A Nature journal has posted a editor’s note to a recent letter on potential unintended consequences of CRISPR gene editing, after an executive at a company trying to commercialize the technology said the paper should be retracted.
The original article, published on May 30 as a correspondence in Nature Methods, suggested that using CRISPR in mice can lead to unexpected mutations. But last week, the journal added an “Editorial note” online. Nature Methods says the notice is not an expression of concern, which would be a stronger suggestion that the paper is problematic; it simply wants to alert readers to the fact that, as the note states:
…the conclusions of this paper are subject to criticisms that are being considered by editors. A further editorial response will follow the resolution of these issues.
As reported by Technology Review, the prospect of CRISPR causing widespread collateral genomic damage hurt the stock prices of Editas Medicine and Intellia Therapeutics, which are trying to develop CRISPR-based gene therapies. In response, researchers at both companies have written separate letters to the editor criticizing the methodology used in the paper. Editas’s scientists wrote first, joined by the firm’s co-founder and renowned geneticist George Church at Harvard University; Intellia followed less than a week later, posting the letter to its website.
This isn’t the first time we’ve seen corporations calling for the retraction of articles that aren’t good for their bottom line. The episode raises questions about how critics and authors alike should engage with ideas as they develop in the lab and in the literature.
Church told us that he began discussing the paper with other CRISPR researchers as soon as he found out about it, and that several of his Editas co-founders are planning their own replies to the journal.
Keith Joung, of Massachusetts General Hospital, told us he’s one of them; he has obtained data from the original researchers and is analyzing them in his lab.
Intellia CEO Nessan Bermingham has been the most forceful critic. Prior to the note addition, he told TechReview:
Given the issues around the design and interpretation I believe it is appropriate that the Nature Methods editorial board retract this paper.
Church told Retraction Watch he wasn’t sure if it deserved a retraction yet, “but it’s pretty darn close,” he said:
It’s not that the data are wrong, it’s that the experiment was not designed to support the question they were asking.
There should at least be an interpretation clarification.
A Nature spokesperson told us that the editorial note does not have its own DOI; it’s a response to “technical criticism raised in regard to this paper, and [the] editors are investigating this criticism.”
Nature wouldn’t say whether the corporate letters helped push them to issue the note, which was posted “following careful consideration of all communications sent to us:”
Our policy is to consider all criticism of work we publish very carefully and to publish relevant communications following appropriate technical review. However, for reasons of confidentiality we cannot comment on individual submissions to the journal.
Study co-author Alexander Bassuk of the University of Iowa told Retraction Watch that his team was not expecting this kind of response.
We were not thinking about industry at all. We simply made an unexpected observation using unbiased whole genome sequencing and wanted to share it with the research community.
He has been in contact with the journal editors about the editorial note, but they’ve not mentioned the possibility of an expression of concern, a correction, or a retraction, Bassuk said.
In their letters, the Editas and Intellia researchers suggest that the Iowa team chose improper controls, and should have performed sequencing of the parent mice to make sure the genetic variation they observed is due to CRISPR editing, and isn’t inherited. They also pointed to the small study size — two mice, one control — as a shortcoming.
Bassuk told Retraction Watch that they explain in the paper they used a so-called “colony control,” a similar mouse cohabiting with the subjects, rather than a mouse from the same litter:
Similar papers in Nature Methods and other journals have used the same [colony] control. Our study was designed the same way as previous in vivo studies – none of which sequenced parental controls.
But Church told Retraction Watch that if the authors had “contracted just about anybody who had worked on inbred strains or CRISPR in mice,” they would have learned that different mice from the same litter can have 1,000 genomic differences between them. “Two mice from the same colony are even less related,” Church said:
It’s enough to explain the result. If they haven’t ruled out that it’s due to the strain differences, it’s probably due to the strain differences, based on published strain characterizations.
As for how the journal is handling the situation, Church said of the editor’s note:
This seems like an adequate response for now, although to many, the correct explanation is already documented.
And it’s not just the study’s authors who missed this explanation, he told us, but the editors and reviewers as well:
I think everybody should have caught it.
Hat tip: Antonio Regalado
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