478 THE BACTERIOPHAGE AND ITS BEHAVIOR 



the virulence of the last and upon the capacity of the first to develop a 

 resistance. If virulence is the factor which prevails, the bacteria are 

 bacteriophaged, as in the three cultures mentioned above; if the resist- 

 ance dominates, a mixed culture is formed. 



Another fact of equal importance may be deduced from the results 

 reported above, and that is, that the adaptation of the bacteriophage 

 appears to be accomplished more readily and more rapidly in vivo than 

 in vitro. This situation is readily comprehended. In vitro, the bac- 

 terium has to struggle against the bacteriophage only; in vivo, this 

 struggle is superimposed upon the attack which the body itself makes, 

 and certainly the body is not passive. Phagocytic processes, in partic- 

 ular, must enter into the struggle, and we have already emphasized 

 the potency of the "products resulting from bacteriophagy" as regards 

 opsonic action. 



The conclusion of all of these studies is that recovery in typhoid 

 fever, as well as in the paratyphoid fevers, is caused by an adaptation 

 of the intestinal bacteriophage to parasitism of the pathogenic bacterium 

 and by the in vivo bacteriophagy which results. In typhoid fever, as 

 in dysentery, the reactions of the body itself seem to have but a second- 

 ary influence in the processes of recovery, an influence which is Hmited 

 to favoring the action of the bacteriophage. 



As for the deaths which occur from typhoid fever (excluding the com- 

 plications, such as intestinal hemorrhage) we have seen that these result, 

 either because of an inertia of the bacteriophage or because the bacterium 

 has a chance, and a capacity, to acquire a refractory state. This re- 

 fractory state results in the formation of a mixed culture in the body, 

 and recent studies indicate that in such a case there may be a formation 

 of "ultrabacteria" of B. typhosus, with an invasion of all of the organs 

 by these filtrable forms. 



Friedberger and Meissner* inoculated some fragments of the organs 

 of patients who had died of typhoid fever into the peritoneal cavity of 

 guinea pigs. They then made a series of passages by inoculating into 

 the peritoneum of each new guinea pig a fragment of the brain (or of 

 any organ) of the preceding pig. From the second passage on it was 

 impossible for them to disclose any bacteria of any kind in the organs 

 of the sick guinea pigs, nevertheless, these organs were infected, since 

 the disease was transmitted serially. Cultures of these infected organs 

 gave no growth on the usual media. 



* Friedberger, E., and Meissner, G. — Zur Pathogenese der experimentellen 

 Typhusinfektion, Klin. Wchnschr., 1923, 19, 403. 



