PROTECTIVE INOCULATIONS. 361 



taneously into guinea-pigs. The experiments of Lote also indicate 

 that an "attenuation of virulence" has occurred in the cultures pre- 

 served in Koch's laboratory, originating in 1882 from the lungs of a 

 tuberculous ape. The author named made experiments with cultures 

 from this source (ninetieth to ninety -fifth successive cultures), and at 

 the same time with a culture obtained from Roux, of Pasteur's labor- 

 atory. Rabbits inoculated with cultures from the last-mentioned 

 source developed a hectic fever at the end of two weeks, and died tu- 

 berculous at the end of twenty -one to thirty-nine days. Twelve rab- 

 bits were inoculated with the cultures from Koch's laboratory ; the 

 injections were made either subcutaneously, or into a vein, or into the 

 pleural cavity, or into the cavity of the abdomen. No elevation of 

 temperature occurred in any of the animals, and they were found at 

 the end of a month to have increased in weight. At the end of six 

 weeks one of them was killed and tubercular nodules were found in 

 various organs. The remaining animals were killed at the end of 

 one hundred and forty -four to. one hundred and forty -eight days. 

 The two inoculated subcutaneously presented no sign of general tu- 

 berculosis, but a small yellow nodule containing bacilli was found at 

 the point of inoculation. Those inoculated by injection into a vein 

 showed one or two nodules in the lungs containing a few bacilli. In 

 Koch's original experiments rabbits were killed by intravenous inocu- 

 lation of his cultures in from thirteen to thirty-one days. That this 

 attenuation of virulence depends upon a diminished production of 

 toxic product to which the bacillus owes its pathogenic power appears 

 to be very certain, in view of the fact that the late cultures in a series 

 have a more vigorous and abundant development than the more patho- 

 genic cultures obtained directly from the animal body. 



The discovery by Koch of a toxin in cultures of this bacillus, 

 which is soluble in glycerin, and which in very minute doses pro- 

 duces febrile reaction and other decided symptoms when injected 

 subcutaneously into tuberculous animals, must rank as one of the first 

 importance in scientific medicine, whatever the final verdict may be 

 as to its therapeutic value in tuberculous diseases in man. 



The toxic substance contained in Koch's glycerin extract from cul- 

 tures of the tubercle bacillus, now generally known under the name of 

 tuberculin, is soluble in water, insoluble in alcohol, and passes readily 

 through dialyzing membranes. It is not destroyed by the boiling 

 temperature. According to the chemical examination of Jolles, the 

 " lymph " contains fifty per cent of water and does not contain alka- 

 loids or cyanogen compounds. It contains albuminates, which are 

 thrown down as a voluminous white precipitate by tannic acid, and 



