A legal defense grounded in genetics: Is DNA testing the magic wand to winning (or losing) a negligence case? – Genetic Literacy Project

Among the four elements required to establish liability for the tort of negligence is causation. In addition to proving that the defendant was careless or otherwise breached the legal standard of care, the plaintiff must establish that the wrongful conduct caused the harm the plaintiff suffers. This 1941 New Hampshire Supreme Court decision explains:

Necessary elements of a cause of action based on negligence are the causal negligence of the defendant plus the resultant harm to the plaintiff. Putting it another way, there must be negligence and harm and they must have a causal connection.

At the height of asbestos litigation, mesothelioma, a cancer of the lining of the pleural (lung) cavity or the abdominal cavity (peritoneal mesothelioma) was believed to be pathognomonic of asbestos exposure, meaning that the disease was a signal cancer of asbestos exposure, and only asbestos exposure. A diagnosis of the disease was tantamount to legal recovery (and virtually certain and swift death). No longer.

Today, it is recognized that mesothelioma has other causes, including erionite, another naturally occurring mineral used in pet litter, soil conditioners, animal feed, wastewater treatment, and gas absorbents. Radiation is also a recognized cause of mesothelioma, either from employment-related exposures, or older therapeutic uses which are now known to cause disease. And then there are causes we dont even yet know about as well as those arising spontaneously. These are known as idiopathic causes.

Asbestos exposure significantly declined beginning in the 1970s when the first OSHA asbestos laws were enacted. However, the incidence of mesothelioma, even with its notoriously long latency or delay period, is increasing in women, and has remaining constant overall. This lends credence to the fact that mesotheliomas arises from causes other than asbestos or even arises spontaneously, meaning the body needs no help from asbestos or anything else in generating them.

Of course, spontaneously does not mean magically or out of the blue. Rather, of the estimates that perhaps twenty to fifty percent of mesotheliomas dont arise from asbestos, it appears some are attributable to genetic misfirings, or mutations, that arise over time, some occurring as we age, and our defenses or repair mechanisms are no longer functioning optimally. (Think how slow your older computer worked compared to the new one you bought when old-trusty melted down.)

These genetic mutations are not necessarily inherited (although some are), but rather occur in clusters - or more rarely, singly due to natural causes or DNA breakage. The mutations can cause mesothelioma, either alone or by increasing susceptibility to minute exposures. The difference in the causal mechanism, however, has a huge impact on legal liability. And so it is that attention to genetics is now finding its way into the courtroom.

Courts are becoming more attentive to the need to establish that a potential carcinogen is responsible for causing the disease in a particular person, rather than based on its statistical or historical significance for a general population. Recently, in toxic tort cases, some courts are requiring a two-stage level of proof:

Specific causation requires showing that the plaintiff was exposed to a sufficient dose which is capable of causing the disease in that person. The application of this requirement is derailing some talc-mesothelioma cases.

But attention to the plaintiffs burden of proving specific causation is not the only monkey-wrench appearing in toxic tort cases these days. And not all courts are requiring specific quantification of plaintiffs exposure to prove causal-negligence, i.e, that the defendants asbestos caused the particular plaintiffs disease.

This situation invites another option for defense lawyers to protect their clients: genetics. And so we find defense lawyers turning to genetics to establish the defense that it wasnt exposure to asbestos per se, that caused the plaintiffs mesothelioma. Rather it was something else notably, something in their genes.

The genetic defense has found itself into other types of cases as well. And as we learn more about the genetic components of disease, we can expect to find its use burgeoning. Take the case of Bowen v. EI Dupont, in which the plaintiff alleged her retarded fetal growth and birth defects were caused by exposure to the fungicide Benlate during her gestation, when her mother was spraying houseplants.

The defendant obtained a court order to genetically test the plaintiff for a specific genetic variation (CHD7) that causes a specific condition (the CHARGE syndrome, a rare condition that causes birth defects), that resembled the plaintiffs condition. The defense argued that the mutated CHD7 was the sole and proximate cause of the plaintiffs condition a CHARGE syndrome-driven birth defect, a theory with substantial support in the record and substantiated in peer-reviewed literature. After the testing and finding the mutation present, the court dismissed the case.

In a similar case, Naomi Guzman v. ExxonMobil Corp, the plaintiff claimed that she was exposed to radioactive material as a bystander to her fathers work as an oil pipe cleaner. The court granted the defendants request for genetic testing of plaintiffs preserved thyroid tissue.

Genetic tests revealed both that the plaintiff did not have the genetic signature for radiation-induced cancer. It also revealed that plaintiff had several hereditary gene mutations predisposing her to thyroid cancer, leading the defenses expert-toxicologist to conclude her thyroid cancer was caused by her genetic predisposition and not exposure to her fathers drilling pipe. The jury agreed and sided with the defense.

Genetic defenses, however, must be used with care. In some cases, exposure to a chemical overwhelms multiple natural genetic repair mechanisms, leading to the cancer or disease. In those cases, the genetic defense may not work.

Thus, the failure of a genetic-defense mechanism to activate (or activation of a susceptibility gene) may not absolve the defendant, since it was the impact of exposure (to their asbestos or whatever chemical) that caused these genes to malfunction, and which in turn began the chain-reaction leading to the disease.

Instead, focusing on point mutations, where cancers occur as the direct result of a consequential change in a particular genetic set of alleles (subparts of a gene responsible for expression of a particular trait), independent of exposure, present the genetic alterations generating the most success in legal cases.

So far, two genes have been implicated as causally-related to mesothelioma in the absence of asbestos exposure. One, is a mutation on the AKL gene. While the discovery may not help plaintiffs in a legal setting, such discoveries do bode well for enhanced therapeutics and treatment.

Other studies have identified mutations on the BAP1 gene, discoveries that again bode well for possible treatment, although not necessarily for success in the legal setting. The BAPI gene is also related to several other cancers, including melanoma, so the causal connection is not one-on-one. But the BAP1 gene also has an additional effect- not only has it been related to direct causation of mesothelioma, it is also known to enhance susceptibility to prior exposures to asbestos. And that poses a legal problem.

The published findings do not establish a synergistic gene/environment interaction as a causal factor for the development of mesothelioma [and Bap1].,,, At present, it is estimated that between 1 and 8 percent of all spontaneous mesothelioma cases involve BAP1 germline mutations.

Bernier et al.

In law, the defendant is said to take the plaintiff as one finds him/her. That means if a plaintiff, by virtue of his or her individual make-up, is unusually susceptible to a condition, the defendant is still liable for all incident harms of their negligence. These include even those that might not have happened if the same wrongdoing was inflicted on a hardier plaintiff. (The term got its name from a case about running over a plaintiff with a skull as thin as an eggshell).

That maxim makes finding a BAP1 gene problematic. In some cases, the gene will render the plaintiff unusually susceptible to a small amount of exposure; in others it can cause mesothelioma, outright. Where the gene acts as a susceptibility gene, the defendant is still liable. Where it causes the disease outright, the plaintiffs case fails.

At the end of the day, the answer becomes a matter of fact for the jury to decide after listening to a battle of experts. But recent research shows that up to one-third of all cancers are produced by the bodys own mutation errors, and not by environmental causes. The complete genetic-cause defense would likely work best in cases of teenagers or women who were unlikely to have been exposed to significant levels of exposure.

To maintain a genetic defense, the plaintiff would have to petition the court to compel genetic tests of the plaintiff and sometimes the family to show a hereditary defect. Courts usually direct the plaintiff to submit to genetic testing (via blood test or tissue swipe), if the requested tests are particularized enough, although they will often reject requests to compel family-testing.

Is this forced test legal? Yes. First because such tests are not usually invasive; and second, by bringing the lawsuit, the plaintiff has put his condition into controversy and hence waives some rights.

To date, a few dozen personal injury cases have involved court-ordered genetic testing. Most courts have allowed it, especially as the tests are not painful, protracted, or intrusive. (Although, when the genetic tests are to be used for prospective or predictive purposes, such as medical monitoring or gauging the likelihood of future disease severity or longevity, the courts may not agree. In these cases courts often conclude that DNA tests are more speculative in prediction than identifying causal genes in those already suffering a disease).

Most important, however, a defendant who wants to compel a test must seekprecise information or evidence. In other words, like in any litigation discovery procedure, neither party is given largesse to go on a fishing expedition, for example by seeking reems of data, hoping to uncover an unanticipated smoking gun.

This objection wouldnt be typical in the asbestos cases, since specific and responsible genetic culprits have been identified. But we can see the abuse in other cases, notably birth-related negligence cases which often result in a surfeit of issues, such as brain damage, developmental issues, and physical disabilities. To be sure, such conditions can be caused by environmental exposures, poor pre-natal care, or even the birth process itself, especially if negligently performed.

In one birth-related negligence case, Fisher for XSF v. Winding Waters Clinic, the defendant sought a court order compelling the plaintiff to submit to genetic testing to confirm whether their impairments are more likely than not the result of a genetic condition unrelated to prenatal care

The problem was that the defendants had no specific condition in mind. They sought a WES (Whole Exome Sequencing) array meaning they wanted to look through the plaintiffs entire genomic vocabulary in the hopes of finding one or more errors to explain the condition. The court rejected the request.

Recognizing that overbroad requests promote the possibilities for abuse, including privacy violations or the potential to uncover genetic predispositions to numerous unrelated conditions, the court noted that the defendants request was particularly troubling.

Nevertheless, we can expect an onslaught of compelled genetic testing arising out of litigation to continue. As to where the results take us, thats an interesting and open- question. Perhaps the most curious case is the pending matter of Lohmann v. Aaon Inc. There, the defendants experts sought evidence of the BAP-1 disorder. Not only did they want to use it for the litigation, they wanted it for their own research purposes, as well.

Seems the value of these tests is greater than we might imagine. No word yet, on the legal resolution. But Id bet the judge denies the request.

Dr. Barbara Pfeffer Billauer, JD MA (Occ. Health) Ph.D. is Professor of Law and Bioethics in the International Program in Bioethics of the University of Porto and Research Professor of Scientific Statecraft at the Institute ofWorld Politics in Washington DC. Find Barbara on Twitter@BBillauer

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A legal defense grounded in genetics: Is DNA testing the magic wand to winning (or losing) a negligence case? - Genetic Literacy Project