Crispr’s Next Big Debate: How Messy Is Too Messy? Megan Molteni June 4 2017


CRISPR-CAS9 gene editing complex
Getty Images

When it comes to Crispr, the bacterial wünderenzyme that allows scientists to precisely edit DNA, no news is too small to stir up some drama. On Tuesday morning, doctors from Columbia, Stanford, and the University of Iowa published a one-page letter to the editor of Nature Methods—an obscure but high-profile journal—describing something downright peculiar. About a year ago, they used Crispr to edit out a blindness-causing genetic defect in mice, curing two of their cohort. Later, they decided to go back and sequence their genomes, just to see what else Crispr did while it was in there.

A lot, it turned out. With their method, the researchers observed close to 2,000 unintended mutations throughout each mouse’s genome, a rate more than 10 times higher than anyone had previously reported. If that holds up, Crispr-based therapies are in for some serious trouble. No one wants to go in for a vision-restoring treatment, only to wind up with cancer because of it.

The ensuing headlines were gleefully apocalyptic: “Crispr May Not Be Nearly as Precise as We Thought,” “Crack in Crispr Facade after Unanticipated In Vivo Mutations Arise,” and my personal favorite, “Small Study Finds Fatal Flaw in Gene Editing Tool Crispr.” And then the biotech stocks went into a tailspin. The big three Crispr-based tech companies got hit the hardest. By the close of trading Tuesday, Editas Medicine was down nearly 12 percent, Crispr Therapeutics fell more than 5 percent, and Intellia Therapeutics had plunged to just over 14 percent.

This was far from just a blip in the nerdy news cycle. A reaction to a single scientific publication on this scale raises important questions about science’s incentive structure, its processes for publicly evaluating evidence, and what happens when those butt up against the prevailing philosophies of other professions—namely, medicine.

A decade ago, most of the conversations about this letter would have happened in laboratory hallways. But this week, geneticists, microbiologists, and molecular bioengineers took to Twitter to digest the paper in public. While some experts decried the paper as unnewsworthy (everyone’s known about Crispr off-target mutations forever!) the majority of threads ticked off the experiment’s flaws: Tiny sample size! Insufficient controls! Weird Crispr delivery! Out of date/inefficient version of Crispr! The list goes on. Many doubted if it had been peer-reviewed. (It had.) The hashtag #fakenews even made a few appearances.

To be sure, the results do not match up well with what’s already in the literature on this subject. And, as the paper itself says, “The unpredictable generation of these variants is of concern.” Which is to say, the authors have no idea why or how these mutations are happening. Derek Lowe, a longtime pharmaceutical industry researcher who writes a blog on the subject for Science, had enough doubt in the results that he bought up some Editas and Crispr Therapeutics stocks while they were down.

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