Toxicogenomics: new chapter in causation and exposure in toxic tort litigation: this new science has the potential to identify biological clues to disease, and both plaintiffs and defendants will strive to use it to their advantages.

• Author: Childs, John C.

CAUSATION and exposure have always been the key issues on which toxic tort cases are won or lost. Most toxic tort litigation involves diseases, such as cancer, for which there are numerous possible causes and where there is little objective, scientific proof that the claimant's disease was caused by the alleged exposure. Given the large number of potentially toxic chemicals to which people are exposed, it should be no surprise that there are few epidemiological or mechanistic studies of the toxic effects of many of these substances that are alleged to cause disease.

Faced with this lack of scientific certainty, courts have seized on the U.S. Supreme Court's decision in Daubert v. Merrell Dow Pharmaceuticals Inc. (1) as a way of requiring experts to present more than conclusionary opinions of causation and exposure in toxic tort actions. In Daubert, the Court recognized the difficulty between the "quest for truth" in the courtroom versus the scientific arena, holding that the trial judge must act as a gatekeeper to, on occasion, exclude novel, albeit "authentic," scientific views. Rather, experts now are routinely asked to identify the factual bases for their conclusions and to explain their methodology, demonstrating that both are scientifically reliable.

A NEW FIELD: TOXICOGENOMICS

1. What Is It?

   Toxic tort litigation as most trial attorneys know it today is about to undergo a drastic, irrevocable change. Genetic evidence has the potential to revolutionize in this area. The sequencing of the human genome and the creation of DNA (deoxyribonucleic acid) databanks now offer scientists the unprecedented research opportunity to understand the causation of disease. (2) Cellular and molecular testing made possible by recent DNA research analyzes what cellular changes cause disease and looks at the mechanism responsible for the onset of that disease process.

   This new scientific field, which has launched a new chapter in the proof of causation and exposure in toxic tort cases, is called toxicogenomics. It is the study of the impact of potentially toxic compounds on gene expression. A gene "expresses itself" by acting on proteins and other body processes in very complex ways to affect how the body grows and develops. (3) Toxicogenomics is the study of the alteration of those mechanisms that leads to conclusions about disease and disease processes. It combines the emerging technology of genomics and bioinformatics to identify and characterize the mechanisms of action of known and suspected toxins.

   The premier toxicogenomic tools now are the DNA microarray, also called the DNA chip, which is used for the simultaneous monitoring of gene expression levels, sometimes a hundred to a thousand at a time. (4) The results of these tests offer insights into the relationship between our genetic inheritance, exposure to chemicals and the environment, and the onset of disease.

2. Use in Litigation

   The value of toxicogenomics to toxic tort litigators is quite apparent. For plaintiffs who have insufficient scientific proof that a product was more likely than not to cause cancer, the ability to show that an exposure to the product resulted in a genetic polymorphism or gene sequence difference, which increased cancer susceptibility, could be outcome determinative. Comparing DNA test results from before and after the use of the product provides an opportunity to develop quantitative proof of genetic changes. Before-and-after genetic snapshots will allow plaintiffs to prove that their injuries did not pre-date exposure to defendants' toxins. If these biological changes are specific to a defendant's product, then both causation and exposure have been shown.

   Defendants also may be able to use toxicogenomics to buttress their defenses. They could cite the absence of genetic biomarkers as evidence that claimants in fact were not harmed by the chemical in question. Genetic tests performed on plaintiffs may point to a genetic susceptibility to other potentially carcinogenic substances, in addition to the targeted product, and any one of those alternative exposures could have caused cancer.

   Genetic testing also may reveal that a plaintiff is genetically predisposed to a disease. The defendant could argue that the plaintiff, s genes, not the defendant's product, caused the disease. (5)

3. Testing Uncertainties

   Building a toxic tort case or defense based solely on genetic and molecular testing is still far off. Despite the acceptance of DNA testing in the paternity and criminal areas, it is still very new and its uncertain results are subject to much scientific debate. Genetic research is primarily laboratory testing and is not based on animal or human studies. Consequently, it is done "apart from the human body," either literally or virtually, in a petri dish or test tube. Scientists identify specific genes and proteins that relate...