Presentation Speech by Professor J. Sjöquist, member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute, on December 10, 1923

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

The Professorial Staff of the Caroline Institute has resolved to award to Dr. Frederick Grant Banting and Professor John James Richard Macleod the Nobel Prize for 1923 in Physiology or Medicine for the discovery of insulin.

Although the disease which has received the name of «diabetes mellitus» has evidently been known from immemorial time – Celsus and Araeteus in their writings in the first century of our era described an illness which was characterized by an enormous secretion of urine, an unquenchable thirst and a considerable loss of flesh – it was not until the seventeenth century that the Englishman Thomas Willis made the important observation that the urine in this illness contains a sugar-like substance; and it was not until more than a hundred years later that his countryman Dobson was able to produce from such urine the kind of sugar in question. This discovery, it is true, led the study of the mysterious disease into the right paths; but nevertheless it was a long time before any real progress was made. At the time the sugar was regarded as being a substance foreign to the animal organism, which was formed only under diseased conditions. It is true that the observation by Tidemann and Gmelin in 1827, that starchy foods are under normal conditions transformed into sugar in the intestinal canal and that this is absorbed by the blood, marks an important advance; but really epoch-making was the discovery of the great French physiologist Claude Bernard in 1857 that the liver is an organ that contains a starch-like substance, glycogen, from which sugar is constantly being formed during life; in the words of Claude Bernard, the liver secretes sugar into the blood.

In connection with his investigations into the circumstances that affect the formation of sugar, Claude Bernard observed that in certain lesions of the nervous system the sugar content of the blood was increased and that the sugar passed into the urine of the animals in the experiments. For the first time, therefore, an appearance of sugar in the urine – a glycosuria, though of a transitory nature – was experimentally produced; and consequently this discovery by Claude Bernard may be characterized as the starting-point of a series of experimental researches into the causes and nature of diabetes.

Even before this, however, in the post-mortem examination of persons who had died of severe diabetes, pathologists had made the observation that the pancreas sometimes exhibits diseased changes. The attention of Claude Bernard was directed to this point, but he did not succeed in producing glycosuria by ligation of the duct which leads the secretion of the gland to the bowel or by injecting coagulating substances into it; the removal of the whole gland by operation he regarded as technically impracticable.

Hence it aroused an intense interest when in 1889 two German investigators, von Mering and Minkowski, succeeded in carrying out this operation on dogs. It was still more remarkable that the animals thus operated on, now not only excreted sugar in the urine but also became the victims of a lasting disease which in all essentials resembled the most acute form of diabetes in man, even to such an extent that the content of sugar in the blood rose above the normal and that the disease inevitably led to death with symptoms of poisoning. If a part of the gland was left behind or if a bit of it was sewn under the skin, diabetes failed to develop.

It thus became clear that the disturbance in the sugar economy of the body that appeared after the complete removal of the gland could not well be due to the failure of the pancreatic juice to pass into the bowel, but rather to the loss of some other function of the gland.

During the eighteen-eighties, above all through the investigations of the Frenchman Brown-Séquard, attention had been directed to the importance for the vital functions of certain ductless gland-like organs. Time permits me in this place only to point out that, according to the view now generally entertained, these glands exercise their effect through passing into the blood and tissue juices of certain chemically effective substances, which are called by the general name of hormones; the glands themselves, owing to the fact that they have no ducts, are called endocrine glands or glands with internal secretion. As regards the pancreas itself, it is true that it is a secreting gland, which by means of a duct pours secretion of the gland into the intestinal canal, where that secretion has certain important functions to perform in the process of digestion; but, as Langerhans showed as long ago as 1869, the pancreas also contains anatomical formations which have no direct connection with the duct, and which, after their discoverer are called «the cell islets of Langerhans» or «insulae». In the beginning of the eighteen-nineties Laguesse expressed the surmise that it was just these cell islets that produce the inner secretion which is so important for the combustion of sugar.

Ever since the discovery by von Mering and Minkowski of the importance of the pancreas for the sugar economy of the organism and evidently also for the development of diabetes – that is to say, for more than a third of a century – a large number of investigations in different countries have devoted a great deal of work to discovering a remedy for diabetes from the pancreatic gland. It was natural to imagine, of course, that that disease was caused by the loss of power of the pancreatic gland to produce a hormone or to produce it in sufficient quantities, and that the introduction of this hormone in the diseased organism ought to be able to exercise a favourable influence on the disease, all the more as analogous conditions were well known with regard to other organs with internal secretion, especially the thyroid gland. Many of these investigations failed, while others succeeded in actually producing extracts or juices which, when injected into the blood of diabetic dogs and even human beings, showed themselves able to bring down the increased content of sugar in the blood, to diminish or even to stop altogether the excretion of sugar into the urine, and to bring about an increase in weight. Amongst these I should like especially to mention Zuelzer, who in 1908 produced an extract which was undoubtedly effective, but which also showed injurious by-effects – consequently it could not be used to any great extent therapeutically – and also Forschbach, Scott, Murlin, Kleiner, Paulesco, and many others.

The problem was in about this position when a young assistant in physiology at the Western University in London, Ontario, Frederick G. Banting, conceived an idea that was to prove of extraordinary importance for its further development. He thought to himself that the reason for the failure to produce effective pancreatic extract, was to be sought in an antagonistic or destructive effect on the hypothetical hormone of trypsin, the protein-splitting enzyme that is produced by the secreting cells of the gland, and that there would be a greater prospect of success if these cells were destroyed by ligation of the duct of the gland and the remaining part of the gland were then used as the original material. It had previously been observed by Schulze and by Ssobolev that the ligation of the duct involved the atrophy of the acini but not of insulae. He imparted his idea to Professor Macleod of Toronto after which, together with several fellow-workers, among whom I should like especially to mention Best and Collip, he began to work under Macleod’s guidance and in his laboratory in May 1921. The very first experiments in diabetic dogs were crowned with success. After the method of producing the effective extract, which at the suggestion of Sir Sharpley Schafer had been called insulin, had been improved by Collip, and after its effect on the sugar content of the blood, on the respiratory quotient, and on the capacity of the liver for forming glycogen had been established, and also the dangers which might be produced by an overdose of the remedy through an excessive reduction of the sugar content of the blood had been determined by experiments on animals under Macleod’s guidance, and after it had further been proved that the trypsin in an alkaline solution really destroys the hormone, the first injection of insulin was made in a youth of fourteen years, who suffered severely from diabetes, on 23 January and the following days in 1922. The result was that the sugar content of the blood of the patient fell to the normal, the passing of sugar into the urine was reduced to a minimum, and the general state of poisoning, acidosis, which is caused by certain injurious substances which are formed in this kind of diabetes mainly through disturbance in the fat metabolism, often in great quantities, was checked. Since then the new remedy, the production of which does not offer any great technical difficulties, has come into use in practically all countries and with favourable results.

We must not imagine that insulin is able to cure diabetes. How could that be possible if the cause of diabetes is to be found in the fact that the cells within our organism that produce the hormone necessary for the combustion of sugar are definitively destroyed? But insulin gives us the possibility of transforming the severe form to a milder one and thereby of restoring his capacity for work and a comparative state of health to the hopeless invalid who, despite the most trying and rigorous restrictions in diet, is constantly threatened by a fatal state of poisoning. Most striking is the effect of insulin in the cases in which the state of poisoning has already passed into that of diabetic coma, against which we have hitherto been helpless and which, before the days of insulin, inevitably led to death.

It could be prophesied with a very great degree of probability that such a substance as insulin some day would be produced from the pancreatic gland, and much of the work had been done beforehand by previous investigations, several of whom very nearly reached the goal. Consequently it also has been said that its discoverer was in a preeminent degree favoured by lucky circumstances. Even if this be so, yet there would seem to be cause to remember Pasteur’s words: «La chance ne favorise que l’intelligence préparée.»

The Professorial Staff of the Caroline Institute has considered the work of Banting and Macleod to be of such importance, theoretically and practically, that it has resolved to award them the great distinction of the Nobel Prize. Doctor Banting and Professor Macleod not having the opportunity of being present today, I have the honour of asking the British Minister to accept from His Majesty the King the prize, and to transfer it to the Laureates, together with the congratulations of the Professorial Staff of the Royal Caroline Institute.