The 2019 prize was awarded to William Kaelin, Sir Peter Ratcliffe, and Gregg Semenza to discover a basic mechanism in animal life: how cells respond to oxygen.
Three scientists have been awarded the Nobel Prize in Physiology or Medicine for their work discovering how cells sense and respond to oxygen, a necessary process for all animal life.
William Kaelin of the Dana-Farber Cancer Institute at Harvard University, Sir Peter Ratcliffe of Oxford University, and Gregg Semenza of Johns Hopkins University were jointly awarded the prize for their discoveries identifying the molecular machinery enabling cells to respond to varying levels of oxygen.
Their research has medical implications in the treatment of anemia and potential new methods of preventing cancer tumor growth.
“These basic discoveries have greatly enhanced our understanding of how the body adapts to change, and the application of these findings is already starting to influence how medicine is practiced,” said Randall Johnson of the Karolinska Institute, on Monday morning at the Nobel Prize Selection Committee in Stockholm. “Three laureates this year have greatly expanded our understanding of how physiological response makes life possible.”
All animal cells are fuelled by oxygen, a necessary ingredient in the process of converting food into usable energy. In 1931, for his research showing that this transformation is an enzymatic process that requires oxygen, the Nobel Prize was awarded to Otto Warburg.
What was not understood was how individual cells experience and respond to oxygen level fluctuations. Cells are continuously experiencing fluctuations in the availability of oxygen, such as when muscles function during exercise, changes in elevation, or even when a wound reduces the flow of local blood.
Low levels of oxygen — also known as hypoxia — cause a spike in the erythropoietin hormone (EPO), resulting in increased red blood cell output.
Semenza of Johns Hopkins University’s earliest work of the three Nobel Prize winners found that this rise in EPO during hypoxia was due to a specific part of the EPO gene called the hypoxia-response component (HRE). Semenza was able to demonstrate that HRE responded to changing oxygen levels using genetically modified mice.
Kaelin of the Harvard Dana-Farber Cancer Institute, independently from Semenza and Ratcliffe’s research on the EPO gene, researched a genetic disease called von Hippel-Lindau’s (VHL) disease associated with a significantly increased risk of certain cancers. Kaelin found that mutations in the VHL gene are associated with higher expressions of hypoxia-regulated genes, even linking the VHL gene with the response to hypoxia. Ratcliffe later showed that the VHL gene interacts physically with the protein he and Semenza had been researching, HIF-1α, demonstrating how it degrades the protein at normal levels of oxygen.
“When we began the research, we didn’t really anticipate the large effect of this process,” Ratcliffe said after the ceremony in a telephone interview with the Nobel Prize. “It is critical that scientists have the courage to extract information for their own sake, irrespective of the perceived value at the point of creation.” The work of the three scientists is now also entering the production of drugs, including drugs to increase HIF used to treat anemia and to suppress HIF used to treat certain forms of cancer. Tumors have increased HIF expression to help them cope with low indoor oxygen levels and new drugs are experimenting with ways to cautiously inhibit HIF
“This is such a fundamental aspect of how our cells deal with receiving oxygen and then adapting to its use, that one can almost assume the applications will be, I don’t want to say infinite, but very, very large,” said Johnson.
With their research, the three scientists would share the 9 million Swedish kronor award, around $908,000.
The other scientific Nobel prizes will be announced later this week, with Tuesday’s physics and Wednesday’s chemistry.