To unfold the mystery of nature regarding which is the inheritance molecule many of the great scientists worked hard. It took a very long time to discover and prove that DNA is the genetic material. By 1926, the quest to determine the mechanism for genetic inheritance had reached the molecular level.
In 1928, Frederick Griffith, in a series of experiments with Streptococcus pneumoniae (bacterium responsible for pneumonia), witnessed a miraculous transformation in the bacteria. In his experiment, bacteria had changed in physical form. When he grew the respective bacteria in a culture plate, he noticed some produced smooth shiny colonies(S) while others produce rough colonies. This was due to S strain bacteria have a mucous(polysaccharide) coat, while R strain does not. So he infected mice with both the strain and noticed, mice infected with the S strain die from pneumonia infection but mice infected with the R strain do not develop pneumonia.
S Strain  injected into mice → mice  died
R strain → injected into mice →  mice lived
Then to his curiosity what Griffith did was, he killed bacteria by heating them and to his amusement he observed that heat-killed S strain bacteria when injected into mice, he saw mice were alive and when he injected heat-killed R strain, the mice died. And to his wonder, he discovered living S bacteria from dead mice.
S Strain (heat-killed)   injected into mice →  mice died
R strain (heat-killed)→  injected into mice →  mice lived
From his observation, he concluded that R strain bacteria had somehow transformed by the heat-killed S strain. He invoked there is some ‘transforming principle’ that had enabled the R strain to synthesis, a smooth polysaccharide coat and become virulent and concluded this is due to transfer of genetic material. But biochemical nature of genetic material was not defined from his experiments.
Biochemical characterization of transforming principle
 
Oswald Avery, Colin Macleod, and McCarty worked to determine the biochemical nature of ‘transforming principle’ in Griffith experiment. They purified biochemical’s (protein, DNA, RNA etc…) from the heat-killed S cells to see which ones could transform live R cells into S cells. They discovered that DNA alone from S bacteria caused R bacteria to become transformed.
They also discovered that protein-digesting enzymes( proteases) and RNA-digesting enzymes (RNases) did not affect transformation, so the transforming substances was not a protein or RNA.
 Digestion with DNase did inhibit transformation, suggesting that the DNA caused the transformation.  


This basic experiment led to the discovery of DNA which is the genetic material that is passed on from generation to generation.
 
   
     
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