PATHOGENICITY AND EXPERIMENTAL INFECTION OF ANIMALS 427 



ment but no macroscopic tubercle formation. Microscopically, the lungs contain enormous 

 numbers of bacilli, while in smears of the spleen, liver, and kidneys the organisms are 

 usually plentiful but not abundant. Smaller doses give rise to a less rapidly fatal disease, 

 in which there is time for the pulmonary tubercles to become partly aggregated into 

 irregular, hard, caseous masses. Small doses cannot be relied upon to cause progressive 

 infection when injected intraperitoneally, but intravenous inoculation with as few as 10-100 

 living baciUi has, in our experience, often been followed by chronic disease. If the animals 

 are killed within 3 months after such small doses, no tubercles may be visible in the lungs, 

 but quantitative bacteriological examination leaves no doubt that the bacilli are actively 

 proliferating (Schwabacher and Wilson 1937). Left to themselves, the animals may hve 

 for several months or even a year ; at post mortem some of them show miliary tuber- 

 culosis of the lungs. Mice may also be infected with very small numbers of bovine 

 tubercle bacilli if these are inhaled in the form of an aerosol mist (Glover 1944). The 

 virulence of the human and bovine types for mice seems to be very much the same 

 (Lange 1922, Stamatin and Stamatin 1939). The avian type was found by Gunn and 

 his colleagues (1934) never to cause fatal disease after intravenous inoculation of 0-25 mgm., 

 but our experience does not bear this out. We do, however, find that the avian bacillus 

 is less virulent than the mammalian types. According to Lange (1922), tuberculous 

 mice appear to be relatively non-allergic. Field mice {Arvicola arvalis) were found by 

 Koch (1886) to be more susceptible than house mice; after subcutaneous inoculation 

 they died in 4 to 6 weeks with extensive tuberculosis of the lungs, Uver, and spleen. 



Voles. — Wells (1938) found that the vole {Microtus agrestis) was useful for distinguish- 

 ing between the human and the bovine types of tubercle bacilli. In his experience bovine 

 bacilli in a dose of 0001 mgm. intraperitoneally produced extensive and progressive 

 disease, whereas human bacilli, even in a dose of 1 mgm., produced no more than an 

 insignificant lesion in the mesentery. Griffith (1939a, 1941a, e) states that the vole is 

 susceptible to infection with all three mannnalian types and with the avian type. The 

 bovine type is the most virulent, giving rise when inoculated parenterally or introduced 

 by feeding to generalized progressive tuberculosis, which runs a rapid course and is char- 

 acterized by widespread caseation of the lymphatic glands and great multipUcation of 

 bacilli in the lesions. The human and the avian bacillus can multiply in the tissues of 

 the vole, but have little tendency to produce macroscopic lesions. The murine type 

 gives rise to generalized tuberculosis, which runs a more chronic course than that caused 

 by the bovine type, and is distinguished by the occurrence in the areolar tissues of masses 

 of necrotic or caseous material composed largely of acid-fast bacilli. 



Other Animals. — The dog is relatively resistant to experimental tuberculosis, but 

 young animals may be infected by intraperitoneal inoculation with the mammaUan types. 

 Horses and asses are also resistant ; subcutaneous injection sets up no more than a local 

 lesion. Cats are highly susceptible to bovine bacilli, slightly susceptible to avian, and 

 resistant to human bacilli. Subcutaneous injection of 0-1 mgm. of bovine bacilli sets up 

 invariably a rapidly fatal generaUzed tuberculosis. Monkeys and anthropoid apes are easily 

 infected either by subcutaneous inoculation or by feeding with the human and bovine 

 types, but are comparatively resistant to the avian type. The golden hamster (Cricetus 

 auratus) is very susceptible to experimental infection with the bovine and slightly less 

 so to the human type, both of which produce progressive generaUzed tuberculosis. The 

 murine type causes generalized tuberculosis of slow development with the production 

 of lesions that do not undergo necrosis or caseation. The avian type is the least virulent 

 and rarely gives rise to macroscopic lesions (Griffith 19396, 19416). Ferrets in captivity 

 brought up on raw milk sometimes contract tuberculosis. Experimentally they are 

 susceptible to the bovine but only very slightly to the human type of bacillus (Dunkin, 

 Laidlaw and Griffith 1929, Balling and O'Brien 1935). 



Birds. — With the exception of the parrot, the cockatoo, the canary, and possibly 

 certain birds of prey, birds are resistant to infection with the mammalian bacilli. Sub- 



