March 5, 2020
Authored by: Susan Brice
What is Genomics?
Genomics is the study of all the genes within an organism, including humans, and how all of those genes are interrelated and influence the organism. Genetics is primarily focused on single genes. Genomics involves sequencing and analysis of genomes through the use of DNA sequencing and bioinformatics.
How are Genomics Being Used in Toxic Tort Litigation?
The use of genomics to defend toxic tort claims is emerging. For example, defendants in recent cases involving asbestos, benzene, low-dose radiation and other substances have used genomics successfully. These successes tend to occur after an early and careful look at the facts of a case.
For example, defendants recently and successfully used a genomic causation defense in two mesothelioma cases involving males, who developed peritoneal mesothelioma in their 30s, with little or no known exposure to asbestos fibers. The early age of cancer onset was a material fact suggesting a genetically caused cancer. Another fact suggesting that genomics should be considered is the presence of a family history of cancer, especially early onset cancers or multiple cancers in particular family members. Contrary to what one might assume, the family history does not need to involve the same cancer or the same organ. That is because adverse germline mutations (ones that are inherited) can cause cancers located on different organs.
What can Genomics Reveal about Cancers?
As explained by members of ToxicoGenomica, a multidisciplinary group of scientists and lawyers that provide services for using genomic and systems biology data in civil litigation, the application of Next Generation Sequencing (“NGS”) technologies in toxic tort cases can “reveal the presence or absence of evidence of toxicant exposure and damage that is locked within the genetic blueprint of an individual, and in appropriate cases, can assess alternative causation.”
In other words, the process can reveal objective evidence showing that adverse gene mutations were sufficient to cause a cancer without regard to exposure to a particular substance (such as asbestos fibers).
How is the Genomic Information Obtained?
The initial steps in the gene sequencing process are not complex. The first step is to obtain a source from which laboratory technicians can obtain DNA that meets standard criteria. Typically, DNA is either extracted from small samples of fresh blood (about two teaspoons) or from tumor biopsy tissue samples that include some non-cancerous tissue.
In some situations, old biopsy material may serve as a source of DNA, even if the biopsy sample was taken for reasons not involving cancer.
Reasons Why Using Genomic Evidence is a Good Idea.
1) To break up purported class actions. By exposing the material physical differences between plaintiffs, class claims can be defeated.
2) To force plaintiffs to back down. In toxic tort litigation, some of the most financially successful plaintiffs’ firms use templates for their cases. This allows them to recycle the same theories and defenses with only a modest investigation of the individualized facts. Firms using such a model are disinclined to invest the time and money needed to understand genomics and the genomics of a particular plaintiff. Instead, they may dismiss claims or settle for a relatively small amount.
According to a lawyer affiliated with ToxicoGenomica, “we are seeing an increase in cases settling quickly after disclosure of a high quality expert report that proves up the existence of combinations of adverse germline mutations inherited by a person with cancer and a family history of cancer.”
3) To dispute exposure. Some forms of genomic analysis can be used to generate data to show whether a plaintiff has or has not been exposed to a particular toxicant. For example, increasing numbers of studies evaluate the presence or absence of exposures based on patterns involving small or large segments of RNA. Studies of this sort are increasingly used to assess genomic changes related to use of tobacco.
4) To combat the scope of general causation. Genomic evidence can provide previously unknown, but objective evidence, to dispute general long-held beliefs about general causation. For example, for years, juries were unpersuaded by the argument that mesothelioma could be “idiopathic,” meaning cause unknown. Today’s jurors, raised on TV shows such as CSI, expect and want to see objective scientific data. Recently, researchers used new scientific tools (e.g., “CRISPR”) to create genetically engineered mice that developed mesotheliomas without asbestos exposure when given mutations that promoted general cancer development, supporting the argument that mesotheliomas can be idiopathic or at least not related to asbestos exposure. These new genomic and molecular tools, such as CRISPR, are of paramount importance for litigation. It allows researchers to perform studies and experiments that were previously not possible to determine the impact of various substances on humans and even a given individual. Risk managers, lawyers and others do not need to know the nuances of how to use these tools, but they should know of their existence. To read more on this subject, see my three-part Article “Using Genetic Evidence to Defend Against Toxic Tort Claims,” co-authored with Dr. Whitney Christian and initially printed in the Intellectual Property & Technology Law Journal (2017). https://www.bclplaw.com/images/content/9/9/v2/99117/IP-Reprint-Article-complete.pdf
5) To demonstrate alternative causation. Genomics can provide objective evidence of the presence or absence of adverse germline mutations known to play a causative role in the hundreds of known familial cancer syndromes. Persons who inherit these adverse germline mutations are genetically predisposed to develop cancers and/or other conditions attributable to inherited mutations.
6) To demonstrate a plaintiff’s susceptibility to or resistance to a particular toxicant.
The presence of a protective mutation (an allele) may make it less likely that the substance in question actually caused the disease. For example, in a benzene case, the plaintiff’s expert claimed that the plaintiff likely had a genome that made him more susceptible to a disease when benzene was metabolized. The scientists at ToxicoGenomica assessed his relevant genes and found the opposite, that he had a favorable genome that helped his body resist possible adverse effects. After receiving the data generated by ToxicoGenomica, the plaintiff’s expert changed his mind and agreed that: 1) the plaintiff was not susceptible and 2) had a robust genome with respect to metabolism of benzene.
7) To contest specific causation. Genomics increasingly can identify somatic signature mutations patterns or non-inherited mutations in tumors. These patterns of somatic mutations increasingly can be used to provide objective evidence showing that a particular toxicant caused the tumor. Extensive somatic mutation pattern analysis of lung cancers in smokers has produced large amounts of data objectively showing that particular lung cancers arose from tobacco smoking instead of something else. In other instances, the pattern may suggest that the tumor arose because of an inherited mutation in a gene such as KRAS.
8) To tackle specific causation. In some cases, gene expression profiling can be used to determine with more precision whether a person’s disease was or was not caused by a specific toxicant. Exposure to certain substances leaves behind “genetic fingerprints.” If those fingerprints are missing, then it is reasonable to conclude that the toxicant did not cause the disease.
This technique was used successfully in a case involving naturally occurring radioactive materials. The defendants were able to show that the footprints were missing and that the plaintiff’s gene expression instead supported that view that she had developed cancer from inherited mutations. 
Caution for the Defense Attorney. While genomic evidence can help defendants, it can certainly be used to support a plaintiff’s claim and provide evidence of both exposure and causation. As a result, it would be wise for counsel to assess carefully whether genomics is appropriate in a given case.
An example of genomics aiding plaintiffs lies in a federal multi-district litigation involving a diabetes drug known as Actos, which was alleged to cause bladder cancers in some people. The MDL court held an extensive Daubert hearing, which included expert opinions on how genomics could provide a logical explanation for why cancers developed in an unusually short time period (less than 1 year). The court decided to admit the genomic evidence, which made plaintiff’s claims much more plausible. After that ruling, and after some other trial losses, defendants subsequently agreed to pay over $2 billion in settlements.
 The collection, classification and analysis of biological information using computers.
 See Krishnan et al, A comprehensive study of smoking-specific microRNA alterations in head and neck squamous cell carcinoma. Oral Oncol. 2017 Sep.;72:56-64.
 Kukuyan et al., Inactivation of Bap1 Cooperates with Losses of Nf2 and Cdkn2a to Drive the Development of Pleural Malignant Mesothelioma in Conditional Mouse Models. Cancer Res. 2019 Aug 15;79(16):4113-4123.
 See Lindor NM, et al., National Cancer Institute, Division of Cancer Prevention, Community Oncology and Prevention Trials Research Group. Concise Handbook of Familial Cancer Susceptibility Syndromes – Second Ed. J Natl Cancer Inst Monogr. 2008;(38):1-93.
 See Alexandrov et al., Signatures of Mutational Processes in Human Cancer. Nature. 2013 Aug 22; 500(7463):415-21.
 See Jarvis, Sensenbrenner and Whitmore, Game Changer: Genetics and Genomics: Making the Invisible Visible, For The Defense, April 2015 at 64.