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Type 1 diabetes ruled Brian Shelton’s life.

When his blood sugar dropped, he would lose consciousness without warning. His motorcycle crashed into the wall. He passed out during mail delivery in a client’s yard. After this incident, his supervisor told him to retire after a quarter of a century in the Postal Service. He was 57 years old.

His ex-wife Cindy Shelton took him to his home in Elyria, Ohio. “I was afraid to leave him alone all day,” she said.

Earlier this year, she saw a call for people with Type 1 diabetes to participate in a clinical trial by Vertex Pharmaceuticals. The company was testing a cure developed over decades by a scientist who promised to find a cure after his young son, and then his teenage daughter fell ill with the devastating disease.

Mr. Shelton was the first patient. On June 29, she received an infusion of cells, such as insulin-producing pancreatic cells grown from stem cells but not found in her body.

His body now automatically controls his insulin and blood sugar levels.

Mr. Shelton, now 64, may be the first to cure the disease with a new treatment with specialists daring to hope that help will come to many of the 1.5 million Americans with Type 1 diabetes.

“This is a whole new life,” said Mr. Shelton. “It’s like a miracle.”

Diabetes experts were surprised but urged caution. The study is ongoing and will run for 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.

D., a diabetes specialist at the University of Washington and not involved in the research. “We’ve literally been looking for something like this to happen for decades,” said Irl Hirsch. He would like to see the result replicated in many more people, which has not yet been published in a peer-reviewed journal. He also wants to know if there will be unexpected side effects and whether the cells will last a lifetime or if the treatment needs to be repeated.

However, “all in all, it’s a great result,” he said.

D., a diabetes specialist at UCLA and not involved in the research. Peter Butler agreed, presenting the same caveats.

Dr. “This is an outstanding result,” Butler said. “Being able to reverse diabetes by giving them back the missing cells is comparable to the miracle that insulin was first made 100 years ago.”

And it all started with the 30-year search of Harvard University biologist Doug Melton.

‘A Horrible, Horrible Disease’

Dr. Melton didn’t think much about diabetes until 1991, when her 6-month-old baby boy, Sam, started shaking, vomiting, and gasping for breath.

Dr. “She was very sick and her pediatrician didn’t know what was going on,” Melton said. He and his wife, Gail O’Keefe, rushed their baby to Boston Children’s Hospital. Sam’s urine was full of sugar – a sign of diabetes.

The disease, which occurs when the body’s immune system destroys the insulin-secreting islet cells of the pancreas, usually begins around the age of 13 or 14. Unlike the more common and milder Type 2 diabetes, Type 1 is rapidly fatal unless patients receive an injection of insulin. . No one can heal on their own.

UCLA’s Dr. “This is a terrible, terrible disease,” Butler said.

Patients are at risk of going blind – diabetes is the leading cause of blindness in this country. It is also the leading cause of kidney failure. People with type 1 diabetes are at risk of amputation and death at night due to low blood sugars during sleep. Diabetes greatly increases the chances of having a heart attack or stroke. It weakens the immune system – Dr. One of Butler’s fully vaccinated diabetes patients recently died from Covid-19.

Adding to the burden of the disease is the high cost of insulin, whose price increases every year.

The only treatment that has worked so far is a pancreatic transplant, or transplantation of clumps of insulin-producing cells of the pancreas, known as islet cells, from the pancreas of an organ donor. But the shortage of organs makes such an approach impossible for the vast majority with the disease.

A transplant surgeon at the University of Pennsylvania who pioneered islet cell transplantation and is the principal investigator of the study currently treating Mr. “Even if we were in utopia, we would never have enough pancreas,” said Ali Naji.

blue tips

Dr. For Melton and Mrs. O’Keefe, caring for a sick baby was scary. Ms. O’Keefe had to pierce Sam’s fingers and feet four times a day to check her blood sugar. Then she had to inject him with insulin. For a baby that small, insulin wasn’t even sold in the proper dose. His family had to dilute it.

Dr. “Gail said to me, ‘If I’m doing this, you have to solve this damn disease.’ Over time, their daughter Emma, ​​four years older than Sam, would also contract the disease when she was 14.

Dr. Melton was working on frog development, but left it determined to find a cure for diabetes. He turned to embryonic stem cells, which have the potential to develop into any cell in the body. His goal was to transform patients into islet cells to treat them.

One problem was the source of the cells – they came from unused fertilized eggs from a fertility clinic. But in August 2001, President George W. Bush banned the use of federal money for research on human embryos. Dr. Melton had to separate his stem cell lab from everything else at Harvard. The Howard Hughes Medical Institute received private funding from Harvard and philanthropists to set up a completely separate laboratory with an accountant who kept all expenses separate from the light bulbs.

With over 20 years of working with a lab of about 15 people to successfully transform stem cells into islet cells, Dr. Melton estimates the project cost to be approximately $50 million.

The challenge was figuring out which chemical message sequence would convert stem cells into insulin-secreting islet cells. The work involved unraveling normal pancreatic development, figuring out how islets are made in the pancreas, and doing endless experiments to turn embryonic stem cells into islets. It was going slow.

After years of nothing working, a small team of researchers, including postdoctoral researcher Felicia Pagliuca, conducted another experiment in the lab overnight in 2014.

“We weren’t very optimistic,” he said. They put dye in the fluid in which the stem cells grew. If the cells make insulin, the liquid turns blue.

Her husband had already called and asked when he would be home. Then he saw a pale blue color that was getting darker and darker. He and the others were ecstatic. For the first time, they made functioning pancreatic islet cells from embryonic stem cells.

The lab was celebrated with a small party and cake. They then made bright blue wool caps for themselves with five circles of red, yellow, green, blue, and purple to represent the stages that stem cells must go through to become functioning islet cells. They had always hoped for purple but until then they were stuck on green.

Dr. The next step for Melton was to start a company, knowing it would need more resources to make a marketable drug.

Moments of Truth

His company, Semma, was founded in 2014 as a mix of the names Sam and Emma.

One challenge was figuring out how to grow islet cells in large quantities in a method that others could replicate. This took five years.

Led by Bastiano Sanna, a cell and gene therapy expert, the company tested its cells in mice and rats, showing that the cells work well and improve diabetes in rodents.

At this point, the next step – a clinical trial in patients – required a large, well-funded and experienced company with hundreds of employees. Everything had to be done to the Food and Drug Administration’s rigorous standards—thousands of pages of documents were prepared and clinical trials were planned.

Luck intervened. At a meeting at Massachusetts General Hospital in April 2019, Dr. Melton, professor of genetics and medicine at Harvard and a former colleague of the Broad Institute, Dr. He ran into David Altshuler. At lunch, Vertex Pharmaceuticals chief scientific officer Dr. Altshuler, Dr. He asked Melton what was new.

Dr. Melton pulled out a small glass vial with a bright purple pellet at the bottom.

“These are the islet cells we made at Semma,” he told Altshuler.

Vertex focuses on human diseases with an understanding of biology. “I think it could be an opportunity,” Altshuler said.

Meetings followed, and eight weeks later Vertex bought Semma for $950 million. With the purchase, Dr. Sanna became executive vice president at Vertex.

The company won’t reveal a price for diabetes treatment until it’s approved. But it is likely to be expensive. Like other companies, Vertex angry patients with high drug prices These are difficult and expensive to make.

Vertex’s challenge was making sure the manufacturing process worked every time and that the cells would be safe when injected into patients. Working under scrupulously sterile conditions, the workers monitored the veins of solutions containing nutrients and biochemical signals that stem cells transformed into islet cells.

Less than two years after Semma was purchased, the FDA allowed Vertex to begin a clinical trial with Mr. Shelton as its first patient.

Like pancreatic transplant patients, Mr. Shelton needs to take immunosuppressants. He says they cause him no side effects, and he finds them much less troublesome or risky than constantly monitoring his blood sugar and taking insulin. He will need to continue taking them to prevent his body from rejecting the grafted cells.

But Dr., a diabetes specialist at the University of North Carolina with no affiliation with Vertex. John Buse said that immunosuppression gave him pause. “We need to carefully consider the balance between the burdens of diabetes and the potential complications of immunosuppressive drugs.”

Mr. Shelton’s treatment, known as the early-stage safety trial, required careful monitoring and had to be started with half the dose to be used later in the trial, said Dr. Shelton’s surgeon at Mass General. He pointed to James Markmann. Working with Vertex in Trial. No one expected the cells to work so well, he said.

“The result is stunning,” said Dr. “This is a real leap forward for the field,” said Markmann.

Last month, Vertex presented the results to Dr. He was ready to explain to Melton. He wasn’t expecting much.

“I was ready to give them a pep talk,” he said.

Normally a quiet man, Dr. Melton was nervous during a moment that felt real. He spent years and all his passion on this project. At the end of the Vertex team’s presentation, a big smile appeared on his face; the data was real.

He left Vertex and went home for dinner with Sam, Emma and Mrs O’Keefe. When they sat down to eat, Dr. Melton told them the results.

“Let’s just say there was a lot of tears and hugs.”

For Mr. Shelton, the truth came when he left the hospital a few days after the procedure. He measured his blood sugar. He was perfect. He and Mrs. Shelton had dinner. Blood sugar remained within the normal range.

Mr. Shelton cried when he saw the measurement.

“All I can say is ‘thank you’.”