Benzer, Seymour

Benzer, Seymour
Oct. 15, 1921-Nov. 30, 2007
American biophysicist


In his profile of the geneticist and behavioral scientist Seymour Benzer for the New Yorker (April 5, 1999), Jonathan Weiner wrote, "Benzer's pioneering work with flies has put him at the center of one of the most controversial issues in science: the extent to which our genes shape who we are and what we do." In conducting his wide-ranging and often pioneering research, Benzer has maintained the work habits he established more than five decades ago. As Jonathan Weiner noted, "He always wore many layers of clothing; he did his best work in the middle of the night; and he amazed [his friends and colleagues] by the things he ate," among them snakes, caterpillars, ducks' feet, and cows' udders. Much of his work has involved fruit flies, known to scientists as Drosophila melanogaster, in a laboratory at the California Institute of Technology (Caltech). There, he has often experimented far into the night, attempting to find flies with genes that had altered their tiny owners' sense of time, their ability to mate, or their capacity to remember learned behavior. Modest about his achievements, which include groundbreaking work in physics during the 1940s, gene mapping in the 1950s, and linking behavior to genetics beginning in the 1960s, Benzer has until recently received little notice outside the worlds of biology and genetics. He has been a member of the National Academy of Sciences since 1961 and has won several major international honors, including the Gairdner Award (1964), the Lasker Award (1971), the National Medal of Science (1983), the Thomas Hunt Morgan Medal for his lifetime contribution to genetics (1986), the Wolf Prize for Medicine (1991), and the Crafoord Prize, from the Royal Swedish Academy of Sciences (1993). The Pulitzer Prize-winning journalist Jonathan Weiner profiled Benzer in Time, Love, Memory, published in 1999, thus bringing the scientist's discoveries to a larger audience.

The third of the four children of Polish-Jewish immigrants, Seymour Benzer was born on October 15, 1921 in New York City. His parents, Mayer and Eva Benzer, both of whom worked in the garment industry, raised him and his three sisters in the Bensonhurst section of the borough of Brooklyn. As the family's only son, Benzer was favored, and thus was given fewer chores than his sisters; he divided his ample free time between his homemade basement laboratory, where he did chemistry experiments, and playing stickball with neighborhood children. For his bar mitzvah, celebrated when he turned 13, he received a microscope as a present. On the first slide that he made, he placed a sample of his own sperm. Houseflies were another early subject. He graduated from high school at age 15 and then enrolled at Brooklyn College, where he paid his tuition with a New York State Regents Scholarship. Eager to dive into advanced biology, he asked to skip the introductory course, which was more akin to natural history than hard science. His request was denied, and "being a stupid, pigheaded, cocky young guy, I told them the hell with it, and didn't take any biology at all," he told Weiner.

In 1942 Benzer earned a B.A. degree in physics. The same year he married Dorothy Vlosky, nicknamed Dotty, and moved with her to Indiana, where Benzer did graduate work at Purdue University, in West Lafayette. He was awarded a master's degree in physics in 1943 and a Ph.D. in 1947. At Purdue, in the latter years of World War II, Benzer worked in a secret wartime laboratory with scientists attempting to develop germanium semiconductors for use in radar devices. Silicon semiconductors, which were being used at that time, tended to burn out when subjected to high voltages. Benzer discovered a crystal form of germanium that withstood such voltages. He and his supervisor in the lab, Karl Lark-Horovitz, were ultimately awarded six patents for their research discoveries, and the crystal form of germanium was later used at Bell Labs to develop the first transistor.

Benzer's career path changed in 1946, after he read What Is Life?, by the Austrian quantum physicist Ernest Schrodinger. The German quantum physicist Max Delbruck had earlier offered ideas regarding the physical makeup of genes, and Schrodinger's book identified this issue as the key question in all of science. Intrigued, Benzer registered for a summer course on bacterial viruses that Delbruck had initiated at Cold Spring Harbor Laboratory, on Long Island, New York. "Within one day," as Benzer told Weiner, he developed a passion for the subject matter and decided to switch his focus to biology. His colleagues at Purdue were dismayed; many of them, as Weiner noted in his article, "were planning to form electronics companies and get rich." "People thought I was nuts," Benzer told Weiner. "Here it was, the semiconductor thing was booming."

Abandoning semiconductors and electronics, Benzer took a leave of absence from Purdue in 1948; the leave stretched into a four-year odyssey into the world of genetics. During that time he worked with four future Nobel laureates in three different laboratories: at Oak Ridge National Laboratory, in Tennessee; at Caltech with Delbruck, who won the Nobel Prize in Physiology or Medicine in 1969; and as a Fulbright scholar at the Pasteur Institute in Paris, where Benzer worked with Jacques Lucien Monod and Francois Jacob under the direction of Andre Lwoff, all three of whom shared the 1965 Nobel Prize in Physiology or Medicine. Benzer also spent a summer working with Cornelius van Niel at the Stanford Marine Station, at Pacific Grove, California.

Benzer returned to Purdue in 1953, to teach physics and biophysics as an associate professor. (He was promoted to professor of biology in 1958.) Soon afterward Francis Watson and James Crick published their findings about the double-helix structure of DNA. Benzer had been engaged in his own genetic research, with viruses and bacteria; he was trying to understand the physical structure of their genes and searching for a possible relationship between their genes and those of larger organisms. Benzer's experiments expanded on the work of the geneticist Thomas Hunt Morgan, who had attempted to map the genes of the fruit fly Drosophila at Columbia University around the turn of the 20th century. In biology in the 1950s, "what was needed was to connect [Watson and Crick's] studies with the classical maps of the genes started by Morgan," Lewis Wolpert, writing for the New York Times Book Review (May 2, 1999), noted in his assessment of Time, Love, Memory, which serves as a biography of Benzer as well as an account of his work. Benzer made that connection "brilliantly," Wolpert continued, "focusing in great detail on a single region of virus DNA; he discovered the fine structure of the gene and how it could change by mutations. He discovered mistakes in a gene-deletions and insertions, rather like the typos we all come across."

Benzer spent a decade mapping rII, a chromosomal region of the bacteriophage T4 (a bacteria-infecting virus), doing pioneering work on splitting the gene. To diagram the interior of a gene in minuscule detail, he created a map that stretched across the walls of his laboratory; when he presented it at conferences, its unfurling made a memorable impact on colleagues. Through his experiments with bacteriophage T4, he became the first to show that the internal structure of a gene itself is linear, similar to the arrangements of various genes on a chromosome. Using a mutant strain of bacteriophage T4 that should not have been able to multiply and overtake a strain of the bacteria E. coli (as the normal form of T4 could), Benzer then combined the first mutant with strains of T4 that had different genetic mutations. By recombining their genetic structures, the T4 mutants were able to restore their original genetic makeup and reproduce, as evidenced by their destruction of the E. coli. Using that system, Benzer was able to detect recombination between two mutations, even if they were only one nucleotide unit away from each other on the DNA of the bacteriophage. That was the key to constructing a fine-structure map of the gene, related to the structure of its DNA. Benzer spent a sabbatical year in 1958-59 at Cambridge University, in England, working with Francis Crick, James Watson, and the geneticist Sydney Brenner.

Despite his research successes, as well as Purdue's willingness to transfer his professorship to the Department of Biology, Benzer felt restless. In the New Yorker, Jonathan Weiner described the prevailing attitude of the time: "By the early sixties, molecular biologists had learned so much about the gene that they doubted whether they would ever encounter any further mysteries to equal the ones they had dispelled." Benzer remarked to Weiner, "It was a little bit like the physicists at the end of the nineteenth century saying 'All we have left to do is find one more decimal place.'" While vacationing at Cold Spring Harbor with his family in the early 1960s, however, Benzer was inspired by a new problem, one that would lead him to blaze a trail in a new field: behavioral genetics. Observing his daughters playing on the beach, he found their differences remarkable; his daughter Barbie had always been more energetic than his daughter Martha, while Martha had always been more placid. Benzer had noticed his daughters' distinctive personalities and behavioral characteristics almost from birth and, as Weiner noted, "he didn't think that he and his wife could possibly have made that much difference in the temperaments of the two girls-the difference had to be in the genes." This revelation inspired Benzer to plunge into the "nature versus nurture" debate, which focuses on the influence of environment on personality, on the one hand, and the influence of heredity, on the other. Weiner described Benzer's motivation: namely, to "try to trace the connections between the gene and the brain, and between brain and behavior." In an effort to understand the physiology of the brain better, he asked his wife to buy from the butcher brains of different species-cow, sheep, goat, chicken, and pig. Working at home in the middle of night, he dissected the brains, examined them, and then cooked and ate them.

In the interest of pursuing his new topic, Benzer went to Caltech in 1965 as a visiting researcher and worked with the psychobiologist Roger W. Sperry, who would later win the Nobel Prize in Physiology or Medicine, in 1981. Benzer's laboratory at Caltech was in the same building where Thomas Hunt Morgan had done his final research; following in Morgan's footsteps, Benzer began to experiment with fruit flies, creating mutant strains and looking for changes in behavior. His first breakthrough was with flies that had maladjusted internal clocks. Ordinary fruit flies hatch at dawn and in the following days maintain a daily routine that always includes becoming active at sunrise, even if they are in a darkened room. In 1968 Benzer and Ronald Konopka, a graduate student, isolated strains of flies whose clocks were broken-some of the flies woke up too early, others "slept in," and still others never went to sleep. Benzer and Konopka linked the various errors in timing to a single gene on the X chromosome and named the gene "period." Benzer and his student Jeff Hall isolated genes that were linked to the fruit flies' courting and mating rituals. One male fly exhibited courting behavior but never mated; Hall named it "celibate." Another male fly began copulation but stopped himself halfway through and rarely produced offspring; he was christened "coitus interruptus." A group of mutant male flies discovered by another researcher were observed exhibiting mating rituals to one another, and the mutant gene responsible was named "fruitless." Other experiments, conducted with Benzer's students Chip Quinn and Duncan Byers, tested the flies' capacity for memory and learning, resulting in the discovery of the mutant "dunce." Throughout the arduous process of working with the insects, Benzer insisted that his research, which many of his students have since continued in their own laboratories at other academic institutions, had relevance to human genetics. "Often the discovery of a gene in the fly has led straight to its discovery in human beings, because key sequences in both genetic codes are very much alike," Weiner wrote in the New Yorker. He continued, "Our clocks apparently work so much like fly clocks that, in laboratory tests, some of our protein gears mesh perfectly with the flies' gears, like parts of the same watch-even though human beings and flies have not shared an ancestor since the Cambrian Period, six hundred million years ago."

Named the James G. Boswell Professor of Neuroscience at Caltech in 1975, Benzer took a brief break from his work in 1978, after the death of his wife, Dotty. He thought about dropping his research with flies and moving on to something else. "Well, I'd jumped before," he told Weiner. But late in 1978 he met Carol Miller, a young neuropathologist associated with the medical school at the University of Southern California. Both were driven to unlock the secrets of the brain-he of flies and she of human beings. They traded tools, tips, and case histories before falling in love and marrying, in 1980. At around that time Benzer began working with flies that had inherited the propensity to develop brain defects, naming each mutant after some food that resembled the shape of its lesions.

Benzer's honors include being named a 1998 Ellison Medical Foundation Senior Scholar (which brought him a grant worth almost $1 million). In 2001 he won the National Academy of Sciences Award in the Neurosciences. His work is not without critics, however. According to a rumor, he was once nominated for a "Golden Fleece Award," with which then- senator William Proxmire of Wisconsin identified projects that, as a member of Congress, he considered examples of wasteful or useless government funding. Benzer himself keeps on the lookout for genetic studies that prove to have been based on weak foundations and whose authors later retract their findings; according to Weiner, Benzer "keeps a file of headlines pertaining to genes and behavior, so that if their claims are discredited he can use them in his lectures as cautionary tales."

Benzer and Carol Miller live a quiet life in San Marino, California; they are the parents of one son, Alexander, born in the mid-1980s. Ignored by the recent debate on cloning because of his focus on fruit flies, Benzer has continued with his experiments. In the late 1990s he found himself in the spotlight, after his laboratory published findings of a mutant fly that had outlived its normal 60-day life span by approximately 40 days. The discovery of the fly, named "methuselah" after the biblical figure who lived to the age of 969, "seems a fitting [77th birthday] present for [Benzer], who still works late into the night and loves the smell of fly food," Lewis Wolpert reported. Shortly after the discovery was made public, Weiner asked Benzer if he was planning to travel during his upcoming vacation. "To me, getting back into the lab would be enough of an adventure," Benzer replied.

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