A conversation with
Gary Yellen, AB ’79, PhD
My research focuses on a remarkably effective, but poorly understood, therapy for epilepsy called the ketogenic diet. It was developed in the 1920s by clinicians at Harvard Medical School and the Mayo Clinic and is basically a high-fat, practically-no-carbohydrate diet, similar to the Atkins diet. Most of the people who use this diet—and for whom none of the medical treatments for epilepsy work—have many fewer seizures.
When you’re on this super-low-sugar diet, your liver breaks down fat, either from your diet or from your body, to produce molecules called ketone bodies, which the brain uses as an alternative fuel. Our hypothesis is that when your brain is on these alternative fuels it is somehow more resistant to epilepsy than when it is on sugar. We’re trying to understand the mechanism behind this.
While these diets can be very effective, nobody likes to be on any sort of a diet. And this diet is really hard. People like sugar, especially children. Compliance with diets is also a big issue clinically and requires intensive management by a dietitian. For example, when children who are on this diet have a candy bar, they immediately lose their seizure resistance. Sugar doesn’t give you seizures, but it prevents you from having this form of seizure resistance.
The more we understand the mechanism behind this diet and seizure resistance, the more likely it is that we can develop new ways to tap into that mechanism and find a pharmacological substitute for this diet. We will also learn some new fundamental biology: why neurons and other cells function differently when they burn different fuels. This has important implications for cancer and neurodegenerative diseases, which all involve major changes in cell metabolism.