This year’s Nobel Prize in Medicine or Physiology was awarded to William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza for the discovery of how cells sense oxygen and adapt their metabolism to different oxygen levels. Their findings are of great clinical relevance and explain, among other things, how erythrocyte formation is regulated and the mechanism for the development of various cancers as also discussed in the K2-editorial in Week 42.
I think it is interesting that all the three award winners are clinicians and have approached the problem of oxygen sensing from different angles. The paediatrician Semenza and the nephrologist Ratcliffe studied erythropoietin regulation, while oncologist Kaelin’s approach was to understand a rare tumour syndrome characterized by stress hormone-producing tumours in the adrenal medulla (phaeochromocytoma), angioblastomas in the central nervous system, and multifocal renal cancer (von Hippel Lindau’s syndrome (VHL)). He found that the VHL protein forms a complex with hypoxia-inducible factor 1-alpha (HIF1a) that leads to degradation of HIF1a. Lack of VHL generates a hypoxic signal eventually leading to angiogenesis and tumour formation.
What can we learn from them? Perhaps one message is that it is difficult to predict where the next major medical breakthrough will come from, and that too much ear marking of research resources in specific directions (read research programs) is less fruitful than letting scientists choose their own problems to study. As one research leader put it: “We don’t care what you do; we want you to be one of the leaders in your field”. Another tenet is the power of translational research in which studies of rare monogenic diseases can lead to breakthroughs in the understanding of basic physiological mechanisms that, in turn, open up to the development of new exciting therapies.
Let this year’s Nobel Prize be an inspiration for good translational research