Time, Love , Memory

by Jonathan Weiner

  Throughout the 1950s Benzer’s scroll map got longer and longer. The gene was no longer a dot, a distant planet seen with the naked eye. The gene was the new territory of molecular biology. In 1959, when a geneticist put together a retrospective volume called Classic Papers in Genetics, he began his anthology with Mendel’s peas, as a point of origin, and ended with Benzer’s rII, as the point of origin for whatever would come next. So it proved. By the last years of the century, gene mapping would have grown into a project costing billions of dollars, the Human Genome Project, often called the Manhattan Project of biology. International teams of molecular geneticists would be racing one another to map every fly gene, every worm gene, and every last human gene at a cost of billions of dollars and at rates of more than one hundred million letters per year.

  “The atom-breaker of biology.” From late 1953 through the early 1960s, Benzer worked on his map of the interior of a gene. He kept the map on a lengthening scroll. Here he poses wearily for a Purdue publicity picture with the scroll unrolled on his laboratory bench. (Illustrations credit 4.5)

  But in the 1950s all this work was still obscure. It was remote from the shapes, colors, and visible wilderness that attracts most biologists to study life in the first place. Even in 1959, most biologists did not understand Benzer, any more than most biologists had understood Morgan back in 1911. He was mapping continents the rest of the world knew nothing about. In the summer of 1959, giving himself a break from his scroll, his years of “hard rII,” as he put it, Benzer took a course in embryology at the Marine Biological Laboratory in Woods Hole, Massachusetts. During one evening lecture he was startled when the professor happened to mention the word “gene.” Suddenly Benzer realized that he hadn’t heard that word all summer, or the word “mutation.”

  “Yes, but what is a mutation?” one of the students asked.

  “Oh, that’s a very deep problem,” said the professor. “We don’t know anything about that.”

  “My God, what am I doing here?” Benzer thought to himself. “I’ll go back to my genes and my mutations.”

  Eventually, to give people a better idea of what he was mapping, Benzer began collecting typographical errors from newspapers (which were now full of stories of the Cold War). Typos come in different categories. There are substitutions, places where one letter replaces another:

  … already the doomsday warnings are arriving, the foreboding accounts of a Russian horde that will come sweeping out of the East like Attila and his Nuns.

  —Boston Globe

  And deletions:

  “I can speak just as good nglish as you,” Gorbulove corrected in a merry voice.

  —Seattle Times

  Insertions:

  “I have no fears that Mr. Khrushchev can contaminate the American people,” he said. “We can take in stride the best brain-washington he can offer.”

  —Hartford Courant

  Inversions:

  He charged the bus door opened into a snowbank, causing him to slip as he stepped out and ran which bus, the beneath fall over him.

  —St. Paul Pioneer Press

  And nonsense:

  Tomorrow: “Give Baby Time to Learn to Swallow Solid Food.” etaoin-oshrdlucmfwypvbgkq

  —Youngstown (Ohio) Vindicator

  Benzer was finding and mapping many of these sorts of mistakes in the rII gene: insertions, deletions, and nonsense. Mutations come down to nothing more than typos. The single chromosome of the phage virus contains about 200,000 letters of genetic code, about as many letters as there are in several pages of newspaper, so even in a single virus there is plenty of room for typos. And mutations that affect a fly, a mouse, or a human being in their repertoires of fundamental behavior will come down to typos too. In a sense, rII itself is a behavior gene, since damage there affects the behavior of the virus. Damage at any one of the thousand points in Benzer’s map produced an identical change in the behavior of the virus. That is, a typo at any one of those thousand points in the map would wreck the rII gene. There is an old saying, “Each finger can suffer.” In the genome, each gene can suffer, and each letter in a gene can suffer too.

  In the summer of 1960, in the basement of Caltech’s Church Hall, the physicist Richard Feynman took up what was known in those days as “Benzer mapping.” Feynman loved Benzer’s tricks for finding the single rare phage particle he was looking for in a dish of bacteria. He told friends it was like “finding one man in China with elephant ears, purple spots, and no left leg.” And soon afterward in the Cavendish Laboratory, where Watson and Crick had put together the double helix, Crick and Sydney Brenner used rII mutants and Benzer mapping to help crack the genetic code. Crick and Brenner knew that they were looking at a four-letter code, A, T, C, and G. In an ingenious series of rII experiments, they proved that the code is a triplet. That is, the words are written in groups of three letters: CAT, TGA, ACT. Not long afterward, Benzer went to a meeting in India. Wandering in the street markets looking for exotica—he had acquired a taste for strange foods as well as strange hours—Benzer saw a soothsayer with a bird. Passersby would ask the soothsayer a question. Then the man would ask the bird. The bird would go into the cage, peck among the scraps of paper on the floor, and bring out an answer. Benzer asked, “Is the genetic code universal?” The bird gave the answer “The news from home is good.”

  In Paris, in the attic of the Institut Pasteur, Jacques Monod and François Jacob explored some of the implications of the new view of the gene. Each of us starts out as a single cell, and each of us ends up a collection of cells of many different kinds. Yet each of our cells still contains the same set of genes as the first. In a sense each of our cells knows everything but expresses only a small part of what it knows.

  There is a story in Jewish legend that each baby arrives knowing everything, which accounts for the infinite wisdom we see in the faces of newborns. As the baby comes out into the world an angel places a finger just above its mouth to keep it from expressing all this wisdom, which accounts for the philtrum, the crease above the upper lip. Somehow something like the finger of the angel must touch our DNA and keep most of it from being expressed in each of our cells. Some genes turn on only in a liver cell and others only in a brain cell. Much later, in the 1990s, when molecular biologists began mapping all of the genes in the human body, they would discover several thousand genes that switch on only in the neurons of the brain—twice as many genes are expressed in the brain than are expressed anywhere else in the body. But no cell ever reads all of the words on the scroll. So every living thing and every last cell in our own bodies can say, with the preacher of Ecclesiastes, “When I travelled, I saw many things; and I understand more than I can express.”

  In their rabbit warren of laboratories at the Institut Pasteur, Jacob and Monod discovered the finger of the angel. They identified what they called “repressors” that float through the cell’s nucleus and, by touching the double helix here and there—attaching themselves to strategic places all along its coils—silence most of the genes in most of our cells most of the time, so that only a small part of each double helix is expressed at any moment. The few genes that the cell does need are expressed; the rest only stand and wait. Today molecular biologists can actually watch this happen. Using an instrument called an atomic force microscope, they can watch enzymes sliding down strands of DNA and they can see the strands of DNA unrolling, very much like Torah scrolls, to begin reading or cease reading the portion of the scroll that is appropriate for that moment.

  Jacob and Monod knew that these angelic floating proteins were a first glimpse of the connection between genes and behavior. They were looking at the beginnings of the senses, the tools with which a living thing picks up changes in the environment around it and uses the information to shape its behavior. Everything depends on such small felicitous moments of recognition: on compound meeting compound, shape meeting shape, profile recognizing profile. The shapes of these floating proteins allow a cell to recognize new chemicals ent
ering the cell and to read just the portion of DNA that it needs at each moment in order to respond to each small event in its vicinity. Ezra Pound wrote a poem after spotting friends in the Paris Métro:

  The apparition of these faces in the crowd

  Petals on a wet black bough.

  The fingers of the angels in every one of our cells are engaged in these small moments and shocks of recognition, not just when we are born but every moment of every day in every one of our cells.

  Toward the end of the century a molecular geneticist working with a flock of sheep in Scotland would discover a way to give a cell a little shock of electricity and make the angels, just for a moment, snatch back their fingertips. His work would suggest that any cell—even a cell scraped from the inside of a ewe’s udder or from a human cheek—can be made to express every bit it knows and grow into a lamb or a human baby, philtrum and all.

  Even in the 1950s, the first molecular geneticists knew they were moving into strange new territory, and Benzer’s taste for strange food and strange hours seemed of a piece with it. Benzer worked with Crick in his tower room at the Cavendish, with Jacob and Monod in their mansard rooms at the Institut Pasteur, with Delbrück in a basement at Caltech, and everywhere he went they told stories about his behavior. When Benzer was at the Pasteur, he shared a laboratory with Jacob. Jacob remembers Benzer in his memoirs: “Every day, at lunch, he brought some unusual dish—cow’s udder, bull’s testicles, crocodile tail, filet of snake—which he had unearthed on the other side of Paris and which he simmered on his Bunsen burner.”

  Benzer ate like that at home too: caterpillars, duck’s feet, horsemeat, live snails. His little girl Barbie woke up one morning in Paris with her eyes swollen shut, and he took her to a doctor, who asked, “Has she eaten anything unusual lately?” Benzer was too mortified to be truthful.

  “During the first months, there were few exchanges between us,” Jacob writes, describing his labmate in his memoirs. “We did not keep the same hours. I arrived at nine in the morning; he, around one in the afternoon. As he came in, he would throw out a resounding ‘Hi!’ and then, after lunch, immerse himself in the inspection of his cultures. During the afternoon, he would belch once or twice. Around seven o’clock in the evening, I would bid him good-night and leave him to his nocturnal experiments.”

  CHAPTER FIVE

  A New Study, and a Dark Corner

  Psychology was to him a new study, and a dark corner of education.

  —HENRY ADAMS

  WHEN BENZER was a physicist, he used to marvel at the power of mathematics to predict large portions of the behavior of the universe, from the fall of an apple to the are of a rocket, from the quantum jump of an electron to the shining of the sun. No one could explain the connection between a brief formula and an apple, a rocket, an electron, or a star. No one could understand what one physicist called “the unreasonable effectiveness of mathematics.” A mathematical physicist who helped invent the atomic bomb once wrote, “It is still an unending source of surprise for me to see how a few scribbles on a blackboard or on a sheet of paper could change the course of human affairs.”

  After the discovery of DNA, the whole world marveled at the unreasonable effectiveness of molecules. It was easy to see that the science that Benzer, Watson, Crick, Sydney Brenner, Gunther Stent, and a few others helped to establish in the middle of the twentieth century might someday change the course of human affairs even more powerfully than atomic physics. Crick defined molecular biology as a way of observing “the borderline between the living and the nonliving,” that is, the borderline between the scale on which human beings are warm, laughing flesh and the scale on which we are nothing but atoms. A single human thumbtip contains a trillion trillion atoms. The thumb is alive; the atoms are dead. Molecular biologists would explore the acts of life at the level of molecules, atoms joined elegantly together, the smallest working parts in every fingertip and antenna tip. Sydney Brenner defined the new science as “the search for explanations of the behavior of living things in terms of the molecules that compose them.” A hybrid science, then, requiring a feel for the behavior of living things, a feel for the behavior of matter, and what Crick calls “the hubris of the physicist.”

  By the early 1960s the revolutionaries had already done so much with molecules that during a brief interlude of collective depression they decided that their quest was over and they would never find any mysteries equal to the clouds they had just dispelled. Benzer laughs now when he remembers the mood: “We had this feeling that all the molecular biology problems were on the verge of being solved. It was a little bit like the physicists at the end of the nineteenth century saying, ‘All we have left to do is one more decimal place.’ ” As a small boy Crick had worried that the empire of science was expanding too fast. By the time he was grown up there would be nothing for him to do. (“Don’t worry, Ducky,” his mother had told him. “There will be plenty left for you to find out.”) Now the new molecular biologists thought they had done themselves in: there was nothing left. Many of them got as cranky as homecoming heroes the year after coming home. Benzer was still spending his summers at the Marine Biological Laboratory in Woods Hole, but now his work on genes and mutations was so famous that he couldn’t walk down Water Street without strangers buttonholing him to tell him about their latest results. At Stony Beach he couldn’t get into the water. His cousin Sidney also spent summers at Woods Hole. Sidney’s mailbox read “S. Benzer.” Someone was always ringing Sidney’s bell and asking, “Are you—?”

  “No, that’s my cousin Seymour!” Sidney would shout and slam the door.

  One summer Watson brought a red-hot manuscript to the Benzers’ rented cottage at Woods Hole. “He wanted my wife to read it,” Benzer remembers with a laugh. “He said, ‘These books are bought by housewives, so I want to try it on a housewife.’ Of course I read it too. I couldn’t put it down.” It was Watson’s memoir of his discovery with Crick. His working titles included Honest Jim and Base Pairs. In the manuscript, Watson confessed that he and Crick had peeked at X-ray diffraction pictures of the double helix by their friend Maurice Wilkins and Wilkins’s colleague Rosalind Franklin in order to beat them to the discovery of the century. Watson’s manuscript was so sensational and for its time so unbuttoned (It began, “I have never seen Francis Crick in a modest mood.”) that the Harvard Corporation overruled the editors of the Harvard University Press and ordered them not to publish it.

  After the memoir was published, under the title The Double Helix, and became a best-seller, Crick brooded and planned his own counter-memoir: “I confess I did get as far as composing a title (The Loose Screw) and what I hoped was a catchy opening (“Jim was always clumsy with his hands. One had only to see him peel an orange …”) but I found I had no stomach to go on.”

  What was happening in the phage group is what happens in any primate troop. These were the shufflings and scufflings of chimpanzee politics and gibbon gossip after a shift in power. Power was shifting to the new molecular biologists and away from the old biologists. It was clear to many that research with Arrowsmith’s purity of intention and Gottlieb’s remove from the world was going to be rarer now. The Double Helix replaced Arrowsmith as the book through which young readers were introduced to the life of science. Watson replaced the Martin Arrowsmith ideal with its opposite: the young scientist who does whatever he has to do to get what he wants, his long hair and his loose shoelaces flying behind him. Of course, the power and pace of the new science itself would have changed the moral climate of the field even without Watson’s example. But like the young Arrowsmith, the young Watson would become the standard of a new era—or its harbinger; he spoke to the spirit of the next age.

  Crick was sorry to see what Watson regarded as their base behavior immortalized. To Crick, the search had been something more beautiful and interesting than a mere race. “Jim,” Crick told one historian. “—The only person who thought it was a race was Jim, nobody else did.” He worried that af
ter Watson’s book the two of them would be remembered in the friezes and murals of history as young beasts scrambling over other people’s backs for a bunch of bananas. The reason The Double Helix became a best-seller, Crick wrote, is that it shows that “SCIENTISTS ARE HUMAN, even though the word ‘human’ more accurately describes the behavior of mammals rather than anything peculiar to our own species, such as mathematics.”

  EVEN BEFORE the discovery of the double helix, Delbrück had abandoned the search to his followers and gone off alone. Down in his subbasement laboratory in Church Hall he had begun peering through the microscope at the behavior of single cells, watching E. coli, Euglena, Paramecium, and Rhodospirillum swim or creep toward light. Delbrück had always preferred to work apart from the crowd. Now he spent hours playing with a fungus called Phycomyces, which grows in tiny stalks called sporangiophores—on dung. He was fascinated by the way the sporangiophores of Phycomyces are attracted to light, a piece of behavior that is known in biological jargon as phototropism. Over and over he watched the spore-towers grow toward the light—just as Benzer would later watch flies run toward the light in his countercurrent machine. With phage, Delbrück had transformed the study of the gene; now, with Phycomyces, he thought he could transform the study of genes and behavior.

  When historians look at the great waves of migration from the Old World to the New World, they sometimes speak of the Push and the Pull. Delbrück was feeling both. The old New World was crowded, and he wanted a new New World to live in. He was turning away from the hunt for the gene to ask himself the next great question: How do you go from genes to a living creature that swims, creeps, flies, or grows toward light? What are the atoms of perception? What are the atoms of behavior? These questions were so far ahead of their time that they were guaranteed to get him away from the crowds. Early in 1953, just before the eureka of Watson and Crick, Delbrück dictated a letter to Benzer. Max and his wife, Manny, were sitting in their jeep, “battling our way through the Sunday traffic,” he wrote, returning to Pasadena from a four-day desert camping trip in Ensenada, Mexico. He was driving. Manny was taking down the letter on a portable typewriter in her lap: “I am starting on a new venture tomorrow: some experiments on the phototropism of the sporangiophores of Phycomyces. If they work, I’ll retire from phage.” The camping trip was a “vacation before starting a new life.”