The causative organism in infectious ectromelia

Abstract Infectious ectromelia was described in 1930 by Miss J. Marchal. The disease, which had not been recognised before, occurred in mice of the breeding stock at this Institute. Miss Marchal isolated various kinds of bacteria from the foot lesions of infected mice, but could obtain no experimental evidence that these organisms had causal significance. Ultimately she succeeded in passing the causative agent of the disease through bacteria-proof filter-candles and thereby proved it to belong to the group to which the term "virus" is applicable. The regularity with which ectromelia can be transmitted from mouse to mouse, and the ease with which the disease is identified, provided exceptionally good conditions for a closer study of the infective agent, and particularly for an attempt to discover whether it has the nature of an organism, which can be rendered visible by the microscopic and photographic methods, on the development of which I have been engaged for many years. It has the advantages that it produces typical "inclusion-bodies" in the cytoplasm of epithelial cells which it infects, and that, on the other hand, extracts containing abundant virus, as determined by the dilutions in which they convey the infection, can be obtained from infected organs, such as the liver, in which inclusion-bodies are not present, or are extremely rare. In the case of other virus infections forming inclusion-bodies, it has been proved, on the one hand, that an isolated inclusion-body can transmit the infection, and that its contents, when spread into a film and subjected to certain staining methods, contain minute particles on which the stain becomes preferentially deposited. Such results, however, do not provide very strong evidence as to the identity of such particles with the virus. In the case of the ectromelia virus I have been able to examine the intact, unstained, inclusion-bodies and their expressed contents, and to demonstrate the presence in closely-packed formation of minute refractile particles of uniform size and appearance, unstained and in the living condition. I have, further, been able to examine virus-containing extracts from tissues containing no inclusion-bodies, and to demonstrate the presence in these of minute particles indistinguishable from those with which the inclusion-bodies are closely packed. Of these particles, both from inclusion-bodies or in extracts from organs in which the virus is freely distributed, I have then been able to obtain photographic images with monochromatic ultra-violet radiation which enable the size and shape of the particles to be accurately described, and leave little room for doubt that they represent definite microorganisms, of a size below the limits of ordinary microscopic resolution.