CRICK, Francis, Leslie BARNETT, Sydney BRENNER (b. 1927) and R.J. WATTS-TOBIN. The General Nature of the Genetic Code. Cambridge: [c. 1961].
Mechanically-reproduced typescript, 2°, 21ff, printed on rectos only, stapled. Collation: ff.[i] title; 1-11 text;  acknowledgements;  references;  table 1;  table 2;  table 3; [17-20] figures 1-6, that on f.20 a pasted-on photographic diagram. (Light oxidisation-marking caused by a paperclip, some minor marginal chipping, title and f.20 lightly marked, f.20 detached and with short marginal tears). Modern cloth case with gilt leather lettering-piece on upper cover. Provenance: John Derek Smith (1924-2003, presentation inscription from Crick on title 'John , Hope to write you a long letter in a , day or so , Francis').
A PRE-PUBLICATION, MECHANICALLY-REPRODUCED TYPESCRIPT OF A KEY PAPER IN THE HISTORY OF MUTAGENESIS, PROPOSING THAT THE GENETIC CODE IS A TRIPLET CODE. INSCRIBED BY CRICK TO HIS CAMBRIDGE COLLEAGUE, THE MICROBIOLOGIST DEREK SMITH.
The paper -- 'admired throughout the science as a classic of intellectual clarity, precision, and force' (H.F. Judson The Eighth Day of Creation (London: 1979), p.485) -- was published under the revised title 'General Nature of the Genetic Code in Proteins' in Nature (London: 1961), vol. CXCII, pp.1127-1232, and was the result of work that had begun in 1954 to answer questions raised by the initial discovery of the structure of DNA. The paper states that the genetic code was a triplet code (i.e. that three -- and not two or four -- bases are required to code an amino acid); gives the 'syntax' necessary to 'read' long sequences of bases correctly; and reveals that the code 'is probably "degenerate"; that is, in general one particular amino acid can be coded by one of several triplets of bases' (f.1).
'In a long series of complex experiments, they induced mutations in the DNA of bacteriophage T4, a virus that infects bacteria. The mutations changed individual bases in the DNA, knocking out the function of a crucial phage gene (the B cistron of the rII region of T4; the mutations were produced by proflavin, which adds or deletes a base rather than changing a base). When two or four mutations were together, the gene was still inactive, but when three mutations were put together in the same gene, the gene started to work again. They concluded that the genetic code is a triplet code (three bases code for one amino-acid), and that the code is degenerate (an amino-acid may be coded by more than one triplet of bases)' (The Wellcome Trust, 'Exploring the Crick Papers. 1961 The Triplet Code', online: http://www.wellcome.ac.uk/en/genome/geneticsandsociety/hg13f018.html). The potential importance of the paper's hypothesis is given in its conclusion: 'If the coding ratio is indeed 3, as our results suggest, and if the code is the same throughout Nature, then the genetic code may well be solved within a year or two' (f.11).
The published text generally follows this reproduced typescript closely, with the exception of certain variations, some minor and some significant; in the former category are changes probably due to either Nature's editorial practices (e.g. the substitution of 'that is' for the original 'i.e.') or the correction of typographic errors and stylistic amendments. The significant changes occur on p.1228 of the published version (where one complete and one part-paragraph describing the experimental procedures in detail are omitted and text from the partially-deleted paragraph is inserted later in the text); p.1230 (where the number of examples described and tabulated in table 2 is increased from 27 to 28); p.1231 (where the sentence 'In any case the results of Fig. 5 must be explained by any alternative theory which may be devised to fit our experimental fact' has been removed from the end of the section 'Joining Two Genes Together').
The present copy is from the library of the microbiologist John Derek Smith (himself a pioneer in the field of nucleic acid research), whose work with Roy Markham at the Molteno Laboratory, Cambridge on the separation by paper electrophoresis of single nucleotides and small oligonucleotides obtained from the RNA genomes of plant and animal viruses was of great importance in establishing the chemical structure of RNA in 1952, the year before Watson and Crick's discovery of the structure of DNA. Smith is remembered in the early 1950s by Watson thus: 'We also saw much of Roy Markham and John Smith ("little Smith"), then supported by the conventional plant virologist Kenneth Smith ("big Smith"), all located on the upper floor of the Molteno Institute [...] the only building in Cambridge with effective central heating' (A Passion for DNA (Oxford: 2000), p.18). In the late 1950s Smith went to America, working first at Berkeley and then at Caltech, before taking up a position in the Division of Molecular Genetics at the Laboratory of Molecular Biology, Cambridge (where his colleagues included Francis Crick and Sydney Brenner) in 1962. For the published paper, cf. Garrison-Morton (1993) 256.8; Norman 534.