The future of human genome editing

Journal name:
Nature Genetics
Volume:
49,
Page:
653
Year published:
DOI:
doi:10.1038/ng.3860
Published online

With the advent of precision genome editing, the ability to modify living organisms has proceeded with remarkable speed and breadth. Any application of this technology to the human germ line must be tightly coupled to deliberate consideration of the consequences, both scientific and social, of introducing heritable alterations to the human population. We recommend constant oversight and evaluation of human germline genome editing to balance prudence with discovery, and risk with progress.

Recently, the US National Academy of Sciences and National Academy of Medicine released their report on recommendations for human genome editing (http://nationalacademies.org/gene-editing/index.htm). The committee that authored the report comprised research scientists, clinicians, regulatory agents and bioethicists, and the goal was to reach consensus guidelines for responsible applications of human genome editing in the laboratory and the clinic. This report clearly lays out the scientific and social implications of human genome editing and proposes guiding principles for its use. We strongly support the advance of science while at the same time agreeing that it is prudent to proceed with caution, particularly with regard to rapidly developing technologies that have the potential to have a profound impact on research, medicine and society.

The capacity to edit genes has existed for decades, and genetic modification is common practice in the laboratory. The reason for the heightened attention and concern now is that technological advances have enabled the precise editing of genomes at unprecedented speed and scale. Zinc-finger nucleases, TALENs and, now, the CRISPR–Cas9 system have revolutionized scientific discovery. As such, the applications of these powerful tools must be thoroughly discussed and debated. While applications of genome editing to laboratory organisms, crop plants, domestic animals and disease vectors come with different considerations of varying complexity and consequence, the use of genomic editing to introduce potentially heritable alterations in humans should be in a separate category, subject to greater scrutiny and regulation.

We wrote in these pages last year (Nat. Genet. 48, 103, 2016) that genome editing in crop plants should be regulated on the basis of the end product, not the process by which genetic mutations are introduced. Genome editing is merely a faster and more accurate method than classical breeding and is not fundamentally different. While it may be an appropriate approach for plants and domestic animals, a distinct line can be drawn between these applications and ones involving genetic modification of the human germ line, which justify greater oversight. Although there are regulations for gene therapy, the exceptional versatility and precision of genome editing elevate the possibilities of not only what modifications can be made but also how quickly and accurately they can be introduced. Unintended or long-term consequences of editing humans or human germ cells and embryos have the potential to seriously affect not only the subjects themselves, but also their progeny.

We agree with the National Academies' recommendations that somatic genome editing should fall under existing regulations that apply to human clinical research. Correcting mutation through the germ line is different in kind, not degree. This is due to the fact that changes introduced into germ cells are heritable through subsequent generations. Therefore, these alterations have effects that go beyond a single individual. Data are lacking on the long-term consequences of germline genome editing. Off-target effects and lack of consent are two of the main issues to consider. The National Academies have recommended that germline genome editing trials be permitted, but only when compliant with all standards for human clinical trials along with additional rigorous oversight. They stipulate that such research be restricted to the treatment or prevention of disease. Any other application (for example, genetic 'enhancement') should not be allowed to proceed at this time.

This committee strongly recommended that the public be informed of progress already made in human genome editing as well as any future developments. We think it is especially important for scientists to make public education and outreach an integral part of their research and to have discussions with relevant parties, including members of the public, regulatory agencies and medical professionals. It is critical that the social license to operate these technologies for therapy not be infringed by premature experimentation on heritable genome engineering for proof of principle or academic priority. The future safety of germline edits is an important area for research that we think can readily be explained to the public.

Further, there are currently few genetic arguments for the necessity of correcting the genetic material of future generations given preimplantation diagnosis of monogenic conditions. Therefore, we think it is imperative to discuss future concepts of genome editing that could be considered acceptable therapies. One might discuss a panel of deleterious mutations lacking compensating selective advantages that would be justified for multiplex removal from all in vitro–fertilized (IVF) embryos. If germline editing technology could achieve this end routinely and safely, without genotypic discrimination, it would then be as ready for implementation as a panel of recommended vaccinations.

One can be supportive of scientific advance and at the same time advise reasonable caution in the adoption of powerful new technologies. Much more needs to be known about the safety and consequences of human germline genome editing before it can be considered for medical application. Additionally, the motivation for adopting the technology, together with legal and ethical issues, needs to be thoroughly discussed and revisited as more information becomes available. Allowing for clinical trials to proceed in this area, under strict oversight and without regional loopholes in legislation, will help answer some outstanding questions and usher in this new era with forethought and responsibility.

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