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

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Announcement of the Nobel Prize in Medicine, this Monday, for Gregg Semenza, Peter Ratcliffe and William Kaelin. EFE

The Americans William Kaelin and Gregg Semenza and the British Peter Ratcliffe have today won the Nobel Prize in Physiology or Medicine for their discovery of “how cells sense available oxygen and adapt to it.”

The three scientists share the award equally 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 anaerobic, without air. The three scientists revealed how cells are able to sense the oxygen levels in their environment and adapt the metabolism to them so that more oxygen reaches the tissues. These findings are the basis for current anemia treatments and future cancer drugs. In 2016, the three laureates received the Lasker Prize 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 their discoveries of how cells sense and adapt to oxygen availability.” pic.twitter.com/6m2LJclOoL

One of the award-winning discoveries this year is celebrated for the wrong reasons. Semenza (New York, 1956), a physician and researcher at Johns Hopkins University, focused on the study of the gene EPO, essential to increase 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, carriers of oxygen. The EPO hormone was discovered in 1977 and two decades later it had already become one of the most widely used sports doping compounds. However, the molecular mechanisms that regulate its 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, showed that this mechanism is present in all tissues of all animals, a universality that proves its biological importance.

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

Around 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 the kidneys. Kaelin showed that these patients have the gene turned off VHL, that works as a switch that prevents cancer. Kaelin and Ratcliffe found that the gene VHL not only protects against tumors, but it is an essential part of the cellular oxygen sensor, as it helps preserve the necessary proteins when oxygen is lacking and removes them when it is abundant.

All this sophisticated cellular sensor described by Semenza, Ratcliffe and Kaelin is essential for the functioning of the muscles during intense effort, the correct response of the immune system, the development of new blood vessels or the formation of the embryo and placenta. Her discovery has had an impact on medicine, for example in the treatment of anemia with EPO. Furthermore, it has been shown that tumor cells take advantage of these mechanisms to hijack cellular metabolism and grow faster, which is why new treatments are being investigated to “suffocate” tumors.

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

Since 1901 a total of 219 scientists have received this award in the discipline of Medicine. Only 12 of them are women, 5.4%. The proportion is much more bloody in disciplines such as Physics that have only recognized women three times among a total of 210 winners.

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

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

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Source: https://pledgetimes.com/nobel-prize-in-medicine-for-the-discoverers-of-the-essential-oxygen-sensor-for-animal-life/

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