I wasn’t aware of Chargaff’s rules when he said them, but the effect on me was quite electric because I realized immediately that if you had this sort of scheme that John Griffith was proposing, of adenine being paired with thymine, and guanine being paired with cytosine, then you should get Chargaff’s rules.
I was very excited, but I didn’t actually tell Chargaff because it was something I was doing with John Griffith. There was a sort of musical comedy effect where I forgot what the bases were and I had to go to the library to check, and I went back to John Griffith to find out which places he said. Low and behold, it turned out that John Griffith’s ideas fitted in with Chargaff’s rules!
This was very exciting, and we thought “ah ha!” and we realized—I mean what anyone who is familiar with the history of science ought to realize—that when you have one-to-one ratios, it means things go to together. And how on Earth no one pointed out this simple fact in those years, I don’t know.

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.
[Co-author with Francis Crick]

Of the nucleosides from deoxyribonucleic acids, all that was known with any certainty [in the 1940s] was that they were 2-deoxy-­D-ribosides of the bases adenine, guanine, thymine and cytosine and it was assumed that they were structurally analogous to the ribonucleosides. The chemistry of the nucleotides—the phosphates of the nucleosides—was in a correspondingly primitive state. It may well be asked why the chemistry of these groups of compounds was not further advanced, particularly since we recognize today that they occupy a central place in the history of the living cell. True, their full significance was for a long time unrecognized and emerged only slowly as biochemical research got into its stride but I think a more important reason is to be found in the physical properties of compounds of the nucleotide group. As water-soluble polar compounds with no proper melting points they were extremely difficult to handle by the classic techniques of organic chemistry, and were accordingly very discouraging substances to early workers. It is surely no accident that the major advances in the field have coincided with the appearance of new experimental techniques such as paper and ion-exchange chromatography, paper electrophoresis, and countercurrent distribution, peculiarly appropriate to the compounds of this group.

The essential molecule of reproduction, DNA, … is composed of only four nitrogen bases (adenine, thymine, guanine, and cytosine), the sugar deoxyribose, and a phosphate. DNA’s intermediary, RNA, differs only by the substitution of the sugar ribose for deoxyribose and the nitrogen base uracil for thymine. The proteins of living organisms are made with a mere 20 amino acids, all arranged in a “left-handed” configuration. Taking into account all 28 building blocks, or “letters” (20 amino acids, five bases, two sugars, and one phosphate), the message is clear: With such a limited alphabet, all life must have had a common chemical origin.

The language of the genes has a simple alphabet, not with twenty-six letters, but just four. These are the four different DNA bases—adenine, guanine, cytosine and thymine (A, G, C and T for short). The bases are arranged in words of three letters such as CGA or TGG. Most of the words code for different amino acids, which themselves are joined together to make proteins, the building blocks of the body.

The results serve to disprove the tetranucleotide hypothesis. It is, however, noteworthy—whether this is more than accidental, cannot yet be said—that in all desoxypentose nucleic acids examined thus far the molar ratios of total purines to total pyrimidines, and also of adenine to thymine and of guanine to cytosine, were not far from 1.