Essential Contributions of Pathologists and Laboratory Physicians Leading to the Discovery of Insulin.

CONTEXT.— Frederick Banting, Charles Best, J. Bertrand Collip, and J. J. R. Macleod contributed to the discovery of insulin in 1921-1922. Recent advances in anatomic pathology, experimental pathology, and clinical pathology were necessary for the research in Toronto, Ontario, Canada, to begin and to succeed. OBJECTIVE.— To explore the role of pathology and laboratory medicine in laying the foundation for the discovery of insulin. DESIGN.— Available primary and secondary historical sources were reviewed. RESULTS.— During a 3-decade period, pathologists, through autopsy pathology and experimental animal studies, were able to provide solid evidence that the pancreatic islets were the source of the internal secretion responsible for proper carbohydrate metabolism. Banting, a surgeon with no previous research experience, read about these studies in a case report with an extensive literature review by pathologist Moses Barron; this piqued Banting's interest and caused him to approach Macleod, a Toronto physiology professor, with an idea that initiated the research. Advances in clinical laboratory medicine, which allowed them to measure blood glucose levels using small blood volumes, were critical to their success. CONCLUSIONS.— By 1921-1922, the pieces necessary to solve the puzzle were available. The primary reason that the time was ripe for the discovery was because of the contributions of pathologists and laboratory physicians in the preceding 3 decades. As the 100th anniversary approaches, our profession can take pride in its important contributions to the discovery of insulin, which is broadly recognized as one of the most important medical research advances of the 20th century.

[1]  James R. Wright The Politics Underlying the Provision of and Changes in Pathology and Laboratory Services in the United States During the Roaring Twenties. , 2016, Archives of pathology & laboratory medicine.

[2]  D. Baskin A Historical Perspective on the Identification of Cell Types in Pancreatic Islets of Langerhans by Staining and Histochemical Techniques , 2015, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[3]  R. Tattersall The History of Diabetes Mellitus , 2010 .

[4]  M. Lane The Cytological Characters of the Areas of Langerhans , 2009 .

[5]  James R. Wright Almost famous: E. Clark Noble, the common thread in the discovery of insulin and vinblastine. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[6]  James R. Wright From ugly fish to conquer death: J J R Macleod's fish insulin research, 1922–24 , 2002, The Lancet.

[7]  I. Kleiner Hypoglycemic agents; past and present. , 1959, Clinical chemistry.

[8]  E. Opie The peripatetic education of a pathologist. , 1957, The Medical clinics of North America.

[9]  I. Kleiner THE ACTION OF INTRAVENOUS INJECTIONS OF PANCREAS EMULSIONS IN EXPERIMENTAL DIABETES , 1919 .

[10]  V. C. Myers,et al.  THE LEWIS AND BENEDICT METHOD FOR THE ESTIMATION OF BLOOD SUGAR, WITH SOME OBSERVATIONS OBTAINED IN DISEASE , 1916 .

[11]  J. Homans A Study of experimental Diabetes in the Canine and its Relation to Human Diabetes. , 1915, The Journal of medical research.

[12]  S. Meltzer,et al.  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. , 1915, Proceedings of the National Academy of Sciences of the United States of America.

[13]  N. W. Janney,et al.  THE METABOLIC RELATIONSHIP OF THE PROTEINS TO GLUCOSE III. GLUCOSE FORMATION FROM HUMAN PROTEINS , 1915 .

[14]  S. Meltzer,et al.  The influence of depancreatization upon the state of glycemia following the intravenous injection of dextrose in dogs , 1914 .

[15]  J. Homans Degeneration of the Islands of Langerhans associated with experimental Diabetes in the Cat. , 1914, The Journal of medical research.

[16]  S. R. Benedict,et al.  A method for the estimation of sugar in small quantities of blood , 1913 .

[17]  R. R. Bensley Studies on the pancreas of the guinea pig , 1911 .

[18]  R. Cecil ON HYPERTROPHY AND REGENERATION OF THE ISLANDS OF LANGERHANS , 1911, The Journal of experimental medicine.

[19]  S. R. Benedict A METHOD FOR THE ESTIMATION OF REDUCING SUGARS , 1911 .

[20]  J. Meakins,et al.  DATA CONCERNING THE ETIOLOGY AND PATHOLOGY OF HEMORRHAGIC NECROSIS OF THE PANCREAS (ACUTE HEMORRHAGIC PANCREATITIS) , 1909, The Journal of experimental medicine.

[21]  A. Rothera Note on the sodium nitro‐prusside reaction for acetone , 1908, The Journal of physiology.

[22]  W. G. Maccallum HYPERTROPHY OF THE ISLANDS OF LANGERHANS IN DIABETES MELLITUS , 1907 .

[23]  E. Joslin,et al.  Degeneration of the Islands of Langerhans of the Pancreas in Diabetes mellitus. , 1901, The Journal of medical research.

[24]  E. Opie THE RELATION OE DIABETES MELLITUS TO LESIONS OF THE PANCREAS. HYALINE DEGENERATION OF THE ISLANDS OE LANGERHANS , 1901, The Journal of experimental medicine.

[25]  E. Opie A CASE OF HAEMOCHROMATOSIS.-THE RELATION OF HAEMOCHROMATOSIS TO BRONZED DIABETES. , 1899 .

[26]  V. Schmidt Ivar Christian Bang (1869-1918), founder of modern clinical microchemistry. , 1986, Clinical chemistry.

[27]  C. N. Barron ECTOPIC PANCREAS IN THE DOG , 1959 .

[28]  A. Hartmann,et al.  THE IODOMETRIC DETERMINATION OF COPPER AND ITS USE IN SUGAR ANALYSIS II. METHODS FOR THE DETERMINATION OF REDUCING SUGARS IN BLOOD, URINE, MILK, AND OTHER SOLUTIONS , 1921 .

[29]  E. Opie The etiology of acute hemorrhagic pancreatitis , 1901 .