Abstract
Last month saw the publication of a major report—Heritable Human Genome Editing—coauthored by a diverse group of 18 experts under the auspices of the National Academy of Sciences, the National Academy of Medicine, and the U.K.'s Royal Society. After a year of research and information gathering, this blue-ribbon commission has assessed the clinical implementation boundaries of hereditary human genome editing (HHGE).
The report comes against a backdrop of preliminary but exciting progress as CRISPR-based gene therapies advance in clinical settings. Two years ago, there was a real fear that the actions of He Jiankui in pursuing HHGE might derail the promise of somatic gene editing. Thankfully those concerns have not materialized, but it is incumbent on the scientific community to chart a responsible forward path. Led by two eminent human geneticists, Dame Kay Davies (University of Oxford) and Rockefeller University President Rick Lifton, the International Commission on the Clinical Use of Human Germline Genome Editing has issued a meticulous consensus report that does just that. 1
As the HHGE report makes clear, CRISPR or base editing is not yet ready to be implemented in human embryos. But when those hurdles are overcome, the report offers an admittedly narrow translational pathway that could see the method offered for relatively small number of couples who seek a biologically related child and who lack viable alternatives such as preimplantation genetic testing. This topic was presciently addressed in an article we published 12 months ago, in our first thematic issue on human genome editing. 2
In this issue, we publish three articles that pertain directly to the publication of this report and the intense international discussion about the future of HHGE. On page 325, in an exclusive interview, Kay Davies offers an inside look that sheds some interesting light on the HHGE commission's report. In some ways, the commission was dealt a difficult hand, striving to formulate a translational pathway for HHGE while (for the most part) sidestepping the important ethical questions. These will be the focus of another commission convened by the World Health Organization (WHO), which is expected to report in the next 3–6 months.
Naturally, the HHGE report has provoked a broad range of opinions. On page 333, we publish a fascinating perspective that chronicles the diverse reactions of three-dozen experts—geneticists, ethicists, legal scholars, and more—including several CRISPR pioneers such as Jennifer Doudna, Feng Zhang, David Liu, and George Church. We thank all these researchers for sharing their candid views and critiques.
Last but not least, we also publish an important research article from Francoise Baylis, Marcy Darnovsky, and colleagues, which offers the most comprehensive survey to date of the global policy landscape regarding germline and hereditary genome editing (see page 365). The researchers gathered data on >100 countries, highlighting the variability, and perhaps even the inadequacy, of national policies and regulations that apply to basic and clinical research on human embryos. Clearly this is an especially important topic for our readership and the scientific community, one that we will continue to monitor keenly.
Reaching a consensus seems like a democratic means to define what most would deem acceptable. Of course this process is flawed, such proceedings typically fueled by colorful arguments delivered by opinionated people trained to make their case. Kay Davies freely admits there were such debates on the HHGE commission, but the final report reflected a strong consensus.
But as several commentators note in the perspective, the HHGE report fails to capture the opinions and thus compel buy-in of the general public. This was, let us be clear, beyond the scope of the commission's brief. But the challenge of reaching a societal, not merely a scientific, consensus remains a major hurdle.
Nevertheless, we should heed the commission's central recommendations, notably the establishment of an International Scientific Advisory Panel. This must be done promptly to make sure that the wisdom captured in this report extends beyond academics curious and clinicians responsible enough to read and heed it. The HHGE report should act as a strong deterrent to any future rogue scientists who disregard community-wide guidelines, and we must thus demand oversight by organizations with enforcement power. Without this, the scientific wisdom of the academic world is neither authoritative nor enforceable.
The collage of opinions published in this issue highlights key areas that need further improvements, as well as some gaps to address, as we continue to assess and advance genome editing technology and define if and when it can be responsibly implemented to modify the human germline. We hope the WHO report will exhibit the same degree of research and scholarship. Looking forward, this journal hopes that the sage opinions presented in this volume will be used to inform future committees and organizations tasked with providing responsible guidelines for the use of this promising technology, and developing standards for the oversight of human genome editing.