The Biochemical Identity of the Transforming Principle — Avery, MacLeod and McCarty

Griffith's 1928 experiment had proved that a "transforming principle" existed and could convert harmless R-strain bacteria into virulent S-strain bacteria, but it left the chemical identity of that substance completely open — it could, in principle, have been a protein, a polysaccharide, a nucleic acid, or some other cellular component. Oswald Avery, Colin MacLeod and Maclyn McCarty set out to answer this precise biochemical question, and published their results in 1944 after many years of painstaking work at the Rockefeller Institute in New York.

Their strategy was to purify the transforming principle from heat-killed S-strain bacteria and then, by chemically destroying (degrading) one class of biomolecule at a time, work out which class of molecule was essential for transformation. They treated separate purified samples of the transforming principle with three different classes of enzyme: proteases (which digest and destroy proteins), RNases (which digest and destroy RNA), and DNases (which digest and destroy DNA), and then tested each treated sample for its remaining ability to transform live R bacteria into S bacteria.

The results were unambiguous. When the transforming principle was treated with protease or with RNase, its ability to transform R bacteria into S bacteria was completely unaffected — transformation still occurred efficiently, showing that neither protein nor RNA was the essential transforming substance. But when the transforming principle was treated with DNase, its transforming activity was completely destroyed — transformation no longer took place at all. This was the decisive, purely biochemical result: destroying the DNA in the purified sample (and only destroying the DNA) abolished the biological activity of the transforming principle, which meant DNA itself, and no other class of molecule, must be the transforming principle, and therefore the genetic material. …