What Mad Pursuit by Francis Crick Page A

successfully to help solve the structure of small molecules. There had previously been one or two halfhearted attempts to use it on proteins, but these had failed, probably because the chemistry used was too crude. Nor was I helped by my title. I had told John Kendrew the sort of thing I intended to say and asked him what I should call it. “Why not,” he said, “call it ‘What Mad Pursuit’!” (a quotation from Keats’ “Ode on a Grecian Urn”)—which I did.
    Bragg was furious. Here was this newcomer telling experienced X-ray crystallographers, including Bragg himself, who had founded the subject and been in the forefront of it for almost forty years, that what they were doing was most unlikely to lead to any useful result. The fact that I clearly understood the theory of the subject and indeed was apt to be unduly loquacious about it did not help. A little later I was sitting behind Bragg, just before the start of a lecture, and voicing to my neighbor my usual criticism of the subject in a rather derisive manner. Bragg turned around to speak to me over his shoulder. “Crick,” he said, “you’re rocking the boat.”
    There was some justification for his annoyance. A group of people engaged in a difficult and somewhat uncertain undertaking are not helped by persistent negative criticism from one of their number. It destroys the mood of confidence necessary to carry through such a hazardous enterprise to a successful conclusion. But equally it is useless to persist in a course of action that is bound to fail, especially if an alternative method exists. As it has turned out, I was completely correct in all my criticisms with one exception. I underestimated the usefulness of studying simple, repeating, artificial peptides (distantly related to proteins), which before long was to give some useful information, but I was quite correct in predicting that only the isomorphous replacement method could give us the detailed structure of a protein.
    I was still, at this time, a beginning graduate student. By giving my colleagues a very necessary jolt I had deflected their attention in the right direction. In later years few people remembered this or appreciated my contribution except Bernal, who referred to it more than once. Of course in the long run my point of view was bound to emerge. All I did was to help create an atmosphere in which it happened a little sooner. I never wrote up my critique, though my notes for the talk survived for a few years. The main result as far as I was concerned was that Bragg came to regard me as a nuisance who didn’t get on with experiments and talked too much and in too critical a manner. Fortunately he changed his mind later on.
    I was, incidentally, not alone on my opinion. In those days most of the other crystallographers believed that protein crystallography was hopeless, or likely to come to fruition only in the next century. In this they were carrying their pessimism too far. I at least had a close acquaintance with the subject and could see one possible method of solving the problem. It is interesting to note the curious mental attitude of scientists working on “hopeless” subjects. Contrary to what one might at first expect, they are all buoyed up by irrepressible optimism. I believe there is a simple explanation for this. Anyone without such optimism simply leaves the field and takes up some other line of work. Only the optimists remain. So one has the curious phenomenon that workers in subjects in which the prize is big but the prospects of success very small always appear very optimistic. And this in spite of the fact that, although plenty appears to be going on, they never seem to get appreciably nearer their goal. Parts of theoretical neurobiology seem to me to have exactly this character.
    Fortunately, solving the structure of protein by X-ray diffraction was not as hopeless as it had seemed to some. In 1962 Max Perutz and John Kendrew shared the Nobel Prize for Chemistry