Understanding the genes, Schellenberg thinks, may depend on scientists becoming better at defining and measuring the symptoms. "So out of seven or eight genes, maybe two impact language the most. We need a better description of those language problems," Schellenberg says. Iversen agrees, and the AGRE gene bank, along with other groups, is now developing a project to more accurately define and classify the symptoms of the people whose genetic material has been collected.
As the science of autism has grown, so has Iversen's grasp of it. In the beginning, she struggled to understand the complex technical papers she was reading. But she persevered—peppering her psychiatrist sister-in-law with questions, hiring a tutor, spending a week working in a lab, focusing on one discipline after another for months on end. Scientists have come to expect—and welcome—her calls.
Edwin Cook, a longtime autism researcher now at the University of Illinois at Chicago, recalls Iversen asking about a connection between an old finding of his and a newer one published by another group. "She's reading my papers that I've forgotten about," Cook says. Martha Herbert of the Massachusetts General Hospital (MGH) and Harvard Medical School calls Iversen a "creative out-of-the-box scientific thinker who excels at pulling together her own observations of Dov and other children with findings from across scientific disciplines."
During the 1990s, CAN was among the first to fund Herbert's studies. Using MRI scans, Herbert built on an earlier finding by Eric Courchesne at the University of California at San Diego: In 2001, Courchesne found that the brains of autism patients had an excess of white matter (nerve fibers sheathed in a kind of insulating material called myelin). The white-matter enlargement suggested for the first time where to begin looking for the missing connections afflicting children with autism; and in 2004, Herbert found that the enlargement is greatest in the outer regions of the brain. That work builds on an earlier finding by Courchesne that children who develop autism are born with slightly smaller than average heads (and hence, brains), which then grow much more quickly than normal during the first year of life.
Meanwhile, a team in Pennsylvania was taking a different approach to demonstrating connectivity problems in the brain. Nancy Minshew of the University of Pittsburgh and Marcel Just of Carnegie Mellon University compared brain scans of young "high functioning" autistic adults with those of healthy individuals with similar IQs. Examining language processing in the brain, the researchers found that people with autism had much greater activation of a region known as Wernicke's area, which is involved in understanding individual words. In contrast, Broca's area—a region involved in sentence processing—was less active. The autistic subjects were also much less able to synchronize the activity of the two regions. In experiments with other, nonlanguage tasks, the researchers saw a similar degree of impaired connections between different areas.
These findings, along with the work by Herbert, Courchesne and autism researchers in London, have led to the "underconnectivity theory," which suggests that autism could be a result of a reduced ability to coordinate long-distance processing across different regions of the brain. Intuitively, the theory helps explain the behavior of children who are obsessed with details yet unable to integrate those details into a larger whole.
The cause of the abnormalities that Herbert and Courchesne noted isn't known, but new work suggests one possibility. At Johns Hopkins Hospital, neurologist Carlos Pardo and his colleagues, scanning autopsy slides made from the brains of autism patients, noticed an inflammation in the frontal lobe and cerebellum. That could partly explain Courchesne's observation that overgrowth of the brain is not inborn but develops over time. Though the relationship is unproven, Courchesne and others speculate that brain overgrowth is a response to environmental factors that trigger an inflammatory reaction in genetically predisposed children.
That inflammatory process might also offer a target for drugs aimed at slowing down or reversing the disease.
In 2004 the confluence of these distinct strands of research caught the attention of Iversen, who decided again to push the science. She called Herbert at MGH and asked her to co-chair a kind of "white-matter summit." In February 2005, 25 scientists flew to California to spend a weekend reviewing progress and working out the important questions that need to be tackled. Herbert says the process made her "feel like we are acting as a collective scientific enterprise, like we are supposed to," adding, "And the parent groups are crucial."
Shestack and Iversen didn't set out to become part of the scientific establishment, but that is where they've ended up. "We've gone from being yippies to yuppies in 10 years," says Shestack, who still questions whether they'd be more effective on the outside "chained to the balustrade."
Dov is now 13 years old. After more than a decade in which he seemed to make little progress, he has been receiving some new therapy involving rapid prompting and constant stimulation that has helped him begin to communicate through writing. Still, Shestack says, "he has a long road ahead." 
 Dossier
1. Molecular Genetics of Autism Spectrum Disorder, by Jeremy Veenstra-VanderWeele and Edwin Cook, Molecular Psychiatry, Sept. 2004. A well-referenced overview of the search for autism genes.
2. Why the Frontal Cortex in Autism Might Be Talking Only to Itself: Local Over-Connectivity but Long-Distance Disconnection, by Eric Courchesne and Karen Pierce, Current Opinion in Neurobiology, March 2005. A highly readable review that weaves together the strands of research on brain size, structure, function and pathology in autism.
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