Brian Shelton's life was ruled by type 1 diabetes. When his blood sugar plummeted, he would lose consciousness without warning. He crashed his motorcycle into a wall. He passed out in a customer's yard while delivering mail. Following that episode, his supervisor told him to retire, after a quarter-century in the US Postal Service. He was 57.
His ex-wife, Cindy Shelton, took him into her home in Elyria, Ohio. "I was afraid to leave him alone all day," she said. Early this year, she spotted a call for people with type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a treatment developed over decades by a scientist who vowed to find a cure after his baby son and then his teenage daughter got the disease.
Unlike type 2 diabetes, type 1 is quickly lethal unless patients get injections of insulin. No one spontaneously gets better
Brian Shelton became the first patient. On June 29th, he got an infusion of cells, grown from stem cells but just like the insulin-producing pancreas cells his body lacked. Now his body automatically controls its insulin and blood sugar levels. Shelton, now 64, may be the first person cured of the disease with a new treatment that has experts daring to hope that help may be coming for many of the 1.5 million Americans suffering from type 1 diabetes. "It's a whole new life," Shelton said. "It's like a miracle." Diabetes experts were astonished but urged caution. The study is continuing and will take five years, involving 17 people with severe cases of type 1 diabetes. It is not intended as a treatment for the more common type 2 diabetes. "We've been looking for something like this to happen literally for decades," said Dr Irl Hirsch, a diabetes expert at the University of Washington who was not involved in the research. He wants to see the result, not yet published in a peer-reviewed journal, replicated in many more people. He also wants to know if there will be unanticipated adverse effects and if the cells will last for a lifetime or if the treatment would have to be repeated.
But, he said, "bottom line, it is an amazing result." Dr Peter Butler, a diabetes expert at UCLA who also was not involved with the research, agreed while offering the same caveats. "It is a remarkable result," Dr Butler said. "To be able to reverse diabetes by giving them back the cells they are missing is comparable to the miracle when insulin was first available 100 years ago." And the latest development all started with the 30-year quest of a Harvard University biologist, Doug Melton.
Melton had never thought much about diabetes until 1991 when his six-month-old son, Sam, began shaking, vomiting and panting. “He was so sick, and the paediatrician didn’t know what it was,” Melton said. He and his wife Gail O’Keefe rushed their baby to Boston Children’s Hospital. Sam’s urine was brimming with sugar – a sign of diabetes. The disease, which occurs when the body’s immune system destroys the insulin-secreting islet cells of the pancreas, often starts at about age 13 or 14. Unlike the more common and milder type 2 diabetes, type 1 is quickly lethal unless patients get injections of insulin. No one spontaneously gets better.
“It’s a terrible, terrible disease,” said Dr Butler at UCLA. Those with the disease are at risk of going blind – diabetes is the leading cause of blindness in the US. It is also the leading cause of kidney failure. People with type 1 diabetes are at risk of having their legs amputated and of death in the night because their blood sugar plummets during sleep. Diabetes greatly increases their likelihood of having a heart attack or stroke. It also weakens the immune system.
The only cure that has ever worked is a pancreas transplant or a transplant of the insulin-producing cell clusters of the pancreas, known as islet cells, from an organ donor’s pancreas. But a shortage of organs makes such an approach an impossibility for the vast majority with the disease.
"Even if we were in utopia, we would never have enough pancreases," said Dr Ali Naji, a transplant surgeon at the University of Pennsylvania who pioneered islet cell transplants and is now a principal investigator for the trial that treated Shelton.
For Melton and O’Keefe, caring for an infant with the disease was terrifying. O’Keefe had to prick Sam’s fingers and feet to check his blood sugar four times a day. Then she had to inject him with insulin. For a baby that young, insulin was not even sold in the proper dose. His parents had to dilute it.
“Gail said to me, ‘If I’m doing this you have to figure out this damn disease,’” Melton recalled. In time, their daughter Emma, four years older than Sam, would develop the disease too, when she was 14. Melton had been studying frog development but abandoned that work, determined to find a cure for diabetes. He turned to embryonic stem cells, which have the potential to become any cell in the body. His goal was to turn them into islet cells to treat patients.
The challenge was to figure out what sequence of chemical messages would turn stem cells into insulin-secreting islet cells. The work involved unravelling normal pancreatic development, figuring out how islets are made in the pancreas and conducting endless experiments to steer embryonic stem cells to becoming islets. It was slow going.
Everything had to be done to the exacting standards of the FDA – thousands of pages prepared, and clinical trials planned
After years when nothing worked, a small team of researchers, including Felicia Pagliuca, a postdoctoral researcher, was in the lab one night in 2014, doing one more experiment. "We weren't very optimistic," she said. They had put a dye into the liquid where the stem cells were growing. The liquid would turn blue if the cells made insulin. Her husband had already called asking when was she coming home. Then she saw a faint blue tinge that got darker and darker. She and the others were ecstatic. For the first time, they had made functioning pancreatic islet cells from embryonic stem cells.
The next step for Melton, knowing he’d need more resources to make a drug that could get to market, was starting a company.
His company Semma was founded in 2014, a mix of Sam and Emma's names. One challenge was to figure out how to grow islet cells in large quantities with a method others could repeat. That took five years. The company, led by Bastiano Sanna, a cell and gene therapy expert, tested its cells in mice and rats, showing they functioned well and cured diabetes in rodents. At that point, the next step – a clinical trial in patients – needed the backing of a large, well financed and experienced company with hundreds of employees. Everything had to be done to the exacting standards of the US Food and Drug Administration (FDA) – thousands of pages of documents prepared, and clinical trials planned.
Chance intervened. In April 2019, at a meeting at Massachusetts General Hospital, Melton ran into a former colleague, Dr David Altshuler, who had been a professor of genetics and medicine at Harvard and the deputy director of the Broad Institute. Over lunch, Dr Altshuler, who had become the chief scientific officer at Vertex Pharmaceuticals, asked Melton what was new.
Melton took out a small glass vial with a bright purple pellet at the bottom. “These are islet cells that we made at Semma,” he told Dr Altshuler. Vertex focuses on human diseases whose biology is understood. “I think there might be an opportunity,” Dr Altshuler told him. Meetings followed and eight weeks later, Vertex acquired Semma for $950 million. With the acquisition, Sanna became an executive vice-president at Vertex.
Less than two years after Semma was acquired, the FDA allowed Vertex to begin a clinical trial with Shelton as its initial patient. Like patients who get pancreas transplants, Shelton has to take drugs that suppress his immune system. He says they cause him no side effects, and he finds them far less onerous or risky than constantly monitoring his blood sugar and taking insulin. He will have to continue taking them to prevent his body from rejecting the infused cells.
But Dr John Buse, a diabetes expert at the University of North Carolina who has no connection to Vertex, said the immunosuppression gives him pause. "We need to carefully evaluate the trade-off between the burdens of diabetes and the potential complications from immunosuppressive medications."
Last month, Vertex was ready to reveal the trial results to Melton. He did not expect much. “I was prepared to give them a pep talk,” he said. Melton, normally a calm man, was jittery during what felt like a moment of truth. He had spent decades and all of his passion on this project. By the end of the Vertex team’s presentation, a huge smile broke out on his face; the data was for real.
He left Vertex and went home for dinner with Sam, Emma and O'Keefe. When they sat down to eat, Melton told them the results. "Let's just say there were a lot of tears and hugs." For Shelton the moment of truth came a few days after his procedure, when he left the hospital. He measured his blood sugar. It was perfect. He and Cindy Shelton had a meal. His blood sugar remained in the normal range. Brian Shelton wept when he saw the measurement. "The only thing I can say is: 'Thank you.'" – This article originally appeared in The New York Times