The history of Penicillin

             In 1897 a French physician, Ernest Duchesne at École du Service de Santé Militaire in Lyon, published a medical thesis entitled Contribution à l'étude de la concurrence vitale chez les micro-organismes : antagonisme entre les moisissures et les microbes (Contribution to the study of the vital competition in micro-organisms: antagonism between molds and microbes) in which he specifically studied the interaction between Escherichia coli and Penicillium glaucum.He independently discovered healing properties of P. glaucum, even curing infected guinea pigs from typhoid. It is not known, however, whether the active chemical in these studies was in fact penicillin.E. coli and the causative agent of typhoid are both Gram-negative bacteria and are therefore significantly less susceptible to penicillin than other, Gram-positive, bacteria. In 1895, Italian physician Vincenzo Tiberio from the University of Naples published a study of molds that he found in a well near his house in Arzano, Italy ; he showed that certain molds — among them Penicillium glaucum — produce water-soluble substances that kill bacteria.

The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in 1928. He showed that, if Penicillium rubens were grown in the appropriate substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin. This serendipitous observation began the modern era of antibiotic discovery. The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey, together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley.

Fleming recounted that the date of his discovery of penicillin was on the morning of Friday, September 28, 1928. The traditional version of this story describes the discovery as a fortuitous accident: in his laboratory in the basement of St Mary's Hospital in London (now part of Imperial College), Fleming noticed a Petri dish containing Staphylococcus that had been mistakenly left open, was contaminated by blue-green mould from an open window, which formed a visible growth.There was a halo of inhibited bacterial growth around the mould. Fleming concluded that the mould released a substance that repressed the growth and caused lysing of the bacteria.

Once Fleming made his discovery he grew a pure culture and discovered it was a Penicillium mould, now known to be Penicillium notatum. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould. Fleming asked C. J. La Touche to help identify the mould, which he incorrectly identified as Penicillium rubrum (later corrected by Charles Thom). He expressed initial optimism that penicillin would be a useful disinfectant, because of its high potency and minimal toxicity in comparison to antiseptics of the day, and noted its laboratory value in the isolation of Bacillus influenzae (now called Haemophilus influenzae).

Fleming was a famously poor communicator and orator, which meant his findings were not initially given much attention. He was unable to convince a true chemist to help him extract and stabilize the antibacterial compound found in the broth filtrate. Despite the lack of a true chemist, he remained interested in the potential use of penicillin and presented a paper entitled "A Medium for the Isolation of Pfeiffer's Bacillus" to the Medical Research Club of London, which was met with little interest and even less enthusiasm by his peers. Had Fleming been more successful at making other scientists interested in his work, penicillin for medicinal use would possibly have been developed years earlier..

Despite the lack of interest of his fellow scientists, he did conduct several experiments on the antibiotic substance he discovered. The most important result proved it was nontoxic in humans by first performing toxicity tests in animals and then on humans. His following experiments on penicillin's response to heat and pH allowed Fleming to increase the stability of the compound. The one test that modern scientists would find missing from his work was the test of penicillin on an infected animal, the results of which would likely have sparked great interest in penicillin and sped its development by almost a decade.

References:

Walling, Anne D. (September 15, 2006). "Tips from Other Journals – Antibiotic Use During Pregnancy and Lactation".American Family Physician. Retrieved September 25, 2015.

Tiberio, Vincenzo (1895) "Sugli estratti di alcune muffe" [On the extracts of certain molds], Annali d'Igiene Sperimentale(Annals of Experimental Hygiene), 2nd series, 5 : 91–103. From p. 95: "Risulta chiaro da queste osservazioni che nella sostanza cellulare delle muffe esaminate son contenuti dei principi solubili in acqua, forniti di azione battericida: sotto questo riguardo sono più attivi o in maggior copia quelli dell' Asp. flavescens, meno quelli del Mu. mucedo e del Penn. glaucum."(It is clear from these observations that in the cellular substance of the molds examined are contained some water-soluble substances, provided with bactericidal action: in this respect are more active or in greater abundance those of Aspergillus flavescens; less, those of Mucor mucedo and Penicillium glaucum.)

The First Use of Penicillin in the United States, by Charles M. Grossman. Annals of Internal Medicine July 15, 2008: Volume 149, Issue 2, Pages 135–136

 E. J. Corey; John D. Roberts. The National Academy Press. RetrievedJanuary 28, 2013.

Sheehan, John C. (1982). The Enchanted Ring: The Untold Story of Penicillin. MIT Press.