Time, Love , Memory

by Jonathan Weiner

  IT IS ALREADY POSSIBLE—in fertility clinics it is done every day—to screen the DNA of a set of eight embryos at the eight-cell stage and let the parents pick the one they want to implant in the mother’s womb. The more genes there are to screen and the better these gene complexes are understood, the more wealthy parents will select not only the healthiest but also the best and the brightest embryo they can, designing the genes of their children. With the same tools that Hall used to inject the first instinct into an animal, it may someday be possible for people in fertility clinics to inject a wide selection of human instincts and traits as well. As these choices are made more and more often, the old dream of Galton and the eugenicists who followed him will be fulfilled willy-nilly over the next few centuries whether governments legislate for it or against it. The rich will pick and choose the genes of their children; the poor will not. The gap between rich and poor may widen so far in the third millennium that before the end of it there will be not only two classes of human beings but two species, or a whole Galapagos of different human species. These human species could be prevented from interbreeding by the genetic engineering of chemical incompatibility, so that the egg of one would reject the sperm of the other. Silver is thrilled by the power of his science and by the vision of barriers falling away, and yet looking into the far future he sometimes thinks he sees disaster, a Darwinian nightmare; out of utopian eugenics, a dystopian origin of species.

  “We have reached this point down a long road of travail and self-deception,” E. O. Wilson wrote recently. “Soon we must look deep within ourselves and decide what we wish to become. Our childhood having ended, we will hear the true voice of Mephistopheles.” He is sure we will not want to turn ourselves into protein-based computers; we will not want to lose what makes us human. Wilson’s ants, for instance, never play. We will not want to give up what we have evolved over billions of years, going back to the very origin of life. But what changes will we make in our natures—deliberately or casually and without plan—beginning in the next few years? “What lifts this question above mere futurism,” Wilson writes, “is that it reveals so clearly our ignorance of the meaning of human existence in the first place.”

  ON MOST NIGHTS, by nine o’clock, Benzer is almost alone on his floor of Church Hall. By ten or eleven, his desk lamp is one of the last lights burning in the windows. For Benzer the smell of the fly food has never lost its savor: home, sweet home.

  Sometimes when he is alone in his lab, he thinks of putting up plaques on the doors with the names of the people who worked there. They made his revolutions their beacon, and some of them found harbors and some lost their ships. Not all of Max Gottlieb’s Arrowsmiths stay in the game—and some of Benzer’s first were the first to drop out. Konopka now lives a few blocks away from the Caltech campus, alone in a small house half hidden by palm trees and magnolias, as anonymous as Kafka’s K. Once in a while he gets a new clock paper in the mail. He looks at the tables and he thinks, “Well, heck, these are all my mutants!” He spends his days collecting butterflies now, tipping his forehead sharply forward to peer at them over his glasses. He also collects Grateful Dead tapes and photographs of local waterfalls. He has a big Lionel model train set on the shag carpet by his front door and a pinball machine shoved against the dining room wall: “Gottlieb’s FAR OUT.” Back in the summer of 1968, the scientists in Church Hall said Konopka would never find what he was looking for. Then, when he found it, they said it was meaningless. Now it is meaningful, and he is out of science. “Story of my life,” he says. “They just didn’t believe it. You think scientists are open-minded, but ha, ha, ha.”

  In the middle of the night in Church Hall, Benzer often wanders up to T. H. Morgan’s filing cabinets in the third-floor hall to raid and riffle through the founding papers of genetics, ancient references he wants to see. Then he stops in to see Sturtevant’s old student Ed Lewis. Staring at the baby octopi in Lewis’s aquarium tank at two in the morning, Benzer is filled with the feelings that sometimes come to him down at Sturtevant’s bed of experimental irises. The same thought possesses him even standing over a puddle, thinking of all the microscopic vorticelli and rotifers and pond creatures doing their tricks in there. “It’s a wonderful, fabulous world, and it’s been kicking around a long time,” he says. “And there’s so much going on all the time. It’s just amazing how much we’re neglecting.”

  Through his microscope Benzer zooms in on the eye of the fly. He admires one facet. On this facet there is a hair, and the hair has a nerve that goes into the brain. If he looks at it closely enough, the single facet starts to look like the whole eye. Even through an electron microscope at 20,500 times magnification, he still sees more fine structure. “The more you look, the more you find,” he says. And this is just looking at the surface. Looking inside, you find worlds within worlds of detail: coils and coils of wires, cables, and corrugated gooseneck tubing, buttons and corks, tufts, four-leaf clovers, and odd projections like golf balls on tees. “The eye is the microcosm that contains all of biology in it. Maybe even including consciousness,” says Benzer. “But that’s the way it is; every kernel contains all of biology, practically.” Feynman once said it beautifully: “Nature uses only the longest threads to weave her patterns, so each small piece of her fabric reveals the organization of the entire tapestry.”

  Behavior was fun, hut 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.

  Now here he is old and gray, and once again behavior is looking to him like the new frontier. So is aging, the whole phenomenon of lifespan: How much of that is in the genes? Once again he is wondering if science can find answers to the recurrent questions that Max despaired of answering—find something worth telling Aurora, the goddess of the dawn.

  By 3 a.m., the Church Laboratory is very quiet. At the far end of the hall and down one flight of stairs, a small night shift of lab technicians is washing flasks, racking test tubes, and filling fly bottles for the next day’s rounds of experiments, including hundreds of vials, test tubes, and antique milk bottles marked BENZER. At four o’clock in Church Hall, the night shift will go home. At six o’clock, the day shift will arrive, in the form of a woman whose name happens to be Aurora. And Benzer, going out the door, will meet Aurora, coming in.

  Not long after Benzer married Carol Miller, Francis Crick asked her to show him the human brain. Crick had been thinking and theorizing about the brain for a few years, but he had never actually seen one. He wanted Carol to show him the cerebral cortex so that he could see the edges.

  Just after Benzer’s seventy-seventh birthday, he and two of his postdocs, Yi-Jyun Lin and Laurent Seroude, announced the discovery of a mutant fly that lives more than one hundred days. They named it methusaleh. Other drosophilists had shown that flies’ lifespans are influenced by genes, but none of them had ever cloned one. Now Benzer plans to hunt for more lifespan mutants. He is embarking on the new career he hopes to pursue in his eighties: the genetic dissection of aging. When he introduces methusaleh in lectures, Benzer shows a slide of a mutant with a fly’s eyes and Darwin’s beard. (Illustrations credit 19.1)

  So Carol set a brain on an ordinary white plastic cutting board from the hardware store, while Crick watched in a borrowed white lab coat. Around them the cabinets and shelves held dozens of brains, some intact, some already dissected to bits. On the shelf above the cutting board was a row of straight-sided jars full of grayish eyeballs.

  The convolutions of the cerebral cortex are like the coiling and super-coiling of the double helix: origami tricks by which evolution has managed to pack a great deal of information into a very small space. Carol explained that if she could spread it out, its edges would fall off the cutting board on all sides—almost a square yard of cortex. There were millions of nerve cells packed into every square inch, each nerve making thousands of contacts with its near and distant neighbors according to patter
ns that were laid down first by the genes and the growing nerves in the embryo, then by a lifetime of choices inside that gray-brown sheet.

  Quite a contrast with the brain of the fly, which fits into a head case so small that it is hard for us to see without a magnifying glass.

  The reasons that we evolved such massive brains remain obscure, but one reason may have been to help us at the choice points. Our brains allow each of us to bring a maximum amount of learning and experience to each and every choice point, all that our species has learned and all that we have learned in our lifetimes. A fly does this to some small degree, and we do it to a large degree—more than any other creature on this planet.

  For some years now, Crick and a few colleagues have been trying to figure out the difference between unconscious vision and visual awareness. Crick assumes that there must be some difference in the way incoming information is processed that determines whether we are aware of it or whether we are not. By tracing this difference in the brain, Crick hopes to find a clue to the way in which any experience can become conscious, allowing us to get maximum benefit from our big brains at the choice points. Crick thinks this will be the problem of the twenty-first century, although Benzer raises his eyebrows and smiles his molecular smile whenever they talk about it.

  “He teases me because I’m interested in consciousness and so on,” Crick says with a laugh. “And of course in the case of Drosophila it wouldn’t be very sensible, because we’ve no idea—we hardly know what it means to be conscious in a mammal; when we get down to Drosophila, we really don’t know whether they’re automata or not. So I can see why he doesn’t feel really interested himself in that topic. And I wouldn’t be if I worked on Drosophila.” “You know,” Crick once joked from a podium at a meeting in Pasadena, “Jacques Monod used to say that everything that was true of E. coli was true of the elephant. But I don’t think that even he said that everything that was true of the elephant was true of E. coli. I don’t necessarily think the fly is as smart as Seymour, even though Seymour doesn’t know how to land on the ceiling.”

  Cerebral cortex, drawn by the anatomist Andreas Vesalius. Vesalius published his De Humani Corporis Fabrica in 1543, the same year that Copernicus published his De Revolutionibus Orbium Coelestium. Copernicus opened a journey outward, Vesalius a journey inward. The journey outward has now led to the discovery of light from the Big Bang and the birth of the universe. The journey inward has led to the discovery of the first links between genes and behavior. Someday these discoveries too will be remembered as beginnings, first openings, points of departure. (Illustrations credit 19.2)

  “If you will be good enough as to give me a definition of consciousness,” Benzer retorted (from the floor), “then I will try to devise a test to see whether it is present in Drosophila. But so far you have been unable to come up with a definition.”

  Crick hopes that studies of the human brain’s visual processing system will lead him there. He assumes that there is also a part of the brain devoted to planning and looking ahead, and here he suspects the frontal lobes. The frontal lobes are the most forward part of the human brain, the part just behind the forehead. The very frontmost portion of the frontal lobes, the prefrontal fibers, are thought to be sites of our social reins and bridles; they keep us from saying and doing things that veer off the path of what is socially expected and accepted. The archetypal case of frontal lobe dementia was one Phineas Gage, foreman of a work crew on the Rutland and Burlington Railroad in Cavendish, Vermont. Gage lost much of his frontal lobes in a dynamiting accident on September 13, 1848, when an iron bar rammed into his head just below the left eye, shot through his skull, and flew out through the crown of his forehead, smeared with blood and brains. He astonished his crew by walking, talking, and joking soon after the accident, although it soon became clear, as his doctor’s notes show, that he was “no longer Gage”:

  October 15 (32nd day) … Intellectual manifestations feeble, being exceedingly capricious and childish, but with a will as indomitable as ever; is particularly obstinate; will not yield to restraint when it conflicts with his desires.

  October 20th (37th day) … Sensorial powers improving and mind somewhat clearer, but very childish.

  November 15th (64th day) … Is impatient of restraint and could not be controlled by his friends.

  Studies of patients with damage caused by strokes have suggested that frontal lobes have very specific and localized functions. A lesion in one place produces disinhibition like Gage’s, but a lesion in another place produces apathy. (The prefrontal lobotomy works because it induces apathy.) A lesion in a third place produces blindsight. Subjects with blindsight can see, but they claim not to. They can point to objects around the room when an experimenter asks them to, but they will deny that they can see them. Their eyes work and their brains can process the information, but they are no longer conscious of the results. Carol demonstrates these areas of the brain on a cutting board with the same mix of expressions, half matter-of-fact, half reverent, that Benzer has when he gives guided tours of the brain of a fly. “This is the frontal cortex,” she says. “This is the dura mater. Here is part of the basal ganglia. The apathy area is here. And disinhibition is down here. Frontal temporal dementia.”

  She has begun to apply Seymour’s method of genetic dissection to the frontal lobes. There are forms of frontal lobe dementia that run in families; one form of the disease with late onset (in the fifties or sixties) seems to be linked to chromosome 17. By dissecting the brains of victims of the disease in autopsies and staining them with fly stains to examine fine-scale changes under the microscope, she is trying to trace the links from gene to behavior just as Seymour does in flies. Through the microscope her brain sections stained with fly stains are abstract landscapes, some of them like stylized artist’s impressions of a tree stained pink and some rather beautiful aerial landscape views, with alluvial curves and scallop-edged patterns. The stain swivels and follows the contours and the curves, oblivious to the pathos of mortality. Somewhere in there, Crick believes, may be the answer to the problem of free will.

  THE ROMAN PHILOSOPHER Lucretius imagined that atoms must swerve somehow; “if the atoms never swerve so as to originate some new movement that will snap the bonds of fate, the everlasting sequence of cause and effect—what is the source of the free will possessed by living things throughout the earth?”

  At the end of the day in Cold Spring Harbor, Watson also thinks in terms of some kind of Lucretian swerves. “My hypothesis is that free will comes from the imperfect working of the brain,” he says. “The machine is inherently uncertain.” He smiles at the pun.

  “But on certain occasions I know,” he says, alluding here to a particularly trying meeting he has just endured, a board meeting in which he has listened to the president of a new biotechnology company that Watson thinks is mismanaged. “You know, when I’m in a room, and I hear shit, after a while the word ‘shit’ is going to come out. You just can’t take it anymore. Now that’s, hmmm, a predictable response. It’s hound to come out. I think to myself, maybe I’ll sit through nonsense and not say it. But …” Watson sighs. “So in that sense you don’t have a free will. Your reactions are programmed. You know, you start asking the difference,” he says with a nod toward the Fly Room next door. “What free will is there in Drosophila? You put the question of the free will of a fly. And what’s really different about the fly’s brain from ours—which gives us free will?

  “I’m sure once we know how the brain works, we’ll no longer talk about free will in the Jesuit sense. It will cease to be, you know—” Freedom will cease to be a mystery requiring Jesuitical debate; it will cease to be a theological or philosophical question. “It will just be how the brain works. You will describe how the brain works. You won’t use the words ‘free will’; you know, you’ll understand.… Because you’re asking, how does the brain work?” he says in a softer voice. “That’s what you’re really asking.” The bell in the double-helical bell tower o
utside his office window begins to toll. “And that’s really the ultimate question to ask,” he says, speaking through the tolling of the bell with a pleased chuckle in his voice, suddenly sounding very much like his old friend Crick.

  WHEN BENZER himself thinks about the free-will question, he always remembers his first moments watching the flies in his test tubes run toward the light. In the very first experiment he did, most of the flies went to the light, but some didn’t. He tested them again; most went to the light, but some didn’t. That was why he made the countercurrent apparatus. “If you mean a certain randomness in behavior—then flies have free will,” Seymour says sometimes at the Red Door Cafe when the talk turns to drosophilosophy. Why did each of those individual flies make each of those individual decisions and revisions? “That’s free will if you want to call it that.”