In 1928, an army medical officer, Frederick Griffith (1878–1939), was trying to find a vaccine against Streptococcus pneumoniae. In the course of his work, he found that two strains of the bacteria existed: one had a smooth coat S but was lethal; the other form had a rough coat R, which was nonlethal when injected into mice. He decided to investigate what would happen if he injected both heat-killed S bacteria and live R bacteria into mice. To his surprise, the mice injected with this combination died. Upon closer examination of the blood, living S bacteria were found. Something had occurred that transformed the nonlethal R bacteria into S bacteria. Subsequent experiments throughout the 1940s attempted to find the identity of the transforming factor—and it was eventually found to be DNA. (For more about bacteria, see the chapter “Bacteria, Viruses, and Protists.”)

The proof that the material basis for a gene is DNA came from the work of Canadian-born American physician and medical researcher Oswald T. Avery (1877–1955), Canadian-born American geneticist Colin M. MacLeod (1909–1972), and American geneticist Maclyn McCarty (1911–2005) in a paper published in 1944. This group of scientists followed the work of Frederick Griffith (see sidebar) in order to discover what causes non-lethal bacteria to transform into a lethal strain. Using specific enzymes, all parts of the S (lethal) bacteria were degraded, including the sugarlike coat, the proteins, and the RNA. The degradation of these substances by enzymes did not affect the transformation process. Finally, when the lethal bacteria were exposed to DNase, an enzyme that destroys DNA, all transformation activity ceased. They discovered that the transforming factor was DNA, thus proving that DNA was an agent that carried genetic characteristics, not proteins.