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Nobel Laureate Medicine 2019: Peter Ratcliffe

Peter Ratcliffe Photo jenny Öhman Nordic Life Science
Sir Peter J. Ratcliffe defined a system involved in inflammation, metabolism, cancer, and more. On 7 October 2019, Sir Peter J. Ratcliffe was having a typical scientist’s day, writing a grant proposal. Then, Ratcliffe, who is Director of Clinical Research at the Francis Crick Institute and Director of the Target Discovery Institute at the University of Oxford, got a call. The Nobel Committee told him that he, William Kaelin of Harvard University, and Gregg Semenza of Johns Hopkins University were awarded the Physiology or Medicine prize for “discoveries of how cells sense and adapt to oxygen availability.” We still have much to learn in this area, Ratcliffe says: “Maintaining oxygen homeostasis across the 40 trillion cells in the body requires great precision and accuracy. Even a short lapse in oxygen causes trouble.” Fortunately for the field, he finished the grant proposal, with his coapplicants Drs. Peppi Karppinen and Johanna Myllyharju from University of Oulu in Finland taking over writing while he handled the Nobel publicity. The Oulu scientists took time to celebrate, though. They learned of the award during a campus event to watch the Nobel announcement live. “We guessed as soon as they said ‘William’,” Myllyharju says. The event was chaired by Karppinen, who did postdoctoral work with Kaelin. “Johanna and I quickly organized a celebration for our research groups,” she says. “We toasted the Nobels and sent photos to Bill [Kaelin] and Peter.” Surprisingly widespread The details of how cells sense and respond to lack of oxygen, or hypoxia, were a mystery before the Nobel-winning work. The Ratcliffe, Semenza, and other groups studied how hypoxia increases transcription of the gene for erythropoietin (EPO), a kidney hormone that signals for more red blood cells. The Ratcliffe lab showed that cells that do not produce EPO use the same mechanism, operating on different genes, to respond to hypoxia. “The discovery that this system operates in a widespread fashion meant it doesn’t just regulate EPO but does countless other things. This implied physiological importance in all sorts of cells and potential importance in medicine.” “The discovery that this system operates in a widespread fashion,” Ratcliffe says, “meant it doesn’t just regulate EPO but does countless other things. This implied physiological importance in all sorts of cells and potential importance in medicine.” That impact is seen today in drugs targeting the hypoxia-response system that are in use or development for anemia, cardiovascular disease, cancer, and more.   The hypoxia system is complex. The Semenza lab found the crucial transcription regulator: hypoxia-inducible factor (HIF). The Kaelin lab discovered that
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