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Transformation is the uptake of genetic information from the environment. This usually occurs when a competent cell (a cell capable of being transformed) uptakes a piece of DNA (typically a plasmid) and hence is transformed. The term transformed is used because the uptake of DNA usually introduces new genes which transform the cell and give it new capabilities.

Griffith discovered transformation using smooth (lethal) and rough (non-lethal) strains of S. pneumoniae. He boiled the smooth and rough strains, thereby killing the cells and creating a solution of their intracellular contents. He then mixed the solution with a live rough strain culture. He infected a patient with this mixture, and the patient died. He isolated cells from the infected patient, and found that the rough strain had become smooth. His negative control was to infect a patient with a boiled smooth strain culture, which did not result in death. Based on these results, he formulated the following hypothesis: Genetic material is transferred from smooth cells to rough cells..

After formulating this hypothesis, Griffith performed an experiment to find out what is the genetic material. He purified macromolecules from smooth cells and mixed them with rough cells. He then assayed if the rough cells had become pathogenic. He found that polysaccaride, protein, lipid and RNA have no effect; only DNA is capable of transforming the rough cells. Hence, Griffith showed that cells are able to uptake naked DNA from their environment.