Editing Antibiotic (section)

===Penicillin and other natural antibiotics===
{{See also|History of penicillin}}
[[File:Penicillin core.svg|thumb|upright=0.75|class=skin-invert-image|[[Penicillin]], discovered by [[Alexander Fleming]] in 1928]]
Observations about the growth of some microorganisms inhibiting the growth of other microorganisms have been reported since the late 19th century. These observations of antibiosis between microorganisms led to the discovery of natural antibacterials. [[Louis Pasteur]] observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".<ref name="Kingston2008"/>

In 1874, physician Sir [[William Roberts (physician)|William Roberts]] noted that cultures of the mould ''[[Penicillium glaucum]]'' that is used in the making of some types of [[blue cheese]] did not display bacterial contamination.<ref>{{cite journal | vauthors = Foster W, Raoult A | title = Early descriptions of antibiosis | journal = The Journal of the Royal College of General Practitioners | volume = 24 | issue = 149 | pages = 889–94 | date = December 1974 | pmid = 4618289 | pmc = 2157443 | quote = the first scientific observations of the antagonistic actions of various micro-organisms were made ... by William Roberts of Manchester (1874) and John Tyndall of London (1876). }}</ref>

In 1895 [[Vincenzo Tiberio]], Italian physician, published a paper on the antibacterial power of some extracts of mold.<ref>{{Cite journal |vauthors=Bucci R, Gallì P |date=11 May 2012 |title=Public Health History Corner Vincenzo Tiberio: a misunderstood researcher |url=http://ijphjournal.it/article/view/5688 |journal=Italian Journal of Public Health |volume=8 |issue=4 |access-date=30 September 2017 |archive-date=20 September 2018 |archive-url=https://web.archive.org/web/20180920160850/https://ijphjournal.it/article/view/5688 |url-status=dead }}</ref>

In 1897, doctoral student [[Ernest Duchesne]] submitted a dissertation, "{{lang|fr|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 moulds and microbes),<ref>{{cite book | vauthors = Duchesne E | translator = Witty M |title= Duchesne's Antagonism between molds and bacteria, an English Colloquial Translation| isbn= 978-1-5498-1696-3|date= 23 September 2017 | publisher = Independently Published }}</ref> the first known scholarly work to consider the therapeutic capabilities of moulds resulting from their anti-microbial activity. In his thesis, Duchesne proposed that bacteria and moulds engage in a perpetual battle for survival. Duchesne observed that ''[[Escherichia coli|E. coli]]'' was eliminated by ''Penicillium glaucum'' when they were both grown in the same culture. He also observed that when he [[inoculation|inoculated]] laboratory animals with lethal doses of [[typhoid]] bacilli together with ''Penicillium glaucum'', the animals did not contract typhoid. Duchesne's army service after getting his degree prevented him from doing any further research.<ref name="Academic Press">{{cite book|vauthors=Straand J, Gradmann C, Simonsen GS, Lindbæk M|title=International Encyclopedia of Public Health: Antibiotic Development and Resistance|date=2008|publisher=Academic Press|pages=200|url=http://www.sciencedirect.com/topics/page/Arsphenamine|access-date=31 January 2017|archive-date=4 October 2016|archive-url=https://web.archive.org/web/20161004031024/http://www.sciencedirect.com/topics/page/Arsphenamine|url-status=live}}</ref> Duchesne died of [[tuberculosis]], a disease now treated by antibiotics.<ref name="Academic Press"/>

In 1928, Sir [[Alexander Fleming]] postulated the existence of [[penicillin]], a molecule produced by certain moulds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of [[pathogen|disease-causing]] bacteria when he noticed the [[spore]]s of a green mold, ''[[Penicillium rubens]]'',<ref name="pmid32973216">{{cite journal |vauthors=Pathak A, Nowell RW, Wilson CG, Ryan MJ, Barraclough TG|date=September 2020 |title=Comparative genomics of Alexander Fleming's original ''Penicillium'' isolate (IMI 15378) reveals sequence divergence of penicillin synthesis genes|journal=Scientific Reports|volume=10 |issue=1 |pages=Article 15705 |doi=10.1038/s41598-020-72584-5|pmid=32973216|pmc=7515868|bibcode=2020NatSR..1015705P }}</ref> in one of his [[agar plate|culture plates]]. He observed that the presence of the mould killed or prevented the growth of the bacteria.<ref>{{cite journal | vauthors = Tan SY, Tatsumura Y | title = Alexander Fleming (1881-1955): Discoverer of penicillin | journal = Singapore Medical Journal | volume = 56 | issue = 7 | pages = 366–7 | date = July 2015 | pmid = 26243971 | pmc = 4520913 | doi = 10.11622/smedj.2015105 }}</ref> Fleming postulated that the mould must secrete an antibacterial substance, which he named penicillin in 1928. Fleming believed that its antibacterial properties could be exploited for chemotherapy. He initially characterised 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.<ref name="Fleming1929"/><ref name="Sykes2001"/>

[[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<ref>{{Cite journal|vauthors=Jones DS, Jones JH|date=1 December 2014|title=Sir Edward Penley Abraham CBE. 10 June 1913 – 9 May 1999|url=http://rsbm.royalsocietypublishing.org/content/60/5.1|journal=Biographical Memoirs of Fellows of the Royal Society|language=en|volume=60|pages=5–22|doi=10.1098/rsbm.2014.0002|issn=0080-4606| doi-access = free | title-link = doi |access-date=10 May 2017|archive-date=26 November 2023|archive-url=https://web.archive.org/web/20231126055623/http://rsbm.royalsocietypublishing.org/content/60/5.1|url-status=live}}</ref> 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.<ref name="Use of Micro-organisms for therapeutic purposes"/> 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.<ref>{{cite web |url=https://www.nobelprize.org/prizes/medicine/1945/summary/ |access-date=13 January 2018 |title=The Nobel Prize in Physiology or Medicine 1945 |publisher=The Nobel Prize Organization |archive-date=23 May 2020 |archive-url=https://web.archive.org/web/20200523072137/https://www.nobelprize.org/prizes/medicine/1945/summary/ |url-status=live }}</ref>

Florey credited [[René 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.<ref name=Epps2006/> 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 ''Bacillus brevis''. It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II.<ref name="Epps2006"/> 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 powers|Axis]] and the [[Allied powers of World War II|Allied powers]] during World War II and limited access during the [[Cold War]].<ref>{{cite journal | vauthors = Capocci M | title = Cold drugs. Circulation, production and intelligence of antibiotics in post-WWII years | journal = Medicina Nei Secoli | volume = 26 | issue = 2 | pages = 401–21 | date = 1 January 2014 | pmid = 26054208 }}</ref>