TUBERCULOSIS. 273 



it is still employed on a large scale for diagnostic purposes, 

 and, it appears, with great success. 



The New Tuberculin-preparations, TO and TR. After 

 the failure of the original tuberculin, Koch applied himself 

 unremittingly to the improvement of tuberculin-prepara- 

 tions. He found that immunity could not be conferred 

 upon animals by subcutaneous injection of unchanged 

 tubercle-bacilli. He, therefore, undertook to disintegrate 

 the tubercle-bacilli mechanically, in order to render them 

 the more easily absorbable. The cultures were dried in a 

 vacuum and rubbed up in an agate mortar without addition 

 until only a small number of bacilli were visible micro- 

 scopically. The powder was mixed with distilled water,, 

 and centrifugated for from a half to three-quarters of an 

 hour. In this way Koch effected a separation into two 

 layers an upper transparent, opalescent layer, which con- 

 tained no bacilli, and a densely adherent lower layer. The 

 latter was again dried, rubbed up, and centrifugated in the 

 manner described, and the entire process was repeated until 

 all the bacilli had practically been reduced to solution. 

 Koch then determined that the solutions thus obtained 

 were readily absorbable, and that they did not give rise to 

 the formation of abscesses. It was found, however, that 

 the fluid obtained from the first centrifugation exhibited 

 reactions different from that obtained from the second and 

 from subsequent centrifugations. Koch designated the first 

 tuberculin O (obere, upper TO) ; and all of the others, 

 which were alike in their reaction, tuberculin R (residue 

 TR). TO contains the constituents of the tubercle-bacilli 

 soluble, and TR those insoluble, in glycerin. It can be 

 readily understood that the properties of TO are compar- 

 able, on the whole, with those of the original tuberculin. 

 TR, however, according to Koch, exhibits distinct immuniz- 

 ing properties, and gives rise to reaction in tuberculous 

 subjects only when used in large doses. Its action is 

 entirely independent of the reactions that played so impor- 

 tant a part when the original tuberculin was used. Koch 

 states that in conferring immunity with TR the reactions 

 may be entirely avoided, and, by carefully increasing 

 the dose, tuberculous subjects may be habituated quite 

 rapidly, without any reaction, to considerable amounts of 

 the new remedy. When this has been accomplished, the 

 organism may be considered as immune to the original 

 18 



