Special Article

THE INVITATION with which you have honored me on this memorable occasion has given me a tempting opportunity to discuss certain problems with which my associates and I have been engaged for nearly a quarter of a century, and to correlate the results of some 25 separate studies on the various aspects of pathogenesis, published, mainly in the Journal of Experimental Medicine, during that time. Most of these have dealt with the beginnings and evolution of the disease up to the onset of paralysis, in search of answers to such questions as: How and where does the virus enter the body? Where do the initial lesions occur? What are the sources of viral excretion? How is viremia produced? By what routes is the central nervous system invaded? What is the explanation of silent infections? What are the defenses, natural and artificial, against the disease? And, finally, can a unitarian concept be sustained of the pathogenesis of poliomyelitis in terms of the relation between host and virus? Before discussing these questions, certain prefatory remarks are in order about the host-cell affinities of poliomyelitis virus. While it is interesting and in various ways very important that these can be radically altered in vitro by Enders' methods of tissue culture, and in vivo by pretreating animals with cortisone or ACTH, as shown by Schwartzmann and Aronson, nevertheless such results should be applied with the greatest caution to the pathogenesis of the human disease, in which cytopathic changes in such extraneural tissues as kidney, muscle, skin and testis, when they occur at all, are exceptional and not part of the characteristic pathologic picture.