The Morning Call

3 win Nobel for learning how cells sense oxygen

Discovery paved way for new strategies to fight anemia, cancer

- By Maria Cheng, Christophe­r Chester and Michael Warren

LONDON — Two Americans and a British scientist won the 2019 Nobel Prize for Physiology or Medicine for discoverin­g how the body’s cells sense and react to oxygen levels, work that has paved the way for new strategies to fight anemia, cancer and other diseases, the Nobel committee said.

Drs. William Kaelin of Harvard University, Gregg Semenza of Johns Hopkins University and Peter Ratcliffe at the Francis Crick Institute in Britain and Oxford University will share equally the $918,000 cash award, the Karolinska Institute said.

It is the 110th prize in the category that has been awarded since 1901.

Their work has “greatly expanded our knowledge of how physiologi­cal response makes life possible,” the committee said, explaining that the scientists identified the biological machinery that regulates how genes respond to varying levels of oxygen.

That response is key to things like producing red blood cells, generating new blood vessels and fine-tuning the immune system.

The Nobel committee said scientists are focused on developing drugs that can treat diseases by either activating or blocking the body’s oxygensens­ing machinery.

The oxygen response is hijacked by cancer cells, for example, which stimulate formation of blood vessels to help themselves grow. And people with kidney failure often get hormonal treatments for anemia, but the work of the new laureates points the way toward new treatments, said Nils-Goran Larsson of the Nobel committee.

Reached at his home, Kaelin said he was half-asleep Monday morning when the phone rang. It was Stockholm.

“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,” the 61-year-old said.

Kaelin said he isn’t sure yet how he’ll spend the prize money but “obviously I’ll try to put it to some good cause.” Kaelin is paid by the Howard Hughes Medical Institute, which also supports AP’s Health and Science department.

Ratcliffe, 65, said he was summoned out of a meeting this morning by his secretary, who had “a look of urgency.”

“He had a Swedish accent, so I figured it probably wasn’t one of my friends pulling my leg,” he said of the Nobel caller.

Trained as a kidney doctor, Ratcliffe said his research began when he and colleagues simply wanted to figure out how cells sense oxygen.

“I thought it was a definable problem and just thought we’d find out how it worked,” he said. Ratcliffe said it was about two years into the research program that first began in 1990 when they realized the discovery had much wider significan­ce.

“We saw that it wasn’t just cells in the kidney that know how to sense oxygen, but all cells in the body,” he said. “They use this to do a huge range of other things, reprogram the cells, cause the growth of blood vessels, differenti­ation of cells. There are hundreds and thousands of processes the body uses to adapt to and regulate its oxygen levels.”

He said while some promising drugs have been developed, including for kidney patients who don’t get enough oxygen, it will be years before it’s clear whether such discoverie­s are going to change the lives of tens of thousands.

Ratcliffe described his fellow laureates as “colleagues, competitor­s and friends.” He said felt honored by the Nobel accolade but that his main goal had always been pure science.

“The satisfacti­on is really finding things out that will continue to be true for all time,” he said. “This is for me an eternal truth and as a scientist, we work away, we find these things out and we hope they will be useful.”

Ratcliffe said he plans to have a celebrator­y party at the laboratory and later with his family. “A lot of people came to the office after the phone call and we had some champagne,” he said.

In Baltimore, Semenza, 63, said it was when he and colleagues were studying a gene in a rare cell type in the kidney and they did an experiment that showed the factor they discovered — which was linked to oxygen — that suggested it had widespread physiologi­cal importance. It turns out that the gene turns on erythropoi­etin, or EPO, which controls red blood cell production, when cells don’t get enough oxygen.

“We found it very interestin­g that the body can respond to oxygen,” he said. 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.”

Monday’s announceme­nt kicked off this year’s Nobel Prizes. The physics prize will be handed out Tuesday, followed by the chemistry prize on Wednesday. This year there is a double-header for the Nobel Literature Prize — one each for 2018 and 2019 — which will be awarded Thursday. The Peace Prize will be announced on Friday.

 ?? FRANK AUGSTEIN/AP ?? Dr. Peter Ratcliffe, 65, of Britain’s Francis Crick Institute and Oxford University.
FRANK AUGSTEIN/AP Dr. Peter Ratcliffe, 65, of Britain’s Francis Crick Institute and Oxford University.
 ?? JOHN STROHSACKE­R/GETTY ?? Dr. Gregg Semeza, 63, of Johns Hopkins University in Baltimore, Maryland.
JOHN STROHSACKE­R/GETTY Dr. Gregg Semeza, 63, of Johns Hopkins University in Baltimore, Maryland.
 ?? JOSEPH PREZIOSO/GETTY-AFP ?? Dr. William Kaelin, 61, of Harvard University in Cambridge, Massachuse­tts.
JOSEPH PREZIOSO/GETTY-AFP Dr. William Kaelin, 61, of Harvard University in Cambridge, Massachuse­tts.

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