Ricardo Dolmetsch: Regenerating the Cells of Autism

The transformations that take place in Ricardo Dolmetsch's laboratory are, by his own admission, freaky.They begin innocently enough, with a few skin cells in a dish. But when bathed in a precisely mixed potion, those cells grow into little rosettes, which turn into tubes and change again to become miniature brains.It's even stranger when, using a slightly different chemical concoction, he creates heart muscle. "You get these little balls of ventricular and atrial cells, and they beat — and they beat, and they beat," Dolmetsch says. "It feels a little like Edgar Allen Poe."Thanks to these tell-tale hearts, Dolmetsch and his team at Stanford University have identified effective antiarrhythmic drugs for individuals with Timothy syndrome, a rare genetic disorder that causes slow heart rhythms, anxiety and autism.The study, reported in Nature earlier this year¹, was the team's first demonstration of cell reprogramming in individuals with autism.When Dolmetsch first began this line of work a few years ago, "people thought it was very far out," he says. "But we're now convinced this is a very viable approach to studying autism."Dolmetsch speaks as though his lips are trying furiously to keep up with the ideas flipping through his mind. It would be easy to blame his diction on his South American upbringing, except that he seems to move through life at the same rapid clip. He worked as a waiter, a technician in an animal care facility, a photographer and a computer programmer for the World Health Organization, all before he turned 20. He then became a successful scientist, with a streak of high-profile publications. Five years ago, after his son received an autism diagnosis, he turned his attention to the disorder.So far, Dolmetsch, 40, has made reprogrammed cells — so-called induced pluripotent stem (iPS) cells — not only from people with Timothy syndrome, but from those with Phelan-McDermid syndrome, an autism-related disorder that is caused by a deletion on chromosome 22, and schizophrenia. His team is also working on a mouse model of Timothy syndrome and a much-talked about mouse carrying autism-linked deletions on chromosome 16.Dolmetsch has his fingers in many pots, and freely admits that he is "slightly obsessive." When he's curious about a scientific topic, he delves into the scientific literature and learns as much about it as he can. He only sleeps a few hours a night, he says, and rises around 4 a.m. for his daily run.Read more at...SFARI, June 2011.