Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Researchers Wrestle with When to Make the Cut, and When Not

In their seminal 2012 paper describing CRISPR, Jennifer A. Doudna, Ph.D., of University of California, Berkeley, Emmanuelle Charpentier, Ph.D., now of the Max Planck Institute for Infection Biology, and colleagues, more than understated the transformative impact of the technology whose role in genome editing they co-discovered.

Clustered regularly interspaced short palindromic repeats (CRISPR) based on RNA-programmed Cas9, they wrote, offered “considerable potential for gene-targeting and genome-editing applications” as an alternative to zinc-finger nucleases and transcription-activator–like effector nucleases.

That potential has been described as everything from treating diseases with a genetic component, to “playing God” by using the technology for permanent germline editing of human genomes. Over the past 18 months, at least four researcher-driven study groups have weighed the scientific, medical, legal, and ethical implications of gene editing.

“The leaders in this rapidly developing field had been at the forefront in raising the important questions to the larger community and the government,” James E. Haber, Ph.D., director of the Rosenstiel Basic Medical Sciences Research Center at Brandeis University, told Clinical OMICs. “I am not sure how—given the existence of 196 recognized countries who can’t unanimously agree on much of anything—government can be fully effective in containing the technology. But in the USA, the NIH and the US National Academies have played—and should play—a strong role in articulating the ethical use of gene editing.”


Proceeding with Caution

With such a powerful and easy to employ technology beginning to make significant inroads in the clinical research community, stakeholders in the U.S and around the world have begun have begun to dig into the ethical implications and proper uses of CRISPR.

On July 12, the National Academies’ Human Gene-Editing Committee held its fourth meeting aimed at balancing the medical benefits and moral questions of germline gene editing.

The Academies in June recommended a go-slow approach to gene drives, which like CRISPR have raised questions about the potential for impacting not just individual organisms, but entire species and ecosystems. In addition, Three European groups—the Federation of European Academies of Medicine, the UK Academy of Medical Sciences and the Académie Nationale de Médicine France—held an April 28 workshop to discuss genome editing activity in the EU, and the need for a European regulatory framework to govern safe and acceptable use of human genome editing. But it produced no immediate recommendations.

In September 2015, the Hinxton Group international consortium cautiously recommended that human gene editing research proceed—but not clinical applications: “We believe that while this technology has tremendous value to basic research and enormous potential for somatic clinical uses, it is not sufficiently developed to consider human genome editing for clinical reproductive purposes at this time.”

Early last year, 18 researchers met in Napa, Calif., to discuss the scientific, medical, legal, and ethical implications of gene editing. The Napa group included Nobel laureate David Baltimore, Ph.D., and George M. Church, Ph.D., of Harvard Medical School, who with Doudna are among co-founders of Editas Medicine, launched in 2013 to translate their genome editing research into new therapeutics. (Another Editas co-founder, Feng Zhang, Ph.D., of the Broad Institute of MIT and Harvard, is defending 12 CRISPR-related patents awarded to him from a challenge by Charpentier and Doudna being heard in a U.S. Patent and Trademark Office “interference” proceeding.)

Doudna served as corresponding author for the group, which recommended in part that steps be taken to “strongly discourage 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.”

In a Q&A posted on the blog of Paul Knoepfler, Ph.D., of UC Davis School of Medicine, 10 days before online publication of the Napa statement in Science, Dr. Church carved out his own view. He said he didn’t think germline editing was either the next goal or next logical step for gene editing—but might be an acceptable side-effect of treating genetic diseases early, safely, and effectively.

“I really don’t know why people are singling out CRISPR as being different from every other research and clinical application,” Church told Clinical OMICs last month. “How is it different from gene therapy in general, or how is it different from therapies in general? All of them go through exactly the same process.”

That process, he said, is the clinical trials system designed to address the safety and efficacy of new products and technologies: “I don’t see any new ethical problems.”

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This article was originally published in the August 2016 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to www.clinicalomics.com.

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