October 8, 2019

Two U.S. researchers and a British scientist who discovered how cells sense and adapt to changes in oxygen levels have won this year's Nobel Prize in Physiology or Medicine, the Nobel committee announced on Monday.

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The three individuals who won the prize are:

  • William Kaelin, professor of medicine at Dana-Farber Cancer Institute and Brigham & Women's Hospital, which is affiliated with Harvard Medical School;
  • Peter Ratcliffe, the director of clinical research at the Francis Crick Institute in London and director of the Target Discovery Institute at Oxford; and
  • Gregg Semenza, professor of genetic medicine at Johns Hopkins University.

Research details

The Nobel Committee said the researchers won the award for their role in identifying "the molecular machinery that regulates the activity of genes in response to varying levels of oxygen," which is "one of life's most essential adaptive processes."

Since the 1970s, scientists have known kidneys secrete a protein called EPO that travels to the bone marrow and increases the production of red blood cells when oxygen levels are low, according to STAT News. However, scientists for many years did not understand how kidney cells know when to initiate the process.

Semenza in the early 1990s discovered that EPO functions like other genes and requires a nearby piece of DNA to activate to it. Semenza found that levels of the piece of DNA, which he called hypoxia-inducible factor 1 (HIF-1), rise when cells are deprived of oxygen and then HIF-1 enters the nuclei of the EPO to activate it. Once the EPO gene is activated, the bone marrow produces high levels of red blood cells to make up for the low levels of oxygen.

Ratcliffe and Kaelin then conducted research to determine what regulates HIF-1 and independently discovered a protein, called Von Hippel Lindau (VHL), which destroys HIF-1 when there are normal oxygen levels. The researchers surmised that VHL can't survive when oxygen levels dip too low, allowing the HIF-1 to survive and activate the EPO gene.

Reaction

The researchers' findings "have paved the way for promising new strategies to fight anemia, cancer, and many other diseases," the Nobel committee said.

Bridget Lumb, president of the Physiological Society, said, "Thanks to this research we know much more about how different levels of oxygen impact on physiological processes in our bodies. This has huge implications for everything from recovery from injury and protection from disease, through to improving exercise performance."

Jason Sheltzer, a fellow at the Cold Spring Harbor Laboratory, said oxygen-sensing in cells is "a core process involved in metabolism[,] … the generation of new blood cells" and "a process that goes awry in many tumors." He added that their discoveries "explained a fundamental mystery in biology, and it's also leading to many potential medical applications."

For example, Sheltzer said, "Treatments that increase production of HIF … could help individuals with anemia. In contrast, HIF is frequently overactive in cancer, and HIF inhibitors may be useful to treat these cancer types."

According to BioMedTracker, three biotech firms—Gossamer Bio, FibroGen, and Akebia Therapeutics—are developing treatments based on the researchers' discoveries.

Richard Gaynor, Neon Therapeutics' president of research and development, said the discoveries of Nobel laureates are a "tremendous motivating factor for our scientists."

But, according to STAT News, "building a bona-fide biotech company around a single, specific Nobel Prize-winning discovery is still—necessarily—statistically rare."

That being said, there have been few instances in which laureates' discoveries have turned into treatments. For example, last year's Nobel laureates discovered proteins on immune cells that could destroy cancerous tumorous. Their discoveries led to the development of the cancer treatment Yervoy (Begley, STAT News, 10/7; Sheridan, STAT Plus, 10/7 [subscription required]; Kolata/Specia, New York Times, 10/7).

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