JAMA Forum: Heritable Genome Editing: Is a Moratorium Needed?

By Eli Adashi, MD, MS, and I. Glenn Cohen, JD

“If you don’t know where you are going, you might wind up someplace else.”Lawrence Peter “Yogi” Berra.

Image: Bill Oxford/Getty Images

Prompted by the reported birth of twins whose embryonic genomes may have been edited, an international group of 18 distinguished scientists and ethicists recently called for a voluntary global moratorium on all “clinical uses of human germline editing.” The proposed moratorium “does not apply to germline editing for research uses,” they wrote, “provided that these studies do not involve the transfer of an embryo to a person’s uterus.”

The proposed moratorium is envisioned as limited in duration to a “fixed period,” to allow forging of a broad societal consensus through thoughtful deliberation of relevant “technical, scientific, medical, societal, ethical, and moral issues.” An accountable international governance framework is ideally to follow.

Another group of 62 US scientists, bioethicists, and biotechnology executives recently articulated similar sentiments in a letter to the Secretary of the US Department of Health and Human Services.

Moratorium Critics
Conspicuously absent from the calls for a moratorium were some of the leading lights of the genome editing field who have since registered their misgivings. For example, Jennifer A. Doudna, PhD, of the University of California, Berkeley, a towering figure in the genome editing arena, supports “strict regulation that precludes use,” she told the health and medicine news site, STAT. “I prefer this to a ‘moratorium’ which, to me, is of indefinite length and provides no pathway toward possible responsible use.” The word moratorium implies enforcement, she said in an interview with the Washington Post, adding. “I don’t want to drive others underground with this.”

George Q. Daley, MD, PhD, dean of the Harvard Medical School and a fellow critic of the proposed moratorium, told STAT that “a moratorium complicates future discussions rather than clarifies them,” and noted that it is unclear who gets to decide how and when to rescind one.  Robin H. Lovell-Badge, CBE, of the Francis Crick Institute, in London, England, said in a statement that a moratorium is “unlikely to work well,” and that he is “fully supportive of research being carried out on early human embryos in vitro, especially on embryos that are not required for reproduction and would otherwise be discarded.” Nobel laureate David Baltimore, of the California Institute of Technology in Pasadena and chair of the organizing committee of past International Summits on Human Genome Editing, views moratoria as “draconian” and “antithetical to the goals of science.”

Viewed through the lens of US history, open-ended moratoria aimed at human reproduction are par for the course. An exhaustive analysis of these moratoria reveals them to slow scientific inquiry, withhold potential medical care, and foster cross-border medical tourism. Moratoria also run the risk of subjugating scientific inquiry to ideological convictions. A case in point is the statutory US moratorium on “heritable genetic modification,” which was affirmed on December 18, 2015. The US moratorium on the federal funding of human embryo research (also known as the Dickey-Wicker Amendment) was similarly motivated.

Unwitting Targets?
Broadly interpreted, moratoria may also ensnare unwitting targets. The seemingly unintended prohibition of mitochondrial replacement therapy by the US moratorium on “heritable genetic modification” constitutes one such example. Moratoria have also proven unnecessary. One striking example of this is the widely feared prospect of human reproductive cloning which, contrary to predictions, has not materialized in the absence of statutory or regulatory measures intended to prohibit it.

A more forgiving outlook of the moratorium debate might deem it a linguistic tempest in a teapot. Indeed, recent calls for a moratorium appear substantively similar to earlier statements on the subject that assiduously avoided the use of the word moratorium. In a 2015 statement on genomic engineering and germline gene modification, a distinguished academic contingent discouraged “any attempts at germline genome modification for clinical application in humans, while societal, environmental, and ethical implications of such activity are discussed among scientific and governmental organizations.”

The organizing committee of the International Summit on Human Gene Editing followed suit with the conclusion that until there is resolution of relevant safety and efficacy issues and “broad societal consensus about the appropriateness of the proposed application,” proceeding with any clinical use of germline editing would be irresponsible. Viewed collectively, earlier statements on heritable genome editing may have said it all without invoking the word moratorium.

The battle lines over heritable genome editing currently pit those who choose to ask “whether” to proceed against those who ask “how” to press on. The latter hold that the collective ethical good is best served by a “responsible path” toward the prevention of crippling monogenic disorders; they are willing to trust that regulatory agencies such as the US Food and Drug Administration will hold applications for heritable genome editing to rigorous demonstrations of safety and efficacy before they garner agency approval.

Those committed to asking whether to move forward with heritable genome editing espouse the primacy of a “broad societal consensus” as a precondition but have not articulated precisely how such societal accord may be attained. With few precedents or a process to draw upon, public education, discussion, and approval remain a work in progress. These and related challenges must be resolved in a timely fashion to ensure that the prevention of otherwise untreatable genetic maladies is not being held up. Such cures mustn’t wait.

###

About the authors:

Eli Y. Adashi, MD, MS, is a professor of Medical Science and the former dean of Medicine and Biological Sciences at the Warren Alpert Medical School of Brown University in Providence, Rhode Island. (Image: Brown University)

 

 

I. Glenn Cohen, JD, is the James A. Attwood and Leslie Williams professor of Law and director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School, Cambridge, Massachusetts. (Image: Martha Stewart)

 

 

About The JAMA Forum: JAMA has assembled a team of leading scholars, including health economists, health policy experts, and legal scholars, to provide expert commentary and insight into news involving the intersection of health policy and politics, economics, and the law. Each JAMA Forum entry expresses the opinions of the author but does not necessarily reflect the views or opinions of JAMA, the editorial staff, or the American Medical Association. More information is available here and here.



Categories: Health Policy, Law and Medicine, The JAMA Forum

Tags: , , ,