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Biology 1953

Molecular Structure of Nucleic Acids

James Watson & Francis Crick

DNA is a double helix whose paired letters quietly explain how life copies itself.

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In depth · the introduction

DNA is a twisted ladder whose rungs are paired chemical letters — and that pairing is how life makes copies of itself.

The big idea

DNA is the molecule that carries the instructions for building and running a living thing. Watson and Crick worked out its shape: a double helix, like a ladder gently twisted along its length. The two sides are long chemical backbones; the rungs are pairs of four “letters” — A, T, G and C. The crucial discovery was that these letters only pair one way: A always with T, G always with C.

That single rule quietly answers one of biology's oldest questions: how does life copy itself? Unzip the ladder down the middle, and each lonely half automatically spells out exactly what its missing partner must be. Two identical ladders form where there was one. Every time a cell divides, this is what happens — billions of times in your body every day.

How it came about

By the early 1950s everyone knew DNA carried heredity, but no one knew its shape. The race ran between two English labs. At the Cavendish in Cambridge, James Watson and Francis Crick built physical models out of cardboard and wire, hunting for a shape that fit the chemistry. At King's College London, Rosalind Franklin and Maurice Wilkins aimed X-rays at DNA fibres to photograph their structure.

Two clues cracked it. Franklin's astonishingly clear X-ray image — "Photo 51" — revealed at a glance that DNA was a helix of definite size. And the chemist Erwin Chargaff had found that DNA always holds equal amounts of A and T, and equal amounts of G and C. Watson and Crick saw how to put it together: a double helix with A always paired to T and G to C. Their explanation took barely a page in Nature in 1953. Franklin's data was central to it, yet credited only in passing; she died in 1958, and the 1962 Nobel Prize went to Watson, Crick and Wilkins.

Why it mattered

This one-page paper launched molecular biology. Once we understood that life's instructions are written in a four-letter code, we could begin to read it, and eventually to edit it — leading to modern genetics, DNA fingerprinting, gene-based medicine, and tools like CRISPR that rewrite the code on purpose.

A way to picture it

Think of a zip. Each tooth on one side has exactly one tooth it can mesh with on the other. Pull the zip apart and either half tells you precisely what the missing half had to be. DNA's letters are those teeth — A only meshes with T, G only with C — so a single strand is a complete recipe for its partner. That is why one ladder can become two identical ladders.

Interactive DNA: choose a base for each side to see A–T and G–C pair (with two or three hydrogen bonds) while a mismatch fails to bond; then unzip a double-helix ladder so each half rebuilds its complement, turning one ladder into two.

Where it sits

A century earlier Mendel had shown that traits pass down as discrete hidden "factors," but those factors were abstract — no one knew what they were made of. This structure gave the gene a body: a stretch of the four-letter code along the helix. From here the line runs straight to the Human Genome Project and to today's gene-editing medicine.

The original document
Original source text
J. D. Watson & F. H. C. Crick · Nature 171 (1953): 737–738
We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest.
A structure for nucleic acid has already been proposed by Pauling and Corey. … In our opinion this structure is unsatisfactory for two reasons: (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. … (2) Some of the van der Waals distances appear to be too small.
We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis. … We have made the usual chemical assumptions, namely, that each chain consists of phosphate di-ester groups joining β-D-deoxyribofuranose residues with 3′,5′ linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis.
The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. … They are joined together in pairs, a single base from one chain being hydrogen-bonded to a single base from the other chain, so that the two lie side by side.
One of the pair must be a purine and the other a pyrimidine for bonding to occur. … If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms, it follows that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine).
It has been found experimentally that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.
It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
We are much indebted to Dr. Jerry Donohue for constant advice and criticism. … We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King's College, London.
Cavendish Laboratory, Cambridge · April 2, 1953