Every time you breathe in, you supply your body’s cells with the oxygen they need to convert food into energy. Scientists have long known that cells must sense how much oxygen is available to adjust their metabolic rates, so they can efficiently and safely burn fuel to build new tissues after an injury, do their daily chores as a liver cell or neuron, say, and keep you a toasty 98.6 degrees Fahrenheit. But for most of the 20th century, the mechanisms behind this process remained a mystery.
Today, the Nobel committee kicked off its 2019 season by awarding the Nobel Prize in Physiology or Medicine to three scientists—William G. Kaelin Jr., Peter J. Ratcliffe, and Gregg L. Semenza—for their work uncovering the molecular switch that regulates how cells behave when oxygen levels drop. Their discoveries of the ways cells sense and adapt to changing oxygen availability didn’t only uncover the fundamental machinery behind one of life’s most essential processes. They paved the way for promising new drugs to treat anemia, cancer, and many other diseases.
Throughout the 1990s and 2000s, Kaelin, Ratcliffe, and Semenza worked separately to decode the actions of an oxygen-sensitive protein called HIF, for hypoxia inducible factor. They teased apart the network of molecules that direct the proteasome, the cell’s garbage disposal, to destroy HIF in high-oxygen conditions. When oxygen levels drop, the same system causes HIF to rise, cranking up the production of a hormone that in turn triggers the production of red blood cells and blood vessels.
“This kind of basic discovery impacts every aspect of the body,” said Randall Johnson, a member of this year’s Nobel committee, at the award’s announcement at the Karolinska Institute, in Stockholm, on Monday. “The applications will be very wide.”
A drug that hacks the molecular pathways identified by the winners has already been approved in China for treating anemia, by amping up the body’s red blood cell activity. Other drugs that rely on their work are also in development for the treatment of certain cancers. Tumors often have low oxygen levels, and some cancers have developed ways of overriding the HIF system to attract blood vessels to support their rapid growth.
Kaelin has been a cancer biologist at the Dana-Farber Cancer Institute, in Boston, since 1991. In 2002, he became a full professor at Harvard Medical School, and he has also been an investigator of the Howard Hughes Medical Institute since 1998.
Ratcliffe established a new laboratory dedicated to hypoxia biology at Oxford University in 1990 and became a full professor there in 1996. He also directs clinical research at the Francis Crick Institute, in London.
Semenza joined the faculty of Johns Hopkins University in 1990, where he established a lab to study the molecular mechanisms of oxygen homeostasis. Since 2003 he has also directed the Vascular Biology Research Program at the university’s Institute for Cell Engineering.
The three laureates will share the 9,000,000 Swedish krona (almost $1 million) prize equally.
Comments