68o Tuberculosis 



drops may be used. Ordinary tuberculin must be avoided, as 

 the glycerin it contains causes too much irritation and masks the 

 reaction. 



Priority in regard to the theoretic aspects of these reactions 

 seems to belong to Wolff-Eisner,* who was the first to point 

 out that the injection of all albuminous substances resulted in 

 hypersensitivity instead of immunity unless certain precautions 

 were observed. Upon this ground Levyt gives him credit as the 

 founder of the method. The reaction is undoubtedly an allergic 

 phenomenon. 



KlebsJ made strong claims for his own modifications of tuber- 

 culin, known as antiphthisin and tuherculocidin, but according 

 to the experimental studies of Trudeau and Baldwin, antiphthisin 

 is only much diluted tuberculin, and exerts no demonstrable in- 

 fluence upon the tubercle bacillus in vitro, does not cure tuberculosis 

 in guinea-pigs, and probably inhibits the growth of the tubercle 

 bacillus upon culture- media to which it has been added only by its 

 acid reaction. 



The "bouillon-filtrate" (bouillon filtre),of Denys§ is a porcelain 

 filtrate of bouillon culture of the tubercle bacillus and corresponds 

 to Koch's original tuberculin before concentration, except in that 

 it has not been subjected to heat. 



Tuberculin-R. — TR or tubercuIin-R appears to be an important 

 addition to the immunology of tuberculosis, made by Koch.|| 



TR signifies "tuberkel bacillen resten" or bacillary fragments. 



Pursuing the idea of fragmenting the bacilli, or treating them chemically to 

 increase their solubility, Koch found that a lo per cent, sodium hydrate solution 

 3delded an alkaline extract of the bacillus, which, when injected into animals, 

 produced effects similar to those following the administration of tuberculin, 

 except that they were more brief in duration and more constant in result; but 

 the disadvantage of abscess formation following the injections remained. The 

 fluid, when filtered, possessed the properties of tuberculin. 



Mechanical fragmentation of bacilli had been employed by Klebs in his studies 

 of antiphthisin and tuherculocidin, and Koch now used it with advantage. He 

 pulverized living, virulent, but perfectly dry bacilli in an agate mortar, in order . 

 to liberate the toxic substance from its protecting envelope of fatty acid, triturat- 

 ing only very small quantities of the bacteria at a time. 



Having thus reduced the bacilli to fragments, he removed them from the mor- 

 tar, placed them in distilled water, washed them, and collected them by cen- 

 trifugation, as a muddy residuum at the bottom of an opalescent, clear fluid.' 

 For convenience he named the clear fluid TO; the sediment, TR. TO was found 

 to contain tuberculin. In order to separate the essential poison of the bacteria 

 as perfectly as possible from the irritating tuberculin, the TR fragments were 

 again dried perfectly, triturated once more, re-collected in fresh distilled water, 

 and recentrifugated. After the second centrifugation microscopic examination 

 showed that the bacillary fragments had not yet been resolved into a uniform 



* " Centralbl. f. Bakt. u. Parasitenk.," 1904, Orig., xxxvii. 

 t "Verein fiir in'nere Medizin zu Berlin," Dec. 16, 1907. 

 X "Die Behandlung der Tuberculose mit Tuherculocidin," 1892. 

 §"Acad. royale de med. de Belgique," Feb. 22, 1902; abst. "Centralbl. f. 

 Bakt. u. Parasitenk.," Ref., 1902, xxxi, p. 563. 

 II "Deutsche med. Wochenschrift," 1897, No. 14. 



