Three months study of the influence of the anti-diabetic substance on a case of severe diabetes

Aims 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. Methods We have analyzed the experimental procedures and determination of biological parameters used by researchers during the investigated period (1906–1923): 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-Universität (Berlin, DE), Geheimarchiv des Preuβischen Staates (Berlin, DE); Landesamt für Bürger—und Ordnungsangelegenheiten (LABO) (Berlin, DE); Arhivele Academiei Române şi Universitǎții Carol Davila (Bucharest, RO). Main results and conclusions A) The European researchers Zülzer (Z Exp Path Ther 23:307–318, 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 & 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.

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“…Only in this latter case could glycosuria and ketonuria be decreased. On July 26, 1922 blood glucose level went down from 513 to 241 mg/dL [33].…”

Section: John R Murlin (1874-1960)mentioning

confidence: 98%

On the occasion of the centennial of insulin therapy (1922–2022), II-Organotherapy of diabetes mellitus (1906–1923): Acomatol. Pancreina. Insulin.

Leiva-Hidalgo

Leiva-Pérez²

2022

Acta Diabetol

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“…In the years after Joseph von Mering's and Oskar Minowski's successful pancreatectomy experiments in dogs, which resulted in severe and fatal diabetes mellitus, several other groups subsequently experimented with injections and infusions of pancreatic extracts and emulsions in healthy and depancreatized animals demonstrating blood glucoselowering properties of these substances (Forschbach 1909, Scott 1912, Murlin & Kramer 1913, Kleiner & Meltzer 1915, Kleiner 1919, Gibbs et al 1922, Sutter & Murlin 1922). Most of these attempts failed because of the ineffectivity of the extracts or their unclear composition which caused severe side effects or, in some cases, probably hypoglycemic effects, which were not yet known in their symptomatology.…”

Section: Insulinmentioning

confidence: 99%

One hundred years after the discovery of insulin and glucagon: the history of tumors and hyperplasias that hypersecrete these hormones

Herder

Klöppel

2023

Endocrine-Related Cancer

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One century ago, in 1922, Frederick G. Banting, Charles H. Best, James B. Collip and John J.R. Macleod first published their experiments resulting in the isolation of a hypoglycemic factor, named insulin, from a solution extract from a dog’s pancreas. One year later, in 1923, a hyperglycemic factor named glucagon was isolated by Charles P. Kimball and John R. Murlin. In the following years it could be demonstrated that pancreatic islet alpha- and beta-cell neoplasms and hyperplasias could inappropriately secrete excessive amounts of these two hormones. This review is a sequel to the discovery of insulin and glucagon and introduces the history of this fascinating group of neuroendocrine neoplasms and hyperplasias of the pancreas.

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“…The famed nutritionist John Raymond Murlin (1874Murlin ( -1960 (59) with Benjamin Kramer at the laboratory of Physiology at Cornell University described in 1913 pancreatic extracts that were effective in decreasing both glycosuria and hyperglycemia in pancreatectomized dogs (60). After a long gap in investigating pancreatic extracts, in 1922, Murlin, then Professor of Physiology at Rochester University, did some trials on diabetic patients with initial failure due to toxic side effects but later claimed some success (61). In 1923, he discovered glucagon (62).…”

Section: The Main Breakthrough: the 19 Th Centurymentioning

confidence: 99%

Insulin: A 100-Year-Old Discovery With a Fascinating History

Rostène

Meyts

2021

Endocrine Reviews

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Diabetes has been known since antiquity. We present here a historical perspective on the concepts and ideas regarding the physiopathology of the disease, on the progressive focus on the pancreas, in particular on the islets discovered by Langerhans in 1869, leading to the iconic experiment of Minkowski and von Mering in 1889 showing that pancreatectomy in a dog induced polyuria and diabetes mellitus. Subsequently, multiple investigators searched for the active substance of the pancreas and some managed to produce extracts that lowered blood glucose and decreased polyuria in pancreatectomized dogs, but were too toxic to be administered to patients. The breakthrough came 100 years ago when the team of Frederick Banting, Charles Best and James Collip working in the Department of Physiology headed by John Macleod at the University of Toronto managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available. This achievement was quickly recognized by the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923. At 32, Banting remains the youngest awardee of this Prize. Here we discuss the work that led to the discovery and its main breakthroughs, the human characters involved in an increasingly dysfunctional relationship, the controversies that followed the Nobel Prize, and the debate as to who actually “discovered” insulin. We also discuss the early commercial development and progress in insulin crystallization in the decade or so following the Nobel Prize.

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Three months study of the influence of the anti-diabetic substance on a case of severe diabetes

Cited by 12 publications

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On the occasion of the centennial of insulin therapy (1922–2022), II-Organotherapy of diabetes mellitus (1906–1923): Acomatol. Pancreina. Insulin.

On the occasion of the centennial of insulin therapy (1922–2022), II-Organotherapy of diabetes mellitus (1906–1923): Acomatol. Pancreina. Insulin.

One hundred years after the discovery of insulin and glucagon: the history of tumors and hyperplasias that hypersecrete these hormones

Insulin: A 100-Year-Old Discovery With a Fascinating History

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