BEHAVIOR OF BACTERIOPHAGE IN DISEASE 475 



The stained smear prepared on the 2nd day of incubation showed microscopically 

 a few bacilli having the morphology and the staining reactions of the typhoid 

 bacillus. On the third day they were also found, in slightly increased numbers. 

 The number found in the successive smears continued to increase up to the 6th 

 day, and from that time on it progressively diminished. By the 10th day it was 

 impossible to find a single organism in several smears. Meantime, at no period 

 was it possible to obtain a growth of the organisms seen microscopically upon 

 either solid or liquid media. When this culture, which we would term negative, 

 was filtered the filtrate readily yielded a race of the bacteriophage which was 

 very active for B. typhosus. 



What happened here? Apparently, in taking this blood culture we withdrew 

 from the blood stream of the patient both the bacterium of the disease and a bac- 

 teriophage capable of destroying this bacterium. The process occurring in 

 vitro which we have witnessed on the slides probably takes place in vivo also, 

 and undoubtedly with greater rapidity. This would explain the temporary 

 occurrence of bacteria, their disappearance, and the impossibility of securing 

 a positive blood culture at all times. 



Is it not possible to consider this blood culture as being intermediate between 

 a positive culture and a negative culture? Had it been taken a few days earlier 

 it would have been positive. But in the interim, the struggle which has taken 

 place between the bacterium and the bacteriophage has turned the tide to the 

 advantage of the latter. A few days earlier this had not occurred, either because 

 the bacteriophage at that time was not sufficiently active, or because the bac- 

 terium had then an adequate resistance. As a matter of fact, in a series of his 

 communications on the subject of bacteriophagy. Gratia has shown that a pure 

 culture of a bacterium may be dissociated from the point of view of resistance to 

 the action of the bacteriophage. Mutations, reversions in particular, are possi- 

 ble. Thus, it is easy to conceive that a resistant bacterium may give birth to 

 susceptible organisms, and it is probable that such reversions take place with 

 particular facility within the body. 



Had the culture been taken a little later,— a few days or even a few hours,— it 

 is possible that an in vitro destruction the bacterium might not have occurred* 

 for a bacteriophage might have by then disappeared from the circulation. 



The paradoxical situation to which we called attention above, is, therefore, 

 only an apparent contradiction. In all blood cultures made prior to the fall in 

 the temperature the bacteriophage may be found. The culture is positive, or 

 negative, according to whether the specimen is removed before or after the 

 destruction of the bacterium by the lytic principle. 



With these facts at hand, there are still two points which are of very definite 

 interest from the point of view of the study of bacteriophagy. In the first place, 

 we should be quite sure that there is not a bacteriophage present in the blood of 

 the normal healthy individual as well as in the blood of the diseased. And in the 

 second place, we are interested in determining whether this lytic principle is, in 

 fact, identical with the bacteriophage of d'Herelle. 



* It should be remembered that we are here speaking of the culture strain in 

 an artificial mixture of filtrate and bacteria. 



