Editing Alexander Fleming (section)

==== Medical use and mass production ====
In his first clinical trial, Fleming treated his research scholar Stuart Craddock who had developed severe infection of the [[nasal antrum]] ([[sinusitis]]). The treatment started on 9 January 1929 but without any effect. It probably was due to the fact that the infection was with influenza bacillus (''Haemophilus influenzae''), the bacterium which he had found unsusceptible to penicillin.<ref name=":7" /> Fleming gave some of his original penicillin samples to his colleague-surgeon Arthur Dickson Wright for clinical test in 1928.<ref>{{cite journal|last1=Wainwright|first1=M.|last2=Swan|first2=H. T.|date=1987|title=The Sheffield penicillin story|url=https://linkinghub.elsevier.com/retrieve/pii/S0269915X87800228|journal=Mycologist|volume=1|issue=1|pages=28–30|doi=10.1016/S0269-915X(87)80022-8}}</ref><ref name=":11">{{cite journal|last=Wainwright|first=Milton|date=1990|title=Besredka's "antivirus" in relation to Fleming's initial views on the nature of penicillin|journal=Medical History|volume=34|issue=1|pages=79–85|doi=10.1017/S0025727300050286|pmc=1036002|pmid=2405221}}</ref> Although Wright reportedly said that it "seemed to work satisfactorily",<ref>{{cite journal|last=Wainwright|first=M.|date=1987|title=The history of the therapeutic use of crude penicillin.|journal=Medical History|volume=31|issue=1|pages=41–50|doi=10.1017/s0025727300046305|pmc=1139683|pmid=3543562}}</ref> there are no records of its specific use. Cecil George Paine, a pathologist at the [[Sheffield Royal Infirmary|Royal Infirmary in Sheffield]] and former student of Fleming, was the first to use penicillin successfully for medical treatment.<ref name=":6">{{cite journal|last=Wainwright|first=Milton|date=1993|title=The Mystery of the Plate: Fleming's Discovery and Contribution to the Early Development of Penicillin|url=http://journals.sagepub.com/doi/10.1177/096777209300100113|journal=Journal of Medical Biography|volume=1|issue=1|pages=59–65|doi=10.1177/096777209300100113|pmid=11639213|s2cid=7578843}}</ref> He cured eye infections ([[conjunctivitis]]) of one adult and three infants ([[neonatal conjunctivitis]]) on 25 November 1930.<ref>{{cite journal|last=Wainwright |first=M. |last2=Swan |first2=H. T.|date=January 1986|title=C.G. Paine and the earliest surviving clinical records of penicillin therapy|journal=Medical History|volume=30|issue=1|pages=42–56|doi=10.1017/S0025727300045026|pmc=1139580|pmid=3511336}}</ref>

[[File:Professor Alexander Fleming at work in his laboratory at St Mary's Hospital, London, during the Second World War. D17801.jpg|thumb|left|Fleming in his laboratory in 1943]]
Fleming also successfully treated severe conjunctivitis in 1932.<ref name=":4" /><ref name=":8">{{cite journal|last=Howie|first=J.|date=1986|title=Penicillin: 1929–40|journal=British Medical Journal (Clinical Research Ed.)|volume=293|issue=6540|pages=158–159|doi=10.1136/bmj.293.6540.158|pmc=1340901|pmid=3089435}}</ref><ref>{{cite journal|last=Glover|first=J.|date=1986|title=The MRC and informed consent|journal=British Medical Journal|volume=293|issue=6540|pages=157–158|doi=10.1136/bmj.293.6540.157|pmc=1340900|pmid=3089434}}</ref> Keith Bernard Rogers, who had joined St Mary's as medical student in 1929,<ref>{{cite book|last=Heaman|first=Elsbeth A.|url=https://www.worldcat.org/oclc/144085272|title=St Mary's: The History of a London Teaching Hospital|date=2003|publisher=McGill-Queen's University Press|isbn=978-0-7735-7086-3|location=Montreal, Que.|pages=212|oclc=144085272}}</ref> was captain of the London University rifle team and was about to participate in an inter-hospital rifle shooting competition when he developed conjunctivitis.<ref>{{cite book|last=Marko|first=Vladimir|chapter=Penicillin |url=https://www.worldcat.org/oclc/1164582807|title=From Aspirin to Viagra: Stories of the Drugs that Changed the World|date=2020|publisher=Springer|isbn=978-3-030-44286-6|pages=105–106|doi=10.1007/978-3-030-44286-6_5|s2cid=241636139 |oclc=1164582807}}</ref><ref name=":9" /><ref>{{cite book|last=Maurois|first=André|url=https://books.google.com/books?id=qOtWAAAAYAAJ&q=conjunctivitis+rogers+penicillin|title=The Life of Sir Alexander Fleming: Discoverer of Penicillin|date=1963|publisher=Penguin Books|isbn=1-199-30814-5|pages=156}}</ref> Fleming applied his penicillin and cured Rogers before the competition.<ref name=":4" /><ref name=":8" /><ref>{{cite journal|last=Aronson|first=J. K.|date=1992|title=Penicillin|url=http://link.springer.com/10.1007/BF00314911|journal=European Journal of Clinical Pharmacology|volume=42|issue=1|pages=1–9|doi=10.1007/BF00314911|pmid=1541305|s2cid=62877498 }}</ref> It is said that the "penicillin worked and the match was won." However, the report that "Keith was probably the first patient to be treated clinically with penicillin ointment"<ref name=":9">{{cite journal|last=Rossiter|first=Peter|date=2005|title=Keith Bernard Rogers|journal=The BMJ|volume=331|issue=7516|pages=579|doi=10.1136/bmj.331.7516.579-c|pmc=1200632}}</ref> is no longer true as Paine's medical records showed up.<ref name=":52">{{cite journal|last=Diggins |first=F. W.|date=1999|title=The true history of the discovery of penicillin, with refutation of the misinformation in the literature|journal=British Journal of Biomedical Science|volume=56|issue=2|pages=83–93|pmid=10695047}}</ref>

There is a popular assertion both in popular and scientific literature that Fleming largely abandoned penicillin work in the early 1930s.<ref>{{cite journal|last1=Kyle|first1=Robert A.|last2=Steensma|first2=David P.|last3=Shampo|first3=Marc A.|date=2015|title=Howard Walter Florey – Production of Penicillin|journal=Mayo Clinic Proceedings|volume=90|issue=6|pages=e63–64|doi=10.1016/j.mayocp.2014.12.028|pmid=26046419|doi-access=free}}</ref><ref>{{cite journal|last=Shama|first=Gilbert|date=2017|title=Miracle near 34th street: Wartime Penicillin Research at St John's University, NY|url=https://linkinghub.elsevier.com/retrieve/pii/S0160932717300959|journal=Endeavour|volume=41|issue=4|pages=217–220|doi=10.1016/j.endeavour.2017.09.003|pmid=29055651}}</ref><ref>{{cite book|last1=Morin|first1=Robert B.|url=https://books.google.com/books?id=XE2eBQAAQBAJ&q=Fleming+abandoned+penicillin|title=Penicillins and Cephalosporins|last2=Gorman|first2=Marvin|date=2014|publisher=Academic Press|isbn=978-1-4832-7719-6|pages=xxii}}</ref><ref>{{cite book|last1=Ward|first1=John W.|url=https://books.google.com/books?id=5SDkvRBkQXAC&q=Fleming+abandoned+penicillin|title=Silent Victories: The History and Practice of Public Health in Twentieth-Century America|last2=Warren|first2=Christian|date=2006|publisher=Oxford University Press|isbn=978-0-19-974798-6|pages=50}}</ref> In his review of [[André Maurois]]'s ''The Life of Sir Alexander Fleming, Discoverer of Penicillin,'' William L. Kissick went so far as to say that "Fleming had abandoned penicillin in 1932... Although the recipient of many honors and the author of much scientific work, Sir Alexander Fleming does not appear to be an ideal subject for a biography."<ref>{{cite journal|last=Kissick|first=William L.|date=1959|title=The Life of Sir Alexander Fleming, Discoverer of Penicillin|journal=The Yale Journal of Biology and Medicine|volume=32|issue=2|page=140|pmc=2604061}}</ref> This is false, as Fleming continued to pursue penicillin research.<ref name=":11" /><ref>{{cite journal|last=Wainwright|first=Milton|date=2002|title=Fleming's unfinished|url=https://muse.jhu.edu/article/26157|journal=Perspectives in Biology and Medicine|volume=45|issue=4|pages=529–538|doi=10.1353/pbm.2002.0065|pmid=12388885|s2cid=32684352}}</ref> As late as in 1939, Fleming's notebook shows attempts to make better penicillin production using different media.<ref name=":52" /> In 1941, he published a method for assessment of penicillin effectiveness.<ref>{{cite journal|last=Fleming|first=A.|date=1942|title=In-vitro Tests of Penicillin Potency|url=https://linkinghub.elsevier.com/retrieve/pii/S0140673600703680|journal=The Lancet|volume=239|issue=6199|pages=732–733|doi=10.1016/S0140-6736(00)70368-0}}</ref> As to the chemical isolation and purification, [[Howard Florey]] and [[Ernst Chain]] at the [[Radcliffe Infirmary]] in Oxford took up the research to mass-produce it, which they achieved with support from World War II military projects under the British and US governments.<ref>Bickel, L. ''Florey: The Man Who Made Penicillin'', Sun Books, Melbourne, 1972. https://trove.nla.gov.au/work/21266280</ref>

By mid-1942, the Oxford team produced the pure penicillin compound as yellow powder.<ref>{{cite journal|last=Abraham |first=E. P. |last2=Chain |first2=E. |last3=Holiday |first3=E. R.|date=1942|title=Purification and Some Physical and Chemical Properties of Penicillin|journal=British Journal of Experimental Pathology|volume=23|issue=3|pages=103–119|pmc=2065494}}</ref> In August 1942, Harry Lambert (an associate of Fleming's brother Robert) was admitted to St Mary's Hospital due to a life-threatening infection of the nervous system (streptococcal [[meningitis]]).<ref name=":13" /> Fleming treated him with [[sulphonamides]], but Lambert's condition deteriorated. He tested the antibiotic susceptibility and found that his penicillin could kill the bacteria. He requested Florey for the isolated sample. Florey sent the incompletely purified sample, which Fleming immediately administered into Lambert's [[spinal canal]]. Lambert showed signs of improvement the very next day,<ref name=":0" /> and completely recovered within a week.<ref name=":4" /><ref>{{cite journal|last1=Cairns|first1=H.|last2=Lewin|first2=W. S.|last3=Duthie|first3=E. S.|last4=Smith|first4=Honor V.|date=1944|title=Pneumococcal Meningitis Treated with Penicillin|url=http://www.sciencedirect.com/science/article/pii/S0140673600770851|journal=The Lancet|volume=243|issue=6299|pages=655–659|doi=10.1016/S0140-6736(00)77085-1}}</ref> Fleming published the clinical case in ''[[The Lancet]]'' in 1943.<ref>{{cite journal|last=Fleming|first=Alexander|date=1943|title=Streptococcal Meningitis treated With Penicillin.|url=https://linkinghub.elsevier.com/retrieve/pii/S0140673600874528|journal=The Lancet|volume=242|issue=6267|pages=434–438|doi=10.1016/S0140-6736(00)87452-8}}</ref>

Upon this medical breakthrough, Allison informed the British [[Department of Health and Social Care|Ministry of Health]] of the importance of penicillin and the need for mass production. The [[War Cabinet]] was convinced of the usefulness upon which Sir [[Cecil Weir]], Director General of Equipment, called for a meeting on the mode of action on 28 September 1942.<ref>{{cite journal|last=Mathews|first=John A.|date=2008|title=The Birth of the Biotechnology Era: Penicillin in Australia, 1943–80|url=https://doi.org/10.1080/08109020802459306|journal=Prometheus|volume=26|issue=4|pages=317–333|doi=10.1080/08109020802459306|s2cid=143123783}}</ref><ref>{{cite book|last=Baldry|first=Peter|url=https://books.google.com/books?id=rvs8AAAAIAAJ|title=The Battle Against Bacteria: A Fresh Look|date=1976|publisher=CUP Archive|isbn=978-0-521-21268-7|pages=115}}</ref> The Penicillin Committee was created on 5 April 1943. The committee consisted of Weir as chairman, Fleming, Florey, Sir [[Percival Hartley]], Allison and representatives from pharmaceutical companies as members. The main goals were to produce penicillin rapidly in large quantities with collaboration of American companies, and to supply the drug exclusively for [[Allies of World War II|Allied armed forces]].<ref name=":0" /> By [[D-Day]] in 1944, enough penicillin had been produced to treat all the wounded of the Allied troops.<ref>{{cite journal|last=Richards|first=A. N.|date=1964|title=Production of penicillin in the United States (1941–1946)|url=https://pubmed.ncbi.nlm.nih.gov/14164615|journal=Nature|volume=201|issue=4918|pages=441–445|doi=10.1038/201441a0|pmid=14164615|bibcode=1964Natur.201..441R|s2cid=4296757}}</ref>