A previous occasion on which the Croonian lecture was directly concerned with the mechanism of muscular contraction was in 1945, when it was delivered by Professor W. T. Astbury. On that occasion he commented that it was a sign of the times that a physicist should be asked to give the Croonian lecture, and went on to say, and I quote: ‘We are at the dawn of a new era, the era of “molecular biology”, as I like to call it, and there is an urgency about the need for more intensive application of physics and chemistry, and specially structural analysis, to biological problems.’ These were very prophetic words, and, as a physicist just entering biology, I was much interested to read them, and to learn about his experiments. The basic experimental finding which Astbury reported (1947) was that there did not seem to be any important change in the wide angle X-ray diagram from muscle upon contraction; hence it followed that muscles did not contract by any process which simply involved the large-scale disorientation of originally well-ordered polypeptide chains, nor by an alteration in chain configuration in the well-ordered parts of the structure. Astbury suggested instead that there might be ‘specifically active foci’ which one could perhaps paraphrase as ‘larger structural units’ (i.e. larger than individual polypeptide chains) concerned in contraction, which might be studied in the electron microscope or by low angle X-ray diffraction.
Structural basis of the stereoselective formation of the spirooxindole ring in the biosynthesis of citrinadins
