714 ACTIVE IMMUNIZATION 



"When one vaccinates a healthy guinea-pig with a pure culture of 

 tubercle bacilli, the wound, as a rule, closes and in the first few days 

 seems to heal. However, in from ten to fourteen days a hard nodule 

 appears which soon breaks down, leaving an ulcer that persists to the 

 time of death of the animal. There is quite a different sequence of 

 events when a tuberculous guinea-pig is vaccinated. For this experi- 

 ment animals are best suited that have been successfully infected four 

 to six weeks previously. In such an animal the inoculation wound 

 likewise promptly unites. However, no nodule forms, but on the next 

 or second day after a peculiar change occurs. The point of inoculation 

 and the tissues about, over an area of from 0.1 to 1 cm. in diameter, 

 grow hard and take on a dark discoloration. Observation on subsequent 

 days makes it more and more apparent that the altered skin is necrotic. 

 It is finally cast off, and a shallow ulceration remains, which usually 

 heals quickly and permanently without the neighboring lymph-glands 

 becoming infected. Inoculated tubercle bacilli act very differently 

 then upon the skin of healthy and tuberculous guinea-pigs. This 

 striking action is not restricted to living tubercle bacilli, but is equally 

 manifested by dead bacilli, whether they be killed by exposure to low 

 temperature for a long time or to the boiling temperature, or by the 

 action of various chemicals. 



"After having discovered these remarkable facts, I followed them up 

 in all directions and was further able to show that killed pure cultures of 

 tubercle bacilli ground up and suspended in water can be injected in 

 large amounts under the skin of healthy guinea-pigs without producing 

 any effect other than local suppuration. Tuberculous guinea-pigs, on 

 the other hand, are killed in from six to forty-eight hours, according to 

 the dose given, by the injection of small quantities of such a suspension. 

 A dose which just falls short of the amount necessary to kill the animal 

 may produce extensive necrosis of the skin about the point of injection. 

 If the suspension be diluted until it is just visibly cloudy, the injected 

 animals remain alive, and if the administration is continued with one 

 to two day intervals, a rapid improvement in their condition takes 

 place; the ulcerating inoculation wound becomes smaller and is finally 

 replaced by a scar, a process that never occurs without such treatment; 

 the swollen lymph-glands become smaller; the nutrition improves, 

 and the disease process, unless it is too far advanced and the animals 

 die of exhaustion, comes to a standstill. 



"Thus was established the basis for a rational treatment of tuber- 

 culosis. However, such suspensions of killed tubercle bacilli are un- 



