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The most fundamental objection to Gamow’s scheme is that it does not distinguish between the direction of a sequence; that is, between Thr. Pro. Lys. Ala. and Ala. Lys. Pro. Thr…. There is little doubt that Nature makes this distinction, though it might be claimed that she produces both sequences at random, and that the “wrong” ones—not being able to fold up—are destroyed. This seems to me unlikely. That observation, made in passing, was the first acknowledgment of a theoretical question that is still unanswered: in general terms, what does the cell do with information it possesses on the DNA—and some organisms possess some DNA sequences in thousands of copies—that it does not use to code for proteins? This difficulty brings us face-to-face with one of the most puzzling features of the DNA structure—the fact that it is non-polar, due to the dyads at the side; or put another way, that one chain runs up while the other runs down. It is true that this only applies to the backbone, and not to the base sequence, as Delbrück has emphasized to me in correspondence. This may imply that a base sequence read one way makes sense, and read the other way makes nonsense. Another difficulty is that the assumptions made about which diamonds are equivalent are not very plausible…. [Gamow’s idea] would not be unreasonable if the amino acid could fit on to the template from either side, into cavities which were in a plane, but the structure certainly doesn’t look like that. The bonds seem mainly to stick out perpendicular to the axis, and the template is really a surface with knobs on, and presents a radically different aspect on its two sides…. What, then are the novel and useful features of Gamow’s ideas? It is obviously not the idea of amino acids fitting on to nucleic acids, nor the idea of the bases sequence of the nucleic acids carrying the information. To my mind Gamow has introduced three ideas of importance: (1) In Gamow’s scheme several different base sequences can code for one amino acid…. This “degeneracy” seems to be a new idea, and, as discussed later, we can generalise it. (2) Gamow boldly assumed that code would be of the overlapping type…. Watson and I, thinking mainly about coding by hypothetical RNA structures rather than by DNA, did not seriously consider this type of coding. (3) Gamow’s scheme is essentially abstract. It originally paid lip service to structural considerations, but the position was soon reached when “coding” was looked upon as a problem in itself, independent as far as possible of how things might fit together…. Such an approach, though at first sight unnecessarily abstract, is important. Finally it is obvious to all of us that without our President the whole problem would have been neglected and few of us would have tried to do anything about it.
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Horace Freeland Judson (The Eighth Day of Creation: Makers of the Revolution in Biology)