The Chemical Basis of Heredity Determinants 327 



from sensitivity to resistance to penicillin, streptomycin, and sulfanil- 

 amide, and a change from resistance to sensitivity to streptomycin 

 (Hotchkiss et al.). This class of transformation phenomena is of par- 

 ticular interest because the gradations involved (one-step or multistep 

 acquisition of resistance) resemble closely the gradations acquired by 

 a natural process, i.e., spontaneous mutation. 



In summary, then, one can say that the phenomenon of transforma- 

 tion involves a great variety of genetic characters, and, were it not 

 for the nature of the phenomenon, it would closely resemble spontane- 

 ous mutation. 



The Nature of the Transforming Phenomenon 



Although a considerable amount of work has been done in the field 

 of bacterial transformations, the nature of the phenomenon itself re- 

 mains far from clear. At present, the following conclusions appear 

 logical: 



The molecules of the transforming principle are heredity determi- 

 nants because their presence determines the presence of hereditary 

 characters. However, it is not known whether all hereditary characters 

 can be accounted for by the (joint) action of all the molecules of the 

 transforming principle in the cell; it is still conceivable that the 

 determination of the most fundamental features proceeds through an 

 entirely different mechanism. 



The transforming principle seems to consist of DNA molecules. On 

 successful transformation these molecules must reproduce (or be re- 

 produced) because more of them are obtained. The reproduction must 

 take place inside the cell because the DNA is never found outside, 

 and because a thorough destruction of the cell is necessary to isolate 

 the transforming principle. Furthermore, within 3 minutes after the 

 transforming principle is added to the cells, it becomes completely 

 protected against the action of added strong DNAase. 13 Thus, it 

 appears that on transformation the molecule of DNA must penetrate 

 the cell. However, the mechanism of this hypothetical penetration 

 remains unknown; the DNA is composed of giant molecules and ought 

 to be stopped by a normal bacterial membrane; at neutral pH the 

 DNA molecules are highly negatively charged and ought to be repelled 

 by the majority of bacterial cells which are also known to be nega- 

 tively charged, especially when coated with polysugar phosphates. 15 - 16 

 Only a small proportion of receptor cells (about one per hundred in 

 pneumococcus, 10 to 10 3 times less in H. influenzae) is actually sus- 



