THE AGGLUTINATION REACTION 263 



a number of hours the turbidity of the cultures disappeared, while 

 all the bacteria had settled to the bottom. This peculiar behavior, 

 as we now know, is owing to the presence, in the sera in question, of 

 certain antibodies known as agglutinins which are formed as a result 

 of infection (sc., immunization), and are characterized by the fact 

 that in suitable dilution they will cause the arrest of motility, and 

 agglutination of the corresponding organisms (see also section on 

 antibodies). Normal serum, it is true, will also do this to a certain 

 extent, but only when used in a fair degree of concentration, and 

 then only imperfectly, while with immune sera the complete reaction 

 may be obtained even though the serum be diluted many times. 

 In this sense the reaction is specific, and may be employed both for 

 the identification of a given organism, as also for the recognition 

 of the nature of an immune serum. In the first instance an emul- 

 sion of the unknown bacterium is brought together with diluted 

 test sera, corresponding to those organisms which would enter into 

 consideration from a diagnostic standpoint. If, then, the bacterium 

 in question is agglutinated by an antityphoid serum, for example, 

 but not by an anticolon or an antidysentery serum, the inference 

 would be (within certain experimental limitations) that we are dealing 

 with the typhoid bacillus. On the other hand, the unknown serum, 

 in a certain degree of dilution, is tested against a series of organisms, 

 when a positive result with one of these would indicate the nature 

 of the infection. From both standpoints the agglutination reaction 

 has thus a wide sphere of application. 



Very soon after the discovery of Gruber and Durham, Widal 

 found that the formation of agglutinins in typhoid fever begins 

 quite early in the course of the disease, i. e., at a time when from 

 the usual symptoms the diagnosis cannot as yet be made with cer- 

 tainty, and he thus established a method of diagnosis which in some 

 one of its numerous technical modifications is now used the world 

 over, and is generally known as the Widal reaction. Further studies, 

 then, showed that the formation of agglutinins in other infections 

 likewise begins while the disease is in actual progress and that the 

 same principle may be successfully utilized for diagnostic purposes in 

 a number of other maladies besides typhoid fever. This is notably 

 the case in paratyphoid infections, in Malta fever, and in meningo- 

 coccus infections. In other maladies agglutinin formation also takes 

 place, but either does not begin early enough to be of service in 



