Looking Deep, Deep Into Your Genes

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But first, a more fundamental question: Do we even understand what today's chronic diseases are? It is beginning to appear that what we call autism may in fact be many illnesses that we've lumped together because those who are afflicted seem to behave similarly. Doctors base their diagnosis on behavioral symptoms, not on what caused those symptoms. Some scientists now refer to the condition as "autisms," acknowledging that we've yet to find a single, unifying biological mechanism, despite the identification, in some studies, of a handful of genes that may confer increased vulnerability. But then, genes or environmental exposures that appear to be important causal factors in one study may not show up at all in another. This leaves scientists to wonder whether the problem isn't that the disease is so diverse in its biological origins that only a truly massive study -- involving many thousands of patients -- would have the statistical power to tease apart the various factors involved.

The same difficulty probably holds true for many chronic diseases, explains Linda Greer, a toxicologist and director of the health program at NRDC. "What we think of as asthma, for example, is probably not one condition at all. It's probably many different diseases that today we simply call asthma." Seemingly contradictory explanations for the epidemic could all turn out to be true. Until we are able to sift out what makes one asthmatic child different from the next -- how and why their respective molecular makeups differ -- treatments or preventive measures that work for one child will continue to fail for another.

At the Centers for Disease Control and Prevention, Muin Khoury, the director of the National Office of Public Health Genomics, has created theoretical models to try to figure out just how many different factors may be involved in most chronic diseases. His findings suggest that some combination of 10 to 20 genes plus a similar number of environmental influences could explain most of the complex chronic diseases that plague the population. But to analyze how even a dozen genes interact with a dozen environmental exposures across large populations requires vast studies: immense numbers of people and huge volumes of data -- everything from precise measurements of gene activity inside cells to exact recordkeeping of subject'' exposure to environmental hazards. Microarrays and other molecular tools now make such studies possible.

In 2003, Columbia University and the Norwegian government together launched the Autism Birth Cohort, one of the largest autism investigations in history. The study will track 100,000 Norwegian mothers and children -- from before birth through age 18 -- collecting clinical data, blood, urine, and other biological materials. It will also collect RNA in order to analyze gene activity. Though initial results are due in 2011, it will take decades to complete this study, and RNA samples will have to be painstakingly archived while the investigators await additional funding. Although the current study is not focused on environmental health per se, researchers plan to measure a variety of biological exposures -- including infection, environmental toxins, and dietary deficiencies -- in each mother and child. As the children grow up, and as some among them develop disease, scientists will have complete records to analyze for key commonalities and differences. Which genes do the sick children have in common? Which chemical exposures were most meaningful? The answers may provide clues not only to the origins of autism, but to many other disorders, from cerebral palsy to asthma to diabetes. Other archiving projects are even more ambitious, such as the U.K. Biobank project, which has begun to enroll 500,000 people to create the world's largest resource for studying the role of the environment and genetics in health and disease.

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