by Sam Kean
Despite the personality clashes he caused, Muller pushed the fly group to greater work. In fact, while Morgan contributed little to the emerging theory of inheritance after 1911, Muller, Bridges, and Sturtevant kept making fundamental discoveries. Unfortunately, it’s hard to sort out nowadays who discovered what, and not just because of the constant idea swapping. Morgan and Muller often scribbled thoughts down on unorganized scraps, and Morgan purged his file cabinet every five years, perhaps out of necessity in his cramped lab. Muller hoarded documents, but many years later, yet another colleague he’d managed to alienate threw out Muller’s files while Muller was working abroad. Morgan also (like Mendel’s fellow friars) destroyed Bridges’s files when the free lover died of heart problems in 1938. Turns out Bridges was a bedpost notcher, and when Morgan found a detailed catalog of fornication, he thought it prudent to burn all the papers and protect everyone in genetics.
But historians can assign credit for some things. All the fly boys helped determine which clusters of traits got inherited together. More important, they discovered that four distinct clusters existed in flies—exactly the number of chromosome pairs. This was a huge boost for chromosome theory because it showed that every chromosome harbored multiple genes.
Sturtevant built on this notion of gene and chromosome linkage. Morgan had guessed that genes separating 2 percent of the time must sit closer together on chromosomes than genes separating 4 percent of the time. Ruminating one evening, Sturtevant realized he could translate those percentages into actual distances. Specifically, genes separating 2 percent of the time must sit twice as close together as the other pair; similar logic held for other percent linkages. Sturtevant blew off his undergraduate homework that night, and by dawn this nineteen-year-old had sketched the first map of a chromosome. When Muller saw the map, he “literally jumped with excitement”—then pointed out ways to improve it.
Bridges discovered “nondisjunction”—the occasional failure of chromosomes to separate cleanly after crossing over and twisting arms. (The excess of genetic material that results can cause problems like Down syndrome.) And beyond individual discoveries, Bridges, a born tinkerer, industrialized the fly room. Instead of tediously separating flies by turning bottle after bottle upside down, Bridges invented an atomizer to puff wee doses of ether over flies and stun them. He also replaced loupes with binocular microscopes; handed out white porcelain plates and fine-tipped paintbrushes so that people could see and manipulate flies more easily; eliminated rotting bananas for a nutritious slurry of molasses and cornmeal; and built climate-controlled cabinets so that flies, which become sluggish in cold, could breed summer and winter. He even built a fly morgue to dispose of corpses with dignity. Morgan didn’t always appreciate these contributions—he continued to squish flies wherever they landed, despite the morgue. But Bridges knew that mutants popped up so rarely, and when they did, his biological factory allowed each one to thrive and produce millions of descendants.*
Muller contributed insights and ideas, dissolving apparent contradictions and undergirding lean-to theories with firm logic. And although he had to argue with Morgan until his tongue bled, he finally made the senior scientist see how genes, mutations, and natural selection work together. As Muller (among others) outlined it: Genes give creatures traits, so mutations to genes change traits, making creatures different in color, height, speed, or whatever. But contra de Vries—who saw mutations as large things, producing sports and instant species—most mutations simply tweak creatures. Natural selection then allows the better-adapted of these creatures to survive and reproduce more often. Crossing over comes into play because it shuffles genes around between chromosomes and therefore puts new versions of genes together, giving natural selection still more variety to work on. (Crossing over is so important that some scientists today think that sperm and eggs refuse to form unless chromosomes cross a minimum number of times.)
Muller also helped expand scientists’ very ideas about what genes could do. Most significantly, he argued that traits like the ones Mendel had studied—binary traits, controlled by one gene—weren’t the only story. Many important traits are controlled by multiple genes, even dozens of genes. These traits will therefore show gradations, depending on which exact genes a creature inherits. Certain genes can also turn the volume up or down on other genes, crescendos and decrescendos that produce still finer gradations. Crucially, however, because genes are discrete and particulate, a beneficial mutation will not be diluted between generations. The gene stays whole and intact, so superior parents can breed with inferior types and still pass the gene along.
To Muller, Darwinism and Mendelism reinforced each other beautifully. And when Muller finally convinced Morgan of this, Morgan became a Darwinian. It’s easy to chuckle over this—yet another Morgan conversion—and in later writings, Morgan still emphasizes genetics as more important than natural selection. However, Morgan’s endorsement was important in a larger sense. Grandiloquent theories (including Darwin’s) dominated biology at the time, and Morgan had helped keep the field grounded, always demanding hard evidence. So other biologists knew that if some theory convinced even Thomas Hunt Morgan, it had something going for it. What’s more, even Muller recognized Morgan’s personal influence. “We should not forget,” Muller once admitted, “the guiding personality of Morgan, who infected all the others by his own example—his indefatigable activity, his deliberation, his jolliness, and courage.” In the end, Morgan’s bonhomie did what Muller’s brilliant sniping couldn’t: convinced geneticists to reexamine their prejudice against Darwin, and take the proposed synthesis of Darwin and Mendel, natural selection and genetics, seriously.
Many other scientists did indeed take up the work of Morgan’s team in the 1920s, spreading the unassuming fruit fly to labs around the world. It soon became the standard animal in genetics, allowing scientists everywhere to compare discoveries on equal terms. Building on such work, a generation of mathematically minded biologists in the 1930s and 1940s began investigating how mutations spread in natural populations, outside the lab. They demonstrated that if a gene gave some creatures even a small survival advantage, that boost could, if compounded long enough, push species in new directions. What’s more, most changes would take place in tiny steps, exactly as Darwin had insisted. If the fly boys’ work finally showed how to link Mendel with Darwin, these later biologists made the case as rigorous as a Euclidean proof. Darwin had once moaned how “repugnant” math was to him, how he struggled with most anything beyond taking simple measurements. In truth, mathematics buttressed Darwin’s theory and ensured his reputation would never lapse again.* And in this way the so-called eclipse of Darwinism in the early 1900s proved exactly that: a period of darkness and confusion, but a period that ultimately passed.
Beyond the scientific gains, the diffusion of fruit flies around the world inspired another legacy, a direct outgrowth of Morgan’s “jolliness.” Throughout genetics, the names of most genes are ugly abbreviations, and they stand for monstrous freak words that maybe six people worldwide understand. So when discussing, say, the alox12b gene, there’s often no point in spelling out its name (arachidonate 12-lipoxygenase, 12R type), since doing so confuses rather than clarifies, methinks. (To save everyone a migraine, from now on I’ll just state gene acronyms and pretend they stand for nothing.) In contrast, whereas gene names are intimidatingly complex, chromosome names are stupefyingly banal. Planets are named after gods, chemical elements after myths, heroes, and great cities. Chromosomes were named with all the creativity of shoe sizes. Chromosome one is the longest, chromosome two the second longest, and (yawn) so on. Human chromosome twenty-one is actually shorter than chromosome twenty-two, but by the time scientists figured this out, chromosome twenty-one was famous, since having an extra number twenty-one causes Down syndrome. And really, with such boring names, there was no point in fighting over them and bothering to change.
Fruit fly scientists, God bless ’em, are the big exception. Morgan’s
team always picked sensibly descriptive names for mutant genes like speck, beaded, rudimentary, white, and abnormal. And this tradition continues today, as the names of most fruit fly genes eschew jargon and even shade whimsical. Different fruit fly genes include groucho, smurf, fear of intimacy, lost in space, smellblind, faint sausage, tribble (the multiplying fuzzballs on Star Trek), and tiggywinkle (after Mrs. Tiggy-winkle, a character from Beatrix Potter). The armadillo gene, when mutated, gives fruit flies a plated exoskeleton. The turnip gene makes flies stupid. Tudor leaves males (as with Henry VIII) childless. Cleopatra can kill flies when it interacts with another gene, asp. Cheap date leaves flies exceptionally tipsy after a sip of alcohol. Fruit fly sex especially seems to inspire clever names. Ken and barbie mutants have no genitalia. Male coitus interruptus mutants spend just ten minutes having sex (the norm is twenty), while stuck mutants cannot physically disengage after coitus. As for females, dissatisfaction mutants never have sex at all—they spend all their energy shooing suitors away by snapping their wings. And thankfully, this whimsy with names has inspired the occasional zinger in other areas of genetics. A gene that gives mammals extra nipples earned the name scaramanga, after the James Bond villain with too many. A gene that removes blood cells from circulation in fish became the tasteful vlad tepes, after Vlad the Impaler, the historical inspiration for Dracula. The backronym for the “POK erythroid myeloid ontogenic” gene in mice—pokemon—nearly provoked a lawsuit, since the pokemon gene (now known, sigh, as zbtb7) contributes to the spread of cancer, and the lawyers for the Pokémon media empire didn’t want their cute little pocket monsters confused with tumors. But my winner for the best, and freakiest, gene name goes to the flour beetle’s medea, after the ancient Greek mother who committed infanticide. Medea encodes a protein with the curious property that it’s both a poison and its own antidote. So if a mother has this gene but doesn’t pass it to an embryo, her body exterminates the fetus—nothing she can do about it. If the fetus has the gene, s/he creates the antidote and lives. (Medea is a “selfish genetic element,” a gene that demands its own propagation above all, even to the detriment of a creature as a whole.) If you can get beyond the horror, it’s a name worthy of the Columbia fruit fly tradition, and it’s fitting that the most important clinical work on medea—which could lead to very smart insecticides—came after scientists introduced it into Drosophila for further study.
But long before these cute names emerged, and even before fruit flies had colonized genetics labs worldwide, the original fly group at Columbia had disbanded. Morgan moved to the California Institute of Technology in 1928 and took Bridges and Sturtevant with him to his new digs in sunny Pasadena. Five years later Morgan became the first geneticist to win the Nobel Prize, “for establishing,” one historian noted, “the very principles of genetics he had set out to refute.” The Nobel committee has an arbitrary rule that three people at most can share a Nobel, so the committee awarded it to Morgan alone, rather than—as it should have—splitting it between him, Bridges, Sturtevant, and Muller. Some historians argue that Sturtevant did work important enough to win his own Nobel but that his devotion to Morgan and willingness to relinquish credit for ideas diminished his chances. Perhaps in tacit acknowledgment of this, Morgan shared his prize money from the Nobel with Sturtevant and Bridges, setting up college funds for their children. He shared nothing with Muller.
Muller had fled Columbia for Texas by then. He started in 1915 as a professor at Rice University (whose biology department was chaired by Julian Huxley, grandson of Darwin’s bulldog) and eventually landed at the University of Texas. Although Morgan’s warm recommendation had gotten him the Rice job, Muller actively promoted a rivalry between his Lone Star and Morgan’s Empire State groups, and whenever the Texas group made a significant advance, which they trumpeted as a “home run,” they preened. In one breakthrough, biologist Theophilus Painter discovered the first chromosomes—inside fruit fly spit glands*—that were large enough to inspect visually, allowing scientists to study the physical basis of genes. But as important as Painter’s work was, Muller hit the grand slam in 1927 when he discovered that pulsing flies with radiation would increase their mutation rate by 150 times. Not only did this have health implications, but scientists no longer had to sit around and wait for mutations to pop up. They could mass-produce them. The discovery gave Muller the scientific standing he deserved—and knew he deserved.
Inevitably, though, Muller got into spats with Painter and other colleagues, then outright brawls, and he soured on Texas. Texas soured on him, too. Local newspapers outed him as a political subversive, and the precursor to the FBI put him under surveillance. Just for fun, his marriage crumbled, and one evening in 1932 his wife reported him missing. A posse of colleagues later found him muddied and disheveled in the woods, soaked by a night of rain, his head still foggy from the barbiturates he’d swallowed to kill himself.
Burned out, humiliated, Muller abandoned Texas for Europe. There he did a bit of a Forrest Gump tour of totalitarian states. He studied genetics in Germany until Nazi goons vandalized his institute. He fled to the Soviet Union, where he lectured Joseph Stalin himself on eugenics, the quest to breed superior human beings through science. Stalin was not impressed, and Muller scurried to leave. To avoid being branded a “bourgeois reactionary deserter,” Muller enlisted on the communist side in the Spanish Civil War, working at a blood bank. His side lost, and fascism descended.
Disillusioned yet again, Muller crawled back to the United States, to Indiana, in 1940. His interest in eugenics grew; he later helped establish what became the Repository for Germinal Choice, a “genius sperm bank” in California. And as the capstone to his career, Muller won his own unshared Nobel Prize in 1946 for the discovery that radiation causes genetic mutations. The award committee no doubt wanted to make up for shutting Muller out in 1933. But he also won because the atomic bomb attacks on Hiroshima and Nagasaki in 1945—which rained nuclear radiation on Japan—made his work sickeningly relevant. If the fly boys’ work at Columbia had proved that genes existed, scientists now had to figure out how genes worked and how, in the deadly light of the bomb, they too often failed.
3
Them’s the DNA Breaks
How Does Nature Read—and Misread—DNA?
August 6, 1945, started off pretty lucky for perhaps the most unlucky man of the twentieth century. Tsutomu Yamaguchi had stepped off his bus near Mitsubishi headquarters in Hiroshima when he realized he’d forgotten his inkan, the seal that Japanese salarymen dip in red ink and use to stamp documents. The lapse annoyed him—he faced a long ride back to his boardinghouse—but nothing could really dampen his mood that day. He’d finished designing a five-thousand-ton tanker ship for Mitsubishi, and the company would finally, the next day, send him back home to his wife and infant son in southwest Japan. The war had disrupted his life, but on August 7 things would return to normal.
As Yamaguchi removed his shoes at his boardinghouse door, the elderly proprietors ambushed him and asked him to tea. He could hardly refuse these lonely folk, and the unexpected engagement further delayed him. Shod again, inkan in hand, he hurried off, caught a streetcar, disembarked near work, and was walking along near a potato field when he heard a gnat of an enemy bomber high above. He could just make out a speck descending from its belly. It was 8:15 a.m.
Many survivors remember the curious delay. Instead of a normal bomb’s simultaneous flash-bang, this bomb flashed and swelled silently, and got hotter and hotter silently. Yamaguchi was close enough to the epicenter that he didn’t wait long. Drilled in air-raid tactics, he dived to the ground, covered his eyes, and plugged his ears with his thumbs. After a half-second light bath came a roar, and with it came a shock wave. A moment later Yamaguchi felt a gale somehow beneath him, raking his stomach. He’d been tossed upward, and after a short flight he hit the ground, unconscious.
He awoke, perhaps seconds later, perhaps an hour, to a darkened city. The mushroom cloud had sucked up tons of dirt and
ash, and small rings of fire smoked on wilted potato leaves nearby. His skin felt aflame, too. He’d rolled up his shirtsleeves after his cup of tea, and his forearms felt severely sunburned. He rose and staggered through the potato field, stopping every few feet to rest, shuffling past other burned and bleeding and torn-open victims. Strangely compelled, he reported to Mitsubishi. He found a pile of rubble speckled with small fires, and many dead coworkers—he’d been lucky to be late. He wandered onward; hours slipped by. He drank water from broken pipes, and at an emergency aid station, he nibbled a biscuit and vomited. He slept that night beneath an overturned boat on a beach. His left arm, fully exposed to the great white flash, had turned black.
