Standing athwart genomic engineering, yelling Stop, is not necessarily something you would expect from a group of scientists. Yet a call for conservatism rose from Science yesterday. The journal published a paper entitled, “A prudent path forward for genomic engineering and germline modification.”

Essentially, the paper advocates a ban on “any attempts at germline genome modification for clinical application in humans”—at least scientific and governmental organizations have a chance to discuss the “societal, environmental, and ethical implications of such activity.”

This proposal was prompted by the rapid development of the genome engineering method known as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. CRISPR-Cas9 is proving so simple, inexpensive, and effective that it promises to realize the long-deferred dreams of “precision medicine.”

“In addition to facilitating changes in differentiated somatic cells of animals and plants, CRISPR-Cas9 technology as well as other genome engineering methods can be used to change the DNA in the nuclei of reproductive cells that transmit information from one generation to the next (an organism’s 'germ line'),” wrote the authors of the Science paper. “Thus, it is now possible to carry out genome modification in fertilized animal eggs or embryos, thereby altering the genetic makeup of every differentiated cell in an organism and so ensuring that the changes will be passed on to the organism’s progeny.”

Because it demonstrates such power, CRISPR-Cas9 also raises ethical issues that can no longer be called theoretical. Such issues, the Science paper insists, should be discussed by diverse stakeholders: the research community, relevant industries, medical centers, regulatory bodies, and the public.

The paper’s authors include David Baltimore, a former president of the California Institute of Technology, and Jennifer A Doudna, a researcher at the University of California, Berkeley, who is one of the pioneers of CRISPR-Cas9 technology. All the authors are from the United States, and they include some of the leaders in the original 1970s discussions about recombinant DNA research at Asilomar and elsewhere.

At present, the authors are following up on discussions that took place in January, in Napa, CA, where the Innovative Genomics Initiative held a bioethics forum. The forum did not address mitochondrial transfer, a technique that does not use CRISPR-Cas9. Mitochondrial transfer, the Science paper stated, “raises different issues and has already been approved by the Human Fertilisation and Embryology Authority and by Parliament in the United Kingdom and is being considered by the Institute of Medicine and the Food and Drug Administration in the United States.”

Instead, the Science paper focuses on concerns that disease-curing applications could place human genome engineering on a “slippery slope” toward germline gene modification, with unpredictable consequences.

“Assuming the safety and efficacy of the technology can be ensured, a key point of discussion is whether the treatment or cure of severe diseases in humans would be a responsible use of genome engineering, and if so, under what circumstances,” the Science paper continued. “For example, would it be appropriate to use the technology to change a disease-causing genetic mutation to a sequence more typical among healthy people? Even this seemingly straightforward scenario raises serious concerns, including the potential for unintended consequences of heritable germline modifications, because there are limits to our knowledge of human genetics, gene-environment interactions, and the pathways of disease.”

Besides encouraging a moratorium on human germline applications of CRISPR-Cas9 technology, the authors of the science paper suggested that bioethical forums should take on educational challenges, research should be made transparent, and a globally representative group of experts should be convened to further consider the issues raised by genome-engineering technology and, where appropriate, recommend policies. This group, the paper read, could include “developers and users of genome engineering technology and experts in genetics, law, and bioethics, as well as members of the scientific community, the public, and relevant government agencies and interest groups.”