Biologists who decoded how cells sense oxygen win medicine Nobel

A trio of researchers has won the 2019 Nobel Prize in Physiology or Medicine for describing how cells sense and respond to changing oxygen levels by switching genes on and off — a discovery that has been key in understanding human diseases such as cancer and anaemia.

The three scientists are cancer researcher William Kaelin at the Dana-Farber Cancer Institute in Boston, Massachusetts; physician-scientist Peter Ratcliffe at the University of Oxford, UK, and the Francis Crick Institute in London; and geneticist Gregg Semenza at Johns Hopkins University in Baltimore, Maryland. The team also won the Albert Lasker Basic Medical Research Award in 2016.

Their work has helped researchers to understand how the body adapts to low oxygen levels by, for example, cranking out red blood cells and growing new blood vessels.

“This is a fundamental discovery that they’ve contributed to,” says Celeste Simon, a cancer biologist at the University of Pennsylvania in Philadelphia. “All organisms need oxygen, so it’s really important.”

“The field really coalesced around this discovery, which was dependent on each one of their findings,” says Randall Johnson, a physiologist at the University of Cambridge, UK, and the Karolinska Institute in Stockholm, and a member of the Nobel Assembly. “This really was a three-legged stool.”

The body’s tissues can be deprived of oxygen during exercise or when blood flow is interrupted, such as during a stroke. Cells’ ability to sense oxygen is also crucial for the proper growth of a developing fetus and placenta, and it’s also important for tumour growth, because the mass of rapidly growing cells can deplete oxygen in the interior of a tumour.

In work conducted in the 1990s, the scientists discovered the molecular processes that cells go through to respond to oxygen levels in the body. They found that central to this is a mechanism involving proteins called hypoxia-inducible factor (HIF) and VHL.

Semenza and Ratcliffe studied the regulation of a hormone called erythropoietin (EPO), which is crucial for stimulating the production of red blood cells in response to low levels of oxygen. Semenza and his team identified a pair of genes that encode the two proteins that form the protein complex HIF, which turns on certain genes and boosts EPO production when oxygen is low.