Time, Love , Memory

by Jonathan Weiner

  Benzer lays the countercurrent machine back down on the benchtop. The flies at the bottom of Tube Zero are now at one end of a glass tunnel. The only light they can see is the light at the far end of the tunnel, the fifteen-watt fluorescent tube. The flies can stay put in the bottom of Tube Zero, or they can move toward the light. As Pascal says, “There is enough light for those who desire only to see, and enough darkness for those of a contrary disposition.” So the flies are facing a simple choice. If they do not move forward, they will remain in Tube Zero. If they do move forward, they will find themselves in the next test tube, Tube One.

  Some of the flies walk, some of them run, some of them fly, and some of them meander. By the time fifteen seconds have passed, all but two of the flies have gone toward the light.

  Benzer picks up the apparatus and slides the test tubes around. Now the flies that went toward the light—almost all of the winged atoms in the machine—are in Tube One, while the two flies that did not go remain in Tube Zero.

  “Everybody gets another chance,” Benzer murmurs. Again he raps the apparatus on the benchtop. Again he lays it flat on the benchtop. Within fifteen seconds, most of the flies again go toward the light. But this time one of the flies in Tube Zero decides to go too, and a few of the flies that went the first time choose not to go.

  “What are they doing now?” Benzer says. “They’re wandering around.” This is why he built the countercurrent machine in the first place. Facing the same choice point, the flies do not always make the same choice. As a swarm, as a mass, they are predictable, but as individuals they are unpredictable. Even fruit flies in a test tube do not always act the same way twice. Why not? Watching their decisions and revisions by the light of the fifteen-watt bulb back in 1966, Benzer got an inkling that flies might be more than atoms of behavior. He had thought they would be simple, regular, predictable, like the particles in the chemist’s test tubes. Instead the flies act as if they are improvising from moment to moment, based on what each fly sees in front of it, what has happened in its past, and what can only be called the personality of that fly.

  “Flip it over, switch it back.” Now the flies that have chosen the light twice are in Tube Two. The flies that have chosen the light once are in Tube One. The fly that has never chosen the light is still in Tube Zero, moving erratically in the half-dark. To human eyes it looks like a troubled fly.

  “Now we’ll give them another chance.” Benzer rocks and slides his gadget: the same operation, the same fifteen-second wait. Then again and again: knock, knock, knock. Each time, most of the flies move toward the light.

  “OK, there we are,” Benzer says at last, switching on the overhead lights. He can read the results at a glance. Tube Six contains flies that moved to the light six out of six times. Most of them are in there. Tube Five contains flies that moved five out of six times. And so on, all the way down to Tube Zero, the home of the troubled fly, which may be damaged goods.

  To prove that he is really testing what he thinks he is testing, Benzer dumps all of the flies back into Tube Zero and sets the apparatus on the benchtop again. This time he sets it down with the flies next to the light. Now the flies face the opposite choice. They are near the light. They can choose to stay where they are, or they can move away. When Benzer runs the experiment this way, most of the flies stay put in the bottom of Tube Zero. They do not hurry into the darkness the way they hurried into the light. Running the experiment backward this way is Benzer’s control. It proves that in the first rounds the flies were not indifferent to the light; they were not advancing through the tubes just for the sake of advancing through the tubes. He is looking at what he thinks he is looking at. The light is the key.

  PHILOSOPHERS used to speak of the ultimities. The last stop of a trip, the highest high C of a musical scale, and the final stage of an alchemical process, when the liquid in a beaker had traveled “from Crudity to Perfect Concoction,” as Sir Francis Bacon put it—these were ultimities.

  In science, the ultimities are the ultimate questions. These are the questions that so many generations have raised that they have come to seem eternal, always to be asked and never to be answered. They are the problems that interest us so much that solving them—finding even a small piece of them—would feel like finding the secret of life. The origin of species was once one of the ultimities of science, until Darwin. The origin of the universe is one of the ultimities today. So is the origin of life. And the most intimate, the most immediate, in some ways the most intricate and the most important for our inquiring species, will always be the origin of behavior. We have asked these questions from the beginning: How much of our fate is decided before we are born? What is written and in what code and of what materials? What are the connections between atoms, thoughts, feelings, behavior? How much of our behavior is passed down from one generation to the next?

  Benzer’s countercurrent machine was a point of origin for the science of genes and behavior, a point of origin for the headlines that have punctuated the news for the last ten years and sometimes seem likely to dominate it within another ten years. It was the beginning of what Benzer calls the genetic dissection of behavior.

  This is a science that is dedicated to exploring the inward infinity that Pascal imagined and to reading the writing on John Locke’s slate—for even Locke knew that the slate is not blank. He thought that our temperaments are at least partly innate: “Some men by unalterable frame of their constitution are stout, others timorous, some confident, others modest and tractable.” He did not think that very much else about our minds is innate, although other eighteenth-century philosophers argued that we are born knowing a great deal: “that sweetness is not bitterness,” to give one of the examples that Locke cited; or “that ‘two bodies cannot be in the same place,’ and that ‘it is impossible for the same thing to be and not to be,’ that ‘white is not black,’ that a ‘square is not a circle,’ that ‘yellowness is not sweetness.’ ” Many philosophers assumed that “these and a million of other such propositions,” as Locke skeptically wrote, “must be innate.” Today, these are questions that the science of genes and behavior can begin to test at the level of the hipbone-is-connected-to-the-thighbone.

  Sigmund Freud tried to make a solid science of human behavior. “Have you not noticed,” he wrote early in the century, “that every philosopher, every imaginative writer, every historian and every biographer makes up his own psychology for himself, brings forward his own particular hypotheses concerning the interconnections and aims of mental acts—all more or less plausible and all equally untrustworthy? There is an evident lack of any common foundation.” Freud tried to establish a foundation as solid as the foundations in physics and chemistry; but today the most interesting effort in progress is founded on physics, chemistry, and Benzer’s beginning.

  The new effort also builds on Darwin, and on the Darwinian studies of behavior that were attempted in the 1930s and 1940s by Konrad Lorenz, Niko Tinbergen, Karl von Frisch, and their students, who called themselves ethologists. One of Tinbergen’s books is illustrated by the silhouette of a bird in flight. When newborn goslings see that silhouette in the sky, they read the shape as a goose if it is moving to the left, a hawk if it is moving to the right. The silhouette of the goose does not scare goslings, but the silhouette of the hawk sends them scurrying. That kind of hard fact fascinated the ethologists. Goslings don’t learn to make that distinction between friend and enemy from their mothers. They know it from the first moment they see the sky. They know it when they are still standing in the nest with caps of eggshell on their heads. How do they know? Ethologists looked at such pieces of behavior and tried to dissect them into routines and subroutines, which they called “atoms of behavior.” Now with the tools of genetic dissection biologists can actually begin to study the instincts of goslings and newborn babies at the level of the atoms.

  In the 1970s, E. O. Wilson, inspired in part by his studies of ant societies, tried to extend the work of the ethologists to
human beings in a new synthesis he called “sociobiology.” Wilson was attacked by social scientists, on the one side, because they hated his attempt to biologize human nature, and he was attacked by biologists, on the other side, because they felt he had built castles in the air and had not acknowledged the need for hard molecular biologists to put foundations under them. Today many of those sociobiological speculations can be explored in the code of the ants, the code of the flies, and the code of human beings; and Wilson himself wants to claim the genetic dissection of behavior as a cornerstone of his foundation. “Better Benzer than Freud! Quote me. Better Benzer than Freud!” Wilson says, standing in his office by one of his celebrated colonies of leaf-cutter ants, to which he feeds Drosophila—preferably wingless mutants.

  What are we born knowing? This shape is often the first thing that newly hatched goslings see in the sky. If the shape is gliding to the left, the goslings stay in their nest; to the right, they scatter. Leftward means safety (goose); rightward means danger (hawk). All animals—including the human animal—inherit pieces of behavior. Biologists are now beginning to dissect some of our oldest and deepest instincts at the level of the genes. (Illustrations credit 1.1)

  “THERE IS GRANDEUR in this view of life,” Charles Darwin writes in the last lines of The Origin of Species. Darwin found grandeur in the thought that life, “having been originally breathed into a few forms or into one,” has gone and is still going in so many astonishing directions; that life, “whilst this planet has gone cycling on according to the fixed law of gravity,” has produced and is now producing so many astonishing species and varieties, from viruses and bacteria to grass, from oaks to peacocks, great apes, and great whales; that “from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”

  Of all the endless forms that have been and are being evolved on this planet, some of the most wonderful (if not the most beautiful) have emerged from the laboratories of Seymour Benzer and his school. The science they make possible is changing our view of life; and both the most passionate proponents and opponents of the science believe that in the twenty-first century it may change the conditions and prospects of life. Many compare this moment to the sudden acceleration of science itself in the seventeenth century, Pascal’s century, or of atomic physics in the first half of the twentieth century. Others say the pace is unprecedented. “To compare the speed with which understanding is being deepened in the life sciences with what happened in physics in the 1920s is probably flattering to physics,” the former editor of the journal Nature wrote not long ago in his farewell editorial, after several decades of watching the molecular revolution. “Can there ever have been a time when there have been so many people pushing at an open door?”

  As the twentieth century ends, more and more of the best and brightest in science are being drawn to the effort. Molecular biology has made biologists the royalty of science. James Watson has installed one of the science’s golden boys—one of Benzer’s best students’ best students—next to his own office at Cold Spring Harbor Laboratory, New York, where Watson is the director. Sometimes late in the evening Watson wanders into the Fly Rooms and looks at the madding crowds in the tidy bottles. He has a nimbus of white hair, but he is still almost as gaunt and gangly as he was at the age of twenty-four, when he cleared a space on his desktop, slid together a few puzzle pieces of tin and cardboard, and saw the double helix. Now when he looks at the mutants in the Fly Rooms next to his office, he feels that he is looking at the beginning of the twentieth century and also the beginning of the twenty-first. This is where his science started, and this is where it is going. “And—I just find it very—” Watson says with a blue-eyed cosmic stare. “You know, just divorcing yourself from humans—just forgetting about us. That there are certain complicated behaviors that seem to be inherited. That’s really—” Fie laughs through his teeth with what sounds like a snicker of glee, as he must have laughed four decades ago when he was talking with Crick about the physical structure of the gene. “You know,” he says, and he snickers again, “that’s the problem to solve.”

  In the study of the physical links between genes and behavior, many of the first answers and half answers came from flies: time, love, memory, as viewed through a compound eye. In one way, this is a parable of the strangeness of life: so much millennial science from such tiny and alien creatures. In another way, it is a parable of the unity of life, since not only flies and human beings but everything alive springs from even homelier materials: the same genes, the same atoms, the same clay, the same simple beginnings. In the first view, the whole world looks alien to us; in the second view, there is nothing on earth that is not familiar.

  Knowing what he does now, Benzer would not dream of calling a fruit fly just an atom of behavior. His research has reached that penultimate stage during which he would rather work than eat or sleep. In the middle of the night, after putting his test tubes back on their shelf, he unhoods a microscope and examines the head of a fly. “About the size of the head of a pin,” he says. “A hundred thousand angels on it. Dancing.”

  CHAPTER TWO

  The White-Eyed Fly

  Those who love wisdom must be inquirers into many things indeed.

  —HERACLITUS

  THE QUANTUM PHYSICIST Richard Feynman once gave a lecture on color vision in Caltech’s Beckman Auditorium. He explained the molecular events that take place in the human eye and brain to show us red, yellow, green, violet, indigo, and blue. This chain of reactions was one of the early discoveries of molecular biology, and it fascinated Feynman. “Yeah,” someone in the audience said, “but what is really happening in the mind when you see the color red?” And Feynman replied, “We scientists have a way of dealing with such problems. We ignore them, temporarily.”

  That line still makes Benzer smile in the middle of the night, which is the middle of his working day. He often repeats it to the postdoctoral students in his laboratory. “We ignore them, pause, temporarily. I thought that was a wonderful statement,” he says. “You know, we do that all the time. The problem you have an instinct for, a feeling for, may be a problem that you’re not going to be able to solve, and you sort of shy away from it, temporarily. The philosophers, of course, don’t ignore them. Maybe they have a penchant for unsolvable problems. If it’s solvable, it’s not really interesting.”

  The problems that Benzer and his students are solving are problems that scientists and philosophers from the beginning of recorded history have been unable to solve and also unable to ignore. In the fifth century B.C. Hippocrates, the great-grandfather of modern medicine, dropped in on Democritus, the great-grandfather of atomic physics. He found Democritus sitting in a garden with the bodies of dead beasts cut open all around him. Democritus was sleeping and waking over his notes, trying to find the cause of melancholy, so that he could cure it in himself and teach others to cure it too. It was a first attempt at the dissection of behavior, approximately twenty-five centuries too soon.

  In the second century A.D. the Greek physician Galen reported that he and a few of his friends had delivered a young goat by cesarean section “so that it would never see the one who bore it.” They took the kid from its mother’s womb and placed it in a room in which there were bowls of wine, oil, honey, milk, grains, and fruits. “We observed that kid take its first steps as if it were hearing that it had legs,” Galen wrote; “then, it shook off the moisture from its mother; the third thing it did was to scratch its side with its foot; next we saw it sniff each of the bowls in the room, and then from among all of these, it smelled the milk and lapped it up. And with this everyone gave a yell, seeing realized what Hippocrates had said: ‘The natures of animals are untutored.’ ”

  Hippocrates and Galen tried to relate human temperaments to the elements: fire, air, earth, and water. The word temperament comes from the Latin temperare, “to mix”; in Galen’s scheme every human being is a mix of those elements. Astrologers tried to relate temperamen
ts to the stars, looking for connections between the two infinites, the skies over our heads and the skies inside our heads. Some of the symbols on fly bottles are astrological. Virgo is one of the twelve signs of the zodiac, part letter, part hieroglyph, part Hebrew, part Phoenician, and on a fly bottle it means what it has always meant, Virgin. The circle with the pendant cross, meaning Female, was once the sign for the planet Venus, with connotations of fertility. The circle with the angry arrow, meaning Male, was once the sign for the planet Mars, with connotations of calamity.

  “What a wonderful thing it is that that drop of seed from which we are produced bears in itself the impressions, not only of the bodily shape, but of the thoughts and inclinations of our fathers!” Montaigne wrote in the sixteenth century. “Where can that drop of fluid harbor such an infinite number of forms? And how do they convey those resemblances, so heedless and irregular in their progress, that the great-grandson shall be like his great-grandfather, the nephew like his uncle?” The questions were just as unanswerable in Montaigne’s century as in Galen’s.

  Shakespeare seems to have been the first to use the words “nature” and “nurture” in brooding about these mysteries. In his last play, The Tempest, which he completed in 1612, Prospero (the character who comes closest to a self-portrait in any of Shakespeare’s plays; the archetype of all artists, scientists, and philosophers) complains about his adopted son, Caliban:

  A devil, a born devil, on whose nature

  Nurture can never stick; on whom my pains

  Humanely taken, all, all lost, quite lost.

  In one way or another, the paradoxes of nature and nurture fascinated every poet, every playwright, and every pair of parents from the first. Abel was a keeper of sheep, but Cain was a tiller of the ground. Yet they both sprang from Adam and Eve. Esau was a cunning hunter, a man of the field; but Jacob was a plain man, dwelling in tents. Esau was also a hairy man, but Jacob was a smooth man. Yet Jacob followed Esau out of the womb with his hand on Esau’s heel.