Profile of Jeffrey C. Hall Hen Geneticist Jeffrey C

PROFILE Profile of Jeffrey C. Hall hen geneticist Jeffrey C. Hall looks back on his career path, he offers praise for each of the personali- Wties he has encountered, from his deaf undergraduate advisor to his fellow Civil War scholars—not to mention the small, elegant, and urbane fruit fly. ‘‘They’re very complex organisms, quite sophisti- cated and interesting,’’ he says of Dro- sophila, the neurobiology and behavior of which have occupied his research since college. To Hall, Drosophila are valuable for more than just their easily manipulated genomes. As he grew to ‘‘love the fly,’’ he also began to delve into the insect’s genetics, neurobiology, and behavior at a deep level. Convinced of the worth of analyzing Drosophila mutants for studying behavior, Hall has dedicated his career to probing the neurobiological underpinnings of the fly’s courtship and behavioral rhythms. His research with Jeffrey C. Hall Drosophila genetics has elucidated the mechanisms of biological clocks and opened a window into the basis for fruit flies. Ives, who had been a student sophila laboratory of Lawrence Sandler, sexual differentiation in the nervous of geneticist Albert Sturtevant, lost his also a research descendent of Stur- system. hearing in graduate school and was rele- tevant’s. Hall worked with Sandler on Hall, a Professor of Biology at Bran- gated to a non-tenure-track research several research projects, starting with deis University (Waltham, MA), was a career that included shepherding under- the analysis of age-dependent enzyme recipient of the Genetics Society of graduate students like Hall through changes in Drosophila (2) but with a America Medal in 2003, the same year small projects. Yet Ives excelled as a main focus on the genetic control of he was elected to the National Academy researcher and was dedicated to his chromosome behavior in meiosis (3). of Sciences. His Inaugural Article in this mentoring role. He exhorted his stu- After a few years of research, Hall dents to ‘‘love the organism,’’ Hall says. issue of PNAS (1) investigates the fruit- was summoned into the office of Her- ‘‘This sort of resonated, because I really less gene, which controls behavior such shel Roman, the department’s founder, did like the little fruit flies. They’re ex- as the recognition by a male of whom chair, and longstanding father figure. tremely appealing, one reason being that he might ‘‘choose’’ to court and court- Roman took a sharp interest in the fate they’re small and cute, as silly as this ship singing behavior, by analyzing the of his department’s students, and he rec- may seem.’’ As a model for research, behavioral meaning of this gene’s ommended that Hall do postdoctoral Drosophila strike a good balance of work with Seymour Benzer at the Cali- expression within various regions of qualities, Hall points out, in that they the nervous system. fornia Institute of Technology (Pasa- are small enough to handle in large dena, CA). Hall knew Benzer to be a Small and Simple Research numbers, large enough to facilitate ob- highly regarded geneticist who had servations, and simple enough to yield moved from research on bacterial vi- Born in Brooklyn, NY, Hall grew up in large amounts of data but ‘‘not so pa- the suburbs of Washington, D.C., where ruses during the 1960s to study behav- thetically simple as to be dreary and ioral genetics and neurogenetics. Benzer’s his father worked as an Associated Press boring.’’ reporter, covering the U.S. Senate. His signature approach was to induce ran- With Ives, Hall spent a year studying dom mutations in fruit flies, screen father’s attitude permeated his con- recombination and translocation induc- sciousness in many ways, Hall says, caus- them for noteworthy behavioral charac- tion in Drosophila. This research project, teristics, and then use the genes defined ing him to, for example, ‘‘read more which Hall describes as ‘‘intrinsically than just the sports section each morn- by these mutations to dig as deeply as rather silly,’’ turned out well, and de- possible into the neurobiology of such ing.’’ A good but not stellar student in partment faculty took notice, recom- high school, Hall planned to attend behaviors. mending that he pursue graduate studies Roman phoned Benzer as Hall sat in medical school when he entered Am- at the University of Washington (Seat- herst College (Amherst, MA) in 1963. his office, and two days later Hall was tle), which had the unusual distinction on a plane down to southern California Halfway through earning his bachelor’s of having an entire department devoted to interview with Benzer. At the end of degree, however, he found his curiosity to genetics. ‘‘I applied there, just follow- the brief visit, Benzer offered him a for medicine replaced by one for basic ing orders,’’ Hall says, ‘‘but I’m glad I science. did, because they were absolutely right.’’ For his senior honors project, Hall This is a Proﬁle of a recently elected member of the National hoped to gain experience in formal re- A Push Down the Coast Academy of Sciences to accompany the member’s Inaugural search and began working with Philip When Hall arrived in Seattle in 1967, he Article on page 16550. Ives, a genetics researcher who studied already knew he wanted to join the Dro- © 2005 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0508533102 PNAS ͉ November 15, 2005 ͉ vol. 102 ͉ no. 46 ͉ 16547–16549 Downloaded by guest on September 25, 2021 spot in his laboratory, and Hall finished low from England to work specifically his doctoral work and moved to Ben- on the neurogenetics of singing behav- zer’s laboratory in 1971. ior. Kyriacou’s analyses revealed that the Drosophila courtship song is pro- Universal Slices of Courtship duced rhythmically with a normal peri- Hall soon realized that Benzer ran ‘‘a odicity of about one minute. When Hall lab where you make your own way,’’ in saw these findings, he recalled the pe- which students and postdoctoral fellows riod mutants generated by Ronald J. were encouraged to pursue research in- Konopka in the late 1960s in Benzer’s dependently. Benzer’s main suggestion laboratory. Konopka’s mutants displayed to Hall was to work with Doug Kankel, daily sleep–wake rhythms deviating from another postdoctoral fellow in the labo- the 24-hour cycle, and so Hall suggested ratory. Hall found Kankel to be replete to Kyriacou that they check whether with detailed knowledge of Drosophila these mutants had altered courtship biology that extended to neuroanatomy song cycles as well. In basketball terms, and neurochemistry, all of which Hall Male Drosophila following and courting a female this suggestion was ‘‘throwing up a gratefully absorbed. The pair began by singing to her. prayer,’’ Hall says. ‘‘It was crazy. There collaborating on two projects, both of was no reason to think that the control which progressed surprisingly well, Hall of this one-minute rhythm would have says (4, 5). courtship, anybody who is listening in- anything to do with the regulation of Hall left Benzer’s laboratory before stantly knows what you’re talking daily rhythms.’’ publishing any results, however. During about.’’ Yet Hall was mindful of the To their surprise, Hall and Kyriacou Hall’s third postdoctoral year, Roman conservative academic nature of many found that the period mutations affected called from Seattle to say that he had biologists at the time, and he kept these the courtship song just as they changed been lobbying on Hall’s behalf for open inchoate hopes for greater human signif- the circadian rhythms, by stretching, faculty positions at the University of icance largely to himself. shrinking, or obliterating both cycles Missouri (Columbia, MO) and Brandeis similarly (7). Using the then-emerging University. Such promotion was a gener- Transatlantic Songs tools of molecular genetics, Hall, Kyria- ous act of faith on Roman’s part, Hall Hall’s study of Drosophila courtship be- cou, and Michael Rosbash, a colleague says, because Roman was unfamiliar havior eventually encompassed the at Brandeis University, set out to isolate with Hall’s research in California. Bran- male’s courtship song, a pattern of the period gene. deis University offered Hall a faculty sounds emitted from a male’s vibrating position, and he joined the university as wings as he follows a female. In the Cracking the Case of Circadian Rhythms an Assistant Professor of Biology in mid-1970s, Hall began collaborating Hall and his colleagues used fruit fly 1974. with Florian von Schilcher at the Uni- molecular genetics to study biological At Brandeis, Hall carried forward the versity of Munich to correlate song clocks, but traditional circadian rhythm momentum of his work with Kankel, qualities with genetic sex. Hall gener- researchers had long preferred a nonge- who by that time was working at Yale ated Drosophila mosaics and shipped netic approach using a variety of organ- University (New Haven, CT). A particu- isms. ‘‘Many of them loudly and publicly larly intriguing research thread sprang denounced the genetic approach to from an offhand suggestion from Kankel ‘‘Singing behavior is study rhythms,’’ Hall says. He now con- during Hall’s last months in California. siders this a mixed blessing, in that the They had been generating fruit fly sex one of the exquisitely distaste of some researchers for molecu- mosaics—organisms part male and part lar genetics kept the number of compet- female—and staining them to determine quantiﬁable features itors to a minimum. The only other which nerve cells were male and which group also hunting for the period gene were female. Kankel mentioned that of courtship.’’ was Michael Young’s laboratory at The they should be examining each mosaic Rockefeller University (New York), before dissection to see whether male or which had been prompted by Young’s female courtship patterns were present.

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