16 CELL HEREDITY 



every respect with the known properties of DNA. With every refinement 

 of techniciue and new method of analysis, the identity of transforming 

 principle as DNA has become more firmly established. 



At the time, however, the finding that transforming principle was 

 DNA came as a shock to its discoverers, who had rather expected that 

 it would be the capsular polysaccharide itself, on the hypothesis of 

 identity between the hereditary material and the observed trait. When 

 polysaccharide could not be found in the active extract, it seemed 

 reasonable that it might be a protein, for in 1944 onfy proteins were 

 considered by most investigators to be sufficiently complex to determine 

 cellular specificity and heredity. With the eventual identification of the 

 transforming principle as DNA, based upon the most meticulous experi- 

 mentation, Avery, McLeod, and McCarty established with great clarity 

 two points of central importance in genetic theory: (1) the chemical 

 dissimilarity between a hereditary determinant and the phenotypic trait 

 which it determines; and (2) the ability of a molecule of deoxyribonucleic 

 acid to carry hereditary information. 



One may then ask whether transformation experiments exclude the 

 possibility that DNA acts not as hereditary material but as a mutagenic 

 agent which induces a change in the hereditary determinants of the 

 receptor cell. This alternative has become steadily less probable with 

 further studies of the transformation process. For example, with the 

 use of DNA containing radioactive phosphorus, P^~, in transformation 

 experiments, the actual incorporation of P^^-DNA into the receptor cells 

 has been measured. It has been clearly shown in such experiments 

 that the yield of transformed receptor cells closely parallels the extent 

 of DNA incorporation. 



Transformation has been achieved for a large number of different 

 traits, but in all instances receptor cells are transformed only for the 

 particular traits of the donor cells. The mutagen hypothesis would 

 require that DNA be a highly specific mutagen corresponding precisely 

 to the traits of the donor. In effect, then, the specific mutagen becomes 

 operationally indistinguishable from a hereditary determinant. 



Type transformation in pneumococcus thus provided the first system in 

 which the chemical nature of a hereditary determinant was established. 

 This first demonstration of the genetic significance of DNA was of epoch- 

 making importance. The repercussions are only beginning to be felt in 

 the recent acceleration of new findings in this field, which has appro- 

 priately been called genetic chemistry. On the one hand, the trans- 

 formation experiment provides the chemist with the only available 

 method for determining the biological intactness of the material that he 

 extracts from the cell for analysis. Thus the biological assay is an 



