“The relationship between genes and the environment can be compared to a loaded gun and its trigger. A loaded gun by itself causes no harm; it is only when the trigger is pulled that the potential for harm is released,” said Kenneth Olden and Samuel Wilson in their article on environmental health and genomics, which was published in the November 2000 issue of Nature Reviews in Genetics.

Wayne State University’s Craig Giroux, PhD, has been studying this concept of genetic susceptibility for years. As he says, “Imagine the loaded gun as a combination of genes that make you susceptible to a certain disease and the trigger as a particular environmental exposure. There is a huge class of such genes that are associated with increased risk for developing a disease, but which do not automatically cause the disease per se.”

According to Dr. Giroux, assistant professor in the Center for Molecular Medicine and Genetics, the Human Genome Project has yielded remarkable insights into single gene disease models, but there is still much to be discovered about the diseases which are influenced by a combination of genetic factors. He says, “Some genes are direct causes of a disease. For example, a mutation in one specific gene is associated with sickle cell anemia, which makes this gene amenable to correction by new genetic technologies. But, what about heart disease, breast cancer, diabetes or asthma, which involve a great number of genes? There isn’t a single gene that ‘causes’ these conditions, but instead an entire set of genes interacts with environmental factors to put you at higher risk.” 

In the old model for studying the genetics of human disease, each researcher focused on one gene, often for an entire career.  With the revolution of information flowing from the Human Genome Project, this single-gene approach is no longer adequate. Dr. Giroux’s work shows the importance of studying each gene in relation to the elements with which it interacts. This perspective examines how each gene is integrated into a larger system—not just with other genes or disease states, but with the environment at large.

With more than $1 million from the United States Office of Naval Research, Dr. Giroux is developing genomics-based cellular biosensors for environmental hazards. Through this grant, he hopes to provide new information about gene/environment interactions and to identify the genetic factors that predispose an individual to environmentally responsive disease. He is developing novel biosensors which will both identify hazardous chemicals in the environment and predict which genes make an individual susceptible to these specific hazards. This prediction is made possible by construction of a yeast genomics model for the human cellular stress response to environmental toxicants. By studying the target pathways that confer sensitivity to chemical agents in the yeast cell model, broader conclusions may be deduced about oxidative stress and molecular damage in the tissue and organ systems of exposed individuals.

“This concept of gene/environment interaction creates a major paradigm shift,” said Dr. Giroux. “In previous disease models, you find the physiological problem and fix it to cure the disease. Applying this new concept, you identify the environmental sensitivities and then change your environment to positively influence your health and well-being. It opens the door for very individualized preventive medicine. We may not be able to control all of our genes, but we can certainly exercise more control over our environment.”