Editing Élie Metchnikoff (section)

==Career and achievements==
Metchnikoff was appointed [[docent]] at the newly established [[Odessa University|Imperial Novorossiya University]] (now [[Odesa University]]). Only twenty-two years of age, he was younger than his students. After being involved in a conflict with a senior colleague over attending scientific meetings, he transferred to the University of Saint Petersburg in 1868, where he experienced a worse professional environment. In 1870 he returned to [[Odessa]] to take up the appointment of Titular Professor of [[Zoology]] and [[Comparative Anatomy]].<ref name=nobelbio/><ref name=encyclo/>

In 1882 he resigned from Odessa University due to political turmoils after the [[Assassination of Alexander II of Russia|assassination of Alexander II]]. He went to [[Sicily]] to set up his private laboratory in [[Messina]]. He returned to Odessa as director of an institute set up to carry out [[Louis Pasteur]]'s [[vaccine]] against [[rabies]]; due to some difficulties, he left in 1888 and went to Paris to seek Pasteur's advice. Pasteur gave him an appointment at the [[Pasteur Institute]], where he remained for the rest of his life.<ref name=nobelbio/>

[[File:Professeur Metchnikoff, portrait du scientifique dans un laboratoire de recherche.jpg|thumb|Metchnikoff in his laboratory, 1913]]
Metchnikoff became interested in the study of [[microbes]], and especially the [[immune system]]. At Messina he discovered [[phagocytosis]] after experimenting on the [[larva]]e of [[starfish]]. In 1882 he first demonstrated the process when he inserted small [[citrus]] thorns into starfish larvae, then found unusual cells surrounding the thorns. He realized that in animals which have blood, the white blood cells gather at the site of inflammation, and he hypothesised that this could be the process by which bacteria were attacked and killed by the white blood cells. He discussed his hypothesis with [[Carl Friedrich Wilhelm Claus]], Professor of Zoology at the [[University of Vienna]], who suggested to him the term "phagocyte" for a cell which can surround and kill pathogens. He delivered his findings at Odessa University in 1883.<ref name=nobelbio/>

His theory, that certain [[white blood cell]]s could engulf and destroy harmful bodies such as bacteria, met with scepticism from leading specialists including Louis Pasteur, [[Emil von Behring]], and others. At the time, most bacteriologists believed that white blood cells ingested pathogens and then spread them further through the body. His major supporter was [[Rudolf Virchow]], who published his research in his ''Archiv für pathologische Anatomie und Physiologie und für klinische Medicin'' (now called the ''[[Virchows Archiv]]'').<ref name=encyclo/> His discovery of these [[phagocytes]] ultimately won him the Nobel Prize in 1908.<ref name="nobel" /> He worked with [[Pierre Paul Emile Roux|Émile Roux]] on [[calomel]] (mercurous chloride) in ointment form in an attempt to prevent people from contracting the [[sexually transmitted disease]] [[syphilis]].<ref>{{Cite journal|last=Worms|first=Werner|date=1940|title=Prophylaxis of Syphilis by Locally Applied Chemicals. Methods of Examination, Results, and Suggestions for Further Experimental Research|journal=[[Sexually Transmitted Infections (journal)|British Journal of Venereal Diseases]]|volume=16|issue=3–4|pages=186–210|doi=10.1136/sti.16.3-4.186|pmc=1053233|pmid=21773301}}</ref>

In 1887, he observed that [[leukocytes]] isolated from the blood of various animals were attracted towards certain bacteria.<ref>{{cite journal | vauthors =  Metchnikoff E | title = Sur la lutte des cellules de l'organisme contre l'invasion des microbes | journal = Annales de l'Institut Pasteur | year = 1887 | volume = 1 | pages = 321 }}</ref> The first studies of leukocyte killing in the presence of specific antiserum were performed by Joseph Denys and Joseph Leclef, followed by Leon Marchand and Mennes between 1895 and 1898. Almoth E. Wright was the first to quantify this phenomenon and strongly advocated its potential therapeutic importance. The so-called resolution of the humoralist and cellularist positions by showing their respective roles in the setting of enhanced killing in the presence of [[opsonin]]s was popularized by Wright after 1903, although Metchnikoff acknowledged the stimulatory capacity of immunosensitized serum on phagotic function in the case of acquired immunity.<ref>{{Cite book|title=Metchnikoff and the Origins of Immunology: From Metaphor to Theory|last=Tauber& Cherniak|publisher=[[Oxford University Press]]|year=1991|isbn=0-19-506447-X|location=Oxford, UK|pages=155}}</ref>

This attraction was soon proposed to be due to soluble elements released by the bacteria<ref>{{cite journal | vauthors = Grawitz P | title = unknown title | journal = Virchows Adz. IIO | volume =  I | year = 1887}}</ref> (see Harris<ref>{{cite journal | vauthors = Harris H | title = Role of chemotaxis in inflammation | journal = [[Physiological Reviews]] | volume = 34 | issue = 3 | pages = 529–62 | date = Jul 1954 | pmid = 13185754 | doi=10.1152/physrev.1954.34.3.529}}</ref> for a review of this area up to 1953). Some 85 years after this seminal observation, laboratory studies showed that these elements were low [[molecular weight]] (between 150 and 1500 [[Dalton (unit)]]s) N-formylated oligopeptides, including the most prominent member of this group, [[N-Formylmethionine-leucyl-phenylalanine]], that are made by a variety of replicating [[gram positive bacteria]] and [[gram negative bacteria]].<ref>{{cite journal | vauthors = Ward PA, Lepow IH, Newman LJ | title = Bacterial factors chemotactic for polymorphonuclear leukocytes | journal = [[The American Journal of Pathology]] | volume = 52 | issue = 4 | pages = 725–36 | date = Apr 1968 | pmid = 4384494 | pmc=2013377}}</ref><ref>J Exp Med. 1976 May 1;143(5):1154–69.</ref><ref>J Immunol. 1974 Jun;112(6):2055–62.</ref><ref>{{cite journal | vauthors = Schiffmann E, Showell HV, Corcoran BA, Ward PA, Smith E, Becker EL | title = The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli | journal = [[Journal of Immunology]] | volume = 114 | issue = 6 | pages = 1831–7 | date = Jun 1975 | doi = 10.4049/jimmunol.114.6.1831 | pmid = 165239 | s2cid = 22663271 | doi-access = free }}</ref> Metchnikoff's early observation, then, was the foundation for studies that defined a critical mechanism by which bacteria attract leukocytes to initiate and direct the [[innate immune response]] of acute [[inflammation]] to sites of host invasion by [[pathogens]].<ref name=":1" /><ref name=":2" />

Metchnikoff discovered fungal infections causing insect death in 1879 and became involved in the biological control of insect pests through his student [[Isaak Krasilschik]]. They were able to make use of [[Green muscardine disease|green muscardine]] for control of insects in agricultural fields.<ref>{{Cite journal |last1=Zimmermann |first1=Gisbert |last2=Papierok |first2=Bernard |last3=Glare |first3=Travis |date=1995 |title=Elias Metschnikoff, Elie Metchnikoff or Ilya Ilich Mechnikov (1845-1916): A Pioneer in Insect Pathology, the First Describer of the Entomopathogenic Fungus Metarhizium anisopliae and How to Translate a Russian Name |url=https://www.tandfonline.com/doi/full/10.1080/09583159550039701 |journal=Biocontrol Science and Technology |language=en |volume=5 |issue=4 |pages=527–530 |doi=10.1080/09583159550039701 |bibcode=1995BioST...5..527Z |issn=0958-3157}}</ref><ref>{{cite journal |year=2015 |title=Secvenţe din istoria cercetării filoxerei viţei-de-vie în Basarabia|journal=Enciclopedica. Revistă de istorie a știinţei și studii enciclopedice |url=https://ibn.idsi.md/sites/default/files/imag_file/8-18_1.pdf |volume= 2|issue=9 |pages=8–18|first=Asea |last=Timuș}}</ref>

Metchnikoff also self-experimented with cholera that initially supported the [[probiotic]] notion. During the [[1881–1896 cholera pandemic|1892 cholera epidemic]] in France, he was surprised by the fact that the disease affected only some people but not others when they were equally exposed to the infection. To understand the differences in susceptibility to the disease, he drank a sample of cholera but never got sick. He tested on two volunteers of which one was not affected while the other almost died. He hypothesised that the difference in cholera infection was due to differences in intestinal microbes, speculating that those who have plenty of beneficial ones would be healthier.<ref>{{Cite web |last=Lewis |first=Danny |date=2015-05-07 |title=Probiotics Exist Thanks to a Man Who Drank Cholera |url=https://www.smithsonianmag.com/smart-news/thank-man-who-drank-cholera-your-yogurt-180955197/ |access-date=2022-06-21 |website=Smithsonian Magazine |language=en}}</ref>

The issues of aging occupied a significant place in Metchnikoff's works.<ref>{{cite web |author=Elena Milova |url=https://www.lifespan.io/news/dr-elie-metchnikoff/ |title=Commemorating the Work of Dr. Elie Metchnikoff |language=en |work=[[Life Extension Advocacy Foundation|Lifespan.io]] |date=12 May 2017 |access-date=12 May 2021 |archive-date=12 May 2021 |archive-url=https://web.archive.org/web/20210512151343/https://www.lifespan.io/news/dr-elie-metchnikoff/ |url-status=dead }}</ref> Metchnikoff developed a theory that [[senescence|aging]] is caused by toxic bacteria in the gut and that [[lactic acid]] could prolong life. He attributed the longevity of Bulgarian peasants to their yogurt consumption<ref>{{cite journal |last1=Brown |first1=AC |last2=Valiere |first2=A |year=2004 |title=Probiotics and medical nutrition therapy |journal=Nutrition in Clinical Care |volume=7 |issue=2 |pages=56–68 |pmc=1482314 |pmid=15481739}}</ref> that contained what was called the Bulgarian bacteria (now called [[Lactobacillus delbrueckii subsp. bulgaricus|''Lactobacillus delbrueckii'' subsp. ''bulgaricus'']]).<ref name=":0" /> To validate his theory, he drank [[yogurt|sour milk]] every day throughout his life. His scientific reasonings on the subject were written in his books ''The Nature of Man: Studies in Optimistic Philosophy'' (1903) and more expressively in ''The Prolongation of Life: Optimistic Studies'' (1907).<ref name=":3">{{cite journal |last1=Podolsky |first1=Scott H |year=2012 |title=Metchnikoff and the microbiome |journal=The Lancet |volume=380 |issue=9856 |pages=1810–1811 |doi=10.1016/S0140-6736(12)62018-2 |pmid=23189332 |s2cid=13290396}}</ref> He also espoused the potential life-lengthening properties of lactic acid bacteria such as ''[[Lactobacillus delbrueckii subsp. bulgaricus]]''.<ref>{{cite journal|last1=Mackowiak|first1=Philip A.|title=Recycling Metchnikoff: Probiotics, the Intestinal Microbiome and the Quest for Long Life|journal=Frontiers in Public Health |year= 2013 |volume= 1 |page= 52 |doi= 10.3389/fpubh.2013.00052 |pmid=24350221|pmc=3859987|doi-access=free}}</ref> This concept of [[probiotic]]s, which he termed "orthobiosis,"<ref name=":3" /> was influential in his lifetime, but became ignored until the mid-1990s when experimental evidence emerged.<ref name=":0" /><ref>{{Cite journal| last1= Gasbarrini |first1= Giovanni |last2=Bonvicini|first2=Fiorenza|last3=Gramenzi|first3=Annagiulia|date=2016|title=Probiotics History|journal=Journal of Clinical Gastroenterology|volume=50|issue= Suppl 2 |pages=S116–S119 |doi= 10.1097/MCG.0000000000000697| pmid= 27741152|doi-access=free}}</ref>