INTRODUCTION
When the scientific body that awards the Nobel prize each year met to consider the award for 1923, there was no question or debate as to the discovery that merited the honor. The prize was granted to Doctors F. G. Banting and J. J. R. MacLeod of Toronto for their work in the discovery of insulin, and each immediately donated one-half the award to colleagues who had shared in this discovery, Doctors C. H. Best and J. B. Collip.
In November, 1920, Dr. Banting, who had returned from war service, was practicing medicine in London, Ontario, and was demonstrating physiology in the medical school of Western University at that place. While reading an article in a surgical magazine, he chanced on a sentence which aroused the train of thought that finally led to his discovery of insulin—a substance that means a longer and more satisfactory life to diabetics.
The article which he read concerned a gland, known as the pancreas, that lies close to the stomach and the upper part of the intestines.This gland is composed of two portions, one of which creates a juice poured into the intestine, which aids in the digestion of food; it is the external secretion and it contains trypsin and two other digestive ferments. The pancreas contains also certain cells which, when seen through the microscope, are marked off from the remaining tissue and which are known by the peculiar name “Islands of Langerhans,” the latter being the name of their discoverer.
Diabetes centuries old.—Now diabetes is no new disease.
It was described by Aretaeus, a Greek who lived in the third century, A.D., and hundreds of scientists have worked steadily on the problem ever since that time. Indeed the history of the discovery of insulin is typical of all great medical discoveries of modern times. It represents the summation of a vast amount of knowledge contributed bit by bit by scientists all over the world. When Banting conceived his idea, he took it to Dr. MacLeod, director of physiologic research in the University of Toronto. Professor MacLeod, seeing the possibilities in the investigation, gave him opportunity to work, and provided him with a young assistant, Dr. C. H. Best. The particular problem on which they were to work was the extractionfrom the pancreas of another secretion, an internal secretion, not poured by the pancreas through a special duct into any other organ or to the exterior, but going instead into the blood stream.
Pancreas yields substance.—Previous investigations had indicated that this secretion was manufactured in the Islands of Langerhans. It was known that when the tube which carries the external secretion—trypsin—was tied, the trypsin would back up into the pancreas, and by its digestive action would destroy the glandular tissue, leaving an organ which consisted chiefly of island tissue.
The investigators did such an operation on a dog. It was also known that an animal might be made diabetic by removing the pancreas; this operation was performed on another dog. Then, when sufficient time had elapsed to permit the breaking down of the pancreas in the first animal, it was painlessly chloroformed, the pancreas removed and an extract made from it. The extract consisted chiefly of island tissue, and this extract was injected into the diabetic dog. The result was the discovery that such injections produced a lower amount of sugar in the dog’s blood and in its urine. This and similar experimentsestablished positively the fact that there was present within the pancreas, and quite certainly in the island tissue chiefly, some substance, not available in the body of the diabetic, which was capable of meeting a deficiency and aiding the diabetic to make proper use of sugar.
Drug dosage and animal experiments.—It now became necessary to devise a method of obtaining the extract in such form as to permit injections into the human being without danger from poisoning by extraneous and unnecessary substances, in other words, a pure product. It also became necessary to devise a method for measuring the dose to be given. How many persons who receive a dose of a medicine realize the amount of investigation necessary to determine these factors? It is necessary to test the effects of a drug on animals before it can be tried on the human being, and it is necessary to study very carefully the changes in the body following the administration of the drug, in order to be certain that no undesirable actions occur.
The Canadian investigators worked in a wholly scientific manner. Their experiments show great attention to the matter of controls. For each animal that was tested, there was anormal animal with which to compare it. The investigators used many dogs, and a vast number of rabbits in making these necessary tests. Not until all the factors of danger had been thoroughly controlled was the drug administered to man. Had it been given without the guiding knowledge obtained by the observations on rabbits, it seems certain that overdoses might have been administered and patients have died.
Overdose of insulin dangerous.—The effects of an overdose of insulin are striking; there is too great a lowering of the amount of sugar, and severe convulsions ensue which may lead to death. Insulin is a powerful remedy; its effects are certain and accurately measurable. If a human being is given too much, his blood sugar falls to a lower concentration. When he gets it around 0.07 per cent he begins to be anxious and nervous about himself. He is likely to become pale, or to flush and perspire profusely. If the blood sugar concentration goes still lower his speech may become disturbed, and he may even manifest mental disturbances. These things too may be prevented, and immediately stopped once they have ensued, by the giving of a small amount of sugar, as for example in the form of four to eightounces of orange juice. These facts also were discovered by properly conducted experiments.
The investigators now turned their attention to the problem of this disease in human beings, and the results have already been broadcasted through medical periodicals, newspapers and magazines. They are far beyond the early hopes of scientific investigators of the disease. In that terminal stage of diabetes known as coma, when the patient sinks into unconsciousness, insulin seems actually to restore life. Of far greater importance, it offers for the vast majority of diabetics comfort and extended existence. Its administration is closely bound with a knowledge of the food taken into the body, for it is known that a certain amount of insulin will aid the body in handling a certain amount of sugar. When the physician decides to place his patient on the insulin treatment, he usually asks that the patient come into a hospital so that he may first find out the patient’s normal ability to digest sugar, and it is this ability that the physician supplements by the giving of insulin.
Manufacture and sale.—One of the unusual aspects of the insulin discovery was the method of control in its sale. The discoverers did not wish to profit unduly by their work, but theywere anxious that its manufacture and application on a large scale be scientifically controlled. Arrangements were therefore made to have it manufactured under accurate supervision in the United States by the Eli Lilly Company, and in Canada by the Connaught Laboratories, and more recently in certain other home and foreign laboratories.
The process of manufacture is an interesting one. The Islands of Langerhans constitute a small portion of what is relatively a small gland. In stock yards and packing houses this gland is called sweet breads; the sweet breads served under glass in the restaurants are usually the pancreas of the sheep or hog, since these are small. The beef pancreas is a much larger organ, weighing about a pound or a pound and a half.
The method devised by Collip for obtaining insulin from the pancreas involves repeated extraction of the ground-up pancreas with alcohol, in order to remove the unnecessary tissue substances. When this is done on a small scale in the chemical laboratory, there is, of course, considerable wastage of raw material and of substances used in the extraction.
The application of the matter on a commercial scale involved additional problems. They were not only overcome successfully, but continued improvements have made possible the provision of the life-saving remedy at a reasonable price.
Juvenile diabetes.—One of the most striking effects of the work was the result of the use of the remedy in the diabetes of children, or juvenile diabetics. This condition had previously been considered invariably fatal. Now the child may be treated satisfactorily, and it seems possible that its development under the influence of the drug may permit a gradual lowering of the dosage to amounts that may be administered with little expense or difficulty.
After the investigators had completed the trials of the preparation in their own hospital, plans were made for extensive clinical investigation in other institutions in which there were men capable of conducting scientific studies on diabetes. More than 50 institutions were utilized in order to give the drug the most complete possible scientific trial before offering it to the medical profession in general; and when at last these trials were completed and the co-operating manufacturing concernshad fully developed the machinery for production of the drug on a large scale, it was released to the medical profession throughout the world.
Patients must do their part.—It should be understood that if the patient is to receive the greatest benefit from this new remedy, he must co-operate fully and intelligently with his physician. As soon as he discovers through competent examination that he is excreting sugar in his urine, he should consult his physician as to the use of the drug and a proper diet.
In many instances, the use of insulin is unnecessary because the patient is able to live satisfactorily without insulin on a diet with the proper amount of sugar or carbohydrate material. In other instances, the dosage of insulin may be very small, but this will depend on a careful and intelligent study of each case.
It is now rather generally known by the public that insulin is a preparation which is administered hypodermically, that is, injected with a needle under the skin. It cannot be taken by mouth, because the substance is digested before it can be absorbed into the blood. This does not mean that the patient must seek his physician for every treatment, becausemany competent specialists in the treatment of this disease have found that patients may be taught to regulate their diet and use the drug intelligently.
Recognition of the work.—As soon as it became known that this discovery was available, diabetics flocked to their physicians and began to inquire as to the possibilities of its use to “cure” the disease; but the drug is not in the usual sense of the word a “cure” for diabetes. Diabetes represents the absence from the body, probably as the result of disease, of certain substances which are responsible for the control of the digestion and use of sugar, and insulin cannot restore these tissues or substances any more than the injections of other glands can restore youth to the aged. It can only replace temporarily the substances that are absent; but in the case of a diabetic, this constitutes the difference between life and death.
Naturally Doctors Banting, Best, Collip and MacLeod have received great honors at the hands of their colleagues and of the world. The Canadian government has granted to Dr. Banting the sum of $7,500 per year for life; the Ontario government has provided $10,000 a year for a chair of medical research, now heldfor the first time by Dr. Banting; learned societies throughout the world have greeted him with the applause usually accorded only to military heroes.
The victor in the conflict of science with disease is certainly deserving of the wreath of the conqueror.
MORRIS FISHBEIN.