Researchers now believe that autism can be caused by genes in combination with environmental triggers. The question is, what are those triggers?
Nancy Duley wants desperately to know why her daughter Kira, happy and healthy in her first year of life, then "slipped away into her own little world" -- the isolation of autism. To that end, when Duley was recently pregnant with her third child, she eagerly gave blood samples to researchers, and kept batches of urine samples in her freezer for them to collect.
"When no doctor can tell you why your child has autism, or how you could avoid it or treat it or cure it, as a parent that is the most horrifying feeling to have -- that there are no answers," Duley, a resident of Fairfield, Calif., said last week.
She was speaking at a press conference at the University of California at Davis announcing $7.5 million in new federal funding, including about $2 million for a groundbreaking study that seeks to track, earlier and more closely than before, potential environmental triggers for autism -- beginning in the womb.
As the ranks of children diagnosed with autism grow, researchers are focusing more on such efforts. They are casting an ever-widening net to try to detect possible environmental factors -- such as chemicals or infections -- that could be interacting with genetic risk factors.
Money is beginning to stream toward researchers who are on that trail, supporting a new wave of studies.
"Environmental research will be a much bigger field going forward," said Dr. Thomas Insel, director of the National Institute of Mental Health. "A lot of parents have been telling us about their concerns; now we're listening very closely."
Until recently, about 90 percent of autism research has focused on genetics, and only perhaps 10 percent on environmental factors, said Dr. Gary Goldstein, chairman of the scientific board of Autism Speaks, a national research and advocacy group. In the coming years, he expects the ratio to be 1 to 1.
Dr. Martha Herbert, a Harvard neuroscientist and Massachusetts General Hospital neurologist, said a few years ago, autism researchers would be marginalized if they talked about environmental factors. But now, "any major article or proposal concerning the causes of autism is coming to be considered incomplete if it doesn't talk about a potential role of environmental factors."
Some say this shift in autism research did not happen sooner because it has been so hard to find obvious targets to track.
"There's been no smoking gun," Insel said. "There's been nothing like tobacco and lung cancer."
For years, many parents have argued that the smoking gun was thimerosal, a mercury-based preservative used in many vaccines. But studies have failed to bear that theory out, and autism rates continue to rise even though thimerosal was removed from most childhood vaccines several years ago.
The dispute over thimerosal long tainted the whole idea of environmental triggers for autism, discouraging scientists from entering the field, some researchers and parents say.
Career-wise, "It has not been safe for scientists to work on this problem" of possible environmental factors in autism, said Mark Blaxill of Cambridge, cofounder of Safe Minds, a parent group. But the rates of autism have reached epidemic proportions, he contends, and clearly, genes cannot account for such rapid change.
Even with broad agreement that the attempt is worthwhile, the challenge of pinpointing environmental triggers remains daunting. Researchers must examine thousands of chemicals in the environment that could be damaging children's brains and creating the social and communication impairments of autism.
Last month, California public health researchers reported early findings that among 29 women who had lived near farmland sprayed with pesticides called organochlorines during the first trimester of pregnancy, eight bore children who developed autism. That was six times the risk of autism in a control group who did not live near sprayed farmland. The researchers cautioned that the findings were highly preliminary, but called for further research into a possible pesticide-autism link.
And toxic chemicals are only one category of possible environmental factors: There may be infections, medical procedures, medications.
"We are starting with such an open field," said Irva Hertz-Picciotto, an environmental epidemiologist at UC Davis, who focuses largely on autism.
One of her current studies is gathering data on a wide array of possible environmental exposures from parents of more than 500 children with autism. It asks hundreds of questions about the mother's pregnancy: Did you have a urinary tract infection? What household products did you use? And it continues with questions encompassing childhood exposures: Were pesticides sprayed near the home? Did you use flea powders on your pets?
It also examines biological specimens: blood drawn from the child as a baby, locks of baby hair, and urine samples, looking for signs of everything from heavy metals to infection.
Hertz-Picciotto and colleagues are also leading the new study whose funding was announced last week with Duley's help.
Markers of Autism Risk in Babies -- Learning Early Signs, or MARBLES, includes the sophisticated analysis of specimens from women even before they give birth, along with cord blood from the baby at birth and the mother's breast milk later on.
Duley, one of its first participants, said she hopes to answer the "burning questions" that torment many parents of children with autism: "Why is this happening? What did I do? Is there anything I could have done to prevent this?"
A huge study underway in Norway aims similarly to follow 100,000 children from the womb through age 6 in search of causes of a broad range of diseases, and its leaders have agreed to collaborate with Columbia University researchers to try to track factors in autism.
The US Centers for Disease Control and Prevention are also gathering biological and environmental data on hundreds of children with autism, and planning to examine hundreds more.
Herbert, the Harvard neuroscientist, argues that environmental exposures might not only help trigger autism, they may also continue to influence an autistic child's health and mental state, creating "striking good hair days and bad hair days." The mechanism may involve the immune system or brain chemistry or the body's metabolism -- or all three.
If continued exposure is part of the problem, she says, perhaps such ongoing effects could be treatable, even reversible.
Goldstein, who is also president of the Kennedy Krieger Institute in Baltimore, recalled wistfully the success of epidemiologists who cracked Reye's Syndrome, a rare brain-swelling disease that killed young children in the wake of benign infections such as chicken pox. Researchers figured out that Reye's was triggered among genetically vulnerable children by that staple of the sickroom: aspirin.
"The proof of the pudding was, take away the aspirin and it's gone," he said. "Wouldn't it be wonderful if we found something like that?"