Avery, MacLeod, and McCarty’s 1944 experiment identified DNA as the bacterial transforming principle.
The researchers studied two forms of Streptococcus pneumoniae: a disease-causing smooth form and a harmless rough form. Material extracted from smooth bacteria could permanently transform rough bacteria into the smooth type. The team purified the active substance and tested enzymes that destroyed different classes of molecules.
Transformation stopped when the extract was treated with deoxyribonuclease, which breaks down DNA. Enzymes that destroyed protein or RNA did not eliminate the effect. The result strongly indicated that DNA carried hereditary information.
Some scientists initially remained cautious because proteins were widely regarded as more likely genetic material. The later Hershey–Chase bacteriophage experiment provided another major line of evidence, but it is a separate experiment.