The early work on the structure and constitution of the nucleic acids by biochemist Phoebus Levene did not help to spark interest in these molecules. If anything, his studies achieved precisely the opposite effect. Levene managed to distinguish the deoxyribonucleic acid (DNA) from ribonucleic acid (RNA), and to find some of their properties. But his results generated the impression that these were rather simple and dull substances unsuited for the complex tasks of governing growth and replication. In the words of cytologist Edmund Beecher Wilson (in 1925): “The nucleic acids of the nucleus are on the whole remarkably uniform . . . In this respect they show a remarkable contrast to the proteins, which, whether simple or compound, seem to be of inexhaustible variety.” This impression persisted throughout the 1940s. By then, DNA was known to be composed of unbranched chains of units called nucleotides. The nucleotides themselves also appeared to be fairly uncomplicated, with each one containing three subunits: a phosphate group (a phosphorus atom bonded to four oxygen atoms), a five-carbon sugar, and one of four nitrogen-containing bases. The four bases were: cytosine and thymine, which were single ringed; and adenine and guanine, which were both double ringed (see figure 13). What was still not known, even in 1951, was the actual structure: how exactly the subunits connected to each other to form nucleotides, and the nature of the links between the nucleotides themselves. However, while all of this seemed to be fairly interesting from a chemical perspective, at the end of 1951 most geneticists still believed that DNA’s only role was structural, acting perhaps as a scaffold for the more sophisticated proteins rather than being directly related to heredity.

This fact in itself was somewhat surprising, given that in a paper published back in 1944, biologists Oswald Avery, Colin MacLeod, and Maclyn McCarty provided strong experimental evidence that the genetic material of living cells was composed of DNA. Avery and his colleagues grew large quantities of virulent bacteria, and after managing to separate them into their biochemical constituents, they concluded that DNA molecules—and not proteins or fats—were the components responsible for converting nonvirulent bacteria into virulent ones. In a May 1943 letter describing the results to his bacteriologist brother, Roy, Avery concluded, “So there’s the story, Roy—right or wrong it’s been good fun and lots of work.” The reason that Avery’s findings did not get the attention they deserved may have had to do with the fact that since none of the three scientists was a geneticist, their conclusions were formulated with such caution that many of the life scientists failed to appreciate their full import. The statement in the paper read: “If it is ultimately proved beyond reasonable doubt that the transforming activity of the material described is actually an inherent property of the nucleic acid, one must still account on a chemical basis for the biological specificity of its action.” Still, careful readers should have taken notice of the paper’s summary: “The data obtained . . . indicate that, within the limits of the methods, the active fraction contains no demonstrable protein . . . and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid [DNA].”

Figure 13

Pauling was familiar with Avery’s work, but even he admitted in a later interview that at the time he did not believe that DNA had much to do with heredity: “I knew the contention that DNA was the hereditary material. But I didn’t accept it; I was so pleased with proteins, you know, that I thought that proteins probably are the hereditary material, rather than nucleic acid.” Chemist Peter Pauling, Linus’s son, also affirmed that this had indeed been his father’s attitude. In a short article written in 1973, Peter reported, “To my father, nucleic acids were interesting chemicals, just as sodium chloride [ordinary table salt] is an interesting chemical, and both presented interesting structural problems.”