Q.Who revealed biochemical nature of the transforming principle? How was it done?

Oswald Avery, Colin MacLeod, and Maclyn McCarty revealed the biochemical nature of Griffith's transforming principle in 1944. They set out to identify which molecule—protein, RNA, or DNA—was responsible for transforming non-virulent R-strain bacteria into virulent S-strain.

Their approach was systematic and elegant:

• They purified the transforming principle from heat-killed S-cells and treated separate samples with enzymes that destroy specific molecules.
• Protease (protein-digesting enzyme) and RNase (RNA-digesting enzyme) were added to different samples, yet transformation still occurred—ruling out proteins and RNA.
• When DNase (DNA-digesting enzyme) was added, transformation was blocked completely. …

Frederick Griffith's 1928 experiment had demonstrated that something from dead virulent bacteria could transform harmless bacteria into killers, but he never identified what that "transforming principle" was. The question hung in the air for sixteen years: was it protein, RNA, DNA, or some other molecule that carried genetic instructions?

The answer came from three American scientists working at the Rockefeller Institute in New York. Oswald Avery, a physician-scientist, led the work alongside Colin MacLeod and Maclyn McCarty. By 1944, they had designed a series of elegant experiments to chemically identify Griffith's mysterious transforming substance.

The experimental strategy

Their approach was beautifully simple in concept: purify the transforming principle from heat-killed S-strain bacteria, then systematically destroy different types of molecules and see which destruction stops the transformation. If destroying a particular class of molecule prevents transformation, that molecule must be the transforming principle.

They began by extracting and purifying the transforming substance from heat-killed S cells. This extract, when added to living R cells, could still cause transformation—proof that the active ingredient was in their preparation.

The elimination experiments

Now came the critical tests. They treated their purified extract with different enzymes, each specific to one type of biological molecule:

• Protease treatment (protein-digesting enzymes): Transformation still occurred. So protein was not the transforming principle.
• RNase treatment (RNA-digesting enzyme): Transformation still occurred. RNA was ruled out.
• DNase treatment (DNA-digesting enzyme): Transformation was completely blocked. No transformed S cells appeared.

The conclusion was inescapable. Only when DNA was destroyed did transformation fail. DNA had to be the transforming principle—the molecule carrying genetic information from one bacterium to another. …

Instead of listing the three enzyme treatments as parallel facts, use elimination logic: of protein, RNA and DNA, digesting two of them (protease, RNase) left transformation intact, so the transforming ability was carried by neither -- only digesting the third (DNase) killed the ef …