THE AGGLUTININS 2IQ 



saturating the serum with all the allied bacteria on which it can 

 act, we might theoretically, at least remove all the partial 

 agglutinins, leaving only the main agglutinin, which acts on the 

 proteid formed by the typhoid bacillus, and by it only, and so 

 obtain a truly specific clumping serum. 



Castellani's test seems to be generally correct, though excep- 

 tions have been recorded. 



Further, bacilli of the same stock can be made to vary greatly 

 in their sensitiveness to the action of agglutinin by various 

 methods. These have been carefully studied by Bordet, Nicolle, 

 Kirschbruch, and others, and it has been found that the 

 sensitiveness of typhoid bacilli is diminished by washing, by 

 culture at high temperatures (40 C.) or low temperatures, by the 

 addition to the medium of minute traces of antiseptics, and is 

 less in old cultures and in those that have been recently isolated 

 from the living animal. It is found in general that bacilli just 

 isolated from a typhoid patient clump badly, and that they 

 gradually increase in sensitiveness for six months on cultivation in 

 artificial media : a very faintly acid medium is the most suitable. 

 Sometimes a culture alters very rapidly without obvious cause, 

 and this is a possible source of error in the clinical application of 

 Widal's reaction. The author in one case found a culture which 

 was clumped by a certain serum at i : 60 was clumped by the 

 same serum at i : 250 three days later. 



Another method by which bacteria can be made to diminish in 

 their sensitiveness to clumping is by cultivation in specific 

 immune serum. This was first observed by Ainley Walker, and 

 since it is of some theoretical interest in connection with Welch's 

 theory of the nature of the unknown toxins, requires a short 

 description. He found that when typhoid bacilli were grown in 

 immune serum (of course, devoid of complement) diluted with 

 broth, they gradually lost their agglutinability, and became more 

 virulent. Thus both of the effects of" passage " were reproduced 

 in vitro, and Walker further found that bacilli thus treated re- 

 moved the agglutinin from the serum in which they were grown, 

 and believed his results could be best explained on the supposition 

 that the bacilli produced specific anti-agglutinins. This, of course, 

 tends to corroborate Welch's interesting suggestion that some of 

 the organisms for which no exotoxins have been discovered exert 

 their lethal action by producing antibodies against the blood of 

 their host. 



