Academic journal article Environmental Health Perspectives

Signs of the Times: Biomarkers in Perspective

Academic journal article Environmental Health Perspectives

Signs of the Times: Biomarkers in Perspective

Article excerpt

During the last decade, the health sciences have experienced a major shift in orientation. With the rise of genomics and advances in molecular biology, scientists have increasingly moved away from population-based approaches to health toward studies of disease susceptibility among individuals. That change is reflected by the push for personalized medicine, which targets the underlying susceptibilities that make some people prone to particular diseases. It's also reflected by recent goals for personalized exposure assessment in environmental health, and efforts to understand why some people seem particularly vulnerable to the harmful effects of pollution and other environmental toxicants.

The focus on individuals could make public health strategies more effective by allowing practitioners to direct resources toward those with the greatest need. But the success of these efforts will depend largely on the continued identification of biomarkers that reflect the individual's health status and risk at key time points.

Scientists rely on biomarkers to track each phase of the dose-response continuum, from exposure through effect. In a broad sense, biomarkers include physical parameters that can be clearly anchored to a disease or class of diseases. In medicine, they can include measures such as heart rate or serum cholesterol, both of which correlate directly with cardiac disease risk. For environmental health purposes, biomarkers include a range of additional exposure-related indices, such as pollutant measures in tissues and bodily fluids; exposure-induced changes in cells, proteins, DNA, and other molecules; and inherited gene variations that influence how individuals respond to their environments. Single-nucleotide polymorphisms (SNPs), for instance, which are simple inherited gene variations, can increase or lessen disease susceptibility following environmental exposures.

Biomarker investigations are now an integral part of environmental health research. Through its Exposure Biology Program, established in 2006, the NIEHS will commit substantial resources to the search for biomarkers, focusing particularly on those that reflect the human response to environmental agents. Likewise, the EPA Office of Research and Development has committed at least $3 million annually since 2000 to biomarker investigations.

But even as the public health community ramps up its efforts in this area, the search for new biomarkers has been slow and often frustrating. Scientists can propose biomarkers on the basis of animal research or limited studies in humans, but to confirm their relevance to broad human populations, biomarkers must be validated in population-based studies often involving large cohorts, ideally using prospective studies that involve repeated sampling of individuals.

Repeated sampling assures scientists that biomarkers reflect actual disease processes, instead of measurement errors or other incidental variations. Yet prospective studies that incorporate multiple sampling rounds for biomarker validation are time-consuming and expensive, so very few have been conducted, says John Groopman, chairman of the Department of Environmental Health Sciences at the Johns Hopkins Bloomberg School of Public Health. "That really hinders our ability to make intermediate linkages between exposure and disease outcome," he explains. Consequently, biomarkers that reflect the full response spectrum from exposure through effect have been identified for just a few agents, notable among them benzene, aflatoxin [B.sub.1], and UV radiation.

The Basis of the Field

The use of biomarkers in the environmental health sciences arguably dates back to the early 1970s, with Herbert Needleman's groundbreaking work on lead neurotoxicity in children. Now a professor at the University of Pittsburgh Medical Center, Needleman was an assistant professor at Harvard Medical School when he used blood lead as a biomarker to show that even at the lowest detectable levels, lead could impair a child's IQ. …

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