328 Essays in Biochemistry 



ceptible to transformation; such cells must therefore be in a special 

 physiological state. 17 



Upon entering the susceptible cell the DNA may become fixed to 

 the genetical "locus," presumably on bacterial chromosomes. That 

 some sort of "fixation" or precipitation is necessary has been postulated 

 on the demonstration that the molecule of DNA of E. coli in solution 

 is actually longer than the cell itself. 18 The fact that the transforming 

 principle as extracted from the cell seems to be in the form of a 

 nucleoprotein 3 * 19 also indicates some binding of DNA. In such an 

 hypothetical fixation or acceptability inside the cell, two or more 

 transforming principles may compete for the substrate. A phenomenon 

 of competition (a vs. b, or b vs. c) has indeed been demonstrated in 

 H. influenzae ; 17 such competing transforming principles can be demon- 

 strated to obey the law of mass action. 



The problem of hypothetical competition for the "locus" may be 

 closely connected with the problem of possible DNA exchange. When 

 an R (non-encapsulated) cell is transformed into an S (encapsulated) 

 cell, one may suppose that a missing transforming-principle molecule 

 has been added (to a bare locus?) ; however, one may also postulate 

 that an inactive (or less active) molecule has been replaced by an 

 active one. This latter explanation appears more probable for the 

 following reasons: (1) Many gradations of "roughness" are known, 

 corresponding to various amounts of polysaccharide produced, and in 

 some cases introduction of a transforming principle may abolish the 

 action of an already existing gene (compare "allelism" in higher 

 organisms). (2) S cells of one type can be transformed directly into 

 S cells of another type. 20 



The Transforming Principle 



From the foregoing discussion one can easily appreciate the poten- 

 tialities of using the transforming principle for the study of the chem- 

 istry of heredity determinants; since no other form or system of 

 heredity determination offers such possibilities, most of the chemical 

 work was indeed done on this substance. The transforming principle 

 can be extracted from the cell, purified, chemically identified, and 

 analyzed. It can be subjected in vitro to the action of physical and 

 chemical agents stronger than those which can act on the living cell 

 without killing it; after removal of excess reagent, the nature and the 

 extent of changes induced in the DNA molecule can be estimated; 

 and, finally, such changed transforming principle (DNA) can be re- 



