Under conditions closely simulating the natural modes of tuberculous infection in man normal guinea pigs have acquired tuberculosis by being exposed under two degrees of crowding to tuberculous cage mates in ordinary cages, where the food became soiled with excreta, bearing tubercle bacilli, and in special cages, with wire-mesh floors, where this source of infection was almost entirely eliminated. Guinea pigs were also exposed in the same room but not in the same cage with tuberculous animals. It was found that the relative tuberculous involvement of the mesenteric and tracheobronchial nodes showed a gradation of change from an almost completely alimentary infection to a completely respiratory infection. The disease involved the mesenteric nodes predominantly in the crowded ordinary cages, with much less or no affection of the tracheobronchial nodes. It was similarly, but less markedly, enteric in origin in the less crowded ordinary cages, the mesenteric nodes again being larger than the tracheobronchial nodes, but the difference in size was not so great. In the more crowded special cages the relative affection of these two groups of nodes alternated, so that in some the mesenteric, in some the tracheobronchial nodes were more extensively tuberculous. A disease characterized by less or no affection of the mesenteric nodes and by extensive lesions of the tracheobronchial nodes was seen in the less crowded special cages. Finally there was a massive tuberculosis of the tracheobronchial nodes with usually no affection of the mesenteric nodes in the frankly air-borne tuberculosis acquired by guinea pigs exposed in the same room but not to tuberculous cage mates.
This gradation in the rô1e played by the enteric and respiratory routes of infection, as first the one and then the other becomes the more frequent channel of entrance for tuberculosis, would indicate that the penetration of tubercle bacilli by the one portal of entry inhibits the engrafting of tuberculosis in the tissues by way of the other portal of entry. It is apparent that in the special cages the opportunities for inhaling tubercle bacilli are at most equal to if not much less than in the ordinary cages; for in the latter dust from the bedding, laden with tubercle bacilli, is stirred up almost constantly by the animals, whereas in the special cages there is no bedding at all, and therefore, presumably, no more tubercle bacilli in the air than may occur in any part of the room. Nevertheless the route of infection was predominantly the respiratory tract in the special cages, especially in the less crowded, apparently because the enteric route had been largely eliminated. The greater predominance of the respiratory route amongst guinea pigs that acquired tuberculosis in the less crowded ordinary cages as compared to the lesser significance of this route in the more crowded ordinary cages would point in the same direction. These observations are in harmony with our knowledge that tuberculosis once implanted in an organism confers a certain degree of immunity to the disease. It is noteworthy that in a study of human autopsy material Opie (3) has found that when healed lesions are present in the mesentery focal tuberculosis in the lungs is seldom found, and that when first infection occurs by way of the lungs it tends to prevent the engrafting of the disease by way of the intestinal tract.
Estimating the Mutual Information between Two Discrete, Asymmetric Variables with Limited Samples