Genes or the environment? Advances in genomics science provide a new legal framework for a genetic defense to toxic tort claims.
Legacy (re)insurers holding or acquiring toxic tort liabilities may be relying too heavily on outdated legal strategies to defend their policyholders. In our view, millions (perhaps billions) of dollars might be saved if reinsurers embrace transformative new developments in genomic science. And while all agree that the diseases underlying plaintiffs’ claims are tragic, developments in genomic science increasingly tell us that, in many instances, those diseases are the result of a person’s genetic makeup — not due to the alleged exposure.
Genomic sciences are modern tools that can, in many cases, definitively and quantitatively determine the cause of specific injuries. Because cancer is a disease of the genome, all cancers can ultimately be attributed to genetic factors. Some genetic factors are inherited from the plaintiff’s ancestors while other genetic errors are induced or enhanced by environmental exposures and/or random variation. Today it is standard medical best-practice at all cancer centers of excellence to sequence a patient’s DNA for data to make life-changing preventative or treatment decisions. Yet genomic evidence is not routinely sought after by insurers, nor is it commonly explored as a cause of injuries in toxic tort cases.
Toxic tort cases involve two factors alleged by plaintiffs to be causally related: (1) a single or multiple exposure (usually a chemical); and (2) an injury (often cancer). Depending on the facts of the case, the defense strategies can vary. Some defendants will simply argue a disease is “idiopathic” (i.e., of unknown origin) and will not seek to provide concrete information that may help a jury to determine the actual cause of the disease. More commonly (e.g., in asbestos cases), counsel for the defense often argues that the exposure at issue was not their client’s, but rather another defendant’s exposure.
But there is another, much more compelling alternative; especially when evidence of exposure is questionable or non-existent: i.e., the plaintiff inherited genetic factors that caused the injury. This alternative is preferable because it tells the jury exactly what caused the injury (and that explanation does not involve the alleged exposure).
This article describes the power of genetic science as a tool that should be sought after by insurers and their counsel to better defend toxic tort cases.
Genetic Predisposition as a Defense in Toxic Tort Cases
Genetic predisposition refers to the likelihood that an individual will develop a specific disease (e.g., cancer, birth defect, autoimmune disease) due to his or her genetic makeup. A genetic predisposition is inherited from the individual’s parents as gene variants that increase his or her likelihood of developing that disease independent of other environmental factors.
An extreme example of genetic predisposition is cystic fibrosis. If an individual inherits specific genetic mutations from both parents, there is absolute certainty that these genetic factors will drive the development of the disease independent of any other factor. Not all genetic predispositions lead to the certain development of a disease. For example, a woman who inherits a defective BRCA1 or BRCA2 gene variant has a very high (45 – 65%) probability of developing breast cancer compared to the 12% probability of women without these variants. Nevertheless, it is the inheritance of these genetic factors that dramatically affect the likelihood of developing the cancer. No other genetic factor or toxicant exposure is necessary to drive the development of cancer if one of these gene variants is inherited.
As can be seen from these examples, demonstration of a genetic predisposition empowers the defense to confidently point to specific, measurable genetic factors as a cause of an injury (in the absence of exposure to any alleged toxin).
Genetic Causes of Mesothelioma
Most seasoned asbestos lawyers assume that asbestos was the cause of an individual’s mesothelioma (somewhere, somehow). By this logic, all cases of mesothelioma are caused by asbestos exposure. Yet, evidence is mounting that mesothelioma is no different from any other cancer – i.e., it is a disease of the genome. There is no doubt that asbestos is a cause of mesothelioma; however, it is not a cause of every mesothelioma case. Some mesothelioma cases are clearly caused by inherited genetic factors. How do we know this?
The idea that some mesothelioma cases are caused by inherited genetic factors (as opposed to asbestos exposure) comes from two lines of evidence:
- Inactivating specific genes (e.g., BAP1, NF2, and TP53) in genetically engineered mouse models causes mesothelioma in the absence of asbestos exposure; and
- Individuals with mesothelioma who have no evidence of asbestos exposure present with rare genetic mutations (often the same genetic mutations as from the mouse models) known to be associated with mesothelioma.
Every insurer with an asbestos docket should be on the lookout for mesothelioma cases that are caused by underlying, inherited genetic factors. Ultimately, the question is how to separate cases of mesothelioma that are genetically induced from mesothelioma cases that are caused by asbestos exposure. Broadly speaking, mesothelioma cases that are most likely induced by inherited genetic factors are relatively young (under 45 years of age) plaintiffs with a family history of certain cancers, and little to no evidence of asbestos exposure.
It is important to highlight that the use of genetics in mesothelioma cases is not science fiction or an aspirational concept that might someday be utilized. Genetics is currently being used as a tool by defendants in asbestos cases around the country.
Using Genetics in the Courtroom
The logistics of bringing genomics into the courtroom is not complicated. The process starts with a review of the medical records for clues of genetic causation and the availability of samples to determine if the case is a good genetics candidate. Depending on the type of cancer involved it may be possible to use freshly collected blood samples, clinically preserved biopsies, buccal swabs, or even saliva as the source for DNA. Next in the process is DNA extraction and quality control, followed by sequencing, then interpretation of the data using peer-reviewed published medical and scientific literature, and finally expert report development. In our experience, most cases that rely upon genetic data to demonstrate alternative causation end in rapid settlement once the report is introduced.
In the rare instances where a case goes to trial, we have thus far had great success in using genomics to expose the truth. Genomic science will not always support a defense argument, it is quantitative and factual; however, careful selection allows for targeting of the highest impact cases for the investment.
Cost of a Genetic Defense
This discussion leads to a factor critical to all litigants: cost; genomics testing is still expensive. But many cases will not require any additional genetic testing expense because genetic information is often already present in the medical record history. In our experience, this preexisting information can often lead to a powerful affidavit or expert report, and even settlement.
In other situations, a strong case can be made from targeted genetic sequencing panels or other existing specialized genetic tests. Custom gene panels developed specifically for toxic tort cases can be implemented most cost-effectively. We also can evaluate a full genome or exome sequence on the plaintiff, providing the most powerful evidence if genetic predisposition exists. However, because full genome sequencing is not always feasible, cases can often be screened for those most likely to have inherited factors in order to achieve the best return on investment.
Unlike the more common epidemiologic inferences from population-based studies, genomic science can often provide a roadmap as to how an injury developed in a specific individual. In other words, it can often uncover the ‘real truth’.
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David H. Schwartz is a principal at Innovative Science Solutions, Inc, a consulting company that provides scientific and regulatory support to industry and counsel as well as ToxicoGenomica, a strategic alliance designed to provide a genetic defense in toxic tort cases. Dr. Schwartz has worked as a consultant with insurers and legal counsel for the last 30 years to provide scientific insights in the defense of toxic tort cases. If you want to learn more about topics like how to select the best cases for a genetic defense, types of sequencing, how to determine genetic predisposition, hereditary cancer syndromes, and other aspects of courtroom relevant genomics, download our whitepaper or subscribe to our blog on our website:
