Upon learning that Shestack and Iversen planned to start an organization, the Londons invited them to join NAAR's board. But Shestack was impatient with what he considered NAAR's overly cautious commitment to working within the scientific establishment. During lunch one day, Shestack recalls, London told him, "You can't hurry science."
"I work in the movie business," Shestack says. "I know you can hurry anything. You put more guys on the job, you spend more money. You just can't do it for free."
In its first year, CAN raised $400,000 and spent almost all of it on research grants, advocacy, education and outreach. CAN and NAAR now have annual science budgets of more than $6 million and $7 million, respectively. NAAR's early goal was to establish an autism brain bank; CAN focused on genetics. "We couldn't even define autism in those days," recalls London.
NAAR's autism tissue program began the postmortem collection of brains from autism patients and their family members—about 100 have been amassed—so scientists can search for chemical, cellular and anatomical clues about the underlying disease. In contrast, genetics researchers work from blood samples, comparing the genes and chromosomes of patients with those of unaffected siblings and parents.
Despite the strong evidence that autism has a genetic cause, finding the genes involved has proven exceedingly difficult. Studies implicate at least 15 genes and possibly many more, though any individual patient is likely to have just a few of them. To tease apart the intricate clinical picture—a complicated genetic disease possibly triggered by environmental factors—scientists need genetic information from a large number of autistic children, their siblings and their parents. Yet during the mid-1990s, most research groups were working with relatively small amounts of data, and each group jealously guarded its findings. Shestack and Iversen set out to change that.
Their brainchild, the Autism Genetic Resource Exchange (AGRE), would find the families, have blood samples taken and arrange for clinical assessments. But the scientific community was skeptical. The initial reaction was "quite negative," says Daniel Geschwind, a neurologist CAN brought in as an adviser. The chief concern, he says, was whether a parents' organization could carry out the work with the necessary scientific rigor.
Shestack thinks the real objection was the requirement that data be freely shared. AGRE would open its files only to qualified researchers who promised to share the raw data from their analyses, rather than just the summary statistics that usually appear in scientific publications. He tells the story of a meeting at the NIH at which several established autism researchers threatened to withdraw from the field if AGRE went ahead. In response, Shestack says, he reached into his wallet for a photo of Dov. "There are 500,000 of these people," he said, passing the photo around, "and six of you. Which side do you think I should err on?"
Though it's difficult to confirm Shestack's version of the story, the confrontational approach would not be out of character. Says Clara Lajonchere, director of the AGRE program: "He will put people on the spot and might raise his voice to get the point across, but it gets people moving."
While wrangling with scientists, Shestack also lobbied on Capitol Hill for funding, and he proved adept at finding sympathetic legislators. Congress established an autism committee to coordinate research efforts between various branches of the NIH. During a seven-year period, autism spending at the National Institute of Mental Health (NIMH) quadrupled.
During its first year, AGRE enrolled 100 families—a remarkably fast start. In 2002 the NIMH announced $6 million in additional funding to expand the AGRE program, and the database now stands at more than 600 families. Then, in 2003, NAAR launched the Autism Genome Project to bring together large autism gene banks from around the world, including AGRES. The initiative combines data from 1,500 families, and the sharing of raw data has become standard in the field. Yet, despite all that, a complete picture of the genetics of autism has been slow to emerge.
Many scientists doubt that genetic research, by itself, will ever solve the puzzle of autism. "The work so far has mainly been done on autism vs. no autism," says Gerard Schellenberg, a geneticist at the University of Washington. He thinks further progress will depend on more carefully differentiating the disorder's symptoms. Like many researchers in the field, Schellenberg suspects that autism may not be a single, narrowly defined illness but a collection of overlapping symptoms and syndromes. In that case, jumbling together the genes of 1,000 patients with "autism" might actually camouflage important genetic pathways.
|
