In the last years of the century, Lewis, standing by his old teacher Sturtevant’s iris bed or besieged by reporters in the faculty parking lot, would say with a grin, “It was pure genetics. It was pure genetics.” Nothing molecular about it. He would remember how Delbrück had pounded the table and denounced the fly, and he would murmur, so softly that the reporters had to ask him to raise his voice, “I’m glad I stayed with it.”
MEANWHILE, Jeff Hall accumulated a shelf of bottles of mutants with interesting courtship problems. One mutant male courted vigorously but never copulated. Hall named him celibate. Another male mutant disengaged after only about ten or twelve minutes and rarely fathered any children. Hall named him coitus interruptus. Then there is stuck, which was discovered in another fly lab. A stuck male has trouble withdrawing his penis after copulation. “The pair just sticks together,” Benzer says, “and they keep pulling against each other for hours or days on end. Sometimes they die of starvation.”
In the wild, of course, a mutation like stuck could not last long. A male that is stuck will not pass on his genetic inheritance. But this particular mutation is recessive, which means that flies with one mutant copy and one normal copy of the gene can court and mate normally. In the Church Laboratory, Benzer and Hall began collecting and breeding these courtship mutants, keeping them going from generation to generation like seedless grapes.
The most surprising courtship mutant was discovered at Yale. A graduate student in a Fly Room there was studying the process of egg formation. He zapped flies with X rays and looked for sterile female mutants. In his fly bottles he happened to notice a few mutant males that were courting each other. Ordinary males will bump and bustle and dodge around other males in a fly bottle or a petri dish without ever touching one another for long. Watching them is like looking down at a sea of strangers in Penn Station. If two males do collide in the crowd, they may retreat a step or two and begin grooming themselves, almost as if they were embarrassed, like two cats. If a normal male sees another male approaching him with a wing out, he starts flicking his own wings violently in rejection. But these males at Yale sang to each other. Tests showed that their sperm was healthy and that they would court females but would not copulate. They would go through all the steps of foreplay, but the last step they would not do.
Sometimes three males, or five, ten, or more would form chains and follow each other around in the fly bottle in long, winding conga lines. They would chain for hours. They tended to stay down around the food at the bottom of a bottle, but when the dancing had reached a certain pitch of frenzy they would get right up onto the glass walls of the bottle and chain. Often they broke up and then came back together. They took little breathing spaces and went right back to chaining.
Those who have worked with this mutant have found that food is important: Giving the flies good food and keeping them at a nice warm constant temperature seems to encourage chaining. “Sometimes it takes a few days,” one technician says. “It’s like a social thing. They all get to know each other.” The food, the climate, and perhaps the social environment have to be right. “When they are really happy,” she says, with a half-apologetic smile for talking about the happiness of flies, “then you get these chains.”
The investigator at Yale published a note about this mutant, which he named fruity. Then he went back to his home country, India, where he was never heard from again, and fruity was left an orphan. When Hall read about it, he decided that this was the quintessential courtship gene. He sent to Yale for a bottle of fruity, although he decided that the name had to go. He chose fruitless.
In Dante’s vision of the tenth circle of Hell, sodomites go round and round with their bodies linked in a wheel, circling on burnt sand in a whirl of ever-moving feet. In Benzer’s Fly Room, the scene looked like Dante’s. The male mutant flies whirled in bottles and petri dishes and test tubes—long swirling sinuous chains, males only, winding their way around and around, hour after hour. The males never tried to copulate. They only formed these long conga lines in their milk bottles and test tubes and danced, sometimes sticking out one wing and singing the love song of their kind while they danced, as if they were shaking a tambourine.
In the 1970s, most aspects of sexual behavior were still a black box, at the level of atoms, molecules, and genes. Biologists had collected observations of sexual behavior in tens of thousands of species. The importance of the instinct, which is after all indispensable, and the phenomenally variable behavior of closely related species like Hawaiian Drosophila suggested that in most cases every step of the instinct must be inherited. And for the atomic theory of behavior, fruitless would provide the first way in.
The fruitless males chained on the floor of their bottle. They chained on the sides of the glass in big wheels and zeroes all day long, more and more of them spiraling up the walls toward dusk. And when Jeff Hall dumped them out of their bottle, he could see them chaining all the way down the funnel, chaining into the morgue.
CHAPTER TEN
First Memory
Memory is a passion no less powerful or pervasive than love.
—ELIE WIESEL,
All Rivers Run to the Sea
BENZER’S FRIEND Gunther Stent loved to philosophize, and Benzer was always quick to help him get to the bottom line. Once Stent inhaled for what was clearly going to be a long verbal essay. He began, “All reasonable men—”
Benzer cut in: “No men are reasonable.”
Benzer and his circle had an interest in the truth and a cavalier impatience with mouth artistry and eloquence, and their attitude, their style of science was extremely appealing to a certain kind of student. It is an old saw in organic chemistry that “like dissolves like.” That is the principle of the countercurrent method by which the chemist separates oil-lovers from water-lovers. In the first days of their genes-and-behavior projects, Benzer with his flies and Brenner with his worms attracted some students and repelled others. Those who gravitated to them were a special breed, looking for a certain kind of adventure. Like Benzer and Brenner, they hated the safe, careerist path. “There were a lot of young people who were already feeling that molecular biology and genetics had reached a kind of confined road,” Brenner says. “In other words, they didn’t feel there was opportunity for originality or initiative anymore. So we attracted a large number of people who were willing to take the chance and enter the field. And, of course, those are the people you want.” Most of their students were coming to them from classical phage genetics. “And for a lot of those people that was quite a big step into the void.”
Those who visited Benzer’s Fly Room found an atmosphere not unlike Morgan’s Fly Room, which had been a madhouse. Morgan had wedged eight desks into his little room at No. 613 Schermerhorn Hall for his Raiders. Escaped flies drifted around the desks and the garbage can, which was never completely empty. More flies swarmed around a bunch of bananas that hung in the corner. When the boys came into the room in the mornings, bearing stolen milk bottles, they would pick and eat bananas and drop the peels into their desk drawers. “During the two years I worked in the inspiring spiritual atmosphere of the Fly Room,” wrote one of Morgan’s finest, Curt Stern, “I never opened my desk drawer without looking away for a while to give the cockroaches a chance to run into the darkness. Once I said breathlessly, ‘Dr. Morgan, if you put your foot down you’ll kill a mouse.’ He did!”
“Morgan was a bit crazy,” says Jeff Hall. “He used to say, ‘To know your organism, you must eat it.’ Not just the flies: the pupae. And not just to horrify people, but to know. Grape Nuts had just been invented, by C. W. Post. One of the first breakfast cereals.” (Post put Grape Nuts on the market in 1897.) “So Morgan justified eating the pupae—when people stared at him, he said, ‘They taste like Grape Nuts.’ ”
Benzer brought to his own Fly Room a growing fascination with the bizarre, the extremities and ultimities of human behavior. “The whole lab was infected by his spirit of the unusual,” says Bill Harris,
who was a graduate student in those early days and is now the chairman of the department of anatomy at Cambridge University. Benzer took his students and his wife, Dotty, to the Charles Manson courtroom. He visited the grave of Marilyn Monroe and crashed Hollywood funerals. And of course Benzer often brought surprises to his lab’s lunchroom, known locally as Seymour’s Sandwich Shop. Harris remembers in particular a Chinese century egg, an egg that had been buried in the ground for years. The white of the egg was a translucent red, and the yolk a very dark green. “He ate it up and made everyone taste some. My old boss—always liked to challenge his palate.”
For Benzer it was all part of the same curiosity: “All part of the same aberration,” he says. And his students saw it that way too, according to Harris. “That was one of the most attractive things about his science. I didn’t know him in his early years, when he was working on the gene. But this was definitely science at the fringe.” There was so much wide-open space between a mutation and a piece of behavior. Benzer was always quoting Samuel Butler: “A hen is only an egg’s way of making another egg.” Behavior, Benzer said, is “the way that the genome interacts with the outside world,” the way the egg produces that next egg. Benzer’s approach, getting a mutant and looking at a behavior, underscored how little was known about the whole circle from the egg to the winged life and back to the egg. “There was so much uncharted territory in between,” Harris says, “that most scientists believed it was an unfillable gap. And most of us were attracted to it because of that.” They did not know that the tools of molecular biology would soon allow them to follow up these first explorations with fantastic power, allowing them to study the links between genes and behavior at a new level. “But we knew that it was a process, that little by little we would inch away at this problem,” says Harris. Precisely because the gap was so wide and because many scientists thought the project was absurd, it attracted a certain kind of student. “It was not a step,” Harris says. “It was kind of like a leap.”
“The lab in those days was very laissez-faire,” says Chip Quinn, who joined it as a postdoc in 1971 and now runs a Fly Room at the Massachusetts Institute of Technology. “There were these fairly interminable lunches, which were sometimes movies and bullshit and sometimes real science. I think at that time in the lab nobody knew exactly what should be done. There was this whole cafeteria of things that one might do.” Quinn remembers one student who made the rounds of Benzer’s three-ring fly circus looking more and more disgusted. “He said, ‘Well, here I am training for Harvard Neurobiology and it’s sort of like all these guys with coonskin caps. And you want me to come here and put on a coonskin cap and be a pioneer.’ ” That student went off and did something safer.
No one knew how important these experiments would turn out to be. “Nobody knew,” says Quinn. “Seymour always thought, you know, enlightenment is just around the corner. He really had confidence in himself as he came off the big successes in phage, and he thought, ‘Well, we can do it, we can figure out the nervous system.’ ” To Quinn it was a noble gamble, like Pascal’s wager. “If you think you can’t do anything, then you are guaranteed that you can’t do anything,” he says.
OF ALL THE PROJECTS in the lab, Quinn’s was the farthest out. Quinn wanted to dissect the invisible events that take place in the brain during and after each experience, the changes we call learning and memory. Quinn even hoped to find the engram, which is the holy grail for scientists who study nerves and brains. The engram is the seat of memory, the physical change in a brain that encodes memory itself. “Tell me what is a thought, & of what substance is it made?” asks William Blake, as if he were asking an unanswerable question. The engram is the substance of memory. In 1971 it was still a cloud-wrapped, faraway summit, but Quinn thought it might turn out to be easier to reach than some of the other summits on the horizons of science. “What’s the trick or the set of tricks that the brain uses to encode a change based upon experience?” he asked years later, after his own experiments and those of many others had brought them closer to the summit. “It may be relatively simple. I mean, there’s really that hope: the brain is too complicated, and intelligence is too complicated, and consciousness is too complicated, but there is a possibility of understanding this trick.”
This is the trick Quinn wanted to study using the tools of genetic dissection, the trick that allows us to catch something from our experience in a kind of mesh of the nerves and hold it there for the rest of our lives. Somehow the memories are written in atoms, and somehow we keep the memories even though we lose the atoms.
And of course there is a wide range from individual to individual in our ability to remember. The psychologist A. R. Luria wrote a famous memoir of his encounters with a newspaper reporter who was sent to him by the reporter’s editor because the man seemed to forget nothing. Luria sat him down and read out a short table of numbers, and afterward the reporter repeated them back to him digit by digit.
1 6 8 4
7 9 3 5
4 2 3 7
3 8 9 1
The psychologist read him longer and longer tables, row after row, stream after stream of digits, and the reporter kept repeating them back. He could recite them backward, forward, or even diagonally. At last, the psychologist writes in his memoir, The Mind of a Mnemonist, “I simply had to admit that the capacity of his memory had no distinct limits; that I had been unable to perform what one would think was the simplest task a psychologist can do: measure the capacity of an individual’s memory.”
This subject had a special interest to the Lords of the Flies in the Benzer lab because many of them had bottomless memories themselves. They needed them for their work. Ron Konopka was born with a photographic memory. Jeff Hall carried in his head thousands of references to papers in genetics, and often he could remember not only the authors of a paper and the genealogies of the flies but also the year, volume, and page numbers. Sturtevant used to read the Encyclopaedia Britannica for pleasure in the evenings, and in his later years he had a hard time finding an article that he had not already read and committed to memory.
This is the phenomenon that Quinn wanted to explore through genetic dissection. He also hoped to explore the way the dance of the atoms changes over time. As we get older, most of us feel the holes of the sieve widening and widening, the mesh fraying, so that more and more of what happens from morning till night falls through. This change in our daily experience probably corresponds to a change in the sieve and mesh of the molecules and neurons of memory. Something changes in the way we store memories or in the way we retrieve and read them. Quinn hoped he could find clues to those changes too with the dissecting needle of the genes.
“For us to learn anything at all, we must already know a lot,” says another early postdoc of Benzer’s, Yadin Dudai, who now runs a Fly Room at the Weizmann Institute of Science in Rehovot, Israel. We have to know how to live to know how to learn. As Dudai writes in his book The Neurobiology of Memory, “What the frog’s eye tells the frog’s brain is based on a memory established during millions of generations; so is the escape of the fly from the frog’s tongue.” In this very broad sense, genes themselves are ancestral memories of life on earth. Near the beginning of Remembrance of Things Past, Proust says that memory is “a rope let down from heaven to draw me up out of the abyss of not-being.” All of DNA is a twisted rope ladder let down from heaven to draw us up from the abyss of not-being. We do not lift a finger without three kinds of information: the information we are getting from our senses at that moment; the information we have gotten from our senses in the past; and the information our ancestors have acquired since life began on Earth—that is, the information that is represented by genes themselves. Evolution is learning. Species store learning in chromosomes the way individuals store learning in their brains and societies store learning in books.
In this sense our ability to learn and remember is itself a memory. It is the memory of a discovery that has been passed down from generation to generati
on since near the beginning of life, a discovery approximately as old as the sense of time, perhaps almost as old as the instinct to reproduce. And of all the discoveries that living things have acquired in their 3.5-billion-year tenure on Earth, the mnemonic device of memory itself is one of the most crucial. For an individual to be able to profit from its experience and carry each experience forward to the next choice point is one of the most useful adaptations ever evolved.
A sentimental sense of history. Once, back in the 1940s, Benzer had traded haircuts with his mentor Max Delbrück. Now, in the 1960s and 1970s, while he explored the molecular biology of behavior, Benzer traded haircuts with his postdocs. Here Chip Quinn endures the tradition, in June 1974. (Illustrations credit 10.1)
Quinn had picked up an interest in the memory problem from Benzer, but he felt almost mystically primed for it. As Quinn puts it, “I think that it was my karma as well as his.” To Quinn, the engram, the secret of memory, was by far the most exciting problem he could hope to study in Benzer’s lab. “Everything else seemed trivial compared to that.”
AT THAT TIME, flies were assumed to be hard-wired. That is, every one of the hundred thousand neurons in their brains was thought to be glued, taped, or soldered to its neighboring neurons in a pattern that was laid down once and for all in the embryo. The layout of the nerves was supposed to be as fixed and standardized as the layout of the six legs and two wings. A fly’s brain never changed no matter what happened to that fly between the moment it eclosed from the egg and the moment it met its maker (or mutater). Without memory, John Locke once wrote, each of us would be no better than “a looking-glass, which constantly receives a variety of images, or ideas, but retains none; they disappear and vanish, and there remain no footsteps of them; the looking-glass is never the better for such ideas.” A fly was thought to be as unimpressionable as a looking glass. All it had to fly on was the ancestral memories in its genes: a pure robot, a set of instruments flying on instruments. Students in Benzer’s lab sometimes wondered if worlds exist where there is no other sort of memory but this, the slow, instinctive memory built up out of thousands and millions of generations. It was an amazing thought. What would such a world be like? Billiard balls, pure billiard balls! A planet almost as barren as a planet without life. Our own planet in the days of the very first living forms must have been like that, before an organism somewhere in the sea learned to profit even dimly from experience—learned to learn.
Time, Love , Memory Page 15