In the novel, Arrowsmith makes himself a disciple of Max Gottlieb, a man of “tyrannical honesty” who paces night after night in his laboratory and who tells his students, “I make many mistakes. But one thing I keep always pure: the religion of a scientist.” From Gottlieb, Arrowsmith learns to scorn the kind of careerist in medicine who thinks only about the practice and the fee; or the kind of plodding scientist who “never ventured on original experiments which, leading him into a confused land of wondering, might bring him to glory or disaster.” Arrowsmith ventures; he meets and marries a wonderful nurse named Leora; he finds both glory and disaster.
As soon as Benzer finished reading Arrowsmith, he bought the finest-pointed fountain pen and the blackest ink he could find and began to imitate Max Gottlieb’s handwriting, just as Sinclair Lewis describes it in the novel, “that dead-black spider-web script.”
When he graduated from high school at the age of fifteen, no one in his family had ever gone beyond the twelfth grade, and the Great Depression was dragging down his father’s business. But Seymour was the egg with two yellows, and he entered Brooklyn College on a Regents Scholarship. There, in his freshman year, he met a twenty-one-year-old nurse named Dora, nicknamed Dotty. Dotty took night duty at the hospital so that they could sneak time with each other while the patients slept, just like Martin Arrowsmith and his Leora.
NOT MANY PEOPLE have both a feeling for physics and a feeling for the study of life. In the original Fly Room, the raider with the strongest interest in both these sciences was a short, high-strung, nervous, visionary young man named Hermann J. Muller. From the beginning, Muller was eager to prove that genes are solid objects and to find out what they are made of. This interest helped to set him apart from Morgan’s other raiders, as Sturtevant later told the historian Garland Allen: “The rest of us would have gone along without, and thought, ‘Well, maybe our great-grandchildren will know a little something about it’—this was kinda the attitude.”
It was Muller who eventually found a way to accelerate the flies’ mutation rates, the project that had frustrated Morgan in the years before the arrival of the white-eyed fly. Long after Muller graduated from Morgan’s Fly Room to a Fly Room of his own, he managed to induce mutations in Drosophila. He did it by bombarding the flies with radiation, much the way atomic physicists were now inducing transmutations in atoms. Muller zapped flies with such powerful doses of X rays that he increased their mutation rates by about 15,000 percent. The X rays killed billions of sperm cells in the flies, but of the sperm cells that survived, almost half carried new mutations. Muller’s flies still looked and acted the same after their radiation treatments, but their children looked different in the wings (expanded, mussed, splotched) or the hairs (ruffled), or the body (stumpy, cloven thorax). Some of these changes Muller noticed only when he knocked out the flies with ether and inspected them through the microscope. But many changes he could see with the naked eye. One of the mutants was a white-eyed fly.
In Germany, a young atomic physicist named Max Delbrück heard about these “raying” experiments and decided that the transmutation of genes might be even more interesting than the transmutation of atoms. He left Germany and joined Thomas Hunt Morgan at Caltech, where Morgan’s experiment in the unification of the natural sciences was still just getting going. At Caltech, chemists and physicists felt a wide gulf between their world and the world of the biologists, and vice versa. When Delbrück found his way to the Fly Room, Sturtevant told him to start by clearing up certain small points of confusion in the map of the fly’s fourth chromosome. Sturtevant handed Delbrück a stack of reprints, and Delbrück took them to a room across the hall. There he pored through them, more and more disconsolately. To him they were much harder than atomic physics: “Forbidding-looking papers, every genotype was about a mile long, terrible, and I just didn’t get any grasp of it.”
Bridges tried to help. A genotype is a description of the genes of a living thing: the lines of genetic code that it has inherited. A phenotype is the expression of the genes: the living thing itself, the way it looks or behaves. They had named their first gene white after the white-eyed fly. But the white gene comes in more than one form. Most flies carry two copies of the normal form of the white gene, and they have red eyes. Some flies carry one copy of the normal form and one copy of the mutant form, and they have red eyes, too, because the normal form is dominant, even though they have one mutant form of the gene in their genotype. Here and there a fly carries only the mutant form of the gene, and that fly has the signature white eyes. In spite of these complexities of genotype and phenotype, Morgan’s Raiders called the gene white, and they also called a white-eyed fly white.
Now, every fly in the Fly Room carries not one but many mutant genes. So does every fly outside the Fly Room (known in the jargon as “wild-type”) and so does every human being (wild or not). Most of these mutant genes are not expressed. Drosophilists often breed flies to make double mutants, triple mutants, and more. A fly’s genotype, scrawled on the label of a fly bottle, may begin f; cn bw; TM2/tra … Any young Lord of the Flies can read that formula at a glance. It means the fly in the bottle carries the mutation forked on its X chromosome. The word forked is short for forked bristles. The fly carries cinnabar and brown on its second chromosome. Although cinnabar and brown both refer to eye color, when both mutations come together in a single fly they tend to produce white eyes. The fly also carries tra, or transformer, on its third chromosome. If a fly with two X chromosomes has tra on its third chromosome it grows up with a male’s inky-black abdomen, a male’s penis, a male’s sperm, and it mates with females, even though having two X chromosomes makes it, genetically speaking, a female fly. TM2 is a long story.…
Delbrück liked Sturtevant and Bridges, but he could not absorb all this lore and jargon. He had grown up in Berlin on the same block as Max Planck. As a student he had rubbed shoulders with Niels Bohr, Werner Heisenberg, Erwin Schrödinger, Albert Einstein. Now he missed the deep, clean simplicity of Planck’s E = nhv and Einstein’s E = mc2. He felt he had to get out of the Fly Room or die. Eventually he found a microbiologist down in the basement who was experimenting with bacteria, and with viruses that kill bacteria. The bacteria were Escherichia coli, the common bacteria of the human gut. The viruses were bacteriophage (from the Greek phagein, “to devour”); phage for short. E. coli was a well-known organism. Bacteriophage was well known too, partly through fiction, as Arrowsmith’s path to glory and disaster.
In bacteriophage, Delbrück saw a way to escape from the Fly Room. With phage and E. coli he could reduce the phenomena of inheritance to the kind of deep, clean, simple problem that he loved in physics. He allowed E. coli bacteria to expand like a living carpet across the bottom of a petri dish. Then he scattered some predatory particles of bacteriophage into the dish, and within a few hours the phage ate holes in the carpet. A bacterium is too small to see with the naked eye, and a single virus particle is too small to see even with the most powerful light microscope. But Delbrück could distinguish different strains of phage just by glancing at the holes they ate in the carpets: some strains ate big, shaggy holes, some ate neat, tiny ones. In other words, as Delbrück once put it, strains of viruses make themselves known by their behavior, the way “a small boy announces his presence when a piece of cake disappears.” And these differences in behavior are in the genes.
During the World War II years, Delbrück stayed on in the United States. (He and his family were ardent anti-Nazis; it would have been dangerous to go back to Berlin even if he had wanted to.) He and a small but expanding circle of friends, including another resident enemy alien, the Italian biologist Salvador Luria, carried out a series of phage experiments—elegantly simple experiments, in the style of physicists—trying to find the particles of heredity and figure out how they work. They were going now where Morgan had dreamed his students would go, investigating the behavior of copulating chromosomes at a level beyond reach of the microscope. (“They must come toget
her with extraordinary precision,” Morgan had written, “which implies probably that we are dealing with events of a molecular order. We can go no further until physics has furnished us with a key to unlock these extraordinary events.”) A key discovery came in 1944, when a microbiologist’s study of bacteria hinted that the crucial substance might be deoxyribonucleic acid, or DNA. But not many biologists noticed that study. Morgan himself was now in his last years—he died in 1945—and he did not dream that the answer to the question was close. “He just didn’t feel as though there was any toehold,” Sturtevant told Garland Allen, the historian, in their unpublished interview. “I remember one of the last times I ever talked to Morgan—not very long before his death. He said he hadn’t been keeping up with things, but this is the thing he’d always wanted to know.” What are genes? What passes between the chromosomes?
“This was the atmosphere,” Sturtevant summed up, speaking for the vast majority of biologists who were still in the dark in 1945. “ ‘Boy, if we could only get going on it—but how?’ Nobody had any ideas.”
SEYMOUR MARRIED DOTTY in January of 1942, just as the U.S. swung into the war, and the two of them hopped on a train for Purdue University in Indiana, where he enrolled as a graduate student in the physics department. Almost immediately he was recruited for a secret wartime project. Physicists in a far-flung Allied effort that rivaled the Manhattan Project in both scale and military significance were trying to build a new, improved radar. At that time, a radar set was built around a device called a silicon crystal rectifier, which is a sort of one-way turnstile for electricity: in a rectifier (unlike an ordinary copper wire) electric current can flow in only one direction. These rectifiers were unreliable, and the leader of the Purdue team, a Viennese physicist named Karl Lark-Horovitz, was trying to replace the silicon with germanium. Most of the physicists on the team were young and inexperienced, but then, so was the science of electronics. Physicists did know that germanium and silicon conduct electricity better than wood and worse than copper, which is why they are called semiconductors. But for some aspects of semiconductor behavior, the physicists were still in the dark—which is where Benzer, from the beginning, has done his best work. He made some of the basic discoveries that led to the construction of a stable germanium rectifier. Among other things, he discovered a germanium crystal that could withstand very high voltages.
The young atomic physicist Max Delbrück advanced the study of the gene through elegant experiments with viruses and bacteria in petri dishes. Here Delbrück looks over the shoulder of his first partner in these experiments, Salvador Luria, at Cold Spring Harbor Laboratory in 1941, the year the two men began working together. Their meeting was the beginning of molecular biology and would lead to a joint Nobel Prize. (Illustrations credit 3.2)
As a student of physics and chemistry at Brooklyn College, Benzer peers at the spectrum through a spectroscope. Biology needed help from chemistry and physics, but not many people in the late 1930s had a feeling for all three sciences. Today much of the science of molecular biology traces back to Benzer and a few other physicists-turned-biologists. (Illustrations credit 3.3)
Earlier in the twentieth century, physicists had thought of the electron as an otherworldly curiosity. Young physicists at the annual Christmas dinner of the Cavendish Laboratory in Cambridge used to shout a toast: “The electron! May it never be of any earthly use to anybody.” But of course even pure, romantic, otherworldly research—Arrowsmith’s kind of research—can change the world. During the war, Purdue’s germanium crystal recitifers made their way to Bell Laboratories in New Jersey. There a team of physicists, using Purdue’s germanium, took the semiconductor a crucial step further after the war was over and invented the transistor. Transistors are the central element of radios, televisions, computers—all things electronic. They started a new industrial revolution; electronics is now the biggest industry in the United States. So Benzer had helped put the electron to earthly use, at the age of twenty-three.
In 1946 a friend of his in the secret laboratory passed him a book by the German quantum physicist Erwin Schrödinger, What Is Life? It was a book about the gene problem. Schrödinger had written it in Dublin, where he had gone to escape the war. For a physicist to think about biology was itself a kind of escape from the war.
Seymour and Dotty Benzer got married in New York City in 1942 and hopped on a train to Purdue University, in Indiana. There Benzer would help start his first revolution—electronics. (Illustrations credit 3.4)
In What Is Life? Schrödinger tried to connect the world of atomic physics with the world of genetics. He suggested that the gene might turn out to be a novel kind of crystal, an aperiodic crystal, in which the message is locked into the crystal lattice like a series of letters, and those letters might carry the secret of life. “We seem to arrive at the ridiculous conclusion that the clue to the understanding of life is that it is based on a pure mechanism,” Schrödinger wrote. That is, the secret of life is nothing more than a kind of clockwork. “But please, do not accuse me of calling the chromosome fibres just the cogs of the organic machine,” he wrote. Any cog that does what these cogs can do is “not of coarse human make”; it must be “the finest masterpiece ever achieved along the lines of the Lord’s quantum mechanics.”
To Benzer, Schrödinger was thrilling on the theme of the hereditary substance, whose permanence, he noted, is “almost absolute. For we must not forget that what is passed on by the parent to the child is not just this or that peculiarity, a hooked nose, short fingers, a tendency to rheumatism, hemophilia, dichromasy, etc.” What is passed on is not only three-dimensional but four-dimensional: a whole human being moving through time.
What Is Life? did not offer any hard news about the nature of the gene. The book’s chief reference was some obscure work that Max Delbrück had done before he left Germany on the idea that a mutation is like a quantum jump. Schrödinger made that idea his book’s centerpiece: he called it “Delbrück’s Model.” Actually, that work of Delbrück’s was already years out of date; because of the war and the walls that still existed then between physics and biology, Schrödinger knew nothing about Delbrück’s work with phage. Still, What Is Life? had an enormous effect on a whole generation of young scientists because it made the gene problem sound like the problem to solve. At the Admiralty Headquarters in London, in a windowless pile known as the Citadel, the young physicist Francis Crick, who had spent the war working on mines, read What Is Life? and decided to become a biologist. At the University of Chicago, an undergraduate named James Dewey Watson picked up the book. He had been studying birds, “but,” he later wrote, “from the moment I read Schrödinger’s What Is Life? I became polarized toward finding out the secret of the gene.”
At Purdue, reading What Is Life? made Benzer wonder if his own doped crystals of germanium might somehow be related to the mysterious crystals of inheritance. Benzer could not help lingering a little sentimentally over the name Max Delbrück, which has the same romantic aura of Germanic genius in What Is Life? as the name Max Gottlieb has in Arrowsmith. Through the grapevine, Benzer learned that Delbrück was now working at Caltech and that he was working on viruses and bacteria, like Max Gottlieb. Benzer had already found his Leora—this sounded like his Max. At a meeting of the American Physical Society in Bloomington, Indiana, Benzer was invited to dinner at the home of a biologist by the name of Salvador Luria. Benzer asked Luria if he happened to know anybody who worked on viruses.
“Well, yes, I work on viruses,” said Luria.
“Tell me,” Benzer said, “did you ever hear of Delbrück?”
Luria went to a drawer and pulled out a snapshot of Delbrück. He and Delbrück had been working together since 1940; Luria was Delbrück’s first serious collaborator in bacteriophage. Benzer could not have been more impressed. Before the evening was over, Luria was urging him to take a summer course in bacteriophage at Cold Spring Harbor, a course that Delbrück had established a few years before in order to do just wh
at Morgan had been trying to do—to draw more hard scientists, and especially more physicists, into the biological fold.
Benzer did take the phage course that summer. By now Delbrück, Luria, and their friends had begun to speak in a jargon of their own to describe a change in the fate of a cell: induction, transformation, cell determination, cell commitment. Within one day, Benzer says, he became instantly induced, transformed, determined, and committed to be a biologist. When they got back to Purdue, he and Dotty drove out of Lafayette, parked out in the Indiana flatlands, and talked things over. Not all children of the Great Depression would have considered the choice that they were looking at. They had a one-year-old baby girl. Seymour’s family had been poor, and Dotty’s had been poorer. She had worn one skirt all through high school, very shiny in the back.
“People in my group at Purdue thought I was nuts,” Benzer likes to say now. “Here it was, the semiconductor thing was booming, Lark-Horovitz and I had gotten six patents on the work we had done with the semiconductor.” The other veterans of the secret lab at Purdue were already planning to form electronics companies and get rich. “Are you crazy!” they told him. “You can ride in on the tide!”
But ever since his Arrowsmith years, Benzer had believed that happiness is the pursuit of curiosity and that a fall from pure science is a fall from grace. “I’m interested in biology,” he said simply. And Lark-Horovitz, who must have seen that his golden boy was already gone, gave him his blessing.
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