VII. Resurrections in Toronto

There was no time to bask in their glory. Even as kudos for the achievement began to roll in — along with innumerable requests from diabetics and their physicians for access to insulin — the Toronto team found itself in a dreadful predicament. It could not make insulin!

Photograph of lab equipment ca. 1923<br />
Photograph of lab equipment ca. 1923

When Collip made his breakthrough in January, the group decided to develop it under the auspices of the University of Toronto's Connaught Anti-Toxin Laboratories, a small vaccine production facility created a few years earlier by a dynamic professor of hygiene, J.G. Fitzgerald. Collip was placed in charge of insulin manufacture and special equipment was installed.

But when he tried to make large batches of insulin Collip found they had no potency. And when he reverted to his original methods in his own lab, they did not work either. Everyone pitched in to try to rediscover the route to insulin, but it remained maddeningly elusive. From about the beginning of March, 1922 to mid-May, Toronto suffered a horrible insulin “famine”. It led to the death of one patient, who could not carry on when the supply gave out (others, such as Leonard Thompson, were able to survive by reverting to their diets), and to a fundamental change of course in insulin production.

Photographs of insulin stills ca. 1923<br />

Photographs of insulin stills ca. 1923.

The group did, finally, regain the knack of making a few ccs. of potent insulin (the problem, as so often in early biochemical extractions, was to control all the variables in the procedures and the primitive apparatus; the scientists were like a chef trying to recreate a delicate and complex recipe in a frying pan on a wood stove). But they now saw the importance of taking legal steps to protect their priority in insulin development and the necessity of getting help.

It was decided to take out Canadian and American patents on the processes of isolating the internal secretion. These eventually were issued in the names of Banting, Best, and Collip. The three patentees then formally transferred their rights to the Board of Governors of the University of Toronto, which would license manufacturers through a special Insulin Committee. Royalties from insulin sales would support further research.

As well, because of the production problem, the Toronto group decided to enter into a special relationship with Eli Lilly and Company of Indianapolis, whose research director, Clowes, had kept urging collaboration. At the end of May, 1922, Lilly and Toronto agreed to work together on insulin, pooling all their knowledge. In return for contributing its resources to the work, Lilly would receive an exclusive headstart in the big U.S. market (Connaught would handle Canada; the Medical Research Council in Great Britain would undertake development there; other manufacturers would be licensed in due course). His temporary appointment in Toronto having expired, Collip returned to the University of Alberta.

Most of the tiny batches of insulin that could be produced towards the end of May went to a single patient in the United States. The physician to a dying young man in Rochester, New York, named James Havens, had pleaded so eloquently with the Toronto team that they agreed to give Havens priority. Havens got his first injection of Toronto insulin on the evening of May 21, 1922, making him the first person treated with it in the United States. After two weeks of treatment Havens was able to get out of bed and walk.

Photograph of James Havens ca. 1921

James Havens, ca. 1921, first American diabetic to receive insulin. 

A small handful of other starved children received insulin in Toronto in the late spring and summer of 1922. Eli Lilly, which had poured resources into the production problem, was able to begin shipping potent insulin to Toronto by early July, after which there was a gradual easing of the situation. In early August a select group of leading American clinicians began administering Lilly "Illetin" to a handful of their neediest cases.

"Diabetics swarm from all over," Banting wrote Best that July, "and think we can conjure the extract from the ground."

The doctors chose to treat the most seriously ill. When Banting told the physician-uncle of five-year-old Theodore Ryder to bring the boy to Toronto in September, the reply was, “He won’t be alive in September.” So Ted Ryder, a 26-pound human skeleton, received his first injection in Toronto on July 10.

On that same day Banting wrote to the wife of the United States Secretary of State, Mrs. Charles Evans Hughes, denying her request for treatment of her daughter, Elizabeth. Elizabeth Hughes was fourteen years old: under the care of Dr. Frederick Allen she had been slowly starving since the onset of her diabetes in 1919. Now she was close to death from starvation.

Photograph of Elizabeth Hughes ca. 1923

Photograph of Elizabeth Hughes, ca. 1923.

By August the insulin shortage had eased enough - and perhaps there had been further pleading from Allen and the family - that Banting was able to change his mind and accept Elizabeth Hughes for treatment. He examined the little girl in Toronto on August 16, three days before her 15th birthday:

wt 45 lbs. height 5 ft. patient extremely emaciated, slight aedema of ankles, skin dry & scaly, hair brittle & thin, abdomen prommt. shoulders drooped, muscles extremely wasted, subcutaneous tissues almost completely absorbed. She was scarcely able to walk on account of weakness...

Elizabeth became the prize patient, not only because of her family’s prominence, but also because she had sunk so low and responded so beautifully to insulin injections. Her complete patient record has survived. She was also an engaging, delightful girl, who poured out her experiences in a series of letters to her mother that are a wonderful window on a glorious time in the history of medicine.

I declare you'd think it was a fairy tale ... I look entirely different everybody says ... gaining every hour it seems to me in strength and weight... it is truly miraculous....Dr. Banting considers my progress simply miraculous, none of his other patients coming near me in diet etc., and so I consider myself especially lucky. He brings all these emminent Doctors in from all over the world who come to Toronto to see for themselves the workings ofthis wonderful discovery, and I wish you could see the expression on their faces as they read my charts, they are so astounded in my unheard of progress ....

Imagine, I have to take 5cc. at a time. Isn't that awful? But it seems they have had no extractfor the lastfew days and I suppose we were lucky to have even that poor stuff. We only have a two cc. syringe you know and so Blanche fills that and gives it to me and then unscrews it from the needle which is left sticking in to me (I feel like a pincushion) fills it again, and gives me that (am left a pincushion once more), and then have the fifth cc. It really is quite a process, and altogether takes about twenty minutes for the whole performance. My hip feels as if it would burst too, but it doesnt although my whole leg is numb until I walk on it a bit, then it recovers rapidly, and within an hour I would hardly know anything had been given

I want if you can possibly find them, the links that were taken out of my little silver watch and my gold bracelet Mrs. Crazier gave me. My arm is fattening out so much you will be glad to hear that my watch is really becoming quite uncomfortable, so I need another link put in and I saved them for this special immergency, although I must say I didn’t ever expect it to come.

The stories of the awe-inspiring impact of insulin were beginning to multiply beautifully by the autumn of 1922, first in Toronto, then rippling across North America and ultimately around the world. Banting discovered that insulin would make possible amputations on otherwise-doomed diabetic patients. Eleven-year-old Elsie Needham was brought out of diabetic coma at the Hospital for Sick Children — it seemed like bringing a person back from the dead. Jim Havens’s doctor, J.R. Williams, wrote “The restoration of this patient to his present state of health is an achievement difficult to record in temperate language. Certainly few recoveries from impending death more dramatic than this have ever been witnessed by a physician.” Rawle Geyelin in New York and Ralph Major in Kansas City took the “before and after” pictures that still imprint the impact of insulin in our memory.

And it was Elliott Joslin of Boston, a gentle doctor close to his Puritan heritage, who best summed up the spiritual dimension of the discovery of insulin:

By Christmas of 1922 I had witnessed so many near resurrections that I realized I was seeing enacted before my very eyes Ezekiel’s vision of the valley of dry bones:

... and behold, there were very many in the open valley; and, lo, they were very dry.

And he said unto me, Son of Man, can these bones live?

And... lo, the sinews and the flesh came upon them and the skin covered them above: but there was no breath in them.

Then said he unto me, Prophesy unto the wind, prophesy, Son of Man, and say to the wind. Thus saith the Lord God: 'Comefrom the four winds, O breath, and breathe upon these slain, that they may live.'

So I prophesied as he commanded me, and the breath came into them, and they lived, and stood up upon their feet, an exceeding great army.

By the end of 1922 the discovery in Indianapolis and St. Louis of the importance of adjusting the iso-electric point in insulin manufacture had ended the production problem. By the end of 1923 insulin was available across North America and in many parts of Europe as a maintenance therapy for cases of severe diabetes.

VII. Resurrections in Toronto