UC Davis researchers have launched several major new studies to unlock the mysteries surrounding autism.

They hope to answer a fundamental question: Do environmental factors combine with genetics to cause the disorder?

The research, expected to break ground in an area where little is known, will take place over the next few years.

Next month, investigators from the UC Davis Center for Children's Environmental Health will begin enrolling 2,000 California children in the study.

They plan to include 700 autistic children, 700 who have mental retardation or developmental delay but not autism, and 600 who have developed normally.

Researchers will then analyze blood, urine and hair samples from the children and their family members to search for the presence of toxic substances.

They will compile comprehensive histories on the mother and child, looking at exposure to everything from vaccines containing a mercury preservative to pesticides, PCBs and chemicals used in industrial processes.

The work will be much like fitting together the pieces of a giant jigsaw puzzle without knowing what the final picture looks like. Investigators will search for patterns of differences between the children with developmental problems and those without.

"We're casting a really wide net and that's because we really don't know a lot about autism," said Irva Hertz-Picciotto, a UC Davis professor of epidemiology and preventive medicine who oversees one of the studies.

"This is really the first big, comprehensive effort to enroll a lot of children and look at a combination of environmental and genetic factors," she added. "It's likely that both play a role."

Autism, a severe developmental disorder that undermines a child's ability to connect with the world, has no known cause and no cure.

Autistic children often have difficulty making eye contact and carrying on a conversation. Many engage in ritualistic behavior such as hand-flapping and obsessively following routines.

The search for answers takes on added urgency because of a recent explosion in the numbers of autistic children in the United States, England, Scotland and elsewhere.

While some experts believe the increase is a result of better diagnosis, others note that a recent study by UC Davis researchers concluded that it appears to be a real phenomenon.

Scientists now believe as many as five to 15 genes play a role in causing autism, said Isaac Pessah, a UC Davis professor of pharmacology and toxicology who directs the center.

But Pessah and other experts wonder if an unknown environmental factor pushes genetically vulnerable children over the edge into autism.

"We know that genes by themselves don't cause epidemics," said Rick Rollens, the father of an autistic boy. "There must be something else going on."

A couple of years ago, Rollens joined other parents of autistic children in urging Kenneth Olden, director of the National Institute of Environmental Health Sciences, to establish several autism research centers around the country.

"Really for the first time, autism research has been expanded to include new disciplines and new ideas about possible causes of autism," Rollens said.

UC Davis officials succeeded in obtaining grant money to open the center in late 2001.

With an annual budget of $1.6 million, it receives funding from the National Institute of Environmental Health Sciences, the Environmental Protection Agency and UC Davis' Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute.

Investigators at the M.I.N.D. Institute, who do research on autism, collaborate closely with those at the center. Together, the two institutions place the Davis campus at the forefront of those seeking to unravel the disorder.

Hertz-Picciotto's study will focus on children between the ages of 2 and 5 living in Solano County, the Central Valley, Sacramento and Napa areas, and Los Angeles.

Researchers selected these areas to include children likely to be exposed to pesticides and other chemicals found in agricultural regions, as well as those from urban centers.

"We want a real dichotomy of environmental exposures," Pessah said.

The autistic children will be recruited from those who receive services through the state Department of Developmental Services regional centers.

The normally developing children will be selected at random from state birth certificate files.

Hertz-Picciotto hopes to have some preliminary results within two years. But the study has funding for five years and could last much longer.

After obtaining blood samples, researchers will analyze if the immune systems of autistic children function differently than those of other children. They will look at cell-to-cell communication and metabolism.

Other researchers at the center have begun to tackle one of the most controversial theories surrounding autism: Could it be triggered by thimerosal, a mercury-containing preservative in several vaccines until the U.S. Food and Drug Administration asked manufacturers to voluntarily phase it out in 1999?

Vaccine manufacturers insist thimerosal is safe. But it has spawned class-action lawsuits in California and at least 10 other states by scores of parents who blame the preservative for their child's slide into autism.

To find answers, center investigators have begun to ask if thimerosal influences social behavior in mice. The question is significant because social behavior is a key criteria for diagnosing autistic children.

Center researchers have injected mice with thimerosal at about the same rate that children received it as part of their routine vaccination schedule, with an adjustment to account for the smaller size of the mouse. Researchers then analyze if the behavior of the mice changes.

Most mice like to huddle with their mother and littermates after they're born and will emit ultrasonic cries of distress if separated from the group, Pessah said. Researchers hope to discover if mice who have received thimerosal no longer want to huddle with others, echoing the isolation exhibited by autistic children.

Center officials hope to release some findings on thimerosal early next year, Pessah said.

Parents around the world eagerly await answers on autism.

"We think it's not going to be one single factor that's going to turn out to explain it all," Hertz-Picciotto said. "It may be a combination of things. We're really at the very beginning of understanding this complicated disorder."