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Human Embryo Editing Study Shows We Still Have a Lot to Learn About CRISPR

September 1, 2017

The first human embryos edited in the U.S. appear to have had a faulty gene repaired—but now a debate is raging as to what actually happened.

In late July, MIT Technology Review broke the story about the work, in which researchers edited about 150 early-stage embryos using the CRISPR gene-editing technique. In the subsequent paper published in Nature, the team revealed that it was able to successfully eliminate a genetic mutation that causes a deadly heart condition. Importantly, the results suggested the edits occurred with a far higher level of precision than anyone else had managed before in embryos. One of the study's authors, Shoukhrat Mitalipov, talked of clinical trials being near at hand.

But questions have emerged this week about how, exactly, the faulty gene was removed. The authors of the original study claim the gene was repaired as CRISPR cut out only the faulty DNA, which was on the paternal side, then used normal maternal DNA as a template to correct the mutation—a previously unknown phenomenon. (Watch our CRISPR explainer)

On Monday, a different group of researchers called this account into question in a paper posted on bioRxiv. They pointed out that Mitalipov's team only showed that the faulty gene is absent from embryos after editing, not that the gene had been repaired. What's more, paternal and maternal DNA are still distinct in the embryos the team was using. So how could the two have interacted?

Instead, the cross-examiners suggest—and many have subsequently agreed—that it's possible that CRISPR could have been making much larger deletions of the embryos' DNA. If that's true, then the faulty gene would fail to show up when Mitalipov's team went looking for it, but the embryos could have a great deal of genetic damage besides. Without ruling out this possibility—or else figuring out another way to avoid so-called "off-target" effects—it would be irresponsible to suggest that CRISPR-edited embryos be implanted and allowed to grow into children.

Mitalipov has responded to the criticism by encouraging scientists to perform their own experiments to confirm his team's findings—an admirably scientific way to both stand by one's work and acknowledge that the case is far from closed. In the meantime, those clinical trials may be on hold for a while longer yet.

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