THE BACTERIOPHAGE AND THE BACTERIUM 73 



B. typhosus, B. coli, B. proteus, and B. pestis. Each bacterial 

 strain possesses an individual resistance, particularly when freshly- 

 isolated, which renders it more or less resistant to a bacteriophage 

 accustomed to an in vitro existence. Later we will see that this 

 resistance increases by a phenomenon of natural selection. 



All of the phenomena in which the bacteriophage is involved, 

 whether taking place in vitro or in vivo (the first are only an artifi- 

 cial reproduction of the last) are dominated by two factors, — the 

 virulence of the bacteriophage and the resistance of the bacterium. 



THE ORIGIN OF SECONDARY CULTURES 



What is the intimate mechanism of the process that results in 

 the formation of secondary cultures? A priori two hypotheses 

 can be formulated. Two factors are present, a bacteriophage 

 whose virulence may be attenuated, and a bacterium whose 

 resistance may be augmented. Thus, are secondary cultures due 

 to a weakening of the activity of the bacteriophage, or, do there 

 exist in the bacterial suspension certain individual cells which 1/ 

 acquire an immunity to the bacteriophage, thus leading to the 

 development of a resistant race? The following experiments 

 clearly settle the question in favor of the last hypothesis. 



In the chapter treating of the isolation of the bacteriophage 

 we have seen that in the large majority of cases the strains which 

 are freshly isolated are of too low activity to effect a complete 

 lysis of a bacterial suspension; cases where the presence of the 

 ultramicrobe could only be detected by the presence of plaques 

 upon the agar slants. These same strains were able to acquire, 

 by successive passages, a very high activity, a potency which 

 enabled them to bring about lysis of very heavy suspensions. 

 This method of serial passages of the bacteriophage, in which it is 

 forced to develop in vitro at the expense of a given bacterium, 

 corresponds exactly with the method of Pasteur for effecting an 

 enhancement in virulence of a bacterial race by repeated passage 

 through a given animal species. 



This single experiment, repeated a considerable number of 

 times, — in fact, each time that a bacteriophage of low virulence is 

 isolated from the body — shows that secondary cultures are not 

 produced by a simple diminution in the virulence of the bacterio- 



