What Mad Pursuit by Francis Crick Page B

for their work on the structures of hemoglobin and myoglobin respectively. Jim Watson, Maurice Wilkins, and I shared the Nobel Prize for Medicine or Physiology in that same year. The citation reads: “. . . for their discoveries concerning the molecular structures of nucleic acid and its significance for information transfer in living material.” Rosalind Franklin, who had done such good work on the X-ray diffraction patterns of DNA fibers, had died in 1958.

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The α Helix
    S IR LAWRENCE BRAGG was one of those scientists with a boyish enthusiasm for research, which he never lost. He was also a keen gardener. When he moved in 1954 from his large house and garden in West Road, Cambridge, to London, to head the Royal Institution in Albemarle Street, he lived in the official apartment at the top of the building. Missing his garden, he arranged that for one afternoon each week he would hire himself out as a gardener to an unknown lady living in The Boltons, a select inner-London suburb. He respectfully tipped his hat to her and told her his name was Willie. For several months all went well till one day a visitor, glancing out of the window, said to her hostess, “My dear, what is Sir Lawrence Bragg doing in your garden?” I can think of few other scientists of his distinction who would do something like this.
    Bragg had a great gift for seeing problems in simple terms, realizing that many apparent complications might fall away if the basic underlying pattern could be discovered. It was thus not surprising that in 1950 he wanted to show that at least some stretches of the polypeptide chain in a protein folded up in a simple manner. This was not an entirely new approach. Bill Astbury, the crystallographer, had tried to interpret his X-ray diagrams of keratin (the protein of hair and fingernails) using molecular models with regular repeats. He had found two forms of these fiber diagrams, which he called α and β. His idea for the β structure was not far from the correct answer, but his suggestion for the a structure was completely wide of the mark. This was partly because he was a sloppy model builder and was not meticulous enough about the distances and angles involved and partly because the experimental evidence was misleading in a way that would have been difficult for him to foresee.
    It was well known that any chain with identical repeating links that fold so that every link is folded in exactly the same way, and with the same relations with its close neighbors, will form a helix (sometimes incorrectly called a spiral by nonmathematicians). The extreme solutions—a straight line or a circle—are regarded mathematically as degenerate helices.
    Bragg’s initial training had been as a physicist, and much of his work on molecular structure had been on inorganic materials such as the silicates. He did not have a detailed familiarity with organic chemistry or the related physical chemistry, though naturally he understood the elements of both these subjects. He decided that a good approach would be to build regular models of the polypeptide backbone, ignoring the complexities of the various side-chains.
    A polypeptide chain has as its backbone a regular sequence of atoms, with the repeat . . . CH-CO-NH . . . (where C stands for carbon, H for hydrogen, 0 for oxygen, and N for nitrogen). The actual way that atoms are linked together is shown in appendix A. To each CH is attached a small group of atoms—often called R by chemists, where “R” stands for “Residue.” Here we shall call R the side-chain. We know now that there are just twenty different side-chains commonly found in proteins. For the smallest residue, glycine, R is just a hydrogen atom—hardly a chain at all. The next largest is called alanine and has a methyl group (CH 3 ) as its side-chain. The others are of various sizes. Some carry a positive electric charge, some a negative one, and some no charge at all. Most of them are fairly small. The largest two,