The unknown story of egos and rivalry behind the discovery of insulin 100 years ago

Behind one of the most important discoveries in medicine, there were several feuding scientists who fought for the credit of the discovery of insulin.

When Frederick Banting's phone rang one morning in October 1923, it was the call many scientists dream of receiving.

On the other end of the line, an excited friend asked Banting if he had seen the morning papers.

When Banting said no, his friend broke the news: Banting had just received the Nobel Prize for his discovery of insulin.

Banting told his friend to "go to hell" and hung up the phone.

He then he went out and bought the morning paper. Sure enough, there, in the headlines, he saw in black and white that his worst fears had come true.

It was true that he had received the Nobel, but it had also been given to his boss, John Macleod, professor of physiology at the University of Toronto.

Thus begins a story of monstrous egos, toxic professional rivalries, and injustice. But of course, there is another character in this drama: diabetes itself.

According to a recent report from the World Health Organization, about 9 million people with type 1 diabetes are alive today thanks to insulin.

I am one of them and it was my own shocking diagnosis of this disease, just over ten years ago, that first led me to investigate the discovery of insulin, the drug that I must inject myself several times a day for the rest of my life. my life.

"The evil of piss"

Diabetes derives its name from the ancient Greek word for "flow", a reference to one of its most common symptoms and for which the 17th century English physician Thomas Willis (1625-1675) gave it the much more memorable name of " bad piss".

But frequent trips to the bathroom were the least of a patient's worries.

Before the discovery of insulin, a diagnosis of type 1 diabetes meant certain death.

Unable to metabolize the sugar in the carbohydrates in their diet, patients gradually weakened until, due to the production of toxic compounds known as ketones, they slipped into a coma and died.

Even in the early 20th century, there was little that could be done for patients with this condition, other than put them on a starvation diet that could, at best, delay the inevitable.

It's no wonder then that doctors were surprised by the discovery of a hormone that could return elevated sugars in diabetic patients to healthy levels and even bring them out of a coma.

And since it was produced from tiny islet-like patches of tissue in the pancreas, this substance was given the name "insulin," derived from the Latin for "island."

When the eminent American diabetes physician Elliott Joslin first used insulin to treat his patients in early 1922, he was so amazed by its power that he compared it to the "Vision of Ezekiel," the Old Testament prophet who he says he saw a valley of dry bones rise up, clothe itself with flesh, and come back to life.

Joslin's colleague, Walter Campbell, was similarly impressed, but much less poetic.

He described the crude pancreatic extracts as "thick brown slime."

And while the thick brown mud was saving lives, it soon became clear that it could kill them too.

If injected at the wrong dose, it would cause the patient's blood sugar levels to plummet, causing hypoglycemic shock and the possibility of a fatal coma.

To the newspapers, however, insulin was hailed as a miracle. And the compliments quickly began to flood the discoverer of him.

Banting received a letter from Canadian Prime Minister Mackenzie King granting him a life pension from the Government of Canada; he was invited to open the Canadian Exhibition (an honor reserved for "a distinguished Canadian or British citizen") and was even summoned to an audience at Buckingham Palace with King George V.

Then came the Nobel Prize.

Why so angry?

But why was Banting so furious? As far as he was concerned, having to share the prize with Macleod was not just a farce, it was an insult.

He thought that Macleod had no right to claim the discovery of insulin, as a diary entry of his written in 1940 makes very clear:

Macleod, on the other hand, was never to be trusted. He was the most selfish man I have ever met. He looked for every possible opportunity to progress. If you said anything to Macleod in the morning, it would be published or at a conference on his behalf at night... he was unscrupulous and would steal an idea or credit for the work from any possible source.

And yet, had it not been for Macleod, Banting may never have received the Nobel in the first place and probably would have remained a scrappy family doctor in the province of Ontario.

After his return to Canada from the Western Front as a wounded war hero, Banting found that his career was rapidly going downhill.

He had trained as a doctor and hoped to establish a private medical practice. But such hopes seemed to evaporate quickly, and he found himself cooking his meals with a Bunsen burner, writing recipes for baby food, and couldn't even afford to go to the movies.

Hopes for an alternative career as a landscape painter were quickly dashed when his creative endeavors were met with disdain by a local merchant.

In every direction he looked Banting saw a hostile world.

This also turned out to be the case in his first meeting with Macleod.

Banting had approached him with what he believed to be a novel approach to isolating the long-sought antidiabetic hormone produced by the pancreas that might finally control diabetes.

But instead of being greeted with boundless enthusiasm, Banting recalled that Macleod listened for a while and then began reading some letters at his desk.

It wasn't that Macleod lacked enthusiasm. Rather, he was simply concerned that while Banting had the inspiration for the job, he lacked the specialized surgical skills to pull it off.

However, he gave Banting the benefit of the doubt and arranged for him to start working with Charles Best, an outstanding senior.

Their partnership has since been described as "an historic collaboration", though, as Banting later recalled, it didn't get off to the best of starts.

Because when he found some serious discrepancies in some of Best's initial data, he laid down the rules in no uncertain terms:

I was waiting for him, and seeing him I gave him a severe reprimand. He thought he was God's and Macleod's appointee, but when [I] finished speaking he wasn't sure anymore... We understood each other much better after this meeting.

With these initial problems resolved, Banting and Best toiled in the laboratory throughout the summer of 1921, making pancreatic extracts and testing their effects on blood sugar levels in diabetic dogs.

Banting may have been harsh with Best, but for his lab dogs he had nothing but love and affection:

I will never forget that dog as long as he lives. I've seen patients die and I've never shed a tear. But when that dog died, he wanted to be alone because the tears fell no matter what he did.

With Macleod in Europe for the summer, Banting excitedly wrote to tell him of his latest results. But his answer was a disappointment.

Macleod helpfully pointed out that some of the experimental results were inconsistent and lacked proper controls .

Upon his return at the end of the summer, Macleod informed Banting that the University of Toronto could not accept a list of his demands for more laboratory space and resources.

Banting then stormed out of the room saying "I'll show that little son of a *** that he's not the University of Toronto", and threatening to take his work elsewhere.

By the end of 1921, things had taken a turn for the worse. Macleod felt that it was time for Banting and Best to present their work in public at a formal scientific conference.

But when Banting appeared before the American Professor of Physiology at Yale University that December, the prestige of the audience gave him a nervous breakdown.

His presentation was a disaster. He later he wrote:

When they called me to present our work, I almost froze. I couldn't remember and I couldn't think. Never before had he spoken before such an audience, he was in awe. I didn't present it well.

Desperate to snatch victory from the clutches of defeat, Macleod stepped in, took over, and ended the presentation himself.

For Banting, this was a brazen jab by Macleod to steal credit for discovering insulin.

And to add salt to the wound, he had delivered this blow in front of the most eminent doctors in the field.

This confirmed Banting's growing suspicions that the insulin was getting out of hand, and he desperately needed to reassert his authority over the discovery.

The opportunity to do just that came in January 1922.

When 14-year-old Leonard Thompson's father brought the boy to Toronto General Hospital, he was near death from type 1 diabetes.

Banting described how the boy's illness had left him "undernourished, pale, weighing 60 pounds, hair falling out, smell of acetone on his breath... seemed bored, spoke quite slowly, very willing to lie down all day".

A final-year medical student gave a blunt and grim prognosis: "All of us knew he was doomed."

On the afternoon of January 11, 1922, Thompson was injected with 15 ml of pancreatic extract that had been prepared by Best.

Hopes were high, but the effect was disappointing .

Despite causing a 25% drop in Leonard's blood sugar levels, he continued to produce ketones, a sure sign that the extract had only limited anti-diabetic effect.

But much more serious was the fact that the extract had triggered a toxic reaction that resulted in the eruption of abscesses at the injection site.

Reporting this work in the Journal of the Canadian Medical Association, Banting and Best came to the sad conclusion that "no clinical benefit was evident" from injection of their extract.

Two weeks later, on January 23, Thompson was injected once more. And this time, the result was completely different.

When they published his work, the Toronto team recorded that Thompson "became brighter, more active, looked better, and said he felt stronger."

His blood sugar levels dropped noticeably. But perhaps the most important result of all was that this time there were no toxic side effects.

"I would punch him"

So what had changed in those two weeks?

The answer was that this second batch of extract had not been prepared by Banting and Best but by their colleague James Collip.

Collip was a biochemist by training, and with his experience he had been able to remove enough impurities from the crude pancreatic extract that, when injected, it would not cause a toxic reaction.

Collip's secret to success was alcohol. Banting and Best had used alcohol to cleanse their preparations of impurities, but it was Collip who really figured out the method of making an extract that could be used to successfully treat a patient without adverse reactions.

He had also discovered that while insulin could save lives, it could also kill them .

Because when Collip injected some of his purified preparation into healthy animals, they became convulsive, comatose, and eventually died.

This was because Collip's preparations were now so pure that they were sending the animals into hypoglycemic shock.

This is a danger that all type 1 diabetes patients today are taught to recognize and also, again thanks to Collip's work, to know how to remedy with a little fast-acting sugar.

For Banting, however, Collip's discoveries were not cause for celebration but a new threat.

When Collip was reluctant to divulge the secrets of his success, Banting's temper boiled over:

I grabbed him with one hand by the coat in front of him and almost lifting him, I sat him down hard on the chair. I don't remember everything that was said, but I do remember telling him that he was lucky to be so much smaller, because otherwise, "I'd send him to hell knocked out."

As he sank deeper into a festering state of fear and suspicion, Banting began calming his nerves with alcohol stolen from the lab. "I don't think there was a single night during the month of March 1922 that I went to bed sober," he said.

Two months later, when Macleod made the first formal announcement of the discovery of insulin to the scientific world at a meeting of the American Medical Association in Washington, Banting was not present. He claimed that he could not pay the train ticket.

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But Banting wasn't the only person to be furious at the Nobel committee's decision. There was one more expert he could claim that he discovered insulin, more than 20 years before the Canadians.

The tragedy of Georg Zuelzer

In 1908, the German physician Georg Zuelzer had shown that pancreatic extracts could not only reduce sugars and ketones in the urine of six diabetic patients, but also bring at least one of those patients out of a diabetic coma.

Calling his preparation "Acomatol", Zuelzer was so sure of its efficacy in treating diabetes that he had even filed a patent.

Zuelzer's work stopped with the First World War .

Like Banting and Best, he too had struggled with side effects.

Impurities in the preparation had caused fever, chills, and vomiting in patients, and Zuelzer knew that this would have to be overcome if Acomatol was ever to be used clinically.

But he also knew how to do it, because in his patent he had explained how alcohol could be used to remove these impurities.

By 1914, things looked hopeful. Zuelzer now had the support of the Swiss pharmaceutical company Hoffman La Roche and, best of all, his preparations caused no signs of fever, chills or vomiting.

But then Zuelzer noticed some serious new side effects.

The test animals became convulsive and sometimes fell into a coma. And before Zuelzer had a chance to find out what was going on, disaster struck.

With the outbreak of World War I in the summer of 1914, Zuelzer's research on insulin came to an abrupt halt and he never recovered.

Then, almost a decade later, came the news that the Nobel Prize had gone to Banting and Macleod. This was a severe blow, and it was quickly followed by another.

Only now did Zuelzer realize that the side effects of seizures and coma were not due to impurities, but rather to symptoms of hypoglycemic shock arising from an insulin preparation that was so pure that it was causing catastrophic collapse in the blood sugar levels.

Not surprisingly, historians Paula Drügemöller and Leo Norpoth have compared Zuelzer to a character in a Greek tragedy.

He had a potent insulin preparation in his hands, only to have it taken from him by circumstances beyond his control.

"That motherfucker Best"

The tragedy of Georg Zuelzer

In 1908, the German physician Georg Zuelzer had shown that pancreatic extracts could not only reduce sugars and ketones in the urine of six diabetic patients, but also bring at least one of those patients out of a diabetic coma.

Calling his preparation "Acomatol", Zuelzer was so sure of its efficacy in treating diabetes that he had even filed a patent.

Zuelzer's work stopped with the First World War .

Like Banting and Best, he too had struggled with side effects.

Impurities in the preparation had caused fever, chills, and vomiting in patients, and Zuelzer knew that this would have to be overcome if Acomatol was ever to be used clinically.

But he also knew how to do it, because in his patent he had explained how alcohol could be used to remove these impurities.

By 1914, things looked hopeful. Zuelzer now had the support of the Swiss pharmaceutical company Hoffman La Roche and, best of all, his preparations caused no signs of fever, chills or vomiting.

But then Zuelzer noticed some serious new side effects.

The test animals became convulsive and sometimes fell into a coma. And before Zuelzer had a chance to find out what was going on, disaster struck.

With the outbreak of World War I in the summer of 1914, Zuelzer's research on insulin came to an abrupt halt and he never recovered.

Then, almost a decade later, came the news that the Nobel Prize had gone to Banting and Macleod. This was a severe blow, and it was quickly followed by another.

Only now did Zuelzer realize that the side effects of seizures and coma were not due to impurities, but rather to symptoms of hypoglycemic shock arising from an insulin preparation that was so pure that it was causing catastrophic collapse in the blood sugar levels.

Not surprisingly, historians Paula Drügemöller and Leo Norpoth have compared Zuelzer to a character in a Greek tragedy.

He had a potent insulin preparation in his hands, only to have it taken from him by circumstances beyond his control.

"That motherfucker Best"

So why don't we remember Zuelzer? According to the late historian Michael Bliss, the answer has a lot to do with Charles Best, who, like Zuelzer, resented the award given to Banting and Macleod.

When Banting first heard that he had received the Nobel, he sent a telegram to Best, who was in Boston at the time, saying: "The Nobel trustees have awarded the prize to Macleod and me. You are with me on my side always." ".

True to his word, he publicly announced that he would share half of his C$20,000 prize with Best.

But if Banting hoped that this would offer Best some consolation for not having shared the prize, he was wrong.

Best's resentment at being overlooked began to irritate Banting.

In 1941, shortly before boarding a flight on a secret wartime mission to the UK, Banting made it clear that his earlier generosity to Best was long gone:

This mission is risky. If I don't come back and they give my [faculty] chair to that motherfucker Best, I'll never rest in my grave.

His words turned out to be tragically prophetic. Shortly after takeoff, Banting's plane crashed and he was killed.

As Macleod had died in 1935, Best and Collip were the only remaining members of the original Toronto research team that had discovered insulin.

And Best was determined that his name be remembered. But to assert his claim to the discovery of insulin, Best needed to clarify exactly when it happened.

Had it been during the summer of 1921 that, working alone, he and Banting had isolated pancreatic extracts that could lower blood sugar levels in a diabetic dog?

Or had it been in January 1922, when Leonard Thompson had first been successfully treated?

If it was the latter, then Best had to somehow deal with the inconvenient fact that it had been Collip's preparation, not his, that had actually been used to successfully treat Leonard Thompson.

As Best's star began to rise in American medical circles, he gave many speeches in which, if he mentioned Collip's contribution, it was downplayed or used only to highlight the crucial role Best had played in the recovery of the disease. insulin production after Collip had temporarily lost the secret of his purification.

Best insisted that the turning point in the history of insulin had been when Leonard Thompson was injected for the first time on January 11, 1922, with an extract made by himself and Banting.

The fact that the actual moment of therapeutic success was two weeks later, when the child had been treated with Collip's preparation, was conveniently downplayed.

At the same time, Best also claimed that the crucial innovation of using alcohol to remove toxic impurities had been largely his own.

He would later go further by insisting that insulin had been discovered during the summer of 1921 when he and Banting had been working alone, testing its extracts on diabetic dogs, long before Collip arrived in Toronto.

Meanwhile, Collip's response was largely one of stoic silence.

convincing the world

Best seemed to have finally secured his place in medical history.

At least that's how it seemed until the late 1960s, when he received a letter that dealt another blow to the hornet's nest.

It revealed that during the summer of 1921, just as Banting and Best were embarking on their own investigation, a Romanian scientist named Nicolai Paulescu had already published similar experiments in a European scientific journal.

But Paulescu's scientific work has since been overshadowed by the ugly exposure of his anti-Semitic politics and the role he played in inciting the Holocaust in Romania.

When Best was asked if researchers like Paulescu, Zuelzer, and a handful of others, like Rockefeller scientist Israel Kleiner, deserved any credit for the discovery of insulin, his response spoke volumes:

None of them convinced the world of what they had... This is the most important thing in any discovery. You have to convince the scientific world. And we did.

Michael Bliss, who has written extensively on the work of Banting and Best, has spoken of how Best seems to have been "deeply insecure and obsessed with his role in the story".

He notes, "The clumsy attempts to manipulate the historical record would have been pathetic and hardly worthy of comment had they not been so grossly unfair to Best's former associates and, for a time, so influential."

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convincing the world

Best seemed to have finally secured his place in medical history.

At least that's how it seemed until the late 1960s, when he received a letter that dealt another blow to the hornet's nest.

It revealed that during the summer of 1921, just as Banting and Best were embarking on their own investigation, a Romanian scientist named Nicolai Paulescu had already published similar experiments in a European scientific journal.

But Paulescu's scientific work has since been overshadowed by the ugly exposure of his anti-Semitic politics and the role he played in inciting the Holocaust in Romania.

When Best was asked if researchers like Paulescu, Zuelzer, and a handful of others, like Rockefeller scientist Israel Kleiner, deserved any credit for the discovery of insulin, his response spoke volumes:

None of them convinced the world of what they had... This is the most important thing in any discovery. You have to convince the scientific world. And we did.

Michael Bliss, who has written extensively on the work of Banting and Best, has spoken of how Best seems to have been "deeply insecure and obsessed with his role in the story".

He notes, "The clumsy attempts to manipulate the historical record would have been pathetic and hardly worthy of comment had they not been so grossly unfair to Best's former associates and, for a time, so influential."

wall street gold

Whatever judgments we may make of Best, there is no denying that he had grasped a crucial insight into an important way science was changing.

Doing experiments in the lab was only half the story: scientists also had to persuade the rest of the world of the value of those experiments.

And at the time of his death in 1978, this was a lesson scientists were taking to heart.

That September, a team of scientists from City of Hope Hospital in Southern California and the biotech startup Genentech in San Francisco held a press conference to announce that they had done something incredible.

Since the days of Banting and Best, patients with type 1 diabetes had to treat themselves by injecting insulin recovered from the tissues of cows or pigs as a byproduct of the meat industry.

Now, thanks to the Genentech/City of Hope collaboration, they could, for the first time, inject human insulin.

This achievement was a decisive victory in helping to win the hearts and minds of the media and the public that were fearful of the new technology. And Wall Street loved it too.

When the bell rang to open trading on the stock market on the morning of October 14, 1980, brokers went into a frenzy to buy shares of the newly launched Genentech.

This made its founders, venture capitalist Bob Swanson and scientist Herb Boyer, billionaires .

But diabetes remained an incurable chronic disease.

Even as he compared his power to "Ezekiel's Vision," Elliott Joslin was also offering a stern warning: "Insulin is a remedy, which is primarily for the wise and not for the foolish."

Joslin's point was that insulin could only be effective if its use was accompanied by discipline, thought, and responsible behavior on the part of the patient.

This lesson applies in other situations as well, but it may very well be one that we don't always want to hear.

Speaking at the recent COP26 summit in Glasgow, the UK government's chief science adviser, Patrick Vallance, said that we cannot expect technology alone to solve all the problems we face .

The truth is, as much as we want technology solutions to do all the heavy lifting, they can only be effective when accompanied by changes in our behavior.

This is as true for managing diabetes with insulin as it is for meeting the challenges of a pandemic through vaccines, masks, and social distancing, or climate change through carbon sequestration, electric cars, and turning off the lights when we leave home. the room.

And so, as we face the challenges of the future, the insulin story holds important lessons for all of us.

* Kersten Hall is an author and Honorary Fellow of the School of Philosophy, Religion and History of Science at the University of Leeds. This article originally appeared on The Conversation. You can read the English version here .

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