Douglas Wallace watched with anticipation as a mouse navigated chambers in a habitat in his lab in Philadelphia, Pennsylvania. For the most part, it was a typical lab mouse: a few months old, with plain black fur. But deep within its cells, it carried a single change in the DNA that runs its mitochondria, the organelles that generate the body’s energy.
Wallace, a mitochondrial geneticist at Children’s Hospital of Philadelphia, had previously discovered that a similar change could cause an eye disease in people. But no one knew whether the mutation could affect behavior and contribute to autism. To find out, Wallace had spent decades developing the mouse now on the table in front of him. He was about to have his answer. “It’s a very simple question,” Wallace says. “And it only took 30 years to get there.”
Wallace — whose son has autism — is perhaps the most passionate member of a growing group of researchers committed to the idea that mitochondria are an overlooked factor in autism and related conditions such as fragile X syndrome. These researchers, some of whom have adopted monikers such as ‘mitomaniac’ and — Wallace’s term — ‘mitochondriac,’ subscribe to a simple, if fundamental, idea: Mitochondria generate energy, and the brain uses a lot of it — about 20 percent, by most estimates. So it makes sense that changes in mitochondria could lead to changes in the way the brain functions or develops and, in at least some cases, to autism.
Mitomaniacs still represent a small minority of autism researchers. Studies of mitochondria’s role in autism or autism-related conditions represent just 0.4 percent of all papers in that field, according to a Web of Science search of titles and abstracts.