552 THE BACTERIOPHAGE AND ITS BEHAVIOR 



For this difference in behavior and in effect there must be a cause. 



Marcuse'*''^ attributes the failures in typhoid fever to the assumption 

 that a contact between the bacteriophage and the bacteria does not 

 occur. It is necessary to have recourse, therefore, in typhoid fever to 

 intravenous injections given in conjunction with ingestion. It is possi- 

 ble that this may account for the failure in some cases, but I do not think 

 that it will explain all of them. 



The thought naturally occurs that while the dysentery bacilli are a 

 homogeneous species, the typhoid and paratyphoid bacilli are a hetero- 

 geneous species, and that this might explain the difference in the be- 

 havior of the bacteriophage suspensions when introduced into the body 

 of the patient. Here again, certain failures may be explained upon 

 such a basis, but I do not think that this can be the principal cause of 

 lack of success. 



Very recently Hauduroy has discovered a fact which may better ex- 

 plain the failures.^"^ He has found that in vitro the addition of bile to 

 the medium inhibits bacteriophagy. The bacteriophage protobe is 

 not destroyed, but its action is completely inhibited. In vivo the 

 bacilli which are found in the gall bladder are thus completely protected 

 against bacteriophagy, and consequently when the infection involves 

 the bladder the administration of bacteriophage can have no effect 

 upon the course of the disease. 



An earher finding of Hauduroy is in accord with this conclusion. He 

 observed in a case where the administration of the bacteriophage had no 

 effect upon the course of the disease that there was, nevertheless, a 

 diminution and even a disappearance, of the typhoid bacilli from the 

 feces. But this disappearance was only transitory, for a short time 

 afterward they were again present as abundantly as before the ad- 

 ministration of the bacteriophage. 



The inhibitory action which bile exerts on bacteriophagy will cer- 

 tainly explain some of the failures, but it is probable that even this is 

 not the key to the situation. 



Is the typhoid bacillus which we know, which we see under the 

 microscope, always the agent of the typhoid and paratyphoid fevers? 

 In the forms of the disease of average severity, and more probably in 

 the benign forms, it is probable; in the severe forms, it is doubtful. 

 What, then, is the true agent in these? 



We have discussed this question in an earlier chapter, and recent 

 experimental studies show, that in reahty certain forms of typhoid 

 fever, the most severe ones, must unquestionably be double infections 



