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Nobel Prize Awarded for Discoveries on How Cells Adapt to Oxygen
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    [Image: Portrait of William G. Kaelin]  
    William Kaelin Jr.


    [Image: Portrait of Peter J. Ratcliffe]  
    Peter Ratcliffe

    University of Oxford

    [Image: Portrait of Gregg L. Semenza]  
    Gregg Semenza

    Johns Hopkins Medicine

    William Kaelin Jr. (left), Peter Ratcliffe (center) and Gregg Semenza were awarded the 2019 Nobel Prize in Physiology or Medicine.

    HHMI; University of Oxford; Johns Hopkins Medicine

    Scientists now target this machinery in the development of treatments for anemia, strokes, cancer and other conditions in which oxygen levels seem to be critical.

    Perhaps equally tantalizing is that this mechanism — or at least a much simpler version of it — is responsible for what life on Earth looks like today. Hundreds of millions of years ago, life transformed from mainly microbial organisms to a vastly diverse array that included animals. These creatures had to adapt to rising levels of oxygen in their environment, and scientists are now looking into the role that HIF proteins might have had in that process. Some researchers think the mechanism could lie at the very root of how animals made the jump to the greater complexity we now take for granted — including animals’ ability to form highly specialized tissues, maintain stem cell populations, and expand into new habitats.

    How organisms deal with oxygen, in fact, has been a pivotal factor in evolution for billions of years. “Right there at the beginning, you’ve got a fundamental sort of transition within life where oxygen goes from being toxic to becoming a vital part of our physiology,” said Andrew Murray, a researcher in metabolic physiology at the University of Cambridge. “Of course, the latest challenge then is to respond to fluctuations in oxygen supply, and that’s what this [Nobel-awarded] work has shown.”

    And as always, evolution continues onward. Murray notes that people who have been native to the Tibetan plateau for the past 10,000 years carry a genetic variant for one of the factors interacting with HIF — a variant that helps them survive the high altitude (and low oxygen levels) by suppressing the overproduction of red blood cells. “What’s exciting about this is that this is human evolution in action,” Murray said. “It shows just how fundamental this work is,” and how fundamental it continues to be, for understanding how life thrives.

    This article includes contributions from Elena Renken.

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