Frederick Griffith was working with streptococcus pneumoniae ( also called pneumococcus ) , a bacterium that cause pneumonia . Griffith used two strains of the bacterium the S strain , which produces smooth, shiny colonies and is virulent (highly infectious) and the R strain , which produces rough colonies and is nonvirulent ( harmless). Strain S was polysaccharide coat – a capsule – surrounding each cell. The R strain is genetically identical expect that it carries a mutation that prevents it from making the polysaccharide coat . A mutation in a gene affects the ability of the bacterium to make the coat and hence, alters the virulence state of the bacterium.
There are several types of S strains, each with a distinct chemical composition of the polysaccharide coat. Griffith worked with IIS and IIIS strains, which have type II and type III coats, respectively . Occasionally, S – type cells mutate into R- type cells , and R- type cells mutate into S- type cells. The mutations are type – specific – meaning that , if a IIS cell mutates into an R cell , then that R cell can mutate back only into a IIS cell , not a IIIS cell.
Griffith injected mice with different strains of the bacterium and observed their effects on the mice. When mice were injected with IIR bacteria ( R bacteria derived by mutation from IIS bacteria), the mice lived. When mice were injected with living IIIS bacteria, the mice died, and living IIIS bacteria could be isolated from their blood . However , if the IIIS bacteria were killed by heat before injection, the mice lived. These experiments showed that the bacteria had both to be alive and to have the polysaccharide coat to be virulent and kill the mice.
In his key experiment , Griffith injected mice with a mixture of living IIR bacteria and heat – killed IIIS bacteria. The mice died, and living IIIS bacteria were present in the blood . These bacteria could not have arisen by mutation of the R bacteria, because mutation would have produced IIS bacteria. Griffith concluded that some IIR bacteria had somehow been transformed into smooth, virulent IIIS bacteria by interaction with the dead IIIS bacteria . Genetic material from the dead IIIS bacteria had been added to the genetic material in the living IIR bacteria . Griffith believed that the unknown agent responsible for the change in the genetic material was a protein ;but this was a hunch , and he turned out to be wrong . He had no experimental evidence one way or the others as to the material acting as the agent bringing about the genetic change . Griffith called this agent the transforming principle.

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