After the discovery of the DNA double helix, Watson put off a return to his previous field of research, bacterial viruses,
in order to study the structure of ribonucleic acid (RNA), the single-stranded companion molecule to DNA which he and Crick
recognized to be the key intermediary in protein synthesis. In this letter, Watson relayed his thoughts about how DNA specified
the synthesis of RNA, namely by acting as a template, and whether one or both strands of DNA act as a template.
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1954-10-15 (October 15, 1954)
Watson, James D.
Original Repository: Wellcome Library for the History and Understanding of Medicine. Francis Harry Compton Crick Papers
I have meant to reply sooner but have been rather preoccupied with work. Though I have the strongest intentions of returning
to the lab and phage, my spirit remained with RNA and the TIECLUB and so Leslie Orgel and I went back to model building. After
first trying to make sense of TMV (prompted by Rosie's visit -- very amiable!) we tried the old problem of how DNA could
make RNA. To our surprise we have an answer which is not ugly. Our reasoning is the following.
DNA could make RNA by either chemical conversion or acting as a template. The former is ruled out by isotope experiments and
so we have to decide whether the two strand or one strand stage of DNA is active. If a one strand stage operates it likely
does it by a DNA like base pairing mechanism. The answer in this case is trivial, even if it proved possible to stick a RNA
strand in a two stranded structure. Of this I'm sceptical [sic]. Moreover I don't like the idea of the two strands
having to separate since we have no reason to believe it would be stable. Still more I can't see an easy answer of why
ribonucleotides and desoxynucleotides [sic] wouldn't occassionally [sic] get mixed up and thus cause mistakes in the replication
We therefore consider it likely that the two stranded helix is the functional beast. For an attractive force only hydrogen
bonds need to be considered since
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van der Walls [sic] forces would not distinguish Adenine from guanine with the required accuracy. Likewise Uracil from Cytosine.
Two types can be formed NH . . . O and NH . . . N. The latter is too weak if used only about 3 times rk(a) and so the NH .
. . O bond must be employed. The requirement is that the 4 base pairs yield 4 specific holes in such a way that a regular
backbone (1) of RNA can be formed. We have found only one arrangement which works. It employs an 11 diad as follows [diagram]
and so on. The hydrogen bonding is not perfect in that the NH vector in 2 out of 4 cases has approximately 20 degrees from
the CN . . . O angle of 120 degrees. However Pauling and the other chemists are not bothered. The bond is still strong enough
to be useful. In this way we define exactly the backbone arrangement of the third RNA chain. Its diameter is about 15 angstroms.
At first site [sic] this seems nasty especially as the glucosidic angle does not point toward the center. In fact I don't
think it can be built even by cheating with the radius. The main difficulty is the OH groups of the sugar. This problem can
be resolved by eliminating it to form the cyclic anhydride. When this is done, a very very pretty [diagram] helix results
in which everything fits nicely. It of course will be unstable but this shouldn't bother us as we had a device to remove
the RNA once formed from its DNA. That is we postulate its anhydride to decompose to yield normal RNA
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The scheme is completely hypothetical but yet at the same time structurally possible. I don't have the coordinates yet
for the third chain but I know that this will not be an obstacle as there are no bad contacts at all.
It is likely that we shall write up the structure immediately and submit it to the Proceedings of the National Academy. Of
course it may by wrong but at least it's a try to find a template in DNA and until a better one comes along, its useful
to consider. As soon as we get a MS, I'll send it to you for comments. The writing should take about 2 weeks.
I was in Woods Hole during "Edna" -- rather fun -- Szent Gyorgyi's cottage was blown to pieces during "Carol"
and "Edna" blew the pieces still further away.
Regards to Odile, John, Max, etc
P.S. The first RNA TIE has been woven. More on order and The SMOG IS HELL