LONDON – Clinical trials involving genome editing in gametes or early embryos could be permitted in the future, but only for serious conditions and under stringent oversight, said experts after a year-long review of the scientific and ethical issues thrown up by CRISPR/Cas9.

Germline gene editing is contentious because the genetic changes would be inherited. However, it would give people who are carriers of inherited diseases their best option for having genetically related children who are free of disease, and for this reason germline gene editing should not be prohibited, according to the Committee on Human Gene Editing.

While heritable germline editing does not yet reach the necessary risk/benefit standards for clinical trials, the technology is advancing rapidly, making heritable editing, "a realistic possibility that deserves serious consideration," the committee said in its report published Feb. 14, 2017, by the U.S. National Academies of Sciences and Medicine.

The committee was set up in December 2015 following a summit on the issue in Washington, convened by the national academies of China, the U.K. and the U.S. in response to concerns about the potential misuse of CRISPR/Cas9. (See BioWorld Today, Dec. 8, 2015.)

A number of countries have signed an international convention banning germline editing and at present it is prohibited in the U.S.

The current effect of this provision is to make it impossible for U.S. authorities to review proposals for clinical trials of germline genome editing, and therefore to drive development of this technology to other jurisdictions, some regulated and others not, the committee noted.

If the current restrictions on the FDA were to be removed, several criteria would have to be met before there are any clinical trials. They include: the absence of reasonable alternatives; only editing genes that are known to cause or strongly predispose to a serious disease; rigorous oversight of clinical trials with comprehensive plans for long-term, multigenerational follow-up; and continued reassessments of health and societal benefits.


Clinical trials using edited somatic (non-heritable) cells are in progress and the committee said they should continue to be regulated using the existing framework for the development of gene therapies.

However, the report draws a distinction between ex vivo editing of cells, where the edit can be checked before the cells are administered, and in vivo administration of a genome editing construct into the bloodstream or target organ, where technical challenges remain.

Those include off-target effects and the inadvertent editing of germline cells. But despite greater technical challenges, trials of in vivo editing are in train in hemophilia B and mucopolysaccharidosis, implying the current regulations are fit for purpose.

Similarly, basic research involving genome editing of human cells and tissues is suitably covered. "Basic laboratory research in human genome editing is already manageable under existing ethical norms and regulatory frameworks," the report said.

In view of the shadow cast by eugenics and in the face of public disquiet, the committee concludes there should be no use of somatic gene editing for the enhancement of human traits, such as height or physical strength, at this time.

However, the committee did not rule out the use of genome editing for enhancement, but said there should be consultation first.

"Broad public input and discussion should be solicited before allowing clinical trials for somatic gene editing for any purpose other than treating or preventing disease," the report stated. One of the key issues to be dealt with will be defining enhancement. Using genome editing to enhance musculature of patients with muscular dystrophy is evidently curative, doing it for someone with no known pathology to make them stronger could be enhancement.

Co-chair of the committee, Alta Charo, professor of law and bioethics at the University of Wisconsin-Madison said genome editing to enhance traits or abilities raises concerns about whether the benefits outweigh the risks, and also "about fairness if only available to some people."

Because CRISPR/Cas9 is so precise and efficient, it has opened up possible applications that previously were viewed as largely theoretical. The versatility, ease of use and low cost has led to widespread uptake and successful genome editing by CRISPR/Cas9 that can be done by researchers with standard degree level skills in molecular biology.

The Washington summit and the subsequent formation of the committee were prompted by concerns that the potential for misuse of genome editing might stand in the way of its application in biological research and human therapies.

In 2016 the committee held a series of meetings in Washington and Paris where it heard evidence from invited experts and the public. While the resulting report is broadly in line with the conclusions of the December 2015 summit, the difference now is that ethicists, health care providers, patients, research funders, regulators and the public have contributed their views to a peer-reviewed report that has fully scoped the technology, its applications and the technical and ethical constraints.

The immediate impact will be in underlining that the current regulations are adequate for overseeing basic research and somatic gene therapies that use CRISPR/Cas9, and no specific rules are needed for the technology in these applications.

And whether the report will in any way influence attitudes to editing somatic cells for human enhancement or germline alterations to treat serious diseases will be in the hands of a Trump administration that is on the one hand socially conservative and on the other intent on reducing the regulatory burden.