Public Release:  Genomic technologies to identify toxic chemicals should be developed

National Academy of Sciences

WASHINGTON -- A new report from the National Research Council recommends that government agencies enhance their efforts to incorporate genomic data into risk assessments of chemicals and medicines, and calls for a concerted effort to fully develop these methods' potential to protect public health. Chemicals and drugs often cause health problems by altering gene expression and other cell activity, and research on these processes -- called toxicogenomic research -- could eventually lead to more-sensitive toxicity tests that can supplement current tests, the report says. Toxicogenomic tests can also pinpoint individuals with genetic vulnerabilities and help them avoid chemicals or medications that might make them ill.

A major, coordinated effort approaching the scale of the Human Genome Project is needed both to develop these technologies fully and to address the ethical challenges they pose, such as protecting the confidentiality of individuals' genetic information, the report says. As part of this endeavor, which could be called a "human toxicogenomics initiative," a new database is needed to consolidate the massive amounts of data currently being generated by toxicogenomic studies.

"We have just begun to tap the potential for toxicogenomic technologies to improve risk assessment," said David Christiani, chair of the committee that wrote the report, and professor of occupational medicine and epidemiology at the Harvard School of Public Health. "To harvest public health benefits requires both greater investment in research and coordinated leadership."

Toxic substances and drugs can potentially disrupt gene processes within cells, thus disturbing the cells' healthy functioning. In addition, an individual's genetic variations can leave him or her particularly susceptible to the effects of chemicals or side effects of medications. For example, studies have shown that certain inherited gene variations may make some people more prone to symptoms such as nausea and impaired muscle function when exposed to a common pesticide, the report notes.

Using new toxicogenomic technologies, researchers can identify toxic processes as they unfold at an early, molecular stage, long before symptoms appear. This knowledge will support the development of tests that can more accurately predict whether a chemical will be hazardous, and at what dose. The tests' sensitivity also could lead to better prediction and prevention of damage to fetuses at critical stages of development. Finally, toxicogenomic studies can inform individuals about their particular genetic vulnerabilities.

Given the potential of toxicogenomics to reduce and prevent health risks, regulatory agencies should expand their research and enhance efforts to use these methods to aid risk assessments, the report says. It also calls on the National Institute of Environmental Health Sciences and other stakeholders in government, academia, and industry to explore the feasibility of implementing a concerted human toxicogenomics initiative.

A crucial part of this effort will be the creation of a single public database to collect toxicogenomic data and integrate it with data on health effects generated by traditional toxicology studies, the report says. Such a database will let scientists see connections between activity at a molecular level and the symptoms that result, and decipher how multiple genetic reactions at the cellular level can combine to cause adverse outcomes. New studies will also be needed to generate data on the genomic effects of chemicals for which traditional toxicity data already exist. And a national "biorepository" for physical samples -- human blood and tissue, for example -- will be useful for future toxicogenomic studies. Every effort should be made to use samples already being collected for other research, the report urges.

The generation of data from such studies, and toxicogenomic research in general, raises a host of social, legal, and ethical questions that the new initiative needs to address -- including protecting the privacy of genetic and health data, the report says. Individuals might decide against genetic testing if there is a danger that health insurers or employers could access their information and use it to deny them insurance or work. Safeguarding the privacy of this data will be increasingly challenging as the use of electronic medical records grows.

Improved legislation is needed to protect the privacy, confidentiality, and security of health information anywhere it is collected, stored, and transmitted -- not just at organizations already subject to privacy rules under the Health Insurance Portability and Accountability Act. The decision to learn about one's genetic vulnerabilities should rest with the individual, the report says. And except in rare circumstances, people who choose to get tested to learn about their particular genetic susceptibilities to a workplace chemical should be allowed to decide for themselves whether to accept the risks involved in employment.

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The study was sponsored by the National Institute of Environmental Health Sciences. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are private, nonprofit institutions that provide science, technology, and health policy advice under a congressional charter. The Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering. A committee roster follows.

Copies of Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment will be available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at http://www.nap.edu. Reporters may obtain a pre-publication copy from the Office of News and Public Information (contacts listed above).

Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology

David C. Christiani (chair)
Professor of Occupational Medicine and Epidemiology
Harvard School of Public Health, and
Professor of Medicine
Harvard Medical School
Boston

Cynthia Ann Afshari
Associate Director
Toxicology Department
Amgen Inc.
Thousand Oaks, Calif.

John M. Balbus
Health Program Director
Environmental Defense; and
Adjunct Associate Professor of Environmental Health
Johns Hopkins University
Baltimore, and
George Washington University
Washington, D.C.

James S. Bus
Director of External Technology, Toxicology, and Environmental Research and Consulting
Dow Chemical Co.
Midland, Mich.

C. Thomas Caskey
Managing Director
Cogene Ventures
Houston

Bruce Demple
Professor of Toxicology
Department of Genetics and Complex Disease
Harvard School of Public Health
Boston

Linda E. Greer
Health Program Director
Natural Resources Defense Council
Washington, D.C.

Sharon Lee Reilly Kardia
Director
Public Health Genetic Program, and
Co-director
Life Sciences Values and Society Program and the Michigan Center for Genomics and Public Health
University of Michigan
Ann Arbor

George D. Leikauf
Professor
Department of Environmental Health, and
Director
Molecular Toxicology Division
University of Cincinnati
Cincinnati

Daniel C. Liebler
Professor of Biochemistry and Pharmacology
School of Medicine, and
Director
Proteomics Laboratory
Mass Spectrometry Research Center
Vanderbilt University
Nashville, Tenn.

Gary Marchant
Executive Director
Center for the Study of Law, Science, and Technology, and
Lincoln Professor of Emerging Technologies, Law, and Ethics
Arizona State University
Tempe

John Quackenbush
Professor
Department of Biostatistics and Computational Biology
Dana-Farber Institute, and
Professor
Department of Biostatistics
Harvard School of Public Health
Boston

Kenneth S. Ramos
Professor and Chair
Department of Biochemistry and Molecular Biology
University of Louisville Health Sciences Center, and
Director
Center for Genetics and Molecular Medicine
Louisville, Ky.

Mark A Rothstein
Herbert F. Boehl Chair of Law and Medicine, and
Director
Institute for Bioethics, Health Policy, and Law
University of Louisville
Louisville, Ky.

Raymond E. Stoll
President
Stoll and Associates LLC
Storrs-Mansfield, Conn.

Roger G. Ulrich
Senior Scientific Director
Rosetta Inpharmatics LLC, Merck and Company Inc.
Seattle

Helmut Zarbl
Full Member
Divisions of Human Biology and Public Health Sciences
Fred Hutchinson Cancer Research Center (FHFRC), and
Director and Principal Investigator
FHFRC/University of Washington Toxicogenomics Research Consortium
Piscataway, N.J.

RESEARCH COUNCIL STAFF

Karl Gustavson
Study Director

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