DNA as Carrier of Genetic Information

It took years for scientists to accept the fact that DNA, and not a protein, was the critical chemical in heredity. In 1927, the Russian biologist Nikolai Koltsov first proposed that inherited traits were passed on to offspring by a “giant hereditary molecule” made up of two strands that could replicate, with each strand serving as a template. Though he never lived to see it—Koltsov had died at the hands of the secret police of the Soviet Union in 1940—this notion was confirmed one-quarter century later by Watson and Crick.

Independently, the British bacteriologist Frederick Griffith was interested in the pathology underlying pneumonia while working as a medical officer at the Ministry of Health’s Pathological Laboratory during the 1920s. He injected mice with one of two forms of pneumococci—the rough non-virulent (R), or the smooth virulent (S)—with the expected fatal outcome involving the latter. But when Griffith administered a heat-killed S-form, the mice did not develop pneumonia. In the critical experiment, he injected mice with a mixture of the R-form and the heat-killed S-form, and the animals developed pneumonia and died. He concluded that the R-form was transformed to S but did not speculate about the nature of the “transforming factor.”

In the 1940s, the Avery-MacLeod-McCarty experiment provided critical evidence that DNA—not a protein—carries genetic information.

During the 1930s and early 1940s, Oswald T. Avery, a Canadian-born physician and foremost expert on pneumococcus, attempted to identify Griffith’s “transforming factor.” With his colleagues Colin MacLeod and Maclyn McCarty at Rockefeller University Hospital, in the so-called Avery MacLeod-McCarty experiment, Griffith’s experimental design was repeated and extended. Instead of heat killing the S-form, S-microbes were treated with chemicals that removed or destroyed various organic compounds from bacteria, including a protease enzyme that inactivated proteins. Only after the deoxyribonuclease enzyme was added, destroying DNA, was the transforming factor rendered inoperative, and in 1944 DNA was established as the critical carrier of genetic information.