The EGP at five years.

More than 100 scientists, public health professionals, and physicians gathered in Boston 7-9 June 2003 for a symposium, Genes, Environment, and Disease, that provided research updates on the NIEHS Environmental Genome Project (EGP) and its associated Comparative Mouse Genomics Centers Consortium (CMGCC). The EGP was initiated in 1998 with a dual goal: providing information on how individual genetic differences affect disease risk from environmental agents, and proposing appropriate environmental policies in response to that information. In embarking on that quest, the NIEHS divided the work into a number of subject areas ranging from the identification of variations in environmental response genes to the broad examination of the ethical, legal, and social implications of the findings of the EGP.

The symposium occurred only weeks after completion of Phase 1 of the EGP, which called for the resequencing of more than 200 environmentally responsive genes for the purpose of identifying single-nucleotide polymorphisms, or SNPs, that are important in determining disease susceptibility. The mission of Phase 2, which is currently under way and expected to extend to 2004, is to conduct functional analysis studies to characterize the SNP variants discovered in Phase 1. Phase 3 of the EGP, now in its initial planning stages, will include the Molecular Epidemiology Program, in which population-based epidemiologic studies will be initiated to understand the role of gene variations in human genetic susceptibility.

Because animal models are an essential part of Phase 2, the NIEHS created the CMGCC, which consists of five universities. The consortium is charged with developing mouse models containing, among other SNPs, the human polymorphisms identified in Phase 1. The focus to date has been on modeling mice with variants in environmentally responsive cell cycle and DNA repair genes.

At the symposium, NIEHS deputy director Samuel Wilson said that "all of us at the [NIEHS] are very pleased" with the work done so far. But he also suggested that much work lies ahead and warned against succumbing to pressure brought by the public or the media, who may be anxious to see genetically based disease cures. "It's too easy to fall into the trap of 'tell me what it means next week,'" he said. "It's an ongoing activity we're talking about. We're not looking to an end point of five years or even fifty years." He emphasized the importance of sound polymorphic studies, because "otherwise we'll be doing superficial science."

Joan Packenham, the NIEHS program director for the CMGCC, and Kimberly Gray, a health science administrator with the institute's Susceptibility and Population Health Branch, presented overviews of various facets of the EGP. They were followed by CMGCC directors Raju Kucherlapati of Harvard Medical School and Jan Vijg of the University of Texas Health Science Center at San Antonio, who described consortium accomplishments. For example, the CMGCC recently launched the Mouse Federated Database, an integrated bioinformatics tool that allows access to the biological data on CMGCC mouse models. Richard Sharp, an assistant professor of medicine at the Baylor College of Medicine, gave an introductory talk about the ethical, legal, and social implications of the EGP, discussing privacy issues arising from individual participation in research and protection of racial or ethnic groups in which certain genetic variants may be more common.

The balance of the agenda was devoted to presentations by researchers working on a variety of studies related to the scientific interests of the EGP. For example, Jeanne Manson, a research scientist in human genetics and molecular biology at the Children's Hospital of Philadelphia, described her work to identify and evaluate risk factors for hypospadias (an abnormality of the urethral opening on the penis) in 250 families to date. Among her findings, she said, are a relationship between hypospadias and exposure to pesticides, paints and stains, fuels, and solvents. Susan L. Lindquist, director of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, reported on her research on prion proteins in baker's yeast. Prions self-perpetuate by inducing other proteins to assume their same shape. The research, she said, has advanced understanding of mammalian prions, which cause spongiform encephalopathies that can spread through the environment.

Packenham said the symposium was intended to make the scientific community aware of research being conducted within the EGP and the consortium, and was organized specifically to bring together scientists from two different communities under the EGP: mouse modelers and epidemiologists.

One of those mouse modelers, David Johnson, director of the University of Texas M.D. Anderson Cancer Center Comparative Mouse Genomics Center in Smithville, agreed, pointing out that the utility of the two disciplines meeting with each other went beyond just mutual edification. "We could see where we could help each other," he said. "We [mouse people] needed help identifying which SNPs to model, for instance. And [the epidemiologists] were interested in what we've already found so they can identify the most promising SNPs to do association studies with."

He also noted that there are certain big-picture benefits to meeting with other scientists working within the broad EGP. "I got a much clearer picture of what the overall Environmental Genome Project is and how we fit in," he said. "I also got an idea about how much progress has been made."