Seattle Geneticist Wins Nobel for Work on Cell Division
For discovering how cells divide--work that goes to the heart of understanding the chaotic, lethal growth of cancer--a Seattle geneticist and two British scientists shared the 2001 Nobel Prize in Medicine on Monday.
On the 100th anniversary of what is considered the world’s most prestigious award, Leland H. Hartwell--born in Los Angeles, schooled in Glendale, educated at Caltech, mentored at the Salk Institute, and now head of Seattle’s Fred Hutchinson Cancer Research Center--awoke to find himself an instant icon of human progress.
Hartwell will share the $943,000 prize purse with Sir Paul Nurse and Timothy Hunt at the Imperial Cancer Research Fund in London.
Together, their work offered the first clear understanding of how cells grow, divide and multiply, in a basic molecular ballet of life common to all complex organisms.
Working independently, the three pioneers “opened up a new chapter in cancer research, and it’s fantastic that this has been recognized in this way,” Hunt said.
In a series of independent discoveries starting in 1970, the three cancer researchers showed that the same underlying mechanism controls cell division in all organisms, from the simplest fungus to the living constellation of 100,000 billion cells that comprise a human being.
Their work offers an avenue into what goes wrong when healthy cells suddenly go haywire and grow out of control, as happens in cancer, and offers the possibility of correcting it.
Their discoveries are of “central importance” to biology and medicine, the Nobel Assembly at the Karolinska Institute in Stockholm, which makes the prize selections, said in its citation. “This may in the long term open up new possibilities for cancer treatment.”
Their discoveries triggered an explosion of new research as scientists and pharmaceutical companies sought to find ways to block or repair the cells that go awry in breast cancer and brain tumors.
Several experimental drugs based on the work of the three winners--all aimed at inhibiting tumor growth--are in clinical trials.
Hartwell was sleeping in Seattle when a staff member at the research center called and woke his wife at 2:45 a.m. “You won’t believe this,” she said, rousing Hartwell from bed. The Nobel Committee had been trying to contact him for hours but couldn’t find his unlisted phone number. The staff member saw the announcement on the Nobel Foundation’s Web site and called with the news.
“It struck like a thunderbolt,” Hartwell said.
Nurse, director of the Imperial Cancer Research Fund, learned of his Nobel Prize from a voicemail message left on his cell phone. As he digested the news in the middle of a business meeting, he was “not too coherent,” he said. “I couldn’t quite believe it was true.”
Nurse said he might treat himself to a new motorcycle, then donate the rest of his prize money to cancer research.
“I am over the moon to win this award,” said Hunt in London.
The work was hailed by others in the field. “For many years, people have thought that the key for understanding the cancer problem would be understanding the cell cycle in its complete manifestation. And it has turned out to be a big chunk of the problem,” said Steven Smith, professor at City of Hope Medical Center in Duarte.
“The work they did has given us kind of a map of how the cell cycle works--in terms of what are the control points, what are the decisions that have to be made by the cell in deciding whether it’s ready to commit to cell division.”
Each scientist took his own approach to the problem of cell growth, seeking in the natural kingdom’s smallest and simplest citizens the biochemical secret of growth and development.
Hartwell led the way through his study of how genes regulate the growth of one-celled baker’s yeast, while Nurse investigated the life cycle of a similar type of yeast called Saccharymyces cerevisiae. Hunt used spiny sea urchins to understand how levels of some crucial proteins called cyclins rise and fall as a cell grows and divides.
“You could do such fantastic experiments with yeast, such beautiful experiments,” said Nurse in London. “You could really make progress in understanding the fundamental mechanism of life.”
In the 1970s, Hartwell and his laboratory colleagues were the first to use the emerging tools of molecular biology to identify and isolate the genes that control the way that cells grow and multiply.
“It was quite mysterious at the time,” Hartwell said. “There was some faith involved.” At the time, “we did not know if the way the yeast cells did it was the same way that human cells did it.”
His experiments encompassed a decade or more of work at the cancer center and at the University of Washington, where he is now a professor of genetics and medicine.
Eventually, he discovered more than 100 of what are called regulatory genes. He also developed a sense of how cells monitored their own internal well-being, allowing them to check their growth temporarily when DNA damage arises and to repair the damage before moving on to the next phase of the growth cycle.
“People just didn’t understand the fundamentals of cell-division regulation until Lee came along,” said Dr. James Roberts, a Howard Hughes Medical Institute investigator. “He was not merely a cataloger of genes, but he also was able to explain how they worked.”
Working along similar lines in London, Nurse discovered a key gene in his yeast species that helped control cell division. He quickly showed that it was identical to a gene that Hartwell had isolated earlier in his yeast organisms. The gene gives cells the instructions to produce a protein belonging to a family called cyclin dependent kinases, or CDK. The gene was dubbed CDK1.
Then in a crucial breakthrough, Nurse demonstrated that the same gene also regulated human cell growth. In the years since, researchers have found a half-dozen different CDK molecules in human cells.
“Paul picked the right gene,” Hartwell said. “He unified the whole thing across all biology by doing a superb job of studying this one gene. He showed it was generalized to all cells.”
In the early 1980s, Hunt, head of the cell cycle control laboratory at the Imperial Cancer Research Fund, discovered proteins in sea urchins that bind to the CDK molecule to moderate or enhance its activity during each cell cycle. Together, the CDK molecule and the newly discovered substance drive the cell from one phase of its growth cycle to the next. The new molecules were named cyclins because the levels of these proteins vary periodically during the cycle.
Hunt later discovered cyclins in other species, showing that they too were integral cogs in the universal cell machinery. Today, 10 different cyclins have been found in humans.
Taken together, the findings give cancer researchers a way to approach the genetic instability responsible for many forms of cancer.
“It helps us understand the disease much better,” Nurse said. “It may give us much more subtle and specific ways of combating it.”
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Times medical writer Rosie Mestel contributed to this report.
