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Guest Editorial Gould E. 2009. Childhood lead poisoning: conservative estimates of the social and economic benefits of lead hazard control. Environ Health Perspect 117:11621167. Gump BB, Stewart P, Reihman J, Lonky E, Darvill T, Parsons PJ, et al. 2008. Low-level prenatal and postnatal blood lead exposure and adrenocortical responses to acute stress in children. Environ Health Perspect 116:249255. Hu H, Shih R, Rothenberg S, Schwartz BS. 2007. The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect 115:455462. Jackson LP. 2009a. Testimony of Lisa P. Jackson, Administrator, U.S. Environmental Protection Agency (EPA), Hearing on Scientic Integrity before the Environment and Public Works Committee, U.S. Senate. Available: http://epw.senate.gov/public/index.cfm?FuseAction=Files. View&FileStore_id=0cf4a4fd-d31c-4348-a713-2e1640b82060 [accessed 8 July 2009]. Jackson LP. 2009b. Memo to EPA Employees. Scientific Integrity: Our Compass for Environmental Protection. Available: http://www.epa.gov/administrator/scientificmemo.html [accessed 8 July 2009]. Jackson LP. 2009c. Administrator Lisa P. Jackson, Remarks to the Children's Health Protection Advisory Committee, As Prepared. Available: http://yosemite.epa.gov/opa/admpress.nsf/ dff15a5d01abdfb1852573590040b7f7/8ab7ca2f78ebcbec85257590006f2561!OpenDocument [accessed 8 July 2009]. Jacobs DE, Clickner RP, Zhou JY, Viet SM, Marker DA, Rogers JW, et al. 2002. The prevalence of lead-based paint hazards in U.S. housing. Environ Health Perspect 110:A599A606. Lin C, Kim R, Tsaih SW, Sparrow D, Hu H. 2004. Determinants of bone and blood lead levels among minorities living in the Boston area. Environ Health Perspect 112:11471151. National Research Council. 2007. Evaluating Research Efficiency in the U.S. Environmental Protection Agency. Washington DC:National Academies Press. Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ. 2007. Lead exposure and cardio vascular disease--a systematic review. Environ Health Perspect 115:472482. Nriagu J, Burt B, Lindar A, Ismail A, Sohn W. 2006. Lead levels in blood and saliva in a lowincome population of Detroit, Michigan. Int J Hyg Environ Health 209(2):109121. Peters JL, Kubzansky L, McNeely E, Schwartz J, Spiro A III, Sparrow D, et al. 2007. Stress as a potential modifier of the impact of lead levels on blood pressure: the Normative Aging Study. Environ Health Perspect 115:11541159. President's Task Force on Environmental Health Risks and Safety Risks to Children. 2000. Eliminating Childhood Lead Poisoning: A Federal Strategy Targeting Lead Paint Hazards (Report and Appendix). Washington, DC:U.S. Department of Housing and Urban Development and U.S. Environmental Protection Agency. Sargent JD, Bailey A, Simon P, Blake M, Dalton MA. 1997. Census tract analysis of lead exposure in Rhode Island children. Environ Res 74:159168. Shih RA, Hu H, Weisskopf MG, Schwartz BS. 2007. Cumulative led dose and congnitive function in adults: a review of studies that measured both blood lead and bone lead. Environ Health Perspect 115:483492. Taha T, Kanarek MS, Schultz BD, Murphy A. 1999. Low-cost household paint abatement to reduce children's blood lead levels. Environ Res 81:334338. U.S. EPA (U.S. Environmental Protection Agency). 2007. Framework for Assessing the Public Health Impacts of Risk Management Decisions. Available: http://www.epa.gov/hhrp/files/ hhrp-framework.pdf [accessed 8 July 2009]. U.S. EPA (U.S. Environmental Protection Agency). 2008a. Regulatory Impact Analysis of the Proposed Revisions to the National Ambient Air Quality Standards for Lead. Available: http:// www.epa.gov/ttn/ecas/regdata/RIAs/finalpbria.pdf [accessed 8 July 2009]. U.S. EPA (U.S. Environmental Protection Agency). 2008b. U.S. EPA's 2008 Report on the Environment (Final Report). EPA/600/R-07/045F. Washington, DC:U.S. Environmental Protection Agency. U.S. EPA (U.S. Environmental Protection Agency). 2008c. Economic Analysis for the TSCA Lead Renovation, Repair, and Painting Program. Final rule for target housing and child-occupied facilities. OPPT-2005-0049-0916. Available: EPA-HQ-OPPT-2005-0049-0916 [accessed 8 July 2009]. Andrew Geller is the assistant laboratory director for human health at the U.S. EPA's National Health and Environmental Effects Research Laboratory (NHEERL). He has also worked in NHEERL's Neurotoxicology Division, where he conducted research on the effects of environmental toxicants on the visual system and co-led the development of the U.S. EPA's Aging Initiative, and in U.S. EPA's Region 5 Office of Enforcement Compliance and Assurance. Building Exposure Biology Centers to Put the E into "G E" Interaction Studies doi:10.1289/ehp.12812 Adverse geneenvironment interactions (G E) probably influence most chronic diseases, including neurologic disorders and cancer. The genetic (G) contribution to different diseases varies, but several lines of evidence clearly show that nongenetic factors have high attribut able risks, often in the range of 8090% (Willett 2002). The domi nance of nongenetic components highlights the importance of the environment (E) to chronic disease risks. Genomic tools arising from the Human Genome Project (HGP), combined with bioinformatics studies, have allowed epidemiologists to examine the genetic component of chronic diseases. Genome-wide association studies offer glimpses of the roles that particular genes play in disease development. However, the genetic factors identified thus far have generally been of low penetrance (a few percent at most) and have mainly offered clues as to which G E (and G G) effects might be worth pursuing. In contrast, the tools for quantitative assessment of exposures-- based on measurements of chemicals in air, water, food, and the human body--have changed little since the 1970s. The lack of high-throughput methods of exposure assessment has motivated epidemiologists to rely upon self-reported data to categorize chemical exposures from envi ronmental, endog enous, and dietary sources. With the Martyn T. Smith Stephen M. Rappaport possible exceptions of smoking and alcohol consumption, such self-reports have been unreliable predictors of long-term exposure lev els and are poorly suited for detecting G E effects. Although 30 years of investment in G now illuminates genetic determinants of diseases, we are still in the dark ages when it comes to quantifying E (i.e., human exposures). Recognizing the disparity in current knowledge between genes and environmental exposures, Wild (2005) defined the "exposome," representing all environmental expo sures (including those from diet, lifestyle, and endogenous sources) from conception onward, as a quantity of critical interest to disease etiology. If we expect to have any success at identifying the effects of E, G, and G E on chronic diseases, we must develop 21st-century tools to measure exposure levels in human populations. That is, we need an HGP-like commitment to quantify the exposome. A 334 volume 117 | number 8 | August 2009 Environmental Health Perspectives Guest Editorial Elaborating the exposome will be challenging, but some promis ing analytical approaches are emerging from microfluidics, nano technologies, and mass spectrometry (MS). For example, a capillary lab-on-a-chip system has been developed to detect polycyclic aro matic hydrocarbons at parts-per-billion levels on the surface of Mars (Stockton et al. 2009), and surface enhanced Raman spectroscopy using silver nanoparticles has detected (and speciated) arsenic at parts-per-billion levels in water samples (Mulvihill et al. 2008). Both of these devices are portable, capable of high throughput, and can be adapted to other contaminants of interest. Technologic developments with liquid chromatography/tandem MS (LC-MS/MS) now motivate ultrasensitive measurements of pro tein adducts; these are excellent long-term biomarkers of exposure and internal dose for carcinogens (Rubino et al. 2009). Indeed, with National Institutes of Health Genes and Environment Initiative fund ing, we are using protein adductomics to profile human exposures in archived serum from cancer casecontrol studies. We ultimately envision an analytical platform to rapidly quantify protein adducts in much the same way that the DNA sequencer made possible the success of the HGP. Given the relentless improvements in MS sensi tivity, it is realistic to expect that this technology will be applied with a single drop of blood. In fact, our recent measurem ent of a benzenerelated adduct in dried blood spots opens the door to measurements of in utero chemical exposures, using archived neonatal blood spots (Funk et al. 2008). Simple and inexpensive monitoring methods can motivate reduc tions in exposures to toxic chemicals, as has been observed with inor ganic lead (Pirkle et al. 2005). Indeed, given people's concerns about elevated levels of xenobiotic chemicals in their bodies, commercial markets could ultimately develop for exposure sensors. However, without a regulatory mandate, we cannot rely upon the free mar ket alone to generate an exposure-sensing industry. We must focus instead upon the profound shortcomings that epidemiologists face in discovering environmental causes of chronic diseases without adequate exposure data. Facing a similar dilemma three decades ago, the HGP created several DNA sequencing centers to rapidly sequence the genome, and thereby created an infrastructure from which we still benefit. Imagine if we could build six or seven exposure biol ogy centers to quantify chemical exposures rapidly and at low cost. The impact such centers would have on our understanding of E and G E as determinants of human disease would be extraordinary. True, an HGP-like effort for the environment would require a large investment. However, at a government cost of $2.7 billion (in $1991), HGP technologies will generate a projected $45 billion this year in sales. It does not require a great leap of faith to expect a simi lar multiplier from concerted action to quantify human exposures. As important sources of exposure are recognized and controlled, one can also anticipate reductions in morbidity and mortality that would translate into enormous savings in health care expenses. The researchers are supported by grants P42ES04705 and U54ES01611 from the National Institute of Environmental Health Sciences. The authors declare they have no competing financial interests. Martyn T. Smith Stephen M. Rappaport School of Public Health University of California Berkeley, California E-mail: martynts@berkeley.edu srappaport@berkeley.edu References Funk WE, Waidyanatha S, Chaing SH, Rappaport SM. 2008. Hemoglobin adducts of benzene oxide in neonatal and adult dried blood spots. Cancer Epidemiol Biomarkers Prev 17(8):18961901. Mulvihill M, Tao A, Benjauthrit K, Arnold J, Yang P. 2008. Surface-enhanced Raman spectroscopy for trace arsenic detection in contaminated water. Angew Chem Int Ed Engl 47(34):64566460. Pirkle JL, Osterloh J, Needham LL, Sampson EJ. 2005. National exposure measurements for decisions to protect public health from environmental exposures. Int J Hyg Environ Health 208(1-2):15. Rubino FM, Pitton M, Di Fabio D, Colombi A. 2009. Toward an "omic" physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds. Mass Spectrom Rev doi:10.1002/mas.20207 [Online 6 January 2009]. Stockton AM, Chiesl TN, Scherer JR, Mathies RA. 2009. Polycyclic aromatic hydrocarbon analysis with the Mars organic analyzer microchip capillary electrophoresis system. Anal Chem 81(2):790796. Wild CP. 2005. Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev 14(8):18471850. Willett WC. 2002. Balancing life-style and genomics research for disease prevention. Science 296(5568):695698. Martyn T. Smith is professor of toxicology in the Division of Environmental Health Sciences in the School of Public Health at the University of California, Berkeley. He has served as director of the Superfund Research Program at Berkeley since 1987. He is well-known for his work in molecular epidemiology, especially in regard to the toxic effects of benzene exposure. Stephen M. Rappaport is professor of environmental health sciences at the University of California, Berkeley. He is a pioneer in the emerging field of exposure biology, and much of his current research involves the development and application of blood protein adducts as biomarkers of exposure to toxic chemicals. Environmental Health Perspectives volume 117 | number 8 | August 2009 A 335