THE AOGLUTININS. 153 



cloudiness throughout the fluid, while the surface is covered by a 

 scum ; but in immune serum the microbes sink to the bottom of the 

 tube, w^hile the supernatant fluid remains clear. This condition con- 

 tinues for from eight to nine days, and it is not until the tenth day 

 that the culture becomes cloudy and a scum appears on the surface." 

 While the above-mentioned observations were made as herewith 

 stated, they attracted no special attention, and in all probability 

 their significance was not appreciated by the observers themselves, 

 and our knowledge of the phenomenon of aggintination may be said 

 to have originated in the classical research of Gruber and Durhamy^ 

 ■which was reported in 1896. These investigators found that when 

 a suspension of an agar culture of the cholera or typhoid bacillus is 

 mixed with its homologous serum, the ibacteria lose their motility and 

 form large clumps or masses. They attributed this phenomenon to 

 the presence of specific substances in the serum, for which they pro- 

 posed the term agglutinins, and suggested that the phenomenon 

 might be designated that of agglutination. Their researches showed 

 that this reaction is specific, within certain limitations : For instance, 

 a cholera serum has no agg'lutinating effect upon the vibrio of Fink- 

 ler, that of Metschnifcoff or that of Rumpel, and typhoid serum is 

 without action upon any of the colon germs, but a cholera serum 

 does agglutinate, v. Ivanoff, v. Berolinensis and v. Seine- Versailles. 

 In all instances in which cholera serum was found to have an agglu- 

 tinating action, it was also found to protect animals against inocula- 

 tion with the germ, and these two properties vary in the same pro- 

 portion, that is, the greater the agglutinating action the greater is 

 -the 'protective power against the same germ. Typhoid serum was 

 found to agglutinate typhoid-like bacilli, which were positively 

 known not to be real typhoid germs. For instance, bacillus enter- 

 itidis is agglutinated in a typical manner by a highly active typhoid 

 serum. However, there is easily observable a quantitative difference 

 in the agglutinating action of both cholera and typhoid sera upon 

 other than their homologous bacteria. Moreover, the agglutinating 

 action of typhoid serum is apparently more strictly specific than is 

 that of cholera serum, but in making a practical test with either, as 

 we shall see later, dilution of the serum is necessary in order to 

 avoid error. Gruber and Durham also pointed out the fact that 

 normal sera may have a more or less marked agglutinating action 

 upon both the vibrio of Asiatic cholera and the bacillus of typhoid 

 fever, and they stated that in order to use this reaction for the pur- 

 pose of identifying bacteria it would be found to be necessary to dilute 

 the serum employed. It seems to have been in the mind of these in- 

 vestigators at the time of the publication of their first paper that the 

 reaction described by them would find its practical application in the 

 detection and the definite recognition of specific microorganisms 

 ' MUnchmer med. Wochenschrijl, 43. 



