Developmental Biology, Neuroscience
Dr. Eggan is also a professor of stem cell and regenerative biology at Harvard University.
The first meeting between Kevin Eggan and the man who would become his mentor unfolded like a scene from “The Godfather.” In 2001, Eggan was approaching the end of his doctoral thesis at the Massachusetts Institute of Technology when a lab mate delivered a mysterious message: “I have a friend in Doug’s lab who tells me that Doug wants to meet you.”
Doug Melton, codirector of the Harvard Stem Cell Institute and an HHMI investigator, could aptly be called a benevolent godfather of stem cell research, both for his advocacy for stem cell research and for his mentoring of young researchers. Melton had pegged Eggan as a rising star for his doctoral research on the genetic problems that arise when mice are cloned.
During their conversations, the two came up with an idea that would become a major career focus for Eggan: What if you could reprogram a sick patient’s cells to become embryonic stem (ES) cells, the do-it-all cells found in embryos that can differentiate into any cell type in the body? Such a feat would not only give Eggan an infinite supply of cells to study in the lab, but those cells would possess the built-in genetic underpinnings of disease.
“I really believed that we could help many people by doing this. It seemed like such a fundamentally simple idea that it just had to be true,” says Eggan. He went to straight to work trying to generate “disease-specific” ES cells for from patients suffering from amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disorder caused by the degeneration of motor neurons, the nerve cells that control the movement of voluntary muscles.
“We don’t know much about why we get sick, because it’s really hard to study disease in people,” says Eggan, now at Harvard University. For researchers studying ALS and other diseases, a supply of the relevant cells—in the case of ALS, neurons—is essential for experiments. But collecting enough cells from patients is tricky. “People are pretty loathe to part with parts of themselves,” Eggan says.
For Eggan, there is an even more compelling reason to pursue disease-specific stem cells, one that keeps him awake some nights. In a small fraction of patients, ALS is passed from parent to child via an inherited mutation. In his early days at Harvard, Eggan had been studying the disease in an animal model that incorporates this rare mutation.
“I was concerned that I spent 99 percent of my time studying the two percent of ALS cases caused by inherited mutations, and that those might not tell us anything useful about the other 98 percent of ALS patients,” he says. “In most cases, we don’t know what the genes are, but each patient has some genetic variation that comes together in some kind of devious collaboration with their environment.”
Wouldn’t it make more sense, he reasoned, to study each patient’s genetically predisposed cells in the lab dish and “watch” as the cells become sick to uncover the mechanisms that are at play?
“It’s pretty exciting to make motor neurons and ask, is there something that makes these more likely to get sick?” he says.
In fact, Eggan’s group has now successfully derived motor neurons from the skin cells of ALS patients with sporadic instances of the disease. The researchers take a small patch of skin cells, genetically reprogram them to become ES cells, and guide those ES cells to become spinal motor neurons. These can then be compared to motor neurons generated the same way from healthy patients.
Although Eggan works in a politically controversial research area, he is undaunted. An increased wariness of crank calls did, however, cause him to refuse one of the most important phone calls of his career—from the MacArthur Foundation board, telling him he’d won the so-called “genius grant.” Luckily, they called back.
“It was a wonderful and slightly terrifying moment,” he recalls. He says the distinction, like the HHMI Early Career Scientist award, carries the expectation that what you do as a young scientist will have an impact on the world. “Nothing makes you want to work harder than being recognized for your potential.”