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

by Sam Kean

  The triplicate rediscovery of Mendel in 1900 further galvanized the anti-Darwinists by providing a scientific alternative—and soon an outright rival. Mendel’s work emphasized not murder and starvation but growth and generation. Moreover, Mendel’s peas showed signs of jerkiness—tall or short stalks, yellow or green peas, nothing in between. Already by 1902 the English biologist William Bateson had helped a doctor identify the first known gene in humans (for an alarming but largely benign disorder, alkaptonuria, which can turn children’s urine black). Bateson soon rebranded Mendelism “genetics” and became Mendel’s bulldog in Europe, tirelessly championing the monk’s work, even taking up chess and cigars simply because Mendel loved both. Others supported Bateson’s creepy zealotry, however, because Darwinism violated the progressive ethos of the young century. Already by 1904, German scientist Eberhard Dennert could cackle, “We are standing at the death-bed of Darwinism, and making ready to send the friends of the patient a little money, to ensure a decent burial.” (A sentiment fit for a creationist today.) To be sure, a minority of biologists defended Darwin’s vision of gradual evolution against the Dennerts and Batesons of the world, and defended it fiercely—one historian commented on both sides’ “remarkable degree of bitchiness.” But these stubborn few could not prevent the eclipse of Darwinism from growing ever darker.

  Still, while Mendel’s work galvanized the anti-Darwinists, it never quite united them. By the early 1900s, scientists had discovered various important facts about genes and chromosomes, facts that still undergird genetics today. They determined that all creatures have genes; that genes can change, or mutate; that all chromosomes in cells come in pairs; and that all creatures inherit equal numbers of chromosomes from Mom and Dad. But there was no overarching sense of how these discoveries meshed; the individual pixels never resolved into a coherent picture. Instead a baffling array of half theories emerged, like “chromosome theory,” “mutation theory,” “gene theory,” and so on. Each championed one narrow aspect of heredity, and each drew distinctions that seem merely confusing today: some scientists believed (wrongly) that genes didn’t reside on chromosomes; others that each chromosome harbored just one gene; still others that chromosomes played no role in heredity at all. It’s whiggishly unfair to say, but reading these overlapping theories can be downright frustrating today. You want to scream at the scientists, like a dimwit on Wheel of Fortune or something, “Think! It’s all right there!” But each fiefdom discounted discoveries by rivals, and they squabbled against each other almost as much as against Darwinism.

  As these revolutionaries and counterrevolutionaries bitched it out in Europe, the scientist who eventually ended the Darwin-genetics row was working in anonymity in America. Though he mistrusted both Darwinists and geneticists—too much bloviating about theory all around—Thomas Hunt Morgan had developed an interest in heredity after visiting a botanist in Holland in 1900. Hugo de Vries had been one of the trio who rediscovered Mendel that year, and de Vries’s fame in Europe rivaled Darwin’s, partly because de Vries had developed a rival theory for the origin of species. De Vriesian “mutation theory” argued that species went through rare but intense mutation periods, during which the parents produced “sports,” offspring with markedly different traits. De Vries developed mutation theory after spotting some anomalous evening primroses in an abandoned potato field near Amsterdam. Some of these sport primroses sported smoother leaves, longer stems, or bigger yellow flowers with more petals. And crucially, primrose sports wouldn’t mate with the old, normal primroses; they seemed to have jumped past them and become a new species. Darwin had rejected evolutionary jumps because he believed that if one sport emerged, it would have to breed with normal individuals, diluting its good qualities. De Vries’s mutation period removed this objection at a stroke: many sports emerged at once, and they could breed only with each other.

  The primrose results scored themselves into Morgan’s brain. That de Vries had no clue how or why mutations appeared mattered not a lick. At last Morgan saw proof of new species emerging, not speculation. After landing a post at Columbia University in New York, Morgan decided to study mutation periods in animals. He began experiments on mice, guinea pigs, and pigeons, but when he discovered how slowly they bred, he took a colleague’s suggestion and tried Drosophila, fruit flies.

  Like many New Yorkers then, fruit flies had recently immigrated, in their case arriving on boats with the first banana crops in the 1870s. These exotic yellow fruits, usually wrapped in foil, had sold for ten cents per, and guards in New York stood watch over banana trees to prevent eager mobs from stealing the fruit. But by 1907 bananas and flies were common enough in New York that Morgan’s assistant could catch a whole horde for research simply by slicing up a banana and leaving it on a windowsill to rot.

  Fruit flies proved perfect for Morgan’s work. They bred quickly—one generation every twelve days—and survived on food cheaper than peanuts. They also tolerated claustrophobic Manhattan real estate. Morgan’s lab—the “fly room,” 613 Schermerhorn Hall at Columbia—measured sixteen feet by twenty-three feet and had to accommodate eight desks. But a thousand fruit flies lived happily in a one-quart milk bottle, and Morgan’s shelves were soon lined with the dozens of bottles that (legend has it) his assistants “borrowed” from the student cafeteria and local stoops.

  Thomas Hunt Morgan’s cluttered, squalid fly room at Columbia University. Hundreds of fruit flies swarmed around inside each bottle, surviving on rotten bananas. (The American Philosophical Society)

  Morgan set himself up at the fly room’s central desk. Cockroaches scuttled through his drawers, nibbling rotten fruit, and the room was a cacophony of buzzing, but Morgan stood unperturbed in the middle of all, peering through a jeweler’s loupe, scrutinizing bottle after bottle for de Vries’s mutants. When a bottle produced no interesting specimens, Morgan might squash them with his thumb and smear their guts wherever, often in lab notebooks. Unfortunately for general sanitation, Morgan had many, many flies to smush: although the Drosophila bred and bred and bred, he found no sign of sports.

  Meanwhile Morgan got lucky in a different arena. In autumn 1909, he filled in for a colleague on sabbatical and taught the only introductory course of his Columbia career. And during that semester he made, one observer noted, “his greatest discovery,” two brilliant assistants. Alfred Sturtevant heard about Morgan’s class through a brother who taught Latin and Greek at Columbia, and although just a sophomore, Sturtevant impressed Morgan by writing an independent research paper on horses and the inheritance of coat color. (Morgan hailed from Kentucky, and his father and uncle had been famous horse thieves behind Union lines during the Civil War, leading a band known as Morgan’s Raiders. Morgan scorned his Confederate past, but he knew his horses.) From that moment on, Sturtevant was Morgan’s golden boy and eventually earned a coveted desk in the fly room. Sturtevant cultivated a cultured air, reading widely in literature and doing trickier British crossword puzzles—although, amid the fly room’s squalor, someone also once discovered a mummified mouse in his desk. Sturtevant did have one deficiency as a scientist, red-green color blindness. He’d tended horses on the family fruit farm in Alabama largely because he proved useless during harvest, struggling to spot red strawberries on green bushes.

  The other undergrad, Calvin Bridges, made up for Sturtevant’s poor eyesight, and his stuffiness. At first Morgan merely took pity on Bridges, an orphan, by giving him a job washing filth from milk bottles. But Bridges eavesdropped on Morgan’s discussions of his work, and when Bridges began spotting interesting flies with his bare eyes (even through the dirty glass bottles), Morgan hired him as a researcher. It was basically the only job Bridges ever had. A sensuous and handsome man with bouffant hair, Bridges practiced free love avant la lettre. He eventually abandoned his wife and children, got a vasectomy, and started brewing moonshine in his new bachelor lair in Manhattan. He proceeded to hit on—or flat-out proposition—anything in a skirt, including colleagues’ wives.
His naive charm seduced many, but even after the fly room became legendary, no other university would blacken its reputation by employing Bridges as anything but a measly assistant.

  Playboy Calvin Bridges (left) and a rare photo of Thomas Hunt Morgan (right). Morgan so detested having his picture taken that an assistant who once wanted one had to hide a camera in a bureau in the fly lab and snap the photo remotely by tugging a string. (Courtesy of the National Library of Medicine)

  Meeting Bridges and Sturtevant must have cheered Morgan, because his experiments had all but flopped until then. Unable to find any natural mutants, he’d exposed flies to excess heat and cold and injected acids, salts, bases, and other potential mutagens into their genitals (not easy to find). Still nothing. On the verge of giving up, in January 1910 he finally spotted a fly with a strange trident shape tattooed on its thorax. Not exactly a de Vriesian über-fly, but something. In March two more mutants appeared, one with ragged moles near its wings that made it appear to have “hairy armpits,” another with an olive (instead of the normal amber) body color. In May 1910 the most dramatic mutant yet appeared, a fly with white (instead of red) eyes.

  Anxious for a breakthrough—perhaps this was a mutation period—Morgan tediously isolated white-eyes. He uncapped the milk bottle, balanced another one upside down on top of it like mating ketchup bottles, and shined a light through the top to coax white-eyes upward. Of course, hundreds of other flies joined white-eyes in the top bottle, so Morgan had to quickly cap both, get a new milk bottle, and repeat the process over and over, slowly dwindling the number with each step, praying to God white-eyes didn’t escape meantime. When he finally, finally segregated the bug, he mated it with red-eyed females. Then he bred the descendants with each other in various ways. The results were complex, but one result especially excited Morgan: after crossing some red-eyed descendants with each other, he discovered among the offspring a 3:1 ratio of red to white eyes.

  The year before, in 1909, Morgan had heard the Danish botanist Wilhelm Johannsen lecture about Mendelian ratios at Columbia. Johannsen used the occasion to promote his newly minted word, gene, a proposed unit of inheritance. Johannsen and others freely admitted that genes were convenient fictions, linguistic placeholders for, well, something. But they insisted that their ignorance about the biochemical details of genes shouldn’t invalidate the usefulness of the gene concept for studying inheritance (similar to how psychologists today can study euphoria or depression without understanding the brain in detail). Morgan found the lecture too speculative, but his experimental results—3:1—promptly lowered his prejudice to Mendel.

  This was quite a volte-face for Morgan, but it was just the start. The eye-color ratios convinced him that gene theory wasn’t bunk. But where were genes actually located? Perhaps on chromosomes, but fruit flies had hundreds of inheritable traits and only four chromosomes. Assuming one trait per chromosome, as many scientists did, there weren’t enough to go around. Morgan didn’t want to get dragged into debates on so-called chromosome theory, but a subsequent discovery left him no choice: because when he scrutinized his white-eyed flies, he discovered that every last mutant was male. Scientists already knew that one chromosome determined the gender of flies. (As in mammals, female flies have two X chromosomes, males one.) Now the white-eye gene was linked to that chromosome as well—putting two traits on it. Soon the fly boys found other genes—stubby wings, yellow bodies—also linked exclusively to males. The conclusion was inescapable: they’d proved that multiple genes rode around together on one chromosome.* That Morgan had proved this practically against his own will mattered little; he began to champion chromosome theory anyway.

  Overthrowing old beliefs like this became a habit with Morgan, simultaneously his most admirable and most maddening trait. Although he encouraged theoretical discussions in the fly room, Morgan considered new theories cheap and facile—worth little until cross-examined in the lab. He didn’t seem to grasp that scientists need theories as guides, to decide what’s relevant and what’s not, to frame their results and prevent muddled thinking. Even undergraduates like Bridges and Sturtevant—and especially a student who joined the fly room later, the abrasively brilliant and brilliantly abrasive Hermann Muller—grew hair-rippingly frustrated with Morgan in the many quarrels they had over genes and heredity. And then, just as exasperating, when someone did wrestle Morgan into a headlock and convince him he was wrong, Morgan would ditch his old ideas and with no embarrassment whatsoever absorb the new ones as obvious.

  To Morgan, this quasi plagiarism was no big deal. Everyone was working toward the same goal (right, fellas?), and only experiments mattered anyway. And to his credit, his about-faces proved that Morgan listened to his assistants, a contrast to the condescending relationship most European scientists had with their help. For this reason Bridges and Sturtevant always publicly professed their loyalty to Morgan. But visitors sometimes picked up on sibling rivalries among the assistants, and secret smoldering. Morgan didn’t mean to connive or manipulate; credit for ideas just meant that little to him.

  Nevertheless ideas kept ambushing Morgan, ideas he hated. Because not long after the unified gene-chromosome theory emerged, it nearly unraveled, and only a radical idea could salvage it. Again, Morgan had determined that multiple genes clustered together on one chromosome. And he knew from other scientists’ work that parents pass whole chromosomes on to their children. All the genetic traits on each chromosome should therefore always be inherited together—they should always be linked. To take a hypothetical example, if one chromosome’s set of genes call for green bristles and sawtooth wings and fat antennae, any fly with one trait should exhibit all three. Such clusters of traits do exist in flies, but to their dismay, Morgan’s team discovered that certain linked traits could sometimes become unlinked—green bristles and sawtooth wings, which should always appear together, would somehow show up separately, in different flies. Unlinkings weren’t common—linked traits might separate 2 percent of the time, or 4 percent—but they were so persistent they might have undone the entire theory, if Morgan hadn’t indulged in a rare flight of fancy.

  He remembered reading a paper by a Belgian biologist-priest who had used a microscope to study how sperm and eggs form. One key fact of biology—it comes up over and over—is that all chromosomes come in pairs, pairs of nearly identical twins. (Humans have forty-six chromosomes, arranged in twenty-three pairs.) When sperm and eggs form, these near-twin chromosomes all line up in the middle of the parent cell. During division one twin gets pulled one way, the other the other way, and two separate cells are born.

  However, the priest-biologist noticed that, just before the divvying up, twin chromosomes sometimes interacted, coiling their tips around each other. He didn’t know why. Morgan suggested that perhaps the tips broke off during this crossing over and swapped places. This explained why linked traits sometimes separated: the chromosome had broken somewhere between the two genes, dislocating them. What’s more, Morgan speculated—he was on a roll—that traits separating 4 percent of the time probably sat farther apart on chromosomes than those separating 2 percent of the time, since the extra distance between the first pair would make breaking along that stretch more likely.

  Morgan’s shrewd guess turned out correct, and with Sturtevant and Bridges adding their own insights over the next few years, the fly boys began to sketch out a new model of heredity—the model that made Morgan’s team so historically important. It said that all traits were controlled by genes, and that these genes resided on chromosomes in fixed spots, strung along like pearls on a necklace. Because creatures inherit one copy of each chromosome from each parent, chromosomes therefore pass genetic traits from parent to child. Crossing over (and mutation) changes chromosomes a little, which helps make each creature unique. Nevertheless chromosomes (and genes) stay mostly intact, which explains why traits run in families. Voilà: the first overarching sense of how heredity works.

  In truth, little of this theory originated in M
organ’s lab, as biologists worldwide had discovered various pieces. But Morgan’s team finally linked these vaguely connected ideas, and fruit flies provided overwhelming experimental proof. No one could deny that sex chromosome linkage occurred, for instance, when Morgan had ten thousand mutants buzzing on a shelf, nary a female among them.

  Of course, while Morgan won acclaim for uniting these theories, he’d done nothing to reconcile them with Darwinian natural selection. That reconciliation also arose from work inside the fly room, but once again Morgan ended up “borrowing” the idea from assistants, including one who didn’t accept this as docilely as Bridges and Sturtevant did.

  Hermann Muller began poking around the fly room in 1910, though only occasionally. Because he supported his elderly mother, Muller lived a haphazard life, working as a factotum in hotels and banks, tutoring immigrants in English at night, bolting down sandwiches on the subway between jobs. Somehow Muller found time to befriend writer Theodore Dreiser in Greenwich Village, immerse himself in socialist politics, and commute two hundred miles to Cornell University to finish a master’s degree. But no matter how frazzled he got, Muller used his one free day, Thursday, to drop in on Morgan and the fly boys and bandy about ideas on genetics. Intellectually nimble, Muller starred in these bull sessions, and Morgan granted him a desk in the fly room after he graduated from Cornell in 1912. The problem was, Morgan declined to pay Muller, so Muller’s schedule didn’t let up. He soon had a mental breakdown.

  From then on, and for decades afterward, Muller seethed over his status in the fly room. He seethed that Morgan openly favored the bourgeois Sturtevant and shunted menial tasks like preparing bananas onto the blue-collar, proletariat Bridges. He seethed that both Bridges and Sturtevant got paid to experiment on his, Muller’s, ideas, while he scrambled around the five boroughs for pocket change. He seethed that Morgan treated the fly room like a clubhouse and sometimes made Muller’s friends work down the hall. Muller seethed above all that Morgan was oblivious to his contributions. This was partly because Muller proved slow in doing the thing Morgan most valued—actually carrying out the clever experiments he (Muller) dreamed up. Indeed, Muller probably couldn’t have found a worse mentor than Morgan. For all his socialist leanings, Muller got pretty attached to his own intellectual property, and felt the free and communal nature of the fly room both exploited and ignored his talent. Nor was Muller exactly up for Mr. Congeniality. He harped on Morgan, Bridges, and Sturtevant with tactless criticism, and got almost personally offended by anything but pristine logic. Morgan’s breezy dismissal of evolution by natural selection especially irked Muller, who considered it the foundation of biology.