Oswald Avery, Colin MacLeod and Maclyn McCarty ($1933$-$44$), worked to determine the biochemical nature of 'transforming principle' in Griffith's experiment. They purified biochemicals (proteins, $DNA$, $RNA$, etc.) from the heat-killed S cells to see which ones could transform live $R$ cells into $\mathrm{S}$ cells. They discovered that $DNA$ alone from $S$ bacteria caused $R$ bacteria to become transformed.

They also discovered that protein-digesting enzymes (proteases) and $RNA$-digesting enzymes ($RNases$) did not affect transformation, so the transforming substance was not a protein or $RNA$. Digestion with $DNase$ did inhibit transformation, suggesting that the $DNA$ caused the transformation. They concluded that $DNA$ is the hereditary material, but not all biologists were convinced.