The Double Helix: A Personal Account of the Discovery of the Structure of DNA

by James D. Watson

Worrying about complications before ruling out the possibility that the answer was simple would have been damned foolishness. Pauling never got anywhere by seeking out messes.

I had decided to build two-chain models. Francis would have to agree. Even though he was a physicist, he knew that important biological objects come in pairs.

I suspected that we now had the answer to the riddle of why the number of purine residues exactly equaled the number of pyrimidine residues. Two irregular sequences of bases could be regularly packed in the center of a helix if a purine always hydrogen-bonded to a pyrimidine. Furthermore, the hydrogen-bonding requirement meant that adenine would always pair with thymine, while guanine could pair only with cytosine. Chargaff’s rules then suddenly stood out as a consequence of a double-helical structure for DNA. Even more exciting, this type of double helix suggested a replication scheme much more satisfactory than my briefly considered like-with-like pairing. Always pairing adenine with thymine and guanine with cytosine meant that the base sequences of the two intertwined chains were complementary to each other. Given the base sequence of one chain, that of its partner was automatically determined. Conceptually, it was thus very easy to visualize how a single chain could be the template for the synthesis of a chain with the complementary sequence.