Time, Love , Memory

by Jonathan Weiner

  So the study of genes and behavior defines the depth as well as the height of the twentieth century, because it traveled in both directions, like angels ascending and descending Jacob’s ladder. The gas chambers of the Holocaust were built on Galton’s principles. Auschwitz was allowed to operate to the very end of the war without Allied interference because many of Germany’s enemies shared Germany’s prejudices. The Holocaust was Galton’s flower.

  “In some sort of crude sense which no vulgarity, no humor, no overstatement can quite extinguish, the physicists have known sin,” Robert Oppenheimer said after the war, speaking for the men and women he had led at Los Alamos in the Manhattan Project; “and this is a knowledge which they cannot lose.” Many physicists in those postwar years turned from the atom to the gene as if they were turning from sin to virtue, from darkness to light. “Such a change is highly significant psychologically,” Richard Rhodes writes in his history The Making of the Atomic Bomb. But biologists had lost their innocence long before the war. The study of genes and behavior was born in sin, and the possibility of sin would cling to it. After the war, the editors of The Eugenics Review commissioned articles about Hitler’s perversion of Galton’s principles (“A girl of sixteen was sterilized for answering the question ‘What comes after the Third Reich?’ with ‘The Fourth.’ ”). The journal’s editors were horrified, but they kept on publishing The Eugenics Review, with Galton’s flower on the cover.

  BENZER WAS AWARE that a pendulum had swung back and forth between nature and nurture, propelled partly by science and partly by politics. When Galton first proposed the idea of eugenics, almost nobody understood what he was talking about. His audiences found the very word heredity novel and foreign. But by the time Galton published his Natural Inheritance in 1889 he could state as a matter of common knowledge that talents like “the Artistic faculty” are hereditary. “A man must be very crotchety or very ignorant, who nowadays seriously doubts the inheritance either of this or of any other faculty.”

  In that decade the anthropologist Franz Boas, who left Germany and physics for the United States partly to oppose the politics of Galton and his followers, began arguing the other way. Boas believed that peoples are determined more by culture than by biology. This view was advanced by Boas’s students Margaret Mead and Ruth Benedict. Freud and his followers strengthened it by arguing that an individual’s problems are determined more by experience than by wiring; so did the behaviorists, who argued the same way. Revulsion at the Nazi eugenics experiments made all of this intellectual current the new orthodoxy. By the 1960s, when the first molecular biologists began looking at the problem of nature and nurture, the pendulum had swung all the way back to where it had been before Galton. In 1966, when Benzer proposed his study of genes and behavior, many thoughtful people of goodwill believed that absolutely everything about a human being can be shaped from the outside. There were no innate differences between the minds of American men and women in the 1960s—or if there were, it was not politically correct to talk about them. There were no innate drives and instinctive mechanisms either; or if there were, they were not fashionable for liberal psychologists and biologists to study, not in America in the 1960s. The behaviorists’ vision of human beings as blank slates was popular among liberals; they wanted the club of science to smash the hydra heads of the eugenics movement whenever those heads reared up again. The doctrine that human beings have no instincts seemed like prudent politics if not good science. In the shadow of the Holocaust the anthropologist Ashley Montagu wrote in an influential treatise against racism that a human being is “nothing but the form in which his particular culture molds his plasticity.” Most American psychologists supported the learning theory, remembers Mark Konishi, a colleague of Benzer’s at Caltech who now studies genes and behavior in owls: “Everything is learned, nothing is instinctive. I discuss this with Seymour from time to time, and we always laugh.”

  In the last decades of the twentieth century the pendulum would swing again, and this time the strongest push would come from molecular biology. Max Delbrück was one of the first molecular biologists to realize that the kind of work they did might have serious political implications. Delbrück had left the atom for the gene, but he never believed that in doing so he had escaped from sin. “Other people want to obtain power by going out into the world,” he sometimes said, “but the scientist really wants to obtain power by retreating from the world.” Having served his apprenticeship as a physicist in the laboratory that had discovered the possibility of atomic fission, Delbrück knew early on that a scientist can change the world more than a Hitler or a Caesar. “And you can sit very quietly in a corner and do that.”

  Benzer’s view was narrower—or more modest. Caltech’s in-house historian once asked him if the phage group had known in the late 1940s that they were the dawn of a new day. Benzer answered, “Oh, I don’t know. We loved what we were doing, but I don’t recall having any sense that ‘we’re making history.’ Delbrück had a sense of history; his father was a famous historian. But my father had no history; I had no history. It wasn’t part of my thinking. It was always exciting to be doing the experiments.”

  By the time Benzer started building his countercurrent machine at Caltech in 1966, he had seen enough of the surprises of science to know that what he and his friends were about to do might matter and that no one could predict where their work would go; although Benzer did have an idea that it might go far. Like every human being, he was really interested in human behavior. By studying genes and behavior in the fly, he was postponing what he really wanted to know, temporarily. But he suspected that if he looked deep enough, almost any creature with neurons might lead to fundamental discoveries that would illuminate every creature on the planet, including himself.

  The idea of beginning the quest with flies had a kind of simplicity and whimsy that were typical of Benzer. (Feynman, the physicist, once described his own research style as “aggressive dopiness.”) The project suited Benzer’s down-to-earth style of talking and experimenting, and his 360-degree curiosity, the same curiosity that makes Benzer a demon to travel with, because he tries to see and explore everything, especially behind locked doors (“A closed door is always a challenge.”). What Sinclair Lewis says about Martin Arrowsmith also describes Benzer: “no decorative heroisms.” “He presented neither picturesque elegance nor a moral message.… But he had one gift: curiosity whereby he saw nothing as ordinary.”

  Going back to the once fabled and now scorned flies required someone with Benzer’s omnivorous curiosity, his knowledge of the gene, his care and caution in the laboratory, his relaxed confidence in working at the fringes of science, and his appetite for the bizarre. Although he wore his fame lightly, the project probably needed that too: an obscure biologist could never have lured top-notch students into a project this far out. “If he hadn’t done it,” Crick sometimes says, “no one else would have done it.”

  With the distant blessings of Sturtevant and the day-by-day or night-by-night help of Ed Lewis (“I actually gave him the best technician I had,” says Lewis), Benzer set up a Fly Room in Church Hall. Since he found the research interesting but could not know how the world would use it, he would, within limits, follow his curiosity. “Maybe that’s a cop-out,” Benzer would say to his first students in Church Hall in the 1960s. But he always ended their bull sessions and his own rare midnight soliloquies the same way: “Just do the experiments.”

  CHAPTER EIGHT

  First Time

  —As if the idea of time had been disturbed.—

  —CHARLES DARWIN,

  the M notebook

  A SINGLE DROSOPHILA is not much bigger than an asterisk. It is so small that an escapee from a fly bottle (the flies are always escaping, always in orbit around the four comers of every Fly Room) does not even buzz—unless it flies into a drosophilist’s ear. They seem silent without a microphone and they look like nothing without a microscope. But even in Benzer’s first nights among his first h
alf-pint milk bottles, he felt that fruit flies might turn out to be a magic well.

  When he placed a dozen of them in an upside-down watch glass, covered the watch glass with a piece of glass for a ceiling, and observed them at low power, at twenty or thirty times life size, the flies groomed and preened, each head twisting from side to side between the forelegs, each head “all eyes.” They rubbed their forelegs together in the inverted dome of the watch glass with a scheming “Ah-hah” look. When two or three met, he could see little flickering exchanges of the forelegs. The flies wandered around the watch glass, finding the very edges, and there preening again, the way a sheep will browse grass at the edge of a fence or a mouse will scratch its head at each dead end in a maze. Sometimes a fly would poke a few of its legs partway over the wall of the watch glass into the outer air and rest there, nine tenths a prisoner and one tenth free. Then, with a sudden—to human eyes instantaneous—rearrangement of parts, the fly was gone, off to another square centimeter inside the dome, exploring space and other flies.

  Gradually more and more flies would cluster around the edges of the watch glass. Through the microscope the cuticles of their exoskeletons were brown but shiny, like armor. Light caught the neat red facets in the domes of their eyes. Here and there, Benzer saw a proboscis mumble its bristles against the inner walls of the glass like a baby elephant’s trunk, in and out, flashing and then withdrawn. Again and again the shiny wings bent, flexing backward and downward with the movements of the hind legs. At twenty- or thirty-power magnification, every bristle on every fly’s head stood out, sharp and countable—and Benzer knew that Drosophila had meant so much to thousands of geneticists that every bristle on the fly’s head had in fact been counted and given a name.

  Seeing all this action, it was easy to hope that the lessons he wanted might come out of this small theater. The flies were as quick and deft as birds and almost as expressive. When they rubbed their forelegs together, they had, to human eyes, an attitude of scheming or of prayer; and when they rubbed their wings with their hind legs, they gave an impression of agility, expertise. The neatness and deftness of their behavior matched the neatness and deftness of their bodies, both sculpted by natural selection and both intricately and invisibly linked.

  A human head could grow dizzy trying to go from the flies’ universe to ours, so unutterably distinct and so uncomfortably alike. Sometimes one of the flies would slip from the ceiling of the glass dome and fall flailing on its back in a panic of legs: awful to see, panic at thirty power, mildly contagious even across the gulf of the microscope.

  Flies were as easy to play with as phage. “The work can be done almost pretty well anywhere,” as Morgan used to say, “so long as we have a table, and an electric bulb.” For Benzer, the chores were lightened because Ed Lewis already ran a spotless Fly Kitchen on another floor of the building. Working in the middle of the night, a team of lab assistants mixed fresh batches of yeast and molasses to order in a fifty-gallon vat, glopped measured amounts of fly food into the bottoms of freshly autoclaved milk bottles and test tubes, and wheeled warm, rattling racks of glassware to Lewis’s and Benzer’s labs every morning for their next rounds of experiments. Lewis’s former technician Evelyn Eichenberger taught Benzer how to knock flies out with ether so he could examine them under the microscope without letting too many of them escape. She also set up the standard morgues in the Fly Room: traditionally beer or wine bottles with funnels in their mouths and oil at the bottom. Any flies that did escape eventually found their way down the funnels and drowned in the oil. Each morgue slowly filled with sedimentary layers of mutant flies.

  Sitting in the half-dark, Benzer sent mutagenized flies by the hundreds jitterbugging through his first countercurrent machine. From almost the first runs he noticed a few individuals here and there that stood out from the crowd in one way or another. Some of the flies did not move right along—they trudged so slowly that they looked depressed. While most of the flies around them made it all the way to Tube Six, these flies moped from One to Two. Benzer collected them by sucking them up one by one with a plastic straw (guarded at the top by a piece of fine mesh) and transferring each one to a bottle of its own. When he and his technician bred those flies, many of their children and grandchildren acted the same way.

  Here and there in the countercurrent machine, Benzer saw a fly go into what looked like an epileptic seizure when he rapped the machine on the benchtop. He bred those flies, and some of their children acted the same way too.

  He also noticed a few flies that seemed to march right through the countercurrent machine whether the light was ahead of them or behind them. Benzer bred those flies, and once again many of their children and grandchildren acted the same way. He wondered if these flies could see the light at all, and he asked one of the first postdoctoral students in his Fly Room, Yoshiki Hotta, who had just graduated from the medical school of the University of Tokyo, to check their eyes.

  After considerable work, using a microscopic electrode, Hotta managed to record signals from the tiny nerves that run between the mutant fly eye and brain. As Benzer had suspected, the electrode’s readings, the electroretinograms, were abnormal. One of the first mutant flies that Hotta tested this way was tan, which has a light tan body and light tan antennae, and was first discovered in one of Morgan’s milk bottles. The tan fly was half-blind.

  Benzer also built a flight tester. It was a 500-milliliter graduated glass cylinder with its walls coated on the inside with paraffin oil. He and Hotta put flies in at the top. Each animal, as it fell into the cylinder, would try to fly off horizontally. Those that flew strongly would get stuck in the oil near the top of the cylinder; those that flew more weakly would get stuck lower down. Those that could not fly at all would plunk to the bottom of the cylinder. The design was pure Benzer: simple and to the point. When he and Hotta collected flies from the bottom of the flight tester they found mutants that could not fly, just as in the countercurrent machine they found mutants that could not see. Together they dissected these flightless mutants under the microscope and found congenital defects in the flies’ wing muscles.

  To Benzer, all these blind eyes and mangled wings were a proof of concept. But to the skeptics upstairs in the Sperry lab, they proved nothing. What did Benzer expect to find if he poisoned a fly? A sick fly. What could he learn from a sick fly? Sigmund Freud used to get the same reaction: “And you claim that you have discovered this ‘common foundation’ of mental life, which has been overlooked by every psychologist, from observations on sick people?”

  Even Hotta sometimes worried that their research was way out. “When I decided to go to Seymour’s lab, nobody said, ‘Oh, that’s a very nice idea,’ ” he says. His advisers at the University of Tokyo had heard of Benzer’s adventures in rII; but not many of them liked the sound of his fly genes–and–behavior project. Packing for America, Hotta had told his professors, his friends, his family, and himself that he was willing to gamble: “ ‘It’s OK, I may be able to find something, may not.’ But I didn’t care. Of course,” Hotta adds now, “I probably cared.”

  Delbrück, down in the basement of Church Hall, was feeling doubts about his own research. By now he had spent fifteen years on and off with his fungus Phycomyces, trying to understand something basic about the way the stalks tilt toward light—trying to see how to go from molecules to the senses. Delbrück and his students would mutagenize spores and let them grow with a light shining underneath them. Normal fungus would grow down over the rim of the agar plate toward the light. But here and there a mutant would grow straight up. Students down in the subbasement of Church Hall named the mutants that rejected the light mad in honor of Max.

  As a laboratory organism, unfortunately, Phycomyces was as inconvenient as phage and flies were convenient. The fungus was harder to breed and cross, and its repertoire of behavior was, of course, limited. Delbrück was always trying to attract other fungus watchers the way he had attracted phage watchers. Sometimes he envied etholog
ists like Konrad Lorenz, playing outside by ponds and riverbanks. Delbrück wrote to his friend George Beadle, who was studying the genetics of another fungus, that he was “trying all kinds of things, from lunatic fringes to sober photochemistry.… Perhaps I should train a duck to follow me around, that sounds like a very appealing way of life.”

  THERE WAS NO NAME for the science they were trying to start. It was not ethology, psychology, or behaviorism. It was not classical genetics, because classical geneticists like Morgan and his Raiders or Ed Lewis arranged their crosses and mapped their genes without reference to molecules. Nor was it behavior genetics, because behavior geneticists also bred animals without studying the underlying molecules. It was not traditional neurobiology, the study of the workings of nerves and brains; Sperry and his students were neurobiologists, and they were less than impressed. Benzer did not think that what he was doing was molecular biology, either, because his prime interest was animal behavior. An atomic theory of behavior was new science. Since it is a research program that moves from gene to nerve and from nerve to behavior, it is sometimes called neurogenetics. Given its deep roots in the natural sciences, it might also be called natural psychology. “I don’t care what you call it,” Benzer says. “I’ve often said, I don’t care about disciplines, I care about nondisciplines. What do you care about names?”