A Lecture on INSULIN: Delivered to a General Session of the Eleventh International Physiological Congress, Edinburgh
Authors: J. J. R. Macleod
Journal: BMJ (1923)

SPEAKING for my collaborators, as well as-myself, I wish to assure you that we consider it a very great honour that an account of our researches on insulin should be given so prominent a place on the programme of the XIth Inter- national Congress of Physiologists.In accepting the invita- tion to address you on this work,.fully realize the great responsibility that I have assumed, the more so since at the present time there yet remains so much that is obscure and unfinished, particularly with regard to the physiological aspects of the subject.There is no other problem in the whole vast field of medical science that has attracted such diverse groups of workers as that of the relationship between the pancreas and disturbances in carbohydrate metabolism.'Anatomists, pathologists, biochemists, physiologists, and physicianshave contributed much to it, each adding some new and funda- mental fact, and the knowledge thus acquired has formed the foundation upon which the present investigations depend.I shall not occupyyour time here with a review of this earlier work except in so far as it is essential to an understanding of its relationsliip to these investigations. HISTORICAL,Towards the end of the seventeenth century Brunner, in his celebrated researches on tho digs?tive functions of the pancreas, had occasion to remov tlie gland, and he descr-ibed symptoms in the operatedanimals whlich were without doubt thiose of diabetes.This was, however, some time before the disease had come to be recognized'as a clinical entity, and it was 'not until considerably later that physicians began to point out the frequeiit occurrence of morbid changes in the pancreas of'patienfAs wholhad died of it.'.-The clue which this observation offered suggested to experimentalists, among thenm Claude Bernard, the a'dvisability of seeing whether removal or destruction of the pancteas might cause diabetes.The experimentswei'e without-success until 1885, wheni vonI Mering and Minkowski announced their well known discovery, as a result of which Minkowski subse- quently published a complete account of the pathological chemistry of the diabetic condition' as observed in depan- created animals.As the cause of the diabetes Minkowski suggested the removal from the organism of "a something"' that is essential for the metabolism of carbohydrates.He clearly meant' an internal secretio,n, although it is in the writings of LeTpine that for the first time we find this term actually -used in connexion-with the paneleas.But the existence of an internal pancretict 'sec-retioe could 'not be considered as an established fact iuntil it 'could be shown that the administration of an extract of the gland to de- pancreated animals is capable of renmoving the diabetic symptoms, and this none of the investigators of this period could suieceed in doing.These failures led some to suppose that the pancreas must control the metabolism of carbo- hydrate otherwise than by an internal secretion, although the majority considered that it was merely owing to destruction of the active principle during tlie preparatiorJ of the extracts' that the failure to' obtain it in extracts was due, At the same time as these experimental investigations were in progress most valuabloe work *as being' done Oin tlle minute aiiatomy of the pancreas, particularly with regard to the islets of cells which had been described in 1869 by Langerhans as distinct and separate from the secreting acini.Among these workers I cannot refrain from paying tribute to Laguesse and Diamare and,, among 'FAULTY NUTRITION AND EPITHELIOMA CONTAGIOSUM.t fTzBrnu.~~~~~~~~~~~~~~~~~~~~~~~~~IBRILium