Scientists Who Discovered Proteins That Can Possibly Cure Cancer Awarded Nobel Prize for Physiology

By Jiya Chatterjee

Published in Horace Mann Spectrum Magazine November, 2019

Winners of the Nobel Prize for Physiology and Medicine 2019

Imagine a world where the fight against cancer has been won in the same way that diseases like the plague, polio and smallpox have been beaten. Every little but meaningful discovery that leads towards a future where a new set of life threatening diseases has been defeated is thrilling. The Nobel Prize is one of the most prestigious awards given today for such stunning discoveries. It is awarded to people whose work and actions have helped the world for the better in different aspects. This year, the Nobel Prize for Physiology and Medicine was presented to scientists William G Kaelin Jr. of Harvard University, Sir Peter Ratcliffe of Oxford University, and Gregg L. Semenza of Johns Hopkins University. Their work addressed the topic of how cells respond to different levels of oxygen. The discovery of this molecular switch in cells has revolutionized the field of medicine, and this is what is helping researchers develop new drugs to cure diseases such as anaemia, kidney failure, and cancer by controlling the flow of oxygen to particular cells. 

Cells have variable oxygen requirements at different times, depending on the nature of the activity they are performing. The supply needed varies based on the activity being performed. For example, more oxygen is required when participating in exercise or sports. However,cells act differently when there is less oxygen. These three scientists’ work revolved around how cells react to different levels of oxygen. 

Semenza began by studying the gene for a hormone that we produce called erythropoietin (EPO). EPO is a hormone that produces more red blood cells when oxygen levels are low. What was unknown was what triggered EPO to increase production of red blood cells. Semenza identified a protein complex called Hypoxia-inducible factor (HIF) that binds to a DNA segment next to the EPO gene to regulate EPO gene expression. The curious characteristic of HIF is that it is only present when oxygen levels are low, but it disappears when there is an abundance of oxygen. HIF was altering the behaviour of the DNA, which was resulting in the increased production of red blood cells. 

Ratcliffe and Kaelin discovered how a second protein called von-Hippel-Lindau (VHL) regulates the level of HIF. They saw that when oxygen levels were normal, cells continued to produce HIF, but it was immediately destroyed by VHL. This was due to enzymes called prolyl hydroxylases, which chemically modified the HIF, causing it to bind with the VHL and allowing its destruction. However, when oxygen was scarce, this enzyme became inactive, leading the HIF to travel to the cell’s nucleus, bind with the EPO gene, and cause changes such as an increase in the production of red blood cells. 

This work involving how cells react to hypoxia has started a wave of new research directed towards finding cures for illnesses such as anaemia and cancer. Anaemia is a condition that causes a deficiency in red blood cells, leading to weariness and abnormally pale skin. It usually occurs when a person is unable to produce a sufficient amount of EPO. By harnessing what HIF does to EPO and applying it to the case of a scarcity of red blood cells, new drugs for anaemia can be developed. 

Cancers also need oxygen to propagate. Cancers enable this need for additional oxygen by relying on additional red blood cell production and blood vessels to carry oxygen via red blood cells to tumour sites. As tumors grow and consume oxygen, portions of the tumor become hypoxic. To sustain further tumor growth, cancer cells from these hypoxic regions migrate to other regions of the body to avail of additional oxygen supply, thereby resulting in cancer spreading. This is called metastasis. Therefore, a number of anti-cancer drugs aim to modulate tumor hypoxia to prevent cancer growth. The work of these scientists has found the trigger that can be controlled: the level of HIF.

  While anaemia and cancer are two of the diseases currently being discussed in the context of oxygen availability, hypoxia plays a role in many diseases. As cellular biologist Celeste Simon said, “Oxygen limitation is a part of virtually all diseases, not just solid tumours or stroke, but inflammation, wound healing, peripheral arterial disease”. The drugs that can be made based on this powerful research are endless, and can help eradicate many diseases. 

The groundbreaking work that Semenza, Ratcliffe, and Kaelin have done represents how quickly the field of science and medicine is progressing. Researchers are finding ways to cure what was otherwise considered incurable, which will lead to countless lives being saved. The discovery of HIF and how cells respond to hypoxia can result in the elimination of many illnesses that plague the world today. This is why the committee for the Nobel Prize for Physiology and Medicine of 2019 recognized these hard working scientists. 

The hope now is to expand on the knowledge that these scientists have given the world, and by understanding how our body works better, we will now know how to help it fight diseases better. The use of drugs that regulate HIF can have many effects, some of which may be undesirable. This is why any drugs being developed must be monitored carefully and tested rigorously before they are approved for treating patients. However, the important point is that these findings have given us the power to change the world for the better, and help doctors cure illnesses that would have otherwise been considered possibly fatal and untreatable. 

References

Foley, K. E. (2019, October 7). Winners of the 2019 Nobel Prize in medicine figured out how our cells adapt to oxygen levels. Retrieved October 14, 2019, from https://qz.com/1723227/hypoxia-researchers-win-the-2019-nobel-prize-in-medicine/

Gallagher, J. (2019, October 7). How our cells sense oxygen wins Nobel prize. CNN. Retrieved from https://www.bbc.com/news/health-49959737

Hamzelou, J. (2019, October 7). Nobel prize for medicine goes to discovery of how cells sense oxygen. Retrieved October 14, 2019, from https://www.newscientist.com/article/2218951-nobel-prize-for-medicine-goes-to-discovery-of-how-cells-sense-oxygen/

Kupferschmidt, K. (2019, October 7). Medicine Nobel honors work on cellular system to sense oxygen levels. Retrieved October 14, 2019, from https://www.sciencemag.org/news/2019/10/medicine-nobel-honors-work-cellular-system-sense-oxygen-levels

Lewis, A. (2019, October 9). Nobel prize in medicine awarded for new discovery on how humans respond to oxygen. CNN. Retrieved from https://www.cnn.com/2019/10/07/health/nobel-prize-for-medicine-2019-intl/index.html