Human embryonic stem cells have the remarkable capacity to mature into all of the 200 kinds of cells that make up the human body: skin, bone, nerve, blood, heart, and so on. By this very nature, the cells hold great promise for treating devastating diseases like Alzheimer's, Parkinson's, cancer, and diabetes. For more than a decade, Douglas A. Melton has studied how embryonic stem cells give rise to the pancreas and its insulin-producing beta cells, which are destroyed in patients with type 1 diabetes. Ultimately, his studies could lead to ways to generate new pancreatic beta cells that could be used as a treatment for diabetes.
Melton was a well-established scientist studying frog development in 1993 when his infant son was diagnosed with type 1 diabetes. This more severe form of the disease requires that diabetics take daily injections of insulin to survive. Without insulin, the body can't convert glucose into energy. Hoping to find a cure for the millions who suffer from type 1 diabetes, Melton turned his attention to stem cells. "When my son Sam was diagnosed, I did what any parent would do: I asked myself, 'What can I do?'" Melton recalled.
Melton set to work studying pancreatic development in frogs and mice, establishing many of the basic facts about how the pancreas is made in vertebrates. In the late 1990s, when other scientists demonstrated it was possible to grow human embryonic stem cells in the laboratory, he turned his attention to human cells. Using the information gained from studying the normal development of the pancreas, his work has focused on identifying the factors that could transform human embryonic stem cells in the laboratory into pancreatic beta cells that secrete insulin. In addition to the scientific unknowns that made this a challenging project, it soon became clear to Melton that a major limitation was the number and quality of human embryonic stem cell lines that were available.
With this in mind, Melton initiated a collaboration among Harvard University, Boston IVF, and HHMI to develop additional human embryonic stem cell lines. The IVF clinic, one of the nation's largest fertility clinics, has supplied frozen embryos, with the donors' consent, left over from fertility treatments. Due to restrictions on using federal funds to develop new human embryonic stem cell lines, the project is being funded by HHMI. Through this partnership, Melton has developed a number of new human embryonic stem cell lines, which are being distributed free of charge to scientists for further study. The new lines have also enabled Melton to study, in great detail, the various steps in the development of insulin-producing beta cells in humans.
Through ongoing research projects, Melton has identified several hundred genes that are likely to be involved in shaping the properties of stem cells and steering them to develop into specialized cells. He and his Harvard colleagues also have explored a way to turn adult skin cells into human embryonic stem cells by fusing the cells, a method that does not require human embryos in the process. The fusion technique reprograms the genes in the skin cell, essentially converting that cell into an embryonic stem cell. More work remains before the technique has widespread application because the fused cells have two sets of chromosomes, but this approach may provide an alternative method for producing human embryonic stem cells and reduce some of controversy that has surrounded stem cell research.
Melton, whose daughter Emma also was diagnosed with type 1 diabetes, has become a passionate advocate for the embryonic stem cell research, testifying before Congress on several occasions and speaking out in the public arena. "Among the many lessons I've learned is that we, as scientists, should make greater efforts to explain what we are doing and why we are doing it," he said. "For better or worse, this needs to be done in newspapers and on TV, not just in scientific journals."