The Relation of the Bacillus Tuberculosis of Man to that of Cattle. On the discovery of the bacillus tuberculosis it was largely assumed that it was the same in all tuberculous animals, in all organs and in all circumstances. But it was soon found that the bacillus of chicken tuberculosis differed materially from that of the mammalian, that it could be inoculated only with difficulty on cattle or Guinea pig, as could that of the latter on the bird. The bacillus of the chicken found a most receptive home in the rabbit and horse, and was more easily started in artificial culture in glycerine bouillon, than was that of man or ox. But presently it appeared that the affinities and disparities did not end here. The bacillus from man or ox led to much more pronounced lesions in Guinea pigs than in rabbits, and the abdominal bacillus of the horse was inoculable on the chicken. Both horse and parrot proved receptive to the bacillus from man. Swine, like Guinea pigs showed a receptiveness to the bacillus of man or ox. The bacilli from the sputum, open tuberculous sore, or bones of man showed less virulence for Guinea pigs and rabbits than did those from tubercles in the human lungs and liver. The bacillus from the ox showed a greater virulence toward rodents and other small animals than did the bacillus from man. The bacillus of human sputum inoculated on the ox did not habitually cause generalized tuberculosis, but oftentimes a local tubercle or group of tubercles, and sometimes the inoculation wound healed without permanent lesion. These last points were seized upon to sustain a doctrine of probable duality for the microbe of tuberculosis, but if duality it was quite evident it could not end there, but must be extended to multiplicity, each small group of genera having a tubercle bacillus peculiar to itself. Those who thought their interest lay in arresting all sanitary control of tuberculous cattle and their products, became urgent in opposition to active government measures, demanding mathematical proof of the infection of man from cattle, under conditions that would exclude the remotest possibility of the introduction of infection from another source. The clearest and most abundant circumstantial evidence would not suffice, they must have direct experimental inoculation under conditions of precaution against outside germs, which were practically impossible in any community, conveniently ignoring that such inoculation, if successful, would have amounted to manslaughter, and that no such experimental evidence has been had, or can be had, of any of the deadly diseases of man. Infection by exposure and accidental inoculations can be had in abundance, just as they can in tuberculosis, but never under the rigid precautions which would exclude the possibility of extraneous infection.
The subject has assumed such importance that I may be excused for introducing a portion of my paper read before the New York State Medical Society in 1900.
1. This Variability is Common to Microbes Generally. Certain bacilli, like those of anthrax, grow in the living body as rods only, but become long filaments in given artificial media. They produce no spores in the living tissue, but do so readily in the carcass or soil. Transferred from ox to ox they are generally fatal, but if grown for several generations in Guinea pigs, and then transferred to cattle, the resulting disease is slight (Burdon-Sanderson, Duguid, Greenfield). Rabies passed from dog to dog is almost constantly fatal, but if passed through the ape and then back to the dog it is comparatively harmless (Pasteur). In both these cases the inoculated animals become immune from the more virulent germs, showing that they have passed through the actual disease in an unusually mild form. The later system of Pasteur is founded on this same general truth, as are also the methods of lessening the pathogenesis of germs by subjecting them to compressed oxygen, to graduated heating, to an altered chemical condition of the culture medium, to antisepsis, etc. For a time such weakened cultures often retain their lessened pathogenesis, even through a succession of cultures in a susceptible animal body, acting as if the germ were indeed a distinct species. But it might well have been considered that a microbe which had changed its aptitudes in a given environment could presumably revert to its original habits under the incentive of a suitable medium. And this is precisely what does take place. Pasteur has shown that the less potent rabic virus becomes more potent when passed several times through the body of a rabbit, and that the weakened anthrax germ acquires greater force when passed through a series of small birds or newly-born mammals.
To come to tuberculosis, Trudeau tells us that a culture of bacillus tuberculosis from man inoculated on the rabbit, and then cultivated for two years in vitro, becomes much less destructive to Guinea pigs, and that after six years of such artificial culture all the Guinea pigs inoculated with it live for many months, some for two and a half years, and some even recover. The usual life of the Guinea-pig after inoculation is seventeen days.[[3]] All of our zymotic diseases have in a similar way cycles of malignancy and benignancy. For a series of years measles, scarlatina, diphtheria, smallpox, or grippe have an unwonted mildness, and, again, one or another merges into a cycle of extreme and fatal malignancy. Rinderpest on the steppes of Asia is comparatively harmless to the native stock, but among outside cattle imported into the steppes or attacked in their native lands it is habitually fatal. Texas fever is mild among the indigenous cattle in the Gulf States, but very deadly to Northern stock. Glanders is not at all fatal to horses of the plains, the Rockies, or the Sierras; but it becomes redoubtable when these horses carry it to the Eastern seaboard, and still more so in Western Europe. It is a common experience to see a malady transformed through the effects of heredity or acquired immunity, through environment or the temporary mitigation of virulence in the germ; and again we see the same disease, no longer restrained by such inhibitory conditions, bursting forth as a malignant and deadly plague. We have, therefore, no warrant for the hypothesis that a pathogenic germ which, under given conditions of life, has lost in pathogenesis, but not in vitality, should continue forever to exist as a harmless microbe.
[3]. Johns Hopkins Hospital Reports, Bulletin 100.
2. Varying Malignancy of the Tubercle Bacillus in Man. Nothing is more familiar to physicians than the slow progress of tuberculosis of the lymph-glands and bones, on the one hand, and its frequent rapid progress in pulmonary, abdominal, or encephalic organs on the other. It has on this account been rather difficult to persuade many of the etiological identity of scrofula and consumption. In experimental tuberculosis the same truth constantly crops up. Arloing and his followers found that the tubercle bacillus from the lymph-glands of man proved less virulent and deadly than that from the human lungs (Lecons sur la Tuberculose). As early as 1880, Creighton drew attention to this in his work on Bovine Tuberculosis in Man.
But the bacillus from the lungs is subject to variations of this kind. Among seven specimens of human sputum, cultivated by Theobald Smith, six had a fair average vitality, while the seventh failed to perpetuate itself on dog serum.[[4]]
[4]. Journal of Experimental Medicine, 1898, No. 111.
It should be strongly emphasized in this connection that the failure of extension and generalization of the sputum germ when transferred to cattle does not distinguish it from the tubercle bacillus as conveyed from ox to ox. Everyone at all experienced with the tuberculin test well knows that in most herds the majority of the tuberculous animals show no generalization, but only a localized tuberculosis. There is reason to believe that even recoveries take place after slight infection, and it is certain that many tuberculous cattle continue for years in what appears to be good general health. Unless in particularly susceptible subjects or under specially poor hygienic conditions, or unless in case of reinfection, the average bacillus of bovine origin habitually fails to produce in other cattle a rapid extension and generalization.
3. Interchangeability of Bacillus of Man and Bird. Of all known forms of tubercle bacillus that of birds is the most distant from that of man or ox, and yet the beautiful experiments of Nocard[[5]] serve to establish their essential identity. Taking the bacillus of human sputum, which would not infect the fowl, he enclosed it in collodion capsules, which confined the bacilli while allowing transudation of the animal fluids, and left these in the abdomen of the chicken for not less than four months. He repeated this three times in succession with the product of the original sputum germ, and obtained a bacillus which was actively pathogenic for the chicken, though it had been harmless after the sojourn of four and eight months respectively.