I-European research, the cradle of the discovery of the antidiabetic hormone: the pioneer roles and the relevance of Oskar Minkowski and Eugène Gley

Abstract

Aims: The introduction of hormonal treatment in severe diabetes in 1922 represented a clinical and social impact similar to that of antibiotic therapy. In October 1923, the Assembly of the Karolinska Institute decided to award the Nobel Prize in Physiology or Medicine to the Canadian Frederick Grant Banting and the Scottish John James Rickard Macleod, researchers at the University of Toronto (UT), for "the discovery of insulin a year before". A few weeks later, European and American researchers protested the decision. The controversy remains to this day.

Methods: We have conducted a comprehensive review of primary and critical sources focused on the organotherapy of animal and human diabetes mellitus since 1889, when Oskar Minkowski demonstrated the induction of experimental diabetes by total pancreatectomy in the dog, until the spring of 1923, when the Nobel Foundation had already received all the nominations for the award in Physiology or Medicine.

Results: The in-depth analysis of all these sources revealed that Europe was the cradle of the discovery of the antidiabetic hormone. The discovery involved multiple research steps headed by a long list of key investigators, mainly European.

Conclusion: Marcel Eugène Émile Gley was the first to demonstrate the presence of the "antidiabetic principle" in extracts from "sclerosed" pancreas. The French physiologist pioneered the successful reduction of glycosuria and diabetic symptoms by the parenteral administration of pancreatic extracts to depancreatized dogs in experiments developed between 1890 and 1905, antedating insulin in two decades.

Keywords: Antidiabetic hormone; Diabetes; Organotherapy; Pancreatectomy; Pancreatic extracts.

Fig. 1

Left image: F.G. Wirsüng (1642). Original copperplate exhibited in the Palazzo del Bò, Padua (Edizione Universitarie Patavine, Padua) [1]. Right image: Illustration of the pancreatic-duodenal area. Henry Gray (1918) Anatomy of the Human Body, Fig. 1100. Provo, Utah. Brigham Young University: Lea & Fibiger; p. 1202. Internet Archives. https://www.bartleby.com/107/illus1100.html

Fig. 2

Bernard C (1856): “Mémoire sur le pancréas et sur le rôle du suc pancréatique dans les phénomènes digestifs”. First edition. Published in vol I of Supplement aux Comptes Rendus, pp 379–563. Selected plates [5]

Fig. 3

Claude Bernard. Oil painting by Charles Auguste Mengin (1870). (Internet Archives). Leçons sur le diabète et la glycogenèse animale. Sacarimeter used by Bernard (1877) [19]

Fig. 4

Photograph, Paul Langerhans (unknown author and date). Dissertation. University of Berlin, 1869 [23] [1]

Fig. 5

Étienne Lancereaux. Author and date unknown. The National Library of Medicine. Plate depicting atrophy of the pancreas in a case of severe diabetes [29]

Fig. 6

In 1889 Oskar Minkowski, with help from Joseph von Mering, discovered that diabetes is a pancreatic disease [39]

Fig. 7

Left: Portrait of Oskar Minkowski. Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie Collection BIU Santé-Licence ouverte. Unknown author. Right: Minkowski O (1893) Untersuchungen über den Diabetes mellitus nach Exstirpation des Pankreas. Leizpig: F.C.W. Vogel [42]

Fig. 8

Picture of Lydia Maria Adams DeWitt. Unknown Author and Unknown Date. (Internet Archives). Dissection of the pancreas of the cat clearly reveals the ductal system and its relationship to the venous system (DeWitt, 1906) [46]

Fig. 9

Portrait of Eugene L. Opie. Images from the History of Medicine (IHM). National Library of Medicine (NLM Image ID: B020236. http://resource.nlm.nih.gov/101424810 [1]. Drawing of the islands of Langerhans cells partly transformed into hyaline material (Opie, 1903) [52]

Fig. 10

Emmanuel Hédon. Photograph of P. Sollelliano (Collection BIU Santé Medecine, Université de Paris). In 1891 he described his original technique of complete pancreatectomy of the dog, performed in two operative stages [53]

Fig. 11

Eugène Gley. For many years he collaborated with the Société de Biologie (Paris) and its journal, C.R. Soc. Biol. Wellcome Collection Library, London, reference 127,961. Probable date: 1925

Fig. 12

Gley’s treatise “The Internal Secretions (their Physiology and applications to Pathology)”, translated into English in 1917 by Maurice Fishberg, professor at New York University, has been described as being of historical interest. The photograph of the French professor comes from the Institute of Physiology of the University of Barcelona [1]. Probable date: 1919

Fig. 13

E. Gley published in 1900 series of experiments performed in his laboratory since 1892 describing in detail the metabolic actions of the pancreatic extract [“Diabète Pancreatique Expérimental: Essais de Traitement”] [79]

Fig. 14

E. Gley: Detail, enlarged, of the text of the sealed letter "Sur la sécrétion interne du pancréas et son utilisation thérapeutique" (1905). Gley's photograph, date unknown, is from the Wellcome Collection Library (date unknown; author, Lafayette Ltd., public domain)