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Disease study's focus on habitat

Chicago Tribune - 8/4

When Dr. John Snow removed the pump handle from a town well in London in 1848, he wanted to prove two things: Water from the contaminated well was spreading cholera, and forcing people to drink clean water would stop the deadly epidemic.

He was right on both counts.

Today medical scientists stumped by more modern epidemics--including asthma, autism, retardation, attention deficit hyperactivity disorder, diabetes, childhood cancer, depression and schizophrenia--are turning again to Snow's tactics.

Researchers are planning what could become the largest, most intense and costliest study ever undertaken to find out if many, and possibly most, diseases are linked to environmental exposures that occur as early as conception and continue during fetal development and early childhood.

They are launching a massive search of children's neighborhoods for what might be causing the alarming increases in these health problems.

Expected to get under way in 2005 or 2006, the study will cost an estimated $3 billion, the approximate price tag of the Human Genome Project, the ambitious effort to decipher all human genes.

Drawing on the latest advances in genetic science, researchers will attempt to draw connections among infants' genes, environmental exposures and subsequent diseases. The goal is to develop ways to better prevent and treat the ailments.

"A big study like this provides an opportunity to study all of the determinants of these kinds of problems, from the lead paint in your house to the water quality to the social structure of your family, your neighborhood, your diet, poverty, all of those things that contribute to health in the population," said Gwen Collman, scientific program director of the National Institute of Environmental Health Sciences.

"If you conduct a well-designed longitudinal study, you can weigh all of those factors and look at the complex interactions between them," she said.

Called the National Children's Study, the research will involve 100,000 children and their families as well as the resources of NIEHS, the National Institute of Child Health and Human Development, the Environmental Protection Agency and the Centers for Disease Control and Prevention.

The study will include women before they conceive in order to study environmental conditions that may have an impact on conception. Environmental influences will be monitored throughout pregnancy and during the first 21 years of each child's life.

"We now have probes that will help us characterize the genetic factors of disease, and we can measure environmental exposures and body concentrations of a broad range of chemicals," said Dr. Donald Mattison of the National Institute of Child Health and Human Development.

"We're getting better at characterizing stress, and we're getting a better understanding of what the impact of a family structure is on growth and development," he said. "We now have some beginning understanding of the way that these exposures might be linked to health outcomes later in life."

How genes and the environment can combine to cause a common disease was recently reported by University of Wisconsin scientists. They found that people who inherit two copies of the short version of a gene that regulates serotonin, an important neurotransmitter involved in mood control, are 2 1/2 times more likely to become depressed under typical life stresses than people who inherit the long version.

Fragility of fetal development

Scientists know that fetal development is a time of extreme vulnerability to outside influences. A single cell multiplies into a baby with 100 billion cells in nine months as genes issue trillions of instructions in response to chemical messages cells send and receive.

When wrong messages are sent, it can have disastrous effects on the forming nervous system and body, such as when excessive alcohol consumption by pregnant women results in fetal alcohol syndrome.

"There is growing evidence suggesting that adult diseases or the risk factors for adult diseases are influenced substantially by fetal well-being," Mattison said.

Infancy is another critical period, especially for the rapidly developing brain, which can be stunted by even modest amounts of lead poisoning, a continuing threat to 1 million American children.

Even childhood infections can set the stage for adult diseases. Eighty-five percent of peptic ulcers in adults, for instance, are caused by a childhood infection with H. pylori bacteria, which may smolder for decades as a symptomless infection of the stomach lining.

Now scientists will study other childhood infections to see if they are linked to adult heart disease, cancer and diabetes.

They also will look for the ways in which genetic susceptibilities and environmental triggers interact to result in disease. Obesity and lack of exercise, for example, are major risk factors for type 2 diabetes, which is reaching epidemic proportions in children. Yet it is clear that there is a strong genetic susceptibility for the disease, since only 15 to 30 percent of obese people become diabetic.

The University of Chicago's Graeme Bell is searching for the genes that predispose people to diabetes, hoping the information could help develop strategies to prevent the disease in those at risk.

"We will be able to tell one individual with certain genetic risk factors for diabetes that he should avoid a high-fat diet and another, who has a different genetic risk, that he should exercise a little more," Bell said.

Even normal genes can cause problems when they are exposed to bad environments. Radiation and some toxic chemicals can damage genes to cause cancer, for example.

Scientists have discovered about 200 of these kinds of genes, called environmentally responsive genes, which increase the risk of such chronic conditions as cancer, heart disease, diabetes and asthma.

Exposure to chemicals

Among the other factors the researchers will consider is the effect of chemicals in the environment, such as whether herbicides may be implicated in Parkinson's and Alzheimer's diseases.

"Children have greater exposure, pound for pound, than adults to environmental toxins because of their metabolism, their hand-to-mouth behavior and the fact that they often play close to the ground," said Philip Lee, consulting professor in the Program in Human Biology at Stanford University.

Since the 1950s the number of chemicals people may come in contact with has increased dramatically. The EPA estimates that 10,000 to 15,000 chemicals are in general use for making various products or as part of manufacturing processes. So far 1,500 have been withdrawn from use because of potential harmful effects.

The latest CDC study on human exposure to environmental chemicals found that a random sample of Americans had traces of 116 chemicals in their urine. The EPA reports that 8 percent of women of childbearing age have levels of mercury in their blood that could stunt a fetus' brain development.

There is no question that chemistry has improved life, but the downside to the chemical revolution is that the majority of chemicals have not been adequately tested for toxic effects, said Dr. Philip Landrigan, head of community and preventive medicine at the Mt. Sinai School of Medicine in New York.

"One of the things that people like me worry about is the notion that kids are being exposed today to toxic chemicals whose effects we haven't yet been smart enough to recognize," he said. "And we always wonder if there are various nasty surprises lurking out there because we've really been careless about testing these chemicals."

In a study reported in May in the journal Environmental Health Perspectives, Landrigan and his colleagues estimated that just four diseases linked to environmental exposures--lead poisoning, asthma, childhood cancer and learning disabilities--cost Americans $54.9 billion annually.

The costs include direct medical care and lost income from death or such disabilities as the lowered IQ potential caused by lead toxicity to the central nervous system.

Lead poisoning accounts for $43 billion of the annual loss because the link between environmental exposure to the heavy metal and brain damage is clear, Landrigan said. Environmental causes of the other diseases are based on preliminary findings, but for asthma there is already a strong link with outdoor and indoor air pollution, he said.

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