234 BACTERIA. 



treated the small secondary inoculation wound becomes 

 sealed at first, but no nodule is formed ; a peculiar change 

 takes place at the point of (primary) inoculation. As early 

 as the first or second day the point becomes hard and dark- 

 coloured — a condition that is not confined to the point of 

 inoculation— and spreads around for about 0.5 to i centi- 

 metre. During the next few days it becomes more and 

 more clear that the epidermis thus changed is necrotic, and 

 finally it is thrown off, and a flat ulcerated surface remains, 

 which generally heals quickly and completely, without infec- 

 tion being carried to the neighbouring lymphatic glands. 

 Thus the inoculated tubercle bacilli act quite differently 

 on the skin of a healthy guinea-pig, and on that of a 

 tuberculous one. But this remarkable action does not 

 belong exclusively to living tubercle bacilli, it also be- 

 longs in the same degree to dead ones, whether they be 

 killed by low temperature of long duration, which I at 

 first tried, or by boiling heat, or by the action of certain 

 chemicals. 



" This peculiar fact having been ascertained, I followed it 

 up in all directions, and then further found that pure culti- 

 vations of tubercle bacilli thus killed, after they are ground 

 down and suspended in water, may be injected under the 

 skin of healthy guinea-pigs in large quantities without 

 producing anything but local suppuration. Tuberculous 

 guinea-pigs, on the other hand, are killed by an injection of 

 very small quantities of suspended cultures within a time 

 varying from six to forty-eight hours, according to the dose ; 

 a dose which is just insufficient to kill the animal being 

 sufficient to produce a widespread necrosis of the skin in the 

 region of the point of (primary) inoculation. If the fluid 

 with its suspended matter be still further diluted, so that it 

 is scarcely turbid to the eye, the animals remain alive ; and 

 if the injections be continued at intervals of one or two days 

 a noticeable improvement in their condition soon sets in ; 

 the ulcer at the point of inoculation becomes smaller, and 

 finally cicatrization takes place. This is never the case 

 when such treatment is not resorted to. The swollen lym- 

 phatic glands become smaller, the condition as regards 

 nutrition improves, and the progress of the disease is 

 arrested, if it is not already so far advanced that the animal 

 dies of debility. 



