July 28, 2025

I tried a couple of things differently this week, hopefully cleared up the issue for readers who were unable to read this in weeks past. Please let me know if you still have trouble!

— Frederick Banting

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The modern weight-loss revolution

Go back a bit more than 100 years ago and a diagnosis of diabetes was essentially a slow death sentence.

The disease struck mostly children and young adults, and without treatment, their bodies wasted away. The only option doctors had was a starvation diet: just enough food to delay the end.

There was no cure, and no real hope. Until one summer in Toronto, when some unlikely scientists decided to try something that more experienced researchers had already dismissed.

Frederick Banting was a surgeon without any real lab training. Charles Best was a 22-year-old medical student. But Banting had a theory: he believed there was a substance produced in the pancreas—something not yet isolated—that could control blood sugar. If they could extract it, maybe they could treat diabetes.

They convinced a respected professor, J.J.R. Macleod, to lend them a small lab and an assistant for the summer. Best volunteered for the job, and together they began performing surgery on dogs, removing parts of the pancreas and injecting extracts to see what would happen.

What happened would change medical history.

One dog, named Marjorie, was diabetic. After they injected her with a pancreatic extract, her blood sugar dropped. She perked up. She lived.

They weren't exactly sure what they had, but it worked. They refined the process with the help of a chemist named James Collip, and in January 1922, they tried it on a human patient—14-year-old Leonard Thompson, who was wasting away in a Toronto hospital.

The first injection wasn't pure enough and caused an allergic reaction. But the second dose worked. Leonard's blood sugar fell, he gained energy, and his condition improved. It was a moment no one who witnessed it would forget.

Soon, more patients came. Word spread. Parents brought their children to Toronto hoping for a miracle—and for many, they got one.

What made the story even more remarkable was that after Macleaod, Banting and Best patented insulin, but then sold the patent to the University of Toronto for one dollar each.

As Banting put it, "Insulin does not belong to me, it belongs to the world."

That decision allowed insulin to be shared freely and manufactured quickly. Pharmaceutical companies like Eli Lilly were invited to help produce it at scale. It was a model of scientific generosity that few stories since can match.

Today, more than 100 years later, insulin remains one of the most important medical breakthroughs of all time. But its legacy doesn't end with diabetes.

The modern weight-loss revolution—drugs like Ozempic, Wegovy, and Mounjaro—exists because of the science that began with insulin. These medications were developed from the same broad class of treatments: hormone-based therapies that regulate the body's metabolism. Ozempic and its cousins are GLP-1 receptor agonists that, like insulin, mimic natural hormones to help control blood sugar. But researchers quickly noticed another effect—patients were losing significant amounts of weight.

It's a reminder that progress rarely moves in a straight line. What began as a treatment for diabetes is now reshaping the way we understand obesity, cardiovascular risk, even food addiction. And that entire category of medication—the GLP-1 drugs that dominate headlines today—owes its lineage to a lab in Toronto, a barking dog named Marjorie, and a couple of scientists who refused to give up.

Banting and Macleod were honored with the Nobel Prize in 1923 -- with their assistants, Best and Collip, being mentioned in the official announcement but not technically honored.

Banting was the youngest-ever recipient in physiology or medicine, and he insisted on sharing his share of the prize money with Best; Maclead offered the same to Collip.

In the years that followed, Banting and Best were popularily recognized as the true discoverers, although not without controversy. (One 1993 journal article says the main reason why Banting and Best got the credit was that Best especially worked tirelessly to perpetuate the perception.)

Regardless of who gets the credit, their efforts left a mark that went far beyond the lab. They didn't cure diabetes, but they gave people their lives back. And in doing so, they opened a new world of hormonal science that still drives breakthroughs today.

In 2023, the American Chemical Society estimated that more than 100 million people had lived longer, healthier lives as a result of the insulin discovery.

What began as a desperate experiment with crude tools in a hot summer lab now helps power billion-dollar innovations. And yet the spirit behind it remains the same: a belief that biology can be tamed, that suffering can be eased, that we are not helpless.

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7 other things to know this week ...

Folks: About 4/5 of you liked the new way of doing "7 other things" in Big Optimism. (The original format still applies to Understandably.) I'm going to try it for a bit and see how it goes.

• Sunday July 27: “The age of jet travel is no longer a dream.” — de Havilland Aircraft Company Limited spokesperson, on the occasion of the maiden test flight of the de Havilland Comet 1, the first commercial passenger jetliner, piloted by John "Cats Eyes" Cunningham, a famous British World War II flying ace.
• Monday July 28: “From this moment on, Peru is free and independent by the general will of its people … Long live the nation! Long live the freedom!” — José de San Martín, declaring Peru's independence from Spain in Lima’s Plaza Mayor, July 28, 1821.
• Tuesday July 29: “Children born out of wedlock will stand equal under our law.” — a British MP, upon royal assent of the Legitimacy Act of 1959, guaranteeing equal rights to illegitimate children under British law.
• Wednesday July 30: "We were underdogs in those days. We were fighting the system however inadvertently it may have been. I think that speaks to people."— Daniel Myrick, co-director of The Blair Witch Project, which went into wide release on this day in 1999, en route to making almost $250 million on a $200,000 budget.
• Thursday July 31: "I started smiling. I don’t think I’ve ever done that in a race before." — Michael Phelps, after receiving his 19th Olympic medal in the 4×200 m freestyle relay On July 31, 2012, at the London Olympics, Phelps thus became the most decorated Olympian ever.
• Friday August 1: “Ladies and gentlemen, rock and roll.” — John Lack, with the first words on MTV when it launched on this date in 1981. First song, which you probably know, was “Video Killed the Radio Star” by The Buggles.

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• Saturday August 2: “We glide up and down hills with ease and safety.” —Andrew Smith Hallidie, creator of the cable car system in San Francisco, on the occasion of the debut of the first operational line -- this date, in 1873.