Legal Risks and Liabilities of Human Gene Editing

Somatic Gene Editing

Human gene editing will likely be limited to somatic tissues for at least the near future, so liability risks associated with such somatic treatments are of the most immediate concern. Liability could potentially apply in either the research or clinical context, with research scenarios being the most salient for now, as it will take many years of clinical trials before somatic gene editing will be commercially available in a nonresearch context. In most respects, gene editing research will present similar risk and liability scenarios as current somatic gene therapy trials. A threshold requirement will be an injury to one or more research subjects allegedly resulting from the genetic procedure. But injury alone is not enough to create liability—many medical procedures are inherently risky, and the fact that there is a bad outcome does not necessarily mean that liability should attach.

Rather, there must be a showing of negligence or defect before liability can be imposed. Two important distinctions differentiate the types of claims that can be brought. The first distinction is whether the claim is for negligence or products liability. Negligence will normally apply in a claim for professional malpractice by a physician or researcher, while products liability will apply primarily to the manufacturer or sponsor of a product, but most often will include everyone and all entities in the chain of distribution. The second distinction is between gene editing applied in the clinical versus the research context.

Starting with professional malpractice, the standards for negligence can differ between the research and clinical context. In the clinical context, there is a physician-patient relationship in which the physician has a fiduciary responsibility to the patient. The standard of care in the clinical context is usually based on local custom, measured by what a similar practitioner in the same locale would have done in similar circumstances. All U.S. somatic gene therapy attempts to date, and somatic gene editing for the immediate future, will be in the research rather than clinical context. Here, there is no doctor-patient relationship, and thus no fiduciary duty of the researcher to the research subject.

Yet, while the expectations imposed on the researcher are less burdensome than for a physician, the researcher nonetheless has a responsibility to take due care, and can be sued if an injury results from the lack of due care. Over the past couple decades, there has been an increase in health researchers being sued for injuries they cause in their research subjects. For example, a subject harmed by research will often claim that the researcher failed to provide adequate information about the risks of the proposed treatment to enable the research subject to make an informed decision on whether to undertake the risk, creating a claim of lack of informed consent. Although informed consent documents are reviewed by the institutional review board (IRB), National Institutes of Health (NIH), and Food and Drug Administration (FDA) in gene therapy trials (and presumably in future gene editing), compliance with government requirements for informed consent do not provide immunity to liability from common-law lack of informed consent when the researcher or physician fails to provide information that a judge or jury deems appropriate.

There have been some recent lawsuits against researchers for injuries incurred in somatic gene therapy trials, most prominently the suit brought by Jesse Gelsinger’s family after he died from an adverse response to a gene therapy procedure administered at the University of Pennsylvania in 1999. Although Gelsinger’s family initially indicated it did not intend to file a lawsuit, as further details about the case emerged, including undisclosed changes to and misrepresentations in the informed consent forms and failure to disclose financial interests, the family did file a negligence lawsuit that was subsequently settled for an undisclosed sum. The lawsuit was filed against the researchers, the university at which they worked, the corporate sponsor of the gene therapy “product,” and a bioethicist who advised the study (who was subsequently dismissed from the case prior to settlement).¹

Gene editing research would present similar liability risks as have occurred in gene therapy research. Because the technology is more novel and new, it is possible that it would be more challenging for a researcher to provide fully informed consent, perhaps creating a greater liability risk if harm occurs. On the other hand, if gene editing is more precise than traditional gene therapy, there may be less likelihood of an injury occurring in the first place, thus reducing liability risks.

In addition to malpractice liability for researchers, there is also the prospect that an injured research subject could bring a products liability action against the company developing the gene editing treatment, as was the case in the Gelsinger lawsuit. If “gene editing” is construed as a product, in the same way that a drug or device is a product rather than a procedure, the manufacturer of that product can be liable for any defects in that product, which can include both design defects and failure to warn defects. Products liability brings the potential for more stringent penalties, including strict liability and punitive damages.

Germline Gene Editing

Germline gene editing is not on the immediate horizon, but many believe it is just a matter of time before it is attempted with a viable human embryo (it already has been attempted with nonviable human embryos²). Because every cell in the resulting person and his or her future progeny could be affected by gene editing, the consequences of any error or unanticipated effect would likely be much greater than for somatic gene editing, and hence both the harm and the liability potential could be greater. The legal issues in bringing a liability case for germline gene editing would also be more complex, including what type of cause of action could be brought, who might be the defendant in such a lawsuit, and under what time limits could a case be brought.

In terms of cause of action, the two most likely claims would be wrongful birth or wrongful life. A wrongful birth case is brought by the parents to recover the extra costs and suffering they incurred from having a child with a birth defect where a reasonable healthcare provider negligently failed to warn about or detect such a risk. A wrongful life case is brought on behalf of the child, alleging that he or she would have been better off not being brought into existence had the healthcare provider exercised due care. These types of cases are typically brought when a healthcare provider fails to diagnose or warn about a genetically at-risk pregnancy. Approximately 20 states currently recognize wrongful birth causes of action, whereas only three states recognize wrongful life causes of action.

However, there is an important difference between wrongful birth/life cases that might result from germline gene editing compared to typical genetic misdiagnosis cases. In the typical genetic misdiagnosis case, the healthcare provider did not cause the adverse health problem in the fetus, as that “defect” occurred naturally at the moment of conception through no fault of the healthcare provider. Rather, the healthcare provider’s failure to warn about or diagnose that genetic condition deprived the parents of the opportunity to terminate the pregnancy, the only recourse to prevent the birth of the affected child. Accordingly, a major issue contested in most wrongful birth cases is whether the parents would have indeed aborted the fetus if given timely warning of the genetic affliction—because if they were not willing to abort their fetus, the physician’s negligence would not have had any practical impact. Because of the reliance on abortion in wrongful birth claims, antiabortion groups have opposed recognition of these claims, and have recently successfully combined forces with physician groups to abolish wrongful birth claims in a number of states (e.g., Arizona, Kansas, and Utah).

A gene-editing wrongful birth claim would not have the same connection with abortion. If gene editing created a health problem in a progeny, the provider or researcher who conducted the gene editing would now be the cause of the disability, and if his or her actions were deemed to be negligent, liability should apply whether or not the parents would have aborted the fetus if they knew it was damaged. This means that there no longer would be any need for parents to testify they would have aborted their existing child if they had been informed of the birth defect in utero, and thus no reason for antiabortion groups to oppose such claims. Therefore, when the gene editing professional’s negligence causes the birth defect—as opposed to simply delaying the detection of the defect—it would be a much more traditional and noncontroversial medical malpractice case.

There will also be issues as to who could be sued. The researcher or physician who conducted the germline gene editing and the research institution would be the primary target, along with the product sponsor. Given the novel, and some would say radical, nature of such a procedure, the practitioner who conducted the gene editing would be highly exposed to liability for any adverse effects that should result. The institution that conducted the procedure, the IRB at that institution, and any company that sponsored the trial could also be included in the lawsuit.

A novel defendant may be the parents who allowed their future children to be genetically modified. This could only occur in a wrongful life case brought by the injured child (rather than a wrongful birth action brought by the parents), which is currently only recognized by three states (one of which, California, has provided statutory immunity to parents). So presently only in two states (New Jersey and Washington) would it be possible for an injured child to bring a wrongful life case against his or her parents for negligently risking a gene editing procedure.

The final unique issue is when a lawsuit could be brought for injuries resulting from germline gene editing. An unanticipated effect of gene editing may not be detected immediately, but may be discovered several decades or even generations down the road. Statutes of limitations and repose may limit the rights of a person injured by gene editing from bringing a lawsuit decades after the procedure occurred. A wrongful life suit brought on behalf of the injured progeny would likely have the greatest chance of success, because the statute of limitations generally does not run against the legal rights of minors until they reach the age of majority. But even then, the adverse effect may not be discovered until the person is middle age or later, and it is unclear whether a suit would be allowed then under either a statute of limitations or a statute of repose. Even more problematic would be if the problem was not detected until one or two generations later, which is quite plausible. For example, in the DES litigation, courts have been reluctant to allow third-generation suits by grandchildren of mothers who took DES, based on a jurisprudential need to achieve finality and closure in liability risks for a given action.

Conclusion

In conclusion, while somatic gene editing is likely to present some liability risks that are not that different from current gene therapy trials, germline human gene editing would present some novel and challenging liability issues.

Endnotes

1. See Gene Therapy Death Lawsuit Settled, CBS News (Apr. 13, 2000), http://www.cbsnews.com/news/gene-therapy-death-lawsuit-settled/; U.S. Settles Case of Gene Therapy Study That Ended with Teen’s Death, Univ. Pa. Almanac (Feb. 15, 2005), http://www.upenn.edu/almanac/volumes/v51/n21/gts.html.

2. See Xiangjin Kang et al., Introducing Precise Genetic Modifications into Human 3PN Embryos by CRISPR/Cas-Mediated Genome Editing, 33 J. Assisted Reprod. & Genetics 581 (2016); Puping Liang et al., CRISPR/Cas9-Mediated Gene Editing in Human Tripronuclear Zygotes, 6 Protein & Cell 363 (2015).