The 2003 GSA Honors and Awards

The 2003 Genetics Society of America Medal

THIS year's GSA Medal is awarded to Jeffrey C. Hall for his seminal studies on the genetic and molecular bases of behavior in Drosophila. Over nearly 30 years, Hall has consolidated the field of Drosophila behavioral neurogenetics, which was initiated by his postdoctoral supervisor, Seymour Benzer, and elevated it to a level of molecular sophistication that would have hardly been thought possible when he began his work. He has focused his attention predominantly on two model systems of complex behavior, courtship and biological rhythms. Through all of this work, he has combined deep genetic insight and a firm belief in the power of mutant analysis with the broad biological perspective of placing the genes' actions into their proper anatomical and physiological context. In so doing, he has raised the entire field of animal behavior genetics to a new level and has set the standard for analytical rigor and power.

Prior to his entry into the field, Drosophila courtship genetics consisted principally of descriptive work on a small set of "classic" morphological mutants, selection experiments, and comparative evolutionary studies. Following his stint in Benzer's laboratory in the early 1970s, Hall transformed fly courtship into a mechanistic discipline through his genetic and behavioral studies of the functional neuroanatomy of sexual dimorphisms. Hall took the traditional approach of mosaic analysis and brought it to the cellular level through direct marking of neuronal genotype. This sophisticated use of genetics to define the neuroanatomical focus of a behavior laid the foundation for subsequent interpretations of all mutants affecting courtship. The first mutant he studied, fruitless, later became, through Hall's shepherding, the cornerstone of our current understanding of the genetic point of intersection between sex determination and sex-specific behavior. This work provided the first concrete molecular genetic account of how a gene controlled the sexual identity of the nervous system (rather than sex-specific morphology) and would not have been possible without Hall's foresighted and persistent genetic, behavioral, and anatomical work. Other lines of research on fly courtship launched in Hall's laboratory include the demonstration of a learning component to the otherwise innate courtship ritual, the functional demonstration of pheromonal differences between genetic variants, the genetic dissection of the sensory components of courtship behavior, and the molecular genetic analysis of courtship song.

One of Hall's studies of a gene affecting courtship song, the period gene, led him into his second major set of contributions. In 1979, the genetic study of circadian rhythms had ground to a virtual halt after the initial pioneering studies of Ron Konopka, which had also commenced Benzer's laboratory. After his postdoc Bambos Kyriacou noted that courtship songs from wild-type Drosophila melanogaster males have a rhythmic component with a period of about 1 min, Hall wondered whether Konopka's period mutants, which affected the circadian 24-hr oscillation of behavior, might affect these rhythmic oscillations. Their subsequent findings—that period short-day mutants also had a shorter song cycle, long-day mutants had a longer song cycle, and the song rhythm of arrhythmic mutants was obliterated—launched the extensive series of studies on the genetics of circadian rhythms from the Brandeis group that helped rejuvenate the field and led to the fundamental insights into circadian biology that are so well known today.

Early on, Hall engaged another Brandeis biologist, Michael Rosbash, in the project, and together they inaugurated the molecular genetics of period (also independently undertaken by Michael Young at Rockefeller University). By focusing initially on the biology of the gene's action, these studies resulted in the key discoveries of the pacemaker cells in the fly's brain and the oscillation of period's protein in them. Subsequent demonstration of period's mRNA cycling established its role in the self-sustained autoregulatory feedback loop that provided the core of the circadian clock mechanism—an insight that broke open the problem. In his ongoing collaboration with Rosbash and others, Hall has continued to hammer away at the anatomy and physiology of the fly's pacemaker cells, using genetics as the key tool to dissecting the neurobiology of the clock. He has also sustained the hunt for new clock genes by means of forward genetic screens using a variety of methods such as luciferase reporting. These efforts have resulted in the identification of the pacemaker neurons and the neuropeptide that controls locomotor rhythms, the isolation of mutants identifying two genes, cycle and dClock (née Jerk) that encode transcription factors that control the expression of period, and the isolation of a mutation in the cryptochrome gene, identifying it as the fly's accessory circadian photoreceptor. Throughout this work, Hall has set the standard for care, rigor, completeness, and scholarliness that is unsurpassed in modern behavioral genetics.

Hall's original motivation for undertaking the molecular analysis of period was to test an idea on the genetic basis for evolutionary differences in behavior. He and Kyriacou had mapped a song rhythm difference between D. simulans and D. melanogaster to the X chromosome, where, coincidentally, the period locus resides. With the cloned gene in hand, the experiment that allowed a period gene from one species to "replace" that from the other became possible. The results were spectacular in that a D. melanogaster male host carrying a D. simulans period gene would now sing with the D. simulans song cycle. Similar interspecific transformation studies from the Brandeis group also showed that the species-specific differences between D. melanogaster and D. pseudoobscura locomotor rhythm patterns are also controlled in an all-or-none manner by period. The results from these two sets of studies demonstrated that interspecific differences in adaptive behavior can be transferred between species by means of a single gene, period. The implications for evolutionary mechanisms of Hall and his collaborators' experiments, although under-appreciated at present, may well turn out to be the most profound.

Aside from these scientific accomplishments, Hall occupies a unique position as the conscience of his discipline. He treats collaborators, colleagues, and competitors with a degree of integrity, honesty, openness, and generosity that is rare. He has extended himself to help younger scientists in their careers, whether or not they were his own students or postdocs, actively engaged in discussions, controversies, and arguments to get to the bottom of any issue, and fearlessly held all (whether junior, peer, or senior) to the highest standards of scientific behavior, sometimes to his own detriment. He is that rarity among scientists, in any era, who combines the strive for excellence with the penchant to do the right thing.

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