In October 2019, a trio of scientists was awarded the Nobel Prize in Physiology or Medicine, in Stockholm - Sweden, due to their discoveries of how cells sense and adapt to oxygen availability. The prize had a value of 9 million Swedish kronor (SEK), about 871,000 euros.
The detection and regulation of oxygen are essential for a large number of diseases. The Nobel Committee believes that the discoveries made by this year's Nobel Prize winners opened the door for the development of new strategies to combat diseases such as anemia or cancer, among many others.
Before explaining how they achieved these findings, let’s know: “Who are these scientists?”
William George Kaelin Jr. (62 years old) earned bachelor’s degrees in mathematics and chemistry from Duke University in 1979, and then he attended medical school, earning a medical degree in 1982. When he moved to Boston, in 1987, he worked as a researcher in medical oncology at the Dana-Farber Cancer Institute, and later became an instructor in medicine at Harvard Medical School. In 2018, he was made Sidney Farber Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School, where he continues to work, even today.
This American scientist is known for his studies of tumor suppressor genes and proteins, in order to achieve one long term goal: novel anticancer strategies. His laboratory uses a variety of molecular and cellular approaches to understand the mechanism of proteins in the prevention of tumor growth. He is also known for his role in identifying the molecular mechanism that allow cells to sense and adapt to changes in oxygen levels, which led him to the Nobel Prize.
Sir Peter John Ratcliffe (65 years old) studied medicine at Gonville & Caius College, in Cambridge, where he graduated with a medical degree in 1987. In 1978, Ratcliffe completed bachelor’s degrees in medicine and surgery at St. Bartholomew’s Hospital in London. Later, in 1989, he established a laboratory at Oxford, with a specific focus on the cellular oxygen-sensing pathways. There, he also studied the regulation of erythropoietin, a hormone that stimulates red blood cell production in response to low blood oxygen levels. From 2004 to 2016 we worked as head of the Nuffield Department of Medicine at Oxford, and in 2016 he was appointed director of Oxford’s Target Discovery Institute and clinical research director at the Francis Crick Institute, London. This British physician and scientist was also awarded the Nobel Prize 2019 thanks to his discoveries concerning the cellular oxygen-sensing mechanisms.
Gregg Leonard Semenza (63 years old) studied pediatric genetics at the University of Harvard, where he earned a bachelor’s degree in 1978. He continued his academic career at the University of Pennsylvania, and there he graduated with medical and doctorate degrees in 1984. Semenza followed postdoctoral studies in medical genetics at Johns Hopkins University, in Baltimore.
In the late 1980s, Gregg L. Semenza became curious about the mechanisms underlying cellular responses to changes in oxygen availability. Subsequently, this American physician and scientist became known for his research of how cells use and regulate oxygen, and for his discovery of hypoxia-inducible factor (HIF) - a molecule (genetic factor) that is activated when cells have reduced oxygen availability and that plays a critical role in enabling cells to survive in certain disease conditions. Due to his research, new doors were opened for the development of new treatments for diseases, like cancer and ischemic cardiovascular disease, in which reduced oxygen availability is a major feature of disease. Thanks to his discoveries, he also was awarded the 2019 Nobel Prize for Physiology or Medicine.
Ok, you already know the academic and professional career of each scientist, so now we are going to tell you what the scientific contribution of each one for this Nobel Prize.
Gregg Semenza, from Johns Hopkins University in the USA, studied the relationship between low oxygen levels and the erythropoietin hormone (EPO), which produces more red blood cells when oxygen concentration is lower. For this purpose, the scientist investigated the EPO gene using genetically modified mice, and he noted the existence of specific DNA segments close to the EPO gene that regulated the cellular response to low oxygen levels.
Peter Ratcliffe, from the Francis Crick Institute in London, also investigated the mechanism of oxygen regulation related to the EPO gene. Independently, both scientists found that this mechanism was present in all tissues, not just kidney cells, where EPO is normally produced. These important discoveries showed that this mechanism was common and functional in many different types of cells.
At the same time that Gregg Semenza and Peter Ratcliffe were studying the regulation of the EPO gene, William Kaelin Jr, from the Dana-Farber Cancer Institute in the USA, was investigating von Hippel-Lindau disease (VHL), a genetic disease which leads to a high risk of certain cancers in families with mutations in the VHL gene. William Kaelin Jr. showed that the VHL gene is involved in the control responses to low oxygen concentrations, since cancer cells without the VHL genes expressed high levels of genes regulated by low oxygen concentrations, but when the VHL genes were reintroduced into cancer cells, levels returned to normal.
The president of the International Society of Physiology, Bridget Lumb, applauded the work of this trio of researchers, and stated that these research works “are improving our understanding of how our body works and thus, are helping us to keep healthy”.
“Thanks to these investigations, we know much more about how different levels of oxygen affect the physiological processes in our bodies. This has huge implications at different levels: from the recovery from injuries and the protection against illness, to the improvement of exercise performance”, concludes Bridget Lumb.
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