8i2 AGGLUTININS AND THEIR APPLICATIONS 



agglomeration into masses visible to the naked eye promptly followed. The serum of a normal 

 rabbit had no such action upon emulsions of cholera vibrios. Bordet observed further that 

 an immune cholera serum heated to 55°-6o° C. retained this property, which fact served to 

 distinguish it from bactericidal power, a study of which was at the time engaging the atten- 

 tion of Bordet and many others. The next year Gruber and Durham' continued and extended 

 the observations of Bordet and for the first time described the agglutination reaction as a 

 separate and distinct characteristic of immune sera. In their first joint publication Gruber 

 and Durham wrote: "By mixing the immune sera .... with the emulsion of the agar cul- 

 ture .... one can see that the bacteria agglutinate in great clumps, and the characteristic 

 motions come to a standstill. These reactions are in the closest relationship to the protective 

 action of sera. In consequence, the bacteria under the influence of the antibodies contained 

 in the immune sera become sticky or glutinous. For this reason we describe the specific sub- 

 stances of the immune sera 'agglutinins.' " Just prior to the appearance of the joint paper 

 by these authors, one of them, Durham,^ had presented a note to the Royal Society of Lon- 

 don in which he indicated that certain immune sera contained a hitherto incompletely recog- 

 nized and inadequately described type of antibody which brought about agglutination. 



Gruber,^ in his first communication, stated that "the essential action of the antibodies 

 of the fluids of immunized animals consists in the fact that they cause the bursting of the 

 covering of the bacteria. This is indicated by the fact that the bacteria which are treated 

 with these fluids become sticky and glutinous, unite in large clumps, and lose their character- 

 istic motility. This fundamental action of immune sera has been completely overlooked by 

 Pfeiffer and his pupils. Metchnikoff and Bordet saw it but did not grasp the importance of it. 

 On account of this fundamental action I shall call the antibodies of specificaHy immunized 

 animals 'glabrificines.' " This first designation of agglutinins was given by Gruber because he 

 erroneously interpreted their mode of action. This he himself recognized, and in his next 

 publication upon the subject he substituted the term "agglutinin" for "glabrificine." Gruber 

 and Durham extended their study of the phenomenon to various species of bacteria and their 

 homologous immune sera, and emphasized the specific nature of the reaction. Some possible 

 practical applications of the reaction of agglutination were indicated by Gruber and Durham. 

 It was suggested by them that bacteria eliminated in the stools of patients suffering from 

 cholera or typhoid fever might be identified by the employment of appropriate immune sera. 



Almost simultaneously publications of Widal^ and Griinbaums described the reaction 

 which occurs when the serum of typhoid-fever patients is added to emulsions of typhoid 

 bacilli. Widal applied the reaction macroscopicaUy and Griinbaum microscopically. The 

 paper by Griinbaum was more extended than that of Widal, but the prior appearance of the 

 latter's note has resulted in this diagnostic procedure being almost universally described as 

 the "Widal or Gruber-Widal test." Griinbaum extended and emphasized the important 

 observation of Gruber that the reaction of agglutination is only relatively specific. He exam- 

 ined thirty-two specimens of sera, nine from normal individuals (three of whom, however, had 

 had typhoid fever previously) and twenty-three from persons suffering from various diseases 

 other than typhoid. Emulsions of cholera vibrios, typhoid bacilli, and colon bacilli were 

 added to varying amounts of sera from different patients. Agglutination of all three species 

 was observed in certain instances; but in higher dilutions sera from normals or from persons 



' Gruber, Max, and Durham, H. E.: MUnchen. med. Wchnschr., 43, 285. 1896. 

 'Durham, H. E.: Proc. Roy. Soc, London, 59, 285. 1896. 

 3 Gruber, M.: Miinchen. med. Wchnschr., 43, 206. 1896. 

 ^ Widal, F.: J. de mid. et chir. prat., p. 533. 1896. 

 5 Griinbaum, A. S.: Lancet, 2, 806. 1896. 



