Monday, September 08, 2008

Potential Uses of Genetic Evidence to Prove Causation and Exposure in Toxic Tort Litigation

This guest post was written by J.C. McElveen of Jones Day and Alice Suh, a student at Georgetown Law School who was a summer associate at Jones Day this year. J.C. and Alice get all of the credit for this post; we had nothing to do with it:

Dr. Victor McCusick died several weeks ago. One of his obituaries said that, after medical school, he thought about practicing cardiology, but he was more interested in the newly emerging field of genetics. Though the scientific community has a great deal to thank Dr. McCusick for, the legal community owes him, and those who followed after him, a debt of gratitude, as well. Genetics may become the new face of the law.

Genetics is already used pretty extensively in the law. DNA evidence is used both to incriminate and exonerate suspects in crimes. It is also used on the civil side, to identify fathers in paternity suits and to assist in identifying individuals being sued civilly in assault or wrongful death cases.

In several toxic tort suits, defendants have sought to introduce genetic test results as evidence to prove that the plaintiff’s preexisting genetic condition, rather than exposure to an alleged toxin, was the cause of injury to the plaintiff. In Cruz v. Superior Court of Orange County, for example, a California appellate court affirmed a trial court’s order to compel genetic testing of the mother of an infant born with brain damage (17 Cal. Rptr. 3d 368, 369 (Cal. Ct. App. 2004). The suit alleged negligence by doctors during the infant’s delivery. Defendants argued instead that a superseding or contributing cause to the infant’s brain damage was actually a preexisting genetic condition in the infant or his mother. Despite plaintiffs’ objections, the court compelled the genetic testing.

In an unreported case, Bowen v. E.I. DuPont de Nemours and Co., Inc., plaintiffs alleged that birth defects in their children (who were born without eyes or with very small eyes) were caused by prenatal exposure to a fungicide (2005 WL 1952859 (Del. Super. Ct.). The defendants were able to compel genetic testing of one of the plaintiffs and, using the results, were able to establish that the birth defects were actually caused by a specific inherited gene mutation.

Efforts have also been made to use genetic testing to prove other things in litigation. For example, efforts have been made to demonstrate that a person is the proverbial “eggshell skulled plaintiff.” In Easter v. Aventis Pasteur Inc., plaintiffs alleged that mercury-based thimerosal used as a preservative in pediatric vaccines caused a child’s autism and developmental retardation [(358 F. Supp. 2d 574 (E. D. Tex. 2005)]. Although plaintiffs could not prove that thimerosal caused autism by reference to epidemiological studies, they claimed “some children are genetically susceptible to mercury poisoning and cannot excrete or otherwise eliminate the mercury in the vaccine preservative.” However, in this case, the plaintiffs admitted that the child did not meet the genetic profile of the alleged genetically vulnerable subpopulation of children. The court was convinced, in part, by this evidence to exclude testimony by the plaintiff’s expert seeking to establish causation. (The court, obviously, does not say what it would have done had genetic evidence shown that the plaintiff was, in fact, unable to process mercury.)

Genetic testing has also been offered to try to establish exposure. In litigation involving the 1979 Three Mile Island nuclear accident, in Pennsylvania, plaintiffs who developed cancer sought to introduce evidence of chromosomal damage (which they alleged was characteristic of radiation exposure) to prove that they were exposed to radiation at the time of the accident, fifteen years earlier. See In re TMI Litig., 193 F.3d 613, 622 (3d Cir. 1999). The Third Circuit held that using these genetic markers “is an accepted method, not simply for determining if the subject of the analysis was irradiated, but also for estimating radiation dose to the individual.” However, the court ultimately rejected the plaintiff’s chromosomal damage evidence because it had been obtained fifteen years after the accident. The court noted that, though the particular chromosomal damage (dicentrics) was stable for up to a year after exposure and could even serve as a sensitive dosimeter until that time, the reliability of that indicator decreased over time. The court held that dicentric counts done 15 years after the alleged exposure were simply not reliable. Furthermore, the plaintiffs had failed to do another genetic test (for reciprocal chromosomal translocations) which would have been better evidence on the issue.

Where might DNA evidence go from here? A news story in the August 6, 2008, Journal of the National Cancer Institute [JNCI 100:15, 1050-1051 (August 6, 2008)] discussed one area that may spawn litigation in the future. The story points out that there is an identified gene (the cytochrome P450 2D6, or CYP2D6 gene) which codes for an enzyme that metabolizes certain drugs. A certain percentage of people carry variant alleles of that gene which code for an impaired enzyme. The particular allele discussed by the story is something called the Star-4 allele (*4). People who have two copies of *4 metabolize certain drugs poorly; people with one copy of *4 and one normal allele process those drugs at an intermediate rate, and people with two normal alleles metabolize the drug quickly. (This variability in the body’s ability to metabolize substances that are foreign to the body is probably caused, at least in part, by polymorphisms in genes that code for metabolizing enzymes.) Therefore, for many drugs and other foreign substances, there are going to be slow metabolizers and rapid metabolizers, and some in between.

Testing for which CYP2D6 genotype you have is now available. In other words, you can find out if you are a rapid or a slow metabolizer.

The drug under discussion in the JNCI story is Tamoxifen, which, according to the story, is the standard therapy for breast cancer in post-menopausal women with estrogen-receptor positive breast cancer.

In 2006, the story says, an FDA Advisory Committee recommended that Tamoxifen’s label be changed to state, among other things, that CYP2D6 genotype testing is available. In addition, the story reports that the Mayo Clinic has begun offering the test to post-menopausal women with estrogen-receptor positive breast cancer who have elected to take Tamoxifen. A Mayo doctor said that, “if the gene test shows a woman will be a poor metabolizer, another treatment is recommended.”

So . . . this little story presents a bunch of the type of questions that lawyers love to think about. Regarding just this one gene, should a doctor always recommend that genetic testing be done on any patient who is prescribed a drug that is metabolized through the CYP2D6 pathway? Would a poor metabolizer of drugs metabolized through this pathway benefit from a higher dose of those drugs, and is the doctor obliged to find that out? Are there downside risks the patients should be warned about, based on their metabolic rate? What happens when it can be shown that a particular chemical (a potential carcinogen, a nervous system toxicant – you name it) builds up in the bodies of poor metabolizers, and the plaintiff is a poor metabolizer? The questions can go on and on.

Well, probably none of this is ready for prime time. As the JNCI story itself says, “some studies suggest that women with variant forms of the CYP2D6 gene may not respond well to Tamoxifen . . . . other studies, however, have found no relationship.” Or, as an interviewee said: “There haven’t been clear guidelines on how tumor marker studies should be done. Most tumor marker studies are studies of convenience. You pull some samples out of the freezer, you run an assay, get a [statistically significant result] and you rush it off to be published. That’s exactly what’s going on with [CYP] 2D6. . . .this field is in its infancy, and we have to be careful about it.”

That’s never stopped lawyers.

1 comment: said...

These people have no right to try to use technology to get out of taking responsibility for the damages they caused. Not only is it unethical, it's very dangerous.