Everyone who studies genes and behavior at the level of genes, molecules, or nerves gets asked questions like this: “Is that all there is?” Anatomists hear the same question when first-year medical students get their first look at the organs inside a cadaver. Behavior geneticists hear this all the time now, and the clock gene in particular attracts the question, Hall said, because a clock is a mechanism that we all understand to be a mechanism. It is the very symbol of mechanism in the heavens and in the body. So the deep assumption of the question, Hall said, is this: “Once you know something about it, it’s not behavior. It remains behavior as long as it sits at the level of mystery and miracle.” In Hall’s opinion, that is why people ask him if keeping track of time is really a piece of behavior when it plainly is, and so is the act of seeing the light from a lightbulb, “some of the most fascinating behavior in the whole history of biological investigation!”
The reporter looked as if he were beginning to be glad he had said the question was his friends’. “Vision!” Hall shouted, waking the dogs under his desk. “It’s not just that you can see! It’s how you respond to the visual world of shapes and movements! And this is not to castigate your friend and say, ‘You’re an idiot!’ This is not to say, ‘Your ignorance is so colossal that you’re doing nothing but sit there and dribble saliva into your lap!’ ” And Hall went through the roof. (“Jeff Hall easily goes through the roof,” says Benzer—which is no more than Hall often says of himself.)
Other clock watchers answer the question in a lower key. Jerry Feldman, who discovered a clock gene in the fungus Neurospora, says calmly, “Call it what you want. You could say any gene that modifies behavior is a behavioral gene. What’s important is the gene. What does it do? Ultimately, how does it couple with behavior? That’s what interests me.”
Kyriacou says cheerfully, “It’s a real behavior gene. What it does, it adds behavior when it’s there. It has rhythms. It’s beautiful.”
TODAY MANY of Benzer’s students credit Hall with the success of the atomic theory of behavior after Benzer’s beginning. “It’s because of what Hall pushed first that the field came of age,” says Tim Tully, one of Benzer’s students’ students.
In the late 1970s and for much of the 1980s, Hall felt embattled and alone, as if he were carrying a fallen banner. Benzer, with his fame, could have been a general not only for Konopka but for the whole field he had started. Benzer could have championed it like another Morgan. But unlike Morgan, Benzer had never had much time for committees or speeches, for writing books or playing scientific politics, and he was not working on behavior anymore.
In those years, Benzer was going more and more deeply into the nervous system of the fly. He had decided that before he went any further with behavior he should study the way genes build bodies. He and his latest students were using genes and mutants to study the way nerves work: doing basic neurogenetics. Tracing the way genes build the nerves in the embryo seemed to Benzer the next logical order of business.
Hall was outraged, but Benzer saw nothing wrong with jumping fields. He had jumped before. At Caltech during a night of skits after Delbrück had won his Nobel Prize, Delbrück’s circle sang a song about Benzer to the tune of “Jimmy Crack Corn.” In the first verses he was a physicist playing with charged particles:
Physics was fun, but I don’t care,
I’m on to something else next year,
I must stick with the new frontier
Until I’m old and gray.
In the next verses he quit physics and mapped the gene:
Genetics was fun, but I don’t care,
I’m on to something else next year,
I must stick with the new frontier
Until I’m old and gray.
In the last verses he quit genetics for behavior:
Behavior was fun, but I don’t care,
I’m on to something else next year,
I must stick with the new frontier
Until I’m old and gray.
It was not only Benzer who was restless; by the late 1970s, many of the founders of the atomic theory of behavior had turned away from the theory. Sydney Brenner was phasing down his studies of worm behavior and studying the wiring diagrams of worm nerves instead. In fact, he had turned in this new direction before Benzer had, and his arguments had helped persuade Benzer that the embryo was the next frontier. Now at meetings, Brenner ragged Hall. “All of you neurogeneticists think you are finding interesting new things from your neural mutants,” he told Hall, “whereas in the end they are all just going to be defective in things like aldolase,” a garden-variety enzyme without which a fly cannot digest glucose and gradually starves to death. This was the same argument that Benzer had heard in the Sperry lab and Hall had heard from Michael Rosbash in the Brandeis locker room: period, fruitless, dunce, and the rest were just sick flies; there was something wrong with their housekeeping genes.
Another phage veteran who abandoned the atomic theory of behavior in those years was Gunther Stent, who had been working on the leech. Now Stent began writing pessimistic essays about the field, just as ten years before, in the brief doldrums of the 1960s, he had written elegiacal essays about molecular biology. Stent had now reconsidered Butler’s saying “A hen is only an egg’s way of making another egg.” If life is a circle, why focus on the genes? Stent was beginning to look at life more in the philosophical spirit of Emerson: “The method of nature: who could ever analyze it? That rushing stream will not stop to be observed. We can never surprise nature in a corner; never find the end of a thread; never tell where to set the first stone. The bird hastens to lay her egg: the egg hastens to be a bird.” Stent doubted that the genetic dissection of behavior or even the genetic dissection of development was going to turn out to be much more informative than dissection with a scalpel.
Meanwhile, Delbrück felt completely defeated. Twenty-five years after dictating his ebullient letter to Benzer about “starting a new life,” Delbrück still could not understand how a stalk of fungus grows toward light. He confided to his diary that he was “sick at heart at the unsolved state of the problem.” He had failed to understand the genetics and mechanics of even one simple-seeming piece of behavior. “I think Max indeed was disillusioned,” Crick says now. “The phenomenon he tried to study was very intricate, and I don’t think he ever got to the bottom of it. And it was, I think, not a wise choice in the first place, and a bit of bad luck as well.”
In 1978, Delbrück’s doctors, taking routine X rays, discovered that cancer was chewing away his ribs. Benzer and dozens of other phage veterans took to visiting him in his living room in the afternoons while he sat in his rocking chair quoting Samuel Beckett (“The light gleams an instant …”). Although Beckett and Delbrück had both won the Nobel Prize in the same year, Delbrück had not met his hero in Stockholm (“No, he didn’t come, the dog.”).
At the same time, Benzer’s wife, Dotty, was in the hospital with breast cancer. The two of them had been unusually close ever since Seymour was sixteen and she was twenty-one. She was a lark and he was an owl, but he always strolled into the laboratory in the afternoons holding hands with her. That was unusual behavior at Caltech, though it was a Fly Room tradition. Thomas and Lilian Morgan had worked side by side among the milk bottles as soon as their children were out of the house. Morgan’s Raiders had named one of their female mutants bobbed. She had short bristles, and they named her after Morgan’s technician, Phoebe Reed, who had just bobbed her hair. Sturtevant married Phoebe Reed.
Benzer had begun transforming himself into an expert on cancer biology and treatment from the moment that he and Dotty knew she was sick. Now he neglected the laboratory for long periods to attend national and international conferences on breast cancer. Even when he was at the lab, he spent hours on international phone calls to specialists in Switzerland; and even when he was satisfied that he was taking Dotty to see the best possible doctor, he would still arrive in the doctor’s office with stacks of technical pape
rs to explain and discuss. Martin Arrowsmith had lost Leora to a tragic illness; Benzer was determined not to lose Dotty.
That June, Delbrück gave the commencement address at Caltech. He spoke in the school’s “Court of Man,” flanked by buildings dedicated to behavioral biology on one side and to the humanities on the other. In a sense, the atomic theory of behavior is an attempt to unite those disciplines, behavioral biology and the humanities. In the long view, it aims to unite all of the sciences, all of philosophy, and all the arts. But Delbrück, speaking to Caltech’s graduating seniors from a wheelchair, predicted that the union would never take place. “Indeed,” he said, “we can take it for granted that science is intrinsically incapable of coping with the recurrent questions of death, love, moral decision, greed, anger, aggression.” And he told a weary fable. Science is like Tithonus of the Homeric myth, he said. When Tithonus was young, the goddess of the dawn, Aurora, fell in love with him. She asked Zeus to make him immortal. Zeus did so—but he did not grant him eternal youth. “Tithonus aged and shriveled and talked incessantly,” Delbrück said. At last he turned into a grasshopper, and Aurora had to keep him in a little box.
“Science does chatter and chirp incessantly,” Delbrück concluded, “sweet music to those few who are tuned in to it, but does it satisfy Auroras yearnings, Aurora the morning dawn?” Does it answer the questions we all want answered?
Benzer’s current crew of postdocs sometimes talks about the history of the laboratory during their brief late-morning cigarette breaks, before Benzer comes in. They sit on stone benches under palm trees and jacarandas outside Church Hall, and they pass on the legends they have heard. For them all of this happened in hearsay time. They say that when Max and Dotty died, Benzer’s friends doubted that he would ever recover. They say that for a while he published nothing, as if what he saw through a microscope was intrinsically incapable of touching the recurrent questions.
CHAPTER THIRTEEN
Reading an Instinct
I am a book I neither wrote nor read.
—DELMORE SCHWARTZ
MOST OF THE FOUNDERS of the gene business left their laboratories sooner or later to run corporations, foundations, universities. Crick served briefly as president of the Salk Institute in La Jolla. Watson became director of Cold Spring Harbor. “And that is apt to happen to people,” says Crick in the cheerfully sturdy tones of Odysseus describing the whirlpool Charybdis. “It’s not likely to happen to Seymour, who is the last person to want to do administration, I would have thought.”
As Benzer’s friends succumbed one by one, Benzer presented each of them with a copy of a little handbook called Microcosmographia Academica: Being a Guide for the Young Academic Politician. The pamphlet (“the merest sketch of the little world that now lies before you,” the preface explains) teaches the skills that Benzer’s former labmates would now need to learn, including propaganda, “that branch of the art of lying which consists in very nearly deceiving your friends without quite deceiving your enemies.”
Benzer, of course, had always preferred solitary work, eased by the company of other night owls in the lab and by his wife and daughters at home. Although he was happy in the old phage days and the first mapping days, there had been moments when the work got too solitary, even for him. Back in the fall of 1952, when he returned from the Institut Pasteur to his lab at Purdue, he had written a lonely letter to Max Delbrück: “After Paris, this local phage isolation is almost unbearable.”
By the mid-1980s, however, the map work that had begun in the night thoughts of Sturtevant and Benzer and a few others was exploding into big science: the biggest single project in the history of biology. One of its formative meetings took place on a weekend in May 1985, when the molecular biologist Robert Sinsheimer, now chancellor of the University of California at Santa Cruz, called in a few other molecular biologists to talk about the idea. UCSC had hoped to build a giant telescope, but the school had lost that project to Caltech. Now Sinsheimer was swiveling his sights around—like Galileo, who had turned his first celebrated telescope into a microscope and stared at a fly in a bottle. Sinsheimer was thinking about a project that he found even more exciting than a big telescope: a group effort to map every single gene in a human being.
This enterprise got away from UCSC too. The Human Genome Project was soon a multibillion-dollar public program with a vast bureaucratic apparatus involving the U.S. Department of Energy (DOE), the U.S. National Human Genome Research Institute (NHGR), for the coordination of international collaboration the Human Genome Organization (HUGO), and many more agencies and acronyms. Laboratories across the United States, France, Italy, the United Kingdom, and Japan began half racing and half collaborating to map and sequence every one of the 3 billion letters in the human genome across 3,600 map units. What Benzer did by hand in individual petri dishes was soon being done day and night by robots that sprayed human DNA into rows of vials; copied each snippet of DNA; chopped it up; sequenced the letters; and stored the letters in computers. By the last years of the twentieth century, the Institute for Genomic Research in Rockville, Maryland, would be sequencing millions of letters of code a year and hoping to go faster. The Washington University Genome Sequencing Center in St. Louis would be sequencing about 100,000 letters a day and hoping to go faster. The map will eventually fill the equivalent of 134 complete sets of the volumes that Sturtevant loved to commit to memory in the evenings, the Encyclopaedia Britannica. Biologists would compete to see how many letters of the human genome their “high-throughput” robots could decipher in how little time in laboratories they called factories. They talked patents and quality control and venture capital and data isolation (meaning secrecy).
James Watson became the first director of the Human Genome Project. He worked the telephone from Cold Spring Harbor in a voice of old celebrity, manipulating the multibillion-dollar government program and the needs of the pharmaceutical companies and biotechnology companies that eventually began taking a bottom-line interest in it. Wall Street trusted that the rational design of drugs would be radically enhanced by knowledge of genes and how they work. The Concorde and the first-class cabins of Boeing 747s were already beginning to fill with instantaires, scientists who had made a killing overnight in computer hardware and software or genetic hardware and software. Entrepreneurs raced through the last years of the century windmilling their arms: “I just sold one hundred thousand genes to SmithKline Beecham!” They were rich men who got to heaven through the eye of a needle—or, in the Arrowsmith view of life, fell from grace. Recently the star molecular biologist at Genset in Paris explained to a reporter from Science magazine why he plays the piano in the evenings. “In genetics there is no mystery,” he said, “but music is all mystery.”
Today in the president’s office at Cold Spring Harbor, Watson deals with the acronyms along with the minutiae of Cold Spring Harbor hirings and firings and high-level dinner parties, conversations in which grungy young drosophilists stopping by from the Fly Room can hear the expensive thunk of limousine doors. “I might be going.… It’s a question of if I can see Bill Gates.” At luncheons Watson talks stocks and bonds and options. Cold Spring Harbor was the scientific center of the eugenics movement in the first half of this century. As the laboratory’s director, Watson has helped preserve its eugenic archives as cautionary tales. But he likes to entertain his luncheon partners, the presidents of nations and corporations, with war stories of the bureaucratic or bio-cratic life, and he likes to strike a cynical tone. When Watson talks about the Human Genome Project’s decision to set aside money for ethics research, for instance, he explains his reasoning with a smile: “To preempt the critics.” At first, ethicists were making the birth of the program a very difficult labor. So Watson allotted them money. “Ethicists are a mixed lot,” he says, “generally not worrying about their own problems, just somebody else’s problems.” He seems to speak with confidence, as if he were absolutely sure of approval.
Watson saw the Human Genome Pr
oject as the logical culmination of a career that began with the double helix, and as with the double helix he did everything he could to make it happen. “There were some specialists who were against it. So we bribed them,” he likes to say with the same smile, explaining the Human Genome Project’s early decision to sequence the genomes of a fruit fly, a nematode worm, a mouse, the bacterium E. coli, and the mustard weed Arabidopsis. But this was not really a bribe. Molecular biologists needed all of these model organisms and more if the code of human beings was to mean anything more at the end of the day than a series of Cs, As, Ts, and Gs. By sequencing the DNA of other species along with the DNA in their own bodies, the biologists would produce a kind of Rosetta stone. They would generate enough different versions of enough different genes to figure out what most of the words mean. It had become not only a question of science but also a question of high finance to figure out the meaning of genes—or even to figure out how to figure out the meaning, a difficult question with writing as ancient and peculiar as this. New companies sprang up just to elucidate the genes in what are usually called (in spite of Benzer’s protests at meetings) the lower organisms.
SO IT HAPPENED that in the 1980s the work that Benzer and his students had started in middle-of-the-night eccentricity and fly-on-the-wall obscurity began heating up. Observers in and around biology were beginning to realize the value of flies and neurogenetics. Jeff Hall thought that Drosophila was becoming industrial. At conferences on Drosophila neurobiology, which were now legion, there were ten scientists competing for every speaking slot. For a while the study of genes and behavior remained a fringe specialty. Most of the great names in neurogenetics did not work on behavior. Instead, following Benzer’s lead, they studied the way fly nerves grow in embryos, the way fly nerves speak to one another in the brain. At fly meetings, behavior was still the caboose of the train. The last session was always the behavioral session, which the chairman of that session had labored to fill because there was still hardly anybody working in the field. Hall often spoke to an audience that, in effect, consisted of the janitor who was cleaning out the auditorium. He says that even neurogeneticists thought he was working with “silly and embarrassing behavioral observations, and titillating mutants.”
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