Time, Love , Memory

by Jonathan Weiner

  A computer operator from the south of France goes back to his ancestral village in Ethiopia. His family left Africa years before he was born. But when he meets his grandfather, who is the chief of the village of Shembe, three hundred miles from Addis Ababa, he sees that they not only look alike, they look at the world alike and move through the world alike. After the computer operator goes home to France, he learns that his grandfather has changed his will and named him the next chief of Shembe.

  A teacher from Texas goes back to his ancestral village in Scotland. His grandparents are dead, but he sits down to tea with a great-aunt. He offers to pour, and as he tips the pot his great-aunt gives a little cry: “Oh, my God, your granny! It’s in your hands!”

  A mother calls a therapist to talk about her son. The boy has just turned fifteen, and he is acting as loutish as his father, a man she threw out of the house a little more than fifteen years ago, a man the boy has hardly met. Does she have a gift for turning men into louts, or is her son his father coming back?

  A mother in Manhattan watches her son’s face as he sleeps. She left his father in Paris soon after the boy was born. Her son hardly knows him. But more and more often, even when he is dreaming on his pillow, she seems to see in his face expressions that remind her of his father, expressions that seem to her impossibly, indefinably French.

  All these anecdotes point in the same direction as the celebrated studies of identical twins raised apart, including the twins who are both gunsmith hobbyists; the twins who are both raconteurs; the twins who are both hysterical gigglers; the twins who can enter the water at the beach only by backing up, timidly, “and then only up to their knees.” Of course, there are anecdotes that point in the opposite direction: the young girl who looks and acts like neither of her parents; the adopted boy who grows up to walk, talk, think, and laugh exactly like his adopted father.

  “I think genes and behavior are such a headline item,” Benzer says, thinking of his clipping file: GENE DISCOVERED FOR BEDWETTING. GENE TIED TO LOVE OF NEW THRILLS. “But the trouble is, when you go look at the data, they are often really fragmentary.” He sees dubious measurements and marginal correlations. “Much as I believe in genes and behavior, the idea has caught on too much. It’s become an idea of complete destiny. I think that’s wrong. Genes are not always expressed. Even if you work with fruit flies, you see that genes are not always expressed.” We each carry many genes we never express. The likelihood that we will express a gene we carry is called the gene’s penetrance. Penetrance is not the same for each gene. “Look at the bible,” says Benzer—meaning the drosophilist’s bible, The Genome of Drosophila Melanogaster, a book that lists every fruit-fly gene ever found since white, and rates the penetrance of thousands of them. “You can have a gene with ten percent penetrance, or five percent, or one percent. So just having that gene doesn’t mean you’ll show that phenotype. Expression depends on a myriad of chemical reactions. And that’s not generally understood. People think if you have the gene, your fate is sealed.”

  Benzer is sure that when the picture of genes and behavior begins to fill in, there will be no such thing as “the gay gene” or “the curiosity gene” or “the happiness gene.” All these traits will prove to be at least as complicated as a fly’s tendency to move toward light—and Benzer now knows hundreds of genes that affect that single trait. Students of genes and behavior will dissect vast complexes and constellations of genes that work together, as in the clockwork in the fly.

  But as the science he helped to start comes closer and closer to home, he sees patterns and questions everywhere. He visits his grandson at his high school during lunch break, and he thinks: What a field for study. His grandson says that every lunch break, the same students stay inside and the same students go outside. Outside, there are the students who lean on the cars, the students who sit around by the bikes, and the ones by the flagpole. Each group has its own attitudes and makes its own moves at the choice points. Benzer is sure that behind these choice points and behind all the schoolhouse culture that surrounds them, there must be a thousand and one differences in the genes. The choices may be too complicated to dissect at the moment, but the influence of the genes is real and ever present. “It’s not random,” he says. “None of it is random.”

  He daydreams now in the middle of the night about simple traits that one might dissect soon. Sometimes he remembers Galton’s old idea about the instinctive dread of blood. Benzer once had a graduate student who was an extreme case. He would faint at the sight of blood, even the mention of it. He passed out once at the Faculty Club, and once at Benzer’s house, too. People would forget themselves as they stood around talking shop and munching adventurous hors d’oeuvres in the living room, and there he would go again. “Try to catch him! A real phenomenon.”

  Then there is the drinking question. When Benzer watched his crews of postdocs back in the bacchanalian sixties and seventies, he used to remember an old Yiddish song from Brooklyn. A Jew goes into a bar, he drinks a thimbleful of wine. A goy goes into a bar, he drinks a barrelful of wine. And the chorus:

  Drunk he is

  drink he must

  because he is a goy—

  Hey!

  Jeff Hall, who is half Irish, likes to make an ironical toast when he hoists another brown bottle at midnight: “Those Irish alleles!”

  The next generation of molecular biologists is trying to study those choices now, and there are signs that this trait, complex as it is, may be illuminated by studies of genes. Lee Silver of Princeton University is another molecular biologist of Hamer’s generation who is moving into the study of genes and behavior, and alcoholism is one of the traits that Silver is studying now. He works with mice, and he finds the current possibilities for research in murine genes and behavior so exciting that he often wishes he could extricate himself from every other project in his lab and do nothing else.

  Of course, for studies of behavior as complicated as alcoholism, a mouse makes a somewhat problematic model, as Silver himself points out. A mouse will never say, “Gee, I’d like another drink, but I guess I shouldn’t.” A mouse will just take that drink. On the other hand, this too makes the mouse useful: all those layers of willpower, experience, education, and nurture do not come into play. In fact, looking for links between genes and behavior is so straightforward with mice that Silver lets his undergraduates do most of the work. Not long ago, one of them designed an experiment in which she offered inbred strains of mice two spigots, one for water and one for alcohol (10 percent ethanol, about as strong as Chardonnay). An inbred mouse strain known as C57BL/6 will drink three quarters or more of its liquid from the alcohol spigot. A second inbred strain, DBA/2, will drink almost none—less than one hundredth of its liquid diet will come from the alcohol spigot. A DBA/2 mouse drinks so little alcohol that it is likely to take no more than a single small taste from the sipper tube and never go back.

  A senior of Silver’s, Justine Jaggard, crossed these alcoholic mice and teetotaler mice. Then she crossed the children with teetotalers. Some of the grandchildren drank a great deal of alcohol. Some drank almost none. Jaggard tested the DNA of the mice for a large number of markers that she knew to differ in the alcoholic and the teetotaler strains. Now she could see which of these markers were most often found in the alcoholic mice. Those markers had to lie next to or near to the genes that made the difference in their behavior.

  One night in June, just before the end of her senior year, Jaggard found a locus on mouse chromosome 2 that seemed to predispose male mice to alcoholism, and a locus on chromosome 11 that seemed to predispose female mice to alcoholism. The gene in the female mice seemed to account for roughly a fifth of the variance in their drinking patterns. She called Silver first thing the next day: “I got an awesome result last night at three o’clock in the morning. I know. I can’t believe this actually worked. I’m so excited. Hooh! But anyway. Well, it’s real! I’m totally, totally excited. But there’s no mistake!”

  Toda
y students of Silver’s are crossing aggressive and passive strains of mice; mice that are subject to seizures when they hear loud and high-pitched noises and mice that are immune to those same noises; mice that are monogamous and mice that are polygamous. With each of these traits Silver expects to begin finding complexes of interacting genes and dissecting those complexes, while he looks for corresponding genes in human beings. He also has a graduate student who is making mouse mosaics to help trace the fine-grained differences of their behavior to their brains. They will engineer a mouse so that half its cells are male and half are female: random bits and blotches of maleness and femaleness, from the fur to the brain. Then they will test these mice and see how their behavior varies, depending on which part of the brain inherits which genes. “It’s a fantastic idea we came up with together,” Silver says. “We get this from Drosophila gynandromorphs. Conceptually, it’s the same thing: genetic dissection as opposed to surgical dissection.”

  Like most biologists in this exploding field, Silver speaks enthusiastically of the genetic dissection of behavior without thinking of the source of the phrase. “A lot of this comes from Seymour Benzer’s vision,” Silver acknowledges. “In the back of my mind, that’s where it’s coming from, even if we don’t express it. He was the one. And from that vision it just goes on everywhere.”

  CHAPTER NINETEEN

  Pickett’s Charge

  Human knowledge will be erased from the world’s archives before we possess the last word that a gnat has to say to us.

  —HENRI FABRE

  OUT ON THE BATTLEFIELD at Gettysburg, more than one hundred molecular biologists gather again and again in great semicircles around their guide, who is shouting out the history of the fight through a white bullhorn in hectic italics, like the hero of a comic book: “This is the Wheat Field, and it’s a shame they don’t keep it planted in wheat! They keep the Corn Field at Antietam planted in corn. As well they should!”

  It is a fine fall afternoon, and the molecular biologists and their families tromp along in broken ranks, chattering among themselves in English, Japanese, Chinese, French, and German. They cannot help marveling at the supernatural quantities of military information that their guide has stored in his head, although when one of the graduate students in the front ranks hurries ahead to compliment the guide himself, he lowers his bullhorn for a moment and replies, “If an idiot savant can be said to know.”

  The symbol on their ID tags is the Princeton University heraldic shield, orange and black, with little legs added to the bottom of the shield to make it look like a virus: a bacteriophage. This is Princeton’s Department of Molecular Biology the university’s wealthiest and fastest-growing department. Their laboratory on the edge of the Princeton campus was designed by Robert Venturi with architectural allusions to the Doge’s Palace in Venice. When the heads of the department chose Gettysburg for this year’s annual retreat, they asked a colleague at Princeton, the historian James McPherson, author of Battle Cry of Freedom, if he would be willing to show them around. McPherson told them to call Jeff Hall. “Hall knows more about the Gettysburg battlefield than I do,” McPherson said, “and Hall is a biologist besides.”

  Last night in the Robert E. Lee Room of the Gettysburg Ramada Inn, the drosophilist Eric Wieschaus, who prepared for this retreat by reading The Blue and the Gray, sat with Hall, talking about Gettysburg and about genes and behavior. Late in the evening, Wieschaus was grappling with the paradoxes of Hall’s field—and grappling with his own hair, shoulders, and torso as he struggled for precise thought. Hall announced to the table, “We’ve just watched Eric Wieschaus wrestle himself to the ground. As he does often.”

  Wieschaus laughed. “Even in the middle of talks,” he said. “Even in the middle of major talks.” Twelve months later he would be getting his dawn call from Stockholm.

  Even out here on the battlefield, most of the molecular biologists in the ranks are talking molecular biology. Their science is racing ahead so last that they rarely take time out for an afternoon like this or for a look backward at the history of their own battlefields. Not long ago in Pasadena, Seymour Benzer’s Korean postdoc brought him a petri dish. He had injected the fly gene drop-dead into the bacteria in the dish, and now the bacteria were dropping dead. Benzer studied the plate with amusement. He knew that his postdoc was disappointed. The postdoc was trying to make the bacteria express the drop-dead gene so he could study the drop-dead protein; instead, the bacteria were simply dying. “I like the idea of making bacteria drop dead,” Benzer said. “I used to make them drop dead with phage.”

  “How do you do that?” asked the postdoc.

  “They eat bacteria. The phage I worked with—” Then it struck Benzer. “You don’t know that? Oh, my God!” he cried with good-natured despair. “So the whole phage literature passed you by?”

  With the science accelerating so rapidly, all of the founders feel like ghosts standing in their own fields. There are postdocs in an institute named for Delbrück in Germany who have no idea what Delbrück did. Postdocs at meetings in Cold Spring Harbor see Watson striding by and exclaim out loud, “He’s still alive?”

  “Molecular biology has no history for the young scientist,” one of the old guard declared not long ago.

  Sydney Brenner qualified that: “I hold the somewhat weaker view that history does exist for the young, but is divided into two epochs: the past two years, and everything that went before.”

  E. O. Wilson believes that this short-term memory may be a good thing. He contrasts it with the veneration that psychologists pay to Freud and Jung or that social theorists still pay to the heroes in their pantheons. “Much of what passes for social theory is still in thrall to the original grand masters,” Wilson wrote recently, “—a bad sign, given the principle that progress in a scientific discipline can be measured by how quickly its founders are forgotten.”

  As Jeff Hall approaches the climax of his story, leading the ranks up the path of Pickett’s Charge, a few molecular biologists, absorbing the spirit of the place, are thinking and talking about the beginnings of their own charge. The Civil War was the moment in time during which Mendel’s peas and T. H. Morgan himself were, as Morgan used to say, “laid down.” The chairman of Princeton’s molecular biology department this year, Arnie Levine (they call him General Levine today), reminisces with Lee Silver about Schrödinger’s What Is Life? Schrödinger speculated in his book that quantum jumps might cause mutations. “It was wrong,” Levine says with a laugh. “But that didn’t matter. It got the physicists in.”

  “Brought in Francis Crick,” Silver agrees. “Seymour Benzer … Gunther Stent.…”

  But like most molecular biologists, Silver prefers looking into the future. He feels his science is racing toward a climax. “We thought there were all these barriers, and they don’t exist,” he often says. “We’re finding things we thought we’d never be able to find. Barriers to knowledge keep disappearing one by one. I think in the end we’re going to know it all. I really do. It’s just a question of how long, just a question of when.”

  Soon it will be straightforward to take a small sample of someone’s DNA and use an electronic device called a DNA chip to probe for variant forms of every single gene. At a glance a molecular geneticist will know what genes that individual carries and what genes are on right now and what genes are off. Genetics start-up companies are already manufacturing the first generations of these DNA chips in a union of computer science and molecular biology that seems likely to race ahead at the customary speed of both.

  By screening the DNA of one hundred thousand people, combining that information with personality tests, and letting a computer crunch it all together, molecular geneticists will put together pictures of gene complexes working together to produce the most complex traits of personality. “It’s going to happen fast!” Silver says. “If there are ten genes that make somebody aggressive, you’re going to see them!” The twentieth century began with a man looking at one white-eyed f
ly in a bottle, he says. Before we are that far into the twenty-first, he says, “we’ll be able to take ten thousand people and match different combinations of alleles across the whole genome and come up with a behavioral profile.” Of course, each profile will have been modified by the environment. “That’s certainly the case,” Silver says. “But it’s an incredible story. I think people don’t realize the power of genetics. You can figure out which genes are responsible for a trait—without knowing anything.” Knowing nothing about the gene, the environment, the psychology, or the physiological machinery, you can find your way in. “Knowing nothing! Because once you figure out what the connection is, then you go back and figure out why. You can do all that afterwards.” Take shyness, which Silver believes is very much genetically determined. With the kind of mass screen that Silver is envisioning, he could find two dozen genes, each with multiple alleles, that contribute to shyness. He could do that without knowing what each gene does. “Then you can ask, What does it do? What protein does it make? When is it turned on? When is it turned off? Incredibly powerful, to do all this.

  “People who don’t believe in relativity don’t understand relativity. People who don’t believe in evolution don’t understand evolution. And it’s the same with genetics. And I think some people are just reluctant to let their imaginations run.

  “My feeling is that molecular biologists are going to move into psychology and take over the field. I think that’s the way psychology is going to be rejuvenated.

  “In the 1970s, they said genetic engineering would be impossible. Then they said cloning would be impossible. Amazing that people can be so shortsighted. It’s an explosion of science. Right now we’re really at the beginning of biology. That’s really the way to look at it. The end of biology in this century is like the end of physics in the last century.”

  JEFF HALL holds his megaphone tipped at a rakish angle to fire out the sound over the heads of the front rows of the crowd. He is bulling into the microphone, angrily miming the action. He is almost at the top of the path of Pickett’s Charge. The statue of General Lee is far behind him, and the statue of George Meade is just ahead, beyond the Clump of Trees. In Hall’s view, the Civil War was the greatest drama in the history of the United States; the battle at Gettysburg was the climax of the war; and “the climax of the climax, the central moment of our history,” as one of Gettysburg’s historians puts it, was Pickett’s Charge. On July 3, 1863, fourteen thousand Confederate soldiers marched up this slope, toward what is now known as Cemetery Ridge. They marched through cannon fire and rifle fire toward a bend in a low stone wall at the top, now known as the Angle. They advanced, flags waving, into the very center of the Union lines at the top of Cemetery Ridge. Only two hundred of Pickett’s troops made it to the Angle, about the size of the band Hall is leading up the path today, counting the children. In that hour the battle was lost and won.