Forty years of screening programmes for antibiotics.

The article gathers the reflections on the experiences of forty years doing research on the screening of natural product in the pharmaceutical industry. Over those years new technologies have improved the methodology. However, the steps followed in such a research are the same: the isolation and cultivation of microorganisms; the definition of assays with well defined targets; the demonstration of their efficacy for the discovery and selection of active substances produced by microorganisms; the classification and structural determination of the new products; and the study of their therapeutical efficiency. Examples of the processes which led to the production of several antibiotics (fosfomycin, cefoxitin and thienamycin) are described. One important lesson that the author has learnt is that microorganisms have unique fingerprints and that generalization should be avoided in the planning of this work.