The Transforming Principle - DNA Might be the Genetic Material

In 1943, Oswald Avery, Colin Macleod, and Maclyn McCarty, at the Rockefeller Institute, discovered that different strains of the bacterium Strepotococcus pneumonae could have different effects on a mouse. One virulent strain (smooth) could kill an injected mouse, and another avirulent strain (rough) had no effect. When the virulent strain was heat-killed and injected into mice, there was no effect. But when a heat-killed virulent strain was coinjected with the avirulent strain, the mice died. What transforming principle was the dead virulent strain giving to the avirulent strain to make it lethal?

Avery and his colleagues separated the dead virulent cells into fractions and coinjected them with the avirulent strain, to see which fraction contained the transforming principle. They discovered that the fraction was DNA. Most scientists at the time, in favour of the theory of protein as genetic material, discounted this result and said that there must have been some protein in the fraction that conferred virulence.

The Hershey-Chase Experiment - DNA is the Genetic Material
Finally, in 1952, Alfred Hershey and Martha Chase performed the definitive experiment that showed that DNA was, in fact, the genetic material. By radiolabelling sulphur in one culture, they could tag the path of proteins and not DNA, because there is no sulphur in DNA and there is sulphur in the amino acids methionine and cysteine. By radiolabelling phosphorous, the opposite effect could be achieved. DNA could be traced and not protein, because there is phosphorous in the phosphate backbone of DNA and none in any of the amino acids. Cultures could be grown in each of these two ways and the phage purified away from the host bacteria, resulting in one culture in which only the phage protein was labelled, and one culture in which only the phage DNA was labelled.

Hershey-Chase Blender Experiment

Side by side experiments were performed with separate phage cultures in which either the protein capsule was labeled with radioactive sulfur or the DNA core was labeled with radioactive phosphorus.

Experiment Summary
# The radioactively labeled phages were allowed to infect bacteria.
# Agitation in a blender dislodged phage particles from bacterial cells.
# Centrifugation pelleted cells, separating them from the phage particles left in the supernatant.

Results Summary:
# Radioactive sulfur was found predominantly in the supernatant.
# Radioactive phosphorus was found predominantly in the cell fraction, from which a new
    generation of infective phage was generated.
# Thus, it was shown that the genetic material that encoded the growth of a new generation of phage
    was in the phosphorous-containing DNA.