Researchers in Australia have retracted a 2016 paper in Nature Chemical Biology after discovering a critical error in their research, bringing some closure to a gut-wrenching case for the scientists involved.
As we reported in January, Nicola Smith, the senior author of the article, titled “Orphan receptor ligand discovery by pickpocketing pharmacological neighbors,” described learning of the error as “the most horrific time” of her career.
Smith, then at the Victor Chang Cardiac Research Institute in Sydney (she’s now at the Orphan Receptor Laboratory at the University of New South Wales) told us that she briefly considered letting the flawed research — which has been cited 26 times, according to Clarivate Analytics’ Web of Science — go uncorrected.
After all, as one colleague told her, the subject of the studies was so arcane that
‘despite the fact that you really care about this receptor, no one else in the world really gives a toss about it.’
Keeping quiet, Smith inferred, would protect herself and her research team from the stigma of retraction.
That thought was fleeting, however, and Smith quickly recognized that suppressing the error would be “utter bullshit.” At that moment, she said:
The weight just lifted off my shoulders; it was the right decision.
Another paper in Science Signaling affected by the mistake was retracted in December 2019. The authors also wrote a book chapter and a review which referenced the invalidated results and required correcting. In the meantime, the group posted a preprint about the errors in the Nature Chemical Biology paper.
The new retraction notice for the NCB paper states:
In this paper, we developed GPCR-CoINPocket, a computational method for identifying pharmacological similarities of GPCRs, including orphan receptors, solely from their sequences. Guided by our GPCR-CoINPocket predictions for the orphan receptor GPR37L1, we reported several compounds as inverse agonists of GPR37L1 constitutive Gαs-directed activity. Unfortunately, after the work was published, we discovered a cloning error in the GPR37L1 construct used for compound screening in Fig. 5 and Supplementary Figs. 5 and 6. The corrected GPR37L1 construct no longer displays constitutive activity, and the predicted compounds do not evoke a GPR37L1-mediated response in the pharmacological assays tested (refer to the accompanying Matters Arising). Therefore, we are retracting this study, and all authors agree with this decision. We sincerely apologize for any impact on the scientific community. The computational method for identifying pharmacological neighbors, GPCR-CoINPocket, is unaffected by this error.
Taking a bit of the sting out of the retraction, Smith’s group is publishing a “Matters Arising” article that corrects the removed paper. (Confusingly, the abstract page for that paper says it was retracted, which we assume is an error on the part of the journal. Ditto the fact that at one point the abstract page of the now-retracted paper refers to a correction.) (Update, 1600 UTC, 3/2/21: Both of these have now been fixed.)
Update, 1800 UTC, 3/1/21: Smith tells us:
I am extremely relieved to have the paper retracted and grateful to the editors of Nature Chemical Biology for their considerate approach to the process. It is great to be able to put this chapter behind us and focus on the new projects we have in the lab with a young and vibrant team of students.
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To err is human; to have the courage and integrity to correct your own mistakes is divine.
Kudos.
Your decision to retract your paper will reach a much wider audience with a significant positive result more than that ‘orphan receptor ligand- whatchamacallit!