Even though the discovery of nuclein by Meischer and the proposition for principles of inheritance by Mendel were almost at the same time, but that the DNA acts as a genetic material took long to be discovered and proven. By 1926, the quest to determine the mechanism for genetic inheritance had reached the molecular level.
Previous discoveries by Gregor Mendel, Walter Sutton, Thomas Hunt Morgan and numerous other scientists had narrowed the search to the chromosomes located in the nucleus of most cells. But the question of what molecule was actually the genetic material, had not been answered.
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 ----> inject into mice ---> mice die
R strain ----> inject into mice ---> 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. 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) ----> inject into mice ---> mice live
S strain(heat-killed) + R strain(live) ----> inject into mice ---> mice die
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 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.
Biochemical Characterisation of Transforming Principle
Prior to the work of Oswald Avery, Colin MacLeod and Maclyn McCarty (1933-44), the genetic material was thought to be a protein. They worked to determine the biochemical nature of ‘transforming principle’ in Griffith's experiment.
They purified biochemicals (proteins, 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 substance was not a protein or RNA.
Digestion with DNase did inhibit transformation, suggesting that the DNA caused the transformation. They concluded that DNA is the hereditary material, but not all biologists were convinced.