RESISTANCE OF BACTERIA 201 



and the result on the corpuscles is the same in both cases,^ — an attenua- 

 tion of virulence. 



Bordet^" has further shown that if a Petri dish is seeded with a cul- 

 ture of B. coli (and all other bacteria behave in the same manner) and if, 

 then, a drop of bacteriophage of moderate or weak* potency is deposited 

 upon the surface the bacteria do not develop in this region, but after 

 some time colonies of resistant bacteria appear. If these mixed colonies, 

 which, as we will see in a later section, contain both bacteria and bac- 

 teriophage corpuscles the latter possess an attenuated virulence. The 

 reason is always the same; virulence becomes attenuated through con- 

 tact with bacteria which have acquired a resistance, Bordet and 

 Ciuca^^ have stated that a bacteriophage attenuated in one or the other 

 of these experiments which have been cited, is no longer able to increase 

 in virulence by passages with susceptible organisms. Brutsaert^"' 

 has shown that this is not the case. After 12 to 20 passages he obtained 

 an increase in virulence to such a degree that it became equal to the 

 virulence of the bacteriophage prior to its attenuation. I have con- 

 firmed this fact entirely. 



The erroneous conclusion reached by Bordet may be ascribed to the 

 fact that the virulence of a bacteriophage attenuated through contact 

 with resistant bacteria becomes increased only very slowly during the 

 first passages with susceptible organisms. It is only after 7 or 8 pas- 

 sages that the virulence begins to be increased to an appreciable degree. 

 Once it has started to augment the increase is rapid. 



One might conclude from these facts that the bacteriophage corpuscles 

 become increased in virulence by passages with susceptible bacteria, 

 and that virulence is attenuated by passages with bacteria which have 

 acquired a resistance, that is, an immunity. Bacteria which have 

 acquired a completely refractory state may even destroy the corpuscles. 

 Here again the manner in which the bacteriophage corpuscles and the 

 susceptible bacterium which has acquired an immunity behave is 

 exactly like that of the pathogenic microorganism and the susceptible 

 animal which has acquired an immunity.! It is, on the other hand, 



* If the bacteriophage is of maximum virulence or is very active no resistant 

 bacterial colonies develop. Bordet did not state, in his paper, the virulence of 

 the bacteriophage with which he worked, but it is obvious that the virulence 

 was weak because of the fact that resistant colonies developed. 



t Among all of the experiments which might be mentioned and which have been 

 of interest to all biologists there is one which is of particular interest because t he 

 conditions, experimentally, are almost identical with those of corpuscles at- 

 tenuated through contact with resistant bacteria. 



WoUmann inoculated a few drops of an attenuated culture of B. anthracis into 



