Doug Melton's life irreparably changed the day his child was diagnosed with a life-threatening illness. But unlike most other parents in that situation, he was a molecular biologist who set up his own way to do something about it.
Now, more than 30 years later, Melton and his colleagues are ahead of a new treatment for type 1 diabetes, which makes healthy insulin-producing cells that can be used to implant patients. Vertex Pharmaceuticals, a Boston-based biomedical company, is conducting clinical trials on methods pioneered by Melton and his colleagues at Harvard University and his startup company.
“There's very little better than having an interesting science puzzle,” Melton said. “It involves educating people, especially and if you succeed, you do good things for people around the world.”
Melton was recently selected as Harvard's first catalyst professor. This is the role of senior faculty members with the aim of promoting collaboration with the private sector. The professor will allow distinguished faculty members to engage in external opportunities while maintaining their educational commitment and contribution to the academic mission of the university.
“It's hard to imagine a better example of how basic scientific discoveries pave the path to a medical breakthrough.”
Hopi Hextra
Hopi Hextra, Dean of the Edgeley Family at the Faculty of Arts and Sciences, praised Melton's work as a classic example of creating advances in medicine as a representative of scientific discoveries.
“When investments in science are under attack, it's hard to imagine a better example of how basic scientific discoveries pave the path to a medical breakthrough, and how research conducted at Harvard University can improve the health of everyday people,” she said.
Biologist hatching
As a child, Melton was fascinated by biology. One question particularly confusing him. How did single-celled eggs grow into complex animals containing billions of specialized cells? “I remember as a boy in Chicago, I thought I'd know if the eggs in the pond were going to make salamanders or frogs,” he recalls. “It really started me out of a career in science.”
That question continued to drive his career. Melton graduated with a degree in biology from the University of Illinois, earned a Marshall Scholarship and studied at Cambridge University, earning a bachelor's and doctoral degrees in history and philosophy of science. In molecular biology. In 1981 he landed at Harvard and spent ten years studying the early development of frogs and mice. He had planned to spend his career investigating how the body was formed in vertebrates.
His life suddenly changed in 1991 when his young son Sam was diagnosed with type 1 diabetes. This is a disease in which the immune system attacks and destroys beta cells, and is the part that produces insulin, a part of the pancreas, and is the hormone that regulates our blood sugar. Such patients are forced to rely on external sources of insulin. “I really didn't even know what that meant,” recalls Melton. “But we knew right away. My wife was really Sam's pancreas and injecting insulin all her time.”
Two young children, Melton and his wife were overwhelmed. Half the joke, she turned to her husband and suggested that he make herself productive. “She looked at me and said, 'You know, you're a bit useless,'” he recalled. “You should be able to do something. Why not try and tackle this?”
So he did. Melton switched his research to diabetes. His jump wasn't as radical as it looked. The development of tissue and organs contained the same mysteries that fascinated him from the beginning. He began studying how beta cells form in frogs and mice, and eventually reached a new realm of biology: stem cells. These developing cells are precursors that differentiate into all cell types in the body. The idea he hatched with his imagination: collects embryonic stem cells and manipulates them to become cells that produce insulin.
“What I couldn't do would never have happened to me,” Melton said. “I didn't know how to do that.”
The rising global burden
Diabetes is a disorder that does not properly metabolize glucose, our main source of energy, blood sugar level. Glucose is usually regulated by insulin produced by beta cells in clusters of endocrine cells called islets of Langerhan, scattered throughout the pancreas.
In Type 1, it can appear in childhood any time, but the body's own immune system attacks and destroys beta cells. In type 2 diabetes (often presenting later in life and associated with obesity), beta cells become dysfunctional and cannot provide adequate insulin.
38 million
According to the CDC, Americans suffered from diabetes in 2021
More than 38 million Americans, about 11% of the population, suffered from diabetes in 2021, according to the Centers for Disease Control and Prevention. This is the eighth major cause of death in the country.
The burden of diabetes has risen worldwide, particularly in low- and middle-income countries. According to the International Federation of Diabetes, the disease suffers around 589 million adults worldwide, or around 11% of the world's adult population.
For Melton, this global mission has become even more personal. About ten years after her son was diagnosed with Type 1, her daughter Emma (at the time 14) developed the same disease.
Supported through the cutting of the bush era
The breakthrough occurred over 100 years ago with the development of exogenous insulin therapy. This was originally delivered by injection and now by an insulin pump. However, these advances still require external sources of insulin, and are treatments, not treatments.
Melton sought treatment by deciphering the developmental biology of beta cells. What was the developmental stage that transformed stem cells into beta cells that produced insulin? Can scientists replicate these events and design beta cells that could be implanted into patients?
His research was bold, and Harvard was an unusual place where he could do it. He recalled university support in 2001 when President George W. Bush suspended federal funding for research into human stem cells and later restricted federal funding to existing lines of stem cells. The university built a new lab for Melton to ensure that his research remains separate from federally funded work. In 2004, Melton and his colleague David Skaden founded the Harvard Stem Cell Institute, which currently involves more than 350 research faculties.
“I'm proud that Harvard supported me. We created about 300 stem cell lines and sent them free of charge to researchers around the world,” Melton said. “It really helped the whole field grow.”
Copy nature
Over the decades, Melton and his colleagues have made a series of discoveries that lay the basis for new treatments to restore insulin production in type 1 diabetes patients.
Melton compares this stem cell-derived islet therapy to “educate” stem cells and their offspring. This introduces protein signals that trigger or inhibit developmental processes. This method provides 15 signaling proteins at specific times and locations in 6 steps over 30 days to convert stem cells into insulin-producing beta cells. These cells are implanted in patients with type 1 diabetes.
“I'm proud that Harvard supported me. We created about 300 stem cell lines and sent them free of charge to researchers around the world.”
Doug Melton
After demonstrating how to create beta cells in 2014, Melton founded the company Semma Therapeutics (names are the combination of names of two children) to develop commercial applications. In 2019, the company was acquired at the top and is currently conducting clinical trials for Type 1 people. Melton said more than 12 patients have completed the trial and received the new treatment “more than a handful.”
A continuous glucose monitor measures blood glucose levels every 15 minutes, while beta cells do as many as 1,000 times per second. “I've never invented anything,” says Melton. “I'm trying to copy nature.”
The place of science
This is the first time that stem cells have been cultured completely differentiated from stem cells in a lab and subsequently introduced into human clinical trials. Melton says the technique may ultimately be adapted to treat type 2 diabetes. This method also provides insight into how stem cells are used in other treatments, such as creating dopamine-producing brain cells to treat Parkinson's disease.
“Harvard is the kind of place where you have problems that may not be resolved in a year, or five or ten years,” Melton said. “I think that's one of the great things our institutions can do.”
Harvard was also a great place to develop young talent. And then there's what you learn from them, Melton said. The scientist employs around 50 undergraduate, graduate students and postdocs in his lab. He also enjoys teaching classes such as Developmental Biology and “Frontiers in Therapeutics: Science of Health.”
“I like teaching undergraduates because they have fewer biases and preconceptions about what is valuable and how to do it,” Melton said. “It challenges my own ideas about what we are doing. There is an additional motivation to seduce some of the bright young undergraduates for a career in science.”