The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (8 page)

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.

A
ugust 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.

All the while, beneath his incinerated skin, Yamaguchi’s DNA was nursing even graver injuries. The nuclear bomb at Hiroshima released (among other radioactivity) loads of supercharged x-rays called gamma rays. Like most radioactivity, these rays single out and selectively damage DNA, punching DNA and nearby water molecules and making electrons fly out like uppercut teeth. The sudden loss of electrons forms free radicals,
highly reactive atoms that chew on chemical bonds. A chain reaction begins that cleaves DNA and sometimes snaps chromosomes into pieces.

By the mid-1940s, scientists were starting to grasp why the shattering or disruption of DNA could wreak such ruin inside cells. First, scientists based in New York produced strong evidence that genes were made of DNA. This upended the persistent belief in protein inheritance. But as a second study revealed, DNA and proteins still shared a special relationship: DNA
made
proteins, with each DNA gene storing the recipe for one protein. Making proteins, in other words, was what genes did—that’s how genes created traits in the body.

In conjunction, these two ideas explained the harm of radioactivity. Fracturing DNA disrupts genes; disrupting genes halts protein production; halting protein production kills cells. Scientists didn’t work this out instantly—the crucial “one gene/one protein” paper appeared just days before Hiroshima—but they knew enough to cringe at the thought of nuclear weapons. When Hermann Muller won his Nobel Prize in 1946, he prophesied to the
New York Times
that if atomic bomb survivors “could foresee the results 1,000 years from now… they might consider themselves more fortunate if the bomb had killed them.”

Despite Muller’s pessimism, Yamaguchi did want to survive, badly, for his family. He’d had complicated feelings about the war—opposing it at first, supporting it once under way, then shading back toward opposition when Japan began to stumble, because he feared the island being overrun by enemies who might harm his wife and son. (If so, he’d contemplated giving them an overdose of sleeping pills to spare them.) In the hours after Hiroshima, he yearned to get back to them, so when he heard rumors about trains leaving the city, he sucked up his strength and resolved to find one.

Hiroshima is a collection of islands, and Yamaguchi had to
cross a river to reach the train station. All the bridges had collapsed or burned, so he steeled himself and began crossing an apocalyptic “bridge of corpses” clogging the river, crawling across melted legs and faces. But an uncrossable gap in the bridge forced him to turn back. Farther upstream, he found a railroad trestle with one steel beam intact, spanning fifty yards. He clambered up, crossed the iron tightrope, and descended. He pushed through the mob at the station and slumped into a train seat. Miraculously the train pulled out soon afterward—he was saved. The train would run all night, but he was finally headed home, to Nagasaki.

A physicist stationed in Hiroshima might have pointed out that the gamma rays finished working over Yamaguchi’s DNA in a millionth of a billionth of a second. To a chemist, the most interesting part—how the free radicals gnawed through DNA—would have ceased after a millisecond. A cell biologist would have needed to wait maybe a few hours to study how cells patch up torn DNA. A doctor could have diagnosed radiation sickness—headaches, vomiting, internal bleeding, peeling skin, anemic blood—within a week. Geneticists needed the most patience. The genetic damage to the survivors didn’t surface for years, even decades. And in an eerie coincidence, scientists began to piece together how exactly genes function, and fail, during those very decades—as if providing a protracted running commentary on DNA devastation.

However definitive in retrospect, experiments on DNA and proteins in the 1940s convinced only some scientists that DNA was the genetic medium. Better proof came in 1952, from virologists Alfred Hershey and Martha Chase. Viruses, they knew, hijacked cells by injecting genetic material. And because the viruses they studied consisted of only DNA and proteins, genes
had to be one or the other. The duo determined which by tagging viruses with both radioactive sulfur and radioactive phosphorus, then turning them loose on cells. Proteins contain sulfur but no phosphorus, so if genes were proteins, radioactive sulfur should be present in cells postinfection. But when Hershey and Chase filtered out infected cells, only radioactive phosphorus remained: only DNA had been injected.

Hershey and Chase published these results in April 1952, and they ended their paper by urging caution: “Further chemical inferences should not be drawn from the experiments presented.” Yeah, right. Every scientist in the world still working on protein heredity dumped his research down the sink and took up DNA. A furious race began to understand the structure of DNA, and just one year later, in April 1953, two gawky scientists at Cambridge University in England, Francis Crick and James Watson (a former student of Hermann Muller), made the term “double helix” legendary.

Watson and Crick’s double helix was two loooooooong DNA strands wrapped around each other in a right-handed spiral. (Point your right thumb toward the ceiling; DNA twists upward along the counterclockwise curl of your fingers.) Each strand consisted of two backbones, and the backbones were held together by paired bases that fit together like puzzle pieces—angular A with T, curvaceous C with G. Watson and Crick’s big insight was that because of this complementary A-T and C-G base pairing, one strand of DNA can serve as a template for copying the other. So if one side reads CCGAGT, the other side must read GGCTCA. It’s such an easy system that cells can copy hundreds of DNA bases per second.

However well hyped, though, the double helix revealed zero about how DNA genes actually made proteins—which is, after all, the important part. To understand this process, scientists had to scrutinize DNA’s chemical cousin, RNA. Though similar
to DNA, RNA is single-stranded, and it substitutes the letter U (uracil) for T in its strands. Biochemists focused on RNA because its concentration would spike tantalizingly whenever cells started making proteins. But when they chased the RNA around the cell, it proved as elusive as an endangered bird; they caught only glimpses before it vanished. It took years of patient experiments to determine exactly what was going on here—exactly how cells transform strings of DNA letters into RNA instructions and RNA instructions into proteins.

Cells first “transcribe” DNA into RNA. This process resembles the copying of DNA, in that one strand of DNA serves as a template. So the DNA string CCGAGT would become the RNA string GGCUCA (with U replacing T). Once constructed, this RNA string leaves the confines of the nucleus and chugs out to special protein-building apparatuses called ribosomes. Because it carries the message from one site to another, it’s called messenger RNA.

The protein building, or translation, begins at the ribosomes. Once the messenger RNA arrives, the ribosome grabs it near the end and exposes just three letters of the string, a triplet. In our example, GGC would be exposed. At this point a second type of RNA, called transfer RNA, approaches. Each transfer RNA has two key parts: an amino acid trailing behind it (its cargo to transfer), and an RNA triplet sticking off its prow like a masthead. Various transfer RNAs might try to dock with the messenger RNA’s exposed triplet, but only one with complementary bases will stick. So with the triplet GGC, only a transfer RNA with CCG will stick. And when it does stick, the ribosome unloads its amino acid cargo.

At this point the transfer RNA leaves, the messenger RNA shifts down three spots, and the process repeats. A different triplet is exposed, and a different transfer RNA with a different amino acid docks. This puts amino acid number two in place.
Eventually, after many iterations, this process creates a string of amino acids—a protein. And because each RNA triplet leads to one and only one amino acid being added, information should (should) get translated perfectly from DNA to RNA to protein. This same process runs every living thing on earth. Inject the same DNA into guinea pigs, frogs, tulips, slime molds, yeast, U.S. congressmen, whatever, and you get identical amino acid chains. No wonder that in 1958 Francis Crick elevated the DNA → RNA → protein process into the “Central Dogma” of molecular biology.
^*

Still, Crick’s dogma doesn’t explain everything about protein construction. For one thing, notice that, with four DNA letters, sixty-four different triplets are possible (4 × 4 × 4 = 64). Yet all those triplets code for just twenty amino acids in our bodies. Why?

A physicist named George Gamow founded the RNA Tie Club in 1954 in part to figure out this question. A physicist moonlighting in biology might sound odd—Gamow studied radioactivity and Big Bang theory by day—but other carpetbagging physicists like Richard Feynman joined the club as well. Not only did RNA offer an intellectual challenge, but many physicists felt appalled by their role in creating nuclear bombs. Physics seemed life destroying, biology life restoring. Overall, twenty-four physicists and biologists joined the Tie Club’s roster—one for each amino acid, plus four honorary inductees, for each DNA base. Watson and Crick joined (Watson as official club “Optimist,” Crick as “Pessimist”), and each member sported a four-dollar bespoke green wool tie with an RNA strand embroidered in gold silk, made by a haberdasher in Los Angeles. Club stationery read, “Do or die, or don’t try.”