This year’s Nobel Prize in Chemistry goes to Robert Lefkowitz and Brian Kobilka for their study of how cells interact with their environment. Everyone has heard of various “receptors.” The term has pretty well entered the common lexicon, and much of that is because a large quantity of modern drugs interact with these receptors, called G-protein coupled receptors.
What’s exciting about this work is not that it is a story of how science evolves and deepens over the years, even though it is: from the late 60’s when Lefkowitz enters the picture, through the discovery of the G-proteins (which itself earned Gilman and Rodbell the 1994 Nobel Prize in Physiology or Medicine,) through Kobilka’s discovery of the gene that encodes for a particular receptor of interest – the beta-adrenergic receptor. Any of you who are taking beta-blockers for hypertension are tinkering with the function of this receptor on a daily basis. This long-running line of research recently culminated in Kobilka’s recent publication (Nature 469, 175) of the crystal structure of an activated beta-adrenergic receptor. As the Nobel committee so eloquently put it , this was “a molecular masterpiece – the result of decades of research.”
Rather, what is exciting was Kobilka’s observation that the structure of this beta receptor was substantially similar to the rhodopsin detector in the eye. The implication of Kobilka’s work was that the body was able to use similar structures to accomplish widely different tasks and that at least our ability to see shares a common evolutionary root with other wholly internal sensing mechanisms. It has undoubtedly had and will continue to have a great deal of impact on our search for new pharmaceutical therapies but also on our understanding of the complex biomolecular machinery of life.
As amazing as this work is, I can’t help but feel a bit conflicted about this Nobel Prize. Understand that this has nothing to do with the research or the researchers, but rather is about the choices of the Nobel committee. This award feels like an underhanded way of awarding a second Nobel Prize in Physiology. This may be unfair on two counts. First, there is a long track record of biochemistry receiving well-deserved chemistry prizes for chemical research. The classic example of this was Frederick Sanger, who won the 1958 Nobel Prize in Chemistry for the structure of proteins, particularly insulin, and then shared the 1980 prize for his work on nucleic acid. The work, while on biological substrates, was clearly well ensconced in the fields of chemical research. Second, it is undeniable that certain frontiers of science are in the realm of biological systems and that the research that is timely and novel right now will inevitably have some biological bent. What bothers me is that the motivation of the decades of research was not in my mind the chemistry underlying the receptor, but rather the physiology of the receptor’s behavior and its mechanism of action. Further, the capstone piece of work cited by the Nobel committee was the Nature paper mentioned earlier which dealt with the structure of an activated receptor, which calls Watson and Crick’s 1962 Nobel Prize to mind. It is of note that this work received the Nobel Prize in Physiology or Medicine.
Many chemists struggle with the “bio-creep” of the prizes, which is probably inevitable and a little healthy. I will also admit to have given a little friendly joshing to some of my colleagues who have complained about it. But in this particular case, I share the sentiments expressed at Chembark that this was excellent work deserving of the Nobel Prize in Physiology or Medicine.
(Update: Derek Lowe has written a very well thought out post about this topic as well.)