BACTERIOPHAGE AS AN ANTIGEN 405 



Let US take living dysentery bacilli, instead of toxin, and determine 

 whether a similar sensitizing action is manifested here by the antiserum. 

 Four mice receive subcutaneously a dose of dysentery bacilU equal to 

 one-fifth of the lethal dose. The first mouse is held as a control. The 

 second receives, also subcutaneously, 0.2 cc. of the antiserum, and the 

 last two mice 0.1 cc. of the serum. The control animal Hves, showing 

 nothing abnormal. Those mice which received the antibacteriophagic 

 serum in addition to the bacilli die in 7 to 9 days after the injection. 

 Before death they show a paralysis of the posterior extremities, a 

 symptom of intoxication which as a rule does not appear in mice fol- 

 lowing injections of B. dysenteriae, although a paralysis of this type is 

 a common symptom in rabbits, more or less pecuHar to the species.^^i 



This experiment leaves no room for doubt; the antibacteriophagic 

 serum possesses, not an antitoxic property, but a property which is 

 precisely the opposite of antitoxic. It sensitizes the animal to the 

 toxin. For this state of hypersensitivity I have coined the term "anti- 

 phylaxis."^"'^ 



One other experiment may be cited, since it shows another aspect 

 of the phenomenon of antiphylaxis. Give a group of mice 5 successive 

 injections at weekly intervals, using an old suspension of the Shiga- 

 bacteriophage in doses of 0.01, 0.02, 0.05, 0.1, and 0.15 cc. When 

 tested by the injection of Shiga toxin 15 days after the last injection it 

 is found that these mice are killed by quantities of toxin equal to a 

 fifth of the lethal dose for control mice.^^^ 



That the phenomenon of antiphylaxis occurs has been confirmed 

 by a number of authors, whose contributions to this phase of bacteri- 

 ophagy are of sufficient theoretical interest, as well as of practical 

 importance, to warrant discussion here. 



In the course of experiments on the immunization of rabbits with 

 suspensions of the Staphylo-bacteriophage Gratia^" observed that 

 when the sera had acquired a strong antibacteriophagic power the 

 animals were hypersensitive to the injection of cultures of the staphy- 

 lococcus. With minimal injections of the coccus they died in less 

 than 4 days, one with a mihary infection of the spleen, another with 

 a similar infection involving the kidneys. The normal control rabbits 

 died only after a period of 8 days, and even then only when they had 

 been injected with a much larger quantity of the culture. This shows 

 a diminished resistance to the staphylococcus, comparable to that 

 which I had demonstrated in mice with B. dysenteriae. 



Perhaps even more conclusive are the following experiments of 



