The contribution of Charles C. Shepard to leprosy research: From the mouse footpad model to new DNA technology

Abstract

Based on 88% (159/181) of the publications, Shepard's interests and successful achievements fall into three very different subjects, the timing of which by chance played an important part in determining his entree into the field of leprosy research. The first two publications of Shepard in 1941 and '43 were on mycobacteria, based on experimental pulmonary tuberculosis in the dog. Thus in the period 1955-60 a series of 10 papers were published on the behaviour and growth of several species of saprophitic and atypical mycobacteria and human tubercle bacilli in HeLa and other cell cultures. The studies on mycobacteria in cell cultures preceded Shepard's epoch-making papers in 1960 on the first reproducible multiplication of Mycobacterium leprae using the mouse foot-pad model. This successful model was carefully but remorselessly exploited by Shepard in his remaining 25 years towards the most effective treatment or control of human leprosy. While leprosy dominated his research from 1960 onwards, his laboratory continued to be responsible as a service for rickettsial diseases. Shepard's third contribution to medicine arose from his laboratory being called in to help solve the cause of the acute and often fatal outbreaks of pneumonia in Philadelphia in 1976. His extensive studies with Dr. McDade at CDC led to the successful isolation and identification in 1977 of a new species of bacterium - Legionella pneumophilia - as the causative organism of the respiratory infection now referred to as Legionnaire's disease. This work resulted in a series of 7 publications in the period 1977-79. As early as 1977 Shepard organised a workshop on 'Genetics of M. leprae', by bringing together authorities on the microbiology and taxonomy of mycobacteria with those in the advancing fields of basic recombinant DNA research. This led to studies with M. leprae derived from armadillos from IMMLEP, methods for the successful isolation of adequate quantities of DNA and a series of rapidly advancing technical publications on the specific genome size of M. leprae distinguishing it from other species of mycobacteria as well as genomic libraries of M. leprae.