<P> In 1897, doctoral student Ernest Duchesne submitted a dissertation, "Contribution à l'étude de la concurrence vitale chez les micro-organismes: antagonisme entre les moisissures et les microbes" (Contribution to the study of vital competition in micro-organisms: antagonism between molds and microbes), the first known scholarly work to consider the therapeutic capabilities of molds resulting from their anti-microbial activity . In his thesis, Duchesne proposed that bacteria and molds engage in a perpetual battle for survival . Duchesne observed that E. coli was eliminated by Penicillium glaucum when they were both grown in the same culture . He also observed that when he inoculated laboratory animals with lethal doses of typhoid bacilli together with Penicillium glaucum, the animals did not contract typhoid . Unfortunately Duchesne's army service after getting his degree prevented him from doing any further research . Duchesne died of tuberculosis, a disease now treated by antibiotics . </P> <P> In 1928, Sir Alexander Fleming postulated the existence of penicillin, a molecule produced by certain molds that kills or stops the growth of certain kinds of bacteria . Fleming was working on a culture of disease - causing bacteria when he noticed the spores of a green mold, Penicillium chrysogenum, in one of his culture plates . He observed that the presence of the mold killed or prevented the growth of the bacteria . Fleming postulated that the mold must secrete an antibacterial substance, which he named penicillin in 1928 . Fleming believed that its antibacterial properties could be exploited for chemotherapy . He initially characterized some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists . </P> <P> Ernst Chain, Howard Florey and Edward Abraham succeeded in purifying the first penicillin, penicillin G, in 1942, but it did not become widely available outside the Allied military before 1945 . Later, Norman Heatley developed the back extraction technique for efficiently purifying penicillin in bulk . The chemical structure of penicillin was first proposed by Abraham in 1942 and then later confirmed by Dorothy Crowfoot Hodgkin in 1945 . Purified penicillin displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in humans . Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic sulfonamides . (see below) The development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety . For their successful development of penicillin, which Fleming had accidentally discovered but could not develop himself, as a therapeutic drug, Chain and Florey shared the 1945 Nobel Prize in Medicine with Fleming . </P> <P> Florey credited Rene Dubos with pioneering the approach of deliberately and systematically searching for antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's research in penicillin . In 1939, coinciding with the start of World War II, Dubos had reported the discovery of the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and 80% tyrocidine, from B. brevis . It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II . Gramicidin, however, could not be used systemically because of toxicity . Tyrocidine also proved too toxic for systemic usage . Research results obtained during that period were not shared between the Axis and the Allied powers during World War II and limited access during the Cold War . </P>

When were the first antibiotics used to treat diseases