{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:20:01Z","timestamp":1790817601315,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>We review some of the precursor works of the Pasteurians in the field of bacterial toxins. The word \u201ctoxin\u201d was coined in 1888 by Ludwig Brieger to qualify different types of poison released by bacteria. Pasteur had identified the bacteria as the cause of putrefaction but never used the word toxin. In 1888, \u00c9mile Roux and Alexandre Yersin were the first to demonstrate that the bacteria causing diphtheria was releasing a deadly toxin. In 1923, Gaston Ramon treated that toxin with formalin and heat, resulting in the concept of \u201canatoxin\u201d as a mean of vaccination. A similar approach was performed to obtain the tetanus anatoxin by Pierre Descombey, Christian Zoeller and G. Ramon. On his side, Elie Metchnikoff also studied the tetanus toxin and investigated the cholera toxin. His colleague from Odessa, Nikola\u00ef Gamale\u00cfa who was expected to join Institut Pasteur, wrote the first book on bacterial poisons while other Pasteurians such as Etienne Burnet, Maurice Nicolle, Emile C\u00e9sari, and Constant Jouan wrote books on toxins. Concerning the endotoxins, Alexandre Besredka obtained the first immune antiserum against lipopolysaccharide, and Andr\u00e9 Boivin characterized the biochemical nature of the endotoxins in a work initiated with Lydia Mesrobeanu in Bucharest.<\/jats:p>","DOI":"10.3390\/toxins14110759","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T04:11:31Z","timestamp":1667448691000},"page":"759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["From Bacterial Poisons to Toxins: The Early Works of Pasteurians"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-2106","authenticated-orcid":false,"given":"Jean-Marc","family":"Cavaillon","sequence":"first","affiliation":[{"name":"National Research Agency (ANR), 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"fty019","DOI":"10.1093\/femspd\/fty019","article-title":"Historical links between toxinology and immunology","volume":"76","author":"Cavaillon","year":"2018","journal-title":"Pathog. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.toxicon.2017.10.016","article-title":"Exotoxins and endotoxins: Inducers of inflammatory cytokines","volume":"149","author":"Cavaillon","year":"2018","journal-title":"Toxicon"},{"key":"ref_3","first-page":"497","article-title":"Ueber das schwefelsaure sepsin (das gift faulender substanzen)","volume":"32","author":"Bergmann","year":"1866","journal-title":"Med. Wiss."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/BF01883589","article-title":"Zur kenntniss des tetanin und des mytilotoxin","volume":"112","author":"Brieger","year":"1888","journal-title":"Arch. Pathol. Anat."},{"key":"ref_5","unstructured":"Selmi, F. (1878). Sulle Ptomaine od Alcaloidi Cadaverici e Loro Importanza in Tossicologia, Osservazioni del Prof. Francesco Selmi Aggiuntavi una Perizia per la Ricerca Della Morfina, Presso Nicola Zanichelli."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.micinf.2016.05.008","article-title":"Centenary of the death of Elie Metchnikoff: A visionary and an outstanding team leader","volume":"18","author":"Cavaillon","year":"2016","journal-title":"Microbes Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.micinf.2019.06.006","article-title":"Duclaux, Chamberland, Roux, Grancher, and Metchnikoff: The five musketeers of Louis Pasteur","volume":"21","author":"Cavaillon","year":"2019","journal-title":"Microbes Infect."},{"key":"ref_8","first-page":"929","article-title":"\u00c9tudes sur la flore intestinale","volume":"22","author":"Metchnikoff","year":"1908","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_9","first-page":"755","article-title":"Poisons intestinaux et scl\u00e9roses","volume":"24","author":"Metchnikoff","year":"1910","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1189\/jlb.0712361","article-title":"Sir Marc Armand Ruffer and Giulio Bizzozero: The first reports on efferocytosis","volume":"93","author":"Cavaillon","year":"2013","journal-title":"Leukoc. Biol."},{"key":"ref_11","first-page":"63","article-title":"M\u00e9canisme de la fi\u00e8vre dans la maladie pyoc\u00efanique","volume":"9","author":"Charrin","year":"1889","journal-title":"C. R. Seances Soc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1055\/s-0029-1205597","article-title":"Untersuchungen \u00fcber das Infectionsfieber","volume":"20","author":"Centanni","year":"1894","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF02284303","article-title":"Untersuchungen \u00fcber das Choleragift","volume":"11","author":"Pfeiffer","year":"1892","journal-title":"Z. Hyg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S294","DOI":"10.1086\/513856","article-title":"Cytokines as endogenous pyrogens","volume":"179","author":"Dinarello","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_15","first-page":"173","article-title":"Recherches exp\u00e9rimentales sur les poisons du cholera","volume":"4","year":"1892","journal-title":"Arch. M\u00e9d. Exp\u00e9r. Anat Pathol."},{"key":"ref_16","first-page":"153","article-title":"De l\u2019action des ferments solubles sur le poison dipht\u00e9rique","volume":"44","year":"1892","journal-title":"C. R. Soc. Biol."},{"key":"ref_17","unstructured":"Rueff et Cie, J. (1892). Les Poisons Bact\u00e9riens."},{"key":"ref_18","first-page":"1037","article-title":"La th\u00e9orie des germes et ses application \u00e0 la m\u00e9decine et \u00e0 la chirurgie","volume":"86","author":"Pasteur","year":"1878","journal-title":"C. R. Acad. Sci."},{"key":"ref_19","first-page":"527","article-title":"Relations de la variole et de la vaccine. Chol\u00e9ra des poules","volume":"9","author":"Pasteur","year":"1880","journal-title":"Bull. Acad. M\u00e9d."},{"key":"ref_20","first-page":"390","article-title":"\u00c9tudes des conditions de la non-r\u00e9cidive de la maladie, et de quelques autres de ses caract\u00e8res","volume":"44","author":"Pasteur","year":"1880","journal-title":"Bull. Acad. Med."},{"key":"ref_21","first-page":"320","article-title":"Sur le premier volume des \u201cAnnales de L\u2019institut Pasteur\u201d, et en particulier sur un m\u00e9moire de MM Roux et Chamberland, intitul\u00e9 \u201cImmmunit\u00e9 contre la septic\u00e9mie, conf\u00e9r\u00e9e par des substances solubles\u201d","volume":"106","author":"Pasteur","year":"1888","journal-title":"C. R. Acad. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fimmu.2012.00068","article-title":"Louis pasteur, the father of immunology?","volume":"3","author":"Smith","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_23","first-page":"133","article-title":"Immunit\u00e9 contre la septic\u00e9mie conf\u00e9r\u00e9e par des substances solubles","volume":"7e s\u00e9rie, Tome 5","author":"Roux","year":"1888","journal-title":"Rec. Med. V\u00e9t."},{"key":"ref_24","first-page":"145","article-title":"Le m\u00e9canisme de l\u2019immunit\u00e9 acquise","volume":"7e s\u00e9rie, Tome 5","author":"Chauveau","year":"1888","journal-title":"Rec. Med. V\u00e9t."},{"key":"ref_25","first-page":"629","article-title":"Contribution \u00e0 l\u2019\u00e9tude de la dipht\u00e9rie","volume":"2","author":"Roux","year":"1888","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_26","first-page":"517","article-title":"De l\u2019immunit\u00e9\u2014Immunit\u00e9 acquise et immunit\u00e9 naturelle","volume":"5","author":"Roux","year":"1891","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1055\/s-0029-1207589","article-title":"Ueber das Zustandekommen der Diphtherie-Immunitat and der Tetanus-Immunit\u00e4t bei Thieren","volume":"16","author":"Behring","year":"1890","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_28","unstructured":"Baginsky, A. (1895). Die Serumtherapie Der Diphtherie Nach Den Beobachtungen Im Kaiser und Kaiserin Friedrich Kinderkrankenhause in Berlin, Hirschwald."},{"key":"ref_29","first-page":"183","article-title":"Ueber immunit\u00e4t durch vererbung und s\u00e4ugung","volume":"2","author":"Ehrlich","year":"1892","journal-title":"Z. Hyg. lnfekt. Krankh."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1055\/s-0029-1205722","article-title":"Ueber gewinnung und verwendung des diphtherieheilserums","volume":"20","author":"Kossel","year":"1894","journal-title":"Dtsch. Med. Wochenschr."},{"key":"ref_31","first-page":"748","article-title":"De la transfusion p\u00e9riton\u00e9ale et de l\u2019immunit\u00e9 qu\u2019elle conf\u00e8re","volume":"107","author":"Richet","year":"1888","journal-title":"C. R. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1080\/19420862.2017.1325051","article-title":"Contribution of physiologists to the identification of the humoral component of immunity in the 19th century","volume":"9","author":"Lahaie","year":"2017","journal-title":"Mabs"},{"key":"ref_33","first-page":"63","article-title":"The origin of the production of diphtheria antitoxin in France, between philanthropy and commerce","volume":"27","author":"Simon","year":"2007","journal-title":"Dynamis"},{"key":"ref_34","first-page":"609","article-title":"Contribution \u00e0 l\u2019\u00e9tude de la dipht\u00e9rie (s\u00e9rum-th\u00e9rapie)","volume":"8","author":"Roux","year":"1894","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_35","first-page":"640","article-title":"Trois cents cas de dipht\u00e9rie trait\u00e9s par le s\u00e9rum anti-dipht\u00e9riques","volume":"8","author":"Roux","year":"1894","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_36","unstructured":"Fibiger, J. (1898). Om serumbehandling af difteri. Hospitalstidende, 6."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1136\/bmj.317.7167.1243","article-title":"The controlled clinical trial turns 100 years: Fibiger\u2019s trial of serum treatment of diphtheria","volume":"317","author":"Gluud","year":"1998","journal-title":"Br. Med. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-230X(04)92001-5","article-title":"An analysis of a wrong Nobel Prize\u2014Johannes Fibiger, 1926: A study in the Nobel archives","volume":"92","author":"Stolt","year":"2004","journal-title":"Adv. Cancer Res."},{"key":"ref_39","first-page":"1338","article-title":"Sur le pouvoir floculant et sur les propri\u00e9t\u00e9s immunisantes d\u2019une toxine dipht\u00e9rique rendue anatoxique (anatoxine)","volume":"177","author":"Ramon","year":"1923","journal-title":"C. R. Acad. Sci."},{"key":"ref_40","first-page":"283","article-title":"Diphtheria toxid as an immunizing agent","volume":"4","author":"Glenny","year":"1923","journal-title":"Br. J. Exp. Pathol."},{"key":"ref_41","first-page":"1","article-title":"Proc\u00e9d\u00e9 pour accro\u00eetre la production des antitoxines","volume":"40","author":"Ramon","year":"1926","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_42","first-page":"710","article-title":"Die pathogenie des tetanus","volume":"27","author":"Faber","year":"1890","journal-title":"Berl. Klin. Wochenschr."},{"key":"ref_43","first-page":"69","article-title":"\u00dcber das Tetanus gift","volume":"8","author":"Tizzoni","year":"1890","journal-title":"Zentralbl. Bakt."},{"key":"ref_44","first-page":"83","article-title":"Recherches pr\u00e9liminaires sur la diffusion du poison du t\u00e9tanos dans l\u2019organisme","volume":"3","author":"Bruschettini","year":"1890","journal-title":"Ann. Microgr."},{"key":"ref_45","first-page":"634","article-title":"Sur le poison t\u00e9tanique","volume":"42","author":"Vaillard","year":"1890","journal-title":"C. R. Soc. Biol."},{"key":"ref_46","first-page":"65","article-title":"Contribution \u00e0 l\u2019\u00e9tude du t\u00e9tanos. Pr\u00e9vention et traitement par le serum anti-toxiique","volume":"7","author":"Roux","year":"1893","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0140-6736(01)91998-1","article-title":"Case of chronic tetanus treated by Tizzoni\u2019s antitoxin; recovery","volume":"147","author":"Tracey","year":"1896","journal-title":"Lancet"},{"key":"ref_48","first-page":"801","article-title":"Recherches sur l\u2019influence de l\u2019organisme sur les toxines","volume":"11","author":"Metchnikoff","year":"1897","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_49","first-page":"591","article-title":"Recherche sur la toxine t\u00e9tanique","volume":"11","author":"Marie","year":"1897","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_50","first-page":"481","article-title":"Sur la s\u00e9roth\u00e9rapie du t\u00e9tanos","volume":"8e s\u00e9rie, tome 4","author":"Nocard","year":"1897","journal-title":"Receuil M\u00e9d. V\u00e9t."},{"key":"ref_51","first-page":"485","article-title":"Vaccination du cheval par l\u2019anatoxine t\u00e9tanique","volume":"39","author":"Descombey","year":"1925","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_52","first-page":"245","article-title":"De la valeur antig\u00e8ne de l\u2019anatoxine t\u00e9tanique chez l\u2019homme","volume":"182","author":"Ramon","year":"1925","journal-title":"C. R. Acad. Sci."},{"key":"ref_53","first-page":"106","article-title":"Les \u201cvaccins associ\u00e9s\u201d par union d\u2019une anatoxine et d\u2019un vaccin microbien (TAB) ou par m\u00e9langes d\u2019anatoxines","volume":"94","author":"Ramon","year":"1926","journal-title":"C. R. Soc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1055\/s-0028-1140240","article-title":"Giftigkeit der Cholerabacillen","volume":"45","author":"Cantani","year":"1886","journal-title":"Dtsch. Med. Wochenschr"},{"key":"ref_55","first-page":"257","article-title":"Toxine et antitoxine chol\u00e9rique","volume":"10","author":"Metchnikoff","year":"1896","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/path.1700630417","article-title":"An experimental study of the action of cholera toxin","volume":"63","author":"De","year":"1951","journal-title":"J. Pathol. Bacteriol."},{"key":"ref_57","first-page":"462","article-title":"Les leucocytes et les propri\u00e9t\u00e9s actives du s\u00e9rum chez les vaccin\u00e9s","volume":"9","author":"Bordet","year":"1895","journal-title":"Ann. Inst. Pasteur."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.3389\/fimmu.2019.02114","article-title":"100th Anniversary of Jules Bordet\u2019s Nobel Prize: Tribute to a founding father of immunology","volume":"10","author":"Cavaillon","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rietschel, E.T., and Cavaillon, J.-M. (2002). Endotoxin and anti-endotoxin\u2014The contribution of the schools of Koch and Pasteur: Life, milestone-experiments and concepts of Richard Pfeiffer (Berlin) and Alexandre Besredka (Paris). J. Endotoxin Res., 8.","DOI":"10.1179\/096805102125000038"},{"key":"ref_60","first-page":"149","article-title":"De l\u2019anti-endotoxine typhique et des anti-endotoxines en g\u00e9n\u00e9ral","volume":"20","author":"Besredka","year":"1906","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_61","first-page":"490","article-title":"Technique pour la pr\u00e9paration des polysaccharides microbiens sp\u00e9cifiques","volume":"113","author":"Boivin","year":"1933","journal-title":"C. R. Soc. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1177\/1753425919842307","article-title":"Andr\u00e9 Boivin: A pioneer in endotoxin research and an amazing visionary during the birth of molecular biology","volume":"26","author":"Cavaillon","year":"2020","journal-title":"Innate Immun."},{"key":"ref_63","first-page":"331","article-title":"Contribution \u00e0 l\u2019\u00e9tude des propri\u00e9t\u00e9s et de la nature des m\u00e9langes des toxines avec leurs antitoxines","volume":"16","author":"Danysz","year":"1902","journal-title":"Ann. Inst. Pasteur"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jointm.2021.04.003","article-title":"COVID-19 and earlier pandemics, sepsis, and vaccines: A historical perspective","volume":"1","author":"Cavaillon","year":"2021","journal-title":"J. Intensive Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cavaillon, J.-M., and Legout, S. (2022). Louis Pasteur: Between myth and reality. Biomolecules, 12.","DOI":"10.3390\/biom12040596"},{"key":"ref_66","first-page":"529","article-title":"L\u2019\u0153uvre de Paul Ehrlich","volume":"71","author":"Roux","year":"1914","journal-title":"Berl. Klin. Wochenschr."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/11\/759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:45Z","timestamp":1760144985000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/14\/11\/759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":66,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["toxins14110759"],"URL":"https:\/\/doi.org\/10.3390\/toxins14110759","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]}}}