Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. [With:] Molecular Structure of Deoxypentose Nucleic Acids. [With:] Molecular Configuration in Sodium Thymonucleate

The Molecule That Copies Itself. First edition, in the rare three-paper offprint issue - the author's separate that gathers the whole of the 25 April 1953 Nature announcement - of the discovery of the molecular structure of DNA, the double helix, and with it the mechanism by which living things copy their inheritance. The journal's printer reset the three papers of that issue into a single pamphlet for the authors to send to colleagues. This three-paper offprint is far scarcer than the journal itself. Watson and Crick conducted no experiments of their own. Working at the Cavendish Laboratory in Cambridge across eighteen months, they unified the scattered findings of others into a single structure - two helical sugar-phosphate chains wound about a common axis, running in opposite directions, with the four bases paired across the inside of the ladder. The pairing was the whole of it: adenine always to thymine, cytosine always to guanine, so that the sequence of one strand fixes the sequence of the other. From that single constraint followed the answer to the oldest question in biology - how a gene is copied, with near-perfect fidelity, generation upon generation. The structure the paper sets out is exact and spare. Two right-handed helical chains coil about a common axis, the sugar-phosphate backbones on the outside and the paired bases stacked flat within, perpendicular to the axis; a residue recurs every 3.4 ångström along each chain, the helix repeats after ten residues at intervals of 34 ångström, and the whole forms a cylinder some twenty ångström across. Because the phosphates face outward into the surrounding water, solvent and cations reach them freely, and the model so accounts for the high water content of the fibres that Franklin had measured. Crick's lone schematic - two ribbons winding about a vertical fibre axis, the base-pairs drawn as horizontal rods between them - expresses the entire proposal in a single figure; it is this drawing, since become one of the most reproduced diagrams in modern science, that fills the second page of the present pamphlet. Everything the structure asserts is checked against the X-ray evidence: the perpendicular bases, the regular backbones, the antiparallel chains, each a feature the diffraction pattern demanded rather than a freedom the model-builders allowed themselves. The problem they solved was eighty years in the making. In 1869 the Swiss physiological chemist Friedrich Miescher, washing the pus from used surgical bandages to isolate the proteins of white blood cells, instead struck a substance from the cell nucleus richer in phosphorus than any protein and resistant to protein digestion; he named it nuclein and guessed that a whole family of such molecules might exist. The guess was forgotten. By the early 1950s researchers spoke confidently of the gene as the unit of heredity yet could not say what one looked like or how it was copied. Oswald Avery had shown in 1944 that it was DNA, not protein, that carried hereditary character in pneumococcus, but many held the molecule too monotonous - a backbone of four repeating units - to encode the intricacy of a living thing; the genetic material, they reasoned, surely had to be protein, with its twenty amino acids and endless variety. Crick and Watson grasped early that the three-dimensional shape of the gene was the central problem of the new biology, and that without it heredity could not be understood. They seized it at their first meeting, in 1951, and held to it with a single-mindedness that required them to absorb genetics, biochemistry, physical chemistry, and X-ray crystallography at once. Several disconnected results lay waiting to be joined. Alexander Todd had established that the molecular backbone was a regular chain of alternating phosphate and deoxyribose sugar. Erwin Chargaff had found that, however widely the proportions of the four bases varied between species, adenine and thymine always occurred in equal amounts, as.…