On October 7, William G. Kaelin Jr., the Sidney Farber Professor of Medicine at HMS and Dana-Farber Cancer Institute and senior physician in medicine at Brigham and Women’s Hospital, received an early morning call from Sweden. Foggy with sleep, he listened as the caller from the Royal Swedish Academy of Sciences told him he had won the 2019 Nobel Prize in Physiology or Medicine.
Kaelin shares the award with Peter J. Ratcliffe of the University of Oxford and the Francis Crick Institute and Gregg L. Semenza of the Johns Hopkins University School of Medicine. The trio was cited for the discovery of the pathway by which cells from humans and most animals sense and adapt to changes in oxygen availability, a process essential for survival.
When, in 2001, Kaelin worked out the final details of the mechanism through which cells sense variations in oxygen levels, he said it was very gratifying, as there had been an array of varied, complex theories about how cells sense oxygen.
“When we saw the signal and understood what it meant, it was much simpler than expected,” Kaelin said. “We see it conserved across metazoan evolution.”
Kaelin’s research explores why mutations in genes known as tumor suppressors can lead to cancer. His study of the tumor-suppressor gene VHL provided key insights into the body’s response to changes in oxygen levels. He discovered that VHL helps control the levels of a protein known as HIF-1-alpha, which ratchets up or down the response to low oxygen, by helping spur the production of red blood cells and new blood vessels. His subsequent discovery of a molecular switch that renders HIF-1-alpha oxygen-sensitive was critical to the understanding of how cells react to variations in oxygen level.
This distinguished award joins other recognitions Kaelin has shared with his co-laureates, including the 2016 Lasker Award for Basic Medical Research and the 2010 Canada Gairdner International Award.
Image: Stephanie Mitchell/Harvard University