Prior to the work of Oswald Avery, Colin Macleod and Maclyn McCarty the genetic material was thought to be a protein. They worked to determine the biochemical nature of ‘transforming principle’ in Griffith’s experiment.

They purified biochemical (proteins, DNA, RNA, etc.) from the heat-killed S cells to see which ones could transform live R cells into S cells. They discovered that DNA alone from S bacteria caused R bacteria to become transformed.

They discovered that protein and RNA digesting enzymes did not affect transformation, so the transforming material was neither protein nor RNA. But, digesting with DNase did inhibit transformation, suggesting DNA caused the transformation. They concluded that DNA is the hereditary material.