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scientific paper that purported to lay bare serious flaws in the gene-editing tool known as CRISPR and briefly tanked shares of genome-editing companies has been retracted by its publisher.

The paper, published last year in Nature Methods, claimed that CRISPR wreaked havoc on the genome, causing hundreds of unintended mutations in mice — and that the algorithms typically used to detect these changes were routinely missing them.

Such “off-target effects” had been on scientists’ radars for months, and many said they had begun to develop workarounds to help detect and even mitigate any effects. The news still sent the stock for CRISPR companies like Editas Medicine and Intellia Therapeutics tumbling.

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The paper, led by Stanford scientists, also immediately stirred up controversy, with critics — particularly those at the affected companies — taking exception with their methodology.

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Specifically, they said the paper lacked the appropriate controls and sample size to be taken seriously — and that the Stanford scientists’ use of CRISPR was not necessarily representative of how it’s wielded by others.

Two months after publication of the paper, Nature Methods published an “an expression of concern” about the paper in July.

The retraction notice, appended Friday, goes further, saying the authors did not use mice that had been bred in their own laboratory — so they could not know if any genetic mutations were the result of their intervention with CRISPR editing, or if it stemmed from variations in the mice’s own genomes.

The lead author, Vinit Mahajan, and some co-authors objected to the retraction.

In an editorial, Nature Methods said the central claim of the paper was not sufficiently supported by the data. The publication said the paper had been peer reviewed but should have been subject to more scrutiny.

“On the question of whether CRISPR can be safely used in vivo, the stakes are high for many. But for none are they higher than for the people in whom this technology may be used in the future,” the editorial said. “They are owed a careful and rigorous answer.”

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  • Research papers should have the highest scrutiny. Variables should be few. Those described should result in retraction.

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