A considerable number of investigators, including Chauveau, Vagedes, Ravenel, De Schweinitz, Mohler, De Jong, Delépine, Orth, Stenström, Fibiger and Jensen, Max Wolff, Nocard, Arloing, Behring, Dean and Todd, Hamilton and Young, the German Tuberculosis Commission, and Theobald Smith, have found tubercle bacilli in the bodies of human beings who died of tuberculosis which proved to have about the same virulence for cattle as had the bacilli from bovine animals affected by the disease.
Kossel, in a preliminary report, stated that the German commission had tested 7 cultures of tuberculosis from cattle and hogs—4 from cattle and 3 from hogs. Two proved acutely fatal in cattle after eight to nine weeks; 4 likewise produced a generalized tuberculosis, but which certainly had a more chronic course, while 1 of the cultures caused only an infiltration at the point of inoculation, with some caseous foci in the adjoining prescapular gland and in one of the mediastinal glands, and there was lacking the spreading of the tuberculosis over the entire body which they were accustomed to see after the injection of cultures of bovine tuberculosis. "Hence," says Kossel, "among bovine tuberculosis bacilli there can also occur differences with regard to the virulence."
The German commission also tested 39 different freshly made cultures from tuberculous disease in man. Nineteen did not produce the slightest symptoms in cattle; with 9 others the cattle exhibited after four months very minute foci in the prescapular glands, which were mostly encapsuled and showed no inclination to progress; with 7 other cases there was somewhat more marked disease of the prescapular glands, but it did not go so far as a material spreading of the process to the adjoining glands. There were 4 cultures, however, which were more virulent and caused generalized tuberculosis in the cattle inoculated with them.
It would appear, therefore, that hereafter everyone must admit that it is impossible always to tell the source of a culture of the tubercle bacillus by its effect when it is inoculated upon cattle. One of the bovine cultures failed to produce generalized tuberculosis in cattle, and some of the human cultures did produce it in such animals. Moreover, while some of the human cultures caused no disease at all, others led to the development of minute foci in the prescapular glands, and still others to somewhat more marked disease of the glands. There were, consequently, four degrees of virulence noted in these 39 cultures of bacilli from human sources and three degrees of virulence in the 7 cultures from animal.
Now, if we accept the views of Koch as to the specific difference between human and bovine tubercle bacilli, and that the human bacilli produce only localized lesions in cattle, while bovine bacilli produce generalized lesions in them, must we not conclude that the one non-virulent bovine culture was in reality of human origin, and that the animal from which it was obtained had been infected from man? This is a logical deduction, but reverses the dictum laid down at London that human tuberculosis is not transmissible to cattle. Again, how are we to explain the human cultures of medium virulence? Are they human bacilli which, for some unknown reason, are increasing in virulence and approaching the activity of the bovine bacillus, or are they really bovine bacilli which have multiplied in the human body until their virulence has become attenuated? In whatever manner these questions are decided it would seem that the findings of the German commission, instead of supporting Koch's views that we can decide with certainty by the inoculation of cattle as to the source of any given bacillus, really show that this method of diagnosis is extremely uncertain in the present condition of our knowledge.
It is definitely admitted that 4 of the human cultures caused generalized tuberculosis in cattle; Kossel suggest, however, that it may be possible that the bacilli in cases of human tuberculosis under certain circumstances can likewise attain a very high pathogenic activity for cattle without being for that reason bovine bacilli. Undoubtedly the German commission is confronting the two horns of a dilemma, either one of which is fatal to the views of Koch as stated with such positiveness at London. If we accept this suggestion thrown out by Kossel, we must conclude that Koch was wrong in his claim that human tuberculosis can not be transmitted to cattle, and thus with one blow we destroy the entire experimental support which he had for his argument before the British Congress on Tuberculosis. If, on the other hand, we accept the conclusion which follows from the principle laid down by Koch for the discrimination between human and bovine bacilli, and which appears to be favored by Kossel, we must admit that bovine tuberculosis is an extremely important factor in the etiology of human tuberculosis. Of the 39 cases of human tuberculosis tested, 4, or more than 10 per cent, were virulent for cattle and would be classified as of bovine origin; however, these 4 cases, were all found among the 16 cases of tuberculosis in children which the commission investigated; hence it is plain that 25 per cent of the cases tested of tuberculosis in children would by Koch's method be classified as of bovine origin.
In the Bureau of Animal Industry two distinct lines of experiments have been carried on, in order that one might serve as a check against the other. There has been, however, no discrepancy in the results. De Schweinitz, in the Biochemic Division, Bureau of Animal Industry, isolated 9 cultures from human tuberculosis. Two were derived from human sputum, 3 from cases of generalized tuberculosis in adults, and 4 from cases of generalized tuberculosis in children. By comparing these cultures with a newly isolated virulent culture of bovine tuberculosis, there were found among them 2 cultures from children which were identical in their cultural and morphological characters with the bovine bacillus. These cultures also killed rabbits and guinea pigs in as short a time as did the bovine bacillus. Hogs which were inoculated subcutaneously with these 2 cultures from children died of generalized tuberculosis. Two calves weighing more than 300 pounds each were inoculated subcutaneously with these virulent human cultures, and as a result developed generalized tuberculosis. A yearling heifer inoculated with 1 of the cultures showed generalized tuberculosis when killed three months after inoculation. Both the cattle and the hogs had been tested with tuberculin and found to be free from tuberculosis before the inoculations were made. It is important to observe in this connection that 2 out of 4, or 50 per cent, of the cultures obtained from cases of generalized tuberculosis in children proved virulent for cattle.
Mohler, working in the Pathological Division, Bureau of Animal Industry, obtained 3 very virulent cultures of tubercle bacilli from the human subject. A goat inoculated subcutaneously with 1 of these cultures died in 37 days with miliary tuberculosis of the lungs involving the axillary and prescapular glands. This bacillus was obtained from the mesenteric gland of a boy. Of still greater interest is a bacillus isolated by Mohler from human sputum. A goat inoculated subcutaneously with a culture of this germ died in 95 days of pulmonary tuberculosis. A cat inoculated in the same manner died in 23 days of generalized tuberculosis. A rabbit similarly inoculated died in 59 days of pulmonary tuberculosis. Another rabbit inoculated with a bovine culture for comparison lived 10 days longer than the one inoculated with this sputum germ. Mohler also inoculated subcutaneously a 1-year-old heifer with a culture derived from the tuberculosis mesenteric gland of a boy 4 years of age. This culture was always refractory in its growth under artificial conditions, and the bacilli were short, stubby rods, corresponding in appearance to the bovine type. At the autopsy, held 127 days after the inoculation, the general condition was seen to be poor and unthrifty, and large, hard tumors were found at the points of inoculation. On the right side the swelling measured 3½ by 5 inches, and the corresponding lymph gland was 2¾ inches long by 1¾ inches in diameter. This gland contained numerous calcareous foci; one at the apex was an inch in diameter. The lesions on the left shoulder of the animal were very similar to those found on the right side, but the dimensions of the tumor were slightly less. The lungs presented an irregular mass of tuberculous nodules, and 7 or 8 grapelike nodules were seen on the parietal pleura. Bronchial and mediastinal lymph glands contained numerous tuberculous foci, and the pericardium, peritoneum, spleen, and liver also were affected.
In order to throw some light, if possible, upon the morphological constancy of the different types of tubercle bacilli, Mohler made comparative studies of bacilli from various sources, and which had been passed through various species of animals, by making the cultures upon dog serum after the method described by Theobald Smith. Some important results have been obtained. One culture of human bacilli which had morphological and cultural peculiarities similar to those of the bovine bacillus, and which produced only local lesions in cattle, was passed through a series of five cats. It was then found to be completely changed in its morphological characters, the rods being elongated, slender, more or less beaded, and entirely of the human type. Far from decreasing in virulence, however, as might be expected from its morphological appearance, this bacillus had so increased in its pathogenic activity that it produced generalized tuberculosis in a cow. This cow was inoculated subcutaneously in front of each shoulder with 2 cubic centimeters of a salt-solution emulsion of the tuberculous omentum of the last cat of the series. The cow rapidly lost flesh, had a temperature of 104° F., with the point of inoculation and adjacent glands greatly swollen. The autopsy revealed generalized tuberculosis, involving the lungs, mediastinal glands, spleen, liver, and kidneys. Tubercle bacilli of the bovine type obtained from the mesenteric glands of a sheep, hog, and cow were similarly transformed in their morphological appearance after being passed through a series of cats and recovered on dog serum. These bacilli also increased in virulence, as the last cat in the series invariably succumbed in a shorter time than the first of the series.
These experiments and observations indicate that the types of tubercle bacilli are very inconstant, and that under suitable conditions they readily change both in morphology and in virulence. A similar conclusion was reached by other investigators in working with the avian and porcine types of tubercle bacilli several years ago, and was reasonably to have been expected with the human and bovine types.