Banting Given an Ovation
By Assembly of Scientists
Dr. Murlin of Rochester Says His Feelings are of Mingled Pain
and Admiration, But Noted Medical Men Pav Tribute
to Toronto Discoverers - Murlin Criticized for
Not Purifying Pancreas Extract.
A scene unparalleled in the history of the federation marked the closing session of the convention of federated American societies for experimental biology at the University of Toronto yesterday afternoon, For over three hours the delegates, prominent scientists from all parts of the continent, had been listening to papers dealing with different phases of the work on the insulin treatment for diabetes discovered by Dr. F. G. Banting of Toronto. Dr. Banting himself was present, but had not spoken, although repeatedly called for from all parts of the audience. Finally, at the conclusion of the last scheduled address, he came to the front of the hall.
An ovation that lasted for fully three minutes greeted him and the applause was redoubled at the conclusion of his remarks.
The listen to these papers this afternoon, papers telling of further work along lines on which I worked alone till last year, has been the most gratifying and satisfying moment of my life, he said. Next to that I appreciate most the gratitude of the patients we have treated. There have been cases of diabetic coma where recovery has been sufficient to enable those suffering to commence living useful lives.
Credit to Co-workers.
Much of the success is due to the workers under Prof. J. J. MacLeod, who have aided in the research. They were placed in groups by him and each group was given a definite problem to work on I want to pay a tribute to the work they have done.
The co-operation of clinics in all parts of the United States has been remarkable. When I see what has been accomplished in the past year, I look forward with confidence on the probability of much greater achievements in the future.
It is only a little more than a year ago that Dr. Banting came to the University of Toronto from London, Ontario, a practically unknown laboratory worker, but a laboratory worker with an idea. The facilities of the laboratories of Toronto University were placed at his disposal by Prof. J .J. R. MacLeod and Dr. Banting and C.H. Best commenced their work.
The results of this work have now been heralded all over the world as the greatest discovery in pure medical science in recent years. All the workers in the physiological laboratories of the university are now concentrating on insulin and further experiments are being conducted in laboratories in all parts of America.
Banting Gets His Due.
Complete credit for the discovery was given to Dr. Banting by practically all the visiting scientists. They state that his work was not based on that done previously by any other scientist, but that his success was purely and entirely due to this own efforts.
The claims of Dr. John R. Murlin of Rochester for a share of the credit were not seriously considered by the majority of the delegates present,. This was clearly indicated by the difference in the receptions accorded to papers of the Toronto and Rochester groups and by the criticism which several of Dr. Murlins statements received in the open discussion at the close of the afternoon session.
Dr. Murlin prefaced his first address with a few remarks stating that he had been at work on effects of pancreatic extracts on diabetes long before the Toronto doctors.
Only those who have been hot on a trail, have been thrown off by accident, and have finally regained it to find that someone else is in ahead of them, can realize the feelings with which I speak, he said. I commenced working with pancreatic extracts and their effect on diabetes patients in 1912.
It was by accident I learned of their effect but as there was a certain amount of alkali in the extract I was using, I began working to see if alkali would produce the effects now attributed to insulin. It was not till October, 1921, that I was able to recommence my experiments in the right direction and we had made considerable progress when we heard that Toronto was in it.
In paying my tribute to the Toronto workers, I am torn between pain and admiration.
Dr. A. J. Carlson of Chicago, said that there was joy and unalloyed hope but no pain in the tribute he wished to pay. It was a case of Youre a better man than I am.
He wished to add a word of caution, however. The untoward toxic effects often seen showed the need of caution. He was opposed tot he blood sugar method of assay.
Dr. Frederick N. Allen, Morristown, New Jersey, was unstinted in his praise of Dr. Bantings discovery. Dr. Allen was formerly connected with the Rockefeller foundation, and is one of the foremost diabetic specialists in America. He is at present studying diabetes insipidus following years of research on the subject, and conducts a large hospital for diabetic. His approval and praise of the Banting extract is considered as the last word, in America at least, in recognizing the Toronto discovery of insulin extract as the greatest in medical science of the century.
Dr. Bantings discovery is one of the greatest in medicine, he stated. It came out of a clear sky. It did not grow out of others work. It was absolutely a new discovery.
It is spectacular as anything that concerns the public health is spectacular and it is also spectacular from the standpoint of pure science. We have here a substance whereby a cell is enabled to utilize food and without which the cell cannot utilize food. It will be the basis for a great deal of further work.
Dr. Allen not only commended the work of Dr. Banting but also said that the later work of the entire Toronto group was invaluable.
An Epochal Session.
The comparing of a number of papers tabulating the results of experiments in insulin made in laboratories scattered all over the United States and Canada and the definite conclusions that resulted from this comparison made the whole session an epochal one in the history of scientific medical research. It has not yet been definitely established that insulin is a positive cure for diabetes, but there is not the least doubt that it is an extremely effective palliative.
The paper presented by Dr. G. M. Dobbin based on work done in Toronto by Dr. Banting, Dr. Dobbin and Miss S. Cairns showed that no effective means have yet been discovered, whereby insulin treatment may be given except with needle injections despite several objections to this method. The results of Dr. Philip Shaffers work at Washington University, St. Louis, would seem to indicated that there may be more than one kind of insulin or at least, another substance with properties very similar to the extract used in Toronto.
Three papers were presented by Dr. J. J. R. Macleod. In their preparation he had been assisted by E. C. Noble, K. OBrien, N. A. McCormick, C. H. Best and B. S. Eadie of Toronto. He dealt with Experiments on the mechanism of action of insulin. Some chemical reaction of insulin, and The physiological assay of insulin. The experiments of the Toronto group had been conducted with diabetic dogs and rabbits, but the results when man (Afflicted with diabetes) was treated with insulin was exactly the same. Their research showed that an insulin treatment reduced the blood sugar and lessened the other symptoms of diabetes. In Toronto interesting observations had been made on the migration of fat. A symptom of diabetes was the general loss in weight and the formation of fat in the liver. The fat forming in the liver of diabetic animals had been reduced by insulin treatment. The result in man was just the same.
Experimenting With Fish.
The Toronto group had found insulin a substance produced from the pancreas. They had manufactured it from beef pancreas hash. Dr. Best told how in recent experiments he had allowed the pancreas hash to stand in boiling water for two minutes and then had passed it through a fountain. In this manner the insulin had been produced. Dr. MacLeod told of the discovery of one of the most powerful types of insulin. He had conducted work last summer at St. Andrews near Halifax. Here he had experimented on bony fishes. He had found that in the pancreas of the bony fish there were certain isolated patches known as islets. From these islets a more potent product than any used yet had been extracted. The coming of autumn had cut this work short, said Dr. MacLeod but it is to be continued next summer. These trials with the pancreas of bony fishes were but elementary and they had only served to open up a new and large field.
Dr. MacLeod outlined a very interesting application of the power of insulin. It was a known fact that coal gas poisoning or the administration of ether increased the blood sugar. Thus the ether anesthesia during the operation of a patient afflicted with diabetes was dangerous since it increased the abnormally large amount of blood sugar. Experiment showed that a dose of insulin before the administration of the ether anesthetic to a diabetical patient offset the effect of the ether. Thus insulin provided for safe operations.
Need Normal Rabbits.
Dr. MacLeod warned the scientists that when they were carrying on their research with the use of rabbits they must be careful to choose normal ones. Though a small treatment of insulin should affect a rabbit some were found on which it apparently had no effect. It was just the same as different men being affected in different ways by the same amount of alcohol. These rabbits proved to be very rare but there were some who had to be given doses of increasing amounts to get the required results.
At the conclusion of his address Dr. MacLeod presented a series of slides. Rabbits had been starved for twenty-four hours and then insulin had been injected in the ear veins. The charts showed that in every case the blood sugar had fallen at a uniform rate. After the thirty minutes it began to rise again at varying speeds.
The method at present used for determining the effect of the insulin injections on a patient is by the amount of blood sugar. A fall in the amount indicates an improvement in the condition of the patient. This however is not considered a perfectly satisfactory method of determining its action and others are being sought.
Charles H. Best, of Toronto, told of attempts made to find if there was any parallel in the effects of insulin on humans, dogs and rabbits. The experiments were conducted by himself, Dr. Banting, Dr. Dobbin and Dr. J. A. Gilchrist of the Christie Street hospital clinic. Some sixty preparations of insulin were used.
They found that the effect varied with individual cases and with each species. Some animals and some humans were very resistant to insulin which produced almost no effect when average doses were administered. Others were equally susceptible and there was an immediate lowering in the blood sugar. So far they had found a lack of any definite relation but experiments were still going on. The present insulin unit is the amount required to give a 2 kilo. Rabbit convulsions in 4 hours but it is essential that some means be found of determining the clinical strength of the extract found before it is used extensively on humans, or at least before it can be used extensively by anyone but specialists in the disease who have done considerable personal experimenting.
In the absence of Dr. J. B. Collip of the University of Alberta, Prof. J .J. R. MacLeod presented his paper. Dr. Collip spent some time in the University of Toronto laboratories and then returned to the University of Alberta to continue experiments himself.
His experiments indicated that that portion of the insulin extracted from the islets, small isolated patches in the centre of the pancreatic gland, tended to lower the blood sugar while that portion extracted from the pancreas tissue proper tended to raise it. The presence of this latter extract would explain the action of the injections in certain rabbits where there seemed to be delayed action and the insulin only took effect after from one to four days. Certain methods of extracting the insulin will produce immediate results while others produce delayed results.
Method of Administration.
Dr. G. M. Dobbin, of the University of Toronto, spoke on the different methods of administering insulin. The experiments had been made on dogs, kept on a full diet of meat, oatmeal and grape sugar with a view to discovering some more satisfactory way of treating the patient than by injections with a needle.
The subcutaneous injection, that is one made with a needle directly, under the skin, is the method most commonly used at present. The objections to this are that it causes a certain amount of pain and apprehension on the part of the patient and that the numerous injection required cause soreness and tenderness.
Attempts were being made to find some means of slowing the action so that fewer injections would be necessary.
Intravenous injections, injections direction into the blood stream, were also tried. Here there were objectionable clinical symptoms, the action was immediate, and it was also necessary to use a needle.
Intraperitoneal injections were also the subject of experiment, but produced no better results than intravenous injections, and were much more difficult to do.
An Expensive Method.
Mucous membrane absorption seemed to be the most commendable method, but the results produced in this manner are neither marked nor lasting, although 8 to 17 times as much insulin was administered as when given by the needle. The expensiveness of this method was almost prohibitive.
Spraying through the nostrils produced no effect whatever.
As the use of the needle therefore seemed unavoidable, means of reducing the number of dosages were sought. Solutions in oil cannot be made and emulsion in oil were no better than the pure insulin.
Solutions in one percent agar-agar give a hint of future possibilities. Here the blood sugar was held down for a longer period, and the effect slowed which was to some extent the result sought.
Dr. John R. Murlin, of Rochester, the next speaker, told in detail of the mistake which caused him to believe that the results he obtained in 1916 after four years work, were due to the alkali in the pancreatic extracts he had prepared.
He said that he believed the combustion of sugar was the whole crux of the diabetes question.
Does Not Purify Extract.
Dr. Murlin obtains his insulin in a different way from the Toronto group. He obtains it by perfusion, a system of running streams of water over the gland and washing out the extract. The Toronto men obtain theirs by macerating the pancreas with alcohol or, in some cases, with acid. He concentrates it, but does not go to any lengths to purify it, considering this unnecessary.
It was on this last point that he was most heavily criticized, as many of the biologists considered careful purification an essential necessity.
He used the perusate of pigs pancreas and the pancreas of cats and dogs, and did his experiments on cats. The insulin when given in capsules brought down the blood sugar slightly, but not to any great extent.
Dr. Murlin had a method of assay which he used by building up glucose into higher compounds,. This he considered superior to the blood sugar assay, but there was disagreement on the point among hi hearers.
Dr. Clowes, of the Ely Lilly Institute, which manufactures insulin, was strong in his condemnation of one phase of Dr. Murlins experiments. I was greatly surprised at Dr. Murlins statement that it didnt matter so very much whether the material was purified or not. This was what we considered one o the essential requisites.
He continued to show the federation of the danger in experiments with insulin and diabetical patients. Let me warn those who have listened, said he, that these apparent simple methods of production are not so simple. A life may be lost much easier than it can be saved. But the Toronto group had taken every precaution. They have worked this thing out in a marvellous fashion.
One of the American biologists pointed out that whereas Dr. Murlin had made use of a pancreatic extract, two doctors, one an American studying in Germany and one a research worker at Harvard, had experimented in 1900 and 1905 with muscle extracts, and had obtained results somewhat similar to Dr. Murlins. Neither of these doctors had continued with their experiments and those that they had carried on were very elementary. He suggested that Dr. Murlin might work out some advanced plan of combining the pancreatic extracts with the muscle extracts and thus get more potent results.
A Great Discovery.
Rising to pay tribute tot he work of the Toronto group another American biologist said, I dont feel that any discovery in the last decade has meant as much as this. These workers in Toronto have worked it out for themselves and have made marvellous advances.
He then told that elementary experiments of the same nature were being carried on in New Orleans only the insulin was not produced there. They had received it from the Ely Lily Institute. A man suffering from diabetes had been treated from August to late November of this year. He had been given doses of insulin three times a day and the amount of blood sugar had decreased rapidly.
But the results had been marred, said he. The patient had been allowed out of the hospital for Christmas day. He had eaten some fruit cake, Next day he returned and the blood sugar was the same increased amount as had been in August. The treatments were once more begun but up to date the decrease in blood sugar had not been very rapid.
Method of Extraction.
He described the method used by him in extracting the insulin. One kilo of beef pancreas hash ground fine was mixed with either hydrochloric or sulphuric acid. In the case where the hydrochloric was used, the result had the appearance of distilled water. To this was added 1,200 cc of 95 per cent alcohol and 300 cc of water.
After standing for several hours, it was pressed through gauze an the remaining hash mixed with 60 per cent alcohol. This last was re-filtered and the two liquids mixed before being neutralized with sodium hydroxide. The result was then evaporated to one-quarter to one-tenth its previous volume at a temperature of from 20 to 30 degrees centigrade.
When solid ammonium sulphate was added and a precipitate coagulated a gummy, tarry substance here floated to the top and the solution was drawn out from below leaving the precipitate, which contains nearly all the active element. This was dissolved in water and then centrifuged. Two protein-lie substances both active and insulins were the result of this.
The paper read by Prof. Philip A Shaffer of Washington university was one of the most important on the program. Prof. J. J. R. MacLeod had state earlier in the afternoon that the insulin he had obtained from bony fishes had no protein-like qualities. Prof. Shaffer told of an extract he had prepared which had definite protein-like qualities. This led to the supposition that there might be two entirely different insulins.
Following the report of the Toronto discoveries. Prof. Shaffer had tried making active insulin. He had tried purification and had also tried to identify the active substance without immediate success.
He obtained a white granulated powder, of which a very small amount varying from one-quarter to one-half a milligram, produced the same results as a much larger dose of the usual extract.
I dont know whether or not this is insulin, he said, but whatever it is, it is very powerful stuff.