Unorthodox Approach to the Development of a New Antituberculosis Therapy

The development of TMC207 represents an important advance in the chemotherapy of tuberculosis. It is perhaps most amazing because of the defiantly unconventional nature of the effort. At virtually every step, from the original discovery of the diarylquinolines by screening for compounds that would kill Mycobacterium smegmatis, a saprophytic distant relative of M. tuberculosis, through the phase 2 study by Diacon et al. reported in this issue of the Journal (ClinicalTrials.gov number, NCT00449644),1 this effort flouted conventional wisdom about how to develop new drugs for tuberculosis.It is also a humbling case study that is worth some reflection. Those of . . .