He cured type 1 diabetes. It only took 30 years

By | December 8, 2021

This article first appeared in the Times.

The first sufferer is now free of the genetic form of the disease thanks to the work of Doug Melton, a US scientist inspired by his baby son’s illness.

When Doug Melton set out to cure type 1 diabetes, it is fair to say he underestimated the scale of the task.

Doug Melton - Type 1 Diabetes Cure

It was 1991 and his six-month-old son Sam had just been diagnosed with the autoimmune condition. The symptoms were terrifying: the tiny baby shaking and vomiting until he was given the insulin that would save his life. But even with treatment the consequences were stark — fingerprick blood tests four times a day, regular insulin injections and the looming threat of sight loss, kidney problems and heart disease.

Melton, a Harvard scientist who until that point had been studying the development of frogs, switched his attention to diabetes. He made his wife Gail a promise.

“I told her that within four or five years, I could figure out how to turn stem cells into beta cells,” he says. That challenge — to take blank embryonic cells and turn them into the type of cells that produce insulin in the pancreas — took 15 years, by which point his daughter, Emma, had also been diagnosed. “It shows you how bad I am at predictions,” he says.

Now, 30 years after Melton set out on his mission, the first patient has received the treatment he dreamt of all those years ago. And the results are better than anything he could have hoped for. In June, Brian Shelton, 64, received an infusion of beta cells. He is now living without insulin injections for the first time in four decades.

“It’s a whole new life,” Shelton told The New York Times in an interview last weekend. “It’s like a miracle.”

Melton, 68, has never met Shelton. Vertex, the multinational pharmaceutical giant which owns the rights to his treatment, informed him last month that the first stage of the trial had worked, but at that point Shelton had been listed as an anonymous trial participant. Seeing his picture in the newspaper, complete with his “First in Human” T-shirt, was an emotional moment.

“I just loved reading about him,” Melton says. “I was hoping that in the first patient there would be at least some evidence that the cells produced insulin. But this was the best possible result. Given that the patient only had half of the target dose, for the first result it just couldn’t be any better.”

Despite his excitement, Melton is circumspect. “Let’s remember this is just one patient. And it is only four or five months on. One has to be cautious about reproducing it with other patients.”

Why has it taken so long to get this far? “I have some good excuses,” Melton says. “The political question about whether you could use embryonic stem cells was a much harder problem than I realised.”

Melton’s strategy relies on using embryonic stem cells, the blank cells present in the first days of gestation which have the potential to become any cell in the human body.

In 2001, President George W Bush, spurred on by the pro-life movement, banned the use of federal funding for research using embryos. Melton had to separate his stem-cell lab from everything else at Harvard. He eventually secured philanthropic funding to set up a separate lab, but it set him back years.

Eventually, having proven his technique worked, he formed a company called Semma Therapeutics — named after Sam and Emma — which in 2019 was bought by Vertex for $950 million (£720 million).

The company is testing the treatment on 17 patients. If it continues to show promising results, it has the potential to change the lives of the estimated nine million people around the world living with type 1 diabetes, 400,000 of them in the UK.

Unlike the more common type 2 diabetes, which is linked to lifestyle, diet and obesity, type 1 diabetes is caused by genetics and environmental factors. Most first get ill when the body’s immune system starts attacking the insulin-producing cells of the pancreas. This usually occurs in childhood, but can strike in adulthood, as was the case with Theresa May, the former prime minister.

Without insulin, a hormone that controls glucose, sugar levels rise in the bloodstream to dangerous levels. Until insulin was injected for the first time in January 1922, people who developed type 1 diabetes could be expected to live no more than a year or two. Now they are reliant on constant blood tests and injections.

Advances in technology means this process can be automated, using continuous glucose monitors and insulin pumps. This has improved patients’ lives, Melton says. “But it still means hours every day messing around with the pump in their infusion sets. And I know with my children, putting those infusion sets in is a major trouble. What we’re trying to do is replicate what I would call nature’s solution to the problem, rather than a technological solution.”

Melton’s vision was to use stem cells to recreate the beta cells, deep within the pancreas, which have been destroyed by the malfunctioning immune system. He explains: “A continuous glucose monitor reads blood sugars about every five to 15 minutes. The pancreatic beta cells that we put in the patients read blood sugar every millisecond. They also squirt out just a tiny amount of insulin, just the right amount, rather than the large dose that is given out by a pump. My own view is that the biological solution, nature’s solution, is better long-term.”

Even if the trials are successful, however, there is a key challenge to overcome. The immune system is likely to attack the new beta cells, in the same way that they attacked the originals. To this end Shelton — and the other patients given the stem-cell treatment — will have to take immunosuppressant drugs. Melton admits this is hardly ideal during a pandemic.

Emma, now 34, a lawyer, and Sam, 30, a mathematician at the Massachusetts Institute of Technology, are thrilled, he says. “They were both delighted for Mr Shelton and for the progress we’ve made so far. But they asked me when they would be able to take it without immunosuppressants. Well, that is going to be a while.” Would they be willing to take it with immunosuppressants? “No, I don’t think so,” he says.

To this end Vertex is now working on the next stage in the project, a different mode of delivering the beta cells into the body. “Mr Shelton was treated by introducing naked cells and then drugs to prevent his system from killing those cells,” Melton said. “The next thing is to instead deliver the beta cells using an encapsulation device, which means the immune cells cannot attack the cells.”

Melton, who studied for six years at Trinity College, Cambridge, adds: “Because I’m speaking to an English newspaper, I’ll use my favourite analogy. The encapsulation device works like a teabag. The glucose and insulin can get inside the bag, but the tea leaves — the cells — stay inside the bag so immune cells can’t get in and kill them.”

If the programme, due to start next year, is successful it will be life-changing — for Brian Shelton, for Emma and Sam, and for millions of others around the world.

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