ened resistance and greater susceptibility to temperature conditions. addition to the variations of virulence and growth among tubercle bacilli it has been found that other differences exist according to their habitat.

Theobald Smith has called attention to what he terms "the complex relationship established in time by a selective adaptation between two living organisms, of which one is the parasite of the other." He emphasizes the interdependence of both organisms, and ascribes a disturbed equilibrium between the two as a sufficient cause for important changes in the bacillus as well as in the host. These differences in the cultural attributes of the bacilli, their virulence, and the character of resulting pathogenic processes are capable of explanation upon the basis of fundamental changes in the species, in which the bacillus is permitted to abide with a forced adaptation to the environment.

Irrespective of these broadly conceived hypotheses, which are worthy of the utmost consideration, it is true that essential differences are recognized between several distinct types of tubercle bacilli, i. e., those of human origin, the bovine, the avian, and the bacilli of fish or other cold-blooded animals. The human and bovine forms are described as mammalian bacilli, which, with the avian, have certain characteristics in contradistinction to the bacilli found among fish. The latter bacillus is unable to survive at the temperature of the human body, and, therefore, is incapable of transmitting tuberculosis to man or animals. Among the three varieties of bacilli sometimes found in warm-blooded animals, the avian presents important features of dissimilarity in comparison with the human and bovine forms. Rivolta, Maffucci, Ribbert, Straus, and Koch have pursued investigations concerning the relation of this to the other types of tubercle bacilli. The avian bacillus was found to withstand a greater degree of heat than the human or bovine, its growth not being inhibited until after the temperature was elevated nearly two degrees higher than was required for other forms of tubercle bacilli. Birds upon inoculation with human bacilli were found to exhibit but slight local reaction, without evidence of constitutional change. Nocard showed that mammalian bacilli grown in sacs of collodion within the peritoneal cavity of chickens could be modified to such an extent as to produce tuberculosis in fowl. On the other hand, Courmont and Dor demonstrated that when the avian bacillus was grown at lower temperatures and passed through rabbits it became endowed with pathogenic property for mammalia. Roemer reported that an interesting epizootic among chickens resulted from eating the entrails of a tuberculous cow. Shattock, Seligman, Dudgeon, and Panton, in a recent study of the relationship between avian and human tubercle bacilli, conclude that the human variety is but slightly pathogenic to the pigeon, and when introduced with food into the digestive canal, induces no local lesions of the intestine or abdominal viscera. They report that but slight local or glandular processes are produced by the injection of human bacilli into the muscles or subcutaneous tissues. Curiously conflicting results were obtained from inoculation of the rabbit and guinea-pig with avian bacilli, the former quickly yielding to general infection and the latter exhibiting but slight susceptibility. These results are all the more remarkable in view of the relatively greater resistance of the rabbit than the guinea-pig to human bacilli. Flexner has called attention to the fact that, in spite of the susceptibility of the rabbit to the avian

bacillus, the pathologic processes are radically different from those appearing as a result of infection with mammalian bacilli. He cites the absence of tubercles and caseation in the presence of an enlarged spleen. The avian, although occasionally present in lower animals, have never been discovered in man.

CHAPTER III

THE RELATION OF HUMAN AND BOVINE BACILLI

THE relation of human and bovine tuberculosis for several years has engaged the attention of the best observers. Koch, upon announcing the discovery of the tubercle bacillus in 1882, promulgated the dictum that human and bovine tuberculosis were identical, and that the bovine type was directly transmissible to man. Virchow had stated in 1863 that the two diseases were entirely distinct. This view, however, after the assertion of Koch, was not accepted by the profession in spite of the fact that Chauveau, Günther, Harms, and Bollinger, after feeding calves, swine, and goats with human tuberculous material, had failed to produce tuberculosis, although these animals quickly succumbed if the food contained milk and pieces of lung from tuberculous cattle. In 1893 Baumgarten questioned the complete identity of the two diseases and cited the previous failures to effect a transmission of tuberculosis to cattle through the medium of human bacilli. He also reported work done by Gaiser under his direction to substantiate the correctness of his view. A calf inoculated with human bacilli exhibited no evidence of disease, and when killed after several months showed no trace of tuberculous change. Another subjected to inoculation with bovine bacilli in the anterior chamber of the eye and in the flank, displayed a typical tuberculous process of the eye, and after much emaciation died in six weeks, showing at autopsy general miliary tuberculosis. In 1898 Smith, in this country, obtained negative results from the inoculation of cattle with human bacilli. Similar experiments were recorded by Frothingham and Dinwiddie in the following year. Their conclusions, however, were not to the effect that human tuberculosis was incapable of transmission to cattle, but merely that the bovine bacillus possessed a higher pathogenic power for these animals than the bacilli of human origin, to which the cattle were believed to be more or less resistant. Theobold Smith had expressed doubt as to the absolute identity of the two diseases, but did not advance the theory of impossibility of transmission. Koch, however, in 1901 openly disavowed his previous conclusions and maintained that human tuberculosis differed from bovine and could not be transmitted to cattle. He also assumed that infection from the bovine bacillus rarely, if ever, took place in man.

In substantiation of the first proposition he placed upon record the results of experiments conducted during the preceding two years by Schütz and himself. Nineteen young cattle free from tuberculosis were subjected to prolonged periods of inhalation exposure, to food infection, and to direct inoculation by human bacilli. These animals, after six to eight months, presented no trace of tuberculous lesion at autopsy. The

same attempts with bovine bacilli were attended with constitutional symptoms within one week, and extensive tuberculous changes were found at autopsy two or three months later. Similar experiments with human and bovine bacilli yielded like results in swine, asses, sheep, and goats. In support of his second proposition he pointed to the large number of bovine bacilli contained in butter and milk and to the alleged rarity of primary intestinal tuberculosis in infants. He cited statistical observations concerning the infrequency of this condition, although little children especially were recognized to be exposed and predisposed to infection. But ten cases were observed during a period of five years in the Charité Hospital in Berlin. Baginsky was reported as never having observed, out of 933 cases, an instance of intestinal tuberculosis without simultaneous involvement of lungs and glands. Biedert was quoted as having seen but sixteen cases out of a total of 3104 autopsies upon tuberculous children. Baumgarten, a few months after Koch's address, indorsed the position assumed with reference to the non-transmissibility of the two diseases, and made, as he stated, an important contribution to the subject by recalling the experiments of Rokitansky. The latter, firm in the belief of the unity of human and bovine tuberculosis, had inoculated with bacilli from cattle a number of patients suffering from incurable malignant diseases. This was done in the hope of establishing an antagonism between the tubercle bacilli and the bacteria of previous infection, thus affording a cure to otherwise hopeless invalids. Large numbers of tubercle bacilli of bovine origin were injected without noticeable results other than small localized abscesses at the points of inoculation. The autopsies upon these patients were performed by Baumgarten, and in spite of critical macroscopic and microscopic examination of the tissues and glandular. structures, no evidence of tuberculous infection was discovered. While thus espousing Koch's teaching on account of the failure of inoculation. experiments both upon man and animals, and while denying any especial danger to man from the consumption of bovine products, Baumgarten insisted, however, upon certain strong points of resemblance between the two diseases. He referred to the histologic identity of the tuberculous lesions in man and cattle as established by Schüppel, and pointed to the similar degenerative changes in the two conditions. He cited the production of acute miliary tuberculosis in cattle after infection. with bovine tuberculosis, precisely as in man with the human bacillus. He further called attention to the same reaction in cattle as in man following the injection of tuberculin derived from human bacilli. These various facts, supplemented by a supposed morphologic and cultural identity of the two bacilli, were deemed sufficient by Baumgarten to establish a close similarity of human and bovine tuberculosis, notwithstanding the disparity shown by inoculation experiments.

Virchow, in an address delivered before the Medical Society of Berlin in July, 1901, one or two days following Koch's communication in London, referred to his previous statements in 1863 regarding the non-unity of human and bovine tuberculosis. He said: "I was not surprised to hear that Professor Koch had finally convinced himself that they were two different things, even after my old thesis containing the same statement has been regarded by the Koch school for a considerable length of time with a certain contempt, and I have borne their judgment with patience. I certainly have never understood how any

one could maintain that the two were identical." He further emphasized the existence of true pathologic tubercle as a sine qua non for genuine tuberculosis, insisting that the bovine infection was an example of bacteriologic disease rather than of typical pathologic tissue change. Virchow did not refrain, however, from disparaging Koch's contention concerning the rarity of primary intestinal tuberculosis. He called attention to the existence of unusual intestinal and peritoneal lesions observed at the Charité, exhibiting growths peculiar to the so-called "perle disease" of cattle, but scarcely attributable to human bacilli.

In view of these somewhat contradictory statements from many preeminent European authorities, based upon the results of careful study and experimentation, a renewed impetus was given to a study of the subject. Commissions were appointed in Germany and Great Britain to investigate this matter, and a vast amount of exhaustive research was conducted in the United States. The German authors, as a rule, were inclined to support Koch's views, although several dissenting opinions were expressed, notably those of Behring and Dungern. Weber recently has reported observations of interest and value made by the Berlin Board of Health. The bovine bacillus was found fifteen times in the cervical glands of children. He asserts that this variety occurs almost exclusively in the young, and that a marked tendency toward spontaneous cure is noted. In almost all instances reported the children were under seven years of age. He has been able to dis

cover no instance of transmission of the bovine infection from one human being to another, and is constrained to believe that the danger of infection to man from bovine tuberculosis is insignificant as compared with that from the human variety.

Raw, although recently announcing his conviction as to the dissimilarity of human and bovine bacilli, yet attributes a large amount of tuberculosis in children to the introduction of the latter. He calls attention to the conspicuous differences between the clinical manifestations of pulmonary phthisis and other tuberculous affections, and emphasizes an apparent antagonism between pulmonary and surgical tuberculosis. He asserts that children who have suffered from strumous glands, spinal caries, tuberculous joints, and lupus are immune to phthisis pulmonalis, and, conversely, points to the infrequency of gross tuberculous lesions in cases of pulmonary tuberculosis. Upon the basis of these clinical differences, and the fact that surgical tuberculosis is essentially a disease of childhood, he concludes that the characteristic divergence of lesions is presumptive evidence of dissimilar bacilli. Relying upon clinical and autopsy observation, together with certain inferences from analogy, he submits the provisional opinion that the enlarged lymphatic glands of the neck, tuberculous peritonitis, tuberculous bones and joints, tuberculous meningitis, and lupus are occasioned by the ingestion of bovine bacilli, while the origin of pulmonary phthisis is attributed to the introduction of the human bacillus.

The British Commission, appointed after the close of the International Antituberculous Conference in London in 1901, was composed of the renowned Sir Michael Foster, chairman, and Professors Woodhead, Martin, Boyce, and MacFadyean. Their first report, published in 1904, expressed quite clearly a disinclination to accept the teaching of Koch as to the non-intercommunicability of human and bovine tuberculosis. Numerous experiments were undertaken by the commissioners

to determine primarily whether the disease in animals and man was one and the same, and whether infection could take place from one to the other. Investigations were made by a comparison of the lesions produced in cattle upon the introduction of bacilli of human and bovine origin. Similar experiments were performed upon the anthropoid ape, an animal nearly related to man, and also upon guinea-pigs, rabbits, goats, dogs, cats, and rats. Bacterial cultures of bovine bacilli, as well as emulsions of tuberculous lesions from thirty cases of bovine tuberculosis, were injected into strong, healthy animals previously tested with tuberculin. In some cases the introduction was made subcutaneously, in many, into the veins of the udder, and in others, by means of the food. In numerous cases of subcutaneous injection it was found that the proximal lymphatic glands soon became involved, that fever developed about the twelfth day, and that death took place from the twentieth to the fiftieth day. At autopsy there was found general tuberculosis of the glands and serous membranes, the lungs, liver, and kidneys. In some cases, however, there were merely local symptoms of but temporary duration without especial pathologic change at autopsy. These divergent results were explained by the introduction of varying quantities of infective matter and by a possible difference in the resisting powers of the animals. It was found, also, that those having been subjected to udder injection exhibited a considerable variation in the character of the resulting changes. In some cases death supervened quickly, with postmortem evidences of extensive tuberculous disease. Others displayed but local evidences of infection, which subsided after a short time. Five calves out of six sucking from infected udders showed signs of local and general tuberculosis, as did monkeys, pigs, rabbits, guinea-pigs, and goats after inoculation or feeding with bovine bacilli. More resistance was shown by dogs, cats, and rats. Sharply defined differences were displayed in the virulence of tubercle bacilli taken from fourteen cases of human tuberculosis and injected into animals. In one group general tuberculous changes were produced after inoculation of cows and the other lower animals employed in previous experiments with bovine bacilli. In this group there was but slight variation noticed in the virulence of the two types of bacilli. In another group, however, bacilli or tuberculous material taken from forty cases of human tuberculosis produced merely a slight local inflammatory change, with swelling of the nearest lymphatic glands. In some of these cases the injection of large quantities of infective material did not produce any evidence of a general advancing tuberculosis, either in cattle, cats, or dogs, although there were several instances of slight nonprogressive organic involvement. Monkeys, as a rule, were found to be non-resistant. The Commission attributed the divergent results of these experiments to differences of animal resistance and to variations in the virulence of the inoculated material. The report of the Commission is summed up as follows:

"There can be no doubt that in a certain number of cases the tuberculosis occurring in the human subject, especially in children, is the direct result of the introduction into the human body of the bacillus of bovine tuberculosis, and there also can be no doubt that, in the majority, at least, of these cases, the bacillus is introduced through cow's milk. Cow's milk containing tubercle bacillus is clearly the cause of tuberculosis. A very considerable amount of disease and loss of life, especially