Applying biomarker research.

Public health and environmental professionals have generally focused on monitoring the ambient environment to assess exposures to the public. To understand exposures and effects and predict onset or course of disease, it is also important to look inside the (human) organism. Biomarkers-measurable internal indicators of changes in organisms at the molecular or cellular level-offer great potential to understand environmentally mediated disease and to improve the process of risk assessment. A valid biomarker could also be considered a key event linking a specific environmental exposure to a health outcome. A molecular biomarkers paradigm has its origins in the National Research Council's (NRC) 1983 "Red Book," Risk Assessment in the Federal Government (1). In 1989, the NRC published monographs on Biologic Markers in Pulmonary Toxicology (2) and Biologic Markers in Reproductive Toxicology (3) in which biomarkers of exposure, effect, and susceptibility were discussed as they may relate to disease. In Figure 1, the exposure-todisease paradigm has been drawn to emphasize the application of biomarkers in assessing dose, mode-of-action, and disease etiology. Biomarkers of susceptibility may influence the magnitude of each sequential element in the pathway. Biomarkers useful for disease prevention and intervention may appear anywhere along the pathway. Earlier markers (to the extent that they are measurable at low exposure or dose) have the greatest potential utility to avert disease; later markers are most closely related to the disease. Over the last decade the biomarker model has resulted in considerable research enterprise and nourished and challenged the emerging field of molecular epidemiology. The National Institute of Environmental Health Sciences (NIEHS) and the U.S. Environmental Protection Agency (U.S. EPA), in both their intramural and extramural research programs, have targeted biomarkers for a greater role in human health risk assessment and have worked for their validation in the field and their extension into the clinical environment. At the same time, much of the biomarker research has remained confined to the laboratory, with the promise of successful applications to improve public health or mitigate disease largely unmet. A biomarker should allow better measurements of exposure or earlier identification of health effects. Biomarkers can provide data needed for assessing progress in improving the Nation's health, such as the Healthy People 2010 objectives (4). In summary, biomarkers may break open the black box between exposure and disease and show what individual factors make a difference. Recognizing their substantial investments in intramural and extramural research on biomarkers, the NIEHS and the U.S. EPA held "Biomarkers: Taking Stock, An EPA/NIEHS In-House Workshop on Applying Biomarker Research" on 30-31 August 1999 in Chapel Hill, North Carolina. Approximately 90 participants explored biomarker research through presentations by invited plenary speakers, posters on individual research projects, and breakout discussion groups. Participants focused on both scientific and organizational objectives. Scientifically, they sought to understand the state of the art and current applications of biomarkers of exposure, effect, and susceptibility; to discern research directions that are likely to make the promise of usable biomarkers a reality; and to explore the role of biomarkers in understanding environmentally-induced disease and in assessing human health risk. Organizational objectives were to increase communication among NIEHS and U.S. EPA staff, including those involved in clinical studies; to complement the ongoing environmental genome research at NIEHS and the planned NIEHS workshops on exposure assessment and environmental epidemiology; and to lay the groundwork for a possible extramural conference on biomarkers in spring 2001.