GAMOW'S DISCOVERY OF NUCLEOTIDES

GAMOW, G.

Possible Relation Between Deoxyribonucleic Acid and Protein Structures.

London, Macmillian and Co, 1954.

Royal8vo. Bound in contemporary full cloth with title to spine. In "Nature", Vol. 173, 1968. Library stamp to upper right corner of title page, otherwise a fine and clean copy. Pp. 709-13. [Entier volume: LXVVI, 1246 pp.].


First printing of Gamow's exceedingly influential discovery of four different kinds of acino-acids, nucleotides, which were to influence Watson and Crick in their further work. To Gamow, most famous for his work within physics and cosmology, this was a highly unfamiliar field. His work was described as: "perhaps the last example of amateurism in scientific work on a grand scale".

"In early 1954, less than a year after J. D. Watson and Francis Crick discovered the double helical structure of DNA, Gamow recognized that the information contained in the four different kinds of nucleotides (adenine, thymine, guanine, cytosine) constituting the DNA chains could be translated into the sequence of twenty amino acids which form protein molecules by counting all possible triplets one can form from four different quantities. This remarkable way in which Gamow could rapidly enter a more or less unfamiliar field at the forefront of its activity and make a highly creative contribution to it, often far more by intuition than by calculation, led Ulam to characterize his work as "perhaps the last example of amateurism in scientific work on a grand scale." It earned him membership in a number of professional societies-American Physical Society, Washington Philosophical Society, International Astronomical Union, American Astronomical Society, U.S. National Academy of Sciences, Royal Danish Academy of Sciences and Letters-as well as an overseas fellowship in Churchill College, Cambridge." (DSB)

"Even as he was starting research in relativistic cosmogony, Gamow came to think that the time was nearly ripe for phys-ics to help biology move beyond its descriptive stage. This perception probably derived from Erwin Schrödinger's What Is Life? The Physical Aspect of the Living Cell (1945) and his longtime friend Max Delbrück's successful migration from theoretical physics to experimental genetics. In any case, Gamow got so caught up with the idea that rejecting his initial plans to revive the Washington conferences with one focused on cosmogony, he instead devoted the first postwar gathering to "the physics of living matter." His preparations for the conference held in the fall of 1946, and his subse-quent endeavours to promote the infusion of more physics into biology, led Gamow to believe by the early 1950s that the central "riddle of life" is how each species' genes shape its distinctive proteins. But lacking any notion about the molecular structure of genes, he could not imagine how to formulate this enigma in a tangible way.
In June 1953 Gamow got an idea for doing so from reading James Watson and Francis Crick's soon-to-be-famous Nature paper on DNA's structure. Confident that they were on the right track, he impulsively introduced himself to them by letter, praising them for their success in moving biology into the "exact' sciences" and expressing his hope that he could meet with them in England at the end of the summer to talk about the possibility of using combinatorics to tackle genetic problems. As both were planning to be away then, Watson discussed Gamow's letter briefly with Crick, then filed it away. In late October, undeterred by their failure to respond, Gamow sent a short note off to Nature on a "Possible Relation between Deoxyribonucleic Acid and Protein Structures" (1954). He opened by crediting Watson and Crick with having established that the basic hereditary materials are DNA molecules. Then he daringly outlined what soon evolved into the protein-coding research program. He proposed that each organism's DNA "could be characterized by a long number written in a four-digital system" that "completely determined" the composition of its unique complement of proteins, which in turn "are long peptide chains formed by about 20 different amino-acids [that] can be considered as 'long' words based on a 20-letter alphabet." The problem to be solved was how these "four-digital 26 numbers [are] translated into such 'words.'" Gamow closed by suggesting how this might be done and promising that a fuller account would be published elsewhere.
During the next few months, Gamow plunged into work on the protein-coding problem. He wrote up an expanded version of his note in Nature for the National Academy of Sciences' Proceedings and, when it was not accepted there-possibly because Gamow jokingly listed his fictional character Tompkins as co-author-submitted it successfully (without Tompkins as co-author) to the Royal Danish Society of Sciences' biological series. He also spurred first Crick, then Watson, and then many other researchers-especially those associated with Caltech's Delbrück and Berkeley's Gunther Stent-to join the enterprise of identifying how DNAcoded proteins. As this growing research circle reviewed prior and ongoing experimental work of relevance, a consensus soon emerged that DNA did not serve as a simple template in protein synthesis. It appeared instead that the coding might be a two-step process in which DNA first coded RNA and then RNA coded proteins. Although initially resisting this view, Gamow ended up as the "synthesizer" in the "RNATie Club," founded in mid-1954 to foster the circle's informal communications and camaraderie.
Gamow's involvement in the expanding circle of coding researchers remained intense for another year and a half. He found it stimulating to be once again on the wave crest of an exciting new specialty. Just as important if not more so, he enjoyed being at the center of the ambitious circle's partying and joking. But starting in late 1955, years before a consensus emerged about the coding of proteins, Gamow's engagement with the problem wilted. One reason was that his marriage of 23years had just fallen apart. Asecond, and more compelling reason was that, as he had experienced toward the end of his active participation in nuclear, stellar, and cosmogonical researches, he was getting bored with coding research because the opportunities for someone with his freewheeling style were ever more limited in this increasingly competitive and empirically constrained field" (George Gamow: A Biographical Memoir, National Academy of Sciences).

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