Chyba and Nouri reply:

Concerns about the possible misuse of gene synthesis in particular and biotech more generally are not “science fiction fantasies,” but rather a legitimate cause for concern. Attempts to address these concerns must be carefully balanced against the extremely important benefits that flow from these technologies, as we emphasize in the first paragraph of our Commentary1. The seriousness of the possible misuse of these technologies has been addressed by two National Academy of Sciences committees2,3, and in a workshop held by the Royal Society and the International Council for the Life Sciences4. (For full disclosure, one of us was a member of one of these Academy committees and a participant in the Royal Society workshop that led to the new report.)

Minshull and Wagner criticize our suggestions on three grounds: first, the “cat is already out of the bag” and “anyone who is sufficiently motivated” can already synthesize genes “or even an entire viral genome”; second, the requirement that legitimate users be able to readily bypass any controls will permit “hackers” to bypass these controls; and third, gene synthesis is “an unlikely tool for anyone considering harm” because there are so many other biological and conventional means to cause harm. We acknowledged these objections but did not find them sufficient to mean that nothing should be done.

What is striking is that, despite their rhetoric, Minshull and Wagner obviously agree with us on this. They themselves summarize the controls that their companies, and others, have placed on gene synthesis, based on the select agent lists. They require official permits for certain genes to be produced or shipped. Moreover, they call upon governments in the United States and Europe to “require all makers of synthetic genes to screen” synthesis orders. So, in fact, there is no disagreement in principle between their viewpoint and ours; the difference exists in the specifics of its application.

There is no silver bullet that will somehow solve the security challenge of dual-use biotech. Rather, we must implement a web of measures, carefully calibrated so as not to impede legitimate and lifesaving research, that will make it more challenging—not render impossible—the casual or even dedicated misuse of this technology. The hope is that such misuse will be challenging enough that any individual or group contemplating it will choose an altogether different approach to doing harm. But were the technology to become both extremely easy to use and widely available, further steps might be required to help ensure these favorable outcomes.

We do not suggest that gene synthesis companies drop their controls; in fact in our Commentary we applaud the steps that have been taken. Our concern, rather, lies with a possible future—whose trajectory can already be discerned—in which automated DNA synthesis machines diffuse to a large number of users. In this case, additional proposals beyond those applicable to central providers must be considered. Our suggestions, like those implemented by Minshull and Wagner, build on the select agent list and, like theirs, would require some permit structure for the synthesis of especially dangerous sequences which, like theirs, introduces some vulnerability to misuse that must be managed. In effect, we simply recommend extending their practices to a new technology. Given their call for greater government requirements along these lines for their own industry, we are puzzled why they object to our suggestions.