GREAT SCOTT

ERNEST LYMAN SCOTT'S WORK

WITH

INSULIN

IN
1911

BY
ALEITA HOPPING SCOTT

The Scott Publishing Company
Bogota, New Jersey

Library of Congress, Catalog Number 72-80201
Copyright 1971 by the Scott Publishing Company, Bogota, N.J.

 

CONTENTS


PREFACE
PART I    CONVERSATIONS
              CASE OF THE MURDERED MANUSCRIPT

PART II     LIFE AND DOCUMENTS

PREFACE

The chief advocate of truth is its inherent interest. Darwin found the implications in the presence of fossil shells in Andean mountain strata more interesting than the story that our universe was created in six days.

The first extraction of insulin was made by Ernest Lyman Scott in the University of Chicago in 1911. Insulin was introduced into medical use in 1923. Discovery in fact is more interesting than discovery by fiat. The true story is more interesting than that given to the public, familiar now to many a schoolboy.

My effort to have the 1923 Nobel Prize in Medicine rescinded was thwarted. I was told, "The Committee never reverses an Award." My effort to obtain recognition and rectification of injustice for one of its own from Columbia University met with the answer, "Columbia confers no posthumous awards."

The purpose of this book and the hope that impelled its creation is that the man who made the first usable extract of insulin may win honor in the court of public opinion denied him in the halls of learning. The hearts and minds of the millions who have benefitted from insulin may find some gratitude to the man who did the basic work, and gave the method for its extraction, to those who introduced it into practical use.

This is a documentary.

 

PART 1

CONVERSATIONS

CASE OF THE MURDERED MANUSCRIPT

 

CONVERSATIONS *

*These Conversations, recorded in a handwritten copy, 1964, have become a historical document in the possession of the National Library of Medicine, Bethesda, Maryland.

between Aleita and Ernest Scott
1964

 "You knew interesting people when you worked at the University of Chicago in 1909-11. Waldemar Koch you have often mentioned. What sort of man was he? You had something to do with insulin, did you not?" Aleita questions.

"Waldemar, and he pronounced it as with a gusty ‘V,’ was a nephew of the great Robert Koch, who identified the tubercle bacillus. Fred Koch was no relation. Valdemar stood one day with his back against the doorcase, a favorite posture:

"Thank God! That damn class is over,’ he said with a grin.

"Not that he did not like classes. Carrying classes in two departments and acting as head in each, infringed on his time for research. He kept up his research.

"Fred Koch and I were close in our thinking but Valdemar had more influence on my philosophy.

"The year after I left Chicago, he died. He was only thirty-six. He would have gone far had he lived, I am certain.

"I well remember how furious he was with me once. I had spent thirty-six hours straight on an experiment and the last analysis resulted in a gummy mess. I dropped the flask on my desk in the corner behind the door and went home exhausted. Next morning when I came in Valdemar was furious. He

said, ‘I had a visitor from Germany this morning. What kind of a laboratory will he think I run when he sees that sort of thing on a desk!’

"I sympathized with Valdemar. I did not explain."

Ernest Scott seemed pleased to review his life in Chicago more than fifty years before.

"You have often mentioned Fred Koch. We have a photograph of him. He has a very fine face."

Finding interest in the conversation, Aleita continues:

"What about Fred Koch?"

 

FRED KOCH

Ernest answers: "At the time I was at the University of Chicago, 1909-1911, Fred Koch was a graduate student in the Department of Biochemistry. A.P. Mathews had been head of department but, as rumor had it, he could not get along with Carison, and he went to Cincinnati that year leaving the department hung up without a head."

Fred Koch later became head of biochemistry and was a lifetime friend and admirer of Ernest Scott.

Ernest continues:

"Fred Koch was working for his Ph.D. degree but he did not come in as a beginner, fresh from obtaining a bachelor’s degree. He had come from having worked out for Armour and Company a method for extracting adrenalin by by-passing the Parke-Davis patent. I think, though I am not sure, that he was working on the thyroid at this time. At any rate, he and Valdemar Koch, Professor of Pharmacology, ran the Department of Biochemistry until in 1911 he took his degree and was later made head of the department.

"My work that was done in the extraction of the insulin from the pancreas of dogs was done in the laboratory of the Biochemistry Department. The work was done primarily under the Department of Physiology where the operating facilities were available for animal experimentation.

"Professor Carison wanted me to work on a different problem, but it would have been his problem, not mine. I did not want to do it. I had come with my own problem, to find out something about diabetes, which killed young men in their prime. Had I worked on Carlson’s problem, he might have been more sympathetic.

"In the graduate laboratory in Biochemistry, I shared a table with Fred Koch. There were, perhaps, eight tables. One table was occupied by a fellow from Oregon.

"We had two accidents. Once Fred Koch was using a large Buchner funnel and the bottom fell out and a whole month’s work was lost. The fellow from Oregon was distilling ether over sodium on a water bath and heating with steam. The flask broke. The ether in thc sodium caught fire under the hood but spread outside. The fellow got the fire blanket and stayed there till he got the fire out. Then they took him in an ambulance to the hospital. It was over almost as I watched him. The whole building would have gone.

"Valdemar was rather tall and dark and the kind of a fellow who had initials on his shirt sleeves. H was the kind who was not unacquainted with dress clothes. He said a chemist could work all day in a chemical laboratory in a dress suit and not get a spot on it. He worked under a tent of cheese cloth. He said he did not want stuff falling off the ceiling and getting into his things. He said his idea of Heaven was a chemical laboratory equipped exclusively with Jena glassware.

"I consulted with him frequently but do not remember getting anything of fundamental interest from him, though I probably did. He did not have the technical influence for me that Fred had.

"Other people had tried to extract insulin as the published records show. We were looking for what destroyed it during or after extraction and planned to eliminate oxidation, or action of the digestive enzymes, temperature or whatever. These were the three we took care of. Fred was afraid of oxidation because of his work with adrenalin. I had the idea that insulin might be a protein and thus subject to the proteolytic action of the external secretion of the pancreas, trypsin, and planned to eliminate that. It was proved to be as simple as that."

"And that was what all the big boys wouldn’t look at! Do you think they ever really studied your experiments?" Aleita asks.

"Later, Fred got out the male hormone, the first to do it, and he is remembered for it.

"It was Fred’s work with Armour on adrenalin that influenced me to avoid danger of oxidation by working under an atmosphere of inert gas, probably N2 or CO2. This was shown to be an unnecessary precaution, later, and its abolition simplified the method of extraction.

"My own conviction as a result of studying the available literature, mostly from German universities, was that the various extracts of the pancreas lost potency as a result of action of trypsin, the digestive enzyme. The fresh pancreas of recently killed dogs was extracted with alcohol, absolute alcohol to make 85% with tissue water. The alcoholic extract, evaporated in vacuum to dryness and taken up in isotonic salt solution, when injected into a depancreatized dog, killed the dog before I could get the needle out. This was probably by embolism, that is, an air bubble in the syringe. I was new to such work.

"Decanting the alcohol from the precipitate and preparing a water extract eventually resulted in a potent extract which I was able to prepare. This was my method which was described in the American Journal of Physiology in 1912." Ernest Scott is reviving his early research. Going on:

"It is now seen to have been a highly reasonable procedure since insulin has proved to be a protein, and subject to destruction by digestive enzymes.

"Banting used fetal pancreas for the same reason in an experimental way, an impractical method for massive production for clinical use.

"The time at my disposal at Chicago did not permit me experimentation to determine the question of oxidative action. And I was far from encouraged to continue." Ernest finishes speaking.

I recall asking, although it may be recorded later on, "Were you not offered a continuance on the staff at Chicago?" and his answer, "Yes, at $750.00 a year, but with a wife and a child on the way I had to have money, and so I went to Kansas."

1911-1921

"It is this lag of ten years between the time that you in 1909-11 succeeded in making a potent and safe extract of the pancreas and Banting repeated your work in 1921 and found that it was effective in reducing symptoms of diabetes in animals, thereby winning the Nobel Prize for the ‘Discovery of Insulin’ in 1923 on your work, that interests me," Aleita remarks.

"What was it that prevented recognition of your work? Apparently from his letter that we still have, Fred Koch at the time appreciated its value."

Silence. Ernest does not answer.

Continuing, "Was it a matter of lack of interest on the part of your Head of Department?", Aleita asks. With no answer and to fill the gap, "You know how I abhorred the dictatorial methods of our Head when you and I were working together. Outside, when I met him that summer in the Adirondack Camp with his wife, how much I liked him personally. He was warm and truehearted, among the world’s best. In the laboratory, he was impossible. I remember how unapproachable he was when he took over the Department. Perhaps he was unaware, but most were afraid of him. We dared not speak."

Still no answer to the question, so Aleita talks on.

"I was quite famous with the medical students because I could always demonstrate heart-block in the cat when we were studying the Bundle of His and electrical conduction in the heart.

"One day, Cora and Caroline, two instructors, called on me for help.

"They put me on the spot. They said, ‘You have the reputation. We can’t do it; here is the clamp. Here is the cat with the heart exposed. Show us how to place it’."

Continuing, "I did the best I could but failed too. This particular clamp was a small ‘Erlanger’ as it was called, and the Boss had had it made in the shop to replace the larger type we had always used successfully before, a ‘dog Erlanger’. I do not doubt that he was certain he was doing the right thing but I am also sure he never inquired to find out. He never came into the laboratory, himself, that I ever saw, not the way you were always there in person, on time, every day, when you were running it. Remember, that morning when I came in at ten a.m. instead of nine, and I said my clock had stopped and you answered abruptly, unimpressed, that you had heard that one before."

All quiet, no remarks, Ernest Scott’s lips were sealed.

Aleita, continuing, "I suppose you think I ought to have told him the new clamp was perfectly all right, that the only thing wrong with it was that it didn’t work, but he would have said, I expect, that we were no good. ‘It is the right size clamp. Use it.’ No one took it up with the boss. We all needed to eat. Most of us had others depending on us. We just did not demonstrate heart-block in the laboratory in that way any more. They could read about it in the books. Was it something similar in Chicago?"

Silence. Still silence. Feeling there was something here, something about Carlson, must not give up about Carlson, not giving up, and wanting an answer, Aleita says, "You know it is not necessarily a criticism of Professor Carlson. I know your antipathy to personalities, I mean, your antipathy to criticising people, but there is the quiet, scholarly, devoted, studious, conscientious type, in the words Fred Koch, in his letter we have, used to describe you, and then there is the other type, common everywhere, I imagine, the man who is going to get to the top, who brooks no opposition from anyone. Other people recognize him and get out of his way, if they can. Some of the ones about a man such as this are ‘bootlickers’. Then, they get to be heads of departments in their turn. These men have the drive. Was it like this?"

At last, an answer, Ernest Scott speaks:

"No, he did not like bootlickers. Just get out of his way! But it was a lot bigger than Carlson. There was Macleod and Lusk, and Lusk was bigger than any of them and he could not see it either."

Continuing, "It was more than that. I was a young fellow. No one had ever heard of me. It could not be that I had found the answer when so many others had worked so hard and so long on it and failed. Lusk had Murlin working on the same problem. He was not getting anywhere with it. It was a sheer impossibility that this young fellow from nowhere, working more or less alone, could have found the answer, and in work done only for a Master’s thesis. Utterly impossible!"

Continuing: "So Lusk advised Lee to drop the matter and turn me into something more promising. Lee of course, was head at Columbia then. This was after I had left Chicago, and after my year in Kansas. I had gone to Columbia and was working under Lee." Ernest stops.

"Do you think either of these two men looked at your records, at your publication, read and studied your results with a view to making a fair appraisal on the facts? Did you give them copies, reprints? Did they ask for them?"

"No. I am sure they did not do any of these things. They talked about it and said ‘There is nothing to it’," Ernest answers.

"I am inclined to believe you. I recall one of the younger members, that woman Ph.D. who did so much research and published so much, not long after I started working under you, told me confidentially that you were a ‘charlatan’. I am glad to say I was unimpressed. I had sized you up, can still see you standing there, against the bank of book shelves in Pike’s office, and decided that here was a good man, if there ever was one, and that I could work with you, so what she said meant nothing to me except that she was reflecting talk she had heard from others."

Aleita, again on the track, "Let’s go back to Carlson’s laboratory. What was he doing then, at that time, when you came to him?

"Wasn’t it something unusual for a young man to come with his own problem, as we used to say, and with such a driving impetus to get into it? Wouldn’t that have impressed him with your seriousness and ability? So many of us young graduate students went to study with the leader expecting him to set the problem for us. We did not have the understanding to set our own. So many of us suffered from the bad teaching to which we had been subjected, where what was known was taught but no insight or outsight to envision the areas that were unknown and needed or would profit by investigation. In first year high school I learned all there was to know about botany and zoology, I thought, and was infinitely surprised to find friends at college engaged in those studies!"

Aleita, continuing: "Wasn’t he impressed with the importance of your demand to know more about diabetes? I remember your telling me about that high school student of yours in Bay City, Michigan, who got his death sentence. That was what started you on that path. Didn’t Carlson want to help?"

Driven to answer, his emotion touched, Ernest responds, "He thought it foolish to try. Others, more advanced than I, were doing all that could be done.

"Of course, I by-passed Carlson when I worked on the pancreas anyway, without his backing. He had a problem he wanted me to work on when I came to Chicago. You could not expect him to push my work. He never did," Scott states.

"My crucial work, preparation of the active principle of the gland, was done in another, a different department.

"I could never get up interest in his problem, one of peripheral neurology, or was it central, and I was never interested in either or in neurology in any guise. There was a problem in fundamental science in which I was interested and on which I could have worked with enthusiasm, but this was on membranes and would have been with A. P. Mathews, who was leaving Chicago at that time, but this I did not know until I arrived. Professor Carlson was never interested in the problem I chose, extraction of insulin, nor in the members of the Biochemistry Department. Mathews had left that year as Head, you remember." Ernest Scott stops.

"Looking back on it, I suppose you won a victory, a great victory, in working on the problem at all, considering what you have told about the lack of enthusiasm on the part of your superior. What you did, even though you, yourself, gained no professional advancement from it at the time, and only a very moderate amount later, yet your fundamental work and your success in devising the method that made possible extraction of massive amounts of insulin suitable for clinical use, did make it easy for Banting in 1921-22, who merely had to repeat and verify your method, once he located it in the literature. Over the breakfast table, men are funny. Suppose the man who discovered Mendel’s work in the literature had run off with the glory? I don’t even recall that man’s name," Aleita says.

"You really won a victory when you did the work anyway, that you were even permitted to use the facilities of the laboratory. He certainly had the power to deny you that facility. I do wonder how you managed that.

"What was Carlson working on then? Starvation? He starved himself forty days, water only. A strong man! Only the first four days were hard, I heard he said."

"No, he had done that. He told us all about it," Ernest replies.

"Was it hunger contractions? Those contractions Dr. Beaumont had observed in the gunshot wound of Alexis St. Martin, so long before? Swallowing deflated balloons then inflating them and getting a graphic record of stomach action in a healthy person?", Aleita continues.

"Can’t let the subject of Carlson drop. This stubborn noncommittal! There must be something here," Aleita thinks.

"No. It was something he was doing with the Department of Pathology. It took several months to train the dogs, experimenting and getting them in condition, one normal, the other managed in Pathology. The final step was a crossed circulation between the two dogs. All of us were invited to see the final step, the crux of the two month’s training, work and preparation," Ernest answers and continues:

"Remember that dumb diener I told you about? The one who did the trick with the saline solution, he was fired for that! He was anesthetizing one of the dogs and Russ had the other. The experiment was going along fine. Then five o’clock came. Quitting time! The diener was that kind, his dog died." A diener is a German term for a servant, here, a laboratory assistant, untrained except by experience.

"Was the experiment finished?" Aleita asks.

"No. It had another hour to run before there would be the results," Ernest responds.

"All that work of months by two professors went to waste. For nothing?"

"What else?"

"Dieners, helpers, servants, the lowest in echelon of authority, dieners are important, too," Aleita asserts, and continues:

"Do you remember telling me about Von Mehring’s work and his diener? I always thought that diener quite a hero. He had to face up, doubtless, but perhaps he was not afraid of Von Mehring. Maybe the diener liked him, the diener who does the dirty work.

"That diener was taking care of the animal cages where the normal and the depancreatized dogs were confined. You remember that he told Von Mehring that, try as he may, he absolutely could not keep those operated dogs clean; their cages were always filled with flies. The flies did not bother the well dogs," Aleita recalls the story. Ernest answers:

"True, it was Von Mehring’s laboratory and he was senior author but Minkowski did the work and the diener probably reported to him and not to Von Mehring. Some more seniority."

"You read the story somewhere," Aleita says.

"Yes. At that time I read everything I could find. He, Minkowski went right down to those cages and that was how it was discovered that dogs without a pancreas excreted sugar in the urine," Ernest recalls.

"Good for the diener, I always thought," Aleita remarks.

"Of course, it had long been known in France and in Germany where most of the early work on diabetes had been done that pathological lesions of the pancreas were associated with diabetes. Von Mehring’s and Minkowski’s work was experimental," Ernest Scott remembers his studies:

"It is a long time ago that I did this study but as I remember, this was more talked of in France than in Germany."

Aleita, still looking into that lost ten years, "But Carlson was responsible when he worked over your thesis for publication in the American Journal of Physiology in January 1912, and, without consulting you, you did not know it was there until later you read it in print under your own name, when he put in that damning sentence, the one nullifying sentence in which he made you disclaim any real value for your findings?"

Now, at last, we have an answer, and anger, too, from Ernest Scott. I, Aleita, have touched this gentlest of all men, in the quick. Never before have I seen anger in him, never. Ernest Scott speaks:

"Yes. He was responsible. No one would ever read the thing again after that. And you can prove this! I deposited three copies of my thesis as I had written it, as I expected it to be published in the University Library. It was bound in red buckram, and they had to add twenty-five pages of blank paper to make it big enough to bind," said with a chuckle. How brief the anger!

"In this case, the quality, not the amount determined the value. I did not know a copy of your original thesis existed, "Aleita exclaims.

"I will write to the University of Chicago Library and ask for a complete copy of your thesis. That I will do, and at once."

Professor Carlson had his way. He had not been able to keep this man from working on the problem he had chosen, but he had the last word, and in rewriting the thesis for publication, he won out, for he discredited the man and denegated his findings. Our dialogue will continue on a different level, a reevaluation of the story in its various aspects and its ethical and practical significance.

It was at this point that my interest leaped. These conversations might prove to have historical interest.

"Making those days live again" might prove important.

All of January, all of February, nineteen days in March had passed before my persistent knocking on the locked door of the past yielded a faint murmur within. Some secret was inside the mind alive, wanting perhaps to escape.

"The letter asking for a copy of your original thesis in 1911 has been sent but we must wait and I think these conversations have been very interesting. It is an interesting subject. Remember that woman Head of Department, a Ph.D. who studied a time with us and with whom Christmas cards have held us in touch? Remember she told me, ‘Leave it alone, Mrs. Scott, everyone knows he discovered it. You can’t do anything about it.’ She ought not to have said that to me. They say, I have read, that you ought never dare a Finn. Don’t tell him he can’t do it because that will be the very thing he will do. Remember the army saying I’ve heard you repeat numberless times, ‘If it is possible, it will be done right off. If it is impossible, it will take a little longer.’ I really think that remark of hers set me off. It has become quite fascinating.

"Also, if ‘Everyone knows you had it’ as they say, how come I have a two-inch stack of cards praising Banting’s great discovery, and not a single one praising you! Yet he cites you in his epoch-making paper proving he knew your work."

Silence from Ernest Scott.

"I do agree with you that the whole thing is a lot bigger that Carlson, or Lee, or Lusk, or Macleod. You had approached all of them, directly or indirectly. But I think it has got something to do with the way departments in universities and medical schools always were, and most probably still are run on a system something like military command, where the top man has the power. Do you agree?" Aleita asks.

"There has to be some kind of organization. Sometimes it works out right," is his answer.

"Do you think it either right or ethical for a head of department to alter, change, add and subtract material without consultation for publication under another man’s name?"

No response from Ernest Scott.

"If he has this power, should he not likewise have the responsibility of facing up when his action has been proven wrong? Surely, you do not defend him in this respect, unwilling as you are to criticize," Aleita says.

"No. He should not have done that. It was a terrible thing for me, but all a part of the whole story," is Ernest Scott’s statement.

"Ethical as opposed to moral values have always intrigued me. I take ethical to be the highest set of values whereas morals would be a lower order as customs and would vary from place to place and from time to time," Aleita talks on.

"Why do we submit to these crippling conditions. We all did it. It was a rare one of us who stood up now and again and faced the man. I did it once or twice, myself, and so did you. Remember those signal magnets and the boss said, ‘Don’t you know, Dr. Hopping, that all signal magnets are the same?’ and walking down the hall together, I answered quite pertly, ‘Why, no! I thought they were all different. That is the way they behave on the laboratory tables.’ And you were smarter. You said, ‘Then why do you have the mechanic working on them so often in the shop?’ Then that time when the boss handled an operation and asked someone on the staff to serve as anaesthetist for the cat. The first fellow killed three in swift succession. The boss could not distinguish, doubtless, between the exaggerated reflexes during the incipient stage of anaesthesia and asphyxial convulsions when the animal is going out. Then I was called in. You heard of it and used to laugh over it, how I was told to use cheesecloth in the cone, and I looked him in the eye and said ‘I prefer cotton’. I can still see the sharp look he gave, his very blue eyes, straight into my eyes, perhaps, two feet, eighteen inches apart or less. He dropped his. He let me alone and we did not lose the cat. They fire nurses for challenging the surgeon, you know. Four years supervising those operations and I had never lost an animal. The boys might use several of those nine lives but when the bin was running low, I stepped in so they could see the experimental results that had been planned not losing the whole morning’s work, and if the animal died, the responsibility was mine. Yes, we used anaesthetized animals! God forbid untrained hands learn on my mother, sister, or brother, husband or father. Yet pity and protect the animal.

"Most of the time, all of us conformed to the system. ‘To get along, one goes along’, even if in following the leader it is over the cliff’s edge to destruction.

"We were all young, hearty, and liked to eat. Even were we willing to jeopardize ourselves and our futures by getting in front of the machine, each of us had others on our backs whose welfare we could not jeopardize. We could not afford to be martyrs, for their sakes. One must have his back to the wall or one foot in the grave to speak freely."

No comment from Ernest Scott to this monolog.

Aleita, continuing, "Even Christ, that greatest of men, I have always thought had martyrdom thrust upon him. No one could have chosen to be a martyr who described joy as one ‘Who rejoiceth as a strong man coming out of his wedding chamber’, if he really did say it since the New Testament, I have been told, was not written until fifty years after his death, or who, we believe, preached the beauty of this world as he did in the Sermon on the Mount.

"I think all of us showed good, practical sense in dodging the machine.

"I still think, however, that a democratic system of running a department might have its advantages, might have made the lag so noticeable in the gap between your discovery of insulin (1911) and its practical application (1921-1922) less. Fred Koch was a graduate student at the time. He saw the importance. What about Fred Drennan?", asks Aleita, becoming practical again.

"Fred Drennan and I worked together in all the recovery operations, where we depancreatized dogs. We were the only ones in the department who were doing this experiment.

"Fred was a medical student who took a year in mid-course to get his M.S., then returned to get his medical degree. This is what later, I tried to innovate in Columbia but they stopped me cold." One of his students showed his research training in a summer course by winning one of the few Nobel prizes awarded to men of medicine in Columbia.

"Fred’s mother died of diabetes while we were working together. He had an even stronger incentive, if possible, than mine,’ Ernest goes on.

"Fred did the work then that made him talked about. He found that though a depancreatized dog always died of diabetes a pregnant depancreatized dog did not die until after parturition. The Italian fellow took up from there and showed that the pancreas of the fetus secreted insulin but not trypsin.

"Banting’s work followed his, for he extracted insulin from the fetal pancreas.

"He could not get enough of it to use for clinical use. He had to use my method for that, my method to destroy the other trypsin from adult pancreas.

"Thus, Banting had to come back twice to Chicago, in his work, to Drennan and to me," Ernest Scott concludes.

"What did Drennan do after he left Chicago?", Aleita asks.

"He took over Sippy’s practice. Sippy was the man who developed the bland diet for ulcer patients."

"Yes, I remember Sippy," says Aleita, and continues:

"Did everyone do recovery operations in Chicago? I remember we did little of that in the Department of Physiology when I worked in Columbia.

"What were your facilities for the sterile procedures, in Chicago, as necessary for animals as for people? Where did you work?" asks Aleita.

"We had excellent facilities. There was an operating room with complete equipment and next to it a recovery room and on the other side a preparation room.

"It took the hospitals some time to catch up with you, way back in 1911, that was, and now we hear so much of the wonder of the recovery room. I recall my one or two seances. I recovered in my own room," Aleita comments and asks,

"Was it always used well?"

"Yes, very well except when Carlson used it to do his autopsies."

"You did not like that very much, I can see your expression."

"That didn’t seem exactly necessary, did it," Ernest confirms and says, "Luckhardt was doing very interesting work with the thymus gland. He extirpated it and found the dog survived very well," and continues the story.

"Carlson called one day for one of his operated dogs to demonstrate before the class of medical students. I was there that day listening. He put the dog on the lecture table, lifted up his chin, said, ‘Here, see the scar. The dog is perfectly normal.’

"Then he threw the dog down.

‘Take him away’, Carlson said to the diener.

"Luckhardt met him outside and said he was finished with the dog anyway and would do a post. He opened him up, there was the thymus just as good as ever. It just happened to be one of the normal, control dogs, underwent the same operational treatment but thymus retained.

"The students never knew the difference. I was on the inside and heard that one," Ernest concludes, with the semblance of a grin.

"Before we finish with this question of the man under whom you worked out your extraction of insulin, you have never admitted but you cannot conceal that you did not like him. In fact, you have never spoken criticism of anyone. I, as a woman took a violent dislike, the one time I met him over the dinner table when the Chicago crowd of the old days met together in New York. He and his pal were going off to drink a quart of whiskey, or was it a pint that they mentioned. Not being a drinker, I would not know. That did not appeal to me as being the way to make one’s self big," Aleita speaks.

"You were not alone in that feeling. A lot of people did not like him," Ernest replies.

"What I want to say now, is that when he knew he had belittled your work in 1910-11, why in 1942 when you retired from Columbia and had a farewell dinner given you by your students, and he wrote, by request, a letter about your work at Chicago, and this twenty years after Banting, although he called it ‘Your potent extract of the pancreas’, he noted only that it ‘controlled the hyperglycemia and glycosuris only 4-8 hours, and it elevated the body temperature’, for all the world as though more than twenty years earlier, Banting had never existed, had never acknowledged in print that he used your extract, had through the University of Toronto, patented it, and eventually taken his co-workers along with him to win the Nobel Prize. Even after it was all proven he could not see it. Why?" Aleita demands.

"Picky. Always picky. He could not see it because he did not want to see it," is Ernest Scott’s conclusion.

"That may well be true," Aleita agrees and goes on

"In 1954, you had a letter from a graduate student from the University of Chicago asking for an account of your work at the University. Do you suppose he at last, saw what he had done, that his blind spot had cleared up? Do you suppose he, at last, realized that he had let a wonderful thing slip through his fingers?

"I recall your answering letter was a bit devastating, I cannot find the carbon, how your work had been done against opposition, how that damning sentence had been put in that nearly nullified your eighteen months of sacrificial work, your most important final table of data deleted, you, yourself, permitted to leave the university with no more than a starvation stipend offered to retain you, going to an institution where it was well-known there was no opportunity for research.

"I do well remember your devastating reply. No wonder we heard no more on what to me appeared as an effort to horn in, after forty years, and more, (1911-1954) on the credit, get on the ‘band wagon’," Aleita recalls her secretarial work.

"Before we leave this matter of the placing of responsibility for what you, yourself, have pointed out to me, the deaths and heartbreaks from diabetes over that span from 1911 to 1922, when your extract, your directions for making the potent extract, were there waiting for use, squarely where it belongs, not on your shoulders as that friend of yours did, who said you should have been put in jail for having it all those years and not using it, but upon those of ‘Ajax’, as he was called, the strong man with the Achilles’ heel, his blind spot of not seeing the value of work done by others, for with power, the full power of a somewhat military form of organization of a head of department in a medical school at that time, let us look at what Carlson did to himself," Aleita studies the situation.

"My hero, Hans Zinsser, that man who lectured before his students in our building on 59th Street, like a prancing tiger, I thought, so fascinating to watch I doubt if I understood, or even heard what he was saying, that was in the early 1920’s, I remember him well, says in his autobiography ‘As I Remember Him’, on page, 70: ‘I knew that our intellectual competence as human beings, transitional forms in evolution would never attain the insight to formulate the surely existing thermodynamics of the human spirit!’ This is a great sentence except for the negative," Aleita enjoys philosophizing.

"I would say, however, not only that we can formulate these surely existing laws of the human spirit, but that we must formulate them, if the species is to survive. Geological history is crowded with the records of defunct species. We have seeds of destruction planted within ourselves where all may see.

"The first law in human relations, from what I have seen written and, more forcibly, in unwritten and personal relations, is: ‘Whatever good you may do for another person returns to yourself magnified beyond understanding.’

"If we could only see our great religious teachers as men who show us the way, rather than degrading them into gods to whom, by definition, anything is possible. All such leaders have shown this first principle, regard for the welfare of all, just treatment, with kindliness. Simple application, if practiced on both sides, would solve many of our most pressing social problems.

"Did it ever occur to you what it cost Carlson in his refusal to concern himself in your efforts? Carlson, the strong man, Ajax, who could not see his own good! Did anything in his laboratory come nearer to winning a Nobel Prize, at that time the greatest award in the field of science and medicine?

"Was he not a Swedish immigrant?

"Suppose he had gone back to receive from his own country the award won in another, what a triumph, what an ovation, what a glory!

"He could have led you, on one side, and Drennan, on the other. You, yourself, have noted that Banting had to come back twice to Chicago and who could have said which of the three had made the greatest contribution, teacher or students!

"That is the way it is, with insight, you can forgive, since you can see as here, the man injured himself much more than he did you. I can forgive Carlson for his blindness.

"It may indeed be true that we go up as we help the other fellow but it would be a sad thing were we moving along only on the line of self interest. The lift to the other fellow should be given from the warmth of the heart, from the nobility of human affection, and this must be part of that first law.

"We are waiting for that long lost thesis of yours and it is pleasant to pass the time in expressing one’s thoughts.

"The laboratory at Chicago in those years must have been enormously alive with all you talented young fellows working together. What about Christian Beck, an interesting name? What was he doing? I have heard you mention his name," says Aleita, coming back to reality.

"What Christian Beck was working on then, I do not recall. He was working with Dick Greer. He and Dick handled the Quiz sections in Physiology for the medical students," Ernest answers.

"Dick was up there on the dais, asking questions, leading the class along a line of reasoning he had planned, one after another, and he could not move them. They hung on a dead center but he went on trying.

"Finally, he threw up his hands in despair and shouted:

‘There is no rule, gentlemen, in this class against thinking, if any of you should care to try it.’

Ernest recalls the incident.

"Poor fellows, perhaps they had just come from anatomy learning muscles, tendons and joints and couldn’t get their thinking caps on nor had they arrived at the stage of the surgeon demonstrating to his students, ‘Gentlemen, with one cut of this scalpel, I now cut through two months of anatomy,’ " responds Aleita, adding, "That rule against thinking need not have extended outside the laboratory into the echelons of authority as it appears to have done." In the silence that followed, Aleita remarks:

"It is now March 25, 1964, as we await your M.S. thesis in 1911.

"There was something about your thesis being macerated as it was being prepared for publication in the American Journal of Physiology where it appeared early in 1912. I have heard you speak of it. How was that?" Aleita asks.

"Porter was editor of the Journal at that time. I never blamed him. He was professor of physiology at Harvard and a man of considerable means and he was paying for the publication, or making up the deficit out of his own pocket. He was very nice about it, told me he was sorry but he did not have room for Table 4.

"This omission, though disappointing, could not have been of fundamental importance for Banting still thought the evidence favorable enough to warrant his repetition of the method." Ernest Scott knew the facts.

"That tied it in rather a neat package for you. Porter cuts out your most convincing table, Carlson puts in that damning sentence that it didn’t mean anything anyway.

"A neat piece of maceration and your name on it.

"I do question what will be the outcome of my recent letter to the University Library for a copy of your MS thesis. My letter asked for a typewritten copy, all charges cheerfully paid. Is it still available? Fifty years ago. In the cellar? In the garbage pail years ago?

"Oh! History! How weak are some of your links, Aleita Scott meditates.

THEN and NOW: BLOOD SUGAR METHODS

"Your basic contribution in the logical train of experiments that led to the isolation of the active principle of the pancreas in usable amount for the control of the level of the sugar in the blood was really the method to eliminate the destructive action of the digestive enzyme, trypsin which is formed in adult pancreas, wasn’t it?" asks Aleita Scott.

"Yes. Banting could have done it, so could the others had they thought of it," Ernest Scott answers.

"It all seems so simple now after the mystery has cleared. The real difficulty, perhaps, in bringing about acceptance of your work was in the blood sugar methods. It wasn’t anything then in 1909-11 as it is now.

"You used the old Fehling Solution method and weighed the copper precipitate?" Aleita queries.

"No. I did not do that. I used the dextrose to nitrogen ratio, the Lusk D/N ratio. Lusk had shown a constancy, thus permitting an estimation of the sugar in the blood from determining the nitrogen in the urine.

"There was not, at that time, the emphasis on the sugar in the blood that there is now. Determinations were of urine sugar and nitrogen in the urine and the D/N ratio was a ratio of urine constituents and it was followed as a better measure of the progress of treatment than would be that of sugar in urine, not blood, alone. The nitrogen was determined by the Kjeldahl method, used in straight chemistry departments," Ernest explains.

"How in the world did you know enough chemistry to do all the precise work you had to do! I remember joking about old Dad Seaman’s chemistry in Ohio Wesleyan in the nineties, you were ‘02, weren’t you’ The fellow ‘who didn’t believe in ions’. He was behind the times for it was not even a score of years later, 1913-4, that I was studying the mass of the electron e at Hopkins and we had gotten thru ions into electrons then. Whatever did you do?" inquires Aleita.

"I took a bang-up course in Quantitative Chemistry there at Chicago and there I really learned something, and I had a use for it, an immediate use for it"

"A good way to learn anything, to have a use for it. Why did you not make the determinations directly on the blood?"

"I tried to but the reliable methods in 1909 when I began my work took too much blood. I tried to use Folin’s picric acid colorimetric method but I could not make it work. I could do about as well by looking at the blood in a test tube as by running through this colorimetric method. I had to have something quantitative that I could depend on."

"How much blood did you need for a sample then? Now it is a fraction of a cubic-centimeter, isn’t it?"

"Some of the methods took 20 cc. Figure it yourself. If a cat, a big one, weighs 5 kilos (10 lbs.) and the blood is about 1/14th of the body weight, then therc would be about 0.7 lb. or about 4 to 5 hundred cc. in a very large cat, that is not over 500 cc. and if you wanted to run an experiment as I did for 36 hours taking hourly samples, and 2 samples of 20 cc., one for a control, possibly 40 cc., even the early samples would definitely modify the constitution of the blood, and could not possibly be considered as being independent of the very process of sampling. No. Those determinations directly on the blood were at that time absolutely impossible. Of course, I was working on dogs but that sort of thing could not be done and I simply could not use the blood sugar methods available to me at that day and was forced to use Lusk’s D/N ratio, determining the nitrogen in the urine.

Lusk’s D/N ratio I considered the most reliable method for following the course of experimental diabetes and response to treatment that was then available."

"Those Kjeldahl’s were time consuming and had to be done carefully. I remember doing some research with them."

"Yes. And I had to work on an experiment around the clock once and into the next night. I got pretty tired."

"Weren’t you home one winter fighting tuberculosis when you were working your way through Ohio Wesleyan? Pretty risky work for your constitution, I should think," Aleita says, remembering his youth.

"Along about 2 a.m. the second night when I got to that last determination, the thing simply wouldn’t work. The protein separated out into an ugly colloidal mass and I had reached the limit of my strength. I’d had it! So I left the big Erlenmeyer flask on my desk in the laboratory to clean up the next day and went to bed. The next morning when I ambled into the lab to begin a day’s work, a little late, Valdemar Koch met me at the door. What a bawling out I got! Valdemar said ‘What do you mean by leaving that thing on your desk and I had a guest from Belgium. That’s the way we make blood sugar determinations in Chicago I suppose I was to say’, as he stood furious against the doorcasing in his characteristic pose."

"You told me that before. It must have made an impression. I thought then you said Germany, but it makes no difference. Of course, knowing you, you made no explanation. What did we use in that method (Kjeldahl), concentrated nitric acid?", asks Aleita.

"I don’t know now but I think it was sulfuric, concentrated. One day I went through the swinging door, a flask in each hand, and caught one of my flasks on the corner of the lab table. It broke and went on my new pair of shoes and ruined them." Ernest has not forgotten that catastrophe.

"That was a major calamity, wasn’t it, for you! What were you and Helen living on then, $700 a year, I suppose?"

"No. It was more than that, $750, I think," he recalls.

"That wasn’t much even then for two. In ‘13-’15 I was working at Hopkins for $480, I recall, and only one of me, but when my savings ran out, I had to leave. Like you, I had other commitments. Didn’t they ask you to stay on at Chicago?" she inquires.

"Yes. On the same salary. But there was an increase in my family on the way and I had to have more money."

"So you went to Kansas for $1500 and knew you could do no research there."

"I was there a year, then went to Columbia. For my Ph. D. thesis I worked on a demonstrably reliable method for determining blood sugar and a study of the response of the cat to various laboratory conditions as revealed by the concentration of sugar in the blood."

Dr. Scott was promised opportunity for research in Kansas. The promise was not kept, as I learned later.

"I suppose you had to do that. No one would accept your findings in Chicago," leaving it at that.

MACLEOD
Western Reserve University
1903-1918

"I was always interested in the part Macleod played. It was a very important part, was it not?", questions Aleita.

"Yes. He shared in the Nobel Prize," responds Ernest Scott.

"I did not remember that, always thought of Banting, but I thought you said you approached him with respect to your work, hoping for his backing, at any rate arousing interest. How was that?", says Aleita, following up an old thought.

"I went to see Macleod at the Western Reserve University, Cleveland, around 1911. No. It could not have been, it must have been in summer of ‘12 for Frank was a baby, and that was the pretext I used to gain admittance, consulting him about the baby’s diarrhea." It was really summer of 1913, I think.

"That sounds reasonable, your homefolks in Kinsman sixty miles east, but wasn’t that rather far to go to consult about a baby’s condition!" says Aleita.

"Yes. I talked to Macleod about my work, about my findings, that I had succeeded in extracting a substance from the pancreas that lowered the D/N ratio, that it was important, and should be followed up. He was not interested. He shrugged it off." Ernest Scott could not forget that episode.

"Would you not have thought that later when Banting showed that your claims were substantiated by the results he obtained when he repeated your method, that he might have shown you some appreciation, given some sign of recognition to you?" demands Aleita Scott.

"Yes. I do agree. Macleod was the only one who did not play fair." Ernest Scott decides an issue.

"I suppose you exonerate Carlson because he was honestly stupid, whereas Macleod knew that you had done the work, yet deliberately passed over you, much like a steam roller, or a wolf pack on the trail," Aleita is angry.

"That is, indeed, the ‘cream of the jest’, that the man you approached for help and who refused it, later participated in the Award," says Aleita, scenting betrayal.

"He gave you one sentence in his book, ‘Carbohydrate Metabolism’, I seem to remember." That sentence was that the results didn’t mean anything, quoting the 1912 article, in spite of appropriating both method and theory.

The offence was much greater as a letter in 1922 exists in which the full particulars of the method were given to Macleod for testing and "use" in Banting’s work, a twice made gift, as we shall see in Part II.

"Banting would have done more for me, I think. He was a straight shooter," Ernest Scott affirms.

"I remember someone who knew the facts was talking the matter over and said, ‘That was Macleod’s fault. He did that.’ They patented your extraction method at the University of Toronto, gave you no courtesy," remarks Aleita.

"The stakes were high, the rewards great.

"Who won them!" Only time will tell.

BANTING

"Now, January 20, 1965, before I begin typing what I wrote last April, can’t you remember anything at all about Banting? His personal appearance? That time you heard him read his paper up there at Yale, I think it was, I should think you would." This was at the 1921 AAAS Christmas Meeting at Yale.

"I do not. I would not recognize him if I met him in Heaven," with a laugh, says Ernest Scott.

"Then I will not torment you anymore," relents his wife.

Returning to the Spring of 1964:

"That was a wonderful story as I heard it , of how Banting came to work on insulin. Do you think it true?" Aleita asks.

Eyebrows raised, "I think so. It is the way I heard it. It could be confirmed I expect, Army Records, hearsay as of now," responds Ernest.

"Was he in the R.A.F.? World War I," asks Aleita.

"No. He was in the Medical Corps, I think, the same as I was," replies Ernest.

"As I heard it, interrupt me, please, if I am wrong, Banting had been invalided home, ‘shell shock’ I heard."

"I am not sure of this," says Ernest.

Aleita continuing, "Everyone was in Europe, Macleod too, who was head of department in Toronto in physiology and Banting went back to an empty laboratory to work.

"He was interested in diabetes. What personal tragedy, if any, propelled him, as it did you and Drennan, I never heard mentioned," remarks Aleita, repeating a story she had heard long ago, "But he was free, without interference. He studied the available literature, by the great German investigators, Von Mehring, Minkowski, all of us used to know, and Zuelzer’s extraction used on diabetic patients, that killed as often as it cured and being a Canadian, he had no difficulty in locating your paper lying idle all this while in the American Journal. This he took as encouragement, repeated your technique and found, as you had claimed, and as no one would believe that your extract lowered the blood sugar. He had the courage later to advise its use on diabetic patients, doomed anyway, and found they improved with the treatment. And he had insulin! This is the way I heard it," says Aleita.

"This was after he was convinced that though his extracts of fetal pancreas and of ligated pancreas were potent, the method was not practical because of expense, he concluded that the only practical method was of extraction of the natural, adult pancreas and he tried my method and found that it worked. He was then the first to repeat my work and verify it. Whether he tried any other method or not, I do not know," corrected Ernest Scott, continuing, "If Banting’s statement in the Journal of Lab, and Clin. Medicine (1921-1922) is as I recall it, that he repeated my method with an adult pancreas and got a product active in human diabetes, he confirmed all the claims that I thought that I had made before," Ernest Scott concludes.

He adds, "The role of Collip and the Toronto team and the importance of their contributions will of course depend upon whether or not in their application for a U.S. Patent there is anything that is incompatible with anything in the description of my method. I am perfectly willing to acknowledge that their method is simpler in technique and yields either or both a more effective extract or a larger quantity."

"This was in 1920-21 or thereabouts, and Banting by that time had things well in hand. He had reliable blood sugar methods, not available ten years before to you," comments Aleita Scott, and then waxing somewhat annoyed, "When Macleod came home, the work was done. No quibbling, no sidestepping was now in order. Macleod the promoter climbed on Banting’s work, on his band wagon, or better, perhaps, built one for him and formed a team." This was revealed later as a truthful interpretation of events.

"Repeating your work, the method was simplified, to the extent of eliminating the stage of the prevention of oxidation, Fred Koch’s idea, being shown to be unnecessary, but your essential principles retained, all patented at the University of Toronto, without so much as a word to you," complains Aleita and still wroth, "Wouldn’t you think some of those big boys whom you had approached, might have had the grace to try to make some amends to you for their injustice. Did any of them, Carlson, Macleod, Lusk, do so?"

No answer from Ernest Scott.

"Carlson was still picking on your work forty years later in that testimonial letter from him when you retired, and this twenty years after another University won the distinction of the great Award, what would you expect of Macleod! He most certainly knew of your work since you had gone to him for help in Cleveland in ‘12 or ‘13, and he had refused it. Lusk, doubtless, was too disappointed that the great amount of work done in his laboratory had failed to bring the results he had hoped for," trying to recapitulate the wrongs and continuing, "Murlin was the man who was working with Lusk on diabetes, wasn’t he? The one to whom Lusk referred when he said if their laboratory couldn’t do it, how in the world could a young fellow like you, from nowhere, succeed when he had failed and they were failing, talking to Lee?"

"Yes. It was Murlin. He was doing good work," confirms Ernest Scott.

"Murlin, it was, was it not, who came to you and asked if you did not intend to do anything about it when ‘they patented your extraction method?’ "questions Aleita.

"Yes. It was Murlin. I thought he was right. That I ought to do something. That was when I wrote my Claim to Priority for the Journal of the American Medical Association in 1923," states Ernest Scott.

"Did they ever do anything about it?" says Aleita.

"Did you ever hear of it?" is the answer of Ernest Scott.

Aleita, silently, "I did. That head of department of cardiology at one of the big Fifth Avenue hospitals, whom you had met in France (it always seemed to me you met all your friends in the Medical Corps over in France) and he was supposed to be your friend, and he said to me, as response to the A.M.A. claim, ‘He ought to be jailed if he had it all those years and didn’t use it’, and my eyes blazed, even though then I knew so little of the real story, but believing so wholeheartedly in you, I resented his cruel approach. The next day when I met him, he apologized in a roundabout way, ‘I only meant that I wanted him to have the credit for what he had done.’ I remember the incident well to go along with the appellation of charlatan," all silently thought, and also thought silently, as a woman must, "All cheats together."

NOBEL PRIZE

Considering, "Will the time come when to receive one of these awards will be a disgrace?" cogitates Aleita Scott, and in the spring of 1964, resuming, "I do not like these prizes. They place the emphasis in the wrong place. Look at that old diener in Von Mehring’s laboratory. It took courage to speak up to the big boy and tell him he failed in his duty, that he just could not keep those operated dogs clean, couldn’t keep the flies off them. I think he should have had a prize. At least, we could remember him.

"How did Nobel get his money? They say you can’t make a million if you are an honest man. I shall look it up.

"It takes that library out at Chicago long enough to fulfill that request of mine for a copy of your thesis. If I do not hear soon I shall write again, the President’s Office this time," repeats Aleita Scott, and looking up what passes as facts, later, she states, "It seems Nobel did make his money honestly. He was a Swedish inventor, Alfred Bernhardt Nobel, and he made nine million, mostly as one of the inventors who didn’t starve in a garret, by inventing dynamite and nitroglycerin, together with locating oil in Africa, and he made a fortune. Seeing to what use his explosives were put in our mass murders of mankind, he, doubtless, wished some of his wealth guaranteed to go to a good cause when he founded his awards."

"Dynamite, almost exclusively, and nitroglycerin, largely, are used in industry, not in warfare, nitroglycerin also in medicine," corrects Ernest.

"How right you always are. We could not live without constructive uses of dynamite and nitroglycerin is prolonging your life right here, as you and I struggle with the control of your angina pectoris. You take it daily to ameliorate that scourge of the elderly. Let there be no lack of appreciation there. Yet, in some way I feel an inequity," submits Aleita.

"You wanted most of all to prevent the heartbreak you had seen of the fatal diabetes. You won that. A decade later (and what was the death rate from diabetes before insulin?) that disease has seen some sort of breakthrough and you played a most important part in the breakthrough whatever the public judgment," summing up that much, Aleita continues:

"Looking back, one often wonders what he has lost and what he has gained in the game of life. You played for high stakes. You won what you set out for, to help solve that ghastly problem of dying youth, and you really succeeded beyond your expectations. You did get out a safe and potent extract. All you could not do is to make the blind see. So long as people, and scientists, sadly, are people, so long as they will not look at the evidence before their eyes, will go on hearsay from one to another, follow, not lead, so long will the march of progress be slowed. As it seems so often, man is man’s worst enemy." How can one escape philosophizing when men’s actions come out of their minds, and bear thumbprints of their personalities, is Aleita’s defense.

"Then again, you could hardly have stood the pace that would have been set for you, traveling around, lecturing, your health, could it have stood it? All the honorary degrees."

"I might have had professional advancement. Money! I never had any until after my wife died.

She never had what I tried to give her, that money could have given, perhaps even her life. I never had money until after she had gone," Ernest Scott laments.

"She, too, was martyred by those early years of hardship. I remember about that salmon that smelled of formaldehyde when it went into the frying pan. You could have done with some more food. Though you say the university apartment was heated well enough, so you were not cold," Aleita condoles.

"You won to the extent that you have lived many years and maintained health." This is something. Helen’s loss was pure agony.

"What did you lose? Helen, first. She did not have proper food at Chicago. I mean beyond recognition of your fellow workers? Advancement, respectful council of your peers, all this, and I know what I resent too. It is your name. The name of Scott. You wanted to bring honor to your family name, money, too. The old farm was mortgaged. Your father, the farmer who looked like a professor, of the old school would have taken pride in his firstborn, greater pride, I mean; and your mother who wanted you to go to Ohio Wesleyan to be a minister, not realizing that science, so long as it serves the truth, and is served by it, is a practical amplification of the religious attitude, and beyond money, professional advancement. That greater honor to the name you lost and greatly lost. You earned it. You were deprived of it, and every other man or woman or child who is born to the name of Scott or who chooses it as a given name, loses the honor, that belongs to you, the rightful honor, Ernest Scott, "discoverer of insulin."

WILL THAT THESIS NEVER COME?

"I suppose we must go over some of this again. We are still in the dark after fifty years, as to your original thesis. Boxes of records and belongings had been lost in transit from Kansas in 1912. Only the 1912 publication remains. You went to Kansas with a new job, with a baby on the way, and a wife none too well," Aleita recalls.

"Yes. I was busy that year," Ernest answers.

"Knowing you, I’ll bet you washed diapers, too."

"Yes," with a grin, "When it was needed," as indeed he did.

"When you left Carlson your thesis, did you tell him to fix it up the way he wanted it? Some students do." Aleita asks.

"By no means. I wrote it the way I wanted it to be presented to the public in print. I wanted no changes in it in any way." Ernest Scott makes his assertion.

"I am glad to hear you say that," the woman replies.

BANTING, AGAIN

"When you saw Macleod at Yale that time, did he talk to you at all?" asks Aleita.

"I do not recall it," he answers.

"I wish you would tell me more about Banting. You did meet him once."

"I think Banting, if left to himself, would have given me full credit for having developed an active and safe extract of the pancreas," Ernest Scott affirms, (as he did indeed, in 1921-1922) and says, continuing, "I have always wanted to know what went on in Toronto when Macleod returned from Europe, whether my method was the only one used and what methods for blood sugar and urine sugar were employed, during that first year and a half of that crucial work of Banting’s."

Then, "Some of it is in Banting’s paper. I recall he cited my work. We ought to check all those items." Such work takes time.

"I will do that, when the weather settles out so I can go into the City, I will begin a search of documents," asserts Aleita Scott.

THAT THESIS IS SO LONG IN COMING!

MACLEOD, AGAIN

"What sort of person was Macleod when you went to see him in Cleveland about help in promoting your extraction of the first safe and potent extract of the pancreas, around 1910-1911, really summer of 1913 when you figure it out from when Frank was born. What was he like?" asks Aleita.

Impatiently, "How do you expect me to remember, to remember that! It is over fifty years ago!" Ernest replies.

"But you must remember something, it was so important to you. You could get nowhere with Carlson. You were exploring every pathway you could see, every possible lead to win support for your work. You must remember something."

"I remember, I think, he had a black mustache, rather small," Ernest remarks.

"Was he large, a large man?" she asks.

"No. Rather smaller than middle size, I think."*

*photographs show that the memory picture was correct.

Something to talk about, "Prejudices run deep in the human mind. Often we react quickly without awareness of the cause, do you think Macleod had a prejudice against your name? Was there a feud in ancient times between the Scotts and the Macleods? You were both Scotch. You are ‘black’ Scots," says Aleita, continuing, "I’ve always admired your black, black hair, now at nearly eighty-seven, there is still lots of black in it, close to its roots. My own spun gold locks went silver in my 50s, and it is a personal prejudice of mine, I have always been grateful that you were not, never could be one of those whitehaired boys, supposed to know everything," she dares to say.

Not pleased, he answers, shortly, "I never heard of a feud between the clans, the Macleods, the Scots. I have heard that the Scots were the largest, most powerful clan and it may be, since the country took the name."

"I have taken pride in the name of Scott, a good name," his wife answers.

"It may be that Macleod never thought, never gave a thought to the injustice he did you when he gave you complete discouragement when you approached him for help in 1912 or ‘13, and yet accepted the Nobel Prize on your work, the ‘discovery of insulin,’ in 1923 after Banting in his absence proved your extraction method reliable. He may never have thought of the moral, ethical aspect," Aleita attempts exoneration, and continues, "I never knew the man, never saw him. I am merely imagining how a good, fine man might have done it.

"My acquaintanceship was through his textbook in physiology that we liked in the medical school. It was easy reading. It was remarkably complete. It was an excellent recording of work done by other men. The first edition in 1918, it went through many editions and was a monumental work but not in the same class with Starling’s text," she goes on.

"Macleod was accustomed to using other men’s work. His monograph on carbohydrate metabolism in 1926 showed extensive, enormous reading, complete grasp of the subject, except that he never saw through the maze, as your incisive mind penetrated the same jungle of thought when you attacked the problem in 1909-1911. You succeeded where he failed," she admits.

"One wonders how he could have so completely slighted you, to the extent of patenting your method via his students. His blind spot must have been somewhat similar to that of Carlson, ignoring the rights of the man who stands in your way. You refused to work on Carlson’s problem, believing more in your own and you had no interest in his, Carlson’s neurology research and you were very much more in Macleod’s way. You stood between him and the highest awards possible in the life of a scientist, although he may never have dreamed the furor created by the ‘discovery’ and all the honors pertaining thereto.

"They both pushed you aside as though you did not exist. All that sacrificial, exhausting and heartbreaking effort! A ‘discovery’ by fiat. Power!

"Had you not published that claim to priority in 1923 you would have sunk into oblivion. I am glad you published that. You did well," Aleita summarizes.

Ernest Scott says, "You have something different in mind than I have when you say ‘Discovery of insulin.’ I did not ‘discover’ insulin. Many others suspected its presence. Zuelzer even patented his extract in 1908 the only trouble was that his extract when injected, killed as often as it ameliorated." Hesitating and then continuing, "My contribution was that of producing the first safe and potent extract of the adult pancreas in the treatment of diabetes, experimental, in my work."

"The proof is that Macleod’s students patented it. I know all that too, that you have just reproved me for saying, the early history, but just a bit of carelessness on my part. I followed the manner in which insulin was presented to the public mind, that is, as discovery, rather than the correct term, extraction.

"Macleod was so important in this story. Macleod’s monograph has an index of subjects. There is no index of authors, at least, I did not find it. It may be there," and then, "Perhaps Macleod cared for ideas only, did not care for men, or their feelings, the personal rewards, or professional advancement for their labors.

"In that case, he should have refused the Nobel Prize."

Ernest retorted, "My attitude was somewhat different at the time. I was glad enough that Macleod pushed the thing. I had tried my best to get support, could not overcome the inertia. No one would move. I could not move them. I had other things on my mind, heavy personal burdens. I had given my best, had done all I could, was glad to see the thing I had worked for, to save people from agony, the emotional agony when the disease strikes the young, at the very promise of their youth, that was what I worked for, to see the thing pushed."

"You are a rarity, an unselfish man. I am glad I have, in my life, met several of these. You, the greatest!" Aleita concedes.

She says, "The unselfish man needs encouragement too. He needs the backing, the confidence of other men. His work profits."

Going on, "Our family grew up in the days of horses. Our coal and lumber business depended on them. One principle in management was never to give an animal a burden too heavy to pull. Load his wagon beyond his strength when he cannot draw it, it ‘breaks his spirit.’ I think it was Marcus Cato, in his ‘De Res Rustica,’ the first book on agriculture, who studied animal behavior in order to learn how to treat his slaves. Indeed, we are all slaves, though in different ways. We can learn, or can we?

"I think men are like that. It breaks their spirit when the burden, the cross, sometimes the cross of ignorance is too heavy to bear.

"You never again were able to give that great full hearted, emotional and intellectual vigor to your later undertakings. When they take the heart out of you, something is irretrievably lost.

"I have written to Stockholm. I want the exact wording of that AWARD. Were it for the first successful treatment of human diabetes with that, who could quarrel?

"We have delved into human beings in one of man’s great adventures, conquest or better, more properly, in retrospect, amelioration of a specific disease, illuminating, rewarding, as any such quest may be," Aleita comments and continuing, "I have thrived under the protection of your name but have no share in it, have none of its genetic endowment, nor have I contributed any of its genes to posterity, nevertheless I consider it a great name and a good name. So long as names of men have value to other men, as sources of appreciation and of emulation, or as warning signs of deleterious behavior, so long has a man the right to cherish his name.

"Your first publication, that of your Master’s thesis, in which you claim the method for the first, the very first safe and effective extract which upon injection controlled diabetic symptoms, reduced the D/N ratio, carried your full name, Ernest Lyman Scott. Only one of your later publications does so. Why?

"I think then you had high hope, pride in family. You hoped to contribute in such a way that your family name would be lifted a little higher.

"After your contribution was appropriated by others, by the very ones who had refused you help or encouragement, and you, yourself, pushed aside as a nonentity, you sank to a lower level, enclosed in the human mass of unmarked men. You survived, survived very well, but you were hurt, injured, deprived of your just due.

"Reviewing all this has been fascinating, interesting to see through the windows of men’s actions into their minds, as ‘through a glass, darkly.’

"We learn from mistakes, errors, even more than we do from successes, provided only that we inquire into, arrive at the causes of the mistakes." Aleita Scott expresses her thoughts.

WILL THAT THESIS NEVER COME!

"Macleod was a man who used other people’s work, was he not? I never heard of any research he was known for."

"Macleod had been working on carbohydrate metabolism for years," said Ernest Scott who knew the literature, and continues, "I can see Macleod’s point of view and of Lusk’s. Both had been working in the field for many years and getting nowhere.

"Then along comes this young squirt and gets the answer in six months! Why should they pay any attention to him?" Loud laughter from one who laughs rarely! "It seems ridiculous," agrees Ernest Scott.

"It is like that. Still, taking your method, after its being repeated and found effective, and patenting it without so much as a word, going over you like a steam roller, I cannot see the rightness of it. I seem to boil within as at a gross inequity. I cannot conquer the feeling."

She adds, "That quotation of ‘Making Gods of the Scientists,’ we like the ancients might regard their feet of clay."

"I offer you this," he responds:

"In 1912 when I came to Columbia, I offered my work to P. & S., through Dr. Lee, and they elected to leave it alone. You can see that it was just as open to them as it was to Banting in 1921."

"Ten years went by," she muses, "The Lost Decade," and how many deaths that need not have happened!

"Macleod knew all about your work. You had consulted him and he refused interest," not able to leave the problem, she repeats, "He used that damning sentence Carlson inserted, that you made no claim for it, against you. And here we sit waiting. Will that thesis never come! What is the use of a story like this! Will it go into a pigeon hole somewhere and never be looked at? Was the thesis irretrievably altered? We know that scientists like other professional groups, cover for one another, as certainly do the doctors. Accuse one, the rest rush to his support. Attack the system that gives the Head of a Department murderous control of his subordinates! Off goes your head!" Aleita Scott is not altogether pleased with the system, under which she too has served.

"What other system is there?" remarks the realist, Ernest Scott.

"We hobble along," both concede.

FRED KOCH AND OXIDATION

"We ought to make it clear that Fred Koch, trained chemist as he was, did not solve the problem for you. You have emphasized all along that the chemical part of your work was done in the Department of Biochemistry, not in Physiology." Aleita Scott wants to get the facts straight.

"Fred persuaded you on the possibility of oxidation, did he not? You had not too long to work and you decided to eliminate the possibility of oxidation, did you not? Was it very hard?"

"No. It was not hard. It was just fussy," Ernest answers.

"I’ll draw it for you. Give me your paper.

"I was young then, when I went to the University of Chicago with my mind on the tragedy of diabetes, when I was working on insulin. I thought people were working on a problem to find out the truth of it.

"I was naive. Later, I grew up. I found people, men were working on a problem not to find the truth, but to gain the kudos attached to it.

"Banting, in that early paper, was more or less in my position. Perhaps he grew up more rapidly.

"And Zuelzer, poor old Zuelzer, and all those German workers, they go down the drain." Ernest Scott stops speaking.

"Zuelzer came to your laboratory once in New York, when I was working there," Aleita remembers.

"I seem to have forgotten," Ernest replies.

"Wasn’t he a sort of big man, physically, shambling a bit in his walk?" He had made an impression on the woman.

"Maybe. I seem to recall him. Yes. He was there. His preparation that killed as often as it worked. There were several who were working on it," Ernest Scott recalls.

"Some of the problems seem problems in ethics and morals," Aleita digresses, as the two people await the arrival of the 1911 M.S. Thesis on experimental diabetes. "A distinction should be made. Ethics is the ideal good. Ethos is Greek for character. Morals are matters of custom. "Oh! Tempora. Oh! Mores!" An echo from my 6 years of Latin, sixty years ago, as I remember it, "Oh! Time. Oh! Customs." Custom! What a difference! Someone, at times, must raise his head above what is custom and proclaim what is good. Otherwise old customs would still be with us. During ages past, custom decreed the yearly sacrifice of young kings to insure fertility of old queens, the burying alive of sinning vestals, the burning or hanging of witches. Truth may be proclaimed the pillar of society, the sole god of the scientist, and yet custom, as professional courtesy, may condone infraction, which is the custom today. If a man is big enough, as they say, he can do anything without reproof and with no restitution to the injured party. I say this is unethical, wrong and reprehensible, however august the offender."

A few days ago, April 21, 1964, Prof. Scott had requested a few sheets of university letterhead to which his rank might be considered to entitle him. I suspect he wanted contact with his old domain. His request was met by surly refusal by the then head of department. Had he been accorded his due, his name would surely have been carried on the letterhead during his lifetime honoring it by its presence. Without recognition, he was denied even one sheet of paper. Awards have value.

The Ancients, according to Plutarch in his castigation of Marcus Cato, thought old slaves should be kindly treated, not deprived of privileges to which they were accustomed. Amusing echoes along the corridors of twenty-one centuries! We are all slaves, bound in bodies not of our choosing, chained to circumstances ordained by the universe, in a society to which we are expected to conform yet not of our making.

Interesting, is it not, that a man who, according to Banting and Best, Journal of Laboratory and Clinical Medicine, Vol. VII, No.8, 1922 pages 467-468. gave the principle for the extraction of insulin, which substance extracted by his method, on injection kept diabetic dogs "alive and healthy" for as long as wanted, and later when used on diabetic patients removed their "symptoms of diabetes,’ that this man who made the medical breakthrough of the 20th Century, was unknown in the university where he worked for thirty years and to this day remains generally unknown.

THESIS ARRIVES

These are the dates relating to the exhumatior of M.S. Thesis T-10553, University of Chicago 1911; Letter to the Library, March 19, 1964; letter

to President George W. Beadle, April 17, 1964; receipt of Thesis, May 3, 1964.

After reading the Thesis, Aleita Scott says to Ernest Scott:

"Everything that you have said as you recalled the story has turned out to be true, exactly as you said." She adds, "The MS Thesis (T-10553) which we have received today, May 3, 1964, in typewritten form, as you submitted it in 1911 but yellowed a bit and greyed, which has been returned to you from the Library of the University of Chicago, is as you said it was and this is quite different from what appeared in the American Journal of Physiology, 1912, the version of your thesis that was changed and published without your knowledge or consent. This is the original, the file copy. These are the original typewritten sheets that you gave for publication to Professor Carlson when you left in September 1911," affirms Aleita Scott.

MAY 3, 1964

Affidavit original in National Library of Medicine:

"That dissertation I can recognize, and anything beyond it I cannot recognize. I know nothing about it." Signed: Ernest L. Scott, dated May 3, 1964.

This affidavit was made upon reading his thesis after a lapse from September 1911 until May 1964, and rereading the article under his name appearing in the American Journal of Physiology, January 1912.

TEN YEARS AHEAD OF HIS TIME

"Here is a partial answer to my question, what does it mean to be ten years ahead of one’s time," Aleita speaks.

"It means to be the only person in the world to see the thing straight, to see it as it is, to stand alone. The others could not see it even after they were told," she says and adds, "Why did you not do something about this at the time?"

"Things were hectic at the time, leaving Chicago," replies Ernest, "Helen was in labor, had been in the hospital. A young obstetrician gave me a list of obstetricians at every stop all the way from Chicago to Lawrence, Kansas. I was taking my MS examination, and packing. I was busy that year in Kansas. I have told you. Yes! The rewrite job that I saw in January was a terrible thing for me. What could I do!"

Indeed, a few years later, I do not know the exact date, 1919, perhaps, Helen started a downhill path never to recover. There was a boy to mother and father, for whom to provide a semblance of a home, the boy in eleven different schools before entering college and "never having any money until after she died." Heartbreak? What do you think?

We have come to the denouement of this story.

In my effort to make "those days in Chicago live again" I succeeded so well that the corpse, the murdered MS, the corpus delecti of the mystery story of why the "Man Who Discovered Insulin" was overlooked, this corpse walked. It was lively and after fifty-five years in a locked domicile entered into the light of day walking into international light. This brief publication has power to overturn tradition of worldwide acceptance, the first publication of Thesis 10553, 1911, University of Chicago, in 1966.* Can one make the willfully blind see?

*Ernest Scott’s Thesis of 1911" by Dickinson W. Richards, Perspectives in Biology and Medicine, University of Chicago, Autumn No. 1966, also Part II, LIFE.

There is a question, perhaps, even the same question, Who cares! No one cared to point of action in 1911, or in 1923, or in 1942. Now, in the present?

RETROSPECT

Aside from the mutilated thesis there was another and different reason for the failure to attain recognition. This is a matter of chemistry. It ought not, however, to have blinded people.

Continuing my talks with Ernest Scott, "How much we learn from history depends upon the person who is doing the learning. Looking back upon the fascinating story, one might think that the outstanding point of bright illumination, of scintillation even, is the point of intersection of the line of research on pancreatic function with that of the development in the technique of measuring blood sugar in small samples.

"When you read that second article (J. Lab. & Clin. Med. 1922) by Banting and see how his blood sugar values, on coordinates, dropped down, down and down after injecting the extract prepared after the Scott method, anyone could see that ‘he had it’.

"This fall in blood sugar immediate upon injection was dramatic, awe-inspiring. It was the scintillating, spiculate point in the whole story.

"Everyone, now, could see it, and the ‘wolf pack’ of investigators was on the trail and so continues to this moment.

"All those investigators who made the progress in blood sugar methods get little credit in the story of the ‘discovery of insulin’.

"That story of improvement in such technique is partially recounted, as I recall, in his book, ‘Der Blutzucker’, 1913 by Bang. Your Ph.D. thesis was a presentation of the various available methods. You knew that was where the path ahead lay. Bang, in Copenhagen, McClain in St. Thomas Hospital in London, Folin and Shaffer in this country and many others were improving methods for small samples of blood, and it was all this work done by very careful investigators that made the insulin effect obvious to all when Banting came along in 1920-21.

"You and Fred Koch (his testimonial letter on your retirement in 1942) could see from the urine into the blood, but Lusk, who himself emphasized the value of the D/N ratio could not see it. Carlson could not see it. Lusk and Macleod, the two men who knew the most about carbohydrate medabolism, could not see it."

Ernest explained, "The problem of measuring (identifying) the effect if any, of an extract was not generally recognized. To do this significantly, required from several to many blood sugar determinations. Samples must be taken at short intervals to follow the progress of the effects. Now, at that time, as I said before, but repeat, Folin’s was the only method that had been proposed that even purported to use samples of blood of practical volume. It had been demonstrated that sugar concentrations of the blood would vary from the beginning to the end of a single sample as in two samples of a duplicate determination. Folin’s method might help a clinician in following a patient, but the precision in my hands made it useless for me in research. Hence I turned to Lusk’s D/N ratio, as it permitted samples of urine large enough to give measurable quantities of both sugar and nitrogen with no physiological modification of the subject, and it, the D/N ratio, had been proposed by Lusk, the outstanding authority, as the most significant indicator of the intensity of diabetes."

"You do not like much to talk but I do. Bear with me," Aleita says, "It is not a problem, as I tried to show it, and perhaps confused the issue, of the brute and the scholar, the brute who overrides the vital force of another, or the ineffectiveness of the gentle scholar, it was merely the matter of being able to see, to possess the intellect to consider, evaluate, and conclude. The essential work was chemical and Carlson was no chemist. It was all there but few could see it, you and Fred Koch, and Valdemar Koch, too, but I have often wondered why you did not repeat the work at Columbia, what you had done at Chicago." She considers, then, "Foolish question! I worked at P & S in 1920. I remember ‘the old dump.’ How old was that building on 59th Street then? Cockroaches, creaking wooden floor boards, dark, dirty, a ‘medical school’ of the old days it was. No one in Physiology, as I recall, did recovery operations there at that time. They could not. There were no facilities, no operating room, an autoclave, but no recovery room. Chicago, ten years before was way ahead with its Rockefeller money. Did anyone ever thank the Rockefellers! Recovery operations would have had to be done in Surgery, and with special permission. They may have been cramped for space. But as you say, have said many times no one in Columbia at that time was especially interested in research on diabetes. You were a beginner with only an M.S.

"Most important, rarely reiterated you were waiting for that second man, the man who would repeat it, the method of science, the man who would try it, would refute or verify your claims. You were so sure of it, if they would only try it and see! You did not need to repeat it."

After a lifetime in the educational world, all my adult life either in or connected with universities, I have sometimes felt that appointed heads of departments should be abolished. Elected chairmen might serve the purpose better. Still it is the matter of the man. Some appointed chiefs have been magnificent, capable and admired by all. Sometimes I have felt the Nobel and other prizes should be abolished. Often emphasis is thrown on the wrong aspect. It did in this case dramatize the problem and made the subject of diabetes and insulin important in the public domain and known to all.

What has brought about this confusion in this history of the successful extraction of insulin? We have the right to inquire.

Aleita Scott considers the course of events. She thinks, "There seems no question but that in the interval between September 1911 and when the MS was ultimately submitted to Professor Porter, Editor of the American Journal of Physiology it was so rewritten that it was nearly unrecognizable. As Ernest had felt, on reading the Journal 1912 article and the thesis in sequence, neither could I recognize them as being the same. There seems to be no question as to who did the rewriting."

It is remarkable, indeed, fortunate, perhaps, that the head of department did not "believe" in the work otherwise, as customary, his name would have taken precedence over that of the student.

It is interesting that Dr. Scott had his way at Chicago, remarkable, really, and it was only after leaving the University that the head reasserted his authority. Ernest Scott in spite of being a gentle man does not push easily. When he was gone, it was another matter.

The method and part of the experimental data were left intact, testimony to so much integrity of a scientist on the part of the head of department.

During part of the conversation on May 3rd, (thesis received) Dr. Scott’s reaction was so emotional that, in view of the effect of emotion on angina attacks, I had to change the topic of conversation to divert his attention to less painful thoughts. He had been deeply hurt. For him, it was a "terrible thing," the change in his thesis, destroying its impact and stealing his method, which came later, as we may easily prove, and shall prove in Part II.

ADDENDA

"Those years at Bay City where you taught physics, botany and physiology left a deep imprint on your mind. The way you attacked that problem of making an extract of the pancreas that would work and the way you wrote it up had the precision of a problem in physics, the way I studied it," Aleita continues, "You were sure of your work, willing to put it on the line, never would have given permission for those alterations. ‘He changed it,’ as you said, but what a change! The clarion call of victory into a weak whine!" and analyzing his accomplishment, "With a keen mind, complete devotion, a powerful drive of emotion, you saw the problem, solved it, against all sorts of obstruction. The record of the working of your mind, a rare record, indeed, of the working of a man’s mind, is apparent from the underlined portions of your copy of Hammarsten’s text of Physiological Chemistry, 1909, now in our National Library of Medicine. Only after you left Chicago leaving your chosen work successfully completed, ready for publication, only then was it altered almost beyond recognition. The method was intact. And your original manuscript is a masterpiece of straight thinking with a solution to a problem that until then and a decade later had stumped the world." She is content with her summary. "I can forgive that. Head for his stupidity, quoting Claude Bernard (1813-1878): ‘It is what we think we know that prevents us from learning.’ But how can I forgive him for using another man’s name carelessly!

"I shall never forgive him in keeping silence in the face of your Priority Claim in 1923 knowing what he had done. I shall not forgive him for trying to assume credit for Chicago for the discovery of insulin in that 1954 Seminar Course and for having someone read that 1912 Journal article oblivious to that original thesis still lying there in the files of the library although I was not present to see all this, gathering the details from the correspondence no longer extant. You can have the arrogant Carlson and others like him," the woman dares to speak.

"Were I young again, were I to enter university work again from what I have observed I would go with a well-trained lawyer to defend my basic legal rights, among them the right to my name."

Turning again to the problem of the insulin story, her analysis continues, "We might say that your mistake was in trusting that ‘second worker,’ the one for whom you had searched so long. I admit no mistake on your part. This is the established practice among scientists. That the one to test your method and verify it, later in the Patent claimed it as original was his error, not yours." Condoling the deprived, "You lived with this ‘fox in the bosom,’ gnawing your vitals as your faith in the integrity of your fellow scientists was shaken yet unwilling to accuse another man, for these many years. Do you think, perhaps that some of the trouble devolves from the fact that in this work we are dealing with doctors of medicine, one a doctor of public health? Medicine is an art. Members of that profession, medicine, place loyalty to one another above loyalty to truth. God is TRUTH. Truth is held as the Scientists’ sole God."

HYPOTHESIS AND SOLUTION

"That hunch of yours, that insulin, ‘the hormone’, then, was a protein.. ." Aleita Scott wants it straight.

"Yes. I figured it," answers Ernest Scott.

"Valdemar Koch gave a course that first summer I was in Chicago, it was a bang-up course. That was to fill in an area he thought needed," continuing:

"I got the fundamentals about proteins and their extraction though I did not finish with him," he concludes.

"Valdemar was in Biochemistry, was he not?" Aleita asks.

"No. Pharmacology. He was filling in, in Biochemistry after Carlson ‘drove out’ A. P. Mathews," Ernest replies.

"I never could recall whether A. P. spelled his name with the double t. I liked his text in Physiological Chemistry, a good thick book that ‘had everything’," says Aleita, adding, "You liked ‘A. P.’, didn’t you?"

"Yes. Very much. He liked me. He gave me his room, a nice little room 10 x 12, at Woods Hole, one summer," Ernest recalls.

"What was Valdemar’s research? I do not recall your saying," Aleita inquires.

"I think it was the chemical basis of dementia praecox, but I am not sure," is his reply.

"Ahead of his time, too, wasn’t he?" concludes Aleita. "You said Valdemar influenced your philosophy, not so much your actual research. It seems to me you got a fundamental aspect in your thinking from him."

"Yes. I did, indeed. But it is a long time ago. I had forgotten," he answers.

"He died young, you said, in his early 30s. He did not take care of himself, pneumonia, I think you said. A rare personality. I have a beautiful picture of him in my mind."

Valdemar was "very German." His father, brother to the great Robert, was a practicing physician in St. Louis and he wrote Valdemar in the German way, with a W, but he pronounced it as with a V, just as Pavlov was once written in English as Pawlow. Some of us remember how, in the days before World War I, a German, a German name, or even a German accent was a decided asset among scientists.

It can now be seen that when Ernest Scott had read the available literature in German and in French, and what there was in English, he fitted the parts of the puzzle together within the framework of a "hunch," or hypothesis that the internal secretion of the pancreas was a protein, and when his method yielded experimental results that conformed to his idea, this was what made him so sure that he was right in claiming success.

He said as our conversations ended, "I thought it was a protein and that is what it turned out to be."

This was his success, and his alone. Not until 1955 was its chemical structure revealed. Insulin has a molecular weight of about 6000, and consists of two peptide chains; the A chain of 21 amino acids is acid and has an N-terminal glycine; the B chain has 30 amino acids is basic, and has an N-terminal phenylalanine. The chains are connected by two disulfide bridges. For a protein, it is simple. In 1965 and in 1966, human insulin was first synthesized and said to be the first human protein to be synthesized.

Ernest Scott had guessed the protein nature of the pancreatic hormone in 1909-1911, and had made the first reliable extraction on that basis. He died in January 1966 as insulin was being synthesized. He knew of the work. He went out of this world unthanked and unrecognized.

A CONVERSATION BETWEEN A DIFFERENT PAIR

"Ernest Scott had a hunch that the hormone was a protein. It was as simple as that. Anyone could have done it," remarks Aleita, knowing fully the seeming complexity of data in pre-insulin days, and remembering her own whirling head when first presented with that research data, in 1920.

"Yes. Anyone could have done it. But they didn’t," responded Friend Dick.

"Maybe it wasn’t so simple. Maybe Banting and Best didn’t know what they were talking about in 1921-22, when they said they used the E. L. Scott 1912 method of extraction," retorted Aleita Scott, "and succeeded with its use,"

"But they did," Dick said decidedly.

Actually, in his 1921-1922 publication, Banting never stated that he devised any method of extraction of the active principle, the hormone, from adult pancreas. Failing in his effort with fetal pancreas, he states that he returned to a search of the literature and located the 1912 article, repeated the Scott method among others, and selected it as "the most efficient" among all he tested. He claims no originality nor does he mention any changes in this Scott method, stating that the diabetic dogs became healthy under medication with it and human diabetics recovered. Where is discovery? He "discovered" Scott’s method. Did he discover insulin? Is this a new type of discovery — "In the literature?" There was not so much literature in 1920 to win such accolade, as was later accorded him. Did he deserve all those honors when he discovered that gem, the method of extraction, in the trash of the 1912 re-write job?

Ernest Scott’s life and work merits study. He it was who made the medical breakthrough of the 20th century, he, and none other. Banting tested various methods. Scott evolved a theory, and devised a method based upon it.

PATENT
#1,469,994

October 9, 1923

United States Patent Office

After long delay, finally, a copy of this patent was obtained, in the summer of 1964.

During these months of conversation, I had been going on faith. The beauty of faith is that it needs no proof. Yet proof is sweet.

The time had come to confirm beyond possibility of doubt the claim of Ernest Scott to the first insulin extraction. The patent was needed.

When I tore the wrapper off the mailing package and read in printed form those familiar steps each of which I recognized at once, yet presented under the names of three men with whom I had no acquaintance and never would know, the full enormity of the offense overwhelmed me. I have reason to think that I passed out of consciousness, and this for a considerable time under the emotional shock of it. (I was being driven by my stepson in our car, and I fainted, collapsing in the seat.)

Returning to careful study it became clear that one step only had been added. This step, centrifuging, was in no way essential. It was a first step in purification leading ultimately to synthesis. Its relative importance is illuminated by the fact that centrifuging without the preliminary steps enumerated in the 1912 Scott method and in the Patent could be carried out through all eternity without yielding insulin, whereas following directions without that of centrifuging has been found to result in a 50 per cent drop in blood sugar, and was the form used by Banting himself in his first published article, and in his Nobel Laureate Lecture in 1925, in correcting both experimental and clinical diabetes.

We have the obligation to inquire into events which deprived Ernest Scott of all recognition for his wonderful work and gave all honor to those who repeated his method and thereby proved its reliability. He, himself, had given his method to those same persons "for use."

Few such stories are as well documented as is this true history of the manner in which insulin was first successfully isolated and of the man who made the first successful extraction, and its first use in medicine by the first man to repeat the method.

Ernest Scott’s life follows. The 1et~ters and printed documents which provide the framework of the study appear in chronological order.

PART II
LIFE OF ERNEST SCOTT

1877-1966

"I had done my best.  I could do no more." Ernest L.Scott

LIFE

The dark decade between discovery, that is, first extraction of insulin in 1911 and its first use on human diabetics in 1922 is illuminated by an orderly presentation of Ernest Scott’s life, by letters and by printed documents.

Photographs and stories throw light upon the nature of the man whose single mind unaided evolved a hypothesis that yielded insulin in 1911, never duplicated by another mind, who could not make the blind see, and who chose to stand back in 1923 permitting others to take the honors, when he could have won his case had he taken it to court.

We may conclude that character is the basis of performance, that a man’s integrity is his most precious possession and we may hope that truth may emerge ultimately from confusion and that truth may be accepted by all.

CHILDHOOD

Ernest Lyman Scott was born on August 18, 1877 in the small town of Kinsman in Trumbull County in northeastern Ohio. Kinsman is situated thirty miles south of Ashtabula on Lake Erie, and the same distance north of Youngstown. Kinsman Road runs sixty miles nearly due west to Cleveland. Pittsburgh lies about the same distance southeast. Kinsman known as Farmdale is famous as the birthplace of Clarence Darrow.

Ernest Scott was a farm boy born on a quarter section of 166 acres, the extra six included by mistake but cheerfully received, which had been a U.S. Grant to his great grandfather William Scott not long after the Western Reserve was opened for settlement in 1802. His grandfather was James Scott. Ernest as a boy heard his grandfather tell of driving a team of oxen to Pittsburgh spring and fall for supplies of sugar and coffee and to sell farm pro

Page 64 top missing

Road a failure?

This farm three miles north of Kinsman was beautiful. The land was fertile. Publications of the US Department of Agriculture lay on the table and were studied. Lyman was respected as a good farmer. Crops were corn, wheat, onions, tomatoes. There were orchards of apple, plum, peach and pear. There was horsebreeding too, important in the great horseracing state of Ohio. There were cattle, sheep and pigs, fowl of course.

Why, in 1926 or so, when Hattie and Lyman after their lifetime of mutual love and unremitting hard work, dying in their mid-seventies, in adjoining rooms, each unknowing, nursed by the devoted Nellie Ann and Clyde who never left the farm, why was this rich farmland sold at once following their deaths within a month of each other, for accumulated mortgages?

2.jpg (77605 bytes)
Ernest Lyman Scott
about 2 1/2 years
Kinsman, Ohio---1879 or 80

Lyman was licked before he started although like many another he did not know it.

Other farmers survived the many depressions. Many prospered. Why not the Scotts on Ridge Road?

In the 1880s and 90s there was a succession of depressions. In one never forgotten year the sale of the onion crop did not yield enough to pay for the bags the onions were packed in and men had been hired for weeding. One year a late February freeze not only froze the flower buds on the peach trees but killed the trees. It takes four years to produce a peach crop. Milk was 2 cents a quart. The seven-year-old boy one summer got up at 3 a.m. to bring in the cows from the pasture for a 7 a.m. pick-up of milk cans on the roadside. He remembered, barefoot, pushing a cow aside to find a warm spot for his feet. "Collie" he was sure could count. At the barn, "You missed eight, Collie." Collie would return to the pasture and bring in the eight. Farm work was unremitting dawn to dusk. What pleasure there was, was in the work.

These conditions were the common lot. Why did the Scott Farm fail?

The consensus was that the cause lay in the provisions of an impossible will. James Scott left his son Lyman the full 166 acres but added an annual cash payment to his daughter, Lyman’s sister. These payments were to be made irrespective of the annual income. In bad years money had to be borrowed from a bank to meet the deficit. Lyman, a man of integrity, never failed to make the payment. Often the hearts of the parents were saddened when they could not give their own children the fine educations the sister’s children received. Those who knew the story affirmed, "Under such a will Lyman ought never to have accepted his inheritance." I never saw the will but I believe the story.

Lyman Scott was born, grew up, married and lived his whole life on this land. He must have loved it. It was his whole life.

Ernest Scott grew up on this land. If he loved it, he never said so. The wide slope of farmland from the wooded hillsides stretching to the Pennsylvania state line eight miles eastward and to the horizon twenty miles west, sprinkled with large white flowerlike farmhouses fringed in green, must have made itself a part of him yet he never mentioned its beauty. Even in latter years when youth reasserts itself in memory there seemed never to have been yearning to return. He may have seen it from the first as a losing proposition. He chose his own path. So long as his parents lived his heart was never far away. The great happiness of softening the hardship of their old age was denied him by circumstances beyond his control.

One may wonder why Lyman did not refuse payment of the annual claim in years that yielded little or no profit. His choice lay otherwise. His integrity perhaps was the deciding factor. I never heard the question raised.

The children went to the village school a mile away cross-lots. All classes were in the same room. Years later Ernest recalled the names of most of his schoolmates, their families well-known and sometimes interrelated.

Nothing was permitted to interfere with lessons. They came first. Daily chores must also be done. No young people got into trouble. Sometimes they were too tired to study profitably at night. They were fully occupied and tired out.

High school was in town three miles south on a dirt road. A horse and cart was ready for that. Once on a never forgotten winter afternoon there was no horse and cart and Ernest walked home in the face of a northwest gale at 2 above zero and froze both ears in spite of a pulldown woolen cap. Their helices were scaly and numb everafter.

Three generations on the farm, time for genius to appear! This is America.

Each of the three Scott children in turn was valedictorian of the graduating class in Kinsman High School. Small though these classes were there was incentive to accomplishment.

Kinsman was already famous as the birthplace of Clarence Darrow the great criminal lawyer at the turn of the century, a man who combined force with compassion. The Darrow family lived in the town. The octagonal home in which the family had lived was pointed out with pride. The Darrows were members of a group of "infidels" but there was inspiration toward accomplishment and fame in their name. One of Ernest’s classmates was cousin to Shontz, "The fellow who built the New York subways." In his own family was A. Victoria Scott, M. D., an early graduate of the Woman’s Medical College in Philadelphia. Because of the name, General Winfield Scott, hero of the Mexican war, whose Anaconda Plan ultimately won the Civil War was felt as a family possession. Grandfather Forbes had placed himself on the side of the oppressed by placing his home as one of the recognized stations on the escape-route of runaway slaves. Kinsman a small town was very much in the world and in its consciousness was incentive to accomplishment. A classmate, Guy Britton became one of our first sanitary engineers.

The British colonists of the 1650s among whom we believe the Scotts and the Forbes numbered were middle-class, educated people of some substance. They brought their books and their culture with them. Ernest Scott’s people were British with one grandmother, Ann Fenton, from Cork. I like to think he may have gotten that keen, smiling humor never absent from boy or man from his Irish grandmother. Books were part of living. English and American masterpieces of literature lay on the table and were lived by.

Read Hawthorne’s "The Great Stone Face." You will find an appraisal of this boy named as was Hawthorne’s hero. With Ernest Scott’s name on the flyleaf as I read for the first time this forgotten masterpiece I smiled as I saw the same nobility, the same beauty of character but I smiled, too, with relief since to the all but unbearable sublimity of Hawthorne’s hero, Ernest Scott added his own endearing quality that of humor. Humor, the Janus face of tragedy!

To offset farm drudgery amusing stories were hoarded as gems, told and retold. Some had deeper meaning.

One small boy remarked when his elders were confused by different versions of the same story:

"There’s a lie out somewhere."

Another story was about the town grocer. He was suspected of being superstitious. The town boys made a bull fiddle and hid with it in the cemetery which the grocer had to pass on his way home at night. Going home at closing time, nine o’clock, the deep tones coming from among the tombstones terrified him. Racing home, climbing the stairs and tearing off his trousers, he leaped into safety on the far side of the bed between wife and wall saying, "The devil can’t cross a woman." If I remember correctly, Clarence Darrow tells this same story in his autobiography.

Then there was a story about a loaf of butter. The grocer accepted this in barter. He cut into it and found a core of salt. He placed the cut loaf on a platter as a window display with a card, "Accepted in barter from Willie Jones" or whatever the man’s name was. It may have been done as a joke but the onus was placed on the perpetrator. Small town ethics meant that a man stand by his action. Public opinion was on the side of the grocer. Willie was the joke, if cheating and getting caught is a joke.

3.jpg (124811 bytes)
Graduating Class, Kinsman High School, 1897
Ernest Scott, rear centre. Guy Britton, uper left.

Occasionally tragedy out of the ordinary occurred. A leading citizen, a farmer, one of the best was caught in the squeeze between falling prices and rising costs of bank loans. It was common practice to borrow for spring planting and hired labor, repaying out of harvest crops. Driven to desperation he shot the banker. This banker had bragged, "I am going to be worth a million and I don’t care how I make it." Family status helped in having the murderer declared insane as perhaps he was in despair with a family depending on him. The banker did not make his million.

Hardship does not necessarily breed strength. Ohio at the time was a hotbed of tuberculosis. This disease was latent in Ernest with several acute outbreaks in later life and a sapping of his strength perhaps hardly conscious may have been a contributing factor later in his choice of a career.

Two other factors, each fully understood, drove him off the farm. We have no way of knowing what his internal consciousness of excellence may have been, his inner drive to make his contribution, but there is no question about the doctor’s prognosis that a bad heart gave him a mere ten years of life which made farm work an impossibility. He was forced to choose another field.

A very personal happening influenced him.

He had a colt named Fred. The foal was given him at its birth when he was under ten. Boy and colt grew together. He had exclusive care of Fred. It was his horse. Fred was grandson of the great racing "Morning Star." In a happy family, the boy’s great emotional nature lavished itself upon his colt. We can know only from a few facts how great this love was. The response between man and his animal cannot be measured. Occasionally we see its effects.

Fred was a golden bay. He was not happy in farm work. In it he lagged with downcast head. On a dirt country road when his driver gave the word he was a different animal. Fred came into his own. "Fred could pass anything. He loved to race."

Cash money was hard to get. Cash money was needed. Sons were more important than animals. Fred was sold.

The boy’s agony may be imagined. He said, "What is the use of rearing and loving these creatures if only to sell them." He did not want to live his life on the farm.

Fred’s tale was recognized as immediate tragedy.

"Driven by a strange hand he went crazy at a railroad crossing and killed himself," such was his story as told to me. The boy suffered when he lost Fred. Everyone knew that. How lost Fred was, how can we know but I have thought Fred’s the greater tragedy.

Ernest decided to go to college. He excelled in the hard subjects. Physics, mathematics was his forte. He never could spell though you always knew what he meant. He had no trouble in obtaining a tuition scholarship at Ohio Wesleyan and he registered there in 1897, his year of graduation from Kinsman High School. His mother hoped he would be a minister. It was a Methodist College. He registered for a Bachelor of Science Degree.

Money was needed for living. The scholarship was for tuition. There were expenses for books, laboratory fees, room, food, laundry, clothes, shoes, travel fares.

Walker Jewell, a prosperous Kinsman citizen supplied the money. Remember the name, Walker Jewell. Mr. Jewel! must have seen promise in the young man. He recognized integrity. He made the loan of one thousand dollars at six percent interest with the security of a spoken promise to repay with no limit on time of repayment. It took more than twelve years to repay the loan. The last payment was made from the University of Chicago. At that time Ernest was married and a graduate student.

4.jpg (111308 bytes)
Harriet Forbes Scott, 1847-1925, Kinsman, Ohio
Mother of Ernest Lyman Scott

The loan established a lifetime friendship. A visit to the farm always included a call on Mr Jewell. In the 1940s and not long before Mr. Jewell’s death Ernest was in the hospital to assure the old man then in his eighties of gratitude and affection. Mr. Jewell would have had deserved satisfaction in the public honor that should have rewarded the success of his protege as the first to isolate insulin. A lifetime friendship was maintained, however, between the two men.

In the Department of Natural Sciences at Ohio Wesleyan he found friends. "Eddie" Rice was Professor of Biology. "Louie" Westgate was Professor of Geology. Eddie and Louie were respected, idolized, emulated by the students. The first name usage was token of affection perhaps not used in personal contact. I met them both once. These men found work for him. In time, he became an instructor. He was official photographer on the many field trips.

He had learned the art of photography with a small box camera. His first darkroom was a triangular chimney on the second floor of the old farmhouse in Kinsman. The three fireplaces in the upstairs bedrooms had been sealed off. I never saw that room in the big chimney nor could I imagine how it could be used as a dark room. I know the children slept upstairs in unheated bedrooms and laughed in telling how snow sifted through the ill-fitting window frames of the hundred year old farmhouse. The living rooms and one bedroom downstairs were as warm as wood-burning fires that died down at night could make them. The upstairs chimney darkroom must have been a curiosity. In it he perfected the art of photography. Where was the running water, for washing prints?

He mentioned the heavy equipment he carried on the field trips. He used a large camera on a tripod and glass plates for the exposures. That he performed excellently is confirmed by the fact that Professor Rice used a print "Nighthawk On Its Nest" on a book jacket from a negative Ernest Scott had made fifty years before.

"Whatever Ernest Scott did he did well", was his accolade through life, as with his photography.

For lantern slides he was paid one dollar each. His best customer was the Department of Ancient Languages. He never mentioned how many slides he made.

Though registered in Natural Sciences, at that time four years of college Latin following four years of high school Latin was a requirement. How many years of Greek studies were required, if any, I do not know. I recall no mention of Greek. Unlike myself who placed great value on some mastery of Greek upon which is based the Russian written language with its Cyrillic alphabet, and of Latin, both of which give enlightenment on scientific terms, he seemed resentful of the hours consumed in these studies. Since he was earning his expenses in his spare time he was justified.

He liked the sciences. Otherwise he did not like Ohio Wesleyan. The divinity students, he thought, were career-oriented. They talked more of money than of morals. He thought there was more dedication to human service among scientists than among divines. He thought the college management money-minded. Doubtless it had to be. He would have chosen that it be less obvious.

He resented daily morning chapel attendance, another infringement on free time. "What happened in Chapel this morning?", after a rare cut. "We listened to Professor skinning his teeth."

The famed Professor Peabody increased his love of mathematics. "Dad" Seamans if that was his name, was far out of date in his chemistry. He did not believe in ions, this when electrons were being talked of. Ernest was proficient and happy in the natural sciences. As proven in their correspondence his professors could not give him high enough praise in their appraisal of his intellectual endowment and in his character, Ernest Scott, the young student whom they would send out as their first graduate student. They, too, were denied their due in the fame denied him. There was an enduring friendship between him and Professor Rice throughout life.

College life had little lightness. It was for him all work. The exclusiveness of fraternity life did not appeal to him and he had neither interest, time nor money for it.

Board in 1897 was a dollar and a half a week if I remember. One fellow wanted to pay less for two meals. After a term the housekeeper said, "You pay for three meals whether you eat them or not." Room was a dollar and a half a week. Once he tried a roommate to halve the cost. The fellow had halitosis. No one could stay in the room with him. He bore the name of one of the great New England poets which did not help him. The fellow left college, went to Oregon and was drowned there in his early twenties. Modern surgery might have prevented the tragedy. A room to one’s self was necessary whatever the cost.

5.jpg (142152 bytes)
A faded print. Negative taken by father winter of 1899-1900.
Standing in south door of cow barn, Kinsman
The DREAM--Ernest Scott, Scott Farm

During his college years at Ohio Wesleyan one great pleasure came to Ernest. He spent an Easter vacation with his classmate, Lee Marshall. He would meet Lee Marshall a decade later as a dean at the University of Chicago. It was Lee who later, on a visit to the young couple’s university apartment, said "Even scientists like to eat." On this Easter vacation an early spring flood on the Ohio River washed out the railroad bridge to Zanesville and extended their vacation. They went in on the last train in and out on the first train out ten days later. Once Ernest went on a spring jaunt in cream-colored trousers, blue coat and a straw hat. A late snowstorm gave him a headcold and ruined his hat.

That his college life was rugged beyond endurance is proven by the appearance of tuberculosis. He was forced to give up and to spend his junior year on the farm to recover strength.

A photograph shows a very slender figure on the far side of a two-handed saw as he and sturdy Brother Clyde saw the logs with which to keep warm in winter.

His senior year was completed in June 1902 with the degree of Bachelor of Science. He fell in love with a beautiful classmate, Helen Hotchkiss of Geneva, Ohio. Love strikes strangely. He mentioned the moment. Moving up the aisle of the railway car returning from vacation his eye rested on that beautifully turned cheek and brown curls. He knew that he loved her. She had been in the biology class where he was an instructor. She was not very good in biology. Literature and the classics were more to her liking. She couldn’t draw if I remember correctly. She was a beautiful girl. She was to die in 1927 of tuberculosis. Remember, "Ohio was alive with it. Geneva was a hot bed". He died in spirit with her. Each carried the germs, she from an attack in girlhood, he to survive until streptomycin controlled it in 1952-3. They did not know this is 1902.

College was over, Tributes to his scholarship and character remain. Professors Rice and Westgate recorded their high valuation of his powers. A photograph of him at his desk in the laboratory as he was graduating from Ohio Wesleyan might be taken as a symbol of all youth in its magnificent confidence of self (Frontispiece).

He left Ohio Wesleyan behind him. He carried with him ambition for excellence that would endure. He carried with him inspiration from his two great teachers. This would lead only nine years later to the scientific achievement of making the first reliable extraction of insulin from adult pancreas suitable for medical use in clinical treatment of diabetes.

6.jpg (134817 bytes)
Left, Upper, Nellie Ann, Ernest Lyman, right.
Lower: Lyman Plympton, Walter Clyde, Harriet Scott

Before leaving the college years, we may recall a few stories. The first time he left home for college his mother "sat up all night" as he indulgently put it, "to finish his shirts. She wanted to do it", he said with a smile. When he was very young his mother told him she loved him. He believed her and never doubted her love. Her love was constructive and never traumatic for she was happy in her married life whatever its hardships and burdens.

As Ernest was starting for college, his father had given him a red leather-bound, gilt-edged Bible. The narrow red ribbon marker stays where he left it, Matthew VII. I doubt he ever referred to the Book in later life. He had learned the lesson. Matthew VII is a large order, large enough for any man, large enough for a lifetime. It lay, I think at. the basis of his conviction often stated, "A man cannot be a good scientist unless he is a good man." Matthew VII provides no safeguard against. crucifixion. Perhaps it ensures it. Ernest Scott lived the precepts. He earned the judgment of his intimates, "A better man never lived," "Pure gold we saw him," "He is a saint," the last from a professional superior. The biological principle of self-preservation as the first law of life is absent. "He saves others, himself he cannot save." The individual perishes. The race may or may not survive. I have never heard that Matthew VII is on the required reading list of those preparing for a career in science. It is the way of genius. Ernest Scott went this way. "You shall perish. The house you build on the rock of integrity shall survive." A promise! The promise was fulfilled in him.

STARTING A CAREER

His first assignment was an appointment to the U.S. Coast and Geodetic Survey from June 1902 until January 1903. His work was taking and charting the soundings on Chesapeake Bay. "The Matchless" was a converted yacht. It was a beautiful boat made of mahogany and painted white. He recalled the two Japanese stewards. He thought they knew as much about the business as did the captain. He found them amusing. "Martin. He walk the boom. He capsize." The sailor had not recovered from his week-end leave in Baltimore. "Better have them scrambled, Mr. Scott" was testimony to difficulties in handling food before electric refrigeration.

Ample reward was his with Captain Flower’s remark, "Thank God the soundings cross." Doing his best, his best was sufficient. He supervised and plotted the soundings.

He saw no future for himself in this government service. He accepted an appointment in the High School in Galion, Ohio.

He had little to say about his term in Galion. It was his first experience in teaching. It seemed sufficient to say, "I learned the trajectory of an eraser." He learned more than that. He repeated proudly and with a smile, the remark of the janitor in his next school who said admiringly, "You must have had good discipline where you came from, Mr. Scott."

The next seven years of his life in West Bay City, Michigan, were perhaps his happiest. He taught physics, mathematics, botany, zoology, physiology, and geology. He enjoyed rapport with the students and with the town. He coached the football team. He was part of the town. He sang in the town musicals, bass, of course. He was happily married. He owned his own home. He was a master gardener. This helped out the small salary. In the early 1900s horses were still in use. It was common practice to insure warmth to the lower floor, in his case, of a cellarless house, with a surrounding framework of wood which was filled with horse manure. What that did when turned into the vegetable garden!

7.jpg (143838 bytes)
Clyde and Ernest Scott, 1899-1900.  Two handed saw on the Scott Farm,
Kinsman, Ohio

Temperatures went low in winter. The janitor at the school might stay up all night to keep wood-burning furnaces going. The warmly dressed youth coming into the schoolroom into 40 above, from 40 below would sigh with pleasure, "Way up to forty!" He mentioned walking along sidewalks head-high ‘with snow and the camaraderie of those passing by, "Your cheeks are white. Watch it" or "Watch those ears." The same now but who heats with wood!

Helen and Ernest must have lived carefully on a small salary. He was paying off the college debt. He must have begun, also, with his first pay check a systematic saving for graduate study. The faith of his college professors had put an obligation upon him, however urgent his inner drive to use his God-given talents may have been.

He was happy in Bay City in the years from 1903 to 1909. He enjoyed the town life and being part of it. He enjoyed the men’s choral society. Only once he sang for me. He smiled at my amazement. His voice was as low as a kitten’s purr. It was musical, a deep resonant bass.

In the early 1900s it was the thing to do, ambitious men and women taught a few years in high school to save money for graduate study and a higher degree. His lifelong friend Oscar Riddle, a fellow student in Chicago, did this. Oscar wrote his name permanently in genetic research.

A favorite quote, a remark by a fellow graduate student was, "Yes. I taught four years in high school until I felt the grass growing up my back. Then I got out." The more ambitious and talented did the same. I know of none who regretted the decision.

Two tragedies struck. His first child, a girl, died at birth. A favorite student died at seventeen. These occurrences quickened him.

The lash of tragedy plays its part in the way of genius. Enrico Fermi lost his brother only a year his junior. The mother never recovered from the loss of her young son. Enrico, a very young adolescent turned to study, physics and mathematics. He became famous, and, in this country, worked on the first atomic bomb. Manya Sklodovski lost both mother and sister from the white scourge in Poland, when she was quite young. She spent her free time studying physics, her father’s field of education. After only a few years of married happiness she lost her husband, Pierre Curie. Everyone knows Marie Curie’s dedicated life. Not all know her tragedy. Many have discovered that intense mental concentration can counter both physical and mental agony. Ashes of despair yield fertile soil for a different crop.

Lawrence MacMillan was a fine handsome youth, the most valuable player on the football team because he was smart, could play any position and was fast.

In the fall term "Lolly" did not appear for practice. He had worked at the bank during the summer. Mr. Scott went to the bank.

"Aren’t you coming back to school this autumn?"

"No. I am not coming back. I have diabetes."

‘Have you been to Ann Arbor to ask for help?" This was Michigan.

"Yes. I have been to Ann Arbor. They have told me they have no help. All I can do is die."

Lolly was seventeen.

Ernest Scott never mentioned Lawrence MacMillan in his many years of life without a quaver of emotion. He felt this youth’s tragedy as though it were his own. This boy’s death set him upon a path that would lead in half a decade to first isolation of insulin. He could do nothing about the death of his first-born. He would do something about diabetes. He did. In 1909-1911, he devised a method of extraction that yielded a product that controlled experimental diabetes, as we shall prove.

8.jpg (94284 bytes)
The MATCHLESS--Courtesy of Environmental Science
Service, USA., US Coast & Geodetic Survey

We must remember "Lolly" MacMillan, Bay City, Michigan, 1907 or 1908. He lit the fire in Ernest Scott which led to the medical breakthrough of the Twentieth Century. Publication of the method occurred in 1912. It took another decade to convince an unready world, through no fault of Ernest Scott, and to bring insulin into medical use.

The way of the transgressor is said to be hard. The way of genius seems harder as we proceed with the life of Ernest Scott.

TWO YEARS AT THE UNIVERSITY OF CHICAGO
March 1909 - September 1911

Now began that period of great creativity that in "six short months" was to solve one of nature’s closely guarded secrets. Not until a decade later would it shake the world. In 1911, the world felt hardly a tremor. This young free mind in its confident strength, Ernest Scott was now thirty-one years old. He was his own man in his own right won by application, hard work and much self-denial. He had money in the bank, not much but sufficient for the purpose. What was his course?

He had pursued a correspondence course in "Phanerogams and Cryptogams" under the great C. J. Chamberlain, University of Chicago, and his beautiful plates bear comments in red ink by the professor himself. A head of department then might find time and interest to oversee personally the work of an obscure high school teacher. According to his principles Ernest Scott did his best. A comment in red ink states that his work was "up to the highest standards set by this University" and he was offered a place on the staff of the Department of Botany at the University of Chicago, this offer coming through a correspondence course. The position carried a stipend of $950 a year and there would be opportunity for further study and research.

Through correspondence he had another offer from the University of Chicago. This was an instructorship in the Department of Physiology in the Medical School. The stipend was $750 per year. Tuition fees, laboratory fees, living expenses for two must be paid out of this and from savings. Married women then did not work outside the home. Laboratory fees were high especially in chemistry where he would work. Yet he accepted this lower offer. The decision to work in medical science must have been made long before.

He brought Helen with him and took residence in a University apartment early in 1909. He could have worked under a very famous man, C. J. Chamberlain, and often in review wondered whether he would have been accorded better professional treatment had he made that choice. Had he made the right choice? Only time could tell.

Something basic in the natures of the two men who were now about to meet ensured that they would run counter to one another in actuality and in history. A mutually felt and never expressed antagonism existed perhaps at first meeting. One was a native son nurtured on American tradition, Ernest Lyman Scott. The other was a Swedish immigrant, Anton Julius Carlson, only two years older than the newly entering student. The newcomer to the country had made his way to the top, to a position as head of department in a great American university. The student was fourth generation of Ohio pioneer farmers, the men who had made and were making America.

These two men were antagonists from the start. History provides the answer as to which was the better man, the better scientist, or, as we say, which won: Anton Carlson or Ernest Scott.

Each individual must stand up to facts, to his own act, choice, performance, and abide by the results. If there be interpretation for resulting guidance we must have truth. Without truth there is no history. I am writing history. I must name names. I must present facts.

9a.jpg (15199 bytes)
TAKING THE SOUNDINGS--Captain Flower
on the Matchless. Photo 1902, E.L. Scott

First encounter brought conflict. A master’s thesis is required to obtain the M.S. degree. Original research for this is required with results sufficiently valuable to justify publication. With a strictly limited period of time what will the problem be? It must be chosen at once. The customary procedure is that the head of department choose a phase of his own special field, that is, that he "sets the problem." This is reasonable.

This particular young man, Ernest Scott comes with his mind fixed on a problem that he has set for himself.

Confrontation, hardly recognized as such, occurs.

The student was indomitable.

The head had the right to approve or to disapprove the student’s choice. He had the right to give or to withhold the facilities of the university. Head was "Power".

In this face-to-face confrontation Ernest Scott won. It was his first victory in his search to understand and to control diabetes, experimental in his work. It was undoubtedly his greatest success. He won the privilege of following his own path. The penalty was forfeiture of encouragement or personal help from the head of the department of physiology.

We may recall from the "Conversations": "Didn’t he want to help?" And the answer: "He never did. He thought I was foolish to try." Such words linger.

It is hard to revive the youthful self-confidence of Ernest Scott. Later, innumerable setbacks assailed him, each taking its toll. We know that the immense pride his two great professors at Ohio Wesleyan had in him was a source of great strength in his long struggle to justify even exceed their faith.

Professor Rice was sufficiently well known and respected that he was called upon by the Defense in the famous Scopes Trial, "The Tennessee Monkey Case," to state the position of the theory of evolution.

This case was lost in the law courts. It was won in the court of public opinion. Clarence Darrow led the defense.

Whatever its source, at this flowering period of his life Ernest Scott had enormous drive, self-confidence and strength. He had overcome or, at least, stymied tuberculosis, he had earned some financial strength and he had a happy marriage. With these assets and under urgency of a limited period of freedom he attacked the problem which he had chosen for himself with energy and confidence. He would permit nothing to stop him.

Ernest Scott entered the University of Chicago in the spring of 1909. He said that he spent all the remainder of 1909, all of 1910 and the early part of 1911 in study. He said he took a "bang-up" course in quantitative chemistry, making up what he had missed at college, also courses in the medical school where he served as instructor in physiology, courses in biochemistry and in pharmacology and special courses such as Koch’s course on proteins. Most important to him was the study of publications in German, French, Italian, English and American journals on observational and experimental diabetes. In his 1911 Thesis he lists only ten of these. With languages, his classical education at Ohio Wesleyan must surely have come to his aid.

According to his own statement, confirmed by the date of his first experiment he did not get to his experimental work to test his hypothesis until April 1911. He had spent all but five months of his span in study and in preparation. He would leave the University in September, 1911.

10a.jpg (23925 bytes)

By his study he derived a simple and reasonable hypothesis. This was that the elusive hormone all suspected of being formed in the pancreas was a protein and thus susceptible to destruction by trypsin, a protein-splitting enzyme formed in adult, but

Not in fetal pancreas. He based his method of extraction upon this hypothesis.

He studied with intense interest Hammarsten’s "Physiological Chemistry", a heavy tome just published in 1909. His copy with his name stamped on the inside cover I have given to the National Library of Medicine since it is very revealing as to the course of his thinking. The neatly underlined portions dealing with carbohydrates, proteins, fats, and enzymes were the pieces he put together in his puzzle. Indeed, it might even be amusing to see there the very method he used for extraction of a protein. Of course he chose the simplest. This same method we see reappearing in Banting’s 1921-22 report and in the patent taken out by Banting, Best and Collip in 1923, as we present the documents.

It may be regarded as a happy coincidence in the annals of scientific progress that as Ernest Scott was concentrating on the problem of insulin Valdemar Koch was giving a course on proteins. Professor Koch thought and said he thought that the subject of proteins was what he called a "neglected" area. Ernest Scott thought he saw similarity between the characteristics of protein as portrayed by Professor Koch and the highly elusive agent that could reduce the concentration of sugar in the economy of the body of an animal, the agent he was seeking, later to be called insulin.

I know I am taking liberty with a man’s name. Professor Koch himself wrote his first name Waldemar but in the "Conversations," his student Ernest Scott tells us he pronounced it as with a "gusty" V. Somehow I seem to prefer this famous name worn by kings written as it was spoken. I trust this is a fringe benefit due me as a writer, and historian.

Ernest Scott had nine quarters at the University of Chicago, spring of 1909 through September 1911. In his last quarter he did ten experiments with depancreatized dogs and wrote his MS Thesis.

His first experiment, Dog A started on April 11, 1911 at 5 p.m. At 8 p.m. the pancreas had been removed and after recovery, April 15 determinations of glucose and of nitrogen in the urine were begun. The D/N ratio was 3.31. Total glucose was very high, the diabetic condition. On the 18th his extract of the pancreas (insulin) was injected. The D/N ratio steadied at 1.56 after 3 days and excretion of sugar was reduced from a high of 20 gm. before to a low of 0.5 gm. after injection. The dog looked "brighter" on the day following injection. No more injections were made and Dog A died on April 27, sixteen days after operation. The first page of notes and graphic records we show here since they are the first experiment with insulin. This first experiment was a success as we see from the near absence of sugar in the urine and the brighter look after injection. With no further injection the animal died.

The U.S. National Library of Medicine, Bethesda, Md. has accepted all the source material of Ernest Scott’s early work with insulin.

These experiments were difficult. Animal experimentation is a specialized art. Chemical tests were awkward, exacting, tedious. Studying his experiments, his personal records, we see he had a great deal of trouble. These experiments extended from April 11 through August 5. Some of his dogs did not survive the operation. Some developed infections. He worked alone without help often through the night. Room temperatures in July were recorded in the high 90s — 98.6.

To an arrogant, even antagonistic eye, these neat, painstaking notes could be and were cast aside as worthless. To a friendly eye, to the open-minded men of the Biochemistry Department the records were convincing. History stands at the side of the latter.

As we shall see in due course Frederick Banting used the E. L. Scott extract on diabetic dogs and upon human diabetics in 1921 — 1922 and verified Scott’s claim made in his Thesis, 1911.

In the 1923 Presentation Speech awarding Banting and Macleod the Award, Nobel Prize in Biology and Medicine, Professor Sjoquist remarks: "The very first experiment in diabetic dogs was crowned with success". Frederick Banting had already stated in print that he used the E. L. Scott principle and noted no changes. Did Professor Sjoquist do his research?

11a.jpg (32965 bytes)
The World's first Experiment with adult pancreatic extract (insulin) upon
depancreatized dog

12a.jpg (22376 bytes)

13a.jpg (16671 bytes)

 

 ERNEST LYMAN SCOTT’S THESIS OF 1911

Here forthwith is the thesis as he wrote it in the late summer of 1911. He left it in the possession of the head of the department of physiology, at that time, Anton J. Carlson. He expected it to be published as he had written it. According to university regulations in Chicago, at that time, he gave 3 bound copies to the Library of the University of Chicago. This has proven to be an excellent regulation. The thesis was printed as written not until 1966, fifty-five years after it was written and a few months after the death of its author.

 

THE UNIVERSITY OF CHICAGO FOUNDED BY JOHN D. ROCKEFELLER

THE EFFECT OF PANCREAS EXTRACT ON DEPANCREATIZED DOGS

A Dissertation
Submitted to the Faculty
of the
Ogden Graduate School of Science
in Candidacy for the Degree of
Master of Science
Department of Physiology
by

ERNEST LYMAN SCOTT

Thesis No. T-10553
1911

 

Introduction and Historical

Since the demonstration of pancreatic diabetes by Von Mering and Minkowsky many attempts have been made to relieve or cure both this and diabetes mellitus by the administration of some pancreatic preparation. The theory being that if there is an internal secretion from the pancreas it should be available; so far, however, this seems not to be the case. So striking is the failure to reduce the sugar out-put that Leschke (1) after a thorough review of the literature, and after a series of experiments on frogs of his own, concluded that the injection of an active pancreatic extract not only does not lower the out-put of sugar, but actually increases it, and if given in large amounts causes the death of the subject; while extracts rendered inactive by means of high temperature were largely without effect of any kind.

Zuelzer (2) injected a protein-free extract in depancreatized dogs and human diabetics with apparently favorable results. But in the hands of Forsback (3) the method did not prove so satisfactory. Forsbach attributed Zuelzer’s results to the rise of temperature and consequent lowering of sugar out-put due to the injection, rather than to any internal secretion contained in the extract. Similar results have been obtained by many writers and a fairly complete bibliography will be found in Leschke’s article and in Pfluger’s (9) article published in 1907.

The extracts used by these men were of three main types: 1st, the simple extract made with physiological salt solution; 2nd, a glycerine extract; and 3rd, a press-juice in which the proteins were precipitated by means of alcohol. But since the results were unsatisfactory by whatever method the extract was prepared there is no occasion to enter into details here.

The work of Cohnheim (4) and his followers now demands attention. The method of extraction adopted by these workers consisted essentially of heating the gland in boiling water for a time, then having ground it with sand before or during the process of heating, to extract for varying lengths of time with strong alcohol. The several alcoholic extracts were added to the watery extract from the first boiling and the whole evaporated to dryness. The residue was extracted with ether and ether extract discarded. As much of the remainder as possible was taken up in alcohol and used for their glycolysis work.

It is quite evident that such an extract would have no digestive powers but there seems to be abundant proof that it does have some activities towards dextrose when in the presence of muscle juice as witness the work of Cohnheim, Hall, (5) Levene (6) and Meyer and others.

The idea that there is an internal secretion seems warrantable from the long series of pancreas grafting experiments that have been reported, notably those of Hedon (10) as well as from the recent work of Drennan, (7) and Carison and Drennan. (8) If then, there is an internal secretion that affects the metabolism of the sugar and the Cohnheim extract plus muscle juice has an activity as regards dextrose it would seem reasonable to abandon the preparations previously used for this. But while Cohnheim has taken precautions against any deleterious influence of the digestive enzymes on the supposed internal secretion, a point overlooked by Leschke, and on the experimental animal, had he injected his preparation, he took practically no precautions against oxidation during preparation. Fron the experience with the extraction of adrenalin and from the fact that Drennan found no effect on injection of stale blood, it seemed to me that this was an important omission.

My work then was based on two fundamental principles, 1st, to inhibit the possible action of the external secretion of the pancreas at the earliest possible moment and to ultimately destroy any activity before injection; 2nd, to perform all operations in such a way as to avoid, as far as possible, any oxidation. None of the preparations were heated above 65 degrees Centigrade, and nearly all were kept below 60 degrees.

Methods of Preparing the Extracts

1st, It was hoped that the presence of the digestive enzymes could be avoided by the atrophy of the gland which follows complete ligation of the ducts; but after several attempts which proved futile so far as complete atrophy was concerned, this method was abandoned as impractical. 2nd. Two methods of extraction were attempted; a), an alcoholic extract, and b), a watery extract.

a) The alcoholic extract was prepared by grinding the glands with sand and warm alcohol (40 C.) and extracting with enough alcohol to bring the total alcoholic percentage above 85%. They were extracted three times, 24 hours each time at 35 to 40C. This was then filtered and the filtrate evaporated to dryness under a negative pressure of about 70 cm. and in a slow stream of carbon dioxide; the residue was then extracted with ether at room temperature. The ether extract was discarded and as much as possible of the solid dissolved in 95% alcohol and sufficient alcohol added to make up to such a volume that 10 c.c. of the solution represented 1 gram of the fresh gland. For use such a quantity as was desired was again evaporated as above and dissolved in 0.85% salt solution for injection. The preparations when evaporated for the last time were of a light straw yellow and soluble with some difficulty, in the salt solution, as much as 60 c.c. being required for the larger amounts used.

b) In preparing the watery extract we sought to avoid the blood pressure lowering principle by rejecting all alcohol soluble material. The glands were prepared as for the first method but after the alcohol had thoroughly penetrated the material it was evaporated to dryness under a vacuum and extracted for some time in 150 c.c. of absolute alcohol. This was poured off as completely as possible and the residue extracted for one hour and twenty minutes with water rendered just acid with acetic acid. It was then filtered as rapidly as possible and evaporated as before. When dry it was covered with absolute alcohol and kept for use. For injecting, the alcohol was poured off and 20 c.c. salt solution added. In appearance when dry it was almost the color of the first extract, possibly more colloidal in appearance. It went into solution readily in the quantities of salt solution used, though the solution had somewhat the appearance of a finely divided colloid.

Method of Testing Extracts

Only dogs whose pancreas was completely removed are reported here. This was determined a) by the constancy of the diabetic curve, and b) by autopsy, though it was found that the first was fully satisfactory. While only the significant portions of the tables are here reported we will say here once for all, that the injections were made only after the sugar percentage had descended from the height occurring on the 2nd or 3rd day and had presumably reached the level that it was to hold more or less constant through the life of the dog. While it might have been advisable from some points of view to have secured more D/N ratios before injecting, it was assumed that when this had reached approximately 2.65 that it had reached a constant level and the injection was made. More stress is laid on this ratio than on any of the other factors.

In brief, the results from the alcoholic extract were disappointing; the dogs in general showing an increase of DIN, though this in most cases was not great enough to be significant, it was far from what was hoped. All the dogs showed depression immediately following injection which lasted in some cases for 2 or 3 hours and was so great that we feared for the recovery of the animal. Several of the dogs died within a couple of days following the 1st injection. The tables are records of typical cases.

Table l. Condensed history of three typical dogs treated with Alcoholic pancreas extract. There was depression for 2 or 3 hours following each injection.

Date Hour Vol of Urine in CC Amt. Of Sugar in gm D/N Remarks
          Dog C
5/1 5:00 pm       Operation complete24 Hour sampled
4 7:00 am 500 24.41 2.13  
5 5:45       Injected the extract from 1.5 gm of fresh pancreas
           
           
           
           
           

 

DIN

 

 

2.13

2.00

5/9 12:00m

10 10:45 am 320 13.40

ii 11:00am 455 18.42

12 11:00am 400 16.57

from 5 gm of fresh pancreas

2.34

1.87

2.69

Dead

 

operation completed Injected the extract

13 10:30 am

14 8:00am

14 5:30pm

285 13.77 2.72

395 17.07 2.79

5/22 5:00pm

24 12:30am 575 12.92

24 5:30pm

from 5 gm of fresh pancreas

25

25

26

2.82

3.58

Vol. of Amt. of

Urine Sugar

Date Hour in CC in gin Remarks

Dog C

5/1 5:00 pm operation completed

4 7:00 am 500 24.4i 24 hour sample

5 10:30am 540 24.9i

5 5:45 pm Injected the extract

from 1.5gm of fresh pancreas

6 1:30 pm 530 26.07 2.40

7 6:00pm

Dead

Dog E

operation completed

2.47 six hour sample

Injected the extract

8:00am 700 33.38

9:00am

10:00 pm 340 17.13

Vomiting and depression, condition so bad that dog was killed by ether. Autopsy showed no marked lesions.

 

With the watery extract four dogs were used. The first two dogs and the fourth showed much the same type of D/N history. The third dog showed a fall of this ratio following the injection but the record was so irregular that the results were discarded except for the fact that there was only a rise of temperature of 0.4 of a degree following the injection and this was only of short duration. The first three dogs showed absolutely no depression following the injection and if one dared say it, seemed even brighter for a time after the injection than before it. The fourth dog in which an older extract was used showed a marked depression lasting for an hour and a half.

 

Conclusions

1st. There is an internal secretion from the pancreas controlling the sugar metabolism.

2nd. By proper methods this secretion may be extracted and still retain its activity.

3rd. This secretion is easily destroyed by oxidation or by the action of the digestive enzymes of the pancreas.

4th. The secretion is insoluble or nearly so, in strong alcohol but is readily soluble in acidulated water.

5th. The failure of previous workers to procure satisfactory results was due to their not preventing oxidation or the action of the digestive enzymes.

 

LITERATURE

1—Leschke: Rubner’s Archiv f. Physiol. 1910, p. 401
2—Zuelzer:Zeit. f. Exper. Path. V, p. 307, - 1908
3—Forsbach: Deutch med. Wochensh. 1909, XXXV, p. 2053
4—Cohnheim: Zeitschr. f. physiol. Chem. 1906, XLVII, p. 253
5—Hall: Amer. Jour. of Physiol. 1907, XVIII, p. 283
6—Levene and Meyer: Jour. Biol. Chem., 1911, IX, p. 97
7—Drennan: Amer. Jour. of Physiol. 1911
8—Carison and Drennan: Amer. Jour. of Physiol. 1911
9—Pfluger: Pfluger’s Archives 1907, CXVIII, p. 268
l0—Hedon, E: Arch, Internat. de Physiol. 1911, Fas IV. Vol. X, p.35O

The essence of Ernest Scott’s thinking in evolving a method of extracting insulin from adult pancreas was that the hormone was a protein. If it were a protein it would be destroyed by trypsin. Trypsin is a protein-splitting enzyme which is formed in adult pancreas, but not in fetal pancreas.

This simple idea led to the insulin we know today and its synthesis came later.

ERNEST SCOTT’S 1911 METHOD OF EXTRACTION OF INSULIN

Studying the Thesis we find his method based on this hypothesis, which is unstated. Proteins are soluble in water and in alcohol up to 85%. Proteins are precipitated by higher percentages of alcohol. If the hormone were a protein, it would be destroyed by trypsin during extraction methods using adult pancreas. On his simple assumption, he must destroy the enzyme and he must dissolve and extract the protein. Alcohol in proper concentration would do both. Here is his method, thus interpreted step by step, as I understand it:

SCOTT’S 1911 METHOD OF EXTRACTION OF INSULIN

1. Grind pancreas with sand and alcohol made to 85% with tissue juices. This concentration of alcohol dissolves the protein and destroys trypsin.

2. Filter. Filtrate contains hormone (insulin). Discard sand and tissue. Save filtrate.

3. Evaporate water and alcohol from filtrate. Save dry residue.

4. Treat residue with ether. Ether dissolves fatty components. Discard ether by filtering and save residue. Proteins do not dissolve in ether. Fats do. This is purification.

5. Treat residue with absolute alcohol. Filter. Save residue. Absolute alcohol precipitates all proteins. Insulin, if a protein remains in residue.

6. Extract residue with water made just acid with acetic acid. Protein ("insulin—if" plus other tissue protein) dissolves.

7. Filter. Save filtrate which contains "insulin—if".

8. Evaporate to dryness. Save residue under absolute alcohol.

9. For injection, pour off alcohol, dry, then dissolve in weak, 0.9% saline solution. We have insulin, if a protein.

I did not repeat this method but it is as I understand it.

This turns out to be crude insulin readied for injection.

Later, in orderly sequence, we shall present a Patent for the manufacture of insulin which was taken out in 1923 by Banting, Best and Collip who have been credited with the "discovery" of insulin for half a century. You may wish to compare these steps devised in 1911 with those in the 1923 Patent. Ernest Scott had insulin in 1911. It was a long time before the world had it, in 1923. Why?

Prepared in this way with this product, Ernest Scott obtained his remarkable results, a lowering of the D/N ratio, reduced total glucose in urine and a "brighter" appearance of his diabetic dogs (Thesis —10553, University of Chicago, 1911, and 1912 volume of the American Journal of Physiology). Insulin—if becomes insulin—is, in the mind of Ernest Scott—insulin is a protein.

The first extraction of usable insulin thus was one man’s work. Ernest Scott worked without guidance, even without approval in the department of physiology. He had the use of its facilities for animal experimentation. These included operating room and care during recovery and later maintenance.

Probably no better such laboratories existed in the world at that time. It was fitting that the generosity of the Rockefellers in endowing the University of Chicago should produce such fruit in so brief a period. The chemical analyses of first importance in this research were done in the department of biochemistry, in the University of Chicago.

Professor Koch at that time was bearing responsibility for two departments, his own, pharmacology, and that of biochemistry as changes in personnel were being made in the latter. Professor Koch was working with chemical changes in animal tissues, particularly in the nervous system, in the brain, and in nerve degeneration. He was not at all engaged in carbohydrate metabolism. He was in no position to advise or to plan the work of the student from physiology. He gave what was needed. He gave the facilities of the department of biochemistry for chemical analyses. He gave respect to the student. He gave encouragement as he shared a feeling of friendly comradeship in scientific achievement. Indeed he gave what was needed.

In view of the fame of those who introduced insulin into medical practice to control diabetes a decade later, it is not out of place to give consideration to Professor Valdemar Koch. It was in the department of biochemistry, under his direction in interim, that insulin was first extracted from adult pancreas, in usable form, by a student from physiology, Ernest Scott.

Valdemar Koch was a nephew of Robert Koch, the great German bacteriologist who had isolated the bacillus causing anthrax, and even more important, the tubercle bacillus. He died in 1910, just as insulin was about to be isolated for the first time in the laboratory of’ his nephew. It is true the nephew played no evident part in the thinking that led to the method of extraction but he did give that course on proteins of his own volition. He gave, too, the intangible gift of encouragement so notably lacking in the other department and the lack of which led to a decade’s delay in the introduction of insulin and misprision of its discoverer. Had Valdemar Koch lived, the history of insulin discovery might possibly have been written very differently for he accepted Ernest Scott’s work and had full confidence in the man. There is no harm in remembering Valdemar Koch. He died in 1912 at age 37.

Ernest Scott stated: "The Department of Biochemistry believed in my work. Under that insignia of approval the official journal, the Journal of Biochemistry, would have published my thesis as it was written in 1911 as I wanted it to be published". When it was published in January 1912, it was not published as he had written it. Herein lies the story, or part of it, as appeared in our "CONVERSATIONS".

Thesis T—10553, University of Chicago, 1911, was written in late summer. It was placed in the hands of Professor Anton J. Carlson who was Head of the Department of Physiology. The degree of Master of Science was granted in 1911 to Scott and he was offered a position of instructor in physiology, a renewal of his position in the medical school at the same salary of $750 per year. He refused this offer since he needed money. He was expecting his second child. He accepted a position as assistant professor of physiology in the University of Kansas at $1500 per year and went to Lawrence at the end of September, 1911.

UNIVERSITY OF KANSAS 1911-1912

The year at the University in Lawrence, Kansas, was in the words of both Helen and Ernest Scott, "the worst we ever had." He was overburdened with work at the University. He had been promised time to continue his research. The promise was not kept. Helen’s strength had been lost in Chicago. He took up the slack at home and in caring for his little son, Francis Swan Scott, who was born on October 5, 1911, a few days after his parents’ arrival in Lawrence. "I was busy that year," was the father’s laconic comment. I heard of no permanent friendships made in Kansas, unlike lifelong friends made in Kinsman, at Ohio Wesleyan, in Chicago and at Columbia.

Ernest Scott had left Chicago in fine fettle of success. Friends among the biochemists believed in him. They accepted his experimental work. He believed in himself. He hoped publication of his thesis would set the pace for conquest of human diabetes.

He was sure he had found the answer. Professional advancement and the money he needed would follow. He had exhausted his funds, himself and his family in his tremendous drive. But he had succeeded in what he had planned to do. Insulin, he had it! Read his conclusions in his Thesis-10553, 1911, University of Chicago.12

A CHANGED THESIS

Ernest Scott’s 1911 M.S. THESIS is very different from what appears under his name in the American Journal of Physiology, Vol. XXIX, Jan. 1912 No. III. Since he denied authorship in a 1964 Affidavit now in our National Library of Medicine the article should be stricken from the Journal. We reprint it here.

Summary and Conclusions are in contradiction. The author claims success whereas the other declared the results of small value. The body of the Thesis has been rewritten. Half of the analysis of previous investigators has been cut out. Half of the references, 5 out of 10, is omitted, The whole is obviously the product of another mind. A sole exception to the revision, a crucial one is that the methods of extraction remain as in the Thesis. One table of experimental data is left out.

For so much integrity on the part of his academic superior that the methods of extraction were not tampered with Ernest Scott was grateful. He remarked, "What was left was enough for Banting." Banting did indeed repeat the E. L. Scott method in 1921-1922 as we shall see in due time and got such "favorable results" on diabetic dogs and human diabetics as he says, that insulin went into mass production and into medical use in 1923.

Before leaving this matter of the changed Thesis we must note a discrepancy in the reference to the very important work of Cohnheim which is 1906 in the Thesis whereas it is 1904 in the Journal. We accept the Thesis. Previous work had led to acceptance of the idea of a pancreatic hormone. Cohnheim suggested that failure to secure a potent extract of the pancreas was due to the antagonistic action of digestive enzymes produced in the pancreas.This idea was not enough. Cohnheim failed to extract the hormone. It remained for Ernest Scott in 1911 to put together two ideas: If proteolytic enzymes destroy the hormone then the hormone must be a protein. Here is pinpointed the great breakthrough of the 20th Century in Medicine. He based his successful extraction of insulin on this idea.

The sentence in the spurious Summary, I quote:

"It does not follow that these effects are due to the internal secretion of the pancreas in the extract", deadened all impact of the first successful extraction of insulin.

Ernest Scott must have read the Journal article under his name when he was working in the Medical School, University of Kansas, not knowing of the drastic changes in his Thesis. We may imagine his agonized dismay. "It was a terrible thing for me" he said. Indeed yes, and too for the world of diabetics who would wait a decade for INSULIN.

 

SPURIOUS ARTICLE

This article has been denied authorship in an affidavit now in our National Library of Medicine. A copy appears in the CONVERSATIONS.

It is included here also as an example to confirm Claude Bernard’s famous quip:

"It is what we think we know that keeps us from knowing" his idea in my words.

Claude Bernard is credited with the beginning of the study of carbohydrate metabolism. He noted the presence of animal starch in the liver. He noted the excretion of sugar, glycosuria, in some pathelogical conditions.

Reprinted from the American Journal of Physiology

Vol. XXIX. —January 1, 1912. —No. III.

ON THE INFLUENCE OF INTRAVENOUS INJECTIONS OF AN EXTRACT OF THE PANCREAS ON EXPERIMENTAL PANCREATIC DIABETES.

By ERNEST LYMAN SCOTT.

 

[From the Hull Laboratories of Physiology and Biochemistry.]

IN spite of the many attempts to lower the sugar output in pancreatic diabetes by the administration of extracts of the pancreas, no one seems to have obtained consistent, positive results, or as Hedon (1) has recently pointed out, the positive results are capable of several interpretations. A good review of the subject will be found in the papers of Leschke2 and Pfluger. Leschke showed that the external digestive enzymes of the pancreas have a fatal effect upon the experimental animal; but, in his attempts to destroy these enzymes by heat he evidently destroyed the internal secretion as well, if in fact it was present in active form in his extract. That these external enzymes may destroy the internal secretion also is hinted at by Cohnheim4 and his followers in their method of extraction. Another point that seems not to have been sufficiently considered is the possibility that the internal secretion may be readily destroyed by oxidation during the preparation. This seems probable in the light of our experience with adrenalin. That the secretion is at least very unstable is indicated by Drennan’s work.~ This investigator injected sterile blood from normal dogs into depancreatized dogs and found in every case a diminution of the sugar output in the urine, provided the blood was fresh, but if the blood had stood for a few hours after being drawn, no results followed. It seemed worth while, then, to see if the sugar output could be lowered by an extract in which precautions were taken to prevent (a) the effect of the digestive enzymes on the internal secretion as well as on the subject, and (b) to prevent the oxidation of the internal secretion while being prepared from the gland.

 1. HEDON: Comptes rendus de Ia Societe de Biologie, 1911, lxxi. p. 124,
2. LESCHKE: Archiv fur Physiologie, 1910, p. 401.
3. PFLUGER: Archiv fur die gesammte Physiologie, 1907, cxviii, p. 263
4. COHNHEIM: Zeitschrift fur physiologische Chemie, 1904, xlii, p. 401
5. DRENNAN: This journal. 1911, xxvii. p. 396.

It was hoped that the presence of the digestive enzymes could be eliminated by the atrophy of the gland which follows complete ligation of the ducts; but after several attempts in the dog which proved futile so far as complete atrophy was concerned, this method was abandoned as impractical. In subsequent work these enzymes were rendered inactive at once by a high percentage of alcohol and were later killed by long-continued contact with strong alcohol.

Methods of preparing the extracts. — Two methods of extraction were attempted: (a) by alcohol, and (b) by water rendered slightly acid. The temperature was never allowed to go above 65 C. and usually was kept below 60 C. While the alcoholic extract did not give the results hoped, its method of preparation may be of some interest. The pancreas was ground up with sand and warm alcohol (40 C.) and extracted with enough alcohol to bring the total alcoholic percentage above 85 per cent. The glands were extracted for three twenty-four-hour periods at 35 to 40 C. This extract was then filtered and the filtrate evaporated to dryness under a negative pressure of about 70 cm. and in a slow stream of carbon dioxide, and the residue extracted with ether at room temperature. The ether extract was discarded and the residue dissolved in 95 per cent alcohol, and sufficient alcohol added to make up to such a volume that 10 c.c. of the solution represented 1 gm. of the fresh gland. For use, such a quantity as was desired was again evaporated as above and dissolved in 0.85 per cent sodium chloride solution for injection. The preparations when evaporated for the last time were of a light straw yellow and soluble with some difficulty in the sodium chloride solution, as much as 60 c.c. being required for the larger amounts of pancreas used.

In preparing the watery extract we sought to avoid the blood pressure lowering substances by rejecting all alcohol soluble material. The glands were prepared as in the first method, but after the alcohol had thoroughly penetrated the material it was evaporated to dryness under a vacuum and extracted for some time in 150 c.c. of absolute alcohol at 38 C. This was poured off as completely as possible and the residue extracted for one hour and twenty minutes with water rendered just acid with acetic acid. It was then filtered as rapidly as possible and evaporated as before. When dry, it was covered with absolute alcohol and kept for use. For injecting, the alcohol was poured off and 20 c.c. salt solution added. In appearance, when dry, it was almost the color of the first extract, possibly more colloidal in appearance. It went into solution readily in the quantities of salt solution used, though the solution had somewhat the appearance of a finely divided colloid.

Methods of testing extracts. — Only dogs with pancreas completely removed are reported here. The complete removal was determined (a) by the constancy of the diabetic curve, and (b) by autopsy, though it was found that the first control was fully satisfactory. While only the significant portions of the tables are reported, we may say now, once for all, that the injections were made in each case after the sugar percentage in the urine had descended from the height occurring on the second or third day and had reached the level that is maintained more or less constant throughout the subsequent life of the dog. While it might have been advisable from some points of view to have secured more D/N ratios before the injections, it was assumed that when this had reached approximately 2.65 it had reached a fairly constant level.

RESULTS.

In brief, the results from the alcoholic extract were negative; the dogs in general showing an increase of D/N, though this in most cases was not great enough to be significant. All the dogs showed great depression immediately following the injection and lasting in some cases for two or three hours. Several of the dogs died within two or three days following this injection. The tables are records of two typical cases.

Experiments with the watery extract were made on four dogs. The first two dogs and the fourth showed much the same type of D/N history. The third dog showed also a fall of this ratio following the injection, but the record was so irregular that the results were discarded. The first three dogs showed no depression following the injection and, if one dared say it, seemed even brighter for a time after the injection than before it. The fourth dog, in which an older extract was used, showed a marked depression lasting for an hour and a half.

SUMMARY.

Intravenous injections of the pancreas extract, prepared as above, into dogs rendered diabetic by complete pancreatectomy diminish temporarily the sugar excretion and lower the D/N ratio in the urine. It does not follow that these effects are due to the internal secretion of the pancreas in the extract. The injections are usually followed by a slight temporary rise of the body temperature, and this may be a factor in the lowered sugar output. Physiologists are not agreed as to whether the internal secretion acts by diminishing or retarding the passage of sugar from the tissues into the blood, or by increasing the oxidation of the sugar in the tissues. The pancreas extract may decrease the output of sugar from the tissues by a toxic or depressor action, rather than by a specific regulatory action of the pancreas secretion. If this is the case, we ought to get the same results by extracts of other tissues. The work is being continued in the hope of clearing up these points.

I wish to express my obligation to Dr. A. J. Carlson, who has offered helpful suggestions on the physiological side, and to Dr.W. Koch and Mr. F. C. Koch for assistance in preparing the extracts.

NOTE: We do not reprint Tables I and II but mention that in Table I, Dogs C and E are omitted; In Table II, Dog G is omitted. These records appear in the Thesis.

Italics are mine. Author

 

This first incident played a great part in delaying introduction of insulin for a decade. Pressed for time many persons read only the conclusions as stated by the author, and study the body of the article only if further study is or seems warranted. As Scott himself said, "Who would read the thing when the author says it means nothing."

In this case, it was the executive officer of the department not the author, who decided the research was worthless. The author in the thesis claimed success.

The graphic records which we have reproduced had they been included in the publication must surely have aroused interest. They do not appear in the thesis. Compared to those presented by Banting in 1921-1922, Scott’s "Composite Curves" are more dramatically convincing than Banting’s. They are about in the same class as a graphic record of the slowing of the heart under electrical stimulation of the vagus nerve. Nothing is more startling.

Had the thesis been printed as written and the composite curves included those who repeated the work a decade later could never have claimed discovery of insulin. It would have been in use long before that time, a decade sooner, doubtless, and perhaps under a different name.

Fortunately for the historical record the University of Chicago at that time required that a candidate for a degree deposit three bound copies of the thesis in the University Library. The original typewritten copy in this case was also held by the Library. The curves, however, were not.

This regulation is by no means universal among all Universities. In this case it is crucial evidence. Ordinarily, a publication appearing under a man’s name is assumed to have been written by that man. In this important case it was not.

The law upholds a man’s right to his own name. It is a crime to commit forgery: definition, Webster’s 7th Collegiate-forgery, the crime of falsely and fraudently making or altering a writing or other instrument.

Motive is important. Here the motive was doubtless merely to uphold the honor of a department against what was regarded as unwarranted claims by a student.

My opinion is that this is true. It is also my opinion that the native arrogance of the man led him to overstep his vested authority. Ordinary university routine requires consultation before such changes are made. It was dereliction of duty, however, to defy the judgment of a fellow department and to ignore such remarkable graphic records.

One may conjecture as to what might have happened had Ernest Scott appealed for redress to university authorities. He did not. He went about advancing his career. He hoped his work would be repeated and eventually confirmed. He determined to go further in seeking professional backing and to continue with it. Those few taxing experiments successful as they were demanded more.

He was bitterly hurt. His wound was permanent, would never heal. He was correct in his remark, "Who would read it when the author claims no value." The article was passed over for a decade until Banting discovered it around 1920. He himself never lost faith in his work. He believed in it. So, too, had those in that other department, still in turmoil from death, and personnel changes. A. P. Mathews, if he had only stayed! He had believed in the research but Ernest Scott stood alone.

Whatever motives or intangible factors influenced events there is no question that the changes in the thesis held back the introduction of insulin for a decade. It made possible though it cannot condone actions of those who came later who claimed discovery and reaped the rewards, and the burdens.

A harsher view of the "Murdered Manuscript" might be taken. Knowing both men, the arrogance of the one, the serene strength of the other, I called the act a stab in the back. What was lost in face-to-face encounter was regained, thus, when the student was gone. I grant the man was honest. Otherwise he would not have allowed the medical discovery of the century to have passed out of his grasp because of pique against a disliked student. Life has a way of getting in its own whacks. I thought I saw signs of a caved-in personality of the gentleman in question and felt an odd compassionate disgust, in our single three-hour-long meeting in New York in the 1930s, over the dinner table.

Chicago had been tough. Kansas was impossible. Through a friend of the Chicago days, Frank S. Pike, Ernest Scott learned of a vacancy at Columbia University. He applied and was appointed instructor and associate in Physiology in September 1912, winning a Ph. D. degree in 1914, was appointed assistant professor in 1919, and associate professor in 1922. He retired in 1942. He enjoyed the years in the old P&S building on 59th Street & 10th Avenue, Manhattan, when great men such as Dean "Bill" Darrach, whose dream produced the Columbia - Presbyterian Medical Center and Hans Zinsser, Sr., were his associates and friends. He had charge of graduate studies for higher degrees in physiology. Some of his students attained eminence.

COLUMBIA UNIVERSITY 1912 - 1966

Dr. Frederick S. Lee was head of department in physiology in 1912. A man of personal kindliness he gave every possible assistance to the new member of his staff.

Almost the first thing Ernest Scott must have done, undoubtedly at Professor Lee’s behest, was to send a copy of his January 1912 publication with a letter to Professor E. H. Starling, University of London. One could not overestimate Professor Starling’s prestige, worldwide in his field. He stood at the very pinnacle of achievement in human physiology, in England and in America. We do not have a copy of this letter but we do have Professor Starling’s reply.

This letter, dated October 28, 1912, shows that Professor Starling passed by the opportunity of sponsoring the introduction of insulin. He could have sponsored the then unnamed hormone putting it into medical use had he cooperated with Ernest Scott in 1912. He, from his letter, took no interest in "those brighter looking dogs". Again Ernest Scott was denied aid.

 

UNIVERSITY OF LONDON University College

Gower Street, London W. C.
Institute of Physiology
October 28th, 1912.

Dear Dr. Scott:

I am much obliged for the interesting paper you have just sent to me on the effect of intravenous injection of pancreatic extract. It is quite possible that your method of preparing the extract is better than ours. I merely used the same method that I had adopted ten years ago for making extracts for injection into pancreatic patients. The behaviour of diabetic patients is however so variable that no definite conclusions could be drawn from our experiments. Moreover I do not regard alterations in the D/N ratio, unless they could be prolonged for weeks, as sufficiently definite. More definite evidence of the direct influence of pancreatic extract would be a rise in the respiratory quotient during the three or four hours succeeding the injection, showing that during this time the tissues had regained the power of utilising dextrose. I intend to try this at some time or other, but I should be glad if you or some one else with a respiratory apparatus at disposal would investigate this point. I note that Lusk has a respiratory apparatus which would seem to be particularly adapted for this purpose.

I am more concerned at present with the establishment of the main theses of Knowlton and myself, namely, that the tissues use sugar normally, that they cannot use sugar in a diabetic condition, and that the power of utilisation is restored by pancreatic extracts. There are so many possible fallacies in question concerned with the behaviour of the sugar in the blood that I shall not feel happy about our conclusions until they have been confirmed by different methods both of experiment and of sugar estimation. I value your work as a contribution in this direction, but I should lay much more stress on an alteration in the respiratory quotient.

Believe me,

Yours truly,

ERNEST H. STARLING

Diabetes was outside Professor Lee’s field of research but he lost no time in providing introductions to those who were working on carbohydrate metabolism in this country. He took up the matter personally with Graham Lusk at Cornell University. Graham Lusk was unimpressed. It was impossible that a young man working alone could have anything of value. He did not interview Ernest Scott nor consider his experimental results. He brushed the matter off as of no consequence. Ernest Scott could get no hearing.

No help was to be had from Lusk but Professor Lee suggested another authority on diabetes, J. J. R. Macleod.

Professor J.J.R. Macleod, born in Scotland in 1876 was at that time at Western Reserve University in Cleveland, Ohio.

Kinsman, we recall, is not far from Cleveland. The Ernest Scott family was accustomed to spend a summer vacation on the Scott Farm in Kinsman so that a visit to Cleveland was a simple matter.

In view of the part played by Professor Macleod in the introduction of insulin into medical use in 1923 it is significant that Ernest Scott asked his help - in 1913, probably.

Here is a letter from Ernest Scott to J. J. R. Macleod. The year does not appear on the copy but from other incidents it may safely be placed as 1913, as we know from the "CONVERSATIONS."

This letter is firm evidence that Professor Macleod had the opportunity to introduce insulin in 1913-14 had he chosen to promote, continue and sponsor Ernest Scott’s work done in Chicago, under his direction at Western Reserve.

Letter from Ernest L. Scott to J. J. R. Macleod.

Prof. J. J. R. Macleod
Cleveland

My dear Prof. Macleod:

Prof. Lee wanted me to see you before returning to New York if it is convenient to you and talk over some points in regard to an investigation that I am planning for the coming year. I will be in Ohio until about the 15th of September and can come to Cleveland whenever it is most convenient to you but if there is no difficulty to you would prefer to come during August.

Respectfully,

Ernest L. Scott

 

We know that Ernest Scott was treated civilly enough, but again he found no support. There was no help from Professor Macleod for him in 1913, or ever.

Professor J. J. R. Macleod served in the Medical School of Western Reserve University from 1903 until 1918.

January 6, 1970

Mrs. Ernest L. Scott

64 South Street

Bogota, New Jersey 07603

Dear Mrs. Scott:

Your letter was referred to me by the Secretary of the University. Dr. J. J. R Macleod came to the Medical School of Western Reserve University as Professor of Physiology in 1903. The exact date of his appointment by the Trustees was May 11, 1903. He resigned in June of 1918.

Incidentally you might be interested to know that Case Western Reserve University was created by the federation of Case Institute and Western Reserve University on July 1, 1967.

Sincerely,

Ruth W. Helmuth (Mrs. D. E.)
University Archivist
REH/lc

 

With Ernest Scott’s work denied support on all sides who can blame Professor Lee for advising his junior member to forget the whole matter and then turning him on departmental work. Starling, then Lusk, then Macleod saw no promise. How could Dr. Lee? Yet there were those wonderful charts! Could no one see their significance? Did they study the data? Did they merely say, it cannot be? The last statement was Ernest Scott’s conclusion.

Later, in 1923, to his "Claim to Priority" on the discovery of insulin, other than publication in the Journal of the A.M.A., he received no response, so far as I know. I mentioned in our "CONVERSATIONS" that one of the leading M.D.s in the New York area remarked, "If he had it 10 years and did not use it, he ought to be put in jail".

In this imaginary jail, beside the abjectly putdown young discoverer, what an illustrious company we may provide at his side, all the leaders in the profession! The walls of the jail must fall, however, when we recall that the method itself was published in 1912 and thus was open to all, including the M.D. mentioned above.

It was impossible to repeat the Chicago experiments in New York. Nothing favored repetition. Indeed, method of science is that a second worker repeat, confirm or reject. His life plan of residing in New Jersey and working in Manhattan made experiments stretching over 36 hours impossible. Nor were there the facilities available such as Rockefeller wealth had provided at Chicago. His one effort was a failure but welcome testimony that he had not given up. This article appeared in the Proceedings of the Society for Experimental Biology and Medicine in 1913. His Ph. D. thesis, 1914 dealt with use of small samples of blood for sugar determinations now becoming available, so that one cubic centimeter, in duplicate, could be used instead of 20 c.c. These new techniques greatly helped Banting later.

WORLD WAR I

When our country went to War in 1917, Ernest Scott might have been exempted. He had a wife and six-year-old son. He volunteered. He was appointed Captain in the Sanitary Corps. This is part of the Medical Service. In France he was assigned to Base Hospitals. His work was searching out local sources of fresh foods, supervising food management and forwarding reports on hospital management with respect to food to Washington. In France, on one of his reports, the Colonel in charge of one Base Hospital was sent home in disgrace.

During his service he travelled all over France, not by jeep but by rail. There are five hundred or so post cards in my possession testifying to his presence in seventy-five towns or villages from Quimper to Nancy, from Le Havre to Hyeres. He spoke most often of Tours, Dijon, Chaumont, Clermont-Ferrand, Quiberon, and the French Riviera where he and many others were sent as the war was winding up to recover from the flu. At the war’s end his rank was raised to that of Major, not by the A.E.F. but by the regular army, he seemed pleased to say. He received an honorable discharge from Camp Dix in June 1919. He returned to Columbia from which he had been on leave for the duration, as had been many of his associates. I was led to remark, "It seems to me you met all your friends and acquaintances in France."

Not all the suffering was done in the trenches. He returned from France a man broken in health. "The war did something to him!" said a friend. What did it, I am not sure. He went in, a rounded-cheeked handsome male (photo). He came out a white-faced old man. He looked far older than his 43 years when I met him first in 1920. Whether it was hardships of travel and poor accommodations usually with crawling "bedfellows" in unheated peasant rooms, or evidences of man’s inhumanity to man so evident in Base Hospitals is a question. It is said that President Wilson when visiting one of these Base Hospitals, insisted upon seeing what was behind the curtains and was so shocked by what he saw that he cancelled all his engagements for the day and retired to his room. The novelist Katherine Mansfield wrote that she dared to make one trip from England to Menton and was so worn by hardship of rail travel through war-torn France that the tuberculosis she was hoping to control ran riot instead. Her death followed not long thereafter.

Everything together resulted on Ernest Scott’s return to recurrence of tuberculosis. Removal of tubercular glands in his throat was done by "Charlie" Peck at Roosevelt Hospital across from the old P & S Building on 59th Street and 10th Avenue. Whether this throat operation interfered with his voice I cannot say but I knew him as very soft-spoken. Giving lectures in the large amphitheaters seemed easy for others. For him, it took all his strength. In my opinion he ought never to have been told to do it. He was preeminently a research man. My opinion, too, is that the duodenal ulcers, the "kissing ulcers that never heal," which in later years led to a gastric resection, had their start during the war years. I base this opinion on my study of his white, drained face and slight figure when I met him first in June 1920, only a year after his return from France.

14a.jpg (14798 bytes)
Major Ernest Scott, AEF, WWI, 1917-1919

Fate seems to have been especially cruelly inclined toward Ernest Scott. He had out-thought the scientific world in 1911 and had made the first successful extraction of insulin from adult pancreas. The intent of his work had been destroyed in the first publication under his name. He had approached the leaders and everywhere the answer was "No" to his requests for support of his research. World War I shattered his health. Tuberculosis which he had overcome in college years had recurred in different form. Fate had several more arrows labeled with his name in her quiver.

Helen Scott had seemed well when he had enlisted. When he returned he found her near collapse. She had been told by Dr. Phillips of Englewood, New Jersey, that she had tuberculosis of both lungs. He had advised her to sell the house at 123 West Grove Street, Bogota, chosen in 1914 because it was in good commuting distance to Manhattan. She had sold the house at a good price. He had also advised that she apply at once to a sanatorium such as that under Dr. Trudeau in Saranac Lake, New York. The frail little boy, now 8 years old, had had pneumonia. Dr. Phillips had stayed all night at the boy’s side to save his life. Frank never forgot the toy white rabbit he hugged to his bosom as he went to sleep, which Dr. Phillips had given him. Ernest Scott found chaos when he returned home from the war.

Those were hard years for the Ernest Scott family that followed until Helen Scott’s death in 1927, January, I think. Helen was in several sanatoriums while’ her husband tried to provide some sort of homelife for his growing son in furnished rooms or camping during summer months near her retreat. I learned that the romance of camping out had lost all charm for him.

Indomitable was the word for Ernest Scott. Even though Helen was so grievously ill, with savings from his war years and from a somewhat higher salary as assistant professor in 1919, he proceeded to build a home for his family with hope in his heart.

He selected a piece of level ground that would occasion no uphill walking as had the Grove Street home, at 64 South Street, Bogota. Influenced by the stone architecture he had admired in France he built for long-term occupancy. He was his own architect. All services were on the ground floor. Only a ladder went to the attic. This was so that Helen would not climb stairs. He planned an outdoor, screened-in sleeping porch for her. He built of 8 inch hollow tile with tapestry brick facing. There was a 50 x 100 ft. piece of good ground, once a commercial Hackensack melon patch, for a garden overlooked by the porch at the rear. He built well. After half a century this house ahead of its time in planning had demanded almost no upkeep, standing as built, "built like a fort."

Helen’s stay at Saranac was unproductive. She was dismissed with the sad prognosis that she was incurable. A perfect little home in Bogota was waiting for her. Perhaps at home she could recover

A fellow sufferer in Saranac was Charles Christian Lieb. He, too, was declared incurable. He was sent home to a lovely colonial mansion in one of the Cornwalls in Connecticut to die. He was just turned 40, Helen Scott’s age. On a week-end visit once, he showed us his cot under a window in a large tree-shaded room,

"I lay there. That is where I lay, waiting to die.... But I did not die."

As Hosack Professor of Pharmacology, Columbia, Professor Lieb served as head of department until his retirement. He was a jewel of a man. I remember him well. Tall, heavily built, with a limp, he oversaw every item in his well-run laboratory. I recall his lectures. "Once, we had a pharmacopeia 3 inches thick. Now, I can count on my two hands a dozen drugs only, useful in medicine." Indeed, what changes in these past 50 years! Then, "There is no disease for which alcohol is prescribed which is not served better by another drug." And his unforgettable pronouncement, "Alcohol is a poison, a depressant, working first on the highest centers of the brain and in greater concentrations progressively downward on the nervous system until the entire body becomes comatose." No five million alcoholics if all had heeded "Charlie" Lieb! I recall, too, his pride and pleasure in recounting his activities on a National Council of Churches Committee as a fellow worker with some colored churchman whom he admired. He was greatly loyal to St. George’s Church on Stuyvesant Square, Manhattan: "Why wouldn’t I be loyal and grateful! It gave me everything I had in my youth, my social life, my faith, even my wife." I find no harm in bringing to mind a man I regarded highly as did many others. "Charlie was a prince."

Charles Christian Lieb recovered. Helen Hotchkiss Scott did not.

The house at 64 South Street was occupied for 18 months. It was sold to a neighbor who had watched it being built. Helen Scott was accepted in 1922 in Bonnie Burne Sanatorium in Scotch Plains, New Jersey, and here she remained until her death in 1927.

Ernest Scott once more was homeless. Once more he must make a precarious homelife for his growing son and for himself. This was in 1922. The years 1921-1922 were great years for insulin. These were the years when Frederick Banting was working in Toronto on experimental diabetes and Ernest Scott knew of this work.

Ernest Scott’s second letter to J. J. R. Macleod is extant.

I submit a letter dated February 7, 1922 written by Ernest Scott to J. J. R. Macleod. In it he gives full details of his method which is the same with minor additions as in his Thesis and in the 1912 publication.

He refers to the spurious conclusions in the latter, unfortunately perhaps though it ought not to have made any difference. The method was what was important. If it worked, he, no one else, was the originator. Events had not been kind to Ernest Scott. He was in no position to defy what we now call the establishment. Here, at last, were the second workers he had so diligently sought, failed to find and now we find him urging them on to make use of his work.

Ernest Scott was following the accepted practice among scientists which is to publish your work, and to await repetition of the work by a second worker who will confirm or refute it. Gregor Mendel’s fame came about somewhat in this way.

Ernest Scott’s second letter to Macleod is printed herewith.

February 7, 1922
Professor J. J. R. Macleod
University of Toronto
Toronto, Ontario, Canada

Dear Professor Macleod:

I hope you did not take offence at the rather precipitate manner in which I left you at the door of the Taft in New Haven. No offence was meant, but that train made particularly good connection to my home in New Jersey.

Since returning to my laboratory I have been looking over some of my old work upon the pancreas hormone, and while I am convinced that the hormone is present in my preparation, I would not be warranted in taking a stronger stand for publication than the rather guarded one that I took at that time (Am. Jo. of Physiol. XXIX, f. 306).

I do not believe it probable that one would get the marked reactions with my preparation which you described for yours. Though of this I cannot be sure for I have not put it to the severe trials that you have your preparation.

In regard to the crystalline form in which I obtained the material and keeping qualities; things are much as I described them to you.

The method of preparation as perfected in some later unpublished work was as follows:

1. The pancreas was removed and ground as rapidly as possible with enough alcohol, preferably absolute, to raise the alcoholic concentration above 85%, the tissue water being taken into account.

2. The alcohol and water was now evaporated under reduced pressure, at a temperature below 40 C, a current of CO2 being passed through the mixture by means of a fine capillary. This had the manifold purpose of:

a. preventing bumping
b. preventing oxidation
c. hastening evaporation

3. After the material was dry, a considerable amount of absolute alcohol was added and it was extracted for 24 hr. at 36C. This extraction was repeated 3 times. This extract was discarded as it was found to be extremely toxic. It was injected into a number of animals after the removal of the alcohol and without exception lead rapidly to the death of the animal.

4. The residue was freed as thoroughly as possible from the alcohol, by drainage, (probably filtering on a Buckner would be better) and extracted for an hour and a half with distilled water to which just enough acetic acid had been added to render it acid to litmus. (Possibly extraction for a longer period or additional extractions would give a better yield.) This was not tried as I was afraid of injury of the material by prolonged exposure to the water.

5. The water-acid extract was now separated by filtration on a Buckner filter and evaporated as under 2.

6. When dry it was kept under absolute alcohol or better transferred to a tube and sealed in a vacuum until used.

The extract so obtained was crystalline in appearance and straw color. For use it was dissolved in salt solution or Ringer’s and injected intravenously.

Since this solution had somewhat the appearance of a colloidal dispersion, it is probable that the crystalline appearance was due in part at least, to the presence of salts and that the active substance was not, wholly at least, so highly purified as the appearance of the dry residue would indicate. It was, however, readily taken up by the salt solution.

I see little prospect of getting back to a study of the properties of this material in the near future and would be glad that you make any use of my work that you can. It fits in so well with yours that it is too bad not to get it all cleared up at once.

I should be glad too, to get from you any criticism or suggestions which you care to give in regard to the tentative hypothesis that I myself outlined at the last meeting and, as always, data which would be apropos is very acceptable.

Sincerely,

Ernest L. Scott

A meeting in New Haven of the American Physiological Society in December 1921 was reported in Volume LIX, 1922, of the American Journal of Physiology. In this volume, an article appears by Scott and Ford on glycemia and blood sugar sampling but in the report of the meeting there is no reference to a hypothesis upon which his 1912 method for extraction of insulin was based. His hypothesis must have been voiced in a verbal discussion and was thus open to anyone who cared to consider it. The hypothesis, which by now we ought to recognize as the idea that the hormone was a protein and subject to destruction by proteolytic enzymes, the digestive enzyme, trypsin, formed in the adult pancreas, was mentioned, however, as you may read in the last paragraph of this letter. This hypothesis was the basis of the 1911 experiments where "the first experiment worked."

We know, also, from the CONVERSATIONS that Banting as well as Macleod and Scott attended the "Christmas" Meetings of the A.A.A.S. of which the American Physiological Society is a member in December 1921. The letter confirms the presence of Macleod.

We repeat. In this letter E. L. Scott states that he had given his hypothesis openly and asks J. J. R. Macleod to consider its application and its importance with respect to diabetes.

WHAT BANTING, HIMSELF, SAYS OF THE SCOTT METHOD

Banting and Best tell us that they used the Scott extract on a depancreatized dog and kept this dog alive and healthy for 70 days. The relevant portion of their article in the Journal of Laboratory and Clinical Medicine, St. Louis, vol. VII, No. 8, May 1922, is reproduced here. The experiments continued from November 1921 to January 27, 1922.

A depancreatized dog had been kept alive for some time by injections of fetal pancreas extract which contains no digestive enzyme but which, as we learned from Drennan’s work (CONVERSATIONS) does contain insulin. When decision was made to try extracts from adult pancreas, choosing the Scott method as the "most efficient", consider the following:

EXCERPT

"Since the animal at this stage was still in fairly good condition, even though there had been considerable irregularity in the administration of extract, it was decided to discontinue using it for the purpose of testing the relative potency of different forms of extract and to administer to it the most efficient of these in regular dosage so as to determine for how long a time the animal could be kept alive. On December 7 [1921] the injection was made with fetal calf extract prepared as described above, but on December 8 an extract prepared by extracting the pancreas with alcohol, evaporating to dryness and redissolving the residue in distilled water, was used with the result that 4 c.c. caused the blood sugar to fall from 0.30 to 0.15 percent in one hour.

A second injection of this extract (12 c.c.) was given at l p.m. and at 5 p.m. the blood sugar was 0.12 per cent. It will be seen that the principle upon which the preparation of this latter extract depends is the same as that of E. L. Scott and the favorable results led us to see whether adult pancreas could be used in place of fetal. Six c.c. of whole gland extract prepared as above were therefore injected daily from December 8 to January 3 inclusive. On January 4 the

administration of extract was discontinued and on this day the dog execreted 12.86 grams of sugar in a volume of 450 c c of urine The animal was in good condition and was on a diet of lean meat On January 5 it was not so hungry or so lively as on previous days and 4 grams of sugar in 350 c c of urine were excreted On the next day (January 6) [1922] 3 5 grams of sugar and 320 c c of urine were excreted and the animal was in a very poor condition compared with that of a few days previously On January 6 the diet was changed to one of milk and biscuit along with meat, and the sugar excretion rose to 25 gm At noon on January 7, while on the same diet, 8 c c of whole gland extract were injected and the twenty four hours’ sugar excretion was found to be 22 gm A further injection of 10 c c of extract at 9 a m on January 8 brought the sugar excretion down to 2.0 gm

The original weight of the animal was 10.1 kgm, and one week after the pancreatectomy it was 8.1 kgm This was maintained fairly constant throughout the second and third weeks after the operation and then slightly increased From the fifth to the ninth week (see Figs 1 and 2), during which time daily injections of 6 c c of whole gland extract were given, the condition remained good and was so on the 63rd day when to convince ourselves that the extract was necessary to the health of the animal we discontinued its administration for three days (21, 22, 23 of January) with the result that the dog became so weak that it was barely able to stand Extract was again given on the 24 and 25 of January with decided im provement On January 27 when the dog weighed 7.9 kgm it was killed by an overdose of chloroform and a careful autopsy immediately made by Dr. W. L. Robinson, Pathologist at the General Hospital, Toronto.

PANCREATIC EXTRACTS by
F G BANTING and C H BEST, Toronto, Canada
The Journal of Laboratory and Clinical Medicine, St. Louis Vol. VII, No. 8, May, 1922 pp. 467-468

Italics are mine

If you read this article with care you may realize that Banting, himself, made no effort to devise a method to extract insulin from an adult pancreas He implies he tested methods devised by others, then chose the one that gave the most favorable results He says this quite plainly The one he chose was that of E. L. Scott. Furthermore, he makes no claim to any change in the method as it had kept diabetic dogs alive and healthy as long as wanted and until after it had been used with success, so far as diabetic symptoms were concerned on three human diabetics in the Toronto General Hospital (Nobel Lecture, 1925) Whose method was used? That method of E. L. Scott so simply stated by Banting, "extracting the pancreas with alcohol, evaporating to dryness, redissolving in distilled water". (Apparently, whether distilled water or "weakly acid" as in Scott’s method, is used to dissolve insulin for injection is unimportant since Banting’s 1923 PATENT returns to Scott’s weakly acid solution, although the insulin effect was obtained with either).

The method was not quite so simple as that but it was "the principle of E. L. Scott", the essential part of his 1911 method. Banting mentions no other. He mentions no changes.

We see that Banting and Best are the long sought-for "second" workers who were to repeat, verify and confirm or refute the 1911-12 method. Confirm it they did, on diabetic animals and on diabetic humans since this extract prepared as described by Scott was almost immediately tested on three cases of diabetes mellitus in the wards of the Toronto General Hospital. We read in the NOBEL LECTURE, Sept. 15, 1925 on Diabetes and Insulin by Frederick G. Banting, excerpt:

"Diabetic dogs seldom live more than 12 or 14 days but with the daily administration of this whole gland extract we were able to keep a de-pancreatized dog alive and healthy for ten weeks………Autopsy showed no islet [insulin-forming] tissue."

Continuing:

"The extract at this time was sufficiently purified to be tested on three cases of diabetes mellitus in the wards of the Toronto General Hospital. There was a marked reduction in blood sugar and the urine was sugar-free."

Appearance of sterile abscesses ascribed to the high protein content made inadvisable continued use of the extract. It had corrected the condition of diabetes. The Scott method had extracted all the protein from the adult pancreas. It removed diabetic symptoms but it brought in an unfavorable condition of its own.

This method of extraction as described so simply by Banting in the words, "extracting the pancreas with alcohol, evaporating to dryness, re-dissolving in distilled water," and attributing the method rightly to E. L. Scott, 1912 was, indeed, simple. The team which Macleod quickly formed in Feb. 1922, once convinced of the value of the method, went to work at once to get insulin into quantity production for its introduction into medicine and for this a patent was needed. Remember that Banting states quite clearly that Macleod did not enter the picture until after the Scott method had been used successfully both on experimentally diabetic (depancreatized) dogs and, also, on three diabetics in the Toronto General Hospital. This was in February 1922. Dates here are significant. (Nobel Lecture, Banting 1925. This is out of turn as to chronological records, here, and will be presented in order later). Remember that Macleod shared the 1923 Nobel Award for "discovery of insulin".

According to Banting in his Nobel Lecture, 1925, it was at this point when it was evident to all that the hormone that would control diabetes had been captured, that J. J. R. Macleod turned his laboratory staff over to the preparation of a product suitable for clinical use, this in February 1922. This was hardly "discovery". It was further purification. Scott had used ether to remove fats. To nail down the fractional unit of protein in the protein-mix would naturally follow, and for this, centrifuging was used to fractionate the proteins.

PATENT----1923 #1,469,994

Before turning to the patent taken out the following year application filed January 12, 1923, we should read two letters, one written by Dr. Scott on September 8, 1922, in answer to a letter from Professor John Murlin of the University of Rochester, of which I have no copy, and the second, a very important letter, in reply to Dr. Scott by Dr Murlin, dated September 25, 1922.

The contents of this first letter of Murlin to Scott was to inform Scott that "they are patenting your method," as I recall it was told to me. The sentence I have italicized in the following letter was Scott’s response.

September 8, 1922

Professor John R. Murlin
University of Rockester
Rochester, N. Y.

Dear Professor Murlin:

I was somewhat surprised at the news contained in your letter. I did not expect anything of the kind from Macleod’s laboratory. On general principles, I am against patents in work developed in pure science. In this particular case, the men in question have probably gone farther than anyone else, though I cannot help but feel that the fundamental principles involved were worked out long previously and that, as you say, you and I probably had as much of a hand in it as had Kleiner and Paulesco and possibly Knowlton.

If it would be sufficient to stop this patent to furnish the examiners with this data, I should prefer to let the matter rest at that, rather than take out the patent.

Might it not be possible that the A.M.A. would take it out for the protection of American medicine?

Sincerely yours,

(Signed) Ernest L. Scott

* Italics are mine. Author.

 

The University of Rochester
Department of Physiology

Dr. E. L. Scott

437 W. 59th st., September 25th, 1922.

New York, N. Y.

Dear Dr. Scott:

Yesterday I paid a visit to Toronto and had a good talk with Banting and McCleod regarding the production of insulin. It is true that a patent has been taken out in the names of Best and Collip, Banting having refused to permit the use of his name. The patent was then assigned to the University and the University through a Diabetes Committee has entered into contractual relations with the Eli Lilly and Company for its production. I was interested particularly to learn the attitude of Banting and McCleod toward the production of an anti-diabetic extract by another laboratory. Banting stated that he had no objection whatsoever, but thought Eli Lilly and Company or Clowes at least would set up a claim of interference; so if you have any such design in the back of your head it may be well to consult Clowes first.

During the last six months we have developed in our laboratory by my own method a nearly pure product and have proved its potency in every way even on human subjects. It seems a pity that we should not be able to have it produced independently but such may turn out to be the case.

Your suggestion that a patent might be assigned to the American Medical Association is a good one though of course an Association could not take out a patent; only an individual or individuals can invent anything. It occurs to me that in the event of a hoggish attitude on the part of Clowes it might be necessary for you and me to combine and together apply for a patent which could then be assigned to the American Medical Association or to the National Research Council Medical Division.

You were the first, so far as I am aware, to use alcohol (1) in the extraction of an active agent. The name insulin has been given to the alcoholic extract. A better name for the active agent, which after all is the essential thing, would be something like glucopyrin2 since, as we proved as long ago as 1916 and confirmed again this summer it does without a doubt cause the combustion of sugar. Please tell me how you feel about it.

Very sincerely yours,

(Signed) John R. Murlin

*Italics are mine. Author.
Alcohol was used to precipitate protein. cohngeim (1906) used alcohol unsuccessfully.
Insulin is not a gluco-pyrin.

Before reading the patent, recall Banting and Best’s simple statement, "extracting with alcohol, evaporating to dryness, redissolving in distilled water. . ."

Patented Oct. 9, 1923. 1,469,994

 

UNITED STATES PATENT OFFICE.

FREDERICK G. BANTING AND CHARLES HERBERT BEST, OF TORONTO, ONTARIO, AND JAMES BERTRAM COLLIP, OF EDMONTON, ALBERTA, CANADA. ASSIGNORS TO THE GOVERNORS OF THE UNIVERSITY OF TORONTO, ONTARIO, CANADA.

EXTRACT OBTAINABLE FROM THE MAMMALIAN PANCREAS OR FROM THE RELATED GLANDS IN FISHES, USEFUL IN THE TREATMENT OF DIABETES MELLITUS, AND A METHOD OF PREPARING IT.

Application filed January 12, 1923. Serial No. 612,158. No Drawing.

 

To all whom it may concern:

Be it known that we, Frederick G. Banting and Charles Herbert Best, of the city of Toronto, in the county of York and Province of Ontario, Dominion of Canada, and James Bertram Collip, formerly of the said city of Toronto, and now of the University of Alberta, in the city of Edmonton, in the Province of Alberta, Dominion of Canada, British subjects, have invented an extract obtainable from the mammalian pancreas or from the related glands of fishes, useful in the treatment of diabetes mellitus, and a method of preparing it; and we hereby declare that the following is a full, clear, and exact description of the same, this application being a substitution in part of the application filed by the said James Bertram Collip and Charles Herbert Best on the 22nd day of May, 1922, Serial No. 562,835.

Previous investigators suggested that the ductless portion of such glands the mammalian pancreas and the pancreas of cartilaginous fishes, known as the isles of Langerhans, and related glands (principal islets) of bony fishes contains an internal secretion or hormone capable of alleviating diabetic symptoms in patients and in laboratory animals; and other conducted experiments in which diabetic patients and diabetic laboratory animals were given extracts containing this secretion or hormone.

The results of these experiments were not considered sufficiently satisfactory to justify the continued use of the extracts in the treatment of diabetes in man because of the presence in the extracts of toxic substances, and apparently no definite progress was made towards the preparation of an extract sufficiently pure to be safely administered to human patients until these experiments were continued by us. From our knowledge of the results in the early experiments we concluded that the presence of toxic substances in the extract caused local irritation followed by general reactions unrelated to the physiological and therapeutic effects of the hormone, and these conclusions were confirmed by our early clinical observations. We, therefore, deemed it advisable before further clinical trials were undertaken to prepare the extract containing the secretion or hormone in practically pure form and to devise suitable means for obtaining the maximum yield of it.

This was done by extracting the internal secretion or hormone from the fresh pancreas of mammalia, or, from the fresh pancreas of cartilaginous fishes, or, from fresh related glands, (principal islets), of bony fishes, with a solvent capable of preserving the activity of the internal secretion or hormone and then separating it practically free from injurious substances including inert associated gland tissue, proteins, proteolytic enzymes, salts and lipoids.

The following are steps we employed in several methods for obtaining a practically pure extract from the fresh pancreas of mammalia:

(1) Separation of the internal secretion or hormone from the fresh pancreas by extraction with solvents such as ethyl alcohol, methyl alcohol, methylated spirits, and acetone, or any mixture of these, which are capable of preserving the activity of this internal secretion or hormone by not destroying it and by largely preventing or inhibiting the deleterious action on it of such proteolytic enzymes as trypsin, erepsin, and the proteases, and of other catalysts present, followed by filtration for the removal of the inert associated gland tissue.

(2) Removal of the major part of the proteins by some suitable method of precipitation. For this purpose alcohol, colloidal iron, precipitation at isoelectric point by the use of dilute acid or alkali, or heating to a suitable temperature, may be used.

(3) Concentration of the extracted filtered solution, either before or after the removal of the proteins, as by distillation in vacuo, or evaporation in a dry air current.

(4) Removal of the lipoids after concentration either by mechanical separation or by chemical extraction with solvents such as ether, or toluol.

  1. Removal of the salts and a large part of the remaining impurities by precipitation with alcohol.

(6) Precipitation of the internal secretion or hormone with adherent substances by a higher percentage of alcohol and collection of the precipitate on a filter.

(7) Dissolving the precipitate in freshly distilled water, removing the admixed alcohol from this solution, and concentrating it, as by vacuum distillation, followed by sterilization of the resulting aqueous solution.

[NOTE: Although presented in different sequence, compare these steps with those enumerated under Ernest Scott’s 1911 Method of Extraction of Insulin.]

A potent preparation of the extractive of the internal secretion or hormone of the pancreas of mammalia was prepared as follows:

The fresh pancreas of the ox was minced and then mixed with an equal volume of alcohol. The mixture was strained and filtered to separate the inert associated gland tissue from the substances which had gone into solution in the alcohol. The filtrate was treated with two volumes of the same solvent and allowed to stand several hours with occasional agitation. The greater bulk of the protein was precipitated by this treatment and the resulting precipitate was removed by filtration and this filtrate subjected to vacuum distillation to obtain a concentrated aqueous solution. A buffer solution of 1/2 c. c. of 4% NaHCO solution was added for every 5 litres of filtrate before distillation was commenced, to keep the hydrogen ion concentration within the pH range 4 to 7. The concentrated aqueous solution was twice extracted with ether. The lipoid substances were removed by this treatment. The ether was separated mechanically and the aqueous solution was returned to the vacuum still and concentrated further. Alcohol was then added to make this concentrated solution 80% alcohol and the mixture was thoroughly agitated. The greater bulk of the saline substances were "salted out" by this treatment and there was also precipitation of more protein. It was then centrifuged. After centrifuging four distinct layers were manifested in the tube. The uppermost layer was perfectly clear and consisted of alcohol holding all the internal secretion or hormone in solution. Below this in order were a flocculent layer of protein, a second clear or watery layer saturated with salt, and a lowermost layer consisting of crystali of salt. The upper most layer was next siphoned off and treated with several volumes of 95% ethyl alcohol. The foregoing treatments with alcohol caused fractional precipitation in which the earlier fractions were composed of precipitated proteins and salts and the last fraction was the internal secretion or hormone The mixture was allowed to stand some hours. The precipitate was caught on a Buchner funnel washed with 95% alcohol and finally dissolved in distilled water. The resulting aqueous solution of the precipitate was then concentrated to the desired degree by vacuum distillation at low temperature and filtered through a Berkfeld filter to sterilize it. A preservative such as tricresol was added, the concentration of the same not exceeding 0.7 per cent.

A potent preparation of the extractive of the internal secretion or hormone of the pancreas of cartilaginous fishes and of related glands, principal islets, of bony fishes was obtained as follows:

The fresh gland was removed, cut in small pieces and placed in an equal volume of commercial alcohol. The mixture was allowed to stand at low temperature for several hours, after which the fluid was decanted and the gland tissue or solid residue ground to a fine pulp. The decanted fluid was then added gradually to the pulp with which it was thoroughly mixed by trituration to extract the internal secretion or hormone. The mixture was then strained to separate the pulpified gland tissue from the substance which had gone into solution in the alcohol, and the strained fluid filtered. The residue from this treatment was again extracted as above with fifty per cent alcohol and strained and filtered and the filtrate added to the first one. The alcohol was removed from the combined filtrates by distillation. The resulting aqueous solution was extracted by the use of ether for the removal of lipoids. The clear lipoid-free aqueous solution was then run off from under the ether and transferred to a wide beaker placed on a boiling bath so as to rapidly raise the temperature of the aqueous solution to between 70 and 75 C. at which it was maintained for 3 minutes with constant agitation of the beaker. By this treatment a flocculent precipitate of protein was thrown down and that portion of the ether which went into solution in the water was got rid of. The heated aqueous solution was then cooled, and filtered first through paper and then through a Berkfeld filter to sterilize it.

Dated at the said city of Toronto, this 19th day of December, A.D. 1922.

FREDERICK G. BANTING.
CHARLES HERBERT BEST
JAMES BERTRAM COLLIP.

Witnesses:
Chas. H. Riches,
Robert McClintock

A number of repetitious paragraphs are omitted here, for brevity’s sake. A copy may be obtained from the U. S. Dept. of Commerce, Patent Office, Washington, D. C.

The patent was applied for on January 12, 1923, Serial No. 612,158. It must have been prepared in 1922. Indeed it was signed on December 19, 1922. In spite of verbal camouflage Scott’s method shows clear. A preparation cannot be patented, only a method of producing the preparation can be patented. Yet this method, acknowledged in 1921-22 by Banting and Best as the Scott method, has been presented here as their own invention.

We have come to the end of the story of who discovered insulin and of those who verified the success of the Ernest Scott method. The idea was simple. Evolving the idea had not been simple. One man working in the freedom of his own mind, pushing aside every obstacle, through his own mental capacity made the breakthrough. No one ever equaled him. A decade later, Frederick Banting and assistant Best compared methods of extraction reported in the literature by different authors, chose that of E. L. Scott as "the most efficient of these," kept diabetic dogs alive and healthy for 10 weeks and eliminated symptoms of diabetes in three human diabetics. On human diabetics, further purification however, was found necessary as was only to be expected. Banting, too, worked alone. Best was not even a medical student at the time. I emphasize this aspect, that Scott and Banting each worked alone, because Scott thought that this was the essence of the exploring mind. We might call it freedom. Whereas Scott could get no backing, Banting added to Scott, convinced Macleod. This is where power stepped in. It was not granted to Macleod to solve the problem of the nature of insulin. That was done by a man later chosen to be ignored. However, the introduction of insulin into use in medicine was nothing short of spectacular.

The simplicity of the method demanded a patent. The patent must be taken out in a foreign country since the Toronto group was a group of Canadians.

They did not choose to include E. L. Scott although they were about to patent his method, already admitted by them.

Patent laws in the U.S.A. are stringent. I quote from "Patents U.S. Dept. of Commerce, Jan. 1966, Page 11.

"Only the inventor may apply for a patent. . .If a person who is not the inventor should apply for a patent, the patent would be void. The person applying in such a case would also be subject to criminal penalties for committing perjury . . .

These are the words of the U.S. Government, not mine.

Italics are mine. Author.

  

U.S. DEPARTMENT OF COMMERCE
PATENT OFFICE
WASHINGTON, D.C. 20231

February 14. 1967

Mrs. Ernest L. Scott

64 South Street

Bogota, New Jersey 07603

Dear Mrs. Scott:

We are enclosing two copies of Patent No. 1,469,994 and have applied your check for $1.00 to cover the cost.

The applicant must make oath that he believes himself to be the original and first inventor of the process, machine or composition of matter. The oath has always been required as part of an application for patent.

A patent cannot be obtained if the invention has been described in a printed publication anywhere in the world, or if it has been in public use or on sale in this country more than a year before the date that applicant made his invention. —Sincerely yours,

Robert T. Collins, Asst. Head

Correspondence & Mail Branch

RTC/eh

Enclosures

The Patent adds one step only, that of centrifuging. This is a further step in purification of a crude extract. As to its relative importance we may say that one might centrifuge minced pancreas (adult) through all eternity and fail to get insulin, whereas the preliminary steps of the Scott method yielded a product that kept diabetic dogs alive and healthy and removed diabetic symptoms in humans, according to Banting’s twice-stated account.(Jour. Lab. & Clin. Med. and Nobel 1925 Lecture.)

There is little question but that Ernest Scott would have won his case had he chosen to take Patent #1,469,994, Jan. 1923 to court. That he did not you may decide whether he deserves the less honor.

Ernest Scott did not contest the Patent. Insulin was introduced with all the fanfare of the medical discovery of the century, Nobel Prize, Knighthood, Honorary degrees, Medals, annual stipends for life, prestige and respect beyond measure to the "discoverers of insulin" but nothing for Ernest Scott, the mind existing in the background.

Ernest Scott played fair. He kept faith with the organization. The organization put to use his contribution for the alleviation of human misery, something beyond his power. He could isolate insulin. Medicine must use it.

What did the organization do for him? So far as his work with insulin is concerned, nothing.

This second letter from Murlin to Scott, Sept. 25, 1922, may absolve Mr. Banting from his part in obtaining a patent where he was forced to take a false oath in order to obtain it.

I believe a man is said to be forsworn when he asserts as truth one statement (Jour. Lab, and Clin Med. 1922 pp. 464-468) and then swears under oath to the opposite in another (Patent #1,469,994 1923) and reverts to the first in a third (Nobel Lecture, 1925).

I repeat, both Mr. Banting and Mr. Best in the 1921-1922 article affirm they used the E. L. Scott method of whole gland extract. In the Patent, both Mr. Banting and Mr. Best swear under oath that this method was originated by themselves. Read the Patent.

One or the other of these two statements must be False.

SCOTT METHOD and PATENT

As historical documents, both the 1911 Thesis of Scott and salient portions of the 1923 Patent of Banting, Best and Collip are printed. Deriving the meaning of each may seem difficult unless you recall the simplicity of Banting’s statement already quoted:

"extracting the pancreas with alcohol, evaporating to dryness, redissolving in distilled water. . . ." in saline or acidulated water in Scott’s method in the Patent, also, in acid solution. The "principle" of the Patent is obviously that of E. L. Scott in the 1912 publication and in his 1911 M.S. Thesis, as Banting, himself, stated in 1921-1922, with Best as co-author.

The story of who discovered insulin and who were the first to repeat and verify the discovery has thus come to its end.

Logically, those who had refused help to Ernest Scott in implementing his great breakthrough ought now to have acknowledged their blindness and come to his aid. This did not happen.

The recognition of the successful isolation of insulin was slow, even agonizing. Its introduction into medical practice was immediate. Banting added to Scott convinced Macleod with his official power.

In February 1922, (Banting’s Acceptance Speech, Nobel Lecture Sept. 15, 1925) Banting states, " . . with the daily administration of this. whole gland extract we were able to keep a depancreatized dog alive and healthy." We have read this in Banting’s 1922 article in Jour. of Lab. & Clinical Med. And Banting continues, "The extract . . , .was tested on three cases of diabetes mellitus in the wards of the Toronto General Hospital. There was a marked reduction in blood sugar and the urine was rendered sugar-free." He sticks by his story. He concludes description of first use of insulin on diabetics by the E. L. Scott method of extraction by stating, "high protein content rendered the continuous use undesirable, due to sterile abscesses."

Far from originating methods of extraction of insulin from whole adult pancreas it was not until this late point that Macleod entered the picture, if we may believe Banting who follows the above statement with:

"At this stage of the investigation, February 1922, Professor Macleod abandoned his work on anoxaemia [lack of oxygen] and turned his whole laboratory staff on the investigation of the physiological properties of what is now known as insulin."

What a late arrival was Professor Macleod!

Recognition for the so-called"discovery of insulin", such as life incomes, medals, Nobel Prize, honorary degrees, and others, if truth were served, would now be reapportioned as follows:

Discoverer, i.e. first reliable extraction of insulin from adult pancreas

Ernest Lyman Scott, 1911. University of Chicago

First scientist to repeat the Scott method and to prove its efficacy on experimental and human diabetics

Frederick Grant Banting, 1921-1922. Univer

sity of Toronto, co-worker, C. H. Best.

Patent, with added step of centrifuging to prepare a purer product for clinical use

Frederick Grant Banting

Charles Herbert Best

James Bertram Collip

Locus of Mr. Banting’s work:

University of Toronto

Head of Department of Physiology:

John James Richard Macleod

Remember that Macleod shared the 1923 Nobel Prize with Banting for the "discovery of insulin".

Repeating, insulin had been used successfully on diabetic patients (Banting, Nobel Lecture, 1925) in January 1922 and not until shortly thereafter did Professor Macleod become interested and begin to cooperate, i.e., in February 1922, and to promote the use of insulin in medical practice, after all the work not only of discovery but of verification had been done.

In the account of insulin in the 1964 edition of the Encyclopedia Britannica, signed by J. J. R. Macleod, he writes that he began work with Banting in May 1921, and that insulin, therefore, was extracted under his direction, in his laboratory and this same statement with the same date is repeated by Professor Sjoquist in the "Presentation Speech" in 1923, where the Nobel Prize in physiology and medicine was given to Banting and Macleod for the "discovery of insulin."

Macleod certainly helped to put insulin on the market in 1923. We see that he was a dead weight from 1913 to 1922 with respect to extraction of insulin (1911), i.e. the "discovery of insulin."

If Banting’s account be accepted as true, how did it happen that J. J. R. Macleod shared the Nobel Prize for the "discovery" of insulin? This was a question set by the man who did the original work in 1909- 1911.

"I always wanted to know what Macleod did when he came back from the war," was a question set by E.L. Scott.

We can answer this question from Banting’s 1925 Lecture. "Anoxaemia", i.e., lack of oxygen. Not until February 1922, after the E. L. Scott extract had been used successfully on human diabetics did Macleod begin to work with the product now known as insulin.

Professor Sjoquist follows Macleod: "Under Macleod’s guidance and in his laboratory, in May 1921, Banting began to work . . ." on experimental diabetes.

This is not at all what Frederick Grant Banting says when he places Macleod’s entry into the work as February 1922. This difference of a year, May 1921, Sjoquist and Macleod, and February 1922 in Banting’s Nobel Lecture, 1925, is a crucial year. Banting states positively that Macleod started work after E.L. Scott’s extract had been used successfully on both diabetic animals and upon 3 clinical patients suffering from diabetes. It was the Scott product he used.

We remind you that Banting refused to sign the Patent, obviously E. L. Scott’s method, and yet did sign the Patent. What changed his mind? You may note that he received his M.D. degree in 1922. In Canada, a man may obtain an M.B., Bachelor of Medicine after two years study and permitted to practice medicine, and return later to obtain an M.D., after a second period of study. Banting obtained his M.B. in Toronto in 1916. He was born in 1891.

The confusion in these conflicting dates is mindful of the small boy’s dilemma in similar circumstance. "There’s a lie out somewhere", was his conclusion.

Accepting Banting’s date since he is first Laureate of the pair, it holds the answer set by E. L. Scott, "I always wanted to know what Macleod did when he came back from the war". Macleod was working on something else. He had absolutely nothing to do with the so-called discovery of insulin. He was working on anoxaemja.

The facts are that Macleod’s inertia held back use of insulin for a full decade, 1913-1923, from E. L. Scott’s interview in the summer of 1913 to F. G. Banting’s verification of Scott’s claims in 1921-1922, and only in 1922, ten years after E. L. Scott’s first publication, he "turned his whole laboratory staff" in Banting’s words, in preparing crude insulin into a product useful in medicine.

In Scottish history, the Campbells in 1632 in service to William and Mary are asserted to have collaborated with English soldiers and to have killed their sleeping hosts, the MacDonalds. In Scotland, the Campbells never lived down the infamy.

In this account of first extraction of insulin, and the parts played by two transplanted Scots, I think it was ungallant of Macleod to claim as product of his own craftmanship the gem E. L. Scott gave him, thus in a way reversing the role of host and guest in the historical incident. Scottish history has great men, great affairs and great crimes.

Every honor given for the discovery, so-called, of insulin, in order to serve justice, it is my opinion; must be reassigned. The world is in Ernest Scott’s debt to this extent. He, in addition, shares the recognition for putting insulin into use. He gave the hypothesis and again his method for use in open meeting at New Haven in December 1921. The method had been open to all since 1912.

The following letter from H. H. Dale is interesting.

Professor Dale was nearly as highly regarded as E. H. Starling. Had he read Banting’s 1921-1922 article?

Here he invites the injured man to deny his injury. The Welshman was right.

We have the right to ask, was Mr. Roberts the single man in the entire English-speaking world who could read English with understanding and who was also willing to speak up in defense of truth and fair dealing among scientists?

MEDICAL RESEARCH COUNCIL
National Institute for Medical Research
Hampstead, London, N.W. 3.

Privy Council

5th February 1923

Dear Dr. Scott,

Very many thanks for your splendid letter. I thought that I knew from my conversation with you, when I had the pleasure of meeting you in New York, what your attitude was, and I took the risk of suggesting it in my letter. I am very glad to find that you did not object, and that I correctly interpreted your feeling. I am sure you will understand that my young friend Roberts, who made a quite unnecessary incursion into the discussion of the Insulin problem, was using your name merely as a means of weakening the credit of the Toronto work. I felt sure that you would agree with my feeling that he was not dealing fairly. Fortunately I was able to persuade him that he would do no good to anyone, and harm to himself, by going on with the matter. He is really a very good fellow, but an enthusiastic Welshman, who easily gets carried away, and loses his sense of proportion.

With kindest regards,

Yours very sincerely,

Dr. Ernest L. Scott, H. H. Dale Department of Physiology,

Columbia University,

New York.

One infers Ernest Scott offered no defense

CLAIM TO PRIORITY

Upon the urging of friends, the claim to priority in isolating insulin was made.

PRIORITY IN DISCOVERY OF A SUBSTANCE
DERIVED FROM THE PANCREAS, ACTIVE
IN CARBOHYDRATE METABOLISM

To the Editor:—Since insulin has become a clinical success there seems to be a certain amount of discussion as to priority. Naturally, I have been interested in following this discussion, though I had no intention of partaking in it until pressed by some of my acquaintances, and I now do so with reluctance.

During the spring and summer of 1911, while working in the laboratories of biochemistry and physiology of the University of Chicago, I developed a method for extracting a substance from the pancreas which is active in carbohydrate metabolism. The method of preparing the extract, together with an account of some of its physiologic effects, was published in the American Journal of Physiology (29:306 (Jan.) 1912).

In the Journal of Laboratory and Clinical Medicine (7:467 (May) 1922), Banting and Best state that "the principle upon which this latter extract depends is the same as that of E. L. Scott and the favorable results led us to see whether adult pancreas could be used in place of fetal. Six c.c. of whole gland extract prepared as above were therefore injected daily from December 8 to January 3 inclusive." This, I believe, is the first extract of a whole normal adult pancreas reported by Dr. Banting or his coworkers as having been used in their work, and constitutes the first repetition of my own work, reported in 1911, which is recorded in the literature. The test to which Banting and Best put the extract was much more severe than any that I made, but the favorable outcome indicates clearly that the discovery of the curative power of "insulin" has been open from January, 1912, to any one who cared to repeat and extend my work. This it remained for Dr. Banting to do, and the credit for this extension is clearly due to him.

In spite of simplification and the rather severe modification to which the process has been subjected for purposes of quantity production, it seems that priority on isolation and in the development of the fundamental principles involved in extraction clearly belong to the work reported from the laboratories of the University of Chicago. On the other hand, the present method of final purification by precipitation at the iso-electric point is an addition to the older method, which, though perhaps of extreme importance in obtaining a safe and uniform product for clinical use, is not necessary for obtaining the active principle, as is shown by the experiment of Banting and Best cited above.

I wish again to emphasize that it is no part of my intention to withdraw any of the credit from Dr. Banting and his co-workers for the work they have done in extending our knowledge of the physiologic and therapeutic properties of insulin. I wish also to point out that in the papers which have been published by him and by Professor Macleod, full credit has been given to my work. It is only because it has come to my attention that others are attempting to claim priority for the principles involved in making the extract that I call attention to the papers cited in this note.

Ernest L. Scott, Ph. D., New York

Department of Physiology,

Columbia University

Printed in the Journal of the American Medical Association, October, 1923.

 

The University of Chicago
Department of Physiological Chemistry
and Pharmacology

November 14, 1923.

Prof. E. L. Scott,
Columbia University,
437 West 59th St.,
New York City.

My dear Scott:

Your letter with enclosure [Priority Claim 1923] was received today. It was very nice of you to remember us in connection with the remarkable notoriety of insulin, which you discovered, as we all know, some years ago in our laboratory. I have often thought of it and of you in connection with that work and I usually refer to the matter in my lectures on internal secretion of the pancreas. I do wish that you could also have received some of the financial returns which our Toronto friends are so fortunate in.

I am pleased to hear that you are pleasantly located. We are also very happy at present and things really seem to be moving. We are more hopeful than ever of finally being moved to new and modern quarters. The situation looks very favorable at present.

With kindest regards,

Sincerely yours, (Signed) F. C. Koch Head of Department

The second letter from Professor Koch upon Professor Scott’s retirement from Columbia in 1942:

Fred C. Koch
1534 East 59th Street
Chicago, Illinois

March 1, 1942

Dr. E. L. Scott
Columbia University
New York City

Dear Dr. Scott:

It is a real pleasure and satisfaction to hear of the testimonial dinner arranged in your honor by former students and associates. Too often the modest, earnest and scholarly type of investigator does not receive the recognition he deserves and, unfortunately, in these days of distraction, keen competition and rapid means of communication, this is more true than ever. It is therefore doubly gratifying to me to see you honored at this time.

I have often recalled our graduate school days at the University of Chicago in 1910-11. Both of us had saved up enough to return to graduate work, you in Physiology and I in Biochemistry. You were doing pioneer work on the extraction and detection of the anti-diabetic principle from pancreas tissue. I have always taken great pride in relating to my classes how in 1910-11 Dr. E. L. Scott succeeded in lowering the D/N ratio in depancreatized dogs by means of his extract. I firmly believe that if blood sugar methods had been available in 1910 you would have contributed much to this problem and that the development of a non-toxic insulin preparation would have been associated with your name. It is to be regretted that you were not encouraged with financial aid to continue the work. If you had been thus supported the history of the treatment of diabetes would have been very different.

Your record as a teacher is an excellent one. I am sure that you represent the understanding, patient, conscientious and critical type so rare these days. The testimonial dinner arranged by your former students is the best evidence for that statement.

Permit me to thank your associates for this opportunity to express to you, though very ineffectively, my esteem of you. May you be blessed with many years of good health, success and happiness.

Cordially yours,

(Signed) F. C. Koch

TRIUMPH of an IDEA

Magnificent youth confident of its strength is revealed in the portrait of Ernest Lyman Scott at his desk in Ohio Wesleyan in 1902. We have followed the course of his action. He succeeded far beyond his dream. His mind alone would solve a problem that would affect thousands, mi1lions of people. His hypothesis that the hormone controlling diabetes was a protein yielded insulin in 1911. His method of extraction, though verified, much to his consternation was appropriated and patented by Banting, Best and Collip in 1923 and then insulin went into medical use. This we have proved to our and I hope to your satisfaction.

We turn to the 1923 Nobel Prize awarded for the "discovery of insulin". In the "Presentation Speech by Professor J. Sjoquist, Member of the Committee for Physiology or Medicine of the Royal Caroline Institute". Stockholm, Sweden:

"The Professional Staff of the Carolina 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."

After discussion of previous investigations he continues:

"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 hormone of trypsin, the protein-splitting enzyme. . . and a greater prospect of success if these cells were destroyed by ligation of the duct of the gland. .

There are two ideas here. Ligation of the duct had been tried and discarded as long ago as 1911 by Scott and Banting himself did the same. The other point, the destructive action of "protein-splitting enzymes" was not Banting’s idea but belonged to Cohnheim, 1906, and as we have stated earlier was not sufficient to obtain insulin by Cohnheim. Ernest Lyman Scott made the great connection. The hormone, insulin, must be a protein. His method based on this abstraction yielded insulin, obtained from adult pancreas, a practical method for mass production, and thus went into use in

1923.

Obviously Professor Sjoquist did not read Banting’s 1921-1922 article where he explicitly states that he selected the "most efficient" method of those he tried and got such "favorable" results with the method of E. L. Scott (1912) that diabetic dogs were kept alive as long as wanted and 3 clinical patients cured of their diabetic symptoms. If he had read it, how could he claim "discovery" for Banting?

In Dr. Banting’s Acceptance Lecture, Sept. 15, 1925 he says:

". . . an address in which certain aspects of the work on insulin may be placed before you".

We note the use of "may", which denotes "permission". We ask what restrictions were placed upon Dr. Banting so that he does not tell the whole story? Who placed those restrictions?

We ask why the name of E. L. Scott is placed among those who failed?

If E. L. Scott failed we ask why the Scott Method was patented and sworn to as original by Banting, Best and Collip, Patent 1,469,994, January 1923?

This Nobel Lecture, 1925 by Banting is more interesting for what it leaves out than for what it states.

We have seen how the hypothesis that the hormone controlling diabetes is a protein was evolved in 1909-1911, how an extract based on this idea in 1911 reduced the D/N ratio, reduced the glycosuria and gave a "brighter" look to diabetic dogs, how the ‘thesis-T-10553 1911, Univ. of Chicago was rewritten by another hand, deadening its impact when published, how the long effort to gain academic and Financial backing failed, how in 1921-1922 Banting and Best verified Scott’s claims in his as yet unpublished Thesis, how the hypothesis was given by Scott in open meeting in New Haven, December 1921, Banting and Macleod attending, how the Scott method was patented and claimed as original by Banting, Best and Collip in 1923, we now find the hypothesis certified in the 1923 Nobel Prize for the "discovery of insulin" though assigned to the wrong persons for the wrong reasons.

For this only we may be grateful:
"THE IDEA TRIUMPHED"

 

OATH OF HIPPOCRATES

460-370 B.C.

This stalwart of the millennia reveals the highest ethical intent. Its use as a shield for wrong doing should not be tolerated.

Most persons place confidence in their physicians above all men. Is there a man who escapee the doctor? The physician’s Creed, the Oath of Hippocrates is everyone’s concern. We are its dupe or its beneficiary.

The highest ethical ideals are here. We find, too, the basis for the "Conspiracy of Silence" whereby no physician testifies against another.

None may choose one portion to obey, another to ignore. Any infraction invalidates the whole. The Oath then becomes impertinent to current values, a document solely of historical importance.

High fidelity of student to teacher is the first priority in this OATH.

Professor Ernest Lyman Scott was a teacher in a medical school from 1909 in Chicago, in Kansas 1911, in Columbia from 1912 to his retirement in 1942. Some of his research students did well. His honor is obligatory upon those who recognize the requirements of the Oath and swear loyalty to it. The medical associations over the world owe a debt that is long overdue to this great mind, that of Ernest Lyman Scott, 1877-1966.

THE OATH OF HIPPOCRATES

 

I SWEAR BY APOLLO THE PHYSICIAN

AND AESCULAPIUS AND HEALTH AND ALL-HEAL AND ALL THE GODS AND GODDESSES THAT ACCORDING TO MY ABILITY AND JUDGMENT I WILL KEEP THIS OATH AND THIS STIPULATION—

TO RECKON HIM WHO TAUGHT ME THIS ART EQUALLY DEARTO ME AS MY PARENTS TO SHARE MY SUBSTANCE WITH HIM & RELIEVE HIS NECESSITIES IF REQUIRED TO LOOK UPON HIS OFFSPRING IN

THE SAME FOOTING AS MY OWN BROTHERS AND TO TEACH THEM THIS ART IF THEY SHALL WISH TO LEARN IT WITHOUT FEE OR STIPULATION AND THAT BY PRECEPT LECTURE & EVERY OTHER MODE OF INSTRUCTION I WILL IMPART A KNOWLEDGE OF THE ART TO MY OWN SONS AND THOSE OF MY TEACHERS AND TO DISCIPLES BOUND BYA STIPULATION AND OATH ACCORDING TO THE LAW OF MEDICINE~BUT TO NONE OTHERS. WILL FOLLOW THAT SYSTEM OF REGIMEN WHICH ACCORDING TO MY ABILITY AND JUDGMENT I CONSIDER FORTHE BENEFIT OF MY PATIENTS AND ABSTAIN FROM WHATEVER IS DELETERIOUS AND MISCHIEVOUS • I WILL GIVE NO DEADLY MEDICINE TO ANYONE IF ASKED NOR SUGGEST ANY SUCH COUNSEL AND IN LIKE MANNER I WILL NOT GIVE TO A WOMAN A PESSARY TO PRODUCE ABORTION • WITH PURITY & WITH HOLINESS I WILL PASS MY LIFE & PRACTICE MY ART • WILL NOT CUT PERSONS LABORING UNDER THE STONE’BUT WILL LEAVE THIS TO BE DONE BY MEN WHO ARE PRACTITIONERS OF THIS WORK. INTO WHATEVER HOUSES I ENTER I WILL GO INTO THEM FOR THE BENEFIT OF THE SICK AND WILL ABSTAIN FROM EVERY VOLUNTARY ACT OF MISCHIEF & CORRUPTION AND FURTHER FROM THE SEDUCTION OF FEMALES OR MALES OF FREEMEN AND SLAVES .WHATEVER IN CONNECTION WITH MY PROFESSIONAL PRACTICE OR NOT IN CONNECTION WITH IT I SEE OR HEAR IN THE LIFE OF MEN WHICH OUGHT NOT TO BE SPOKEN OF ABROAD I WILL NOT DIVULGE AS RECKONING THAT ALL SUCH SHOULD BE KEPT SECRET •WHILE I CONTINUE TO KEEP THIS OATH UNVIOLATED MAY IT BE GRANTED TO ME TO ENJOY LIFE ANDTHE PRACTICE OF THE ART RESPECTED BY ALL MEN IN ALL TIMES BUT SHOULD I TRESPASS AND VIOLATE THIS OATH MAY THE REVERSE BE MY LOT

I, the author, request appropriate recognition of Ernest Lyman Scott for the first extraction of insulin from adult pancreas ("discovery") on the supposition that the hormone insulin is a protein.

Insulin was one of the first hormones to be isolated. Its chemical structure as a protein was a revolutionary idea and accounts for the enormous recognition accorded its isolation and synthesis.

Insulin, in spite of its harsh history finally got into use. It has by no means solved all the problems of diabetes. According to its discoverer it may well have multiplied them. Nature was in the way of eliminating the disease by destroying its victims young before reproducing the hereditary malady in another victim.

Penalty of advance is a new vista with new problems. "Diabetes is a disease that won’t go away." No new Scott has appeared on the scene. What can we expect when we kill our best!

To present the truth is the objective of this study of the behavior of men in an important medical advance as I was cognizant of it. It may throw light upon the quality of genius.

THE WHISPER

He sits at home, two weeks of life remaining. His head rests against the chair back. His strength is spent. He smiles — a rare, soft, tender smile. A whisper, he is so weak. This is Ernest Scott in 1966, January.

"I thought it was a protein and that is what it turned out to be".

This is the enduring moment in the history of insulin.

Perhaps the poet only may view such a spirit. Kipling placed it when he wrote in one of his better moments:

"They come in and occupy but His whisper came to me"

The Explorers

 

INSULIN CHEMISTRY

(The Hormones, Clark T. Sawin, M.D.)

Chemistry

Animal insulin was crystallized in 1924 by Kimball and Murlin and in 1926 by Abel. Sanger in 1955 reported its amino acid sequence and primary molecular structure. In 1963 it was synthesized by Katsoyannis in Pittsburgh. In 1965 Chinese workers in Shanghai and Peking made synthetic, characteristic crystals. In 1965 Zahn in Germany, and in 1966 Katsoyannis at Brookhaven, reported the synthesis of human insulin, the first synthesis of a human protein. This synthesis is complex and difficult so that very little synthetic insulin is available.

Insulin consists of two peptide chains, the A chain and the B chain. The A chain has 21 amino acids, is acidic, and has an N-terminal glycine. The B chain has 30 amino acids, is basic and has an N-terminal phenylalanine. The chains are connected by two disulfide bridges.

The molecular weight is about 6000 and varies from species to species.

 15a.jpg (14249 bytes)

 

UNCONQUERED. Pen drawing made in 1927 by Ernest L. Scott from a photograph of a white pine near Boalsburg, Pa.

After the mishandling in Chicago. of his great work his life developed on three lines.

In education he published many scientific papers and he guided graduate students to higher degrees and distinguished careers.

In photography he did exhibition work. His collection of 178 negatives and over 50 prints of the building of the George Washington Bridge 1929-1931 belongs to the New York Historical Society.

In horticulture he made a second career. Twenty-four years of retirement, 1942-1966, resulted in the founding of the National Chrysanthemum Society, Inc., U.S.A. of which he was the first president. This society has 50 chapters and a general membership. He made himself famous growing chrysanthemums. His book, "Chrysanthmums For Pleasure," out of print, is a classic. He created his own Art form in 50 or more geometrics.

He died on January 19, 1966 of a massive coronary attack.

Ernest Lyman Scott will be remembered. He embellished life.

THE END

16a.jpg (29031 bytes)