Dr. Lee Hartwell awarded Nobel prize for yeast genetics research

For biology professor Wendy Raymond and her fellow yeast geneticists worldwide, this month brought long-awaited but nonetheless thrilling news. On Oct. 8, the Nobel Assembly in Stockholm, Sweden awarded Dr. Leland Hartwell the 2001 Nobel Prize in Physiology or Medicine for his pioneering work in yeast genetics. He shares this award with Paul Nurse and Timothy Hunt, both of the Imperial Cancer Research Fund in London, England.

A faculty member at the University of Washington since 1968 and a professor of genetics there since 1973, Hartwell, who presently serves as president and director of the Fred Hutchinson Cancer Reasearch Center in Seattle, has been just as influential for his dedication to training new researchers as for his own work in the field. Among the enthusiastic proteges spawned by Hartwell’s lab is Dr. Raymond, who worked as a post-doctoral student under Hartwell from 1990 to 1994.

“Lee Hartwell is the smartest person I’ve ever met,” Raymond said. “For me, he is a role model of someone who is immersed in and loves thinking about biological problems, but whose life is not subsumed by such thinking? He is not a self-promoter- he generally lets his work speak for itself ? yet his work has influenced the research of thousands of scientists. Lee is a regular guy with extraordinary intellectual gifts.”

More than 30 years ago, Hartwell recognized in baker’s yeast the same stuff used in making bread and beer ? the potential to serve as an outstanding model organism with which to study the cell division process. Yeast, or Saccharomyces cerevisiae, divides rapidly, producing a daughter cell that arises as a bud on the cell surface. The ratio of bud to parent cell size thus serves as a clear visual marker of the position of the cell in the cycle. In addition to being much easier to manipulate than human cells, yeast cells offer a superb way to study basic cellular processes since their cellular machinery is conserved in virtually all nucleated organisms.

A common approach used by geneticists when studying a biological mechanism is to look for mutants ? cases in which the mechanism has gone awry. However, because cell division is such a fundamental life process, an obvious problem with this approach is that cell cycle mutations often mean death to the organism. Thus, one of Hartwell’s first achievements was in finding a way around this experimental obstacle. He did this by looking specifically for yeast colonies that became “stuck” at a certain point in cell division when exposed to a high temperature (36º C), but that could grow and divide normally at a low temperature (23º C). Each of the temperature-sensitive mutants he isolated represented a block at a particular stage in the cell cycle. Thus, the gene responsible for each mutation must code for a protein product with an essential role in the cell division process. These cell-division-cycle, or cdc genes, have since proven invaluable to cancer research, as they basically represent all the important genes involved in controlling cell proliferation.

Not content to be a mere cataloguer of genes, Hartwell began to investigate the bases for accurate cell reproduction in the 1980s. His research centered on the question of how a cell copies its genetic information faithfully and divide in two without transmitting potentially lethal genetic errors. Along with co-researcher Ted Weinert, Hartwell imagined a sort of “checkpoint” control system that could ensure that a cell cycle event had been successfully completed before the cycle continued. By looking for mutants that showed uncontrolled cell division ? essentially cancerous growth ? they discovered a number of these cell cycle checkpoint genes.

The cdc genes governing cell-division, as well as the ordered collection of ?checkpoint? genes that regulate them, are becoming increasingly relevant as researchers pursue novel ways to target cancer and birth defects in which cell division goes awry.

Lee Hartwell’s 35 years of research in yeast has led to a deeper understanding of normal cellular function and the molecular basis of disease, an accomplishment certainly worthy enough in itself for a Nobel prize. But according to Raymond, Hartwell’s greatest contribution to biology has been in the imaginative and elegant way he approaches the problems of science. His extraordinary creativity, when coupled with his long dedication to teaching has inspired and enabled a generation of yeast researchers to go on and make advances of their own. One might say that Lee Hartwell has truly fostered a budding yeast community.