Robert H. Waterston, M.D., Ph.D.
William H. Gates III Endowed Chair in Biomedical Sciences
Professor and Chair, Department of Genome Sciences
Robert Waterston was born in 1943 in Detroit, Mich. He went to Princeton as an undergraduate, where he majored in engineering while spending as much time as possible studying the humanities; he wrote his senior dissertation on the plays of Eugene O’Neill. By this time, he was thinking of switching to medicine but had never studied biology.
While on what might now be called a “gap-year” visit to Germany, he took courses in biology — in German — and returned to take up a place at the school of medicine of the University of Chicago.
By 1972, he had acquired both M.D. and Ph.D. degrees from the University of Chicago, as well as a taste for research. “I was more interested in advancing medicine than going into practice,” he says. A chance meeting with Sydney Brenner on a physiology summer school at the Woods Hole Marine Biological Laboratory in 1969 had introduced him to the grand project then beginning at the Medical Research Council’s Laboratory of Molecular Biology (LMB) in Cambridge, England: to understand life at the molecular level through studying the nematode worm Caenorhabditis elegans. At the earliest possible opportunity, Waterston left for Cambridge to become the third American post-doctoral researcher to join Brenner’s group.
Brenner was looking for worms with mutations that affected their behavior as part of the search for genes that control muscles and the nervous system. Waterston took on the task of looking for abnormalities in the muscle mutants at the molecular level, and, within a few years, he had made discoveries that led to the cloning of genes for two important muscle proteins.
Waterston returned to the U.S. in 1976 as an assistant professor of anatomy and neurobiology at Washington University in St. Louis, and he set up a lab dedicated to studying the molecular biology of muscle in the worm. There, he and his colleagues identified many more muscle genes and investigated their role in muscle assembly and contraction, as well as discovering and analyzing transposable elements and nonsense suppressors. A few years later, he switched to the department of genetics; in 1991, he became chair.
In the mid-1980s Waterston made a sabbatical visit to the LMB, ostensibly to continue his work with Brenner. But the only space available was in the room where John Sulston and Alan Coulson were beginning to map the worm genome. Waterston joined them. After his return to St. Louis, the worm map became a collaborative project between the two labs.
In 1989, one of the first Human Genome Project grants went to Waterston and Sulston to begin the sequencing of the worm genome. They were so successful that, at the same time that the Wellcome Trust established the Sanger Centre with Sulston at its head, Waterston received funding from the National Human Genome Research Institute to undertake large-scale human sequencing at his Washington University lab. The partnership became the first to complete the sequence of a multicellular organism when the worm genome was published in December 1998. Both labs also played key roles in the sequencing of the human genome, with Waterston’s lab contributing more of the finished sequence than any other U.S. lab. The partnership went on to have a leading role in the sequencing of both the mouse and chimpanzee genomes.
Waterston, like his colleague John Sulston, has always been committed to the free release of scientific information, and he was an influential voice in establishing the Bermuda Principles on data sharing in 1996. In the past few years, Waterston and Sulston have jointly won numerous awards for their scientific work and their support for the scientific community, including the Gairdner Award, the General Motors Prize, the Dan David Prize and the George W. Beadle Medal of the Genetics Society of America. Waterston also received the Gruber Prize in Genetics.
In January 2003, Waterston moved from St. Louis to become the first chair of the then-new Department of Genome Sciences at UW Medicine in Seattle. As the William H. Gates III Endowed Chair in Biomedical Sciences, he is leading research into the genetic control of development in the nematode. He has developed novel technology to automatically decipher the dynamic expression of genes with single-cell resolution and minute-time resolution and applied the technology to describe the expression patterns of more than 200 transcription factors.
As part of the National Human Genome Research Institute’s modENCODE project, he and his collaborators have collected data that accurately defines the full complement of both protein- coding and non-coding genes of the nematode. In another modENCODE project, he and collaborators are defining the binding sites for those transcription factors. They are now combining these sets of data to construct increasingly complete regulatory networks directing C. elegans embryonic development. Recently, he has used next-generation sequencing methods to develop a collection of mutant C. elegans strains, containing more than a million mutations, to probe the function of the more than 20,000 C. elegans genes. As chair, he has overseen the development of the Department of Genome Sciences, now a world leader in the field.
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