Hank Greely

Gene drives, which use genome editing (and especially CRISPR/Cas9) to push edited variations of genes through whole populations at great speed, are perhaps the most exciting and frightening products of new biotechnologies, giving humans more control than ever over all life on Earth. Gene drives had been talked about in theory for about fifty years, but the first demonstration of a gene drive was not until early 2015. Yet, because of its (justly) perceived importance, it has already led to a National Academy of Sciences report (perhaps setting a world land speed record). The Report, Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values is available for free download here.  I have read the summary and recommendations carefully and have skimmed the rest. Eight points stand out to me.

One – The Report is useful. It sets out the background facts of gene drives and analyzes helpfully many of the issues they raise. I am pleased that it calls for continued research. I am also pleased that it calls for (great) care in releases and for public consultation in individual cases. And I am pleased that it does not entirely rule out (careful) use. A moratorium, though tempting, would not have been justified.

Two – Phased testing, which the Report endorses, may work in specific locations but that will depend powerfully on the organism, ecology, and other circumstances. Assessing those situations carefully will be, as the Report says, both difficult and crucial. Setting out either more detailed guidance for that testing, or proposing an entity to lay out such guidance, would have been nice.

Three – The Report’s position on where trials will be held seems a bit odd. Repeatedly in its earliest sections (pages 5, 6, 8 and 14), it says the majority of trials will or should be in low or middle-income countries. I’m skeptical. Most of the Report’s case studies were or could have been US based. At another spot, the Report called for making sure host countries have the scientific capacity to handle (or oversee) such trials, which will often (not always, but often) not be the case in middle and low income countries (pages 87, 99, 152). In any event, except in the cases of panic or crisis – such as, perhaps, that caused by Zika virus – I suspect poorer countries be politically unwilling or, for lack of a scientific or regulatory infrastructure, unable to be rich countries’ test sites. Starting with projects in rich countries is likely to be hard but may make more sense in the long term.

Four – The Report pays too little (basically no) attention to private law. Tort, nuisance, product liability suits, and other claims that could have major effects both in enjoining attempted uses of the technology (in trials or general release) and in money judgments for uses that go wrong – or that a jury has been convinced have gone wrong. The Report mentions liability only once (in the context of international uses); courts once (in the context of the National Environmental Protection Act; and damages, injunction, and nuisance law not at all. Private law has powerful regulatory effects when organisms are released into the world; the likely consequences cannot be assessed well without considering them.

Five – The Report’s US regulatory recommendation is vague – “The U.S. government should clarify the assignment of regulatory responsibilities for field releases of gene-drive modified organisms, including the roles of relevant agencies that are not currently included in the Coordinated Framework for the Regulation of Biotechnology.” “Clarified” would be nice but in what ways (who does what) and how (by legislation or otherwise)? It would have been nice to see specific recommendations.

Six – The Report ignores entirely two important issues: commercial control through patents and possible military uses. Patenting is mentioned in passing in 1 1/4 sentences in the Report; “intellectual property” only in one sentence, which appears twice. “Biosecurity” does receive several pages in the last chapter but seems focused on terrorists, not “normal” defense establishments. While I do not think these are as crucial (“evil militaries, evil capitalists, oh my!”) as some might think, as in this opinion piece in The Guardian, they do deserve some attention. After all, intellectual property rights are a form of (private) regulation all their own while military uses often avoid close regulation.

Seven – For the most part the Report seems to assume that local populations are not going to be excited about gene drives in their neighborhoods. The engagement chapter seems to be largely giving advice on how to try to swim upstream. I think that’s generally right, but the Zika epidemic may end up showing how that dynamic may flip. In some cases, particularly where a possible epidemic is causing a panic, the population might end up not as a brake on use of gene drive but as an inappropriate accelerator The Report was undoubtedly drafted before Zika became so greatly feared, but the possible resulting don’t just stand there, do something” reaction needs to be considered.

Eight – Finally, whether it makes sense to break gene drive out from broader issues of non-human uses of CRISPR and other gene editing isn’t clear. I think we need a broad rethinking of our regulatory policies about genetically modified organisms, however they are modified. One NAS committee just issued a report in May 2016 on genetically engineered crops, available here. Another NAS committee is working on “Future Biotechnology Products and Opportunities to Enhance Capabilities of the Biotechnology Regulatory System,” with a report promised by the end of 2016. Yet another NAS committee is looking at uses of gene editing in humans. Whether it made sense for all these different committees to be dealing, largely, with the consequences of the CRISPR revolution in genome editing isn’t clear to me. But I do hope that somewhere, somehow, a great set of recommendations for dealing with this revolution will emerge.

I need to read the whole report more carefully, especially the case studies, which seem fascinating. But so far, I agree with New Yorker reporter Michael Specter, who called it “a worthy, if somewhat tepid, report.”  It’s a useful start, but nowhere near a finish.

Hank Greely is the Deane F. and Kate Edelman Johnson Professor of Law; Professor, by courtesy, of Genetics; and Director of the Center for Law and the Biosciences at Stanford University