The 2021-22 period marks the 100th anniversary of the discovery of insulin at the University of Toronto. In October 2021, the University of Toronto Press will release a revised centenary edition of historian Michael Bliss’ book on the subject, The Discovery of Insulin.[1] The centenary coincides with the Covid-19 crisis, and there has been a related discussion of how the privatization of Connaught Laboratories in Toronto led to Canada being unable to produce vaccines as well as to it being unable to provide the world with inexpensive insulin.

Many unsung heroes were involved in the research that led to the discovery of insulin and in the work that led to mass production of it afterwards, but essentially four people went down in history as the principal actors: Frederick Banting, a practicing physician in London, Ontario who persuaded U of T professor JJR Macleod to provide research space, experimental dogs and a graduate student assistant, Charles Best. The fourth was JB Collip, a visiting professor of biochemistry who joined when his expertise was needed.

There is a mythical story about Banting’s team moving through a ward of dying diabetic children, injecting them one by one with insulin and resurrecting all of them simultaneously with the newly discovered life-saving elixir. Michael Bliss, an expert on this history, discounts this story as a mythical exaggeration. It didn’t happen that way, and it couldn’t have happened that way because the discoverers were keenly aware of the shortage of supply and problems that still had to be worked out in the purification process. The first patients to receive their first product had allergic reactions, so that was another reason to proceed carefully one patient at a time. They were in the horrible position of having a very effective treatment (not a cure) but not having enough of it for every person in the world who needed it. Families could read about the discovery in the newspapers, but they couldn’t obtain insulin. For this reason, the research team was not eager to get too much publicity or have a large group of patients who couldn’t get continuous treatment.

During 1922, insulin was given to only a few patients, two of whom were children of wealthy or politically connected Americans who wrote insistent letters to the team in Toronto. One was the son of the vice-president of Eastman Kodak. The other was the daughter of the then US Secretary of State and future Supreme Court Chief Justice, Charles Evans Hughes.[2] In the research I did for this article I found no critical comments about this preferential treatment or questions about why these patients were chosen for treatment.

Perhaps the most famous aspect of this story is the fact that Banting, Best and Collip filed the patent for the discovery then sold it to the University of Toronto for one dollar each. They had to register a patent to ensure that no one would manufacture a product that didn’t conform to the necessary standards, but they said insulin belonged to the world and they did not want to profit from it. A legend passed down in my family told us that one day in 1922, Dr. Banting walked into my great-grandfather’s Toronto law firm and asked for help in registering this patent from which he didn’t want to profit. My great-grandfather was impressed by his altruism and agreed to do the work pro-bono. Connaught Laboratories, affiliated with the University of Toronto, led mass production for Canada, and the pharmaceutical company Eli-Lilly of Chicago was given a one-year exclusive license to develop a way to mass produce safe and pure insulin. After that, other makers had the right to produce insulin with no royalties owed.

https://suiter.com/patent-history-insulin/

The corporate ethics of Eli-Lilly in the 1920s tell much about the disappearance of such a thing as corporate ethics in recent decades. An editorial in the Toronto Star described the privatization of Connaught Laboratories and the greed and profiteering that occurred as pharmaceutical companies patented synthetic insulin and eliminated inexpensive animal-derived insulin from the market:

But starting in the 1980s, multinational drug companies Eli Lilly, Novo Nordisk and later Sanofi got around patent restrictions by producing a genetically engineered form of insulin. The new insulin turned out to be much more expensive and posed serious risks—including even death—for some users… Even so, the three companies soon phased out the old, animal-based insulin they’d long been producing under Connaught guidelines. They also drove small producers of the old insulin out of business and took over 95 per cent of the world market with the new insulin. Connaught would have protected Canadians from these disastrous changes—except that [in the 1980s] the Mulroney government privatized Connaught, ending its central role in the Canadian and global insulin market. Today, the high cost of insulin means that roughly half the people in the world who need it can’t get it—a much lower rate of accessibility than when Connaught was keeping world prices down.[3]  

The 1923 Nobel Prize was awarded to only two people, as per Nobel rules. It went to Banting and Macleod, leaving Best and Collip out. Within days Banting announced he would share his prize money with Best and Macleod announced he would share his with Collip. The Nobel committee found that Banting took the initiative and led the research, while Macleod, as the only faculty member on the team, was instrumental in harnessing the university’s resources toward the effort. In an article that covers his book, Michael Bliss wrote in 1984:

The discovery of insulin at the University of Toronto in 1921-22 was a sensational event in the history of medicine because this hormone immediately proved to be a dramatically effective therapy for diabetes. In fact it was one of the first “miracle” treatments discovered by modern medical research. The discovery itself was also a highly controversial event, one which was obscured for many decades in a fog of myth and speculation about what really happened during the Toronto research, about the relationship of Toronto’s work to that of other researchers, and about the various causal elements making possible such a momentous discovery in a university and a country which as yet had little distinction in the world of medical research. [4]

Bliss here refers to the fact that researchers in other countries had made important contributions leading up to the breakthrough in Toronto. It was known that there was a hormone secreted in the pancreas which regulated blood sugar. The obstacle was extraction and purification, and since that was the decisive factor, it was Collip, the biochemist, who probably should have received major credit. This controversy, however, was not reported because as Bliss points out, Ernest Hemingway, the journalist assigned to the story, was uninterested and hated Toronto. He was eager to leave and follow the path that would eventually lead him to his own Nobel Prize.

Bliss’ history also reveals that Canadian history is not just a boring tale of kind, polite and altruistic heroes. In the end, the four men who discovered insulin put their mutual hostilities aside and presented a good face for the public and for the historical record. They shared their Nobel money and gave away the patent, but behind the scenes there was plenty of tension. At one point, Banting asked Collip to teach him how to purify the pancreatic extract, and when Collip refused, there was a physical altercation that had to be broken up by Best. Banting and Best were younger than Macleod and Collip, and also of lower professional status. Collip had the essential technical skills, and Macleod was a more experienced communicator among scientists who also had the power to make things happen at the university. Banting and Best were dependent on them and fearful of being sidelined. They didn’t have to worry, though, because they both ended up as national heroes with professorships at University of Toronto. Banting was awarded a generous annuity by the province of Ontario.

Tension was also caused by the fact that there were researchers in other countries who had made key discoveries along the way. The altruism of the patent application had the added benefit of stopping competing claims. Who would dare to challenge patent-holders who had forfeited their rights to profit from a life-saving treatment of such enormous consequence?

Bliss mentions at the end of the article that the discovery of insulin had its detractors:

At every step in the honoring of the work, the organized antivivisectionists presented their objections to this cruel research, and their doubts that insulin would ever amount to anything. They were properly ignored, in part because of all the walking, breathing human beings who from the beginning were living proof that the dogs had been sacrificed.

This tells us that little has changed in a century about the way the public reacts to medical discoveries. The interesting question is who would be, in the time of Covid-19 anxiety, equated with the fools who could not admit the worth of a discovery that saved millions of lives. Do you equate them with the people who have some reservations about mRNA biotechnology or the wisdom of vaccine passports? Or are they like those who slander and suppress the doctors who claim to have discovered inexpensive off-patent treatments for Covid-19?

Consider what Dr. Banting’s team did in Toronto. They made their treatment decisions on their own, free of any interference from non-existent ethics review boards or government regulators. If insulin were discovered today, would people dismiss the discovery because it was “just an observational study” with no large, randomized clinical trials? Detractors might try to associate the treatment with unclean animals. There might be coordinated media attacks on the “cow pancreas juice” responsible for the so-called “miracle of resurrection” in Toronto. After all, maybe those children waking up from diabetic comas were just undergoing a placebo effect. Perhaps Dr. Banting had selected only the healthiest patients, or he had been making sure they followed their ketogenic diets strictly. There are always ways to find fault, call for delays and further studies, and make sure studies have a methodology that will yield the desired results. I can imagine the derogatory headlines: “Banting and Best? Banting and Worst: Cow Juice Treatment Promoters Torment the Desperate with False Hope” or “Oklahoma Diabetics Overwhelm ICUs After Injecting Homemade Pig Pancreas Paste.” (If you don’t know what this refers to, watch here.)

But of course there would have to be a motive for such a smear campaign; that is, it would be used only if pharmaceutical companies had competing patentable treatments and vaccines they wanted to bring to market soon. That motive wasn’t there in 1922, but it was in later decades as pharmaceutical companies patented their synthetic versions of insulin. They couldn’t use a smear campaign because the effectiveness of insulin was beyond doubt, but their actions slowly eliminated access to affordable insulin. A century after society figured out a way to produce insulin cheaply and in abundance, diabetics are dying in the richest nation on earth simply because it is too expensive for them to buy.

But hey, go ahead. “Trust the science” © that is being run by the pharmaceutical industry through the WHO, government agencies and media corporations. They always have our best interests at heart…

According to the American Diabetes Association between 2003 and 2012 the price of insulin in the USA tripled. This has made this life-saving medication difficult and sometimes impossible to afford for those with Type 1 diabetes, not to mention the cost of other equipment and devices to monitor blood sugar levels and administer insulin. Even in Canada, insurance does not always cover the total cost of insulin and many people have to pay out of pocket. This greatly effects people with diabetes who are of low-income. A Diabetes Canada research study that began in 2002 reported that, “57% of Canadians with diabetes say they do not comply with their prescribed therapy because they cannot afford their medications, devices and supplies, thus potentially compromising their diabetes management.” I think looking back on the history and Banting’s sentiment that insulin belongs to the world instead of any individual should inspire discussions surrounding these issues.”[5]

Notes


[1]. Michael Bliss, The Discovery of Insulin: Special Centenary Edition (University of Toronto Press, 2021, first edition by McClelland & Stewart, 1982).

[2]. “The Discovery and Early Development of Insulin—from a Patient’s Point of View,” The Insulin Collections, University of Toronto.

[3]. Linda McQuaig, “Banting and Best would be horrified by the fate of their insulin discovery,” Toronto Star, July 28, 2021.

[4]. Michael Bliss, “Resurrections in Toronto: Fact and Myth in the Discovery of Insulin,” Bulletin of the American Academy of Arts and Sciences 38, no. 3 (December 1984): 15-36.

[5]. Rachel Delle Palme, “Insulin Patent Sold for $1,” Banting House, December 14, 2018.