THE STORY OF INSULIN
Minkowski’s discovery.—The story of insulin began a generation ago with the discovery of German investigators, Minkowski and von Mehring. This was in 1889, and until then the relation of the pancreas to diabetes was scarcely suspected, and no one had an idea where to look for the means to check the disease. The pancreas is an organ about the size of one’s hand which pours digestive juices into the intestine.
Removal of pancreas causes diabetes.—Minkowski was studying digestion and it happened in the course of certain investigations, that it became necessary to operate on a dog and remove this organ. A few days later it was noticed that flies were attracted in great numbers by the urine of this dog. The urine was examined, and the reason for the flies andthe relation of the pancreas to diabetes was at once apparent. The urine contained sugar. Another animal was operated on, the pancreas removed and diabetes followed. Cats, swine, and frogs were then experimented with. In every case, complete removal of the pancreas resulted in severe diabetes, while partial removal caused a more chronic and milder diabetes.
The islands of Langerhans.—Previously, in 1869, Paul Langerhans, described peculiar clumps or islands of cells which differ in appearance from the bulk of the tissue in the pancreas. In 1890, Scobolew and Schulze showed that if the ducts leading from the pancreas were tied off, the islands withstood the destruction that was wrought in the rest of the organ by backing up of the pancreatic secretions. Animals treated in this manner did not develop diabetes, and it was concluded, therefore, that it was the islands that manufactured the anti-diabetic material of the pancreas. The name “insulin” was suggested for this material in 1916 by an Englishman, Shafer.
Previous attempts to obtain insulin.—In the meantime, efforts were being made by numerous scientists to extract from the pancreas the anti-diabetic principle. Some of these attempts nearly succeeded. Many of them failed becauseit was not known then that insulin is rendered inactive when it is given by mouth and subjected to the disintegrating action of the juices in the digestive tract. Innumerable attempts were made to control diabetes by feeding either fresh pancreas, or pills and pellets manufactured from the pancreas. Thus far, all such efforts have been in vain, and yet various drug companies continue to sell pancreatic pills as diabetic remedies. The results obtained by grafting pieces of pancreas into dogs previously made diabetic by the removal of the pancreas have been more successful. The experimental diabetes of animals so treated can be controlled, but such procedures offer nothing to mankind, because grafts made from a lower animal to man invariably atrophy, that is, shrink up and disappear.
Banting’s idea.—Thus the subject stood when, in the autumn of 1920, Frederick Banting, recently home from the war, began his work. The idea came, he writes, while reading an article dealing with the relation of the islands of Langerhans to diabetes. In his own words, it was this: “From the passage in this article, which gives a resumé of degenerative changes in the acini (cells connected with the ducts or passageway system) of the pancreasfollowing ligation of the ducts, the idea presented itself that since the acinous, but not the islet tissue, degenerates after this operation, advantage might be taken of this fact to prepare an active extract of islet tissue. The subsidiary hypothesis was that trypsinogen (one of the digestive ferments prepared by the acinous cells) or its derivatives was antagonistic to the internal secretion of the gland. The failures of other investigators in this much worked field were thus accounted for.” In other words, the failure of his predecessors, Banting thought, was due to the probability that the digestive juices of the pancreas destroyed insulin before it could be extracted from the islands, and his plan was to circumvent this difficulty by first destroying the part of the pancreas concerned in making these juices.
The first insulin.—Banting took his idea to Professor Macleod of the University of Toronto. He received encouragement and facilities for work, and in the laboratory of Professor Macleod, with the skilled assistance of Mr. C. H. Best, he put the idea to the test, and it worked. Dogs made diabetic by removing their pancreas were treated with material obtained from degenerated pancreas, and could be kept alive. The sugar in their blood decreased each timethis material was injected beneath the skin and the sugar in their urines diminished. This was the first insulin. The next step was taken soon after. Banting and Best knew from the work of their predecessors that the pancreas of animals in the womb, that is, of embryos or fetuses, show island tissue some time in their development before the tissue responsible for the digestive juices is fully formed. It occurred to them, therefore, that they could circumvent the destructive action of the juices by making insulin from embryo calves. This was tried, and it succeeded. Enough insulin was obtained to try on a patient. Later developments permitted the preparation of insulin from adult animals. Swine and beef pancreas from the slaughter house became the source of insulin. At first these preparations contained some protein which made it poisonous, and unsuitable for use in patients. Another chemist in the University of Toronto, Professor J. B. Collip, overcame this difficulty, and, with the co-operation of a group of able physicians in the university, Doctors Graham, Campbell and Fletcher, the new insulin was used on a large group of patients, and its value thus became definitely established.
Insulin now available for everyone.—Insulin can now be obtained in every drug store andfortunately, thanks to wise provisions for maintaining control of its manufacture arranged for by the University of Toronto, it is everywhere of uniform strength. This matter of constant strength is of the greatest importance. As will appear later, danger attends its indiscriminate use, and the dose must be made to match the amount of sugar derivable from the diet. Unless the strength of various lots of insulin is constant, accurate treatment would be impossible. This was recognized early by the workers in Toronto and, to protect the public, it was decided that insulin must be patented so that its manufacture could be restricted to those firms who would permit the control of their products by an insulin committee in Toronto. The firm of Eli Lilly and Company of Indianapolis put their plant at the disposal of the insulin committee and assisted in developing methods of large scale production. Subsequently, other firms have been licensed, by the insulin committee, to make insulin.
The patenting of discoveries by physicians is usually frowned on by physicians. It is opposed to the ethical code of the profession. The patenting of insulin, however, does not violate this ethical code because the patent, while secured in the name of Doctor Bantingand his associates, was given outright by them to the University of Toronto to be used, not for any commercial advantage, but as a means to guarantee that this splendid discovery would not be exploited by others to its discredit.
Insulin described.—Today, insulin, as sold, is a clear, watery solution. A small vial contains 50, 100 or 200 units, as indicated on the label. The strength of the unit is standard. A unit of insulin will have a certain definite lowering effect on the sugar in the blood of a normal animal. The rabbit is chosen as the test animal. In the patient with diabetes, a unit of insulin will increase tolerance, that is, it will add to the amount of sugar that can be utilized, from 0.5 gram to 4 grams, depending on the character of the diet and the presence or absence of complications. The average patient uses between 10 and 30 units a day. The cost has been reduced to below one cent a unit, so that insulin is now brought within the reach of everyone. Indeed, the cost is negligible when we consider that patients who, without insulin, were helpless invalids, dependent on relatives or charity, are now as fit and strong as their neighbors, and able to work again.