OCTOBER 7, 2019, New York— Ludwig Cancer Research congratulates Peter Ratcliffe on his receipt of the 2019 Nobel Prize for Physiology or Medicine. He was recognized by the Nobel Committee for his landmark discoveries on the mechanisms by which mammalian cells sense and respond to the availability of oxygen.
A Member of the Oxford Branch of the Ludwig Institute for Cancer Research, Ratcliffe shares the prize with U.S. researchers William Kaelin of the Dana-Farber Cancer Institute and Gregg Semenza of Johns Hopkins University. Their discoveries, which were made largely independently through the 1990s, have had a profound influence on our understanding of biological processes and disorders ranging from heart disease to wound-healing to cancer.
“Despite his modesty and self-deprecating sense of humor, Peter has long been known to us at Ludwig as a scientist of rare quality and creativity, as well as a delightful, generous colleague,” said Chi Van Dang, scientific director of the Ludwig Institute for Cancer Research. “We are, of course, thrilled to learn that he received the Nobel Prize and this well-deserved recognition. Peter’s previous contributions have been very important to science and medicine. But it’s also clear, given the work he’s published just this past year, that Peter isn’t quite done with making important discoveries. Stay tuned for more.”
Soon after completing his training in nephrology at Oxford University in the late 1980s, Ratcliffe grew curious about the body’s ability to respond to subtle changes in tissue oxygen levels. The kidneys were then believed to be central to oxygen sensing due to their production of the hormone erythropoietin (EPO), which stimulates the generation of oxygen-carrying red blood cells. In hunting for the genetic element that drives EPO production, Ratcliffe and his colleagues discovered in 1991, much to their surprise, that all cells of the human body seemed equipped to respond to hypoxia, or oxygen starvation.
The discovery transformed Ratcliffe’s research career, drawing him into a trans-Atlantic race with Semenza and Kaelin to identify the molecular sensor responsible for that capability. Over the next decade, the three researchers built sequentially on discoveries made in each of their labs to identify this universal cellular oxygen sensor. The gene expression driven by oxygen starvation was reported by Semenza’s lab to be governed by proteins known as hypoxia-inducible factors (HIFs), though how they were controlled remained a mystery. Ratcliffe and his team discovered how that control occurs and described the elegant mechanism by which a set of enzymes directly link the oxygen supply to HIF activity. Their findings were simultaneously confirmed by Kaelin and his colleagues.
Ratcliffe has since methodically unraveled the molecular pathways of oxygen sensing and explored their effects on a variety of biological processes, most notably cancer: oxygen starvation at the core of solid tumors is known to contribute significantly to drug resistance and metastasis. Ratcliffe’s discoveries continue to illuminate new approaches to treating cancer, heart disease and a variety of other illnesses.
Some variation of the oxygen-sensing system Ratcliffe discovered has since been found in all animals. More recently, he and his colleagues reported in Science their discovery of an entirely novel cellular oxygen sensor—one so ancient in its evolutionary origins that it is shared by plants.
For more on Peter Ratcliffe and his research career, see this profile in the Ludwig 2019 Research Highlights report.
In addition to his position at the Ludwig Institute, Ratcliffe is the director of the Target Discovery Institute at the University of Oxford and the clinical research director at the Francis Crick Institute.