Time, Love , Memory

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Time, Love , Memory Page 10

by Jonathan Weiner


  As it turned out, what Lewis was learning in his Fly Room would someday thrill a new generation of molecular biologists and would win him a share of a Nobel Prize. But at that time, Lewis saw no point in trying to convince Delbrück that what he was doing was interesting. Lewis was smaller, gentler, and quieter than most of the bullyboys. He liked to keep tanks of rare tropical fish and anemones in his laboratory, and he raised generations of octopi, which Benzer, who had never seen an octopus embryo, found supremely beautiful. Lewis had long, owlish eyebrows like nerve endings looking for a home. And Lewis was an owl, like Benzer himself. Sometimes just before dawn, when Benzer roamed the corridors thinking about genes, nerves, and behavior, he would hear, through Lewis’s closed door, the sounds of a flute.

  BENZER KNEW what he wanted: He wanted to go from the gene to the kinds of instincts that ethologists studied out in the wild. Ethologists studied pieces of animal behavior as pieces of anatomy, portions of our inheritance that have evolved over thousands of generations just like a thorax or a pelvic bone or a braincase. When they studied the imprinting of goslings on geese, the mating dances of ducks and sticklebacks, and the massive collective engineering projects of ants and bees, they tried to break apart each act of instinctive behavior into a series of steps, the steps they called “atoms of behavior.” Of course, most ethologists were field biologists. They worked outside, watching bees, dragonflies, greylag geese, and ruddy Egyptian ducks, as Konrad Lorenz describes in his memoir King Solomon’s Ring. They loved to tramp along streams and riverbanks watching their subjects in action, and a few of them learned to talk in so many languages of duck and goose that sometimes in the heat of the moment one of Lorenz’s field assistants would get mixed up: “Rangangangang, rangangang—oh, sorry, I mean—quahg, gegegegeg, Quahg, gegegeg!” They ignored both genetics and molecular biology. They assumed that variations in behavior do pass down from generation to generation, and they left it at that. “Atoms of behavior” was only a metaphor. They studied instincts from the outside.

  As one of the world’s first molecular biologists, Benzer thought he could do what no one else had done: look at the actual atoms. But after his ten years of hard labor mapping the gene rII, he did not want to have to start mapping genes again. He wanted to get straight to the fun and study the behavior of an animal whose genes had already been mapped.

  More and more often, Benzer found himself strolling out of Sperry’s lab in the middle of the night, sometimes with a book in his hand, and dropping by Lewis’s Fly Room to look at the coral fish and the baby octopi. Whenever he dropped in, Lewis would be busy inspecting mutant flics through the microscope and adding their mutations to the chromosome maps that his teacher Sturtevant had begun in the middle of the night back in 1911.

  If Benzer was ever going to disentangle nature and nurture, it seemed self-evident to him that the thing to do was to keep the environment constant and change the genes. He knew that the maps on Lewis’s walls were still the most extensive genetic maps of any organism in the world. If he worked with them, he would be making a kind of splice between the old and the new, just as he had done in his adventures with rII; and he could ask for help from Sturtevant and Lewis, two of the last Lords of the Flies.

  Of course, his old mentor and Zen master Max Delbrück would cackle. But Max himself had a saying: “Don’t do fashionable research.”

  One night Benzer stopped by Lewis’s laboratory and borrowed a milk bottle full of fruit flies. He also borrowed some test tubes—he couldn’t find a test tube anywhere in Sperry’s lab. He put a lightbulb on his benchtop, held two test tubes mouth to mouth, turned out the overhead lights, and watched a fly run toward the light.

  CHAPTER SEVEN

  First Choice

  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 gene
ticist 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.”

 

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