Part 89

Authorities are, however, not fully agreed as to whether the milk from tuberculous cows in which the udder is apparently not invaded by the disease should be considered dangerous or not. Some incline to the belief that the milk secreted by healthy udders is never infectious, even when the lungs or other organs are affected; that, in other words, the tubercle bacilli are rarely, if ever, separated from the lesions which they produce, and that the udder itself must be diseased before tubercle bacilli can appear in the milk. Experiments made with the milk of tuberculous cows in which there were no indications of udder disease do not bear out this theory, since tubercle bacilli have been found in their milk. Some authorities still believe that the udder is diseased when the milk is infected, but that the disease escapes observation. However this may be, the fact that the udder may be diseased and the disease not recognizable simply casts suspicion upon all milk from tuberculous animals. We know that the milk of tuberculous cattle may or may not contain tubercle bacilli when the udder is apparently free from disease, but we have no rapid method of determining whether in any given case the milk contains tubercle bacilli or not. Moreover, the bacilli may be absent at one time and present at another in milk from the same cow. When we consider, therefore, the extent of tuberculosis and the hidden character of the disease, a certain degree of suspicion rests upon all milk from untested cattle. Fortunately, tubercle bacilli are readily destroyed by the temperature of boiling water, and hence both meat and milk are made safe, the former by the various processes of cooking, the latter by boiling for a few moments. It is incumbent upon all communities to have dairy cows examined and tested with tuberculin. If disease is detected, the affected animal should be killed at once or else all opportunity for the sale of such milk removed by appropriate measures. Where milk or cream is sold to the trade in large towns or cities pasteurization should be required as an additional safeguard.

Recently there has been much discussion of the question as to whether human and animal tuberculosis are identical diseases and as to the possibility of the tuberculosis of animals being transmitted to man or that of man being transmitted to animals.

The fact that tuberculous material from human subjects often failed to produce serious disease in cattle was observed by a number of the earlier investigators who experimented with such virus. It was the experiments and comparative studies of Theobald Smith, however, which attracted special attention to the difference in virulence shown by tubercle bacilli from human and bovine sources when inoculated upon cattle. Smith mentioned also certain morphological and cultural differences in bacilli from these two sources, and in the location and histology of the lesions in cattle produced by such bacilli. He did not conclude, however, that bovine bacilli could not produce disease in the human subject, but said:

It seems to me that, accepting the clinical evidence on hand, bovine tuberculosis may be transmitted to children when the body is overpowered by large numbers of bacilli, as in udder tuberculosis, or when certain unknown favorable conditions exist.

Koch, however, in his address at the British Congress on Tuberculosis, went far beyond this and maintained that "human tuberculosis differs from bovine and can not be transmitted to cattle." As to the susceptibility of man to bovine tuberculosis, he said it was not yet absolutely decided, but one was "nevertheless already at liberty to say that, if such a susceptibility really exists, the infection of human beings is but a very rare occurrence." He emphasizes this view in the following language:

I should estimate the extent of infection by the milk and flesh of tubercular cattle and the butter made of their milk as hardly greater than that of hereditary transmission, and I therefore do not deem it advisable to take any measures against it.

This conclusion was so radically different from the views of most experimenters and so out of harmony with facts which had apparently been demonstrated by others that it at once aroused opposition in the congress, followed by the adoption of dissenting resolutions, and led to numerous investigations in various countries. Koch's conclusions were based upon his failure to produce tuberculosis in cattle and other animals by inoculating them with tuberculous material of human origin and his success in causing progressive and fatal tuberculosis in the same kinds of animals when inoculated with tuberculous material of bovine origin. With such positiveness did he hold to the constant and specific difference between the human and bovine bacillus that he promulgated an experimental method of discriminating between them. Speaking of the etiology of intestinal tuberculosis in man, he said:

Hitherto nobody could decide with certainty in such a case whether the tuberculosis of the intestine was of human or of animal origin. Now we can diagnose them. All that is necessary is to cultivate in pure culture the tubercle bacilli found in the tubercular material, and to ascertain whether they belong to bovine tuberculosis by inoculating cattle with them. For this purpose I recommend subcutaneous injection, which yields quite specially characteristic and convincing results.

These important and comprehensive conclusions followed from a comparatively few experiments upon animals, and apparently no effort had been made to learn to what extent human tubercle bacilli may differ in their virulence for cattle or what grades of virulence there might be among bacilli of bovine origin. Vagedes had already shown that bacilli were sometimes present in human lesions which were as virulent as bovine bacilli, but his work was wholly ignored by Koch.

A considerable number of investigators, including Chauveau, Vagedes, Ravenel, De Schweinitz, Mohler, De Jong, DelÈpine, Orth, Stenstrˆm, 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 3-1/2 by 5 inches, and the corresponding lymph gland was 2-3/4 inches long by 1-3/4 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.

Later investigations made by Park and Krumweide, of the Research Laboratory of New York City, Novick, Richard M. Smith, Ravenel, Rosenau, Chung Yik Wang, and others tend to show the incidence of bovine infection in the human family. Chung Yik Wang stated in 1917 that studies of 281 cases of various clinical forms of tuberculosis in Edinburgh, Scotland, resulted in the isolation of the bovine tubercle bacilli in 78.4 per cent of cases under the age of 5 years, in 70.3 per cent between the ages of 5 and 16, and in 7.8 per cent over the age of 16. This investigator states that from the prophylactic point of view any measure resorted to in combating the disease should be directed not only against the human spread of infection, but also, more particularly in children's cases, against the bovine source of infection.

Ravenel, in summarizing the work of Drs. Park and Krumweide, as well as others throughout the world, gives the following results:

Of 63 children dying of tuberculosis at the babies' hospital 59 cases proved to be human infection and 4 bovine, a percentage of 6-1/3.

Of 9 children dying of tuberculosis at the foundling hospital 4 proved to have derived their infection from human sources and 5 from bovine, a percentage of 55.

Of a total of 88 children under 5 years of age who died of tuberculosis 77 proved to have derived their infection from human sources and 11 from bovine, a percentage of 12-1/2.

Combining the cases studied in New York with those of other observers in different parts of this country and Europe, the following results are obtained:

Adults, 787 cases--777 human and 10 bovine infection.

Children, 5 to 16 years, 153 cases--117 human and 36 bovine infection.

Children under 5 years, 280 cases--215 human and 65 bovine infection.