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Modern Genetic Analysis Chapter 2. The Structure of Genes and Genomes The Nature of DNA
Genetics In Process2-1: Oswald Avery's demonstration that the hereditary material is DNA

In 1928 Frederick Griffith succeeded in permanently transforming a nonencapsulated and nonvirulent strain of the bacterium Pneumococcus into an encapsulated and virulent strain by adding an extract of dead cells of the latter type. The next step was to determine which component of the dead cells was the "transforming principle" because this substance was conferring hereditary properties on the recipient bacterial strain.

Oswald Avery's approach in 1944 was to inactivate all the major categories of chemicals in the extract one at a time and find out if the transformation property was inactivated too. For example, one strong candidate was the polysaccharide capsular material itself, which formed a smooth coat around the bacterial cells. However when this was inactivated, the mixture could still transform. Proteins, fats, and ribonucleic acids (RNA) were all similarly shown not to be the transforming principle. However, when the extract was treated with the enzyme deoxyribonucleotide polymerase, now called DNase (extracted from dog intestinal mucosa or dog or rabbit serum), which breaks up DNA, the transforming principle was destroyed. When these mucosal or serum extracts were heated to denature the DNase, the transforming principle was unaffected.

In a 1943 letter to his brother Roy, Avery wrote

For the past two years, first with MacLeod and now with Dr. McCarty, I have been trying to find out what is the chemical nature of the substance in the bacterial extract which induces this specific change....Some job, full of headaches and heartbreaks. But at last perhaps we have it....But today it takes a lot of well documented evidence to convince anyone that the sodium salt of deoxyribose nucleic acid, protein free, could possibly be endowed with such biologically active and specific properties, and that is the evidence we are now trying to get. It is lots of fun to blow bubbles but it is wiser to prick them yourself before someone else tries to.

By adding DNA alone, Avery could change the genotype and phenotype of bacterial cells, convincingly demonstrating that DNA is the genetic material. It is now known that fragments of the transforming DNA conferring virulence enter the bacterial chromosome and replace their counterparts that confer avirulence.

© 1999 by W. H. Freeman and Company. All rights reserved.