100 Years of Insulin, but Millions Still Without Access

This transcript has been edited for clarity.

It's the 100th anniversary of the discovery of insulin. I'm going to talk about what I think is interesting in its history and then touch on the issues that we currently have with regard to people using insulin.

Insulin is Discovered

The pancreatic islet cells (the islets of Langerhans) were discovered by a medical student named Langerhans in 1869. In 1889, a pancreatectomy in a dog produced diabetes. Subsequently, multiple investigators tried to produce extracts that lowered blood glucose and helped treat diabetes in pancreatectomized dogs. But the extracts that they created were too toxic to be administered to patients.

In 1921, the team of Frederick Banting, Charles Best, and James Collip were working in the department of physiology lab, headed by Dr John Macleod, at the University of Toronto. They were able to make pancreatic extracts, first from dogs and then from cattle, which they found could be used to safely treat humans with type 1 diabetes who had previously been dying of their disease.

From the beginning, these investigators were really altruistic. In 1921, Frederick Banting said, "Insulin does not belong to me. It belongs to the world."

The first human to get the insulin extract was Leonard Thompson in January 1922. He was 14 years old and dying of type 1 diabetes. He was incredibly skinny and very close to death. His first reaction to being given insulin was a bad one. He had a severe allergic reaction to the impurities in the insulin, so it was quickly modified and then given to him again, and he did well. Unfortunately, he lived only another 12 years, dying at the age of 26 of pneumonia. Ironically, his timing was impeccable with regard to the discovery of insulin. But his timing with regard to the discovery of antibiotics wasn't quite the same, because Fleming only discovered penicillin in 1928 and antibiotics weren't widely available until 1940.

The first US citizen to receive insulin was Elizabeth Hughes Gossett. She was the daughter of the governor of New York, Charles Hughes, and she went up to Toronto to get the insulin. She lived to the age of 73, had three children, and died in 1981 of cardiovascular disease. She was true proof of the concept that exogenously administered insulin can help treat type 1 diabetes.

Insulin Is Marketed

Banting, Best, and Collip were given a patent in the United States for their insulin, and they sold the rights back to the University of Toronto for a dollar because they wanted the insulin to be available to pharmaceutical companies to manufacture and distribute widely so people could benefit. The first partner to manufacture insulin was Lilly. The first insulin was called isletin, and it was much like the regular insulin of today. You had to give it as much as four times daily if you really want to mimic physiology. Back then, it was administered with large, reusable glass syringes and needles.

In 1923, Banting and Macleod received a Nobel Prize in medicine. However, Best and Collip were not included in this award. If you want to learn more about this topic, my favorite book is called Cheating Destiny, by James Hirsch.

Isletin was regular insulin, but it wasn't long-acting or short-acting insulin. It was sort of in the middle. So researchers went on to try to make this molecule better. The first thing they did was to add the protein named protamine, because this prolonged the activity of the insulin. The first protamine-based insulin was called PZI. Then we had NPH insulin, which we have to this day and it's widely available. Then we had the lente series of insulin, and in particular ultralente insulin, which was the first truly very long-acting insulin on the market. In the 1980s, recombinant human insulin was developed, and finally, we now have insulin analogues. The real benefit of the insulin analogues that we currently have on the market is the fact that the long-acting insulin analogues are more stable and seem to cause less hypoglycemia than prior insulin analogues.

Insulin Is Out of Reach for Some

These have all been really great advances, but we have a long way to go. One of the biggest problems is access to insulin. I work in an underresourced part of Los Angeles. I see people who have only intermittent access to insulin or who have to ration their insulin, and they have A1c levels well above 10%. Yes, insulin keeps them alive, but they develop complications. I see all of the complications of diabetes in people in their 20s and 30s. We really aren't treating these people well.

And insulin alone is clearly not enough to make a big difference in the treatment of type 1 diabetes. To treat type 1 diabetes, we need the whole bundle. We need to be able to educate people. We need to give them tools. We need to give them support. We need to give them medical care. We need to give them psychological care.

So the biggest barrier now is access, and inherent in that is the cost of insulin. Insulin production is in the hands of three large multinational pharmaceutical companies, and they account for 90% of the insulin market. A lot has been written about the high cost of insulin in the United States. There are many reasons for this, and I don't have time to go into detail about them. Suffice to say that many of us, and many different advocacy groups are working on this issue so patients can afford their insulin.

There are countries around the world, such as Canada, where you can get insulin at an affordable price. But there are many other countries, both middle and low-income countries, where insulin is unaffordable for the people who live there. It's very important to think globally. Worldwide, it is estimated that there are 30 million people who need insulin but can't afford it. Because of the cost and access issues, the World Health Organization just published its new edition of the list of essential medicines that should be available worldwide, and on that list are long-acting insulin analogues. It is hoped that this will result in more quality-assured biosimilar insulins entering the market, so there's more competition, which enables the price to be reduced, and insulin will be more widely available around the world.

So even though I am incredibly happy that we have insulin — I don't know where we'd be without it — I also know that we still have many steps to take until insulin is readily accessible around the world and it is used in a way to provide optimal benefit to all people who need it. Thank you.

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