Time, Love , Memory

by Jonathan Weiner

  So Morgan imagined two of these X chromosomes mating, so to speak—wrapping around each other, aligning themselves so that every point on one X touches the corresponding point on the other. During that intimate moment, Morgan thought, bits of each chromosome might somehow trade places. Genes might cross over from one X to the other. Afterward, the solitary X chromosome that passes into the female fly’s egg would carry some genes from her father’s X and some genes from her mother’s X. And all this shuffling and crossing-over might have caused the oddities that Morgan was trying to explain. The genes on the X chromosomes had shuffled; they had mixed and matched.

  Morgan arrived at this vision of crossing-over toward the end of 1911. In the Fly Room, he shared it with his favorite student, Alfred Sturtevant, then a senior at Columbia. What happened next is one of the most important eurekas in twentieth-century science and deserves to be better known outside the field of genetics. The moment would help to define both the style and substance of the study of life for the rest of the century.

  This crossing-over idea had interesting implications, Morgan told Sturtevant. Picture that female fly and her two Xs just before the shuffle and scuffle of crossing-over. On one X, she has genes for red eyes and long wings. On the other X, she has genes for white eyes and short wings. Suppose these two genes lie very close together on the X. If they are close, then during crossing-over the two genes will be likely to stay together, like two people who are standing right next to each other in a swirling crowd. But suppose the two genes lie at opposite ends of the X chromosome. Then they will have more chance of being separated, like two people who are standing farther apart.

  Morgan thought he could apply this idea to the results of their breeding experiment. If single mutants were rare, that would imply that the gene for eye color and the gene for wing length must lie close together on the X, because the two genes had not been separated very often during crossing-over. But if single mutants were common, that would imply that the two genes must lie far apart on the X, because they had been separated so often. And in fact, the experiment had produced quite a few single mutants: about 30 percent of the sons were single mutants.

  Sturtevant not only followed all this: there in the Fly Room, as he listened to Morgan, he had the idea of his life. By this time, he and Morgan and the other students in the Fly Room had found quite a few genes that seemed to lie on the fly’s X chromosome. Sturtevant realized that if Morgan was right about crossing-over, he might actually be able to figure out where each one of these genes lies on the X. He could test Mendel, he could test Morgan, and he could make a map of genes on a chromosome, all in one stroke.

  That afternoon Sturtevant collected a stack of laboratory records, the complete records of crosses involving half a dozen genes, and he took the papers home. At home he spread out the papers. He imagined a half-dozen beads on a string, or points on a line:

  If genes are real and if they lie in a straight line on a chromosome, they must be in this linear order. A must be closer to B than to C and so on. So in each generation of flies, there should be more ABs than ACs, because A and B are more likely to travel together than A and C. By now Morgan and his students had crossed tens of thousands of flies and they had kept records of each cross. So Sturtevant checked to see which genes had stayed together more often and which genes had parted more often when the flies were crossed.

  In the beginning there was white. Which genes are close to white? Sturtevant thought he could guess one of them. In the Fly Room they had found a gene that affects the body color of the fly. They called this gene yellow because they had first inferred its existence when they came across a yellow-bodied mutant. For his purposes now, Sturtevant needed to see the results of a cross in which one parent had white eyes and a normal brown body, and the other parent had red eyes and a yellow body. If the eye-color gene and the body-color gene were very close together, virtually all of the descendants should be of two kinds: either white-eyed and brown-bodied, or else red-eyed and yellow-bodied. But if the genes were farther apart, they would be separated more often during crossing-over. In that case, many of the two flies’ descendants would have white eyes and yellow bodies.

  Proof that genes are real. This is T. H. Morgan’s own diagram of the phenomenon known as crossing-over, which one biologist has called “arguably the most intimate event in sexual reproduction.” (a) A schematic drawing of a single pair of chromosomes. Morgan pictures the genes on the chromosomes as pearls on strings. The black pearls come from the mother, the white from the father. (b) Just before the creation of an egg cell, the two chromosomes twine together, and genes cross over. (c) Now each chromosome in the pair carries some genes from the mother and some genes from the father. Morgan and his students used crossing-over to make the first genetic maps, in one of the most extraordinary series of experiments in the twentieth century. (Illustrations credit 2.2)

  Sturtevant checked the breeding records he had brought home. In the records, exactly 21,736 flies were the descendants of such parents. Out of those 21,736 fly children, only 214, or about 1 percent, had white eyes and yellow bodies. So those two genes had rarely been separated during crossing-over. That meant the yellow gene must lie very close to white.

  Sturtevant decided to call 1 percent one map unit. He would say that white and yellow are one map unit apart.

  The lab records he had brought home also included a cross between flies with yellow bodies and flies with vermilion eyes. Those crosses had produced 4,551 fly children. Of those children, 1,464 flies, about 32 percent, had inherited both yellow bodies and vermilion eyes. If 1 percent is one map unit, 32 percent is thirty-two map units. So yellow is one map unit away from white and thirty-two map units away from vermilion.

  “Who could have foreseen such a deluge?” Morgan wrote when flies and fly bottles began crowding out everything else in his lab at Columbia. The science was glamorous; the Fly Room was anything but. Morgan and his students arrived at the lab each day bearing more and more empty half-pint milk bottles, which they stole from Manhattan stoops and from the Columbia student cafeteria. Note the bananas hanging in the corner: food not only for the flies but also for the worlds first geneticists. This photograph was taken around 1920. (Illustrations credit 2.3)

  Next came a third cross. In the records, there were 1,584 fly children that had one white parent and one vermilion parent. Of those 1,584 children, he found that 471, about 29 percent, had inherited both white and vermilion. So white was twenty-nine map units away from vermilion.

  Now came the moment that mathematicians, when they describe a brilliant equation, call the beauty part. Generations of geneticists have since retraced Sturtevant’s big night and shaken their heads over the simplicity of the trick that started their revolution. Much later Benzer would return to this trick, give it a twist, and start a second revolution.

  Sturtevant was looking at a simple mathematical puzzle. He knew that white is closer to yellow than to vermilion. He knew that yellow is closer to white than to vermilion. And he also knew that the distance between yellow and vermilion is greater than the distance between white and vermilion. There is only one way to explain those numbers if the genes are on a straight line. They have to be arranged like this:

  yellow white vermilion

  Sturtevant checked the numbers. He had one map unit between yellow and white; thirty map units between white and vermilion; thirty-two map units between yellow and vermilion. So far, then, everything seemed to be in order, “at least mathematically,” as he wrote later. The arithmetic was close enough, given the slight fuzziness in the data. And when he checked the rest of the breeding data, all of the other numbers and distances fit too. He placed a mutation called miniature wing about three map units away from vermilion. The wings of miniature are normal in shape but very short, like human arms and hands that reach only to the belt. He placed rudimentary wing about twenty-four map units from miniature. The wings of rudimentary are a bit of a mess: Some are wrinkled and blistered; some
are truncated; some have irregularly spaced hairs.

  Before dawn, Sturtevant was finished. As a senior at Columbia, he had a full load of assignments from other courses, and he had just put in an all-nighter on a long-shot project that no one had assigned. “I had quite a lot of homework to do,” Sturtevant used to say long afterward, “but I didn’t do any of it; but I did come back with a map the next morning.” In the Fly Room, he laid out the first genetic map, with the genes spaced out in a line:

  yellow white vermilion rudimentary

  Looking at this simple map, Morgan and his students could see that what they had been supposing and assuming month after month in their flyspecked laboratory was almost certainly true. Genes are real, genes are on chromosomes, and genes can be surveyed and explored. It was the biggest lightning (lash and thunderclap in biology since the rediscovery of Mendel in 1900. Morgan, who was not given to hyperbole, once called the view the map opened “one of the most amazing developments in the whole history of biology.” Sturtevant was nineteen years old.

  Morgan and his students would spend the next several decades mapping more and more genes on the X and the other three fly chromosomes, and convincing the doubters inside and outside biology that genes are real.

  Alfred Sturtevant, T. H. Morgans favorite student, figured out how to draw a map of the genes in 1911, at the age of nineteen. His discovery started biology on a long march inward. Sturtevant made gene mapping his life’s work; he never left Morgan. This photo was taken around 1925. (Illustrations credit 2.4)

  Long afterward, when Benzer and his student Ronald J. Konopka found the fly without a sense of time, they would trace its eccentric behavior to that same first chromosome, the X. And when they mapped the mutant gene, they would locate it right next to Morgan’s starting point, less than one map unit away from white.

  CHAPTER THREE

  What Is Life?

  With all his amateurish fumbling, Martin had one characteristic without which there can be no science: a wide-ranging, sniffing, snuffling, undignified, unself-dramatizing curiosity, and it drove him on.

  —SINCLAIR LEWIS,

  Arrowsmith

  MORGAN HAD ENTERED the field as a critic, a gadfly, and he was never as comfortable with the theory of the gene as those who came after him. Unlike Sturtevant, Calvin Bridges, Curt Stern, and many of his other gifted students, Morgan did not have a mathematical mind. He was a born naturalist. He loved to work with starfish, sea anemones, and pigeons, even though bottles of fruit flies eventually crowded them out of his laboratory. In some ways he resembled the German physicist Max Planck, who turned physics upside down in 1900, the same year that biology rediscovered Mendel. Planck described a beam of light as a stream of bits, packets, or quanta of energy, much as Morgan described the transmission of life as a stream of bits. Planck’s quantum theory was so hard for a classical physicist to absorb that Planck himself spent years fighting it. “He was a revolutionary against his own will,” said one of his students, James Franck. “He finally came to the conclusion, ‘It doesn’t help. We have to live with quantum theory. And believe me, it will expand. It will not be only in optics. It will go in all fields. We have to live with it.’ ”

  Morgan’s discovery transformed biology as much as Planck’s transformed physics, and Morgan was sometimes almost as ambivalent about his revolution. In the war between “bug hunters” and “worm slicers,” as the two camps sometimes called themselves, the old-fashioned outdoor naturalists and the newfangled indoor experimentalists, Morgan was an outdoor man who brought biology indoors. He was a “squishy” who fought for the “crunchies.” For years he struggled to keep up with Sturtevant, Bridges, and Stern as they crossed mutants, crunched numbers, and mapped the first, second, third, and fourth fly chromosomes. Morgan did manage to make contributions to the effort, but only through hard work and increasingly strained powers of intuition, as one of his students, Curt Stern, has written. “I remember the ‘awe-full’ moment when Bridges explained to him a particularly intricate new result and the initiator of it all left the room, shaking his head and saying ‘too much for me!’ ”

  Morgan also had trouble seeing the connection between their discovery and Darwin’s. His students tried to explain it to him. What they were doing in the Fly Room is just what natural selection does in the wild: choosing and selecting tiny mutations of the kind that give a fly a red or white eye, a straight or forked bristle, a long or short wing. Over many generations this natural selection of small changes could produce two separate species of flies; and with more generations it could produce bigger and bigger branchings in the tree of life. Some of the greatest biologists of the twentieth century, including R. A. Fisher, Sewall Wright, J.B.S. Haldane, Ernst Mayr, G. Ledyard Stebbins, and Theodosius Dobzhansky (another of Morgan’s students), would eventually unify Darwin’s and Morgan’s theories, bringing together outdoor and indoor nature, visible and invisible life in the synthesis. But in the Fly Room, Sturtevant used to explain Darwin’s theory to Morgan over and over again. “You had to keep working on it,” Sturtevant once told Garland Allen, T. H. Morgan’s biographer, in an unpublished interview. “He wouldn’t stay convinced about that. You had to keep at it. You had a job to do over again every once in a while.”

  It is a mark of Morgan’s courage that he eventually moved his Fly Room to Caltech, which was, then as now, one of the world’s greatest research centers for chemistry and physics. By shifting his operations there in 1928, at the age of sixty-two, Morgan hoped to help unite biology with chemistry, physics, and mathematics. Morgan was not grounded in those subjects himself, but like a general who sees where the war is going he wanted troops for the new front. He did have something of the general in him, by nature or nurture. His father, Charlton Hunt Morgan, had fought under General John Hunt Morgan (Charlton’s brother, Thomas’s uncle) in a legendary band of rebel daredevils known as Morgan’s Raiders. Some of his more distant kin included J. Pierpont Morgan, the robber baron, and Francis Scott Key, the author of “The Star-Spangled Banner.”

  In Pasadena, Morgan and his raiders (including Sturtevant and Bridges, who never left the man they called The Boss) explored and promoted the theory of the gene; and when Morgan was awarded the Nobel Prize for the work, he shared the prize money with Sturtevant and Bridges. But even in his Nobel address in Stockholm in 1934, Morgan expressed some doubts about their discovery. “What are genes?” he asked. “Now that we locate them in the chromosomes are we justified in regarding them as material units; as chemical bodies?” Geneticists, he said, could put that question to one side, temporarily. They could work with genes as mathematical points on abstract maps. This was the kind of work that Morgan and his raiders did, and it would later become known as pure genetics, classical genetics; it was work without molecules, as opposed to the work that Benzer and his circle made possible. When Morgan looked at the points on the maps he still wondered “whether they are real or purely fictitious.”

  BENZER TOOK his first look through a microscope in 1934, the same year that Morgan asked, “What are genes?” Morgan was in Stockholm, receiving his prize. Benzer was in Bensonhurst, Brooklyn, and the microscope was a bar mitzvah present. Benzer carried it down to the basement, where he had built a laboratory. There he performed what seemed to him the obvious first experiment and stared down through his microscope at hundreds of thousands of long, dark, thrashing tadpoles with tiny heads: sperm.

  No one else in the Benzer family cared for science. His parents came from a shtetl west of Warsaw, and they worked in the needle trades. His father would come home from the Garment District of Manhattan with bundles of clothes, which his mother would finish on her sewing machine late at night. Sometimes they asked Seymour to ride the subway to deliver their bundles. But Seymour was the only boy in the family—he was the Benzer prince, “the egg with two yellows,” to use an Old World expression—and on most afternoons and evenings his parents and his three sisters left him free to play stickball on Sixty-eighth Street or to
pursue his researches in the basement. After his bar mitzvah he had nothing more to do with Hebrew School. On High Holidays, Seymour would go with his father to the synagogue, because it was a shame for a father not to have his son beside him on Rosh Hashanah and Yom Kippur. Even then he would smuggle in something to hold over the prayer book. While the rest of the congregation chanted and his father looked the other way, Seymour read Stern and Gerlach’s The Principles of Atomic Physics.

  Seymour Benzer’s first laboratory, his family basement in Bensonhurst, Brooklyn. Here Benzer mixed potions, deconstructed flies, and struck mad-scientist poses. He also read Arrowsmith, the novel that later helped lead him to the study of the gene. He made these self-portraits, with his camera on a timer, in the mid-1930s. (Illustrations credit 3.1)

  Through the microscope he inspected blood, sweat, tears, spit, tongue gook, gutter water, and bee stings. Over and over again he deconstructed flies—house flies. His favorite book as a teenager was Arrowsmith, by Sinclair Lewis. It was almost a prayer book, because it showed science as an adventure, a romance, and a pure faith, a way to live a life. The hero of the novel, Martin Arrowsmith, is born in a small town in the Midwest. As a freshman at the University of Winnemac, he hears rumors about a mysterious German biologist on campus, a man named Max Gottlieb, who studies bacteria. Late one night, after a party, Arrowsmith wanders over to the medical building, stares up at the tall turrets of the Main Medical Building, and sees a single light. Even as he looks, the light goes out, and soon a man comes stooping along the path toward him, an old, gaunt man with his hands clasped behind his back, muttering to himself, and passes him on the path: Gottlieb. “He had worn the threadbare top-coat of a poor professor, yet Martin remembered him as wrapped in a black velvet cape with a silver star arrogant on his breast.”