The brain is so vigorous and active it insinuates itself into all places and times; reaches the heights, searches the depths, peers into all those recluded cabinets of nature wherein she hath stored up the choicer and abstrussest pieces of all her workmanship, and these it contemplates and admires.
—NATHANIEL WANLEY,
The Wonders of the Little World, 1788
I thought of a maze of mazes, of a sinuous, ever growing maze which would take in both past and future and would somehow involve the stars.
—JORGE LUIS BORGES,
“The Garden of Forking Paths”
IN A LABORATORY seminar in 1966, Benzer told Roger Sperry’s students how he had trapped a fly in a test-tube tunnel, with a light at the end of the tunnel. He told them that most of the flies in the tunnel had moved toward the light most of the time—instinctively, the way a moth flies toward a candle flame. He told them that with a series of test-tube tunnels he might be able to separate the light-lovers from the dark-lovers, just as a chemist working with molecules can separate the water-lovers from the oil-lovers.
This countercurrent machine would be just the beginning, Benzer said. It would be the prototype for a whole series of experiments in which he would look for mutant instincts and mutant behavior just the way Sturtevant and Ed Lewis looked for mutant wings and abdomens. Like Sturtevant and Lewis, Benzer would find plenty of mutants, because he would feed his flies a mutagen. Lewis recommended a poison called ethyl methane sulfonate (EMS), a mutagen that he had popularized in Fly Rooms around the world. X rays tend to remove huge chunks of DNA with a single hit—anywhere from a thousand to a million letters. But EMS is kinder and gentler (like Lewis himself), and it will generally change only one letter of the genetic code at a time. By using EMS, Benzer would multiply the chances of finding interesting mutants and interesting behavior.
Finally, Benzer explained, he would be able to work much faster than Morgan’s Raiders with their jeweler’s loupes and microscopes. With a countercurrent machine, instead of examining flies one at a time, he could test a hundred flies at once. The experiments would be very simple and quick, like his phage work. In two minutes he could get as much statistical information as a behaviorist could get in several months of work with rats. He could crack the problem of genes and behavior wide open.
“I laid out this whole plan,” Benzer remembers now. “The whole lab was in a sort of uproar for about a week after that, people arguing with each other. They were pretty much split down the middle between those who thought this was great stuff and others who thought this was pure crap, that I’d never solve any problems that are important. They were really screaming at each other.” It was as if Sperry’s students were stuck in a countercurrent experiment. “Science as something already in existence, already completed, is the most objective, impersonal thing that we humans know, “Albert Einstein once said somewhere. “Science as something coming into being, as a goal, is just as subjectively, psychologically conditioned as are all other human endeavors.” Benzer remembers the reaction in Cold Spring Harbor in June 1953, when Watson first presented the structure of the genetic material. The announcement had not even been on the program; it was inserted as a special lecture. After the lecture some people were literally jumping up and down. Other people were saying, “So, big deal.” “Double helix—so what?”
(The next speaker had a hard act to follow. It was Max Delbrück, announcing his entry into the field of genes and behavior with a talk entitled “Phototropism in Fungi.”)
In the Sperry lab, the scientists who hated Benzer’s idea really hated it. They studied nerves and “brains. Why look at genes if you are interested in nerves and brains? “Obviously, that attitude was completely wrong,” Benzer says now, “because genes are what make all the parts of a nerve. It was obvious to me.”
When the world’s first molecular biologists turned to the study of genes and behavior, their two most successful laboratory animals—worms and flies—were old favorites of the microscopists. These drawings of nematode worms and the head of a fly are from Robert Hooke’s Micrographia, published in 1665. (Illustrations credit 7.1)
“Well, of course they came out of a totally different tradition in the Sperry lab,” explains the Drosophila geneticist Michael Ashburner, who was working in Church Hall at the time. “The idea of using genetics as a tool, rather than a dissecting needle!” He laughs. Benzer’s plan was bound to raise hackles in a laboratory like Sperry’s, he says. “A, of course, it was only insects. Yeah? And B, they would probably have had little idea or appreciation of how powerful genetic analysis could be.”
Either reason would have been enough to turn people off. Many biologists regarded molecular biologists as coldly as the molecular biologists regarded them. In most universities they were locked in the kind of ritual tribal hostilities that E. O. Wilson speculates may be instinctive. That is how Wilson describes the molecular wars at Harvard: “At faculty meetings we sat together in edgy formality, like Bedouin chieftains gathered around a disputed water well.”
But even molecular biologists found Benzer’s idea new and strange at the time.
Then there was the bug factor. So many people are so revolted by bugs that this reaction may be instinctive too, along with our fear of snakes. Darwin once wondered if monkeys’ terror of snakes explains their “strange, though mistaken, instinctive dread of innocent lizards and frogs. An orang, also, has been known to be much alarmed at the first sight of a turtle.” Likewise, many human beings have an instinctive loathing of spiders, and maybe some of us carry that over to the innocent fruit flies. “What sort of insects do you rejoice in, where you come from?” the Gnat asks Alice in Through the Looking Glass. “I don’t rejoice in insects at all,” Alice explains. Of course, some scientists do rejoice in them. Darwin’s first passion as a field biologist was beetles. Mendel bred bees after peas, and he had his bees and beehives painted on the chapel ceiling. The ethologist Karl von Frisch called his bees “my magic well.” E. O. Wilson, when asked what to do about ants in the kitchen, replies, “Watch where you step.” Many biologists who are drawn to pioneering work, drawn to the fringe, are also drawn to organisms that everyone else avoids. As Monod used to say at the Institut Pasteur when his students worried about working on lowly viruses and bacteria, “Remember, there is always plenty of room at the bottom.”
Listening to Roger Sperry’s students snort and snicker about flies, Benzer remembered a story he had heard back in his physics days. The head of Purdue’s secret radar laboratory, Karl Lark-Horovitz, had been one of the first physicists to realize that one might use radioactivity to trace the inner workings of living things. Before the war, Lark-Horovitz had given a lecture on the subject in Vienna, and a woman had come up to him afterward. “Dr. Horovitz, this is fantastic,” she said. “To even give an enema to a cockroach is already a great achievement. But to use radioactive phosphorous is the height of sophistication.”
When Benzer’s mother arrived from Brooklyn for a visit and heard what her only son, her only college graduate, was planning to do now, she said, “From this you can make a living?” She took his wife aside. “Tell me, Dotty, if Seymour’s going to examine the brain of a fly, don’t you think we should have his brain examined?”
“Go it Charlie!” Darwin rode into biology on the back of a beetle. When he was a student in Cambridge, beetle hunting was one of the only pursuits he took seriously. These sketches were drawn by a fellow beetle hunter, Albert Way. (Illustrations credit 7.2)
“Well,” Francis Crick says today, laughing, “most laypeople are astonished that one studies Drosophila at all. I mean, that’s the thing you find if you talk to laypeople: ‘Why should it be of interest?’ You see. And that was always said in the days of genetics. Whereas we know they have been very interesting in genetics.”
THERE WAS ONE more reason why Benzer’s idea sounded outré in 1966. He was not only going back to flies; he was also going back to Galton, or at least to a line of research that Galton had started; and in the United States in the 1960s, Galton was anathema.
Galton had made the inheritance of behavior the first great sustained study in the science now known as genetics because he wanted to breed better human beings. That is why he had been so interested in the idea that inheritance comes in bits: he wanted to rebuild the human race particle by particle. He thought the construction of our bodies and minds must be like the construction of houses he had seen in Italy, many of which are built from pieces of older houses that had been pillaged or torn down. In the facades of these houses, Galton had often noticed a column or a lintel that had been recycled, sometimes bearing fragments of inscriptions from the house before or the house before that. Likewise, in our human inheritance, he wrote, everything comes from the past, lintel from lintel, column from column, chunk of wall from chunk of wall.
Full-face portrait: A bent-wing mutant from the first Fly Room at Columbia at the turn of the century. “You can see it is certainly a very thoughtful and kind animal when you get to know it close up,” Benzer says in lectures. “What is behind this facade is actually a very complicated brain.” (Illustrations credit 7.3)
Pushing this metaphor one step further (“which is as much as it will bear,” Galton wrote), he imagined that it might explain the strange play of family resemblance in looks and behavior. “Suppose we were building a house with second-hand materials carted from a dealer’s yard,” he wrote,
we should often find considerable portions of the same old houses to be still grouped together. Materials derived from various structures might have been moved and much shuffled together in the yard, yet pieces from the same source would frequently remain in juxtaposition and may be entangled. They would lie side by side ready to be carted away at the same time and to be re-erected together anew. So in the process of transmission by inheritance, elements derived from the same ancestor are apt to appear in large groups, just as if they had clung together in the pre-embryonic stage, as perhaps they did.
This is one of Galton’s many visionary passages. He is sketching the principle that later allowed Sturtevant to make the first map of the genes on a chromosome: A, B, C, D, E. It is the same principle that allowed Benzer to make the first detailed map of a gene’s interior, dissecting a single one of Galton’s bits; and Benzer would come back to this principle again.
For Galton, all of this science was part of a Utopian dream. At first he called it “viriculture,” meaning the cultivation of men. Then he hit on the Greek word eugenēs, “namely, good in stock, hereditarily endowed with noble qualities.” And the first premise of eugenics was the link between genes and behavior. “We must free our minds of a great deal of prejudice before we can rightly judge of the direction in which different races need to be improved,” he wrote in the opening pages of his Inquiries into Human Faculty in 1883; but having said that, he felt “justified in roundly asserting that the natural characteristics of every human race admit of large improvement in many directions easy to specify.” Everyone knew, for instance, that women are “capricious and coy”—airheads. Everyone knew that Jews are double-dealing misers. And so on.
Galton, who outlived Darwin by decades, was thrilled to read the papers in which Morgan and his Raiders made genes real at last. The discoveries that poured out of the Fly Room in the first decades of the twentieth century did wonders for the Eugenics Society that Galton had founded in London. Morgan’s flies helped Galton win streams of influential gray-haired converts to the cause. Morgan himself wanted no part of eugenics (“A little goodwill might seem more fitting.”). But Muller, the most visionary of Morgan’s Raiders, became an ardent eugenicist from his first days in the Fly Room. Later on, when Muller discovered how to make mutant flies with X rays, he predicted that his transformation of flies would lead to the transformation of the human species.
Given the prejudices of Galton’s time and class—the assumption that there really are superior and inferior breeds of people, races as different as foxes and hounds or weeds and roses—one can understand how eugenics might have seemed to Galton a beautiful dream. He was very proud when a botanist named a genus of flowers after him (“a whole genus of flowers of singular beauty”), and he put a little picture of Galtonia candicans at the bottom of the last page of his memoir, Memories of My Life, along with a few inspirational lines about eugenics. He hoped the human race would be improved and beautified too. Someone once lamented to Galton (perhaps with an irony he missed) that there would be no room left in his perfected world for pity. Precisely so, Galton said: “But it does not seem reasonable to preserve sickly breeds for the sole purpose of tending them, as the breed of foxes is preserved solely for sport.”
In the United States, Galton’s books started a vogue for eugenics and even a vogue for the name Eugene. Sinclair Lewis satirized the American movement in Arrowsmith with his description of a typical midwestern “Health Fair” in which the chief booth was occupied by the Eugenic Family: “They were father, mother, and five children, all so beautiful and powerful that they had recently been presenting refined acrobatic exhibitions on the Chautauqua Circuit. None of them smoked, drank, spit upon pavements, used foul language, or ate meat.” While the young Martin Arrowsmith works another booth, answering the public’s questions about bacteria and hygiene, a detective recognizes the Eugenic Family as the Holton gang (“The man and woman ain’t married, and only one of the kids is theirs. They’ve done time for selling licker to the Indians.”).
Eugenic Fairs and mass sterilization programs in the United States helped inspire the Nazis in Germany. Two months after they came to power in 1934 the Nazis passed the Law for the Prevention of Genetically Diseased Progeny, which mandated sterilization of the congenitally feebleminded, along with anyone suffering from deformities, epilepsy, manic depression, Huntington’s chorea, hereditary blindness or deafness, even alcoholism.
In London in 1936, Julian Huxley, a brother of Aldous and a grandson of Thomas Henry Huxley, Darwin’s bulldog, gave the keynote speech at the Galton Dinner in the Waldorf Hotel. Huxley called eugenics “one of the supreme religious duties,” almost a platitude by then, and he illustrated it with a mutant fly, abnormal abdomen. After Huxley’s speech, the president of the International Union for the Scientific Investigation of Population Problems, Colonel Sir Charles Close, got up and applauded Huxley for a talk so full of valuable remarks: “We cannot digest all of them at the present time; to attempt to do so might bring us to the condition of that unfortunate fly of which he has spoken, the fly that suffered from a swollen abdomen.” Sir Charles told the audience about a population congress he had recently attended in Berlin. “Present-day Germany must be regarded as a vast laboratory which is the scene of a gigantic eugenics experiment,” he said. “It would be quite wrong and quite unscientific to decry everything which is now going on in that country. There is, as a fact, much being carried out in Germany which deserves our approbation. The authorities there are in the position of being able to carry out the advice of their scientific advisers.”
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.”