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Nobel Prize in Medicine Awarded to 3 for Work on How Cells Manage Oxygen Nobel Prize in Medicine Awarded for Research on How Cells Manage Oxygen
(about 1 hour later)
The Nobel Prize in Physiology or Medicine was jointly awarded to three scientists — William G. Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza — for their work on how cells sense and adapt to oxygen availability. The Nobel Prize in Physiology or Medicine was jointly awarded to three scientists — William G. Kaelin Jr., Peter J. Ratcliffe and Gregg L. Semenza — for their work on how cells sense and adapt to oxygen availability.
The Nobel Assembly announced the prize at the Karolinska Institute in Stockholm on Monday.The Nobel Assembly announced the prize at the Karolinska Institute in Stockholm on Monday.
Their work established the genetic mechanisms that allow cells to respond to changes in oxygen levels, and has implications for treating a variety of diseases, including cancer, anemia, heart attacks and strokes. Their work established the genetic mechanisms that allow cells to respond to changes in oxygen levels. The findings have implications for treating a variety of diseases, including cancer, anemia, heart attacks and strokes.
“Oxygen is the lifeblood of living organisms,” said Dr. George Daley, dean of Harvard Medical School. “Without oxygen cells can’t survive.” But too much or too little oxygen also can be deadly, so the question was, how do cells regulate their responses?
The investigators uncovered detailed genetic responses to changing oxygen levels that allow cells in the bodies of humans and other animals sense and respond to fluctuations, increasing and decreasing how much oxygen they receive. “Oxygen is the lifeblood of living organisms,” said Dr. George Daley, dean of Harvard Medical School. “Without oxygen, cells can’t survive.” But too much or too little oxygen also can be deadly. The three researchers tried to answer this question: How do cells regulate their responses?
The discoveries reveal the molecular mechanisms that control such things as adaptation to high altitudes and also how cancer cells manage to fuel their metabolisms by hijacking oxygen. Randall Johnson, a member of the Nobel Assembly, described the work as a “textbook discovery” and said it would be something students would start learning at the most basic levels of biology education. The investigators uncovered detailed genetic responses to changing oxygen levels that allow cells in the bodies of humans and other animals sense and respond to fluctuations, increasing and decreasing how much oxygen they receive.
The discoveries reveal the cellular mechanisms that control such things as adaptation to high altitudes and how cancer cells manage to hijack oxygen. Randall Johnson, a member of the Nobel Assembly, described the work as a “textbook discovery” and said it would be something students would start learning at the most basic levels of biology education.
“This is a basic aspect of how a cell works, and I think from that standpoint alone it’s a very exciting thing,” Mr. Johnson said.“This is a basic aspect of how a cell works, and I think from that standpoint alone it’s a very exciting thing,” Mr. Johnson said.
The work also has implications for treating various diseases including anemia, heart attacks, and strokes, in which there is too little blood, and also cancers that are fed by and seek out oxygen. The research also has implications for treating various diseases in which oxygen is in short supply — including anemia, heart attacks and strokes — as well as for treatment of cancers that are fed by and seek out oxygen.
William Kaelin, professor of medicine at Dana-Farber Cancer Institute and Brigham & Women’s Hospital Harvard Medical School, was drawn to science for its purity. William G. Kaelin Jr., professor of medicine at Dana-Farber Cancer Institute and Brigham & Women’s Hospital Harvard Medical School, was drawn to science for its objectivity.
“I like mathematics, medicine, and science because I like solving puzzles, and I like answers that are objectively verifiable,” he said when he shared a Lasker award in 2016 with Dr. Ratcliffe and Dr. Semenza. “Like any scientist, I like solving puzzles,” he said in an interview this morning.
But he had an unprepossessing start. When he was a pre-med student, hoping to become a physician researcher, his professor wrote, “Mr. Kaelin appears to be a bright young man whose future lies outside of the laboratory.” But he had an unprepossessing start. When he was a pre-med student hoping to become a physician researcher, a professor wrote, “Mr. Kaelin appears to be a bright young man whose future lies outside of the laboratory.”
He eventually prevailed. He became intrigued by a rare genetically induced cancer, von Hippel-Lindau disease, that is characterized by a profusion of extra blood vessels and overproduction of EPO. Eventually he became intrigued by a rare, genetic cancer, von Hippel-Lindau disease, that is characterized by a profusion of extra blood vessels and overproduction of erythropoietin, or EPO, a hormone that stimulates production of the red blood cells that carry oxygen.
“He was studying a very rare cancer predisposition syndrome,” Dr. Daley said. “It is not a public health menace but it is a fascinating point of curiosity.” The cancer “was really fascinating,” Dr. Kaelin said. It had unusual features, like causing the body to make a substance, vegF, that stimulates the formation of blood vessels. And the cancer can cause the body to make too many red blood cells by increasing the production of EPO.
Dr. Kaelin, in an interview this morning, explained: “Like any scientist I like solving puzzles.” And this cancer, he said, “was really fascinating.” It had such unusual features, like causing the body to make a substance, vegF, that stimulates the formation of blood vessels. And the cancer can cause the body to make too many red blood cells by increasing the production of EPO. He had a hunch about what was going awry: “I thought it had something to do with oxygen sensing.”
He had a hunch about what was going awry. As it turned out, he was right.
“I thought it had something to do with oxygen sensing,” he said.
Of course he was right.
“It is one of the great stories of biomedical science,” Dr. Daley said. “Bill is the consummate physician-scientist. He took a clinical problem and through incredibly rigorous science figured it out.”“It is one of the great stories of biomedical science,” Dr. Daley said. “Bill is the consummate physician-scientist. He took a clinical problem and through incredibly rigorous science figured it out.”
Gregg L. Semenza is professor of genetic medicine at Johns Hopkins and has been the director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering since 2003. He quoted the words of Mary Lasker in as he accepted the Lasker prize in 2016: “I am opposed to heart attacks and cancer the way one is opposed to sin.” Dr. Kaelin said he knew, of course, that today the Nobel Prize would be awarded. But his chances were “so astronomically small” that he stuck with this usual routine and did not stay up last night.
To which he added, “Amen.” He had a dream, though, that he had not gotten the 5 a.m. call from Sweden. He woke up and looked at the time; in fact, it was just 1:30 a.m.
He, like many other researchers, said he pursues his work with “a religious fervor.” He went back to sleep, and when it really was 5 a.m., his phone rang.
He set out to understand what cancer cells are searching for when they spread from tumors into surrounding tissues, and then to blood vessels that let them travel around the body. Gregg L. Semenza, professor of genetic medicine at Johns Hopkins, said his life was changed by a high school teacher, Rose Nelson, who taught biology at Sleepy Hollow High School in Tarrytown, N.Y.
His guess, he said, is that they are searching for oxygen. “She was unbelievable,” Dr. Semenza recalled in an interview. “She transmitted the wonder and joy of science and scientific discovery. She set me on a course to science.”
The work started when he wondered about the gene for EPO. How was that switch turned on when the body is deprived of oxygen? Once it is activated, the body makes more oxygen carrying red blood cells. But what was the molecular signal that set the process in motion? In college, at Harvard, he thought he would get a Ph.D. and do research in genetics. But then a family he was close to had a child with Down syndrome.
His hope, he said during the Lasker talk, was that uncovering the mechanisms that control cells’ responses to oxygen will lead to drugs to increase oxygen sensitivity to treat anemia and cardiovascular diseases. And drugs that do the opposite — decrease oxygen sensitivity — will be developed to treat cancer. “That shifted me from being interested in genetics as kind of a scientific discipline to thinking about the impacts of genetics on people,” he said.
Peter J. Ratcliffe, the third Nobelist, is the director of clinical research at the Francis Crick Institute in London, the director of the Target Discovery Institute at Oxford and a member of the Ludwig Institute for Cancer Research. He became a medical researcher only by chance. After attending medical school at the University of Pennsylvania, Dr. Semenza set out to understand what cancer cells are searching for when they spread into surrounding tissues, and then into blood vessels that carry them around the body.
“I was a tolerable schoolboy chemist and intent on a career in industrial chemistry. The ethereal (but formidable) Headmaster appeared one morning in the chemistry classroom. ‘Peter’ he said with unnerving serenity ‘I think you should study medicine’. And without further thought, my university application forms were changed,” he said in 2016. His guess was that cancer cells are searching for oxygen.
He became a kidney specialist, fascinated by the way the organs regulate production of EPO in response to the amount of oxygen available. Some colleagues, he said, felt this was “a niche area” and not very important. But he persisted, intrigued by the scientific puzzle. That led him to the discoveries that resulted in a Nobel Prize. Dr. Semenza turned his attention to the gene the guides production of EPO. Once it is activated, the body makes more oxygen carrying red blood cells. But how is that switch turned on when the body is deprived of oxygen?
The Nobel Prize Twitter account posted a photo of Dr. Ratcliffe writing a grant proposal on Monday, after learning of his award. As a geneticist, he was trained to study rare genetic diseases. But his work on cellular responses to oxygen led him to study such common diseases as heart disease and cancer.
“I’m honoured and delighted at the news. I’ve had great support from so many people over the years,” he said in a statement released by Oxford. “It’s a tribute to the lab, to those who helped me set it up and worked with me on the project over the years, to many others in the field, and not least to my family for their forbearance of all the up and downs.” At first, he divided his attention between the two conditions. More recently, Dr. Semenza said, he has focused on cancer, looking for ways to use what he has learned to find new ways to attack tumors.
Dr. Kaelin said he knew, of course, that today was Nobel Prize Monday. But, he said, “I try to not pay attention.” The chances, he added “are so astronomically small,” that he stuck with this usual routine and went to sleep. Dr. Semenza was asleep when the call from Sweden came this morning, and did not get to his phone in time to answer it. The phone rang again a few minutes later.
He had a dream, though, that it was 5:30 a.m. and because he had not gotten a 5 a.m. call from Sweden he knew he had not won. He woke up, looked at the time, and saw that it was 1:30 a.m. So he went back to sleep. “I heard this very distinguished gentleman tell me I was going to receive the Nobel Prize,” he said. “I was shocked, of course. And I was kind of in a daze. I’ve been in a daze ever since.”
Then his phone rang at 5 a.m. But he added, “It’s been wonderful.”
He had won. Peter J. Ratcliffe, the third Nobelist, is the director of clinical research at the Francis Crick Institute in London and director of the Target Discovery Institute at Oxford.
The prize last year went to James P. Allison of the United States and Tasuku Honjo of Japan for their work on immunotherapy, or unleashing the body’s immune system to attack cancer. This breakthrough has resulted in an entirely new class of drugs and brought lasting remissions to many patients who had run out of options. He became a medical researcher almost by chance. “I was a tolerable schoolboy chemist and intent on a career in industrial chemistry,” he said in a speech in 2016. “The ethereal but formidable headmaster appeared one morning in the chemistry classroom. ‘Peter,’ he said with unnerving serenity, ‘I think you should study medicine’. And without further thought, my university application forms were changed.”
He became a kidney specialist, fascinated by the way the organs regulate production of EPO in response to the amount of oxygen available. Some colleagues, he said, felt this was not very important.
But he persisted, intrigued by the scientific puzzle. “We set about the problem of EPO regulation, which might have been seen, and some did see, as a niche area,” he said in a telephone interview posted by the Nobel Committee on Twitter.
“But I believed it was tractable, it could be solved by someone. The impact of that became evident later.”
The research is an illustration of the value of basic research, he added: “We make knowledge, That’s what I do as a publicly funded scientist. It is good knowledge. It is true. It is correct.”
But, he added, “We set out on a journey without a clear understanding of the value of that knowledge.”
When the call from Sweden came, Dr. Ratcliffe was writing a grant proposal. Today he will continue working on it.
“I’m happy about it,” he said of the Nobel Prize. But also was not enthusiastic about being thrust into the public eye.
“I’ll do my duty, I hope,” he said.
“It’s a tribute to the lab, to those who helped me set it up and worked with me on the project over the years, to many others in the field, and not least to my family for their forbearance of all the up and downs,” he said in a statement released by Oxford.
The prize last year went to James P. Allison of the United States and Tasuku Honjo of Japan for their work on immunotherapy, for unleashing the body’s immune system to attack cancer. This breakthrough has resulted in an entirely new class of drugs and brought lasting remissions to many patients who had run out of options.
The Nobel Prize in Physics will be announced on Tuesday in Sweden. Read about last year’s winners, Arthur Ashkin, Gérard Mourou and Donna Strickland.The Nobel Prize in Physics will be announced on Tuesday in Sweden. Read about last year’s winners, Arthur Ashkin, Gérard Mourou and Donna Strickland.
The Nobel Prize in Chemistry will be announced on Wednesday in Sweden. Read about last year’s winners, Frances H. Arnold, George P. Smith and Gregory P. Winter.The Nobel Prize in Chemistry will be announced on Wednesday in Sweden. Read about last year’s winners, Frances H. Arnold, George P. Smith and Gregory P. Winter.
The 2018 and 2019 Nobel Prizes in Literature will be announced on Thursday in Sweden. The prize last year was postponed after the husband of an academy member was accused, and ultimately convicted, of rape — a crisis that led to the departure of several board members and required the intervention of the king of Sweden. Read about 2017’s winner, Kazuo Ishiguro. The 2018 and 2019 Nobel Prizes in Literature will be announced on Thursday in Sweden. The prize last year was postponed after the husband of an academy member was accused, and ultimately convicted, of rape — a crisis that led to the departure of several board members and required the intervention of the King of Sweden. Read about 2017’s winner, Kazuo Ishiguro.
The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winners, Nadia Murad and Denis Mukwege.The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winners, Nadia Murad and Denis Mukwege.
The Nobel Memorial Prize in Economic Science will be announced Monday next week in Sweden. Read about last year’s winners, William Nordhaus and Paul Romer.The Nobel Memorial Prize in Economic Science will be announced Monday next week in Sweden. Read about last year’s winners, William Nordhaus and Paul Romer.
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Michael Wolgelenter contributed reporting.Michael Wolgelenter contributed reporting.