PATHOGENICITY AND EXPERIMENTAL INFECTION OF ANIMALS 423 



the murine type is serologically indistinguishable from the human and bovine 

 types. Observations suggest that group-specificity is determined by the poly- 

 saccharides, type-specificity by the proteins (Seibert 1941). There is evidence 

 that the avian type may be divided serologically into a small number of sub-types 

 (Wulff 1925, Furth 1926, Schaefer 1937, Harpoth 1938). It is possible that the 

 cold-blooded and saprophytic acid-fast types are heterogeneous, but insufficient 

 strains have as yet been examined to affirm this definitely. 



It is noteworthy that serological methods are less valuable in classifying 

 the tubercle bacilli than cultural methods ; the bovine and human bacilli can be 

 easily separated by their cultural reactions, yet serologically they form a homo- 

 geneous group. This affords an exception to the rule that serological examination 

 is a far more delicate method of differentiation than cultural examination. 



Pathogenicity and Experimental Infection of Animals. — -Under natural conditions 

 the human tubercle bacillus gives rise to disease mainly in man, monkeys, pigs, 

 and occasionally in dogs and parrots ; the bovine bacillus to disease in cattle, pigs, 

 horses, man, and occasionally dogs, cats, and sheep ; the murine bacillus to disease 

 in voles and possibly other members of the family of Muridce ; the avian bacillus 

 to disease in birds, and occasionally in pigs, sheep and cattle ; and the cold-blooded 

 bacillus to disease in cold-blooded animals and fish. Saprophytic acid-fast bacilli, 

 though occasionally isolated from the tissues, rarely seem able to give rise to 

 progressive disease (see also Chapter 59). 



The virulence of tubercle bacilli is subject to variation. Though usually virulent 

 on isolation, they not infrequently become more or less avirulent during subculture 

 in the laboratory. Very little exact information, however, based on an adequate 

 number of animal tests, is available about the difference in virulence of freshly 

 isolated strains of the same type, or about the factors that are responsible for changes 

 in virulence occurring in vitro or in vivo. 



The experiments of Villemin, recorded in 1868, furnished convincing proof of the 

 transmissibility of human tuberculosis to animals. Material taken from different 

 types of tuberculosis in man — catarrhal pneumonic forms, caseous pulmonary and 

 chronic pulmonary tuberculosis, disseminated tuberculosis, scrofula, sputum, and 

 the blood removed from a tuberculous patient after death — and introduced beneath 

 the skin of rabbits, was successful in setting up the disease in 17 out of 21 animals ; 

 3 of the 4 animals that did not contract tuberculosis died within a week of erysipelas. 

 Villemin also transmitted bovine tuberculosis to rabbits, and made the important 

 observation that material from bovine tuberculosis set up a more rapid and more 

 generalized disease than material from human tuberculosis, when inoculated into 

 these animals. Convincing though Villemin's experiments were, the final proof of 

 the transmissibility of the disease was not furnished till Koch in 1882 succeeded in 

 producing tuberculosis in animals by injection of pure cultures of the tubercle 

 bacillus. In 1898 Smith brought evidence to show that bovine tubercle bacilli 

 were more virulent when injected into rabbits and calves than human bacilli. 

 This difference was substantiated by other workers, in particular by Vagedes (1898), 

 Ravenel (1901), the English Royal Commission on Tuberculosis (Report 1911), 

 Kossel, Weber and Heuss (1904, 1905), and Park and Krumwiede (1910). 



Cattle. — The subcutaneous injection of 50 mgm. of bovine bacilli from young serum 

 cultures into calves sets up an acute, rapidly generalizing disease, proving fatal in about 

 6 weeks to 3 months. At necropsy the main features are a local lesion, focal glandular 

 swelling and abscess formation, generalized glandular lesions, and lesions in the viscera. 



