|NOBLE PRIZE 2019
|Year : 2020 | Volume
| Issue : 1 | Page : 57-58
The Nobel prize in physiology or medicine 2019
Department of Medicine, MGIMS, Wardha, Maharashtra, India
|Date of Submission||06-Jan-2020|
|Date of Acceptance||09-Jan-2020|
|Date of Web Publication||14-Apr-2020|
Dr. O P Gupta
Department of Medicine, MGIMS, Sewagram, Wardha - 442 102, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Gupta O P. The Nobel prize in physiology or medicine 2019. J Mahatma Gandhi Inst Med Sci 2020;25:57-8
Two scientists from the US and one from the UK have jointly won the Nobel Prize 2019, in medicine for discovering how living cells sense and adapt to different levels of oxygen.
“Scientists often toss around this phrase, ‘textbook discovery.’ I'd say this is really and essentially a textbook discovery. This is something that basic biology students will be learning about when they study at age 12 or 13 or younger, biology and learn the fundamental ways in which cells work,” says Randall Johnson of the Nobel Assembly.
The scientists are well aware that the erythropoietin (EPO), the glycoprotein cytokine produced in peritubular fibroblasts of the kidney in response to hypoxia, stimulates the progenitor stem cells in the bone marrow to produce RBCs. However, it is not known exactly how oxygen regulated it. Gregg L. Semenza, the Director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering, was trying to look for the gene that regulated the hormone EPO. In 1995, Semenza discovered the protein complex, the hypoxia-inducible factor (HIF), which increases in quantity when the oxygen level is low., At the same time, in 1989, Sir Peter John Ratcliffe at a laboratory in Oxford University's Nuffield Department of Medicine was trying to explore the regulation of EPO. He discovered that the mRNA from the kidneys was part of the EPO production pathway that was capable of detecting hypoxia. That was also present in several other organs, including the spleen, brain, and testes. Further, the oxygen-sensing capabilities of other cells could be modified by that mRNA. Meanwhile, in 1992, William G. Kaelin studied the von Hippel–Lindau (VHL)gene related to familial cancer known as VHL syndrome at Dana-Farber Cancer Institute, Harvard University. Persons with a mutant VHL gene develop tumors in different parts of the body, including the central nervous system, the kidneys, and the pancreas. He noted increased vascular growth with the tumor, suspected to be linked to oxygen availability. Later working with Ratcliffe, he discovered that in response to changing oxygen availability chemical modification, prolyl hydroxylation of VHL takes place. When oxygen availability is low, this modification does not occur, and it cannot bind to HIF. Thus, the HIF is activated resulting in cellular proliferation.,
Gregg L. Semenza was born in 1956 in New York. He obtained a Bachelor of Arts in biology from Harvard and his M.D./Ph.D. from the University of Pennsylvania, School of Medicine. He did his specialist training in Pediatrics at Duke University. He is a Professor of Pediatrics, Radiation Oncology, Biological Chemistry, Medicine, and Oncology. He is presently the Director of the Vascular Research Program at the Johns Hopkins Institute for Cell Engineering. He discovered HIF-1 which allows cancer cells to adapt to oxygen-poor environment. He is a recipient of several awards, some of which are Stanley J. Korsmeyer Award, American Society for Clinical Investigation (2012), Wiley Prize (2014), and Albert Lasker Award for Basic Medical Research (2016).
Sir Peter John Ratcliffe, a physician-scientist and trained nephrologist, was born in Lancashire, England, in 1954. He completed his MB ChB medical degree with distinction at St. Bartholomew's Hospital Medical College at Queen Mary University of London in 1978 and MD degree from University of Cambridge in 1987. In 1990, it was a turning point when he received a Wellcome Trust Senior Fellowship to study cellular response to hypoxia from low oxygen levels in the blood. In 2003, he was appointed the Nuffield Professor and Head of the Nuffield Department of Clinical Medicine at Oxford. In 2016, he became Clinical Research Director at the Francis Crick Institute and continued as a Member of the Ludwig Institute of Cancer Research and Director of the Target Discovery Institute, University of Oxford. For his scientific research, he received Louis-Jeantet Prize for Medicine, Knight Bachelor, Fellowship of Academy of Medical Sciences, Robert J. and Claire Pasarow Foundation Medical Research Award, etc.
William G. Kaelin, Jr., born in 1957, in New York, earned his MD degree in Duke University. He did his specialist training in Internal Medicine at Johns Hopkins in Baltimore and at Dana-Farber Cancer Institute in Boston. In 1991, he joined as an instructor in Medicine at Harvard Medical School and later became a Professor of Medicine and served as an Associate Director of Basic Science at Dana-Farber Cancer Institute and Harvard Medical School. In 1992, setting up his own research laboratory, he worked on gene underlying VHL syndrome, familial cancer caused by mutation in VHL gene. He subsequently contributed with Prof. Ratcliffe that a chemical modification in the VHL protein facilitates cellular responses to changing oxygen availability, i.e., identifying the molecular mechanisms that allow cells to sense and adapt to changes in oxygen levels. In 2018, he was made Sidney Farber Professor of Medicine at the Dana-Farber Cancer Institute and Harvard Medical School. Kaelin was the recipient of numerous awards and honors, including the Canada Gairdner International Award (2010), the Albert Lasker Award for Basic Medical Research (2016), and Massry Prize (2018). He was an elected member of the National Academy of Sciences (2010).,
“The overall affect was to comprehensively explain the ‘molecular switch’ that regulates how cells adapt when oxygen levels are low,” said Mr. Johnson.
The findings gave impetus to the development of anticancer drugs that block HIF activity. The efforts are being made by academic laboratories and pharmaceutical companies to develop drugs that can interfere with the oxygen-sensing machinery in various diseases, the Nobel citation said.
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