Time, Love , Memory

by Jonathan Weiner

  By arranging marriages for his mutants, Konopka created flies that had one normal copy of the clock gene and one mutant copy. He also made flies that had two normal copies and flies that had two abnormal copies. It was just like breeding Mendel’s pea plants—tall-short, tall-tall, short-short—but this was behavior. He monitored the flies’ children and grandchildren, reading the scrolls of paper day after day. He could see that two of these mutations were at least partially recessive, like shortness in peas, white eyes in flies, or blue eyes in human beings. The short-period mutation was partially recessive. The mutation that destroyed a fly’s sense of time was also recessive. That is, if a fly inherited one broken copy of the gene and one normal copy, its sense of time was almost normal—its clock ran just half an hour slow.

  In test after test, all three mutations mapped to the same spot. They were clearly alternative versions of the same gene. In the jargon of genetics, each spot on a chromosome is a locus. Konopka had discovered three alleles of a locus on the X chromosome that shapes the fly’s sense of time. He had now earned the right to name the gene. Because a change in the gene had the power to change the period of the fly’s days, Konopka called it the period locus.

  He had found a very peculiar gene, and he had found it in his first two hundred bottles. Later on, when Benzer and his students, building on this first success, began to wander in many new directions, Konopka would formulate Konopka’s Law. It was his first law, and so far it is his only law: “If you don’t find it in the first two hundred, quit.”

  WITH THE DISCOVERY of the clock gene, the sense of time, mysterious for so many centuries, was no longer a mystery that could be observed only from the outside. Now it could be explored as a mechanism from the inside. The discovery implied that behavior itself could now be charted and mapped as precisely as any other aspect of inheritance. Qualities that people had always thought of as somehow floating above the body, apart from the body, as if they belonged to the realm of the spirit and not of the flesh, as if they were supernatural, might be mapped right alongside qualities as mundane as eye pigment.

  At the time, not many people at Caltech or elsewhere were prepared to believe Konopka’s mutants or his maps. They could not believe that his X marked the spot. “People really resisted the notion that this had anything to do with the phenomenon,” Konopka says now. “They could never get it through their heads what it meant that these mutations were all at the same locus.” Three different mutations in one locus meant that he had found not just a piece of the clock but a central piece, maybe the central piece, the pacemaker of the fly’s behavior, the piece of living machinery that keeps it waking and sleeping and moving in time with its planet from the moment it is born. His map suggested that a single gene can shape vast arrays of behavior, that individual genes can have extraordinary power to influence a life. He could even hope (though it was only a hope) that the gene he had found in the fly would tell him something about the mechanism that drives our own human sense of time.

  As Konopka made more and more crosses and his map became more and more convincing, Benzer and Konopka got excited—but not the skeptics up and down the hall. “They would try to deny it,” Konopka says now. “They couldn’t think about it. They didn’t appreciate the power of genetics. They refused to believe that anyone would get the pacemaker.” Ever since the turn of the twentieth century, biologists had been trying to approach the mysterious center of life by way of genes. “But they would refuse to believe someone would have a handle on this.”

  Not even Hotta trusted Konopka’s results. “I cooperated with him very heavily,” Hotta says now, “and I constructed the machines he used to assay the behavior. But at that time, I was rather skeptical about the gene, and so I dared not put my name in the paper.” Konopka and Benzer wrote up a report, “Clock Mutants of Drosophila melanogaster,” and sent it to the Proceedings of the National Academy of Sciences. At a party in Pasadena, Benzer told Delbrück that they had found alleles of a new gene linked to behavior. Benzer explained why he and Konopka thought the mutants had something wrong with their sense of time.

  “I don’t believe a word of it!” Max Delbrück doubted the genes-and-behavior stories that began to pour out of the Benzer lab in the second half of the 1960s. Here, Seymour explains and Max doubts, after a seminar at Caltech. (Illustrations credit 8.1)

  “I don’t believe it,” said Delbrück.

  This scene also became part of the Konopka legend. Konopka was standing right next to Benzer and Delbrück at the time.

  “But Max,” Benzer said, “we found the gene!”

  “I don’t believe a word of it,” said Max.

  CHAPTER NINE

  First Love

  What is it men in women do require?

  The lineaments of Gratified Desire.

  What is it women do in men require?

  The lineaments of Gratified Desire.

  —WILLIAM BLAKE,

  “The Question Answer’d”

  DARWIN DIVIDED the adaptations of life into two kinds: the ones we need to survive and the ones we need to reproduce. The clock is one of the oldest adaptations of the first kind. Living things needed clocks as soon as they had begun to accumulate other adaptations: they needed clocks to organize the rest. Having a clock allowed the first simple life-forms billions of years ago to grow on a schedule—to make any compounds they required for photosynthesis before sunup, for instance, and to taper off their production before sundown, as plants still do today; or to hunt for other living things to eat when those things were most plentiful and most vulnerable—which owls and wolves still do today, each to its own clock. Inventing a clock was probably one of the first acts of life, and that is why clocks are ubiquitous. With period, Benzer and Konopka were looking at the first known specimen of one of the oldest instincts on the planet.

  What is going on in our heads when we feel the passage of time is a question that they were wise enough to ignore, temporarily. That problem has defeated philosophers for millennia. Bishop Berkeley tried to define time and found himself “embrangled in inextricable difficulties.” Saint Augustine said that we all know what time is until we try to put it into words. The Roman philosopher Plotinus thought the sources of time must lie inside us, that time springs from the human soul.

  A clock gene is not the same as the sensation of time, any more than a cascade of molecules in the retina is the same as the sensation of sight. Still, without rhodopsin and a long string of other molecules we are color-blind, and without clock genes we are time-blind. So period is a way into one of the sources and wellsprings that Plotinus believed must flow from the soul in “all the dense fullness of its possessions.”

  There was something thrilling but also peremptory, down to earth, even absurd about the discovery of the first clock gene, as there would be about all the rest of the discoveries that followed. To go from the contemplation of time to the contemplation of clock genes means coming down to earth with a bump. To turn from the sublime to a mechanism so anatomically concrete can make us feel ridiculous. In his celebrated M notebook (M for Metaphysics, Materialism, and Mind) Darwin jotted a note to himself about Plato. “Plato says that our ideas arise from the preexistence of the soul, and are not derivable from experience,” Darwin wrote, and he added “—read monkeys for preexistence.”

  But there are wheels within wheels even in period. Eventually molecular biologists in laboratories around the world would be bent over Konopka’s clock gene like scholars bent over a single verse of Hebrew or Greek in which they could almost read the secret of life. “Parmenides,” writes David Park in his book The Image of Eternity: Roots of Time in the Physical World, “was known principally for a poem, written in high poetic style, in which he analyzed the mysteries inherent in the single Greek word esti, ‘is.’ ”

  TO TURN FROM the springs of time to the springs of love means coming down even harder. Love is what wise men and proverbs do not pretend to explain. “Three things are too wonderful for me,”
a verse declares in Hebrew Scripture, “four I do not understand”:

  the way of an eagle in the sky,

  the way of a serpent on a rock,

  the way of a ship on the high seas,

  and the way of a man with a maiden.

  In The Gold Bug Variations, a novel about the cracking of the genetic code, Richard Powers imagines a meeting between Albert Einstein and T. H. Morgan at Caltech. Morgan explains what he is trying to do in his Fly Room, the union he is trying to arrange between biology, chemistry, and physics. “No, this trick won’t work,” Einstein cries. “How on earth are you ever going to explain in terms of chemistry and physics so important a biological phenomenon as first love?”

  In Darwin’s terms, the adaptations of reproduction are as old as the adaptations of survival. Reproduction is one of the defining acts of life; and without reproduction there would be no way for the Darwinian process to begin, since Darwin’s process is evolution by the selective success and failure of populations of reproducing forms. Small differences written in single changes in the letters of the double helix led rapidly under the pressure of natural selection to an extraordinary profusion of forms and also to forms of self-advertising, courtship, and copulation that are as miraculous as any phenomena in the natural world.

  If the clockwork gene stands for all the clockwork of the body’s apparatus of survival, then the instincts of reproduction stand in our minds for all the miraculous complexity of behavior. Males and females need displays to find each other, to recognize each other, and also to impress each other, since virtually every copulation in the world takes place beside a big gene pool of competition. This produces powerful evolutionary pressures that Darwin called sexual as opposed to natural selection.

  Galton assumed that other animals cannot vary their courtship routines the way we humans do with fashions. But humpback whales sing songs that radiate through the oceans for thousands of miles and change from season to season much like the Top Ten songs that fill the airwaves over the whales’ heads. At any one moment in any one ocean all of the males sing the same song. But within a month they will all be singing a new song, and unlike human beings they never sing a golden oldie from a decade or two back. They never repeat themselves. The songs appear to be courtship songs, elaborate displays, like most of ours on the radio. They actually include the use of rhyme; and according to Roger Payne, who has been recording them since the 1960s, the love songs of some whales are audible more than ten thousand miles away. “When you swim up next to a singing whale through the cool blue water,” Payne writes, “the song is so loud, so thundering in your chest and head, you feel as if someone is pressing you to a wall with their open palms, shaking you till your teeth rattle.”

  Male bowerbirds in Australia and New Guinea do not sing fancy songs or flash fancy plumage. Instead they build bowers, pretty little shelters, each species according to its own design. Some build teepee style, with branches leaning in against a sapling that bowerbird watchers call a “maypole.” Others build what are known as avenue bowers, which they invite females to walk through. The satin bowerbird paints the walls with a twig brush; he makes the paint out of chewed fruit, charcoal, and his own saliva. Other bowerbirds drag in live orchids. They throw out the old, wilted flowers every day and redecorate the bower with fresh flowers. Males trash each others’ bowers, steal each others’ flowers, and even barge in sometimes to interrupt other pairs in coitus. The satin bowerbird, which has bright blue eyes, decorates its painted bower with anything blue it can find, according to the ornithologist Frank Gill: “One bower was decorated with parrot feathers, flowers, glass fragments, patterned crockery, rags, rubber, paper, bus tickets, candy wrappers, fragments of a blue piano castor [sic], a child’s blue mug, a toothbrush, hair ribbons, a blue-bordered handkerchief, and blue bags from domestic laundries.”

  These spectacular animals would have been impractical subjects for attempts to isolate links between genes and behavior. Again the molecular biologists had to start simpler. Sydney Brenner studied mutants of courtship and copulation in the nematode worm. The worm is slow and undulant. Watching it through a microscope at high power is like watching whale sinuosities through a porthole. It glides around a petri dish on a bed of agar and around its food, a blob of E. coli in the center of the agar. Generations in Brenner’s school have now gotten to know the slither look of them, the male nosing around the female—wrapping around her, searching efficiently for the vulva, and finding it with the ingenuous directness or excitement of the young Philip Roth. Brenner and his students learned the worm’s ways and habits, which are highly regular (“Let’s give it forty-five seconds, and it will defecate again.”), and they learned to pick them up with toothpicks or titanium wire and to freeze and unfreeze mutants for their genetic dissection experiments. Like the drosophilists, they fell in love with their animals and saw more and more richness of behavior. There is a worm lab just down the hall from Benzer’s Fly Room at Caltech. It is run by a young molecular biologist named Paul Sternberg, who keeps three or four thousand strains of mutants, double mutants, and triple mutants frozen in liquid nitrogen for breeding experiments. Often when he and his group make mutants and something goes wrong, he becomes aware for the first time of some piece of normal behavior that he hadn’t noticed before. “If you’re narrow-minded like we are,” says Sternberg, “you don’t realize it until you perturb it. Then you go back and see it. That’s the code of the geneticist. Of course, an animal behaviorist, an ethologist, would just watch. But I hang around with people who get excited by genes. They get excited when they can talk about genes.”

  In the Hawaiian archipelago, sexual selection pressures have produced fantastic displays even among fruit flies. There are more than four hundred species of Drosophila in the islands, and they all descend from a few flies that blew in on a freak wind millions of years ago, possibly from a single pregnant Eve. Being lovers of dew, the fruit flies live mostly in the rain forests on the cool green windward sides of the volcanoes. The picture-winged Drosophila are some of the most striking-looking—big for fruit flies, six to eight millimeters long—and their courtship is striking too. Courting males fly to a solitary spot on a tree trunk or a large leaf or fern a few feet above the ground. As many as ten males, sometimes from three or four different species, stake out different fronds of the fern or scales of bark or petals of an orchid. This kind of courtship is known as “lekking”: male fruit flies’ equivalent of hanging out at the 7-Eleven. They do wait around almost from seven to eleven—from sunrise to sunset, even through light rains. Males of some species stay motionless; others perfume their spots with tiny anal droplets of male pheromones as advertisements for themselves. Female picture wings are not ready to mate until they are a month old, and they often live another month after that, and they mate only once. So each female takes her time flying from lek to lek, day after day, sometimes for weeks, before she settles down to court and be courted.

  Close up, males of each species court in their own way, according to the drosophilist Herman T. Spieth. A male Drosophila ornata stands directly behind the female with his head under her wing vanes, extends his proboscis, alternately stamps his forelegs against the fern, spreads his wings, straightens his abdomen, elevates the tip, and pulsates an anal droplet. After that, he goes into routines and subroutines. For instance, if the female kicks rearward with her hind legs, Spieth says, the male typically backs away several millimeters, spreads his wings horizontally to forty-five degrees, and exposes certain selected segments and membranes. The male sometimes courts from in front, and there his routine is completely different, including many ritual pawings of the fern, curlings of the abdomen, and what Spieth describes clinically as “contact of the labellar lobes,” explaining, in parentheses, “(kisses).”

  Drosophila hamifera has a different display, including wing vibrations and Elvis-like gyrations of the abdomen. “If the female responds by making labellar contact (kissing), the male then circles rapidly to her rear.
” There he assumes their species’s ritual position, says Spieth. He puts his head under her wings, holds on to her with his hypertrophied labellum (swollen lips), thrusts his forelegs under her abdomen, and moves them alternately to and fro.…

  And so on: innumerable distinct routines and if-then subroutines in a single group of flies on a single isolated group of islands. Many of these pieces of behavior may have evolved the way the flies in Benzer’s Fly Room evolved, bit by bit, with changes of one letter or a few letters of genetic code at a time. The routines help the males do what the humpback’s songs and the bowerbirds’ bowers do: advertise a male as a good choice and set him apart from the rest of the lek. And a surprising number of the Hawaiian fruit flies’ routines include a moment in which the female, after a period of ritualized dodging, stabbing, darting, stamping, fanning, or apparent indifference, will march forward head to head “with the labellar lobes open and firmly ‘kiss’ the male’s open labellar lobes.”

  After the female copulates with the male, she takes off and never sees him again.

  “SURPRISINGLY,” says Michael Ashburner, who is a world authority on Drosophila at Cambridge University, “most entomologists don’t regard Drosophila melanogaster as an insect.” Ashburner laughs. “Well, it is, but because the literature on Drosophila is so huge and a lot of it requires you have some understanding of formal genetics and most insect biologists don’t, they’re scared of it, basically.”

  Nevertheless, Drosophila melanogaster is made of the same stuff as other insects. Put a virgin female and a male Drosophila melanogaster beneath a large watch glass, and the action runs much the same course again and again, more or less like clockwork. The male sees the female, and even if he has never seen a female fly before in his life—even if he has never seen another living thing in his life—he seems to experience, as Benzer puts it, “an immediate ‘aha!’ reaction,” a fly Adam noticing Eve. Within seconds he maneuvers so that he is facing her head from one side. Then he holds out one wing toward her in a kind of salute and sets it vibrating: the love song of the fly. Hurrying around to her other side, he holds out his other wing toward her and vibrates that: second verse, same as the first. To Benzer in his workroom in the middle of the night, the song was just barely audible if he lowered his ear to an open vial: Eine Kleine Nachtmusik. The song of the fly does not sound romantic to a human ear, but then the fly seems unmoved by human songs that blast from the radios, tape decks, and CD players in the Fly Rooms. When Benzer played the fly’s love song at lectures, he used to introduce it with P. T. Barnum—style blarney: “You are privileged to hear a recording of the male courtship song of Drosophila melanogaster, and I hope the ladies will control themselves.” He enjoyed pointing out that at the female fly’s antenna, which is a sound-receptive organ, the love song has a volume of about one hundred decibels, which is comparable to the climax of the “1812 Overture.”