Toxic Products 68 1 



mass, for when TO was subjected to staining with carbol-fuchsin and methylene 

 blue it was found to exhibit a blue reaction, while in TR a cloudy violet reaction 

 was obtained. 



The addition of 50 per cent, of glycerin had no effect upon TO, but caused a 

 cloudy white deposit to be thrown down from TR. This last reaction showed 

 that TR contained fragments of the bacilli insoluble in glycerin. 



In making the TR preparation Koch advises the use of a fresh, highly virulent 

 culture not too old. It must be perfectly dried in a vacuum exsiccator, and the 

 trituration, in order to be thorough, should not be done upon more than 100 mg. 

 of the bacilli at a time. A satisfactory separation of the TR from TO is said to 

 occur only when the perfectly clear TO takes up at least 50 per cent, of the solid 

 substance, as otherwise the quantity of TO in the final preparation is so great as 

 to produce undesirable reactions. 



The fluid is best preserved by the addition of 20 per cent, of glycerin, which 

 does not injure the TR and prevents its decomposition. 



The finished fluid contains 10 mg. of solid constituents to the cubic centimeter, 

 and before administration should be diluted with physiologic salt solution (not 

 solutions of carbolic acid). When administering the remedy to man the injec- 

 tions are made with a hypodermic syringe into the tissues of the back. The 

 beginning dose is ^500 m g-> rapidly increased to 20 mg., the injections being made 

 daily. 



Experiment showed that TR had decided immunizing powers. 

 Injected into tuberculous animals in too large a dose it produces 

 a reaction, but its immunizing effects were entirely independent of 

 the reaction. Koch's aim in using this preparation in the therapeutic 

 treatment 'of tuberculosis was to produce immunity against the 

 tubercle bacillus without reactions by gradual but rapid increase of 

 the dose. In so large a number of cases did Koch produce immunity 

 to tuberculosis by the administration of TR, that he believes it 

 proved beyond a doubt that his observations are correct. 



By proper administration of the TR he was able to render guinea- 

 pigs so completely immune that they were able to withstand inocula- 

 tion with virulent bacilli. The point of inoculation presents no 

 change when the remedy is administered; and the neighboring lymph- 

 glands are generally normal, or when slightly swollen contain no 

 bacilli. 



In speaking of his experiments upon guinea-pigs, Koch says: 



"I have, in general, got the impression in these experiments that full immuni- 

 zation sets in two or three weeks after the use of large doses. A cure in tubercu- 

 lous guinea-pigs, animals in which the disease runs, as is well known, a very rapid 

 course, may, therefore, take place only when the treatment is introduced early 

 as early as one or two weeks after the infection with tuberculosis. 



"This rule avails also for tuberculous human beings, whose treatment must not 

 be begun too late. ... A patient who has but a few months to live cannot 

 expect any value from the use of the remedy, and it will be of little use to treat pa- 

 tients who suffer chiefly from secondary infection, especially with the streptococ- 

 cus, and in whom the septic process has put the tuberculosis entirely in the 

 background." 



One very serious objection, first urged against commercially pre- 

 pared TR by Trudeau and Baldwin,* is that it is possible for it to 

 contain unpulverized, and hence still living, virulent tubercle bacilli. 



* "Medical News," Aug. 28, 1897. 



