When Brenda Gross learned that her 3-year-old son, Dustin, had acute lymphocytic leukemia, she was concerned only about his welfare. When another child living in her small town of Fallon, in Churchill County, Nevada, was diagnosed a short time later with the same disorder, she reached out to help the family.

But when the third child in the county came down with it that year, then the fourth, and a fifth, she grew worried about her entire community. Could something in the environment be causing their children to develop cancer?

The fears held by many of the Churchill County residents are echoed throughout the nation. Urban residents have long feared the paint chipping off their walls, while suburbanites now worry that a summer barbecue may leave them prone to cancer.

"It's natural to be afraid of what we don't understand, but to get hard answers, rigorous scientific research holds the key," said Jonathan Ducore, UC Davis Children's Hospital chief of pediatric hematology/oncology, who treated Dustin as well as other children from the area.

	Environmental epidemiologist Irva Hertz-Picciotto has done extensive research on health outcomes after exposures to pesticides, heavy metals and industrial compounds.

Those hard answers are being sought by scientists at UC Davis, which is at the forefront of environmental epidemiology, a field that has become increasingly prominent as concerns mount about the role the environment plays in health. Singling out a contributor to disease, or even identifying if

disease rates in an area are abnormally high, is tricky. Disease "clusters," like the one in Churchill County, are notoriously difficult to positively identify. When you throw a bunch of chips in the air, they don't fall in an even distribution; some will land in bunches. This is also true of disease incidence — some cases will, by chance, occur more often in one town and less often in others.

Churchill County has now had 15 children diagnosed with the same form of leukemia since 1997. The expected rate is only one child in five years.

"If any place has a true cluster, it's there," said Ducore.

Irva Hertz-Picciotto, UC Davis professor of epidemiology and preventive medicine, is an expert on devising statistical models to tease out what factors contribute to disease. She has done extensive research on health outcomes after exposures to agricultural pesticides, heavy metals such as lead and arsenic, and industrial compounds such as polychlorinated biphenyls (PCBs).

At UC Davis, she is focusing her research on another problem that has alarmed parents and researchers alike because of increasing incidence in recent years — autism. She is leading the Childhood Autism Risks from Genetics and the Environ- ment (CHARGE) Study, the first-ever comprehensive environmental epidemiological study of the disorder.

Up to now, researchers have largely looked to genes to explain why some children develop autism. A complex picture has emerged, however, and it is now believed that a number of different "susceptibil- ity genes" may be involved. While some researchers are pursuing identification of those genes, others are focusing on whether a "second hit," or environmental insult, may be necessary to develop the disorder.

"We know that environmental factors can contribute to autism, because we've seen higher rates when pregnant women had rubella or used thalidomide (a drug that was briefly available to pregnant women and that caused severe limb deformities in newborns)," said Hertz-Picciotto. "So it is worth searching for factors now present in our environment."

"I look at the environment broadly, including everything that is not genetic, such as technologies, medications and even social factors," said Hertz-Picciotto. "So much has changed in recent years, including what we eat, what medications we take, and even what is used to sweeten our beverages."

The case-control CHARGE study is under the auspices of the UC Davis Center for Children's Environmental Health and Disease Prevention, a multi-disciplinary collaborative research organization sponsored by the National Institute of Environmental Health Sciences, the U.S. Environmental Protection Agency and the UC Davis M.I.N.D. Institute.

The study is examining up to 2,000 children between 2 and 5 years of age, including 700 children with autism and no mental retardation, and the rest divided among children with mental retardation but no autism and children who are developing typically.

The three groups are being compared to a broad array of factors, including exposures from chemicals used in industrial processes, medications, vaccinations and consumer products. Clinicians are also obtaining blood and other biological samples to compare levels of toxins as well as immune responses to vaccine antigens.

"Our study is unique in attempting to study all young children with autism in a large geographic area and in looking at many environmental and biologic factors," said Hertz-Picciotto. "We have experts in genetics, metabolism, immunology, molecular biology, epidemiology and developmental pediatrics. This is the first time a group like this has been pulled together to study the causes of autism."

While scientists at UC Davis probe possible connections between environmental exposures and autism, other investigators are asking similar questions about childhood cancers such as the one that struck Dustin.

UC Davis pediatric oncologist Ducore, Dustin's physician, is working with the Northern California Childhood Leukemia Study, run by researchers in the School of Public Health at UC Berkeley. Similar in concept to the CHARGE autism study, it involves conducting in-depth interviews with the families of children with leukemia, as well as with healthy controls. Biological specimens are also taken from the children and their mothers so that DNA can be analyzed, and homes are investigated for the presence of toxic compounds.

The Northern California Leukemia study is not looking into causes in Fallon, Nevada. However, investigators from the Centers for Disease Control are looking in Churchill County, and have found no definitive answers despite an extensive investigation. They did discover high levels of tungsten, an element used to strengthen steel and make light bulb filaments, in the drinking water and in residents' urine samples. However, no one knows whether tungsten can cause cancer, and further study is needed to find out.

Dustin has undergone treatment and is once again a happy, growing boy, but Brenda can't really breathe a sigh of relief until the cause has been found.

At UC Davis, the search for answers continues.

"We live in an increasingly complex world and are exposed to so many different things," said Hertz-Picciotto. "The challenge of environmental epidemiology is to determine which of those myriad factors are benign and which are harmful and need to be eliminated."