{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:31:30Z","timestamp":1761921090995,"version":"3.37.3"},"reference-count":117,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011104","name":"Universitat Aut\u00f2noma de Barcelona","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Diabetes Endocrinolog\u00eda y Metabolismo: Fundaci\u00f3n Diabem"},{"DOI":"10.13039\/501100011104","name":"Universitat Aut\u00f2noma de Barcelona","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011104","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Diabetol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The general objective has been the historiographical investigation of the organotherapy of diabetes mellitus between 1906 and 1923 in its scientific, social and political dimensions, with special emphasis on the most relevant contributions of researchers and institutions and on the controversies generated on the priority of the \"discovery\" of antidiabetic hormone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We have analyzed the experimental procedures and determination of biological parameters used by researchers during the investigated period (1906\u20131923): pancreatic ablation techniques, induction of acinar atrophy with preservation of pancreatic islets, preparation of pancreatic extracts (PE) with antidiabetic activity, clinical chemistry procedures (glycemia, glycosuria, ketonemia, ketonuria, etc.). The field investigation has included on-site and online visits to cities, towns, buildings, laboratories, universities, museums and research centers where the reported events took place, obtaining documents, photographic images, audiovisual recordings, as well as personal interviews complementary to the documentation consulted (primary sources, critical bibliography, reference works). The documentary archival sources have been classified according to theme, including those consulted in situ with those extracted online and digitized copies received mainly by email. Among the many archives contacted, those listed below have been most useful and have been consulted on site and on repeated visits: National Library of Medicine-Historical Archives (Bethesda, MD, USA); Archives, University of Toronto and Thomas Fisher Rare Books Library (Toronto, Ontario, Canada); Francis A. County Library of Medicine, Harvard University (Boston, Mass, USA); Zentralbibliothek der Humboldt-Universit\u00e4t (Berlin, DE), Geheimarchiv des Preu\u03b2ischen Staates (Berlin, DE); Landesamt f\u00fcr B\u00fcrger\u2014und Ordnungsangelegenheiten (LABO) (Berlin, DE); Arhivele Academiei Rom\u00e2ne \u015fi Universit\u01ce\u021bii Carol Davila (Bucharest, RO).<\/jats:p><\/jats:sec><jats:sec><jats:title>Main results and conclusions<\/jats:title><jats:p>A) The European researchers Z\u00fclzer (Z Exp Path Ther 23:307\u2013318, 1908) and Paulescu (CR Seances Soc Biol Fil 85:558, 1921) meet the requirements of the priority rule in the discovery of the antidiabetic hormone. B) Factors of socioeconomic and political nature related with the First World War and the inter-war period delayed the process of purification of the antidiabetic hormone in Europe. C) The Canadian scientist J. Collip, University of Alberta, temporarily assimilated to the University of Toronto, and the American chemist and researcher G. Walden, with the expert collaboration of Eli Lilly &amp; Co., were the main authors of the purification process of the antidiabetic hormone. D) The scientific evidence, reflected in the heuristics of this research, allows to assert that the basic investigation carried out by the Department of Physiology of the University of Toronto, directed by the Scottish J. Macleod, in conjunction with the clinical research undertaken by the Department of Medicine of the University of Toronto (W. Campbell, A. Fletcher, D. Graham) made it possible in record time the successful treatment of patients with what was until then a deadly disease.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s00592-022-02014-7","type":"journal-article","created":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T06:02:26Z","timestamp":1672466546000},"page":"163-189","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["On the occasion of the centennial of insulin therapy (1922\u20132022), II-Organotherapy of diabetes mellitus (1906\u20131923): Acomatol. Pancreina. Insulin."],"prefix":"10.1007","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0419-6771","authenticated-orcid":false,"given":"Alberto","family":"de Leiva-Hidalgo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"de Leiva-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,31]]},"reference":[{"unstructured":"Z\u00fclzer GL (1893) \u00dcber aliment\u00e4re Glycosurie in Krankheiten und \u00fcber puerperale Lactosurie. Dissertation, University of Humboldt, Berlin","key":"2014_CR1"},{"key":"2014_CR2","first-page":"146","volume":"71","author":"F Blum","year":"1901","unstructured":"Blum F (1901) \u00dcber Nebennierendiabetes. Dtsch Arch Klin Med 71:146\u2013147","journal-title":"Dtsch Arch Klin Med"},{"key":"2014_CR3","first-page":"1209","volume":"38","author":"GL Z\u00fclzer","year":"1901","unstructured":"Z\u00fclzer GL (1901) Zur Frage des Nebennierendiabetes. Berl KlinWschr 38:1209\u20131210","journal-title":"Berl KlinWschr"},{"key":"2014_CR4","first-page":"474","volume":"44","author":"GL Z\u00fclzer","year":"1907","unstructured":"Z\u00fclzer GL (1907) Experimentelle Untersuchungen \u00fcber den diabetes. Berl Klin Wschr 44:474\u2013475","journal-title":"Berl Klin Wschr"},{"unstructured":"Mellinghoff KH (1971) Georg Ludwig Z\u00fclzers Beitrag zur Insulinforschung. Dissertation, University of D\u00fcsseldorf","key":"2014_CR5"},{"key":"2014_CR6","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/BF02661302","volume":"23","author":"GL Z\u00fclzer","year":"1908","unstructured":"Z\u00fclzer GL (1908) Ueber Versuche einer specifischen Fermenttherapie des diabetes. Zeitschrift f\u00fc Experimentelle Pathologie und Therapie 23:307\u2013318","journal-title":"Zeitschrift f\u00fc Experimentelle Pathologie und Therapie"},{"key":"2014_CR7","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1055\/s-0028-1135650","volume":"34","author":"GL Z\u00fclzer","year":"1908","unstructured":"Z\u00fclzer GL, Dohrn N, Marxer A (1908) Neuere Untersuchungen \u00fcber den experimentellen diabetes. Dtsch Med Wschr 34:1380\u20131385","journal-title":"Dtsch Med Wschr"},{"unstructured":"Biedl A (1910) Innere Sekretion. In: Ihre Physiologischen Grundlagen und ihre Bedeutung f\u00fcr die Pathologie. Urban und Schwarzenberg, Berlin, Vienna","key":"2014_CR8"},{"key":"2014_CR9","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1097\/MJT.0000000000001070","volume":"27","author":"A de Leiva-Hidalgo","year":"2020","unstructured":"de Leiva-Hidalgo A, de Leiva-P\u00e9rez A (2020) Pancreatic extracts for the treatment of diabetes (1889\u20131914): acomatol. Am J Ther 27:e1\u2013e12","journal-title":"Am J Ther"},{"key":"2014_CR10","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1055\/s-0029-1201850","volume":"35","author":"J Forschbach","year":"1909","unstructured":"Forschbach J (1909) Versuche zur Behandlung des diabetes mellitus mit dem Zuelzerschen Pankreas-hormon. Dtsch Med Wschr 35:2053\u20132055","journal-title":"Dtsch Med Wschr"},{"key":"2014_CR11","first-page":"87","volume":"8","author":"C Reuter","year":"1924","unstructured":"Reuter C (1924) La s\u00e9cr\u00e9tion interne du pancr\u00e9as et le traitement du diab\u00e8te sucr\u00e9. Section des Sciences naturelles physiques et math\u00e9matiques (Nouv S\u00e9rie) 8:87\u2013100","journal-title":"Section des Sciences naturelles physiques et math\u00e9matiques (Nouv S\u00e9rie)"},{"key":"2014_CR12","first-page":"7","volume":"34","author":"E Pierret","year":"1924","unstructured":"Pierret E (1924) La fonction endocrine du pancr\u00e9as et la d\u00e9couverte de l\u2019insuline. Rapport sur la conf\u00e9rence de M. Camille Reuter Bull Soc Nat luxemb 34:7\u201315","journal-title":"Camille Reuter Bull Soc Nat luxemb"},{"key":"2014_CR13","volume-title":"Der Blutzucker","author":"I Bang","year":"1913","unstructured":"Bang I (1913) Der Blutzucker. Bergmann, Wiesbaden"},{"key":"2014_CR14","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/BF01789831","volume":"47","author":"F Schenk","year":"1890","unstructured":"Schenk F (1890) \u00dcber Zuckerbestimmung im Blute. Pfl\u00fcger Arch 47:621\u2013629","journal-title":"Pfl\u00fcger Arch"},{"key":"2014_CR15","first-page":"495","volume":"15","author":"M Abeles","year":"1891","unstructured":"Abeles M (1891) Ueber ein Verfahren zum Enteiweissen des Blutes f\u00fcr die Zuckerbestimmung. Z physiol Chem 15:495\u2013504","journal-title":"Z physiol Chem"},{"key":"2014_CR16","first-page":"1217","volume":"80","author":"HC Hagedorn","year":"1918","unstructured":"Hagedorn HC (1918) Jensen N (1918) Om kvantitativ bestemmelse af minimale glucosemaengder, saerlig i blod. Ugeskr Laeg 80:1217\u20131228","journal-title":"Ugeskr Laeg"},{"key":"2014_CR17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1136\/bmj.1.3236.8","volume":"1","author":"FG Banting","year":"1923","unstructured":"Banting FG, Campbell WR, Fletcher AA (1923) Further clinical experience with insulin in the treatment of diabetes mellitus. Br Med J 1:8\u201313","journal-title":"Br Med J"},{"unstructured":"Z\u00fclzer GL (1923) The overcoming of diabetes. New facts about Insulin. Unpublished article. October 1923, copy in Banting Papers, Box 62, Folder 26, University of Toronto","key":"2014_CR18"},{"key":"2014_CR19","first-page":"1","volume":"47","author":"GL Z\u00fclzer","year":"1923","unstructured":"Z\u00fclzer GL (1923) \u00dcber Acomatol, das deutsche Insulin. Med Klin 47:1\u20133","journal-title":"Med Klin"},{"issue":"3266","key":"2014_CR20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1136\/bmj.2.3266.165","volume":"2","author":"JJR Macleod","year":"1923","unstructured":"Macleod JJR (1923) A lecture on insulin. Br Med J 2(3266):165\u2013172","journal-title":"Br Med J"},{"unstructured":"Macleod JJR (1925) Nobel Lecture, May 26, 1925: The physiology of insulin and its source in the animal body. Nobel Prize. Accessed September 15 2022 https:\/\/www.nobelprize.org\/prizes\/medicine\/1923\/macleod\/lecture\/","key":"2014_CR21"},{"key":"2014_CR22","volume-title":"Carbohydrate Metabolism and Insulin","author":"JJR Macleod","year":"1926","unstructured":"Macleod JJR (1926) Carbohydrate Metabolism and Insulin. Longmans, New York"},{"issue":"8","key":"2014_CR23","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1177\/003693306901400807","volume":"14","author":"I Murray","year":"1969","unstructured":"Murray I (1969) The search for insulin. Scott Med J 14(8):286\u2013293","journal-title":"Scott Med J"},{"key":"2014_CR24","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/BF01228128","volume":"14","author":"A Labhart","year":"1978","unstructured":"Labhart A (1978) Intuition, luck and misfortune in diabetes research. Diabetologia 14:353\u2013358","journal-title":"Diabetologia"},{"key":"2014_CR25","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1203\/00006450-198512000-00032","volume":"19","author":"WW Z\u00fclzer","year":"1985","unstructured":"Z\u00fclzer WW (1985) Reflections of a former pediatrician, accepting the Howland award. Pediatr Res 19:1369\u20131372","journal-title":"Pediatr Res"},{"unstructured":"de Leiva-Hidalgo A (2022) Organotherapy of Diabetes Mellitus (1889\u20131923). Controversies on the priority about the discovery of the antidiabetic hormone. Dissertation, University of Valencia","key":"2014_CR26"},{"key":"2014_CR27","first-page":"62","volume":"25","author":"A de Leiva-Hidalgo","year":"2009","unstructured":"de Leiva-Hidalgo A, Brugu\u00e9s E, de Leiva-P\u00e9rez A (2009) From pancreatic extracts to artificial pancreas: history, science and controversies about the discovery of the pancreatic antidiabetic hormone. I: the pioneers. Av Diabetol 25:62\u201369","journal-title":"Av Diabetol"},{"key":"2014_CR28","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1152\/ajplegacy.1912.29.3.306","volume":"29","author":"EL Scott","year":"1913","unstructured":"Scott EL (1913) On the influence of intravenous injections of an extract of the pancreas on experimental pancreatic diabetes. Am J Physiol 29:306\u2013310","journal-title":"Am J Physiol"},{"key":"2014_CR29","doi-asserted-by":"publisher","first-page":"171","DOI":"10.3181\/00379727-10-69","volume":"10","author":"EL Scott","year":"1913","unstructured":"Scott EL (1913) The relation of pancreatic extracts to the sugar of the blood. Proc Soc Exp Biol Med 10:171\u2013173","journal-title":"Proc Soc Exp Biol Med"},{"key":"2014_CR30","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3181\/00379727-10-108","volume":"10","author":"JR Murlin","year":"1913","unstructured":"Murlin JR, Kramer B (1913) The influence of pancreatic and duodenal extracts on the glycosuria and the respiratory metabolism of depancreatized dogs. Proc Soc Exp Biol Med 10:101\u2013103","journal-title":"Proc Soc Exp Biol Med"},{"key":"2014_CR31","first-page":"19","volume":"2","author":"JR Murlin","year":"1922","unstructured":"Murlin JR, Kramer B, Sweet JE (1922) The influence of pancreatic extracts without the aid of alkali upon the metabolism of the depancreatized animal. J Metab Res 2:19\u201327","journal-title":"J Metab Res"},{"key":"2014_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3181\/00379727-20-30","volume":"20","author":"CBF Gibbs","year":"1922","unstructured":"Gibbs CBF, Clough HD, Stone NC, Murlin JR (1922) The influence of pancreatic extracts upon the carbohydrate metabolism of depancreatized dogs. Proc Soc Exp Biol Med 20:67\u201368","journal-title":"Proc Soc Exp Biol Med"},{"key":"2014_CR33","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3181\/00379727-20-31","volume":"20","author":"CC Sutter","year":"1922","unstructured":"Sutter CC, Murlin JR (1922) Three months study of the influence of the antidiabetic substance on a case of severe diabetes. Proc Soc Exp Biol Med 20:68\u201369","journal-title":"Proc Soc Exp Biol Med"},{"key":"2014_CR34","first-page":"338","volume":"1","author":"IS Kleiner","year":"1915","unstructured":"Kleiner IS, Seltzer SJ (1915) Retention in the circulation of dextrose in normal and depancreatized animals, and the effect of an intravenous injection of an emulsion of pancreas upon this retention. Proc Soc Exp Biol Med 1:338\u2013341","journal-title":"Proc Soc Exp Biol Med"},{"key":"2014_CR35","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0021-9258(18)87274-X","volume":"40","author":"IS Kleiner","year":"1919","unstructured":"Kleiner IS (1919) The action of intravenous injections of pancreas emulsion in experimental diabetes. J Biol Chem 40:153\u2013170","journal-title":"J Biol Chem"},{"issue":"10","key":"2014_CR36","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/nm1010-1100","volume":"16","author":"JM Friedman","year":"2010","unstructured":"Friedman JM (2010) A tale of two hormones. Nat Med 16(10):1100\u20131106","journal-title":"Nat Med"},{"key":"2014_CR37","first-page":"154","volume":"25","author":"A de Leiva-Hidalgo","year":"2009","unstructured":"de Leiva-Hidalgo A, de Leiva-P\u00e9rez A, Brugu\u00e9s E (2009) From pancreatic extracts to artificial pancreas: history, science and controversies about the discovery of the pancreatic antidiabetic hormone. II: Nicolae C. Paulescu: The discovery of pancreine. Av Diabetol 25:154\u2013162","journal-title":"Av Diabetol"},{"key":"2014_CR38","first-page":"1728","volume":"138","author":"NC Paulescu","year":"1904","unstructured":"Paulescu NC (1904) Action des sels des m\u00e9taux alcalins sur la substance vivante. C R s\u00e9ances Acad sci 138:1728\u20131730","journal-title":"C R s\u00e9ances Acad sci"},{"unstructured":"Paulescu NC (1898) Glande thyroide, physiologie normale et pathologique. J de M\u00e9d Int Par: 11\u201314","key":"2014_CR39"},{"unstructured":"Paulescu NC (1899) Recherches exp\u00e9rimentales sur la physiologie des glandes surr\u00e9nales. J de M\u00e9d Int Par 298(I) 364 (II)","key":"2014_CR40"},{"key":"2014_CR41","first-page":"390","volume":"75","author":"NC Paulescu","year":"1913","unstructured":"Paulescu NC (1913) Signification de l\u2019albuminuria. CR Soc Biol 75:390\u2013391","journal-title":"CR Soc Biol"},{"key":"2014_CR42","first-page":"454","volume":"144","author":"\u00c9 Lancereaux","year":"1907","unstructured":"Lancereaux \u00c9, Paulescu NC (1907) Sur un cas remarquable d\u2019an\u00e9vrisme de l\u2019arterie ophtalmique gu\u00e9ri par la g\u00e9latina. C R s\u00e9ances Acad sci 144:454\u2013456","journal-title":"C R s\u00e9ances Acad sci"},{"unstructured":"Lancereaux \u00c9, Paulescu NC (1897) Du traitement des an\u00e9vrisms, en g\u00e9n\u00e9ral, et de l\u2019an\u00e9vrisme de l\u2019aorte en particulierr, per des injections sous-cutan\u00e9es d\u2019une solution g\u00e9latineuse. Bull Acad Med 784\u2013785","key":"2014_CR43"},{"unstructured":"Dworschack FI, Ionescu-Tirgovi\u015fte C (2008) Paulescu and collip: Insulin\u2019s unsung heroes. Editura Ilex, Bucarest","key":"2014_CR44"},{"unstructured":"Paulescu NC (1906) L\u2019Hypophyse du cerveau. Recherches experimentales. \u00c9diteur Vigot Fr\u00e9res, Paris","key":"2014_CR45"},{"key":"2014_CR46","first-page":"441","volume":"9","author":"NC Paulescu","year":"1907","unstructured":"Paulescu NC (1907) Recherches sur la physiologie de l\u2019hypophyse du cerveau: L\u2019Hypophysectomie et ses effets. J Physiol Pathol Gen 9:441\u2013456","journal-title":"J Physiol Pathol Gen"},{"key":"2014_CR47","first-page":"68","volume":"40","author":"SL Teichman","year":"1985","unstructured":"Teichman SL, Aldea PA (1985) Pioneers in pituitary physiology: Harvey Cushing and Nicolas Paulescu. J Hist Med 40:68\u201372","journal-title":"J Hist Med"},{"key":"2014_CR48","first-page":"248","volume":"53","author":"H Cushing","year":"1909","unstructured":"Cushing H (1909) The Hypophysis cerebri: clinical aspects of hyperpituitarism and hypopituitarism. JAMA 53:248\u2013256","journal-title":"JAMA"},{"key":"2014_CR49","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195169898.001.0001","volume-title":"Harvey Cushing: a life in surgery","author":"M Bliss","year":"2005","unstructured":"Bliss M (2005) Harvey Cushing: a life in surgery. Oxford University Press, New York"},{"key":"2014_CR50","first-page":"121","volume":"22","author":"SL Teichman","year":"1985","unstructured":"Teichman SL, Aldea PA (1985) Nicolas Constantin Paulescu (1869\u20131931) discovered insulin before banting and best and inspired Harvey Cushing\u2019s work on the pituitary gland. Rev Roum Morphol Embryol Physiol 22:121\u2013134","journal-title":"Rev Roum Morphol Embryol Physiol"},{"key":"2014_CR51","first-page":"50","volume":"76","author":"NC Paulescu","year":"1914","unstructured":"Paulescu NC (1914) Origines du glycog\u00e8ne. CR Soc Biol 76:50\u201352","journal-title":"CR Soc Biol"},{"key":"2014_CR52","first-page":"562","volume":"82","author":"NC Paulescu","year":"1920","unstructured":"Paulescu NC (1920) Le glycog\u00e8ne dans le diab\u00e8te per extirpattion du pancr\u00e9as. CR Soc Biol 82:562\u2013565","journal-title":"CR Soc Biol"},{"key":"2014_CR53","first-page":"566","volume":"82","author":"NC Paulescu","year":"1920","unstructured":"Paulescu NC (1920) Le glycog\u00e8ne dans le diab\u00e8te phloridizinique. CR Soc Biol 82:566\u2013568","journal-title":"CR Soc Biol"},{"key":"2014_CR54","volume-title":"Trait\u00e9 de M\u00e9decine, 4 vol","author":"\u00c9 Lancereaux","year":"1930","unstructured":"Lancereaux \u00c9, Paulescu NC (1930) Trait\u00e9 de M\u00e9decine, 4 vol. Sibiu, Paris"},{"unstructured":"Paulescu NC (1920) Trait\u00e9 de Physiologie M\u00e9dicale. Cartea Romaneasca, Bucarest","key":"2014_CR55"},{"key":"2014_CR56","first-page":"555","volume":"85","author":"NC Paulescu","year":"1921","unstructured":"Paulescu NC (1921) Action de l\u2019extrait pancr\u00e9atique inject\u00e9 dans le sang chez un animal diab\u00e9tique. C R Seances Soc Biol Fil 85:555\u2013557","journal-title":"C R Seances Soc Biol Fil"},{"key":"2014_CR57","first-page":"558","volume":"85","author":"NC Paulescu","year":"1921","unstructured":"Paulescu NC (1921) Influence du laps de temps \u00e9coul\u00e9 depuis l\u2019injection intraveineuse de l\u2019extrait pancr\u00e9atique chez un animal diab\u00e9tique. C R Seances Soc Biol Fil 85:558","journal-title":"C R Seances Soc Biol Fil"},{"key":"2014_CR58","first-page":"558","volume":"85","author":"NC Paulescu","year":"1921","unstructured":"Paulescu NC (1921) Influence de la quantit\u00e9 de pancr\u00e9as employ\u00e9e pour pr\u00e9parer l\u2019extrait inject\u00e9 dans le sang chez un animal diab\u00e9tique. CR Seances Soc Biol Fil 85:558\u2013559","journal-title":"CR Seances Soc Biol Fil"},{"key":"2014_CR59","first-page":"559","volume":"85","author":"NC Paulescu","year":"1921","unstructured":"Paulescu NC (1921) Action de l\u2019extrait pancr\u00e9atique inject\u00e9 dans le sang chez un animal normal. CR Seances Soc Biol Fil 85:559","journal-title":"CR Seances Soc Biol Fil"},{"key":"2014_CR60","first-page":"85","volume":"17","author":"NC Paulescu","year":"1921","unstructured":"Paulescu NC (1921) Recherche sur le r\u00f4le du pancr\u00e9as dans l\u2019assimilation nutritive. Arch Intern Physiol 17:85\u2013103","journal-title":"Arch Intern Physiol"},{"unstructured":"Ionescu-Tirgoviste C (1996) The re-discovery of Insulin. Editura Geneze, Bucarest","key":"2014_CR61"},{"key":"2014_CR62","first-page":"71","volume":"21","author":"NC Paulescu","year":"1923","unstructured":"Paulescu NC (1923) Quelques r\u00e9actions chimiques et physiques appliqu\u00e9es a l\u2019extrait aqueux du pancr\u00e9as pour le d\u00e9barrasser des substances prot\u00e9iques en exc\u00e8s. Arch Intern Physiol 21:71\u201385","journal-title":"Arch Intern Physiol"},{"key":"2014_CR63","first-page":"215","volume":"21","author":"NC Paulescu","year":"1923","unstructured":"Paulescu NC (1923) Divers proc\u00e9d\u00e9s pour introduire l\u2019extrait pancr\u00e9atique dans l\u2019organism d\u2019un animal diab\u00e9tique. Arch Intern Physiol 21:215\u2013238","journal-title":"Arch Intern Physiol"},{"unstructured":"Lancereaux E, Paulescu NC (1930) Trait\u00e9 de M\u00e9decine, Vol. IV. Imprimerie de l\u2019Ecole Militaire, Sibiu","key":"2014_CR64"},{"key":"2014_CR65","first-page":"373","volume":"26","author":"A de Leiva-Hidalgo","year":"2010","unstructured":"de Leiva-Hidalgo A, Brugu\u00e9s E, de Leiva-P\u00e9rez A (2010) From pancreatic extracts to artificial pancreas: history, science and controversies about the discovery of the pancreatic antidiabetic hormone V: the controversy. Who discovered insulin? Adv Diabetol 26:373\u2013382","journal-title":"Adv Diabetol"},{"unstructured":"Sordelli A, Lewis J (1924) Insulina. El Ateneo, Buenos Aires","key":"2014_CR66"},{"key":"2014_CR67","volume-title":"Histoire et cons\u00e9quences pratiques de la d\u00e9couverte des vitamins","author":"C Funk","year":"1924","unstructured":"Funk C (1924) Histoire et cons\u00e9quences pratiques de la d\u00e9couverte des vitamins. Vigot Fr\u00e8res, Paris"},{"doi-asserted-by":"crossref","unstructured":"Sharpey-Sch\u00e4fer E (1926) The Endocrine Organs, 2nd edn. Longmans, Green and Co. Ltd., New York","key":"2014_CR68","DOI":"10.2307\/3901540"},{"doi-asserted-by":"crossref","unstructured":"Trendelenburg P (1934) Die Hormone. In: Ihre Physiologie und Pharmacologie. Julius Springer Verlag, Berlin","key":"2014_CR69","DOI":"10.1007\/978-3-642-90919-1"},{"key":"2014_CR70","first-page":"256","volume":"7","author":"FG Banting","year":"1922","unstructured":"Banting FG, Best CH (1922) The internal secretion of the pancreas. J Lab Clin Med 7:256\u2013271","journal-title":"J Lab Clin Med"},{"key":"2014_CR71","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0021-9258(18)87566-4","volume":"24","author":"VC Myers","year":"1915","unstructured":"Myers VC, Bailey CV (1915) The Lewis and Benedict method for the estimation of blood sugar, with some observations obtained in disease. J Biol Chem 24:147\u2013161","journal-title":"J Biol Chem"},{"key":"2014_CR72","first-page":"437","volume":"31","author":"M Barron","year":"1920","unstructured":"Barron M (1920) The relation of the islets of Langerhans to diabetes with special referent to cases of pancreatic lithiasis. Surg Gynecol Obstet 31:437\u2013448","journal-title":"Surg Gynecol Obstet"},{"key":"2014_CR73","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1007\/BF01639951","volume":"10","author":"R Heidenhain","year":"1875","unstructured":"Heidenhain R (1875) Beitr\u00e4ge zur Kenntnis des Pankreas. Arch Ges Physiol 10:557\u2013632","journal-title":"Arch Ges Physiol"},{"key":"2014_CR74","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1113\/jphysiol.1903.sp000982","volume":"30","author":"W Bayliss","year":"1903","unstructured":"Bayliss W, Starling EH (1903) The proteolytic activities of the pancreatic juice. J Physiol 30:61\u201383","journal-title":"J Physiol"},{"doi-asserted-by":"crossref","unstructured":"Roberts F (1922). Insulin (Letter). Br. Med J: 1193\u20131194.","key":"2014_CR75","DOI":"10.1136\/bmj.2.3233.1193-a"},{"key":"2014_CR76","volume-title":"Duncan graham: medical reformer and educator","author":"RB Kerr","year":"1989","unstructured":"Kerr RB, Waugh D (1989) Duncan graham: medical reformer and educator. Dundum Press, Toronto"},{"issue":"9","key":"2014_CR77","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.endonu.2011.10.001","volume":"58","author":"A de Leiva","year":"2011","unstructured":"de Leiva A, Brugu\u00e9s E, de Leiva-P\u00e9rez A (2011) The discovery of insulin: continued controversy after ninety years. Endocrinol Nutr 58(9):449\u2013456","journal-title":"Endocrinol Nutr"},{"key":"2014_CR78","first-page":"40","volume":"55","author":"JB Collip","year":"1923","unstructured":"Collip JB (1923) The original method as used for the isolation of insulin in semipure form for the treatment of the first clinical cases. J Biol Chem 55:40\u201341","journal-title":"J Biol Chem"},{"key":"2014_CR79","first-page":"141","volume":"2","author":"FG Banting","year":"1922","unstructured":"Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922) Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 2:141\u2013146","journal-title":"Can Med Assoc J"},{"unstructured":"Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA, Macleod JJR, Noble EC (1922) The effect produced on diabetes by extracts of pancreas. Trans Assoc Am Phys (Suppl): 1\u201311","key":"2014_CR80"},{"key":"2014_CR81","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1152\/ajplegacy.1922.62.1.162","volume":"62","author":"FG Banting","year":"1922","unstructured":"Banting FG, Best CH, Collip JB, Macleod JJR, Noble EC (1922) The effect of pancreatic extract on normal rabbits. Am J Physiol 62:162\u2013176","journal-title":"Am J Physiol"},{"key":"2014_CR82","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1152\/ajplegacy.1922.62.3.559","volume":"3","author":"FG Banting","year":"1922","unstructured":"Banting FG, Best CH, Collip JB, Macleod JJR, Noble EC (1922) The effects of insulin on experimental hyperglycemia in rabbits. Am J Physiol 3:559\u2013580","journal-title":"Am J Physiol"},{"key":"2014_CR83","first-page":"267","volume":"22","author":"JB Collip","year":"1923","unstructured":"Collip JB (1923) The history of the discovery of insulin. Northwest Med 22:267\u2013273","journal-title":"Northwest Med"},{"key":"2014_CR84","first-page":"96","volume":"7","author":"J De Meyer","year":"1909","unstructured":"De Meyer J (1909) Action de la s\u00e9cr\u00e9tion interne du pancr\u00e9as sur diff\u00e9rents organs et en particulier sur la s\u00e9cr\u00e9tion r\u00e9nale. Archives de Physiologie 7:96\u201399","journal-title":"Archivo de Phisiologia"},{"unstructured":"Sharpey-Schafer EA (1916) The endocrine organs. Longmans, Green and Co., London","key":"2014_CR85"},{"issue":"2","key":"2014_CR86","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S0021-9258(18)85499-0","volume":"57","author":"PJ Moloney","year":"1923","unstructured":"Moloney PJ, Findlay DM (1923) Concentration of insulin by adsorption on benzoic acid. J Biol Chem 57(2):359\u2013361","journal-title":"J Biol Chem"},{"key":"2014_CR87","first-page":"141","volume":"2","author":"FG Banting","year":"1924","unstructured":"Banting FG, Best CH (1924) The discovery and preparation of insulin. University of Toronto Medical Journal, 1(3), 94\u201398 Preliminary report. Can Med Assoc J 2:141\u2013146","journal-title":"Can Med Assoc J"},{"unstructured":"Insulin Committee of the University of Toronto (1922). Minutes of the meeting of the special advisory committee on diabetes. Insulin Collection (A 1982-0001, Box 044, Folder 1). University of Toronto Archives. https:\/\/insulin.library.utoronto.ca\/islandora\/object\/insulin%3AW10028","key":"2014_CR88"},{"key":"2014_CR89","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1353\/bhm.2002.0097","volume":"76","author":"C Sinding","year":"2002","unstructured":"Sinding C (2002) Making the unit of insulin. Standards. Clinical work, and industry, 1920\u20131925. Bull Hist Med 76:231\u2013270","journal-title":"Bull Hist Med"},{"unstructured":"Clowes GHA (1923, April 8). [Telegram to Professor JJR Macleod regarding Walden patent]. Insulin Collection. (A1982\u20130001, Box 12, 12). University of Toronto Archives, Toronto, Canada. https:\/\/insulin.library.utoronto.ca\/islandora\/object\/insulin%3AL10254","key":"2014_CR90"},{"unstructured":"Clowes GHA (1923, October 23). [Letter to F. Lorne Hutchison]. A1982-001, Box 53, Folder 13. University of Toronto Archives, Toronto, Canada. Recovered on February 15, 2019. https:\/\/insulin.library.utoronto.ca\/islandora\/object\/insulin%3AL10296","key":"2014_CR91"},{"key":"2014_CR92","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1042\/bj0020007","volume":"2","author":"J Rennie","year":"1907","unstructured":"Rennie J, Fraser T (1907) The islets of Langerhans in relation to diabetes. Biochem J 2:7\u201319","journal-title":"Biochem J"},{"key":"2014_CR93","first-page":"149","volume":"2","author":"JJR Macleod","year":"1922","unstructured":"Macleod JJR (1922) The source of insulin: a study of the effect produced on blood sugar by extracts of the pancreas and principal islets of fishes. J Metab Res 2:149\u2013172","journal-title":"J Metab Res"},{"issue":"2","key":"2014_CR94","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1080\/07341510701810948","volume":"24","author":"M Cassier","year":"2008","unstructured":"Cassier M, Sanding C (2008) Patenting in the public interest administration of insulin patents by the University of Toronto. Hist Technol 24(2):153\u2013171","journal-title":"Hist Technol"},{"unstructured":"Insulin Committee of the University of Toronto (1922). Minutes of the Insulin Committee of the University of Toronto (December 30). Insulin Collection (A1982-0001, Box 044, Folder 1). University of Toronto Archives, Toronto, Canada. https:\/\/insulinlibrary.utoronto.ca\/islandora\/object\/insulin%3AW10028","key":"2014_CR95"},{"issue":"25","key":"2014_CR96","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1001\/jama.1923.02640520033012","volume":"80","author":"GB Walden","year":"1923","unstructured":"Walden GB (1923) Iletin (Insulin-Lilly)\u2014a brand of Lilly. J Am Med Assoc 80(25):1851","journal-title":"J Am Med Assoc"},{"unstructured":"Riches CH (1923). [Letter to Dr. JJR Macleod regarding Walden patent. April, 3]. Insulin Collection (A1982\u20130001, Box 13, Folder 11). University of Toronto Archives, Toronto, Canada. https:\/\/insulinlibrary.utoronto.ca\/\/islandora\/onject\/insulin%3AL10253","key":"2014_CR97"},{"issue":"2","key":"2014_CR98","first-page":"31","volume":"55","author":"EA Doisy","year":"1923","unstructured":"Doisy EA, Somogyi M, Shaffer PA (1923) Some properties of an active constituent of pancreas (insulin). J Biol Chem 55(2):31\u201332","journal-title":"J Biol Chem"},{"unstructured":"Walden GB (1924) United States Patent # 1520673 (Granted on December 23, 1924). Washington, DC: U.S. Patent and Trademark Office","key":"2014_CR99"},{"unstructured":"Lilly (2018). George Walden discovers isoelectric precipitation produces enough insulin for all. Treating Diabetes\u2014a history of incremental advances in treating diabetes. Chapter 6. https:\/\/tacomed.com\/chapter-6-eli-lilly\/george-walden-discovers-isoelectric precipitation-produces-enough-insulin-for-all\/ (Accessed August 15, 2018, currently archived)","key":"2014_CR100"},{"unstructured":"Insulin Committee of the University of Toronto (1922). Minutes of the Insulin Committee. Insulin Collection (A1982-0001, Box 044, Folder 1) University of Toronto Archives, Toronto, Canada. https:\/\/insulinlibrary.utoronto.ca\/islandora\/object\/insulin%3AW10028","key":"2014_CR101"},{"key":"2014_CR102","first-page":"547","volume":"2","author":"FG Banting","year":"1922","unstructured":"Banting FG, Campbell WR, Fletcher AA (1922) Insulin in the treatment of diabetes mellitus. J Metabol Res 2:547\u2013604","journal-title":"J Metabol Res"},{"key":"2014_CR103","first-page":"605","volume":"2","author":"WR Campbell","year":"1922","unstructured":"Campbell WR (1922) Ketosis, acidosis and coma treated by insulin. J Metabol Res 2:605\u2013635","journal-title":"J Metabol Res"},{"issue":"1","key":"2014_CR104","first-page":"15","volume":"27","author":"A de Leiva-Hidalgo","year":"2011","unstructured":"de Leiva-Hidalgo A, de Leiva-P\u00e9rez A, Brugu\u00e9s E (2011) From pancreatic extract to artificial pancreas: history, science and controversies about the discovery of the pancreatic antidiabetic hormone. VII: Early clinical use of pancreatic extract (1921\u20131923). Adv Diabetol 27(1):15\u201326","journal-title":"Adv Diabetol"},{"key":"2014_CR105","first-page":"547","volume":"2","author":"AA Fletcher","year":"1922","unstructured":"Fletcher AA, Campbell WR (1922) The blood sugar following insulin administration and the symptom complex hypoglycemia. J Metabol Res 2:547\u2013604","journal-title":"J Metabol Res"},{"key":"2014_CR106","doi-asserted-by":"publisher","first-page":"e13","DOI":"10.1097\/MJT.0000000000001069","volume":"27","author":"A de Leiva-Hidalgo","year":"2020","unstructured":"de Leiva-Hidalgo A, de Leiva-Perez A (2020) Experiences of first Insulin-treated patients (1922\u20131923). Am J Ther 27:e13\u2013e23","journal-title":"Am J Ther"},{"key":"2014_CR107","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1136\/bmj.1.3236.8","volume":"1","author":"FG Banting","year":"1923","unstructured":"Banting FG, Campbell WR, Fletcher AA (1923) Further clinical experience with insulin (pancreatic extracts) in the treatment of diabetes mellitus. Br Med J 1:8\u201312","journal-title":"Br Med J"},{"key":"2014_CR108","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1159\/000506561","volume-title":"Unveiling Diabetes-Historical Milestones in Diabetology","author":"A de Leiva-Hidalgo","year":"2020","unstructured":"de Leiva-Hidalgo A, Brugu\u00e9s E, de Leiva-P\u00e9rez A (2020) The true Banting and Best story: the priority rule and the discovery of the antidiabetic hormone. In: J\u00f6rgens V, Porta M (eds) Unveiling Diabetes-Historical Milestones in Diabetology. Front Diabetes, Karger, Basel, pp 84\u2013102. https:\/\/doi.org\/10.1159\/000506561"},{"key":"2014_CR109","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1007\/978-1-349-09612-1","volume-title":"The discovery of Insulin","author":"Bliss,","year":"1982","unstructured":"Bliss, (1982) The discovery of Insulin. Chicago University Press, Chicago, p 1982"},{"key":"2014_CR110","doi-asserted-by":"publisher","DOI":"10.3138\/9781442664982","volume-title":"Pathogens for war-biological weapons, Canadian life scientists, and Nort American biodefence","author":"D Avery","year":"2013","unstructured":"Avery D (2013) Pathogens for war-biological weapons, Canadian life scientists, and Nort American biodefence. University of Toronto Press, Toronto"},{"key":"2014_CR111","volume-title":"Biological war","author":"SK Prasard","year":"2009","unstructured":"Prasard SK (2009) Biological war. Discovery Publishing House Pvt Ltd, New Delhi"},{"key":"2014_CR112","volume-title":"Banting\u2014A biography","author":"M Bliss","year":"1992","unstructured":"Bliss M (1992) Banting\u2014A biography. University of Toronto Press, Toronto"},{"unstructured":"Waller J (2002) Fabulous Science. In: Fact and Fiction in the history of scientific discovery. Oxford University Press, Oxford","key":"2014_CR113"},{"key":"2014_CR114","first-page":"554","volume":"56","author":"M Bliss","year":"1982","unstructured":"Bliss M (1982) Banting\u2019s, Best\u2019s and Collip\u2019s account of the discovery of insulin. Bull Hist Med 56:554\u2013568","journal-title":"Bull Hist Med"},{"key":"2014_CR115","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1093\/jhmas\/48.3.253","volume":"48","author":"M Bliss","year":"1993","unstructured":"Bliss M (1993) Rewriting medical history: Charles Best and the Banting and Best myth. J Hist Med Allied Sci 48:253\u2013274","journal-title":"J Hist Med Allied Sci"},{"key":"2014_CR116","volume-title":"Writing history: a professor\u2019s life","author":"M Bliss","year":"2011","unstructured":"Bliss M (2011) Writing history: a professor\u2019s life. Dundur Press, Toronto"},{"key":"2014_CR117","first-page":"1","volume":"43","author":"M Bliss","year":"2013","unstructured":"Bliss M (2013) The eclipse and rehabilitation of JJR Macleod, Scotland\u2019s insulin laureate. J R Coll Phys Edinb 43:1\u20137","journal-title":"J R Coll Phys Edinb"}],"container-title":["Acta Diabetologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00592-022-02014-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00592-022-02014-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00592-022-02014-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T20:05:07Z","timestamp":1701633907000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00592-022-02014-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,31]]},"references-count":117,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["2014"],"URL":"https:\/\/doi.org\/10.1007\/s00592-022-02014-7","relation":{},"ISSN":["1432-5233"],"issn-type":[{"type":"electronic","value":"1432-5233"}],"subject":[],"published":{"date-parts":[[2022,12,31]]},"assertion":[{"value":"2 October 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal and human rights consent statements are not required, due to the historiographical character of this research.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights disclosure"}},{"value":"The authors declare that they have no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}