Will Rhode Island Win the Race to Cure Diabetes?
Local scientists have worked for decades to develop technology that could cure diabetes.
Leonard Thompson was fourteen years old and near death when he helped make medical history. It was 1922, and though what became known as diabetes dated back to ancient times — the Chinese called it “sugar urine disease”— the only treatment for the illness at the time was the starvation diet.
Thompson weighed sixty-five pounds when he was admitted to Toronto General Hospital. A young surgeon named Dr. Frederick Banting convinced his father to let him inject his son with a new drug he was testing in dogs called insulin. Thompson’s health improved dramatically, and news of the medical miracle made the front pages of newspapers around the globe. The next year, the drug manufacturer Eli Lilly began making insulin to treat diabetes.
But though the technology for treating the disease has improved over time, for an estimated three million Americans — many of them children — a diagnosis of type 1 diabetes remains a life sentence. They manage it by monitoring their blood sugar throughout the day and administering insulin. But severe complications later in life can include heart disease, blindness, nerve damage and even amputation. The disease costs an estimated $15 billion a year to treat.
That’s why researchers — and investors — have long considered finding a way to transplant cells that could regulate insulin without getting rejected by the immune system, a holy grail. Scientists in Rhode Island are among those who have been working on and off for decades on achieving it.
About three years ago, Harvard’s Stem Cell Institute announced a major breakthrough in the fight against diabetes. The institute’s co-founder, Dr. Doug Melton, and a team of scientists said that using embryonic stem cells, they were able to develop islets — clusters of pancreatic cells that house beta cells and produce insulin in a healthy pancreas.
The transplantable tissue, which they tested in mice, opened the door to a potential treatment that would enable diabetics to once again naturally regulate their own blood sugar.
“It was gratifying to know that we could do something that we always thought was possible,” Melton said at the time, “but many people felt it wouldn’t work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now I’m really energized.”
Melton had dedicated himself to finding a cure for the disease more than twenty-five years before, when his then-infant son, Sam, and then later his daughter, Emma, were diagnosed with type 1 diabetes. While the cause of type 1 diabetes isn’t known, genetics are believed to play a role.
With venture capitalist Robert Millman, Melton founded a startup called Semma Therapeutics — named for Sam and Emma — to develop the technology for an artificial pancreas and bring it to market. It attracted nearly $50 million in investment from Millman’s firm MPM Capital, medical companies Novartis and Medtronic and later, the California Stem Cell Association.
But it’s a very competitive landscape. Other companies are also working on the creation of artificial pancreases, including California-based VitaCite, which already has clinical trials scheduled.
In addition to creating the islets, scientists also have to figure out a way to keep a person’s immune system from rejecting them. That’s where the scientists and clinicians in Rhode Island come in. Using a method called encapsulated cell technology (ECT), they are developing a semi-permeable membrane to house the islets that will allow oxygen and glucose to diffuse through it, but that the patient’s body won’t reject.
Trying to make that work has occupied scientists in Rhode Island and around the world for more than three decades. In 2015, Semma recruited some of the most prominent people working in ECT in Rhode Island — Dr. Moses Goddard, Christopher Thanos, John Mills and Briannan Bintz — to develop the technology for Melton’s islets.
Over the next few years, they plan to get approval from the Food and Drug Administration for clinical trials with the hope that one day, surgeons can implant healthy new tissue that can regulate insulin in diabetic patients.
But despite the excitement about the prospect of developing a way to potentially cure type 1 diabetes, those involved acknowledge that if it were easy, it would have happened long ago.
“The public definitely doesn’t appreciate that much of science is a failure,” Melton told MIT Technology Review last year.
One of the pioneers in the development of the method that could change the treatment of diabetes was a transplant from Switzerland named Dr. Pierre Galletti. An internationally known scientist, Galletti was the first dean of biology and medicine at Brown University and one of the founders of its medical school.
Galletti worked to develop synthetic solutions for failing organs. He also had an entrepreneurial streak. Galletti published the first really significant paper on ECT in the journal Science in 1973, and it caused a big splash, Goddard recalls.
Galletti advanced the idea that ECT could be used to help treat type 1 diabetes. In healthy people, islets in the pancreas create insulin and secrete it into the blood stream. But in people with type 1 diabetes, the body’s immune system destroys the insulin-producing beta cells. And when they don’t make enough insulin, glucose builds up in the blood.
The idea behind ECT was that scientists could use beta cells from another source — at the time Galletti was using pigs — and put them in an envelope designed to protect them from a person’s immune system, then transplant the cells into the pancreas. And the membrane should be porous enough that blood sugar could diffuse through it and affect the beta cells, and the beta cells could respond with insulin.
Galletti performed the first experiment with ECT on a human in 1983, in what Goddard describes as the “good old days/bad old days of medicine.” The patient was a French nephrologist with type 1 diabetes who was in end-stage kidney failure. Galletti worked with a French endocrine surgeon who extracted islets from an islet tumor. The nephrologist already had an access shunt for dialysis, so Galletti’s lab at Brown built a device with the islets that could be plugged into the shunt.
The doctors took the nephrologist off insulin. He enjoyed a proper French meal with several courses and wine as the doctors measured his blood sugar and treated his diabetes for twenty-four hours.
“That was the kind of thing you did as experiments back in the day,” says Goddard, who was a protege of Galletti’s, along with Patrick Aebischer. Aebischer had earned degrees in medicine and neuroscience in Switzerland before coming to Brown. Goddard, a descendant of the founder of Rhode Island Hospital, had earned undergraduate and medical degrees from Brown. They also recruited a mechanical mind named John Mills.
Meanwhile, some companies were already making commercial versions of membranes to encapsulate cells for a variety of medical purposes. Goddard and Aebischer were consulting for a company that was manufacturing membranes for dialysis cartridges when they realized they could make their own.
The company had maintained that creating the membranes was an extremely complex process that required great expertise and hundreds of employees, Goddard recalls. One day, he and Aebischer had a meeting at the company to discuss the diameter of the membranes they were looking for. A junior employee took them on a tour, and Goddard and Aebischer were allowed to see where the membranes were being made. It was a small room for controlled experiments and they couldn’t see the actual process. But Goddard and Aebischer were convinced that it couldn’t be too hard to figure out how to make their own membranes.
“Patrick dove into the patent literature and figured out what they did,” Goddard says. “We replicated it and really mastered it.”