A group of key researchers and ethicists from seven countries today called for a temporary moratorium on all clinical uses of human germline editing pending the creation of an international governance framework for carrying out the research under certain conditions.

The moratorium envisioned by the experts would apply to changing heritable DNA in sperm, eggs, or embryos to make genetically modified children. It would not apply, however, to germline editing for research uses that do not involve transfer of an embryo to a person’s uterus—or to genome editing in human somatic cells to treat diseases.

“The framework we are calling for will place major speed bumps in front of the most adventurous plans to re-­engineer the human species. But the risks of the alternative—which include harming patients and eroding public trust—are much worse,” the group of 18 experts cautioned in their commentary published in Nature, “Adopt a moratorium on heritable genome editing.”

Eric S. Lander, PhD, president and founding director of the Broad Institute of MIT and Harvard, was one of the five lead authors of the commentary. He was joined by bioethicist Françoise Baylis, PhD, of Dalhousie University; CRISPR pioneers Feng Zhang, PhD, of the Broad Institute and Prof. Emmanuelle Charpentier, PhD, founding and acting head of the Max Planck Unit for the Science of Pathogens in Berlin; and Paul Berg, PhD, co-winner of the 1980 Nobel Prize in Chemistry for his 1971 landmark gene-splicing experiment, and the Robert W. and Vivian K. Cahill Professor of Cancer Research, Emeritus, at Stanford University.

Thirteen researchers and ethicists joined the five lead authors in calling for the moratorium and international framework. The co-authors wrote that they envisioned “an initial period of fixed duration during which no clinical uses of germline editing whatsoever should be allowed.”

Following that period, nations could then choose whether to permit specific applications.

However, nations would proceed “openly and with due respect to the opinions of humankind on an issue that affects the human species” by agreeing not to approve applications without first meeting certain conditions.

The call for a moratorium and development of a governance framework won immediate support from the NIH.

NIH Director Francis S. Collins, MD, PhD, and Carrie D. Wolinetz, PhD, the agency’s Associate Director for Science Policy, said they agreed with the co-authors that the risks of human germline editing far outweigh its benefits, citing “serious and unquantifiable” safety issues, ethical concerns and lack of “sufficiently compelling” medical applications.

“This is a crucial moment in the history of science: A new technology offers the potential to rewrite the script of human life,” Collins and Wolinetz stated in correspondence to Nature. “We think that human gene editing for reproductive purposes carries very serious consequences—social, ethical, philosophical and theological. Such great consequences deserve deep reflection.”

“Societies, after those deeper discussions, might decide this is a line that should not be crossed. It would be unwise and unethical for the scientific community to foreclose that possibility,” Collins and Wolinetz added.

They also noted that NIH policy bars support for germline gene-editing technologies in human embryos. However, the agency considers “among our highest priorities” research on therapeutic uses of gene editing in somatic cells in diseases such as sickle-cell anemia and muscular dystrophy.

“Sufficient” Safety and Efficacy

The co-authors laid out technical, scientific, and medical considerations—as well as societal, ethical, and moral considerations that they said should inform deliberation and eventual decisions on germline editing.

The first consideration is showing “sufficient” safety and efficacy, which has yet to occur: “Although techniques have improved in the past several years, germline editing is not yet safe or effective enough to justify any use in the clinic.”

Another consideration, they said, was understanding long­-term biological consequences of germline editing, both for individuals and for the human species. The experts distinguished between genetic correction such as of a disease-related rare mutation, which they said could have a predictable beneficial effect “assuming that it can be done without errors or off-­target effects” and genetic enhancement, which they acknowledged would be fraught with uncertainty.

“Attempting to reshape the species on the basis of our current state of knowledge would be hubris,” the commentary authors warned. “Genetic enhancement of any sort would be unjustifiable at this time, given the scientific considerations already mentioned.”

Clinical germline editing, the co-authors added, “should not proceed for any application without broad societal consensus on the appropriateness of altering a fundamental aspect of humanity for a particular purpose.”

The co-authors cited a series of events in the more than three years since organizers of the first International Summit on Human Gene Editing, chaired by David Baltimore, PhD, president emeritus of the California Institute of Technology, called for caution.

Three of the lead authors of today’s commentary—Lander, Baylis, and Berg—were members of the Summit’s 12-member organizing committee, which declared in December 2015 in a statement that “it would be irresponsible to proceed with any clinical use” of germline editing technology in children “unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application.”

“This should have been understood to mean that clinical uses of germline editing should not yet proceed anywhere in the world. Yet, subsequent events suggest that this statement was inadequate,” the authors of the today’s commentary lamented.

Outrage Over “CRISPR Babies”

The authors cited He Jiankui, PhD, the Chinese researcher who touched off international outrage in November 2018 following reports that he had supervised the birth of twin girls or “CRISPR babies” following germline editing. At an international genome-editing conference in Hong Kong, He presented details of his work and attempted to justify his decision to target the CCR5 gene to render the newborns resistant to HIV.

In January, He was fired by his university, the Southern University of Science and Technology (SUSTech) in Shenzhen, China. And last month, the editors of The CRISPR Journal agreed to retract a perspective article authored by He on the ethics of gene editing, 12 weeks after its publication. The CRISPR Journal is published by GEN publisher Mary Ann Liebert, Inc.

The co-authors also cited in part the lack of “adequate” measures to stop He’s work by scientists who became aware of it, and the absence of a mechanism since the 2015 Summit to ensure international dialogue about whether and when clinical germline editing may be appropriate. The commentary signatories also cited magazine accounts of growing interest in proposals for genetic enhancement of humans, and statements interpreted as weakening the requirement of broad societal consensus for germline editing.

One example of that, they said, was “Human Genome Editing: Science, Ethics, and Governance,” a 2017 report from the US National Academies of Sciences, Engineering, and Medicine that presented seven general principles for governance of human genome editing: Promoting well-being, transparency, due care, responsible science, respect for persons, fairness, and transnational cooperation.

Another example they cited was the statement from the organizing committee of the Second International Summit on Human Genome Editing, also chaired by Baltimore.

That committee acknowledged that “the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time.” However, the committee’s November 29, 2018, closing statement also declared: “It is time to define a rigorous, responsible translational pathway toward such trials.”

“Proper Consideration”

“A global moratorium and framework are therefore necessary to ensure proper consideration of the relevant issues surrounding clinical uses of germline editing,” the commentary co-authors concluded.

The 13 researchers who joined Lander, Baylis, Zhang, Charpentier, and Berg as co-authors of the commentary were:

Catherine Bourgain, PhD, director, Center for Research in Medicine, Science, Health, Mental Health, and Society (Cermes3), Inserm

Bärbel Friedrich, PhD, director of the Alfried Krupp Institute for Advanced Study in Greifswald from 2008 to 2018

Keith Joung, MD, PhD, Massachusetts General Hospital and Harvard Medical School

Jinsong Li, PhD, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

David R. Liu, PhD, the Richard Merkin Professor and vice-chair of the Faculty at the Broad Institute; professor of Chemistry and Chemical Biology at Harvard University; and a Howard Hughes Medical Institute Investigator

Luigi Naldini, MD, PhD, scientific director of the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy; and professor of Cell and Tissue Biology and of Gene and Cell Therapy at the San Raffaele University School of Medicine

Jing-Bao Nie, PhD, Bioethics Centre, University of Otago

Renzong Qiu, PhD, professor at the Institute of Philosophy, Chinese Academy of Social Sciences, and a Hastings Center Fellow

Bettina Schöne-Seifert, MD, PhD, Institute of Ethics, History and Theory of Medicine, University of Münster

Feng Shao, PhD, investigator and deputy director for Academic Affairs, National Institute of Biological Sciences, Beijing.

Sharon F. Terry, MA, president and CEO of Genetic Alliance

Wensheng Wei, PhD, Center for Life Sciences, Peking University

Ernst-Ludwig Winnacker, PhD, secretary general of the Human Frontier Science Program Organization (HFSPO) from 2009 to 2015 and the first secretary general of the European Research Council from 2007 to 2009.

[This report was updated on March 14 to include the NIH’s endorsement of the call for a moratorium and governance framework for human germline editing].