How could this blunder have happened? Why was Pauling’s model-building approach so spectacularly successful with the alpha-helix and so disastrously ineffective with the triple helix?

Let’s attempt to analyze, one by one, the causes for Pauling’s failing. First, there was the issue of how much time and how much thought he had actually put into solving DNA. Pauling started to think about some aspects of the DNA structure following Ronwin’s paper in November 1951. However, it wasn’t until November 1952, a full year later, that he commenced working earnestly on the problem. Yet by the end of December 1952, after just about a month’s work, he’d already submitted his paper! Compare this to his exertion on the polypeptide structure, where he thought about the issues for about thirteen years, delaying publication several times until he was fairly confident in his model. So, even just in terms of the time invested into thinking about DNA, there is no escape from the conclusion that the DNA model was a rush job. Maurice Wilkins certainly thought so. In an interview on the history of the discovery of DNA structure, he remarked, “Pauling just didn’t try. He can’t really have spent five minutes on the problem himself.” We shall return later to the question of the possible reasons for this haste and apparent lack of focus.

Second, there was a huge difference between the quality of the data on the basis of which Pauling constructed his model for proteins and his model for DNA. In the case of the alpha-helix, Pauling’s collaborator, Robert Corey, had produced a vast arsenal of structural information on sizes, volumes, and angular positions for amino acids and simple peptides. For DNA, by contrast, Pauling was operating almost in a vacuum. The only X-ray photographs available to him were of poor quality and had been produced from a mixture of the A and B forms (unbeknown to him), rendering them almost useless. Worse yet, Pauling was unaware of the high water content of the preparations from which the X-ray diffraction photos were taken. By neglecting the fact that more than one-third of the material in the DNA specimens was water, Pauling obtained a wrong density, which led him to the wrong conclusion of three strands. Lastly, unlike Corey’s extensive work on the building blocks of proteins, there was no equivalent effort on the bases—the subunits of the nucleotides.

Then there were the two astounding memory lapses: one about Chargaff’s base ratios and one about Pauling’s own self-complementarity principle. Chargaff’s findings that the amount of the A base was equal to that of T, and the amount of C equal to that of G, argued for the bases somehow pairing with each other and producing two strands rather than three. Pauling claimed later that he had known about these ratios but had forgotten. Chargaff himself thought that this was the reason for Pauling’s blunder, saying, “Pauling in his structural model of DNA failed to take account of my results. The consequence was that his model did not make sense in the light of the chemical evidence.”

Pauling’s second memory failure was even more astonishing. Recall that Pauling had said in 1948 that if genes consisted of two parts that were complementary to each other in structure, replication was relatively straightforward. In that case, each of the parts could serve as a mold for the production of the other part, and the complex of the two complementary parts as a whole could serve as a mold for a duplicate of itself. Clearly, this principle of self-complementarity suggested strongly a two-stranded architecture, and it was markedly at odds with a structure consisting of three strands. Yet Pauling had apparently completely forgotten this principle by the time he constructed his DNA model.