Hopi Hoekstra, Edgerley Family Dean of the Faculty of Arts and Sciences, praised Doug Melton’s work as a prime example of how scientific discovery can lead to medical breakthroughs.
“At a time when investment in science is under threat, it’s hard to imagine a better illustration of how basic research can lead to real advances in medicine, improving the health of everyday people,” she said.
Melton’s interest in biology began in childhood, driven by a fundamental question: How do single-celled eggs grow into complex animals with specialized cells? “I remember wondering how the eggs in the pond knew whether to become a salamander or a frog,” he recalled. This curiosity sparked his lifelong scientific career.
Melton went on to earn a biology degree from the University of Illinois, followed by a Marshall Scholarship to study at the University of Cambridge, where he earned degrees in history and philosophy of science, as well as a Ph.D. in molecular biology. He joined Harvard in 1981, focusing on early development in frogs and mice, intending to study vertebrate body formation.
His path changed dramatically in 1991 when his son, Sam, was diagnosed with Type 1 diabetes. The disease destroys beta cells in the pancreas that produce insulin, a hormone regulating blood sugar. “I didn’t understand what that meant at first,” Melton said. “But soon, my wife was injecting Sam with insulin constantly.”
Overwhelmed with the responsibility of caring for his son, Melton’s wife encouraged him to focus his research on diabetes. “She said, ‘You’re supposed to be able to do something. Why don’t you work on this?’”
Melton switched gears and began studying diabetes, particularly how beta cells develop. His research led him to stem cells, which are developmental cells that differentiate into all other types of cells in the body. Melton imagined manipulating embryonic stem cells to become insulin-producing beta cells.
“I never thought it couldn’t be done,” he said. “I just didn’t know how.”
Diabetes, which affects the body’s ability to metabolize glucose, is becoming a global crisis. According to the CDC, more than 38 million Americans, or roughly 11% of the population, were diagnosed with diabetes in 2021, making it the eighth leading cause of death in the U.S. The disease is spreading rapidly worldwide, particularly in low- and middle-income countries, with the International Diabetes Federation estimating 589 million adults are affected.
For Melton, this problem became even more personal when his daughter, Emma, was diagnosed with Type 1 diabetes a decade after Sam.
Although advances in insulin therapy have been made over the last century, they remain treatments, not cures. Melton sought a cure by exploring how stem cells can be used to regenerate insulin-producing beta cells. His research at Harvard benefited from the university’s commitment to science during a period when federal funding for human stem cell research was limited. In 2001, President George W. Bush suspended funding for new human stem cell lines, but Harvard supported Melton’s work by creating a separate lab for him. In 2004, he co-founded the Harvard Stem Cell Institute, which now involves over 350 researchers.
Melton and his team made a breakthrough by discovering how to guide stem cells to develop into insulin-producing beta cells. This method involves introducing specific proteins at certain stages, turning stem cells into fully functional beta cells over 30 days.
In 2014, Melton founded Semma Therapeutics to commercialize the technology. The company was acquired by Vertex Pharmaceuticals in 2019, and clinical trials for Type 1 diabetes are now underway. Early trials show promising results, with some patients becoming insulin-independent after treatment.
Melton emphasizes that his work is about copying nature, not inventing new mechanisms. “I’m trying to replicate what nature does,” he said.
This new stem-cell therapy, which has now entered human clinical trials, marks the first time fully differentiated human cells have been cultured from stem cells and tested in people. Melton believes the technique may eventually be used to treat Type 2 diabetes and could also provide insights for other treatments, such as generating dopamine-producing brain cells for Parkinson’s disease.
Harvard’s supportive environment, he says, allows researchers to tackle long-term, complex problems. “It’s a place where you can take on a challenge that might take a decade or more to solve,” Melton said.
Throughout his career, Melton has nurtured young talent, employing dozens of undergraduates, graduate students, and postdoctoral researchers. He also teaches courses that explore how basic science can address medical challenges. “Undergraduates come with fresh ideas and fewer preconceived notions, which challenges my thinking,” Melton said. “It’s a great motivator to attract young people to science.”
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