Do any of the following apply to you?
—You’re hard-pressed to find some good news in the public sphere
—You’re troubled about the anti-scientist trends swirling around
—You have, have had, or know someone who’s had anemia
—You have, have had, or know someone who’s had a heart attack or stroke
—You have, have had, or know someone who’s had cancer
—You’d like to live in a place with a higher altitude than you currently can handle
—You’d like to improve your sports performance
If so, you may find the 2019 Nobel Prize in Physiology or Medicine as exciting as I do. And the above list of diseases and circumstances is merely the beginning of what scientists believe will be the impact of the work the Nobel Committee has just recognized.
The three recipients, two Americans and a Brit, pieced together a series of discoveries—their own and some preceding and/or complementing their work—to discern what one scientist called the “thermostat” that enables cells to regulate the amount of oxygen needed to do its work: convert food into energy. The Nobel Committee referred to this mechanism as “one of life’s most essential adaptive processes.”
As the Nobel Prize press release states:
“The fundamental importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown.”
The “thermostat” the honorees discovered is comprised of a series of molecular occurrences by which cells sense too much or too little oxygen and respond accordingly.
Describing the Breathtaking Work
(From the Nobel press release)
“Thanks to the groundbreaking work of these Nobel Laureates, we know much more about how different oxygen levels regulate fundamental physiological processes. Oxygen sensing allows cells to adapt their metabolism to low oxygen levels: for example, in our muscles during intense exercise.
“Other examples of adaptive processes controlled by oxygen sensing include the generation of new blood vessels and the production of red blood cells. Our immune system and many other physiological functions are also fine-tuned by the O2-sensing machinery.
“Oxygen sensing has even been shown to be essential during fetal development for controlling normal blood vessel formation and placenta development.”
These are the three new Nobel Laureates: William G. Kaelin Jr., MD, of Harvard University in 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.
Concerning the relevance of their findings to major diseases, the Washington Post quoted Isha Jain, a scientist at the University of California in San Francisco:
“If you think of the main causes of death in the US, three out of five are related to lack of oxygen,” [including heart attack, stroke, and respiratory diseases]. “Understanding how the body senses and responds to low oxygen is pretty fundamental to all these diseases.”
Semenza said he and his colleagues hope that new therapies may increase the passage of blood into tissue with reduced blood flow “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.”
And then there’s cancer. The Nobel press release explains:
“The oxygen-regulated machinery has an important role in cancer. In tumors, the oxygen-regulated machinery is utilized to stimulate blood vessel formation and reshape metabolism for effective proliferation of cancer cells.”
Semenza told the Associated Press:
“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.”
From “Bench to Bedside”…
Or from lab to life-saving: such action is well under way, the press release reports.
“Intense ongoing efforts in academic laboratories and pharmaceutical companies are now focused on developing drugs that can interfere with different disease states by either activating, or blocking, the oxygen-sensing machinery.”
The first clinical application, a drug to combat anemia, was recently approved in China, and it is now under consideration in several European countries.
Semenza’s work was seminal to the total effort. In the 1990s, he and his group identified genes that were activated when oxygen levels were low to raise the levels of erythropoietin (EPO), a hormone secreted by the kidneys essential to producing the oxygen-laden red blood cells.
The oxygen-sensing mechanism was originally believed to be located only in the kidneys, but both Semenza and Ratcliffe subsequently found, among other things, that it exists in nearly all cells.
Moving from the profound to the less-so, The Washington Post notes that:
“This is the same basic mechanism behind doping, in which endurance athletes try to increase their supply of oxygen-carrying red blood cells.”
Though Semenza’s early article describing that research has now received thousands of journal citations, it was initially rejected by the “top tier journals,” which, he said, “didn’t find it to be of sufficient interest to warrant publication.”
(A note of encouragement to all who aspire to publication in any field of endeavor, don’t you think?)
For those who are interested in the scientific nitty-gritty, the Nobel release provides the road map of individual discoveries by the three researchers and others that yielded this dramatic finding.
Lessons Beyond the Discoveries Themselves
One of the things I especially like about this story is that these men, while working independently over decades, also shared their unpublished data with one another—“sometimes at scientific meetings, sometimes at the bar,” said Kaelin.
No secret patents here; no rivalry to be “the first.” As one made a discovery that he knew was an important piece of the puzzle, he described it to his colleagues.
I’ve no idea whether, or to what extent, this collaborative approach was influenced by their funding sources, but it’s worth noting that a National Institutes of Health (NIH) press release touted the US government’s role in supporting both American scientists’ work, and the American Heart Association stated it underwrote Semenza’s early work. The European Research Council (ERC) supported Ratcliffe’s work.
Two more issues are worth noting. One is that Semenza, who is a professor of genetics at Johns Hopkins, credited his wonderful high school biology teacher, the late Rose Nelson.
“She used to say to us, ‘When you win your Nobel Prize, I don’t want you to forget that you learned that here.’ She just assumed that one of us was going to do that…She was my inspiration, and I think that is the importance of teachers, to serve as that kind of spark.”
The other is Kaelin’s emphasis, as the Washington Post reported:
“The prize underscores the importance of doing research to follow curiosity and unravel basic biology. He and the other scientists hoped, but did not know, that unraveling how cells sense oxygen could spark ideas for new approaches for human diseases, including stroke and cancer.”
“This kind of research is increasingly under threat. It’s much easier for fundraisers and policymakers to say we will support scientists, but…tell us how it will improve outcomes in five years.
“When you’re doing real science, you have to be prepared to take the road where it takes you—and if you’re doing science, it’s hard to predict where the road is going to take you.”
Will you join me in a virtual round of applause for scientists dwelling for decades on basic research, facilitated by public funding?
Their research won’t always take us where these three eminent researchers have—but when it does, the benefits to us, individually and worldwide, can be immeasurable.