The transformation experiments, conducted by Griffith in 1928 helped in establishing the nature of genetic material. He performed series of experiments by selecting two strains of bacterium Streptococcus pneumonia namely S and R.

(i) S- strain/smooth or capsulated type have a mucous (polysaccharide) coat and produce smooth colonies, these are virulent and cause pneumonia.

(ii) R strain/rough or non-capsulated type have no mucous coat and produce rough colonies. These are nonvirulent and do not cause pneumonia

The experiment can be described in Following 4 steps:

(a) S strain D injected into mice D Mice die  

(b) R strain D injected into mice D Mice live

(c) S strain (heat killed) injected into mice D Mice live

(d) S strain (heat killed) + R –strain (live) D injected into mice D Mice die

Griffith concluded that the R- strain had somehow been transformed by the heat – killed S – strain bacteria this occurred perhaps due to absorption of same transforming principle by rough type bacteria from heat – killed smooth bacteria. It had enabled the R – strain to synthesize a smooth polysaccharide coat and become virulent. However the biochemical nature of genetic material was not defined.

A very, Macleod and McCarty repeated the experiment in-vitro to identify the biochemical nature of the transforming substances. They proved that this substance is DNA.

They purified biochemical i.e., proteins, DNA and RNA from the heat killed S – cell 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 also discovered that protein – digesting enzymes i.e., protease and RNA – digesting enzymes i.e., RNase did not affect transformation, so the transforming substance was not a protein or RNA. Digestion with DNase did inhibit transformation, suggesting that DNA caused the transformation.

Significance: DNA and not protein is the genetic material.