… I became captivated by the edifices chemists had raised through experiment and imagination—but still I had a lurking question. Would it not be better if one could really “see” whether molecules as complicated as the sterols, or strychnine were just as experiment suggested?

A great advantage of X-ray analysis as a method of chemical structure analysis is its power to show some totally unexpected and surprising structure with, at the same time, complete certainty.

From the intensity of the spots near the centre, we can infer that the protein molecules are relatively dense globular bodies, perhaps joined together by valency bridges, but in any event separated by relatively large spaces which contain water. From the intensity of the more distant spots, it can be inferred that the arrangement of atoms inside the protein molecule is also of a perfectly definite kind, although without the periodicities characterising the fibrous proteins. The observations are compatible with oblate spheroidal molecules of diameters about 25 A. and 35 A., arranged in hexagonal screw-axis. ... At this stage, such ideas are merely speculative, but now that a crystalline protein has been made to give X-ray photographs, it is clear that we have the means of checking them and, by examining the structure of all crystalline proteins, arriving at a far more detailed conclusion about protein structure than previous physical or chemical methods have been able to give.

I should not like to leave an impression that all structural problems can be settled by X-ray analysis or that all crystal structures are easy to solve. I seem to have spent much more of my life not solving structures than solving them.

I used to say the evening that I developed the first x-ray photograph I took of insulin in 1935 was the most exciting moment of my life. But the Saturday afternoon in late July 1969, when we realized that the insulin electron density map was interpretable, runs that moment very close.

In 1945 J.A. Ratcliffe … suggested that I [join his group at Cavendish Laboratory, Cambridge] to start an investigation of the radio emission from the Sun, which had recently been discovered accidentally with radar equipment. … [B]oth Ratcliffe and Sir Lawrence Bragg, then Cavendish Professor, gave enormous support and encouragement to me. Bragg’s own work on X-ray crystallography involved techniques very similar to those we were developing for “aperture synthesis,” and he always showed a delighted interest in the way our work progressed.

In my own field, x-ray crystallography, we used to work out the structure of minerals by various dodges which we never bothered to write down, we just used them. Then Linus Pauling came along to the laboratory, saw what we were doing and wrote out what we now call Pauling's Rules. We had all been using Pauling's Rules for about three or four years before Pauling told us what the rules were.

Pauling was shocked by the freedom with which the X-ray crystallographers of the time, including particularly Astbury, played with the intimate chemical structure of their models. They seemed to think that if the atoms were arranged in the right order and about the right distance apart, that was all that mattered, that no further restrictions need to be put on them.

Sodium thymonucleate fibres give two distinct types of X-ray diagram … [structures A and B]. The X-ray diagram of structure B (see photograph) shows in striking manner the features characteristic of helical structures, first worked out in this laboratory by Stokes (unpublished) and by Crick, Cochran and Vand2. Stokes and Wilkins were the first to propose such structures for nucleic acid as a result of direct studies of nucleic acid fibres, although a helical structure had been previously suggested by Furberg (thesis, London, 1949) on the basis of X-ray studies of nucleosides and nucleotides.
While the X-ray evidence cannot, at present, be taken as direct proof that the structure is helical, other considerations discussed below make the existence of a helical structure highly probable.

The present rate of progress [in X-ray crystallography] is determined, not so much by the lack of problems to investigate or the limited power of X-ray analysis, as by the restricted number of investigators who have had a training in the technique of the new science, and by the time it naturally takes for its scientific and technical importance to become widely appreciated.

When I saw the alpha-helix and saw what a beautiful, elegant structure it was, I was thunderstruck and was furious with myself for not having built this, but on the other hand, I wondered, was it really right?
So I cycled home for lunch and was so preoccupied with the turmoil in my mind that didn’t respond to anything. Then I had an idea, so I cycled back to the lab. I realized that I had a horse hair in a drawer. I set it up on the X-ray camera and gave it a two hour exposure, then took the film to the dark room with my heart in my mouth, wondering what it showed, and when I developed it, there was the 1.5 angstrom reflection which I had predicted and which excluded all structures other than the alpha-helix.
So on Monday morning I stormed into my professor’s office, into Bragg’s office and showed him this, and Bragg said, 'Whatever made you think of that?' And I said, 'Because I was so furious with myself for having missed that beautiful structure.' To which Bragg replied coldly, 'I wish I had made you angry earlier.'

While the biological properties of deoxypentose nucleic acid suggest a molecular structure containing great complexity, X-ray diffraction studies described here … show the basic molecular configuration has great simplicity. [Co-author with A.R. Stokes, H.R. Wilson. Thanks include to “… our colleagues R.E. Franklin, R.G. Gosling … for discussion.”]