Science is retracting a 2014 paper from the lab of a Nobel winner after replication attempts failed to conclusively support the original results.
In January, Bruce Beutler, an immunologist at University of Texas Southwestern Medical Center and winner of the 2011 Nobel Prize in Physiology or Medicine, emailed Science editor-in-chief Jeremy Berg to report that attempts to replicate the findings in “MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses” had weakened his confidence in original results. The paper had found that virus-like elements in the human genome play an important role in the immune system’s response to pathogens.
Although Beutler and several co-authors requested retraction right off the bat, the journal discovered that two co-authors disagreed, which Berg told us drew out the retraction process. In an attempt to resolve the situation, the journal waited for Beutler’s lab to perform another replication attempt. Those findings were inconclusive and the dissenting authors continued to push back against retraction.
Berg told us:
The question is more nuanced than with many retractions. It’s not a question about whether the result is “right” or “wrong’ but about how robust it is.
If we had known that it was going to take as long as it did to reach a conclusion, we might have issued an expression of concern.
Finally, about a month ago, Science decided that the journal itself, rather than a subset of co-authors, would retract the paper.
Here’s the full notice, published today and attributed to Berg:
Bruce Beutler has informed Science that experiments performed in his laboratory have failed to reproduce clearly the foundational observations of the 2014 article, “MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses.” In contrast to data presented (Figs. 1 and 3), he now finds that deficiency of MAVS and/or cGAS do not cause a robust decrease in type II T-independent B cell responses. At most, a decreased antibody response is observed in Stinggt/gt mice. Although some of the data shown in the paper may be correct, the core observations and conclusions are not. Beutler and a majority of coauthors have therefore requested retraction of the paper.
The editors nonetheless note that authors Ming Zeng and Xiaolei Shi stand by the findings of the paper. These authors do not agree to this retraction due to disagreement with the design of the reproduction experiments.
The editors have worked with the authors to determine the appropriate outcome and have decided retraction is appropriate in light of the lack of robustness of the main finding.
The paper has been cited 50 times, according to Clarivate Analytics’ Web of Science — including eight citations since the end of January, the month when Beutler first asked for a retraction.
Zeng, the paper’s first author, did not respond to our questions. We were unable to find contact information for Shi, who was listed as a co-second author.
In a statement, UT Southwestern told us:
Dr. Beutler is fully committed to the integrity and transparency needed for the proper conduct of scientific work. He has therefore informed Science that certain experiments performed in his laboratory have failed to reproduce. Specifically, deficiency of MAVS and/or cGAS does not cause a robust decrease in type II T-independent B cell responses.
The school also told us:
Dr. Beutler and his collaborators identified the problem with reproducibility, made multiple attempts to reproduce the data, and based on their results concluded retraction was the appropriate step. No outside labs were involved.
UT Southwestern added that it couldn’t comment on whether Zeng and Shi were still at the school:
As a matter of policy, UT Southwestern does not comment on personal information.
Waiting for clarity
Berg said Science allowed the replication attempt because it was “trying to help [the authors] resolve their differences to find a situation where everyone was comfortable with the retraction.” He said he doesn’t think anyone at Science suggested the idea, but that he and the journal were “supportive” of it.
Berg told us:
We were aware at the time there were three possible outcomes. One, a clear confirmation of results as published. Two, fairly clear evidence they weren’t [confirmed]. And a lot of room in the middle where things were pointed in the right direction but not enough to be clear.
The results ended up right in that “middle ground,” Berg said, where Beutler and the rest of the co-authors weren’t comfortable letting the paper stand, but where Zeng and Shi didn’t believe the results of the replication attempt justified retracting the paper.
Berg said he considered issuing an expression of concern (EoC) at several points, but didn’t because he thought the situation would be resolved sooner. Both in the weeks after receiving Beutler’s retraction request and in June, when the replication study results came in, Berg said:
We thought that things were moving forward so we didn’t issue an EoC.
Even in June, we did not expect that the process would continue as long as it did. Once the results came in, we solicited an expert opinion and then worked with the authors to see how they would respond to the findings. We did not expect that the process to come to a conclusion and agree on final language for the editorial retraction would take as long as it did.
The paper has been cited five times since June, when Science first received the replication study results.
Beutler shared the Nobel in 2011 for helping discover the proteins that recognize pathogens and activate the body’s immune response.
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