Transformation experiments were initially conducted by F. Griffith in 1928 (Fig. 25.1). He injected a mixture of two strains of pneumococcus (Diplococcus pneumoniae)into mice. One of these two strains, S III was virulent and the other strain R II was non-virulent (causing no infection). Heat killed virulent strain SIII; when injected individually did not cause death, showing that infectivity after heat killing is lost. The mice injected with a mixture of R II (living) and S III (heat killed) died and virulent pneumococci could be isolated from these mice. This phenomenon was described as transformation (see Sexuality and Recombination in Bacteria and Viruses).

O.T. Avery, CM. Macleod and M. McCarthy repeated Griffith's experiments in an in vitro system in order to identify the transforming substance responsible for converting non-virulent into virulent type and reported their results in 1944.

Virulence in pneumococcus depends on a polysaccharide capsule which is present in virulent strain S III and is absent in non-virulent strain R II. The cells of non-capsulated type (R II) were treated with an extract of DNA from capsulated strain S III. A few cells of S III type could be isolated from the mixture (Fig. 25.2). This phenomenon of transferring characters of one strain to another by using a DNA extract of the former is called transformation. When the extract was treated with DNAase (an enzyme which destroys DNA) this transforming ability was lost. Proteases (enzymes which destroy proteins) did not affect the transforming ability. These experiments thus indicated that DNA and not the proteins is the genetic material.