"The double helix: a personal view"

Date:: 1973-1974

Reference:: PP/CRI/H/5/10

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Licence: In copyright

Credit: "The double helix: a personal view". Source: Wellcome Collection.

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(Reprinted from Nature, Vol. 248, No. 5451, pp. 766 769, April 26, 1974) The double helix: a personal view Francis Crick Medical Research Council Laboratory for Molecular Biology, Hills Road, Cambridge, UK Francis Crick reviews the papers published 21 years ago on the structure of DNA and the reaction to them. For this anniversary I thought it might be appropriate to look back, in a rather informal way, at the original papers on the structure of DNA to see how they appear today in the light of 21 years of research. During the spring and summer of 1953 Jim Watson and I wrote four papers on the structure and function of DNA. The first appeared in Nature on April 25 accompanied by two papers from King's College London, the first by Wilkins, Stokes and Wilson, the other by Franklin and Gosling. Five weeks later we published a second paper in Nature, this time on the genetic implications of the structure. A general dis cussion was included in the volume that came from that year's Cold Spring Harbor Symposium, the subject of which was viruses. We also published a detailed technical account of the structure, with rough coordinates, in an obscure jour nal 1 in the middle of 1954. The first Nature paper was both brief and restrained. Apart from the structure itself the only feature of the paper which has excited comment was the short sentence: It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mech anism for the genetic material. This has been described as 'coy', a word that few would normally associate with either of the authors, at least in their scientific work. In fact it was a compromise, reflecting a difference of opinion. I was keen that the paper should discuss the genetic impli cations. Watson was against it. He suffered from periodic fears that the structure might be wrong and that he had made an ass of himself. I yielded to his point of view but insisted that something be put in the paper, otherwise some one else would certainly write to make the suggestion, as suming we had been too blind to see it. In short, it was a claim to priority. Why, then, did we change our minds and, within only a few weeks, write the more speculative paper of May 30? The main reason was that when we sent the first draft of our initial paper to King's College we had not yet seen their own papers. Consequently we had little idea of how strongly their X-ray evidence supported our structure. The famous 'helical' X-ray picture of the B form, reproduced by Franklin and Gosling in their paper, had been shown to Watson, but he certainly had not remembered enough details to construct the arguments about Bessel functions and distances which the experimentalist gave. I myself, at that time, had not seen the picture at all. Consequently we were mildly surprised to discover that they had got so far and delighted to see how well their evidence supported our idea. Thus emboldened, Watson was easily persuaded that we should write a second paper. The papers in Nature The two experimental papers of April 25 overlap to a con siderable extent. Rosalind Franklin's paper mentions the crystalline A structure, but only briefly, except for the claim that the Patterson superposition function (which was in the press at the time) supported two chains rather than three. Both papers stress that there must be more than one chain in the structure. Indeed Maurice Wilkins had personally told Chargaff that a year or so earlier. Both present the argu ment that the positions of the intensity maxima ruled out two (parallel) chains related by a dyad parallel to the fibre axis. Neither gave the neat argument, due to Watson, that their own density measurement, together with the observed change in length between the two forms, supported two chains rather than three. Franklin noted that if there were several chains they could not be equally spaced and that 'equivalence' favoured two rather than three. It was not explicitly stated, however, that equivalence implies dyad axes perpendicular to the fibre axis and that therefore the two chains must run in opposite directions. Nor did she realise that the monoclinic unit cell of the A form also suggested this, although we had deduced this from her own experimental data. Both papers correctly concluded from the intensity posi tions that the phosphate-sugar backbone was on the outside of the structure and that the bases were stacked on the in side. Franklin repeated the argument, which she had made to us verbally a year earlier, that the phosphates would be hydrated (in which she was perfectly right) and therefore that they would probably be on the outside of the molecule. In short, both the groups at King's College had obtained a fairly general idea of the structure but they had done no proper model building. Mainly because of this they had missed the pairing of the bases and they had completely overlooked the significance of Chargaff's rule. The omissions in the paper by Watson and myself are also striking. The structure is produced like a rabbit out of a hat, with no indication as to how we arrived at it. No dimen sions are given (let alone coordinates) except that the base pairs were 3.4 Â apart and that the structure had 10 base pairs in its repeat. The exact nature of the base pairing was not immediately obvious; nor even unambiguous since at that time there were two systems for numbering pyrimi- dine rings. Most of this information was provided in the subsequent papers. However the general nature of the structure was clear enough, though the tone of the paper (it must be regarded as unproved until it has been checked against more exact results) was, apart from the short first paragraph, rather muted.