Monday 7 October 2019

Nobel Prize for working out how EPO works!

It’s nice to blog about the science of EPO (erythropoietin) without immediately talking about doping for a change. Today three great scientists were awarded the Nobel Prize in Physiology or Medicine for working out how mammalian cells sense and adapt to oxygen availability. The science underpinning the award to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza is described here. 

Most sports scientists and athletes know that EPO is a protein that increases the number of red blood cells. Altitude training increase levels of EPO and hence increases the number of red blood cells, increasing the amount of oxygen in the blood and potentially increasing performance. The discoveries of Semenza, Ratcliffe and Kaelin revealed that a protein called HIF-1 alpha binds to DNA and increases the production of several proteins including EPO. EPO then binds to other proteins that increase the synthesis of red blood cells. However, in the presence of oxygen HIF-1 alpha is degraded inside the cell in a structure called the proteasome. Thus, when oxygen is abundant there is not enough HIF-1 alpha to bind to DNA, EPO levels fall to normal and red blood cell production decreases. 

Of course, directly injecting EPO or receiving a blood transfusion bypasses the clever biological pathways that safely regulate the number of red blood cells in the body that match oxygen supply and demand. Hence the reason for blood doping being banned in sport. In fact, if you look at current research following on from the work of Kaelin, Ratcliffe and Semenza, you can see other proteins that could be targeted to increase or decrease red blood cell production. This is relevant for developing new drugs to treat anaemia and cancer. Of course it could also be relevant to sports doping; the HIF-1 alpha/ EPO pathway is perhaps the most obvious “known unknown” when it comes to new drugs in sport. By this I mean, we know modifying this pathway could improve sports performance, but it is unknown if anyone is currently exploiting it. Or at least no one has been caught doing it, which amounts to the same thing. But it would not surprise me if people were trying.

In a personal level this is the second time my research career has intersected with research that led to a Nobel Prize. The other time was the role of the gas nitric oxide that controls blood flow in the body. It is one of the privileges of a scientific career to be close to seeing such clever people in action, even if that closeness sometimes just involves admiring their research at conferences and in publications.