Nobel Prize in Medicine for discoverers of the essential oxygen sensor for animal life

Americans William Kaelin and Gregg Semenza and Britain's Peter Ratcliffe today won the Nobel Prize in Physiology or Medicine for their discovery of "how cells feel the oxygen available and adapt to it.

The three scientists are equally divided for having clarified a fundamental mechanism that allows all animals to transform oxygen into energy, a type of metabolism —aerobic — that generates 15 times more energy than the anaerobic, without air. The three scientists unveiled how cells are able to feel the oxygen levels in their environment and adapt metabolism to them so that more oxygen reaches tissues. These findings are the basis for current treatments against anemia and future cancer drugs. In 2016 the three winners received the Lasker Award for Basic Medical Research for these same discoveries.

BREAKING NEWS:
The 2019 #NobelPrize in Physiology or Medicine has been awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza "for discoveries of how cells sense and adapt to oxygen availability." pic.twitter.com/6m2LJclOoL

— The Nobel Prize (@NobelPrize) October 7, 2019

One of this year's award-winning discoveries is famous for the wrong reasons. Semenza (New York, 1956), a physician and researcher at Johns Hopkins University, focused on the study of the EPO gene, which is critical to increasing blood oxygen levels by producing erythropoietin (EPO). This protein is synthesized in the kidneys. Upon reaching the bloodstream it promotes the production of red blood cells, oxygen carriers. The EPO hormone was discovered in 1977 and two decades later it had become one of the most widely used sports doping compounds. However, the molecular mechanisms that regulate their production based on available oxygen were a mystery,

In 1991, Semenza developed transgenic mice that carried the gene EPO human. In them he identified a genetic sequence responsible for initiating EPO production when oxygen levels drop. Two years later, Ratcliffe (Lancashire, 1954), of the University of Oxford, demonstrated that this mechanism is present in all tissues of all animals, a universality that proves its biological importance.

In 1998, Semenza's mice were unable to develop veins, red blood cells, or a heart system when they lacked a complex of two proteins that were christened hypoxia-inducible factor (HIF). Hypoxia is a lack of oxygen and those two proteins seemed like a key piece of biological sensors to detect it. If oxygen abounds, the cell cleaning system kills and removes these proteins, but when it is scarce, it stops to allow tissues to continue generating as much energy as possible

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Almost at the same time William Kaelin (New York, 1957), an oncologist at Harvard Medical School, was studying why some of his cancer patients had excess blood vessels in their kidneys. Kaelin showed that these patients have the VHL gene deactivated, that it functions as a switch that prevents cancer. Kaelin and Ratcliffe found that the VHL gene not only protects against tumors, but is an essential part of the cellular oxygen sensor, as it helps preserve the necessary proteins when oxygen is missing and eliminates them when it abounds,

All of this sophisticated cellular sensor described by Semenza, Ratcliffe and Kaelin is essential for the functioning of muscles during intense exertion, the correct response of the immune system, the development of new blood vessels or the formation of the embryo and placenta. Their discovery has had an impact on medicine, for example in the treatment of anemia with EPO. In addition, tumor cells have been shown to leverage these mechanisms to hijack cellular metabolism and grow faster, so they are investigating new treatments to "choke" tumors.

In 2016, the three recipients received the Lasker Award for Basic Medical Research  for these same discoveries.

A total of 219 scientists have received this award created by Alfred Nobel since 1901. Only 12 of them are women, 5.4%. The ratio is much more bleeding in disciplines such as Physics that have only recognized women three times out of a total of 210 award-winners.

Last year the winners were Japanese Tasuku Honjo and American James Allison for the discovery of "cancer therapy for inhibiting negative immune regulation." Both scientists laid the groundwork for current cancer treatments with immunotherapy. The last woman to win a Nobel Prize in Medicine was the Chinese Tu Youyou, who received the 2015 award for discovering a key compound to treat malaria

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The prize is endowed with nine million Swedish crowns, some 940,000 euros. This award opens the round of announcements this week, which will continue Tuesday with Physics, Wednesday, Chemistry, Thursday of Peace and finally Economics, which will be unveiled on Monday of next week.