From toothpicks and yeast to 'how we think about life'

Nobel honor comes as 2:30 a.m. 'shock' to Center president and director, who will receive shared prize at 100th-anniversary ceremony Dec. 10
Dr. Lee Hartwell at Nobel Prize press conference
Dr. Lee Hartwell, Center president and director, answers questions at a press conference at the Hutch seven hours after he was notified that he had won the Nobel Prize in physiology or medicine. Photo by Michelle Hruby

Dr. Lee Hartwell didn't realize as a child that his youthful predilection for chasing butterflies might be a sign he was a natural-born scientist.

Nor did he anticipate that the simple, single-celled organism he chose as the cornerstone of his research 30 years ago would teach the world something about the unity of life.

Any lingering doubts were erased on Monday, Oct. 8, when Hartwell, Hutch president and director, was awarded the highest honor for outstanding contributions to basic and clinical medical research: the 2001 Nobel Prize in physiology or medicine.

The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, selected Hartwell for his pioneering work in yeast genetics.

Hartwell, also professor of genetics and medicine at the University of Washington, shares the honor with Drs. Paul Nurse and Timothy Hunt, both of the Imperial Cancer Research Fund in London, England. The researchers will share the $934,000 award on Dec. 10, the 100th anniversary of the death of Alfred Nobel, after whom the award is named.

Hartwell received the news about 2:30 a.m., when a phone call from the Hutch media-relations office awakened his wife, Theresa Naujack.

"We were shocked," he told media representatives seven hours later at a press conference in the Center's Sze Conference Room."We're still shocked."

Hartwell, who conducted his groundbreaking research at the UW beginning in 1968, is being honored for the discovery of the universal mechanism that controls cell division in organisms with nucleii, from yeast to frogs to humans. Using simple baker's yeast, Saccharomyces cerevisiae, as a model organism, he was the first to harness the tools of genetics to study how cells function - to determine which genes cause cells to divide.

His colleagues consider this accomplishment a landmark.

"This is the most prestigious award in all of biology," said Dr. Mark Groudine, director of the Basic Sciences Division. "It is awarded to someone who has changed the way we think about life itself.

"Lee's work is a fundamental contribution to our understanding of how cells divide. He had theinsight to realize that genetics could be used to study something as complex as cell division and demonstrated that simple model organisms are paradigms for our understanding of more complex organisms, including humans."

Fundamental to understanding

The regulation of cell division - how cells determine when and how to multiply or otherwise develop, and how that process can go awry - is fundamental to understanding how cancer cells mutate and to developing approaches that predict, prevent or reverse that mutation.

"People just didn't understand the fundamentals of cell-division regulation until Lee came along," said colleague Dr. James Roberts, an investigator in the Center's Basic Sciences Division.

"What Lee did 25 years ago was essentially provide us with a list of all the important genes involved in controlling cell proliferation. This has proven invaluable in interpreting and using today's gene-sequence data.

"Second, Lee provided a logical framework to understand how these genes cooperate and work together to control cell division. Thus, he was not merely a cataloger of genes, but he also was able to explain how they worked."

Hartwell decided more than 30 years ago to study yeast cells because they are simpler and easier to manipulate than human cells.

"The most sophisticated equipment we used then was a toothpick to transfer yeast cells to Petri plates," he said.

In the early days, Hartwell recalled, using yeast as a model was "a fairly risky assumption," as he was the only person using this organism to find genes that control cell development.

Today, what holds the most special meaning for him about his work is that his studies of yeast have helped to illustrate the unity of life.

"We studied yeast because at that time we couldn't study human cells," he said. "We had no confidence that the two would be so similar. It is the common evolutionary heritage of all organisms that has enabled the tremendous amount of medical information that has come from the study of simple model systems."

Superb model

Thanks to Hartwell's groundbreaking efforts, scientists now know that yeast is a superb model for studying many basic cellular processes, since its cellular machinery is found in virtually all nucleated organisms.

More recently, Hartwell and his colleagues have used yeast to develop novel methods for identifying drugs to use against cancer and other diseases.

Today, Hartwell's research interests are focused on the importance of genetic diversity, a topic that he said has been overlooked by scientists.

"As geneticists, we've been working with highly inbred organisms in the laboratory so that we can see the contributions of a single mutation to a cell or organism's ability to function," he said. "But we've neglected the diversity of humans. We're all genetically different, as are all organisms in the wild. I'd like to know what that genetic diversity means for an organism."

Diversity is equally important in the cancer-research community's efforts to develop effective relationships with private enterprise and with the public.

"It takes a partnership between the people who participate in clinical trials and donate tissue samples, academic institutions like our own and private enterprise that develops new technologies to really advance cancer research," he said.

Hartwell joined the UW faculty in 1968 and has been a professor of genetics there since 1973. He also is an adjunct professor of medicine at UW. In 1996, he joined the faculty of the Hutchinson Center as senior adviser and in 1997 became its president and director.

He has received many national and international scientific awards for his work in cell-cycle biology, including the Leopold Griffuel Prize, the Massry Prize, the American Cancer Society's Medal of Honor Basic Research Award, the Albert Lasker Basic Medical Research Prize, the General Motors Sloan Award and the Gairdner Foundation International Award for Achievements in Science. He also is a National Academy of Sciences member.

Since 1901, Nobel Prizes have been awarded annually on Dec. 10, the anniversary of the death of Alfred Nobel, the Swedish-born inventor and international industrialist for whom the award is named. In addition to physiology or medicine, Nobel Prizes are awarded in physics, chemistry, literature, economic sciences and peace.

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