A FURTHER NOTE UPON THE EXPERIMENTAL PRODUCTION OF LEPROSY IN THE MONKEY (MACACUS RHESUS), WITH A CRITICAL STUDY OF THE CULTURE EMPLOYED.

Fatal leprosy, with all its clinical and pathological manifestations in man, may be experimentally induced in the monkey (Macacus rhesus) with a pure culture of the acid-fast bacillus cultivated by one of us (Duval) from a leprous lesion in man. To produce the disease experimentally, it seems necessary to give the animal repeated injections of large numbers of leprosy bacilli at given intervals for a period of months. That the infection is more likely to follow where sensitization is first established is definitely proven by the specific experiments that we have carried out upon a variety of laboratory animals. The first injection, we assume, sensitizes the animal and may consist of either killed or viable lepra bacilli. The necessity of first sensitizing the monkey and then giving repeated doses of viable organisms over a long period might explain the relative infrequency of the disease in man; at least, it offers an explanation of the fact that man rarely, if ever, contracts leprosy, although intimately associated for an indefinite period with those afflicted with the disease. The leprous lesions in the monkey are histologically indistinguishable from those in man and do not essentially resemble the specific lesion of tuberculosis, blastomycosis, or the lesions experimentally produced with saprophytic acid-fast species, since the appearance of large lepra cells and the arrangement of the bacilli in dense packets within these cells to form the so-called globi is a constant and characteristic feature for the experimental as well as the human lesion (figures 17, 18, and 19). The production of leprosy in the monkey proves conclusively that the acid-fast bacillus cultivated by one of us (Duval) from the human lesion is the Hansen bacillus and not some extraneous saprophyte, and that it is the etiological factor in human leprosy. In our experience, it has been extremely difficult to produce, in the lower animals, more than a transient localized lesion with human leprous material rich in the specific bacilli, unless the animal is first sensitized, when lesions histologically identical with those produced by pure cultures are easily induced. Therefore, it is natural to expect that cultures of Bacillus leprœ which are many generations removed from the parent stem are less likely to infect, unless given in larger doses on the ground of loss in virulence. When experimental leprous lesions occur in the internal organs, they are more often found in the liver and spleen, while the experimental lesions occasionally produced in the lower animals with some of the saprophyte species, such as the bacillus of timothy hay, Moeller's grass bacilli, etc., rarely, if ever, occur in these organs (Abbott and Gildersleeve). These authors did not find lesions in the liver and spleen in a single instance after inoculating forty-five rabbits intravenously with large doses of the "confusing group." Furthermore, the cell picture and the appearance and arrangement of these bacilli in the lesions in no way resemble experimental leprosy (Holscher). It is no indication that a given culture is not the Hansen bacillus because the individual organisms differ in size and shape from those in the tissues, since it is a well known fact that marked variations in morphology are common for many bacterial species under natural and artificial conditions. One of us (Couret) has already pointed out that there is a wide variation in morphology for Bacillus leprœ under different environments. The experimental work serves not only to emphasize this fact, but is proof that a transformation from the slender beaded rods of the tissues to solidly staining diplococcoid forms of culture does occur for Bacillus leprœ; and, conversely, that the coccoid forms of culture may again assume the slender beaded appearance by passage through warm-blooded animals.