Nobel Prize Honors Discoveries of Cell Cycle Regulators

	In Stockholm, Dr. Lee Hartwell (left) accepts the Nobel Prize from Swedish King Carl XVI.

Coming of age in California in the 1950s, Lee Hartwell seemed an unlikely future prospect for a Nobel Prize in medicine or physiology. His life revolved around sports and cars.

However, as a young boy he had frequently asked how things, like the neon lights his father installed, worked. Bugs and reptiles had fascinated him, and he read about them in the local library. His desire to learn about the fundamental workings of the natural world resurfaced in his late teens, at about the time that he became unhappy with football and bored with his car club.

When Hartwell asked to attend a different high school, his mother moved the family to an apartment across town and near the school. There his teachers encouraged him. He found he liked math, physics, and mechanical drawing, and he considered becoming an engineer. Upon enrolling at Glendale Junior College, he became the first person in his family to attend college. Noticing his talent, his instructors helped him transfer to the California Institute of Technology.

“In college I experienced real science,” Hartwell wrote in his Nobel Laureate biography, referring to the opportunity to do laboratory research. After completing a Ph.D. degree at the Massachusetts Institute of Technology (MIT), he went to the Salk Institute to study the control of cell growth. None of his three projects worked out as a start to his own research. He left after only 18 months to join the faculty at University of California, Irvine.

While waiting for his equipment to arrive, he tried to figure out a project with possibilities for reaching basic insights on the control of DNA synthesis. A colleague suggested picking an organism that could be a model for genetic studies of cell growth. Hartwell’s reading led him to select simple baker’s yeast. He visited other scientists to learn how to work with yeast cells.

He began his studies by isolating temperature-sensitive mutant yeast, and analyzing their cell division. Through this approach, which he continued after joining the UW faculty in 1968, he identified nearly 100 genes involved in cell cycle control, the cell division cycle (CDC) genes.

One of these genes has a key role in controlling the first step of each cell cycle. Hartwell found that the cell cycle also contains checkpoints, where the cell stops to look for errors and fix mistakes before entering the next phase of the cycle. Hartwell extended the checkpoint concept to include controls that keep the cell cycle phases in correct order.

Genes similar to those controlling cell division in yeast also control cell division in humans. These genes are often altered in cancer cells. Besides having poorly controlled cell division, cancer cells are genetically unstable.

Hartwell’s findings suggest how chromosomal instability develops in cancer cells, particularly how parts of chromosomes might be rearranged, lost, or distributed unequally between daughter cells during defective cell cycle control.

For his investigations of key regulators of the cell cycle, Hartwell received the 2001 Nobel Prize in physiology or medicine. He shared the prize with Paul Nurse and Timothy Hunt, both of the Imperial Cancer Research Fund in London.

Hartwell is a UW professor of genomic sciences and adjunct professor of medicine. In 1996 he joined the Fred Hutchinson Cancer Research Center and became its president and director in 1997.

Hartwell is the Fred Hutchinson Cancer Research Center’s second Nobel Laureate. In 1990 Dr. E. Donnall Thomas was given the prize in physiology or medicine for his work in bone-marrow transplantation. Thomas is director emeritus of Fred Hutchinson’s Clinical Research Division and a UW professor emeritus of medicine and oncology.

The UW has three other Nobel Laureates: Dr. Hans Dehmelt, who received the 1989 prize in physics for the ion trap technique; and Dr. Edmond Fischer and Dr. Edwin Krebs, who received the 1992 prize for discovering protein phosphorylation-dephosphorylation, a switching mechanism in cells.