Felicity is a continual progress of the desire, from one object to another, the attaining of the former, being still but the way to the latter.
—THOMAS HOBBES,
Leviathan
BENZER LEANS BACK against the wall of his laboratory’s meeting room and sips his first cup of laboratory tea. A menu cover on the wall, an old souvenir from an extinct delicatessen, still says SEYMOUR’S SANDWICH SHOP. He wears a rumpled white lab coat over a button-down shirt, a woolen sweater, a loosened tie, the working clothes of the old school since Arrowsmith. Horn-rimmed glasses hang from a white cord around his neck.
Having worked until dawn in his sanctum, as usual, he is settling back to work at one in the afternoon, also as usual, nursing his tea while the young biologists around him chew the last of their lunches. Successful laboratories are like Renaissance studios: generations of students pass through them to learn from a master. Although Benzer retired from classroom teaching when he reached the age of seventy, young Ph.D.s still apply from around the world to work with him in the lab. His current crew comes from China, France, Germany, India, Japan, Korea, and Pakistan. At the moment Benzer himself is the only American in this group.
He has been a legend in biology since before his latest students were born—ever since rII. Postdocs study his face now the way Arrowsmith studied Max Gottlieb’s. They give him their papers to read, and then they bring back his black and spidery marginalia for him to decipher (“almost unreadable, even to me”). They learn how to calibrate his praise, and may know the look with which he dismisses anything that is not solid, not well grounded, not at the root of things, not part of the foundation: a skeptical, fine look, a very slight rolling of the eyes and a slight smile.
Every week or so he invites seminar speakers—friends, famous and obscure—to help his lab follow the explosions of molecular biology. Every Friday afternoon he also herds the postdocs out of the lab and across the campus to the Red Door Cafe for coffee and conversation. Sometimes the postdocs exchange looks before they go. They are a new, driven generation of molecular biologists. For them Benzer’s custom has the odor of the Old World, of Paris and Cambridge, of a more languid and leisurely civilization. One Friday not long ago, Benzer asked them if they had ever read Arrowsmith. The crew looked blank. A few of them knew Aerosmith, the rock group. Only one of them had read the book, and he pulled from his memory the name Leonora. Benzer cried sharply, with real pain in his voice after sixty years, “Leora!”
Sometimes lately he remembers what Salvador Luria told him the night they met—the night he saw Delbrück’s picture, the night he left physics. Luria said something that seemed to him to be extremely important, although Benzer could not follow it at the time. “He said, ‘Everyone keeps going down, down, down, trying to be more reductionist, trying to see finer and finer, to find the basis of structure and function.’ And he said, ‘I think it’s time to start going up again—going in the opposite direction.’
“So I was interested in that,” Benzer says now. “But of course it took a long time before I—it takes a long time of going down before you start looking to go up again. Down is a much easier way to go.”
Now he is using the latest gleaming tools of molecular biology to work up from the gene to the trait and to work down from the trait to the gene. He is pursuing some of the mutants that he found in the first years of the Fly Room, and the excitement of the work is keeping him in the lab all night, night after night. Some of these mutants he has been trying to understand for thirty years; and now, one by one, he can. He follows Changsoo Kim, the Korean postdoc, out of the Sandwich Shop and into his laboratory darkroom, sipping his tea from a paper cup. “Oh, my God!” he cries, looking at Chang’s microphotographs. “What’s wrong with these guys? What are all those spots?”
Through the microscope, Chang has been making a series of micro-portraits of drop-dead, beginning with the mutant as an egg and a pupa and working through a little series of metamorphic stages that are known by the most lyrical name in entomology: instars. The poor mutant drop-dead looks and acts perfectly normal for the first several days of its life, but then it begins to stagger and totter, and suddenly drops dead. Chang has been trying to find out why. This is the kind of laborious work that is required if one is to track the workings of a gene through a fly, and Benzer is happy to be able to delegate some of the bench work to postdocs. Every gene makes its own distinctive protein, and Chang has managed to stain drop-dead’s. First he had to purify the drop-dead protein and inject it into a rabbit. The rabbit made an antibody that attacked the protein. Then Chang purified the rabbit antibody. Now Chang has a pure drop-dead stain, and he can use it like the Alzheimer’s stains that Carol Miller is using. But because he is studying the fly he can stain mutants at every age and stage of their lives.
Benzer is not well known outside science; he is what is sometimes called a scientist’s scientist. Here he talks with three of the most celebrated scientists of his century: with Konrad Lorenz (holding drink), a founder of the science of ethology, in Austria; with Richard Feynman (in white shirt), the quantum physicist, at Caltech; and with James Watson, at Cold Spring Harbor Laboratory. (Illustrations credit 17.1)
Currently Chang spends most of each workday preparing mutants for the microscope. First he freezes a drop-dead fly and slices it into microscopically thin sections, about ten microns thin, on a cryostat. (When they are frozen, flies slice better.) To slice a fly, he freezes some goopy Tissue-tek. The goop turns into a sticky white hill. Then he puts a single fly on the top of the hill and gets it centered. He aims a nozzle at the fly and blasts it with a jet of very cold carbon dioxide gas to keep its walls well frozen. With a fresh razor blade, he whittles away most of the hill’s base, leaving the fly lying at the top of a little white Mayan temple. He puts a can over the temple and floods it with more carbon dioxide. The can fills with white shavings, like snow. Then he shakes out the Mayan temple and mounts it in the slicer. When he turns a dial, the slicer spits out a ribbon of dry ice and fly slices. He uses a toy arrow with a rubber suction cup to lift a glass microscope slide and hold it where it will catch the ribbon of dry ice and frozen fly; he manages this step so deftly that the ribbon of shavings adheres to the very center of the microscope slide. Each slide dries for about one hour. Then there is the staining procedure. Then there are rinses and more stains.
One by one, Chang prepares slides of his drop-dead mutants, and slowly he works his way down each fly. He stains the antennae, the eyes, and the optical centers, which are right next to the eyes. Even the optic lobe has structure. Some cells are vertical, some transversal; it looks very well organized. Then he stains the brain and the esophagus, which in a fly runs straight through the brain (food on its mind). Chang scans them one by one through the microscope. Wherever and whenever the drop-dead gene turns on, at every age and stage of the mutant’s life, the gene makes the drop-dead protein, Chung’s antibody sticks to the protein, and it glows green in the microphotographs that Chang shows Seymour.
“Bright buttons,” says Seymour, sipping his tea. Today Chang has been photographing the fly’s third instar. There are eight spots on two different planes of focus: six in a bunch, like the six spots on the face of a die, and two spots farther up. They are somewhere in the third instars ventral ganglion, among a tangle of nerves and tracheal tubes. All of this work is very tentative. It is at the point now where it feels to Benzer like a murder mystery: Who done it, who killed the fly? “Well, you’ll have to follow those eight buttons,” he says happily, taking the photograph back with him to show off in the Sandwich Shop.
After so many years with drop-dead and so many years on the planet, Benzer cannot help identifying with a mutant that walks along normally and then suddenly keels over. Watching it stagger and fall, he often thinks of the victims of Huntington’s disease, but the cause of death is completely different. He has no idea if the solution to the drop-dead murder mystery will illuminate some aspect of human health. He hopes so, but after all these
years he is just curious to know.
THE LATE SENATOR William Proxmire used to give out an annual “Golden Fleece Award” for scientific research so patently irrelevant that everyone who heard of it would have to agree that American taxpayers were being bilked by the National Science Foundation and the nation’s universities. Benzer may be the only scientist in the country to have been nominated in the same year for a Golden Fleece Award and a Nobel Prize.
At lunch hour in Harvard’s Museum of Comparative Zoology (MCZ), where the old antagonists Richard Lewontin and E. O. Wilson still maintain their laboratories and the views that set them at war twenty years ago, conversations within a few stair lengths of each other are almost as divergent as the views of the old senator and the Royal Swedish Academy of Sciences. When the topic is Benzer, walking from one floor to another at the MCZ is like walking from pole to pole, from one extreme of opinion to the other. “With behavior genetics,” as a molecular biologist once put it after praising the clock genes, the celestial beauties of period and timeless, “you can walk down one corridor at Harvard and walk through all the time zones in the world.”
Lewontin is a fine drosophilist, a great contrarian, and a polemicist against much that is central to Western science. “Darwin’s theory of evolution by natural selection,” he has written, “is obviously nineteenth-century capitalism writ large, and his immersion in the social relations of a rising bourgeoisie had an overwhelming effect on the contents of his theory.”
To which the venerable molecular biologist Max Perutz rejoins, “Marxism may be discredited in Eastern Europe, but it still seems to flourish at Harvard.”
Lewontin’s views on the Human Genome Project and genetic research in general have set him far to one end of the spectrum of debate. He argues that since finding a gene does not tell one what is going on above the gene, a gene is, in itself, worthless information. Benzer and his students would answer: But it is a first step, a way in.
Lewontin has written that the metaphors of science are
filled with the violence, voyeurism, and tumescence of male adolescent fantasy. Scientists “wrestle” with an always female nature, to “wrest from her the truth,” or to “reveal her hidden secrets.” They make “war” on diseases and “conquer” them. Good science is “hard” science; bad science (like that refuge of so many women, psychology) is “soft” science, and molecular biology, like physics, is characterized by “hard inference.” The method of science is largely reductionist, taking Descartes’s clock metaphor as a basis for tearing the complex world into small bits and pieces to understand it, much as the archetypical small boy takes apart the real clock to see what makes it tick.
Many of Benzer’s students would answer: Mea culpa. But look what we found out about the clock!
The clubhouse for the scientists who opened the war on Wilson and sociobiology was Richard Lewontin’s Fly Room in Harvard’s MCZ. Although Lewontin is loathed and feared by students and eminences of genes and behavior (“He lies! He lies! But don’t tell him I said so!”), his Fly Room is decorated like Fly Rooms everywhere. The message BE AFRAID, BE VERY AFRAID blares from the Hollywood poster for the remake of The Fly, the same legend that hangs beneath the rifle in Jeff Hall’s office. Lewontin’s wall clock is decorated with a big paper pair of fly’s wings glued to the cinder block with a legend printed beneath it: MOLECULAR CLOCK.
Lewontin is convinced that the Benzer school can find nothing in the fly that matters to the man or woman on the street. “The implication is that if you understand something about the behavior of flies, then you understand something about the behavior of you-know-who,” he tells one of his favorite postdocs as they sit down together in the lab for lunch. “That’s where the bullshit comes in. Suppose they figure out something about courtship in flies. Maybe they will. They are good scientists. But then what? I don’t know what that has to do with courtship in people. So why study it in fruit flies if you are not interested in fruit flies?
“Always the same story,” Lewontin says world-wearily. “You take a simple organism because it is simpler to study, but you factor out everything that’s interesting in the process. In terms of Drosophila, in terms of the evolution of its courtship, the work is interesting. But it’s like saying someone has understood why I eat what I am eating because of smell perception in fruit flies.” He smiles dourly. The reason he is eating this particular lunch is not in his genes, Lewontin says, holding it up. “I’m eating it because of my social position in this culture and what’s available and what lunch I got to eat when I was a kid.” This is a lunch that is typical of his time and his place and his culture but not of his species. “Most people in the world don’t eat pizza and cookies.”
The postdoc asks Lewontin what he thinks of Tully’s spectacular work on learning and memory. “I’m not going to argue,” Lewontin says, “that learning and memory in fruit flies has anything to do with learning and memory in us.”
Then what did Lewontin teach in the genes-and-behavior course that he himself gave at Harvard some years ago?
“Basic behavior genetics of simple organisms,” Lewontin replies. “But I certainly didn’t say that mutants in Drosophila are why I hate lima beans.”
This is one of Lewontin’s favorite postdocs; if anyone else were asking these questions, Lewontin might chop off his head. When the young man presses him, Lewontin concedes that it may be possible that we, like the flies, carry mutations that shape our behavior at choice points. “I wouldn’t deny that,” Lewontin says in the tolerant tone with which he might concede that there may be life on other planets in some distant galaxy, to be discovered in some far distant millennium. “But what people really want to know is, why do people want to go around bonking each other on the head? Seriously—there is a suspension of disbelief.” Who cares about a clock gene in a fly? “The fact you can find it is nice. But not an earthshaking event.” And that there is a homologous gene in human beings is of purely evolutionary interest.
“And behaviorally.” The postdoc is pushing Lewontin now. If we have clock genes like flies and if variant forms give us variant inner clocks, then the fly work becomes the perfect beginning for the next step, for studies of human clock genes and human behavior, and from there for studies of sex and memory, all working from the genes outward as the Benzer school has done in flies. “So you could pursue a research program using fruit flies as a model,” says the postdoc.
“Wait a minute,” Lewontin says. Not even a human clock gene is ever going to explain what we are interested in, he says. “I couldn’t sleep that night because I had an anxiety attack. Or a fight with my wife. You’ve got to be very, very careful about carryover. We have very, very complicated neurochemistry. And we don’t know how to get at that in fruit flies. We don’t know what fruit flies are thinking. We have no idea how to get at that. Maybe if you could get at that …”
“Have you ever watched a fly sleeping?” the postdoc insists. “Sitting in its tube?”
Now Lewontin delivers his bottom line. As long as you keep the border very clean and simple and straightforward, he says, there’s no problem, no conflict. Flies are flies and people are people. And if there is a gene in common between flies and human beings, he says, “then that may be interesting to people like us, who are interested in evolution—but not to anybody else.”
The conversation is over. Up and down the table, old friends and colleagues with culturally determined paper-bag lunches are pulling up chairs and sitting down. They are joined by Jonathan Beckwith and Ruth Hubbard, colleagues who are still trying, with Lewontin, to put out the fires of genomania wherever they spring up. The lunch speaker this afternoon is a visiting scholar from Seattle who feels that Western philosophy has been built on the wrong foundations; it should be rebuilt on the proper foundations, the ones laid down by Karl Marx.
IN HIS ANT ROOM in the same museum, E. O. Wilson defends Benzer and his school. “I mean, this is the way it goes,” he says in a tone just as theatrically commonsen
sical as Lewontin’s. “Science consists substantially of finding an entry point. And even a small advance following a breakthrough should be regarded as science of the first class. What’s unreasonable is then to demand of the people who are doing that very early work—to demand of them that they come up with a whole explanation of everything. That’s crazy.” Benzer and his students and his students’ students have never claimed to explain everything, he says. Nor has anyone else in the molecular study of behavior. “Nonetheless, they should be regarded as people who are beginning to explain behavior.
“As the data come in and the modeling improves and we can face the implications with increasing honesty and lack of fear, my prediction is that the role of evolutionary biology will become increasingly important,” Wilson says. “If everything else in biology is the product of evolution, then surely we have to constantly examine and reexamine the human mind and human social behavior as products of evolution.”
Lewontin and his group have always argued this way: Until a scientist has proven a particular connection between animals and human beings beyond doubt, they will deny there is such a connection. They will not take the scientific view that the evidence is not in. Instead, they play to the commonsense feeling that there can be no solid connection between animals’ instincts and our own. Lewontin’s circle sees the attempt to draw such connections as one of the lowest and most base aspects of science since science began: an effort by the elite to repress the masses.
As for Wilson, ever since Lewontin led the attack on him in the 1970s and 1980s, he has been studying the history of science. He sees the effort to analyze the biological origins of human nature, and to unite that body of knowledge with the humanities, as the noblest enterprise in science—the enterprise that has animated science from the beginning and now reaches toward its fulfillment. Sir Francis Bacon considered the shaky state of knowledge in his time and saw “a magnificent structure that has no foundation.” There is no other course, Bacon wrote, but “to begin the work anew, and raise or rebuild the sciences, arts, and all human knowledge from a firm and solid basis.” Wilson sees Benzer as part of that effort, and he acknowledges the challenge it presents to many sensibilities—essentially the challenge that Darwin threw down in the nineteenth century, made more acute by coming so close to home. What makes the atomic theory of behavior such a radical theory is that it is a theory of relation, or roots—“radical” meaning “of roots.” It shows us how we are related closely to our siblings and parents; to every member of our species; to every species from which we have descended; and to all the ancestral forms that began the experiment of life on the planet: all one tree, from the crown to the roots.
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