100 years after insulin treatment was invented, researchers hope to ditch needles once and for all

Canadian scientists made one of the most important discoveries in the history of medicine 100 years ago when Dr. Frederick Banting and his assistant, Charles Best, successfully isolated the hormone insulin in Banting's lab at the University of Toronto. 

On November 14th, 1921, the team presented their findings to fellow faculty members and students — they had successfully discovered a treatment for diabetes. It soon found its way to millions of patients, transforming the disease from a death sentence into a manageable, chronic condition.

However, a century later, despite technological advancements, treatment for Type 1 diabetes still often requires invasive and inconvenient therapies, something that biomedical researchers are actively trying to change.

"It's an important achievement, but ultimately, we're still injecting ourselves with insulin," said Michael Sefton, the executive director of Medicine by Design, an incubator for medical breakthroughs based at the University of Toronto, where he's also a professor of biomedical engineering.

Working at the same institution as Banting and Best did a century ago, Sefton is a part of a team trying to find a cure for diabetes so that patients no longer require daily injections.

"It is … kind of in the woodwork here, trying to sort of continue to work on insulin. But it's maybe a little disappointing that we're still talking about the problems of insulin delivery 100 years later," he told Quirks & Quarks host Bob McDonald.

Miracle treatment

Prior to Banting and Best's discovery, diabetes was uncontrollable, and often fatal within a year of diagnosis. The only treatment that could delay the inevitable was a rigorous, near-starvation diet.

Insulin is the vital hormone that the body uses to manage how it turns food into energy. Without insulin, blood sugar cannot be properly regulated. High blood sugar levels can damage blood vessels, leading to blindness, renal failure or heart attacks. Dangerously low levels can lead to diabetic coma and death.

Type 1 diabetes, which used to be called juvenile diabetes, happens when the pancreas produces little to no insulin at all.

"It's an autoimmune disease, so your immune system has turned on your own islets, the insulin secreting cells, and destroys them," said Sefton.

In Type 2 diabetes, the much more common version of the disease, the body doesn't respond properly to the insulin it makes. That's known as insulin resistance. As the disease progresses, the pancreas makes less and less insulin, and patients require more insulin supplementation as a result.

Isolating insulin was an important discovery because it meant that there was a form of treatment beyond a starvation diet. But in later interviews, Best said he wanted to improve on the delivery method.

"I think we'll get much better ways of giving it," Best said in a 1977 interview on CBC's Morningside. "There's work going on here and in other places about an artificial pancreas, which if it can be miniaturized, put under the skin, it would discharge insulin just when it was needed. Or if the cultures of an artificial pancreas could be grafted and the cells which make insulin kept alive, that would do away with the injections."

However, he added, "I don't think either of those are going to happen very soon." 

Best was correct. Even decades after his death, work on these technologies is still ongoing, although Sefton believes that better treatments are on the horizon.

Making diabetes a disease of the past

After training as an engineer, Sefton started working on diabetes in the 1970s, when there was great interest in building a mechanical pancreas that could sense insulin levels and release the hormone as needed.

"We wondered whether the best available glucose sensors were the cells themselves, the normal pancreas cells, what we call the pancreatic islets," he said. "And so the question was, could we transplant pancreatic islets from a normal individual into a diabetic and make them replace the pancreas?"

Sefton's work builds on a 20-year-old surgical procedure called The Edmonton Protocol, where researchers found that implanting donated islet cells into a diabetic patient's liver would allow them to make their own insulin for a period of time. However, in all patients, their diabetes eventually returned.

"The challenge with the liver is it is a somewhat hostile environment for the islets, and so only maybe 60 percent of the islets that are transplanted survive," said Sefton.

His work focuses on using the skin as a transplant site for the islets, as a site that's less invasive for researchers to access, and less hostile to the foreign cells.

By injecting the islets under the skin with a material called methacrylic acid, or MAA, researchers have found that the body creates new blood vessels around the cells, enabling them to deliver insulin throughout the body. "Because those are blood vessels that are grown under the skin, the islets will ingraft, and will function as they are supposed to function," said Sefton.

He is also working to create stem cell-derived islets, to make the cells easier to obtain than relying on donor cells. "The cells that are derived from stem cells work almost the same as the donated islets. That's the beauty of them. But we aren't necessarily very good at that yet. It's still early days."

Sefton believes islet treatments will be a possibility for humans within 20 years. And looking forward to the next 100 years of diabetes treatment, Sefton is optimistic.

"I'm not shy, so I would say it'll be a disease of the past," he said. 

Produced and written by Amanda Buckiewicz.