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Clinical trials on genome editing in humans should only be used for the purpose of treating or preventing serious disabilities and diseases, according to a new report from the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM).

Genome editing isn’t a new concept in basic research, and some clinical trials are already using this method for somatic or nonheritable applications. Emerging gene editing tools—technology that shows promise in adding, deleting, and making changes to the human genome—are garnering attention in the research community. NAS and NAM decided to convene a panel to study the governance, science, and ethical issues related to this technology. 

“The development of new approaches—involving the use of meganucleases; zinc finger nucleases (ZFNs); transcription activator-like effector nucleases (TALENs); and, most recently, the CRISPR/Cas9 system—has made editing of the genome much more precise, efficient, flexible, and less expensive relative to previous strategies,” the committee explained in its report. 

These advances hold the prospect of “editing” the human germline and preventing inherited disease in future generations or perhaps editing somatic cells to revive diseased organs.

“Human genome editing holds tremendous promise for understanding, treating, or preventing many devastating genetic diseases and for improving treatment of many other illnesses,” said Alta Charo, JD, co-chair of the study committee and professor of law and bioethics at the University of Wisconsin-Madison, in a statement issued by the NAS.

Yet, public concerns have arisen over genome editing’s potential to “enhance” physical strength, intelligence or other human traits, and the risks associated with these modifications. As Charo noted, this also brings up questions about fairness—if such enhancements would only be accessible to certain people.

For these reasons, the report recommended against using genome editing to enhance human traits. For now, the primary use of somatic genome editing is to help prevent or treat disability or disease, the committee stressed. Additionally, the public should have the opportunity to provide input should genome editing be used for any other purpose.

Not all countries, including the United States, currently allow the use of germline (heritable) genome editing, which has brought up ethical concerns due to its ability to effect genetic changes in future generations. Authorities in the U.S. aren’t allowed to pursue such research because the U.S. Food and Drug Administration is prohibited from funding trials to assess “research in which a human embryo is intentionally created or modified to include a heritable genetic modification,” according to the report, quoting from the Consolidated Appropriations Act of 2016, Public Law 114-113.                         

For those countries that do allow for germline editing research, the committee decided that this would be permissible. This is “only following much more research aimed at meeting existing risk/benefit standards for authorizing clinical trials and even then, only for compelling reasons and under strict oversight,” the committee recommends.  A trial should proceed only if its focus is on preventing a serious condition or disease and if no other reasonable alternatives to the trial are available. Genome editing should also be limited to genes that have been known to “cause or strongly predispose to the disease or condition.”

In other criteria, a trial must restrict itself “to converting such genes to versions that are prevalent in the population and are known to be associated with ordinary health with little or no evidence of adverse effects,” the committee indicated.

Such trials aren’t likely to happen in the near future, Richard Hynes, PhD, an investigator at the Howard Hughes Medical Institute and professor for cancer research at the Massachusetts Institute of Technology noted in an NAS video interview. “It’s going to take several years of research before one could consider doing germline editing. But one can see a logical way forward to getting there. One can no longer dismiss it as just not possible,” Hynes said.

Once germline editing does get underway, it won’t involve a large number of patients, but still, researchers should proceed with caution, Hynes said. “But caution doesn’t mean prohibition,” he said.

The report’s authors listed a series of principles that all nations should follow to govern human genome editing activities. These include:

●     promoting well-being and preventing harm to affected parties;

●     fostering transparency and sharing of information in a manner that’s accessible to patients, families, and other stakeholders;

●      showing due care toward participants in research studies by proceeding only when supported by strong evidence;

●     adhering to the highest standards of research from “bench to bedside”;

●     showing respect and recognizing the personal dignity of involved individuals;

●     treating all cases equally with respect to risks and benefits; and

●     transnational cooperation, which acknowledges and respects different cultures in collaborations across nations.

“Genome editing research is very much an international endeavor, and all nations should ensure that any potential clinical applications reflect societal values and be subject to appropriate oversight and regulation,” Hynes said in the NAS statement.