manby Gully had had no serious plans to practice medicine while in school, but the family’s coffee plantation in Jamaica went bust after Jamaican slaves gained their freedom in 1834, and Gully had no choice but to see patients full-time. He opened a resort in Malvern in western England in the 1840s, and it quickly became a trendy Victorian spa; Charles Dickens, Alfred, Lord Tennyson, and Florence Nightingale all took cures there. Darwin decamped to Malvern in 1849 with his family and servants.

  The water cure basically consisted of keeping patients as moist as possible at all times. After a 5 a.m. cock-a-doodle-doo, servants wrapped Darwin in wet sheets, then doused him with buckets of cold water. This was followed by a group hike that included plenty of hydration breaks at various wells and mineral springs. Back at their cottages, patients ate biscuits and drank more water, and the completion of breakfast opened up the day to Malvern’s main activity, bathing. Bathing supposedly drew blood away from the inflamed inner organs and toward the skin, providing relief. Between baths, patients might have a refreshing cold water enema, or strap themselves into a wet abdominal compress called a “Neptune Girdle.” Baths often lasted until dinner, which invariably consisted of boiled mutton, fish, and, obviously, some sparkling local H2O. The long day ended with Darwin crashing asleep into a (dry) bed.

  Scenes from the popular “water cure” in Victorian times, for patients with stubborn ailments. Charles Darwin underwent a similar regime to cure his own mystery illness, which dogged him most of his adult life. (Courtesy of the National Library of Medicine)

  Would that it worked. After four months at this hydrosanitarium, Darwin felt bully, better than at any time since the Beagle, able to hike seven miles a day. Back at Down House he continued the cure in a relaxed form, constructing a sweat lodge for use every morning, followed by a polar-bear plunge into a huge cistern (640 gallons) filled with water as cold as 40°F. But as work piled up on Darwin again, the stress got to him, and the water cure lost its power. He relapsed, and despaired of ever knowing the cause of his frailty.

  Modern doctors have scarcely done better. A list of more or less probable retrodiagnoses includes middle-ear damage, pigeon allergies, “smoldering hepatitis,” lupus, narcolepsy, agoraphobia, chronic fatigue syndrome, and an adrenal-gland tumor. (That last one might explain Darwin’s Kennedy-esque bronze glow late in life, despite being a hitherto pasty English
man who spent most hours indoors.) One reasonably convincing diagnosis is Chagas’ disease, which causes flu-like symptoms. Darwin might have picked it up from the South American “kissing bug,” since he kept a kissing bug as a pet on the Beagle. (He delighted at how it sucked blood from his finger, puffing up like a tick.) But Chagas’ disease doesn’t fit all Darwin’s symptoms. And it’s possible that Chagas merely crippled Darwin’s digestive tract and left him vulnerable to deeper, dormant genetic flaws. Indeed, other semiplausible diagnoses, like “cyclical vomiting syndrome” and severe lactose intolerance,* have strong genetic components. In addition, much of Darwin’s family was sickly growing up, and his mother, Susannah, died of undetermined abdominal trouble when Darwin was eight.

  These genetic concerns become all the more poignant because of what happened to Darwin’s children. Roughly 10 percent of leisure-class Victorians married blood relatives, and Darwin did his part by marrying Emma Wedgwood, his first cousin. (They shared a grandfather in Josiah Wedgwood, the crockery maven.) Of the ten Darwin children, most were sickly. Three proved infertile as adults, and three died young, roughly double the child mortality rate in England. One, Charles Waring, survived nineteen months; Mary Eleanor lived twenty-three days. When his favorite child, Anne Elizabeth, fell ill, Darwin took her to Dr. Gully for the water cure. When she died anyway, at age ten, it snuffed the last lingering remnant of Darwin’s religious faith.

  Despite any bitterness toward God, Darwin mostly blamed himself for his children’s infirmity. While most children born to first cousins are healthy (well north of 90 percent), they do have higher risks for birth defects and medical problems, and the numbers can creep higher still in unlucky families. Darwin stood uneasily ahead of his time in suspecting this danger. He tested the effects of inbreeding in plants, for instance, not only to shore up his theories of heredity and natural selection but also to see if he could shed light on his own family’s ailments. Darwin meanwhile petitioned Parliament to include a question about consanguineous marriages and health in the 1871 census. When the petition failed, the idea continued to fester, and Darwin’s surviving children inherited his anxieties. One son, George, argued for outlawing cousin marriages in England, and his (childless) son Leonard presided over the First International Congress of Eugenics in 1912, a congress devoted, ironically enough, to breeding fitter human beings.

  Scientists could possibly identify Darwin’s ailment with a DNA sample. But unlike Lincoln, Darwin died meekly of a heart attack, leaving no bloody pillowcases. And so far Westminster Abbey refuses to allow DNA sampling of Darwin’s bones, partly because doctors and geneticists can’t agree what to test for. Complicating things, some doctors conclude that Darwin’s illness had a serious hypochondriac edge, too, or sprung from other causes that we can’t pin down so easily. Indeed, our focus on Darwin’s DNA might even be misplaced, a product of our times. It should serve as a warning that when Freudianism was ascendant, many scientists saw Darwin’s illness as the consequence of an Oedipal struggle: the claim was that, unable to overthrow his biological father (an imposing man), Darwin instead “slew the Heavenly Father in the realm of natural history,” as one doctor gushed. To such thinking, Darwin’s suffering “obviously” derived from repressed guilt for this patricide.

  Perhaps our groping about in DNA sequences for the roots of illnesses like Darwin’s will look equally quaint someday. And regardless, this groping about misses a deeper point about Darwin and others—that they persevered, despite their illnesses. We tend to treat DNA as a secular soul, our chemical essence. But even a full rendering of someone’s DNA reveals only so much.

  14

  Three Billion Little Pieces

  Why Don’t Humans Have More Genes Than Other Species?

  Considering its scale, its scope, its ambition, the Human Genome Project—a multidecade, multibillion-dollar effort to sequence all human DNA—was rightly called the Manhattan Project of biology. But few anticipated at the outset that the HGP would be beset with just as many moral ambiguities as the venture in Los Alamos. Ask your biologist friends for a précis of the project, in fact, and you’ll get a pretty good handle on their values. Do they admire the project’s government scientists as selfless and steadfast or dismiss them as stumbling bureaucrats? Do they praise the private-sector challenge to the government as heroic rebellion or condemn it as greedy self-aggrandizement? Do they think the project succeeded or harp on its disappointments? Like any complex epic, the sequencing of the human genome can support virtually any reading.

  The HGP traces its pedigree to the 1970s, when British biologist Frederick Sanger, already a Nobel laureate, invented a method to sequence DNA—to record the order of the A’s, C’s, G’s, and T’s and thereby (hopefully) determine what the DNA does. In brief, Sanger’s method involved three basic steps: heating the DNA in question until its two strands separated; breaking those strands into fragments; and using individual A’s, C’s, G’s, and T’s to build new complementary strands based on the fragments. Cleverly, though, Sanger sprinkled in special radioactive versions of each base, which got incorporated into the complements. Because Sanger could distinguish whether A, C, G, or T was producing radioactivity at any point along the complement, he could also deduce which base resided there, and tally the sequence.*

  Sanger had to read these bases one by one, an excruciatingly tedious process. Nevertheless it allowed him to sequence the first genome, the fifty-four hundred bases and eleven genes of the virus φ-X174. (This work won Sanger a second Nobel in 1980—not bad for someone who once confessed he could never have attended Cambridge University “if my parents had not been fairly rich.”) In 1986 two biologists in California automated Sanger’s method. And instead of using radioactive bases, they substituted fluorescent versions of A, C, G, and T, each of which produced a different color when strummed by a laser—DNA in Technicolor. This machine, run by a computer, suddenly made large-scale sequencing projects seem feasible.

  Strangely, though, the U.S. government agency that funded most biology research, the National Institutes of Health, showed zero interest in DNA sequencing. Who, the NIH wondered, wanted to wade through three billion letters of formless data? Other departments weren’t so dismissive. The Department of Energy considered sequencing a natural extension of its work on how radioactivity damages DNA, and it appreciated the transformative potential of the work. So in April 1987, the DoE opened the world’s first human genome project, a seven-year, $1-billion effort centered in Los Alamos, across town from the site of the Manhattan Project. Funnily enough, as soon as NIH bureaucrats heard the B-word, billion, they decided sequencing made sense after all. So in September 1988 the NIH set up a rival sequencing institute to scoop up its share of the budgetary pie. In a scientific coup, it secured James Watson as the institute’s chief.

  By the 1980s, Watson had developed a reputation as the “Caligula of biology,” someone who, as one science historian put it, “was given license to say anything that came to his mind and expect to be taken seriously. And unfortunately he did so, with a casual and brutal offhandedness.” Still, however much he repulsed some of them personally, Watson retained the intellectual respect of his colleagues, which proved crucial for his new job, since few big-name biologists shared his enthusiasm for sequencing. Some biologists disliked the reductionist approach of the HGP, which threatened to demote human beings to dribbles of data. Others feared the project would swallow up all available research funds but not yield usable results for decades, a classic boondoggle. Still others simply found the work unbearably monotonous, even with machines helping. (One scientist cracked that only incarcerated felons should have to sequence—“twenty megabases [each],” he suggested, “with time off for accuracy.”) Most of all, scientists feared losing autonomy. A project so extensive would have to be coordinated centrally, and biologists resented the idea of becoming “indentured servants” who took orders on what research to pursue. “Many people in the American scientific community,” one early HGP supp
orter moaned, “will support small mediocrity before they can even consider the possibility that there can be some large excellence.”

  For all his crassness, Watson assuaged his colleagues’ fears and helped the NIH wrest control of the project from the DoE. He canvassed the country, giving a stump speech about the urgency of sequencing, and emphasized that the HGP would sequence not only human DNA but mouse and fruit fly DNA, so all geneticists would benefit. He also suggested mapping human chromosomes first thing, by locating every gene on them (similar to what Charles Sturtevant did in 1911 with fruit flies). With the map, Watson argued, any scientist could find her pet gene and make progress studying it without waiting fifteen years, the NIH’s timeline for sequencing. With this last argument, Watson also had his eye on Congress, whose fickle, know-nothing members might yank funding if they didn’t see results last week. To further persuade Congress, some HGP boosters all but promised that as long as Congress ponied up, the HGP would liberate humans from the misery of most diseases. (And not just diseases; some hinted that hunger, poverty, and crime might cease.) Watson brought in scientists from other nations, too, to give sequencing international prestige, and soon the HGP had lumbered to life.