The Chemical Basis of Heredity Determinants 329 



introduced into the cell to study the relationship between the change 

 in structure and the change in function. In short, this mode of attack 

 offers possibilities of applying to the problem of heredity the same 

 rational approach which yielded elucidations in so many fields of 

 biochemistry. 



Although the above reasons for interest in the transforming principle 

 appear to the author to be the most important ones, the biochemist's 

 and biophysicist's interest may often come from the application of the 

 biological activity of DNA to the study of DNA itself. In early 

 chemical approaches the DNA was subjected to degradation, with 

 complete disregard of the macromolecular nature of the substance. 

 This error was compensated for in the last decade by extensive bio- 

 physical studies of the giant molecules of DNA. However, the bio- 

 physicist soon faced a dilemma as to whether his substance w T as indeed 

 "native" or still degraded. The discovery that the DNA loses its 

 transforming activity on the slightest degradation suggested a con- 

 venient yardstick of "intactness"; for, although no one can say 

 whether his DNA preparation is in the same state as the DNA that 

 exists in the cell, the "functionally intact" unit seems important enough 

 to warrant study and constant enough to serve as a standard. In such 

 a study subtle reactions of certain agents such as mutagenic, carcino- 

 genic, or carcinostatic agents with the DNA can often be demonstrated, 

 by studying the loss of transforming activity, long before these reac- 

 tions can be discovered by any physical or chemical method. 



In the following, the emphasis will be on the transforming principle 

 itself and the transforming phenomena will be mentioned only in their 

 role as detectors of activity. It must be remembered, however, that 

 a transforming phenomenon may involve several steps, and at present 

 it is not possible to decide which is or are responsible for inactivation. 



The Chemical Nature of the Transforming Principle 



In 1944 Avery, MacLeod, and McCarty found the purified trans- 

 forming principle to have all the properties of a highly polymerized 

 DNA. Their conclusion that the transforming principle is DNA was 

 based on the following observations: (1) Elementary analysis of the 

 transforming principle corresponded to that of DNA. (2) Chemical 

 and physical tests revealed the presence of DNA as the only detectable 

 substance. (3) Serological tests failed to detect the presence of any 

 immunologically active substances (such as polysaccharides). (4) Of 

 several enzymes tested only deoxyribonuclease was able to destroy 

 the transforming activity. At the same time the physical study (vis- 



