Editing Alexander Fleming (section)

=== Discovery of lysozyme ===
At St Mary's Hospital, Fleming continued his investigations into bacteria culture and antibacterial substances. As his research scholar at the time V. D. Allison recalled, Fleming was not a tidy researcher and usually expected unusual bacterial growths in his culture plates. Fleming had teased Allison of his "excessive tidiness in the laboratory", and Allison rightly attributed such untidiness as the success of Fleming's experiments, and said, "[If] he had been as tidy as he thought I was, he would not have made his two great discoveries."<ref name=":0">{{cite journal|last=Allison|first=V. D.|date=1974|title=Personal recollections of Sir Almroth Wright and Sir Alexander Fleming.|journal=The Ulster Medical Journal|volume=43|issue=2|pages=89–98|pmc=2385475|pmid=4612919}}</ref>

In late 1921, while Fleming was maintaining [[agar plates]] for bacteria, he found that one of the plates was contaminated with bacteria from the air. When he added nasal mucus, he found that the mucus inhibited the bacterial growth.<ref name=":2">{{cite journal|last=Fleming|first=A.|year=1922|title=On a remarkable bacteriolytic element found in tissues and secretions|journal=Proceedings of the Royal Society B|volume=93|issue=653|pages=306–317|doi=10.1098/rspb.1922.0023|bibcode=1922RSPSB..93..306F|doi-access=free}}</ref> Surrounding the mucus area was a clear transparent circle (1&nbsp;cm from the mucus), indicating the [[Zone of inhibition|killing zone]] of bacteria, followed by a glassy and translucent ring beyond which was an opaque area indicating normal bacterial growth. In the next test, he used bacteria maintained in saline that formed a yellow suspension. Within two minutes of adding fresh mucus, the yellow saline turned completely clear. He extended his tests using tears, which were contributed by his co-workers. As Allison reminisced, saying, "For the next five or six weeks, our tears were the source of supply for this extraordinary phenomenon. Many were the lemons we used (after the failure of onions) to produce a flow of tears... The demand by us for tears was so great, that laboratory attendants were pressed into service, receiving threepence for each contribution."<ref name=":0" />

His further tests with sputum, cartilage, blood, semen, ovarian cyst fluid, pus, and egg white showed that the bactericidal agent was present in all of these.<ref name=":3" /> He reported his discovery before the Medical Research Club in December and before the [[Royal Society]] the next year but failed to stir any interest, as Allison recollected:<blockquote>

I was present at this [Medical Research Club] meeting as Fleming's guest. His paper describing his discovery was received with no questions asked and no discussion, which was most unusual and an indication that it was considered to be of no importance. The following year he read a paper on the subject before the Royal Society, Burlington House, Piccadilly and he and I gave a demonstration of our work. Again with one exception little comment or attention was paid to it.<ref name=":0" /></blockquote>

Reporting in the 1 May 1922 issue of the ''[[Proceedings of the Royal Society B: Biological Sciences]]'' under the title "On a remarkable bacteriolytic element found in tissues and secretions", Fleming wrote:<blockquote>In this communication I wish to draw attention to a substance present in the tissues and secretions of the body, which is capable of rapidly dissolving certain bacteria. As this substance has properties akin to those of ferments I have called it a "[[Lysozyme]]", and shall refer to it by this name throughout the communication. The lysozyme was first noticed during some investigations made on a patient suffering from [[Rhinitis|acute coryza]].<ref name=":2" /></blockquote>This was the first recorded discovery of lysozyme. With Allison, he published further studies on lysozyme in October issue of the ''British Journal of Experimental Pathology'' the same year.<ref>{{cite journal|last1=Fleming|first1=Alexander|last2=Allison|first2=V. D.|date=1922|title=Observations on a Bacteriolytic Substance ("Lysozyme") Found in Secretions and Tissues|journal=British Journal of Experimental Pathology|volume=3|issue=5|pages=252–260|pmc=2047739}}</ref> Although he was able to obtain larger amounts of lysozyme from egg whites, the enzyme was only effective against small counts of harmless bacteria, and therefore had little therapeutic potential. This indicates one of the major differences between [[Pathogenic bacteria|pathogenic]] and harmless bacteria.<ref name="SingMedJ" />

Described in the original publication, "a patient suffering from acute coryza"<ref name=":2" /> was later identified as Fleming himself. His research notebook dated 21 November 1921 showed a sketch of the culture plate with a small note: "Staphyloid coccus from A.F.'s nose."<ref name=":3" /> He also identified the bacterium present in the nasal mucus as ''Micrococcus Lysodeikticus'', giving the species name (meaning "lysis indicator" for its susceptibility to lysozymal activity).<ref>{{cite journal|last=Salton|first=M. R. J.|date=1957|title=The properties of lysozyme and its action on micororganisms|journal=Bacteriological Reviews|volume=21|issue=2|pages=82–100|doi=10.1128/MMBR.21.2.82-100.1957|pmc=180888|pmid=13436356}}</ref> The species was reassigned as ''[[Micrococcus luteus]]'' in 1972.<ref>{{cite journal|last1=Schleifer|first1=K. H.|last2=Kloos|first2=W. E.|last3=Moore|first3=A.|date=1972|title=Taxonomic Status of Micrococcus luteus (Schroeter 1872) Cohn 1872: Correlation Between Peptidoglycan Type and Genetic Compatibility|journal=International Journal of Systematic Bacteriology|volume=22|issue=4|pages=224–227|doi=10.1099/00207713-22-4-224|doi-access=free}}</ref> The "Fleming strain" (NCTC2665) of this bacterium has become a model in different biological studies.<ref>{{cite journal|last1=Young|first1=Michael|last2=Artsatbanov|first2=Vladislav|last3=Beller|first3=Harry R.|last4=Chandra|first4=Govind|last5=Chater|first5=Keith F.|last6=Dover|first6=Lynn G.|last7=Goh|first7=Ee-Been|last8=Kahan|first8=Tamar|last9=Kaprelyants|first9=Arseny S.|last10=Kyrpides|first10=Nikos|last11=Lapidus|first11=Alla|date=2010|title=Genome Sequence of the Fleming Strain of Micrococcus luteus, a Simple Free-Living Actinobacterium|journal=Journal of Bacteriology|volume=192|issue=3|pages=841–860|doi=10.1128/JB.01254-09|pmc=2812450|pmid=19948807}}</ref><ref>{{cite web|last=Canada|first=Environment and Climate Change|date=23 February 2018|title=Final Screening Assessment of Micrococcus luteus strain ATCC 4698|url=https://www.canada.ca/en/environment-climate-change/services/evaluating-existing-substances/screening-assessment-micrococcus-luteus.html|access-date=17 October 2020|website=aem}}</ref> The importance of lysozyme was not recognised, and Fleming was well aware of this, in his presidential address at the [[Royal Society of Medicine]] meeting on 18 October 1932, he said:<blockquote>I choose lysozyme as the subject for this address for two reasons, firstly because I have a fatherly interest in the name, and, secondly, because its importance in connection with natural immunity does not seem to be generally appreciated.<ref>{{cite journal|last=Fleming|first=Alexander|date=1932|title=Lysozyme|journal=Proceedings of the Royal Society of Medicine|volume=26|issue=2|pages=71–84|doi=10.1177/003591573202600201|s2cid=209362460|doi-access=free|pmc=2204285}}</ref> </blockquote>In his Nobel lecture on 11 December 1945, he briefly mentioned lysozyme, saying, "Penicillin was not the first antibiotic I happened to discover."<ref name=":12">{{cite web|last=Fleming|first=A.|date=1945|title=The Nobel Prize in Physiology or Medicine 1945 – Penicillin: Nobel Lecture|url=https://www.nobelprize.org/prizes/medicine/1945/fleming/lecture/|access-date=17 October 2020|website=NobelPrize.org}}</ref> It was only towards the end of the 20th century that the true importance of Fleming's discovery in immunology was realised as lysozyme became the first [[antimicrobial protein]] discovered that constitute part of our [[innate immunity]].<ref>{{cite journal|last=Gallo|first=Richard L.|date=2013|title=The birth of innate immunity|url=http://doi.wiley.com/10.1111/exd.12197|journal=Experimental Dermatology|volume=22|issue=8|pages=517|doi=10.1111/exd.12197|pmid=23879811|s2cid=23482849}}</ref><ref>{{cite journal|last1=Ragland|first1=Stephanie A.|last2=Criss|first2=Alison K.|date=2017|title=From bacterial killing to immune modulation: Recent insights into the functions of lysozyme|journal=PLOS Pathogens|volume=13|issue=9|pages=e1006512|doi=10.1371/journal.ppat.1006512|pmc=5608400|pmid=28934357 |doi-access=free }}</ref>