Elaine M. Faustman, PhD, Professor Toxicology Program

On 25 April 1953, in an article in Nature, James Watson and Francis Crick described the entwined embrace of two strands of deoxyribonucleic acid (DNA). In doing so, they provided the foundation for understanding molecular damage and repair, replication and inheritance of genetic material, and the diversity and evolution of species.

In 2003, 50 years after the discovery of DNA’s double helix structure by Watson and Crick, scientists announced that they had decoded the underlying genomic sequences that provide the blueprint for human development.

Our department has several initiatives and centers devoted to using this genetic information to further public health.

The genome project has helped us understand how different individuals and populations respond to environmental and occupational exposures—and how these differences can affect health over time.

Genomic information can help bridge the gap between environmental and occupational hygienists. Historically, we have computed exposure, and then linked it with internal dose, biological effects, and ultimately with clinical disease. New techniques allow us to identify early effects at previously unimagined levels of sensitivity. This allows us to understand how genes and proteins respond to exposures (gene expression) much earlier in the disease process.

Here are two examples of how genomic information has revolutionized our field:

Human Variability. In some cases, a single genetic variation (polymorphism) can result in disease, such as Huntington’s disease or cystic fibrosis. However, for most diseases, multiple genetic and environmental factors contribute to the overall risk. In our department, the Center for Ecogenetics and Environmental Health (CEEH), funded by the National Institute of Environmental Health Sciences (NIEHS), is researching how genomic information can help define susceptible populations. This center focuses on understanding how the interplay between genes and environment can result in disease.

For example, it wouldn’t matter whether someone carried a sensitive genotype or a resistant one if no exposure were to occur. But, when an exposure occurs, the individual with the resistant genotype will have some increase in risk, perhaps two-fold, while the individual carrying the sensitive genotype could have a four- or even ten-fold increase in risk. Such genetic susceptibilities have been defined for environmental and occupational toxicants such as benzene or beryllium. Identifying how genetic factors combine with environmental factors can allow us to determine ample margins of safety for workers and the public.

These situations pose profound ethical, legal, and social challenges. How to use genetic information about sensitive genotypes in the workplace in a way that is nondiscriminatory—yet health-protective—is just one such challenge. Such research is taking place in multidisciplinary programs, such as University of Washington’s Public Health Genetics program and CEEH’s Ethical, Legal, and Social Implications (ELSI) program. We have also organized a series of interactive con-ferences with Environmental Protection Agency Region 10, pairing agency and academic researchers, to discuss how and when genomic information can inform policy and regulation.

Exposure and Early Response. A technique called “gene expression microarrays” allows us to monitor tens of thousands of genes simultaneously. Gene expression can be driven by an individual’s cellular makeup, and by external environmental and occupational agents. We can now monitor these changes in concert with physiological or pathological changes.

Numerous projects are underway to classify how chemicals affect “signature” profiles of gene expression. A large project in the NIEHS environmental genome project is evaluating the types of gene expression patterns that are produced by environ-mental and occupational chemicals.

Ideally, this would help us identify hazards before we adopt widespread use of new compounds. In the past, we have studied populations with high occupational exposures to a chemical and extrapolated these data to determine risks at relatively low environmental levels. The new techniques could provide a continuum between these levels of assessment.

Our department is part of an NIEHS-funded Toxicogenomic Consortium that conducts this type of investigation. The consortium is seeking better ways of applying this genomic information to answer public health questions.

Pathologists have been successful in using genomic information to better understand tissue pathology. For example, gene expression profiles can be used to identify distinct types of lung and breast tumors, and this genetic information has been used to determine the best chemotherapy options.

A GENOMIC REVOLUTION

When I was a graduate student, I can remember my excitement at being able to look at the expression of a single gene. The genome project now allows me to look at tens of thousands of genes simultaneously. The challenge is to harness this technique to advance the frontiers of environmental and occupational health.

FOR FURTHER READING

Center for Ecogenetics and Environmental Health http://depts.washington.edu/ceeh/

Nature. The double helix—50 years. Vol. 421, No. 6921 (23 January 2002)
http://www.nature.com/nature/insights/6921.html

NIEHS Environmental Genome Project http://www.niehs.nih.gov/envgenom/home.htm

Science. A history of the human genome project. (16 February 2001) http://www.sciencemag.org/cgi/content/full/291/5507/1195

Toxicogenomics Research Consortium http://www.niehs.nih.gov/dert/trc/fhcrc/home.htm

US Department of Energy Genome Programs. Genomics and its impact on science and society: The human genome project and beyond.
http://www.doegenomes.org/

Watson, JD & Crick, FHC. Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 171, 737-738 (1953)

We are in the midst of a technological revolution that will dramatically change the field that our graduates enter. We have asked two of our senior faculty to reflect on the past and the future of occupational and environmental hygiene.

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Elaine Faustman and Mike Morgan. Gavin Sisk

Hannah-Malia Viernes, a research technologist, prepares to genotype 96 samples in the Functional Genomics Laboratory. Devon DeLapp