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 experiments established 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 a normal 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 eight ounces 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 they were 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.