Last fall, my daughter, Bisi, and I went to a talk by Doug Melton, a co-director of Harvard’s Stem Cell Institute who for the past twenty years has been working to understand and cure type 1 diabetes, the disease that afflicts both of his children (as it does Bisi). At the time, he said that his lab was “in the red zone, almost over the goal line, in terms of making perfect [beta] cells.”
Now, with the publication today of an article in the journal Cell, it appears that Melton’s lab has reached that line. Using human embryonic stem cells as a base, the lab has pioneered a process that can reproduce human, insulin-producing beta cells on a large scale. As Melton said in a conference call with journalists, “What we’re reporting on is something that I think was obvious to many as a possible solution but just turned out to be difficult to achieve, and that is the creation of human beta cells that properly respond to sugar or glucose and secrete the right amount of insulin.” Beyond that, and just as essential, Melton’s lab has figured out a way to produce these cells in the vast quantities required for transplantation into people and for testing out pharmaceuticals in the lab. In describing the work laid out in Cell, Jose Oberholzer—an associate professor of surgery, endocrinology and diabetes, and bioengineering at the University of Illinois at Chicago—told Rob Stein of National Public Radio, “It’s a huge landmark paper. I would say it’s bigger than the discovery of insulin. The discovery of insulin was important and certainly saved millions of people, but it just allowed patients to survive but not really to have a normal life. The finding of Doug Melton would… offer them really something what I would call a functional cure. You know, they really wouldn’t feel anymore being diabetic if they got a transplant with those kind of cells.”
To get to this point has required fifteen years of work on the part of Melton and about fifty other colleagues, testing out 70 different chemical compounds in 150 different combinations to figure out exactly how to instruct a stem cell to become a beta cell. He described the work as empirical science, not discovery science, in that in the former you are “committed to finding the answer to something and try all different methods to achieve it…. It wasn’t any great intellectual insight, I didn’t get an idea in the shower. It was strategic, systematic hard work over a long period of time.” He called the work a personal quest that began about twenty years ago, when his six-month-old son was diagnosed with type 1 diabetes. (His daughter was diagnosed several years later at age 14.) “Since that time I have done what any parent would do—which is to say, I’m not going to put up with this, I want to find a better way.” Melton described his children’s calm reaction when he told them he had succeeded in creating a renewable supply of beta cells. “I think like all kids, they always assumed that if I said I’d do this, I’d do it.”
Melton is not the first researcher to create a functioning beta cell in the lab. What separates this work is the road map it provides for creating a potentially unlimited supply of beta cells, which could be used both to implant into people who now need to take insulin (those with type 1 diabetes, and 10-15 percent of people with type 2), or to discover new drugs that could help preserve or regenerate beta cells. A typical person has about a billion beta cells, though only about a sixth of those, or 150 million, are needed to maintain insulin production. At any one time, Melton’s lab has 6-10 “spinner flasks” whirling cells within a liquid medium—each flask with enough beta cells for one patient.
Using cells from cadavers, some patients already have benefitted from beta cell transplantation, which frees them from injecting insulin for five years or more by providing them with an infusion of cells that secrete their own insulin. But the supply of these cadaver cells is extremely limited. Just 40-50 people a year receive such transplants in the United States, according to Albert Hwa, PhD, the director of discovery research at JDRF (JDRF and the Helmsley Charitable Trust are two of the organizations that have supported Melton’s research). These recipients must all use strong immunosuppressive drugs so their bodies don’t reject the foreign beta cells.
Melton’s beta-cell process could potentially make transplantation accessible to many more people with diabetes. Yet, for people with type 1 diabetes, the problem of the body’s autoimmune attack on beta cells would still need to be solved. Melton is collaborating on that with Daniel Anderson, a professor of chemical engineering at MIT who is working on a process that protects and encapsulates beta cells with an algenate, or algae-like substance. Other scientists are testing out different methods of encapsulation, but progress has been slow. Melton points out that another benefit of an unlimited supply of beta cells is that it will become easier than it has been to test out and perfect encapsulation methods.
A lot of work remains to be done before these cells would potentially be available to patients. Melton’s lab still needs to make the protocol for creating the cells more efficient—right now it takes 30-40 days. They need to come up with a manufacturing plan that complies with FDA standards, and see which kinds of tests the regulatory agency requires. “But I think we’ve shown that the problem can be solved; we’re essentially at the finish line here in terms of how to make beta cells.” He estimates that it will take at least three years until they reach the stage of clinical trials, where they can test out beta cells within an encapsulation device.
Still, it’s hard not to feel a sense of excitement about the potential of these cells. Last night, after giving Bisi insulin before her dinner, I told her about Melton’s upcoming announcement, and then we looked at a video clip from his lab, showing magnified images of beta cells growing over the course of 48 hours. As one of the researchers described it: “The final image shows 6 flasks, enough for 6 patients, spinning away. If you look closely, you can see particles spinning around, the white dust or dots are clusters of cells, each containing about 1000 cells.” As we looked, mesmerized, at what we knew to be hundreds of millions of healthy beta cells spinning in a red liquid, we couldn’t help but hope that a version of these cells would someday help Bisi, and others like her, escape from the day-to-day tyranny of type 1 diabetes.
Katie Bacon is a regular contributor to ASweetLife. She writes the blog Eating with Bisi.