What is it?
Sequencing the human genome was conceived in 1984 as a means to help protect people from environmental mutagens and carcinogens. The concept led to the Human Genome Project in 1990. The Human Genome Project, coordinated by the U.S. Department of Energy and the National Institutes of Health, has six main goals:
- Indentify all the approximate 30,000 genes in the human DNA;
- Determine the sequences of the three billion chemical base pairs that make up the human DNA;
- Store this information in databases;
- Improve tools for analysis;
- Transfer related technologies to the private sector; and,
- Address the ethical, legal and social issues that might arise from the project.
While the public has focused on cloning, technologies from the Human Genome Project affect many areas including those familiar to EHS pros. Fantasy is rapidly
being turned into reality. You can learn about the science behind the Human Genome Project at the following Web site: http://www.ornl.gov/hgmis/project/info.html.
How will it impact EHS?
Almost all human disease results from the interactions between inherited gene variants and environmental factors, according to the introduction to the book, Genetics and Public Health in the 21st Century (http://www.cdc.gov/genomics/info/books/21stcentury.htm#Table). Genetics, in a very specific way, can provide answers to what makes people sick and who is most likely to get sick. This knowledge allows targeted disease prevention strategies. It also brings up complex ethical, legal and social issues.For example, this past July researchers in England found that genetic factors may account for nearly 50 percent of a woman's risk of developing carpal tunnel syndrome. According to the researchers, "?only minor contributions come from known environmental factors." It soon may be possible to screen for who is genetically predisposed to having CTS. Do you screen for these people and keep them away from high-risk jobs?
Or should you reduce workplace risk factors even lower to account for their increased susceptibility?
Here's another example: Research finds that a genetic defect doubles colon cancer risk for Askhenazi Jews (those of Eastern European ancestry). A blood test is available for $200 to detect this defect. Your workplace has hazards that may contribute to colon cancer. What do you do if an Askhenazi Jew applies for a job at your workplace? And what should we do with genetic records once they are created? Tough choices.
If regulations do not adequately protect genetically sensitive individuals, can these individuals take action under workers' compensation laws or can they initiate a toxic tort lawsuit?
Keep up with health research issues at the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/default.htm). Information on ethical, legal and social issues, particularly for EHS areas, can be found at the Environmental Genome Project (http://www.niehs.nih.gov/envgenom/home.htm).
Changes in toxicology
The Human Genome Project is profoundly impacting the practice of toxicology. Traditional toxicology primarily involves time and dose-response tests using individual chemicals and various animal species, such as the rodent. Checks for toxic responses are generally made for one organ system at a time. Contributing variables to disease causation (such as dietary and lifestyle components) must be progressively evaluated. It's a slow and costly process. The traditional Ames test using a bacterium provides a crude marker for genetic (such as mutagenic risk) but species extrapolation and other difficulties have made the test unreliable.In the mid-1990s a new molecular tool called the DNA microarray was developed. The DNA microarray allows for the quantitative and simultaneous monitoring of the expression of thousands of genes at one time. The DNA microarray along with other new technologies such as proteomic characterization and metabonomics have led to a new field of toxicology called toxicogenomics. The National Center for Toxicogenomics (NCT) (http://www.niehs.nih.gov/nct/home.htm) was established in September 2000.
"The promise of this new technology (toxicogenomics) is such that it can be used to generate data on large numbers of chemicals and exposure conditions and to develop an unprecedented knowledge base that can be used to guide future research, improve environmental health, and aid in regulatory decisions," according to Raymond Tennant from NCT.
Measured effects at the gene level can be "digitized" similar to computer code. Exponential growth in "codes" and other results from toxicogenomic studies are being made available to scientists and the public in a Chemical Effects in Biological Systems database. Advances in informatics (such as computational and statistical methods, query algorithms, and relational interfaces) are making it easier to evalaute the data.
Toxicogenomics that look at adverse changes at the DNA sequence level will challenge standard concepts such as "no observed effect level" and "lowest observed effect level." DNA sequence changes, especially when altered by exposures to low dose complex chemical mixtures and associated environmental variables, will eventually impact how EHS pros and legal experts look at exposure standards such as threshold limit values (TLVs) and permissible exposure limits (PELs).
