Genomic technologies to identify toxic chemicals should be developed

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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