Comment
Andrew Huxley, John Eccles and Alan Hodgkin received the 1963 Nobel Prize in Physiology or Medicine "for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane". The experiments that paved the way to the award were completed already in 1952 by Hodgkin and his student Huxley. Briefly, it was shown that nerve impulses are generated by ions flowing in and out of nerve cells. These fluxes are controlled by changes in the nerve cell membrane. The recipients of the 1963 Nobel Prize hence established that chemical processes are crucial to nerve signal transmission and that the latter is not purely electrical, as was believed before.
In the present talk Huxley points out that after finishing his work on ionic mechanisms in 1952 he and his collaborators had arrived at a dead end: while it was now apparent that ion-channels in cell membranes must exist, there was no way of isolating or characterizing them. It took 25 years until two German scientists, Erwin Neher and Bert Sakmann, established the experimental methods to study single ion channels. They received the 1991 Nobel Prize in Physiology or Medicine for their work.
In default of methods to study ion-channels, Huxley changed his scientific focus to the mechanisms of muscular contraction. He remained active in this field until his retirement in 1997. In the present lecture, he gives a review of the history of muscular contraction research, beginning in 1807. It was in this year that Swedish scientist Jöns Jakob Berzelius observed for the first time that contracting muscles release lactic acid. Huxley goes on to tell the story of our current understanding of muscular contraction as a story of several revolutions. In doing so he puts particular emphasis on the notion that these revolutions boosted our level of understanding - but that the sudden shifts in scientific focus also entailed unfavourable losses in scientific expertise.
A first revolution after Berzelius initial observation was the discovery that lactic acid is in fact not triggering muscular contraction and that contracting muscles release phosphate. In the 1940s it was shown that this phosphate originates from ATP hydrolysis. However, according to Huxley this revolution made the scientific community focus too much on the molecular aspects of muscular contraction, neglecting the structural or physiological ones. He himself did not follow the mainstream and, together with others established the revolutionary sliding filament model of muscular contraction in 1954, which is accepted until today. It originated from microscopic rather than chemical observations.
Towards the end of his talk, Huxley suggests that the elucidation of the structures of key proteins involved in muscular contraction, myosin and actin, in the early 1990s could, again, cause an unfavourable shift of the scientific interest towards single molecule events and advises the audience to keep the structural and physiological aspects of muscular contraction in mind.
David Siegel
