Harvard group retracts Nature paper

A group of researchers based at Harvard University have retracted an influential 2017 letter in Nature after a change in lab personnel led to the discovery of errors in the analysis. 

The article, “Microglia-dependent synapse loss in type I interferon-mediated lupus,” emerged from a collaboration including scientists at Harvard Medical School, the Rockefeller University in New York City, the University of Magdeburg, in Germany. 

The senior author of the research letter — which has been cited 75 times, earning it a highly cited designation from Clarivate Analytics’ Web of Science — was Michael C. Carroll, a prominent immunology researcher. [See disclosure at the end of this post.] Also on the list was Ronald Herbst, who at the time was vice president of research at MedImmune but has since left that company for another biotech firm. The first author was Allison Bialas, at the time a post-doc at Harvard. 

According to the abstract: 

Here we report behavioural phenotypes and synapse loss in lupus-prone mice that are prevented by blocking type I interferon (IFN) signalling. Furthermore, we show that type I IFN stimulates microglia to become reactive and engulf neuronal and synaptic material in lupus-prone mice. These findings and our observation of increased type I IFN signalling in post-mortem hippocampal brain sections from patients with SLE may instruct the evaluation of ongoing clinical trials of anifrolumab⁷, a type I IFN-receptor antagonist. Moreover, identification of IFN-driven microglia-dependent synapse loss, along with microglia transcriptome data, connects CNS lupus with other CNS diseases and provides an explanation for the neurological symptoms observed in some patients with SLE.

However, Carroll told us that when Bialas left his lab, her successor found problems with the data: 

We realized that the data supporting the figures noted in the retraction could not be repeated when a  PhD student in the lab took over the project from the lead post-doc. No other retractions are planned.

Here’s the retraction notice: 

In follow-up experiments to this Letter, we have been unable to replicate key aspects of the original results. Most importantly, the findings from behaviour studies and sequencing of microglia isolated from 564Igi autoimmune mice as shown in Figs. 1a, b, d and 3a, b are not substantiated upon further analysis of the original data. The authors therefore wish to retract the Letter. We deeply regret this error and apologize to our scientific colleagues.

‘It’s inspired my group’

The article was considered important enough to merit a News & Views piece in Nature when it appeared. It also garnered some media attention.  We also found evidence that it influenced at least one other scientist. Edward Vital, a lupus researcher in England, tweeted that he was impressed by the results and hoped to apply them in his own work: 

think this is brilliant work by Allison Bialas, Michael Carroll and their co-authors. It changes the way I think about this disease. And it’s inspired my group to take some observations in humans.

Vital, who told us he’d been unaware of the retraction, said: 

The main impact of the research was on my overall concept of autoimmunity. To this end, I had been preparing a review article that included this paper. I’m interested in a range of different results that suggest the “target organs” in autoimmune diseases are not really just passive targets, but play an important role in initiating and driving the disease.

I did conduct a piece of research that was driven by the Carroll paper to some degree. This was by analysing samples and clinical data from humans. I wanted to know whether interferon activity in blood would correlate with cognitive dysfunction in people with lupus. My results weren’t consistent with Carroll’s conclusions. However there may be many other reasons for that; working in humans introduces many other variables.

Disclosure: One of our co-founders, Ivan Oransky, worked in the Carroll lab during college in the early 1990s, producing an honors thesis based on work to help create a transgenic mouse model of lupus.

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