Nature adds alert to heavily debated paper about gene editing

Nature has added an “editor’s note” to a high-profile August paper alerting readers to the fact that the article has been subject to criticism.

Journals often flag papers that are being debated — what’s unusual here is that the journal doesn’t label the notice as an official “Expression of Concern,” which are indexed by PubMed. Yet the Nature notice reads just like an expression of concern.

Here’s the text of the new notice, which was added October 2 (and spotted by Paul Knoepfler):

Editorial Note: Readers are alerted that some of the conclusions of this paper are subject to critiques that are being considered by editors. Some of these critiques have been publicly deposited in preprint form. A further editorial response will follow the resolution of these issues.

We’ve contacted Nature about the decision not to use the term Expression of Concern in the new notice; a spokesperson told us:

We decided to issue an Editorial Note to indicate that we are aware of the discussions in the community, were looking into them and felt it was appropriate to flag them alongside the paper.  We did not feel we had enough information to issue a formal Expression of Concern, which could be added later, as could any other course of action, should they be deemed appropriate once we have better assessed the discussions.

Because the paper was highly publicized, the spokesperson said the publisher alerted the media to the notice:

The press office added information about the editors’ note to the first possible press release once it had been notified that the note was being published.  This was the press release for the Nature-branded research journals and Nature that was sent out on Tuesday at 11.19am EST.

Indeed, in the release, the editorial note appears as the last item, below a long list of new papers.

Critics began raising concerns about “Correction of a pathogenic gene mutation in human embryos” almost immediately after it was published online Aug. 2. On Aug. 28, a group of researchers posted a preprint to biorXiv questioning some of the paper’s conclusions, and proposing alternative explanations for the data. (A middle author on the preprint is George Church of Harvard Medical School, a high-profile geneticist who has questioned other gene-editing papers.)

The last author, Shoukhrat Mitalipov, at the Oregon Health and Science University in Portland, told us:

I assume this editor’s note is simply to keep the readers appraised on the progress of this debate. Meanwhile, we are working on a response to address the questions raised.  However, this will require generating additional dataset and extended timeline to complete these additional assays and experiments. We hope to submit our response soon and resolve all questions.  

Mitalipov added that he did not ask the journal to not label the latest notice as an official Expression of Concern.

Mitalipov is credited with being the first U.S.-based researcher to successfully clone human embryonic stem cells. In 2013, a paper co-authored by Mitalipov in Cell was subjected to extensive corrections.

In August, a news story in Nature summarized the debate over the recent paper:

In contrast to previous human-embryo editing studies, Mitalipov’s team reported a high success rate at correcting a disease-causing mutation in a gene. The team claimed that the CRISPR–Cas9 genome editing tool was able to replace a mutant version of the MYBPC3 gene carried by sperm with a normal copy from the egg cell, yielding an embryo with two normal copies. Mitalipov’s team also introduced a healthy version of the gene along with the CRISPR machinery, but they found that the corrected embryos had shunned it for the maternal version….In their bioRxiv paper, [outside researchers] say that there is no plausible biological mechanism to explain how a genetic mutation in sperm could be corrected based on the egg’s version of the gene. More likely, they say, Mitalipov’s team failed to actually fix the mutation and were misled into thinking they had by using an inadequate genetics assay.

This isn’t the first time we’ve scratched our heads over notices the use (or lack thereof) of Expressions of Concern. Recently, a researcher added the phrase “Expression of Concern” to his letter to the editor about a particular paper, leading it to become indexed as an official Expression of Concern on PubMed, even though it was not officially issued by the journal.

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