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.
As vital to our understanding of human disease as such studies may prove to be, a 50-year-old taking part in the U.K. Biobank project isn't likely to reap the rewards. "It will take a long time to make sense of the data," says Paul Nurse, a 2001 Nobel laureate in medicine and the president of Rockefeller University. According to Nurse, it may well be that most of the researchers starting these studies today won’t see the final results -- the data will be analyzed by their children. In his estimation, that's all the more reason "to get on with it."
In response to concern that environmental exposures were affecting children's health, the Clinton administration in 2000 launched the National Children's Study, the largest such undertaking in the United States, under the auspices of the National Institutes of Health. The goal was to enroll 100,000 children; a genetic biobanking component has since been added. Investigators have not yet recruited participants, in part because of financial uncertainties. The Bush administration's 2007 budget proposal completely eliminated money for the study, though Congress reinstated funding in February.
The irony is that cutting funding for such projects may be the most expensive option of all. Even if we successfully address campaign-dominating political issues like skyrocketing medical costs and the growing ranks of the uninsured, our failure to consider the fundamental mechanisms of disease -- the interplay between our genes and the environment -- could still bankrupt us, socially if not financially. Until we're able to interrupt the slide toward disease much earlier, based on our developing knowledge of how genes and the environment interact, medicine will remain the practice of "putting people back together after they've been hit by the train," says Wayne Matson, a colleague of Martha Herbert's who studies Huntington's and other neurodegenerative diseases at the Edith Nourse Rogers Memorial Veterans Hospital in Bedford, Massachusetts. "It would be a lot better if we knew how to pull that person off the tracks in the first place."
