Genomics and Environmental Regulation: Science, Ethics, and Law

Introduction: Environmental Policy in the Age of Genomics

Introduction Environmental Policy in the Age of Genomics RICHARD R. SHARP, GARY E. MARCHANT, AND JAMIE A. GRODSKY For decades, scientists have recognized that individuals can differ significantly in their susceptibility to environmental toxicants. Using information and tools produced by recent genomic initiatives such as the Human Genome Project, risk assessors may soon be able to conduct far more systematic investigations of individual susceptibilities to toxic substances, potentially transforming environmental risk assessment. Whereas in the past risk assessment was limited to characterizing risks for large, biologically heterogeneous groups, applications of genomics hold the promise of understanding biological features of discrete subpopulations and perhaps even of opening the door to a new era of personalized risk assessment. Although genomics has the potential to make environmental regulation more accurate and precise, its application in regulatory contexts requires that a number of daunting technical and scientific challenges first be overcome. Regulatory applications of genomics will also raise difficult ethical, legal, and policy issues. This book aims to elucidate some of these challenges and to foster ongoing analysis of the scientific, ethical, legal, social, and policy issues raised by the application of genomic technologies to environmental regulation (which we view broadly to include hazard identification, risk assessment, risk management, risk communication , and rule making). Emphasis is placed on the emerging field of toxicogenomics, defined as the application of genomic technologies to the identification and understanding of human and environmental toxicants (Marchant, 2003a). If genomic technologies are to be integrated successfully into ongoing risk-assessment and risk-management efforts, the broader social impact of these applications must be carefully examined and thoughtfully addressed. Genomics and Environmental Regulation By reducing some of the many uncertainties that currently impede risk assessment, genomic data have the potential to greatly improve the precision and effectiveness of environmental regulation (Henry et al., 2002). At the same time, the application of genomic data within the existing matrix of environmental statutes and regulations will raise fundamental issues regarding the validity, reliability, and biological significance of these new data (Bergeson, Campbell, and Bozof, 2002; Marchant, 2003b; Grodsky, 2005). To encourage discussion of these issues, the U.S. Environmental Protection Agency (EPA) has developed an Interim Policy on Genomics (U.S. Environmental Protection Agency [EPA], 2002). This policy conveys the agency’s enthusiasm for the potential use of genomic data for risk assessment and regulatory decisions. For example, the interim policy states that genomic data can be helpful in exploring “the possible link between exposure , mechanism(s) of action, and adverse effects” of potentially toxic substances and “in setting priorities, in ranking of chemicals for further testing, and in supporting possible regulatory actions.” At the same time, the interim policy adopts a cautionary approach with respect to regulatory applications of genomic data, given the many uncertainties that currently exist. The agency notes that at present, such data alone are insuf ficient for regulatory decision making and that the agency “will consider genomics information on a case-by-case basis” (EPA, 2002). One of the most important regulatory applications of genomics, particularly gene expression data, will be in providing more sensitive measurements of adverse effects of exposure to pollutants and other haz2 I N T R O D U C T I O N ardous substances. Many existing regulatory requirements are triggered by the lowest detectable “adverse effect.” For example, the Clean Air Act allows national ambient air quality standards to be set at a level that will avoid adverse effects in sensitive populations. Regulatory standards to be set for many noncarcinogens are based on their reference concentrations or reference doses, which are derived by applying a series of uncertainty factors to what is known as the “no observed adverse effect level” or lowest observed adverse effect level. Similar reporting requirements under statutes such as the Toxic Substances Control Act and the Federal Insecticide, Fungicide and Rodenticide Act also require product manufacturers to report to EPA new findings on adverse effects. A critical question to be resolved is when, if ever, systemic changes in gene expression should be considered an adverse effect under these and other regulatory programs (Grodsky, 2005; Kramer, Cullen, and Faustman , 2006). There are existing regulatory precedents in which subclinical molecular changes have been viewed as adverse effects. For example, molecular changes in erythrocytein levels in response to lead exposure were classified as an adverse effect under the Clean Air Act (Lead...