Avery was looking for a microbe that could break down the polysaccharide capsule of a deadly strain of bacterial pneumonia in the same way that soil bacteria digested decaying organic matter in the woods.

[5] In 1939, with the help of Rockefeller Institute biochemist Rollin Hotchkiss, Dubos isolated the antibacterial agents tyrothricin and gramicidin from the bacterium Bacillus brevis that killed or inhibited Gram-positive bacteria and tested their bacterial, chemical, and clinical properties.

He performed groundbreaking research and wrote extensively on a number of subjects, including tuberculosis, pneumonia, and the mechanisms of acquired immunity, natural susceptibility, and resistance to infection.

In 1948, Dubos shared the Albert Lasker Basic Medical Research Award with Selman Waksman for "their achievement in studies of the antibiotic properties of soil bacteria".

In the 1980s, Dubos held to his thoughts on acting locally, and felt that issues involving the environment must be dealt with in their "unique physical, climatic, and cultural contexts".

[16] The collected papers of Dubos from 1927 to 1982, including correspondence, lecture notes, book and article drafts, laboratory notebooks, photographs, audio and video cassettes, and films, are stored at the Rockefeller Archive Center.