The sequencing of the human genome revealed that the variation in the genetic material between any two individuals averages approximately one variation for every 1,000 base pairs of deoxyribonucleic acid (DNA).¹ Even though we are remarkably 99.9% genetically identical, there are still on average three million genetic differences between any two people, given that the human genome contains approximately 3.1 billion base pairs of DNA. While many of these genetic variations appear to have no functional significance, others have important consequences, including contributing to the significant differences between individuals in their appearance, personality, abilities, and health. Of particular interest here, there are also genetic variations that affect our individual susceptibility² to disease from exposure to exogenous substances that enter our bodies, such as drugs, foods, infectious agents, and toxic substances (collectively referred to as xenobiotics).³

Genetic differences in susceptibility provide an important part of the answer to the age-old question of why do some people get sick from certain exposures while others do not.⁴ For example, it has been known for centuries that some individuals, especially people of Mediterranean and Asian origin, can develop a potentially fatal illness (called favism) from eating fava beans, while most people experience no problems from eating this food product.⁵ This differential response is now known to be caused by a genetic variation in the glucose-6-phosphate dehydrogenase gene.⁶ Every person who has to date succumbed to "mad cow disease," known technically as new variant Creutzfeldt-Jacob disease (vCJD), carried a particular genetic variation that is present in approximately 40% of the population.⁷ Genetic susceptibility [33 ELR 10642] factors now explain many examples of pharmaceuticals that are not effective in some people, or which cause toxicity in others.⁸ Indeed, it now appears to be the general case that for exposure to any xenobiotic, some members of the public will be more susceptible than others due to their genetic profile (or genotype).⁹

This Article examines the implications of recent findings of relatively common genetic variants, known as "polymorphisms,"¹⁰ within the population affecting susceptibility to environmental exposures. In particular, the Article examines the potential applications of such information in toxic tort litigation and environmental regulation.¹¹ The study of differences in genetic susceptibility to environmental toxicants is sometimes referred to as "toxicogenetics."¹² Toxicogenetics, which studies the variations in single genes, is distinct from toxicogenomics, the subject of a previous accompanying Article,¹³ which studies the expression of the entire human genome in response to toxic exposures.