William G. Kaelin, MD, of Harvard University, Boston, Massachusetts, Gregg L. Semenza, MD, PhD, of Johns Hopkins University in Baltimore, Maryland, and Sir Peter J. Ratcliffe, FMedSci, of Oxford University in the United Kingdom have been awarded the 2019 Nobel Prize in Physiology or Medicine for their discoveries on how cells sense oxygen and adapt to it.

The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, made the announcement this morning at a press conference in Stockholm.

The work can inform treatments for fighting anemia, cancer, and other diseases, the Nobel Committee said in a news release. The work will help better understand production of red blood cells, the generation of new blood vessels, and the fine-tuning of the immune system.

“These fundamental findings have greatly increased our understanding of how the body adapts to change,” Randall Johnson, professor at the Karolinska Institute and member of the Nobel Assembly, said, according to the Associated Press (AP). “Applications of these findings are already beginning to affect the way medicine is practiced,” he said.

The Karolinska Institute reports that the three scientists will share equally the cash award of $918,000.

“A Bit Surreal”

The AP reports that Kaelin, who is also a researcher at the Dana-Farber Cancer Institute in Boston, was half asleep this morning when the telephone rang.

“I was aware as a scientist that if you get a phone call at 5 A.M. with too many digits, it’s sometimes very good news, and my heart started racing. It was all a bit surreal,” he said.

Betsy Nabel, MD, president of Brigham and Women’s Hospital in Boston, who is a cardiovascular scientist, said at a press conference this morning at Dana Farber, “The discoveries made by Bill and his colleagues have fundamentally defined how cells in the body sense oxygen and how the cells then respond to an abundance or an absence of oxygen. This oxygen-sensing mechanism is critical for regulating blood vessel tone and is critical in the development of a heart attack and the treatment of heart attack.”

Kaelin said at the press conference, “Like most scientists, and maybe all scientists if they’re being honest, I did occasionally allow myself to dream that maybe one day this would happen.”

He thanked colleagues, family, and mentors and acknowledged, “Science, especially today, is not done by an individual. It’s done by an ecosystem, and I have been aided countless times by collaborators.”

At a press conference at Johns Hopkins, Semenza admitted that he slept through the first call this morning and that he made it to the telephone too late.

“I was a little faster to the phone the second time around,” he said.

This “amazing day” was in stark contrast to “a lousy year for me,” he said, recalling that on May 31, he fell down a flight of stairs in his home and broke his neck.

He likened the work performed by his surgeon at Johns Hopkins, which left him with virtually no deficits, to the support he has received from all colleagues at Hopkins.

Semenza told the AP that he and his colleagues were studying a gene in a rare cell type in the kidney when they realized they were on to something much bigger.

They found the gene turns on erythropoietin (EPO), which controls red blood cell production when cells are deprived of oxygen.

“We found it very interesting that the body can respond to oxygen,” Semenza told the AP. “That discovery has led to treatments for people with chronic kidney disease who become anemic when their kidneys stop making EPO. “Now, drugs can turn on EPO production by increasing these factors.”

He said at the press conference that chronic kidney disease will likely be the first area in which their discovery will be used, but there are many others.

With cancer, cells divide rapidly, consume a lot of oxygen, and become very hypoxic, he noted.

They learned that when the cells become hypoxic, they turn on genes that allow them to metastasize throughout the body.

“Whereas most of the chemotherapy drugs are designed to kill dividing cells that are well oxygenated, there are no treatments that are approved to treat the hypoxic cells within the cancer. We believe it’s these cells that survive the therapy and come back and kill the patient,” Semenza said.

With cardiovascular disease, he said, “We hope there may be the possibility for new therapies to increase the perfusion of ischemic tissue in diseases such as coronary heart disease  and also limb ischemia, which is a major problem, particularly in diabetics, leading in some cases to limb amputation.

“There are a number of disorders where we hope to make an impact.”

Celebrations were happening simultaneously in the United Kingdom.

In an Oxford press release, Sir John Bell, Regius Professor of Medicine at the University of Oxford, said, “Sir Peter Ratcliffe has made a major contribution to our understanding of how cells respond to low levels of oxygen. He identified the problem 30 years ago here in Oxford and has tenaciously worked through the fine detail of how this system works. It is an impressive story of how a clinician scientist can combine groundbreaking basic science with caring for patients within the NHS [National Health System].”

Andrew Murray, of the University of Cambridge, said the winners’ discovery has key implications for heart and lung diseases as well.

“Low oxygen levels are a feature of some of the most life-threatening diseases,” he told the AP. “When cells are short of oxygen, as is the case with heart failure  and lung disease, the tissues need to respond to that in order to maintain energy levels.”

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