Although DNA was discovered in 1869 by Friedrich Miescher as
a new, acidic, phosphorus containing substance made up of very large molecules that he named “nuclein”, its biological role was not recognized. In 1889 Richard Altmann introduced the term “nucleic acid”. By 1900 the purine and pyrimidine bases were known. Twenty years later, the two kinds of nucleic acids, RNA and DNA, were distinguished. An incidental but precise observation (1928) and relevant investigations (1944) indicated that DNA could be the carrier of genetic information.
A. The observation of Griffith
In 1928 the English microbiologist Fred Griffith made a remarkable observation. While investigating various strains of Pneumococcus, he determined that mice injected with strain S (smooth) died (1). On the other hand, animals injected with strain R (rough) lived (2). When he inactivated the lethal S strain by heat, there were no sequelae, and the animal survived (3). Surprisingly, a mixture of the nonlethal R strain and the heat-inactivated S strain had a lethal effect like the S strain (4). And he found normal living pneumococci of the S strain in the animal’s blood. Apparently, cells of the R strain were changed into cells of the S strain (transformed). For a time, this surprising result could not be explained and was met with skepticism. Its relevance for genetics was not apparent.
B. The transforming principle is DNA
Griffith’s findings formed the basis for investigations by Avery, MacLeod, and McCarty (1944). Avery and co-workers at the Rockefeller Institute in New York elucidated the chemical basis of the transforming principle. From cultures of an S strain (1) they produced an extract of lysed cells (cell-free extract) (2). After all its proteins, lipids, and polysaccharides had been removed, the extract still retained the ability to transform pneumococci of the R strain to pneumococci of the S strain (transforming principle) (3). With further studies, Avery and co-workers determined that this was attributed to the DNA alone. Thus, the DNA must contain the corresponding genetic information. This explained Griffith’s observation. Heat inactivation had left the DNA of the bacterial chromosomes intact. The section of the chromosome with the gene responsible for capsule formation (S gene) could be released from the destroyed S cells and be taken up by some R cells in subsequent cultures. After the S gene was incorporated into its DNA, an R cell was transformed into an S cell(4).
C. Genetic information is transmitted by DNA alone
The final evidence that DNA, and no other molecule, transmits genetic information was provided by Hershey and Chase in 1952.They labeled the capsular protein of bacteriophages (see p. 88) with radioactive sulfur ( 35 S) and the DNA with radioactive phosphorus ( 32 P). When bacteria were infected with the labeled bacteriophage, only 32 P (DNA) entered the cells, and not the 35 S (capsular protein). The subsequent formation of new, complete phage particles in the cell proved that DNA was the exclusive carrier of the genetic information needed to form new phage particles, including their capsular protein. Next, the structure and function of DNA needed to be clarified. The genes of all cells and some viruses consist of DNA, a long-chained threadlike molecule.