**FOR PRINT *** Toxicogenomics could lead to explosion of litigation, says expert

By Lois Kapila | Nov 17, 2010



As advances in molecular science develop rapidly in laboratories, legal observers wonder if toxicogenomics will provide the next holy grail for toxic tort litigation -- specific causation.

Andrew Klein, professor of law at Indiana University School of Law, has written that "elucidation of the human genome makes it conceivable that scientists soon will link genetic change to specific exposures, and ultimately clinical disease in a way that used to be unimaginable."

Klein is excited about the potential impact of scientific developments on tort law cases.

"I tend to think they are going to be very helpful down the road," Klein said.

He notes the speed at which scientific advancements have been made in the last 10 to 15 years, from mapping the human genome at all, to mapping it for cheap.

"We are going to find things that we can't even imagine today....we have the potential to make more concrete connections -- today we just extrapolate," he said.

Kirk Hartley, a partner at Childress Duffy in Chicago, believes advances in toxicogenomics could mean an explosion of litigation.

"It could mean that asbestos litigation is just the tip of the iceberg," Hartley said, pointing to statistics for the surging number of cancer cases in the U.S.

According to the American Cancer Society, in 2009, there were an estimated 1,479,350 new cancer cases and 562,340 deaths. 2007 figures from the U.S. National Cancer Institute put cancer prevalence in the U.S. at 11,714,000 cases.

If even a fraction of these were able to prove causation through exposure to a specific product, then the increase in tort litigation would be enormous, Hartley indicated.

Bioinformatics + genomics

Toxicogenomics combines bioinformatics with genomics. Scientists look at the relationship between the structure and activity of a genome and try to shed light on the mechanisms by which chemical substances and toxicants lead to adverse biological effects. This field of science builds on advances in chemical biomonitoring techniques that track substance exposure in human tissue or fluids, and the mapping of the human genome.

Scientists also examine the impact of toxic substances on gene expression, in the hope of identifying biomarkers of a toxic exposure through individual cellular change. Measurements might demonstrate an individual's exposure to a substance (a biomarker of exposure) or the early progression of a disease process (a biomarker of effect). Genetic tests also show whether or not a subject has increased genetic susceptibility to disease.

The fundamental problem of proving or disproving causation has long been one of the most contentious issues in toxic tort cases. The existence of some cases of disease that are not associated with exposure to toxic substances makes it difficult to determine whether or not a substance caused a specific incidence of a disease.

Until now, litigants have relied on toxicology, looking at the mechanisms of toxic effects on animals and extrapolating to humans, or epidemiology, which aims to prove general causation by comparing the incidence of disease in exposed and unexposed populations. But neither of these indisputably prove specific causation. Some argue that evidence produced through toxicogenomics finally could.

But experts differ as to whether toxicogenomic-based evidence will lead to more litigation.

Pro-plaintiff or pro-defendant?

Klein said these scientific advancements are "neither pro-plaintiff or pro-defendant."

He said it could aid the plaintiff's side if it helps prove causation, or it could be pro-defendant if it allows defendants to counter probabilistic proof, or provide more precise evidence establishing some other potential cause.

Steve C. Gold, associate professor of law at Rutgers School of Law, has pointed out that, "in the few cases currently extant, it has usually been the defendant resorting to toxicogenomic (or quasi-toxicogenomic) evidence."

This was the case in both Henricksen v. ConocoPhillips Co., where the defendant argued that the plaintiff lacked chromosomal [rather than genetic] abnormalities frequently associated with carcinogen-induced AML, and in Tompkin v. Philip Morris, where the defendant argued that the plaintiff lacked genetic [as well as cellular] abnormalities frequently found in lung cancers associated with cigarette smoking.

Gold, in fact, is wary of claims that toxicogenomics is a holy grail that will permit causal fact-finding without reliance on inference from population-based studies or traditional toxicological studies.

This is only true, he argues, "to a limited extent."

Some biomarkers, he admits, may be found that are sufficiently consistent and highly correlated, making their presence a very strong indicator that a particular case of disease was caused by a particular exposure, and their absence an indicator that something else must have caused the disease. In other cases, toxicogenomics will not allow for such strong inferences and provide only probabilistic risk information.

In other words, Gold thinks that it will still be a question of strength of correlation, rather than causation.

How the courts deal with toxicogenomic evidence will be key in determining the level of influence new developments will have on rulings in future toxic tort cases.

One potential point of interest concerns the admissibility of evidence. While Klein believes that nothing much will change, Gold has concerns that courts may give a monopoly of authority to evidence garnered through toxicogenomics and molecular epidemiology, even if it provides only probabilistic information and, in cases where scientists have not yet studied potential links between exposure and a certain disease, is quite simply not available.

"I am concerned that courts may incorrectly conclude that...each individual claim of toxic causation would be amenable to so-called 'conclusive' scientific proof [from toxicogenomics and molecular epidemiology], in the absence of which the claim must fail," explains Gold further.

"If courts were to adopt that incorrect view, many...would likely exclude testimony based on other forms of scientific evidence.

"I think that would be a grave error, and would unfairly preclude some claims that would be supported by reliable scientific evidence and could satisfy the preponderance standard."

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