Nobel Prize for Medicine winners uncover ‘a fundamental mechanism of life’
Oxygen effectively sustains all life we know of. That we’ve understood since the onset of modern biology.
But the way in which cells can sense and respond to fluctuating oxygen levels — essential to the survival of virtually all animals — is underpinned by complex molecular behavior that has taken a lot longer to understand.
‘A fundamental mechanism’
In uncovering these processes, the three Nobel Prize winners in the category of physiology and medicine have unpicked “a very fundamental mechanism of life,” says Hellmut Augustin, who’s a professor at the department of vascular oncology and metastasis at the German Cancer Research Center and a director of the European Center for Angioscience.
Willian G. Kaelin, Peter J. Ratcliffe and Gregg L. Semenza were awarded the 2019 Nobel Prize in physiology and medicine on Monday, in what was an “absolutely appropriate” award, Augustin told DW.
“It explains how a change in the environment directly affects gene regulation in the body,” says Augustin. This underpins how animals are able to live at high altitudes and countless biomedical scenarios from exercise to pregnancy, altitude sickness and wound healing.
How we cope with changes in oxygen levels
Every animal needs oxygen to convert food into energy. When animals experience changes in the oxygen levels around them — at different altitudes — their cells undergo fundamental shifts in gene expression, which affect oxygen-dependent responses, like cell metabolism, tissue remodeling and heart rate.
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This is important not only in climbing mountains, said Randall Johnson, professor of molecular physiology and pathology at Cambridge University, but in things like wound healing, too. “In the case of a wound, for example, only part of the body receives little oxygen from a poor blood supply,” he said.
What the work of the winning scientists shows is which components regulate how genes respond to varying levels of oxygen.
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US-born Gregg Semenza is based at John Hopkins University in Baltimore, the US
The key to cell oxygen regulation is a protein complex called Hypoxia Inducible Factor — HIF for short — which is continuously produced in every cell in the body.
When the body is deprived of oxygen, the hormone erythropoietin (EPO) increases, and that boosts the production of red blood cells, which transport oxygen around the body. Until now, it was unclear how exactly a drop in oxygen triggered this response.
Combining their respective research, the scientists found that when oxygen levels decrease, the levels of HIF increase — and when this happens, the protein complex binds to segments of DNA near the gene for EPO, adjusting the expression of the gene and the levels of EPO.
“Why is this so clever?” asks Joachim Fandrey, director of the institute of physiology at the University of Duisburg in Germany. “Because if the cell has a problem, it doesn’t have to produce something completely new, it can just stop degrading [HIF],” pointing out that this is a lot faster than if cells were required to produce a new element from scratch.
When exercising, for example, “over days and weeks, muscle forms new blood vessels so that it’s better supplied with blood, and can therefore get more oxygen,” says Fandrey.
UK-born Peter Ratcliffe is a doctor and cell and molecular biologist, based at Oxford University in the UK
Wide-ranging impacts
The discovery is important not only in informing better cancer treatment but a whole range of diseases that are characterized by hypoxia — when oxygen levels are low in tissues — such as heart failure and chronic lung disease.
But although drugs that neutralize the formation of new blood vessels have been in clinical use since 2005, Augustin stresses they “are not magic weapons.”
“They do not fight the tumor, but have a cancer-suppressing effect — so they prolong the life of the patient,” he told DW.
US-born William Kaelin is a professor of medicine at Harvard University in the US
‘Outstanding’ scientists behind research
Although the two US-based laureates were asleep at the time they were contacted, their award was perhaps not a complete surprise.
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In 2016, the three scientists — who have been working in this area independently since the 1990s — were awarded the Albert Lasker Basic Medical Research Award for their work, which several other Nobel winners have previously won.
Nevertheless, as Augustin pointed out, “They were not sitting by the phone waiting for a call from the Nobel Prize committee.” Indeed, US-based researcher Kaelin told AP, “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.”
“All three researchers are outstanding personalities who have moved an entire field,” says Fandrey.
As the Nobel Committee outlined, such key discoveries are in no way a conclusion to this area of research, but have rather “opened the field and led to an explosion of work.”
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Nobel Prize in Medicine: Achievements to heal and cure
1902: It’s a mosquito’s fault
British researcher Ronald Ross found out that mosquitoes transmit the tropical disease malaria. He showed that the Anopheles mosquito carries one-celled parasites that cause malaria. Today, 200 million people a year still catch malaria, and about half a million of them die because of it. But thanks to Ross’ findings, researchers were able to develop treatments to fight the disease.
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Nobel Prize in Medicine: Achievements to heal and cure
1905: Bacteria cause TB
Robert Koch discovered the tuberculosis pathogen, the bacterium mycobacterium tuberculosis. Tuberculosis is still a globally widespread infectious disease. Treatment is possible but protracted, even though there are antibiotics for the illness today. There is also a vaccine which protects children, but not adults.
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Nobel Prize in Medicine: Achievements to heal and cure
1912: Switching organs and stitching them up
French surgeon Alexis Carrel succeeded at transplanting blood vessels and entire organs. He developed a suture technique with which he could stitch torn blood vessels back together. He also discovered how to store organs outside the human body. Today, doctors transplant roughly 100,000 organs every year.
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Nobel Prize in Medicine: Achievements to heal and cure
1924: Watching the heart beat
Dutch doctor Willem Einthoven developed the electro-cardiogram (EKG) to a point where it could be used in hospitals and doctor’s offices. An EKG records the heart’s electric activity. The data it provides helps doctors recognize an irregular heart rhythm and other heart diseases. It’s a wide-spread method in modern medicine.
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Nobel Prize in Medicine: Achievements to heal and cure
1930: Four types of blood
Austrian physician Karl Landsteiner discovered that mixing the blood of two different people often – but not always – led to clotting. He soon found the cause for that phenomenon: the different blood types A, B and O (which he called C). Later, his colleagues also discovered the blood type AB. Because of these findings, safe blood transfusions became possible.
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Nobel Prize in Medicine: Achievements to heal and cure
1939, 1945 and 1952: Drugs to kill bacteria
Three Nobel Prizes went to the discoverers and developers of antibiotics, among them Alexander Fleming (1945), who discovered penicillin. Today, antibiotics are still some of the most commonly used drugs and often save lives. New kinds of antibiotics constantly need to be developed, however, as bacteria become resistant to the medicines.
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Nobel Prize in Medicine: Achievements to heal and cure
1948: Attacking mosquitoes
The chemical compound DDT kills insects but hardly affects mammals, as Swiss chemist Paul Hermann Müller found out. Following that discovery, DDT became one of the most used insecticides worldwide. But then it turned out that DDT was damaging to the environment, especially to birds, and its use is now frowned upon. But it is still being used is places where mosquitoes are known to carry malaria.
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Nobel Prize in Medicine: Achievements to heal and cure
1956: Straight to the heart
German physician Werner Forssmann received the Nobel Prize together with two colleagues for the development of cardiac catheterization. Forssmann conducted the procedure for the first time on himself. It calls for inserting a tube into an artery in the hand, bend of the elbow or the groin, and pushing it up to the heart.
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Nobel Prize in Medicine: Achievements to heal and cure
1979 and 2003: Looking into the human body
When you wanted to see the inside of a human body, there used to be only one way: X-rays. But by now, doctors have superior methods. One of them is computed tomography (CT), which also uses x-rays, but takes detailed pictures of the body’s “layers” as if it were cut into slices. The discovery was followed by that of magnetic resonance tomography (MRI), which works with harmless magnetic fields.
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Nobel Prize in Medicine: Achievements to heal and cure
2008: Cancer caused by a virus
Thanks to Harald zur Hausen from the German Center for Cancer Research, we know that the human papillomavirus can cause cervical cancer. This knowledge helped the development of vaccines against the virus. Girls and women can now be vaccinated against the viral type of cervical cancer.
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Nobel Prize in Medicine: Achievements to heal and cure
2010: Test-tube babies
Robert Edwards developed the in-vitro fertilization. The first baby that was created this way was born in England in 1978. Advancements improved the method’s success-rate further. Globally, several million in-vitro babies have been born.
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Nobel Prize in Medicine: Achievements to heal and cure
2018: Unleashing the immune system to fight cancer
We all have natural defenses against tumors in us. We only need to release the natural brakes in the immune system. James P. Allison and Tasuku Honjo have laid the foundation for a cancer treatment in which tumors which have already formed metastases recede. At the end of the therapy, many patients remained cancer-free — a huge breakthrough.
Article source: https://www.dw.com/en/nobel-prize-for-medicine-winners-uncover-a-fundamental-mechanism-of-life/a-50722871?maca=en-rss-en-all-1573-rdf