In $1928$, Frederick Griffith, in a series of experiments with Streptococcus pneumoniae (bacterium responsible for pneumonia), witnessed a miraculous transformation, in the bacteria. During the course of his experiment, a living organism (bacteria) had changed in physical form.

When Streptococcus pneumoniae (pneumococcus) bacteria are grown on a culture plate, some produce smooth shiny colonies $(S)$ while others produce rough colonies $(R)$.

This is because the $S$ strain bacteria have a mucous (polysaccharide) coat, while $R$ strain does not. Mice infected with the $S$ strain (virulent) die from pneumonia infection but mice infected with the $R$ strain do not develop pneumonia. .

$S$ strain $\rightarrow$ Inject into mice $\rightarrow$ Mice die $R$ strain $\rightarrow$ Inject into mice $\rightarrow$ Mice live

Griffith was able to kill bacteria by heating them. He observed that heat- killed S strain bacteria injected into mice did not kill them.

$S$ strain (heat killed) $\rightarrow$ Inject into mice $\rightarrow$ Mice live

When he injected a mixture of heat-killed $S$ and live $R$ bacteria, the mice died. Moreover, he recovered living S bacteria from the dead mice.

$S$ strain (heat killed) $+\rightarrow$ Inject into mice $\rightarrow$ Mice die $R$ strain (live)

He concluded that the $R$ strain bacteria had somehow been transformed by the heat-killed $S$ strain bacteria. Some 'transforming principle', transferred from the heat-killed $S$ strain, had enabled the $\mathrm{R}$ strain to synthesise a smooth polysaccharide coat and become virulent. This must be due to the transfer of the genetic material. However, the biochemical nature of genetic material was not defined from his experiments.