Overlooked virus “generated a mess,” infected highly cited Cell, PNAS papers

When Alexander Harms arrived at the University of Copenhagen in August 2016, as a postdoc planning to study a type of antibiotic resistance in bacteria, he carried with him a warning from another lab who had recruited him:

People said, “If you go there, you have to deal with these weird articles that nobody believes.”

The papers in question had been published in the Proceedings of the National Academy of Sciences in 2011 and Cell in 2013. Led by Kenn Gerdes, Harms’s new lab director, the work laid out a complex chain of events that mapped out how an E. coli bacterium can go into a dormant state, called persistence, that allows it to survive while the rest of its colony is wiped out.

Despite some experts’ skepticism, each paper had been cited hundreds of times. And Harms told us:

I personally did believe in the published work. There had been papers from others that kind of attacked [the Gerdes lab’s theory], but that was not high-quality work.

But by November 2016, Harms figured out that the skeptics had been right. 

More specifically, he realized that the mutant bacteria used in the PNAS and Cell papers had been infected by a virus — a common laboratory contaminant, but one that is usually caught before it affects published results. The lab quickly saw that the virus was responsible for the results in the high-profile papers. Research that many had accepted for almost five years had been scuttled. Harms told us:

We know basically less now than when I started.

Gerdes told Retraction Watch that using infected cells was an oversight on his part and realizes his lab had “generated a mess,” but he has taken the lead on cleaning it up. He retracted the Cell paper on Feb. 22, and told us the PNAS paper will be retracted soon, which the journal confirmed. But even before that, his lab published a paper, first to bioRxiv, on Oct. 9, 2017, and then to mBio, on Dec. 12, 2017, explaining the problems. Gerdes told us:

We wanted to put things straight… When you make a mess, you should clean it up.

“My favorite paper of 2017”

When the Cell paper came out, it appeared to answer a fundamental question about how some bacteria survive after exposure to antibiotics.

Kim Lewis, a microbiologist at Northeastern University, who was not involved in the research and who has been skeptical of the Gerdes lab’s explanation for how these so-called persisters formed, told Retraction Watch:

What impressed a lot of people is that Gerdes came up with a very specific and detailed pathway leading from starvation and stress response… to persister formations.

The PNAS paper, “Bacterial persistence by RNA endonucleases” has been cited 293 times, according to Clarivate Analytics’ Web of Science, and the Cell paper, “(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity,” has been cited 251 times. Both papers are deemed “highly cited” papers by Clarivate Analytics, meaning they ranked in the top 1 percent of all papers in their subject area for the year they were published.

Gerdes told us that his lab had shipped bacterial strains to between 20 and 30 other labs. In the retraction notice for the Cell paper, the authors noted that new, uncontaminated strains are now available to researchers.

We asked Lewis if he thought papers from other labs might be retracted in the future. He told us:

That’s an excellent question. I’m sure people are now re-evaluating their papers.

The Gerdes lab’s response has drawn praise from many corners. In January, the American Society of Microbiology blog Small Things Considered included the mBio paper, “Prophages and Growth Dynamics Confound Experimental Results with Antibiotic-Tolerant Persister Cells,” as one of its most notable papers of 2017. Petra Levin, a professor at Washington University in St. Louis, wrote:

This is my favorite paper of 2017 for its high quality, forthrightness, and contrition.

And Lews said:

I want to commend [Gerdes.] I hope everybody who finds themselves in this situation does what they are doing. They’re doing the right thing… Admitting that you were wrong and admitting it in a rather explicit way, publishing a paper about two of your publications, that’s pretty unusual.

Gerdes told us that even before the mBio paper was posted to bioRxiv, he submitted a version of it to Cell as a correction, which the journal rejected. And both Gerdes and Harms said that they urgently pursued the mBio paper because they heard that another group was planning on publishing a paper critical of the model laid out in the Cell paper. Gerdes said:

It would be very embarrassing if someone else figured out what was wrong with our strain. So we wanted to be first.

By the time they posted to bioRxiv, they had known about the problems for over almost a year. Gerdes told us he informed the PNAS editor he had worked with and Cell of the problem in the February 2017. Since the beginning of March 2017, the PNAS paper has been cited 38 times, while the Cell paper has been cited 54 times.

Retraction Watch asked both journals if they considered notifying readers; a Cell spokesperson said the journal did not have anything to add besides what’s already in the retraction notice. And a PNAS spokesperson told us:

Kenn Gerdes contacted the editor of the article directly in early 2017, but the PNAS Editorial Office was not informed until December [2017]. The Editorial Office contacted the authors in January regarding the issues.

Harms told us that he has gained some notoriety from his role in discovering the viral infection:

At meetings people approach me and say, “You’re the one who destroyed these papers?” I say, “I had no intention of destroying anything, I just did my job as a scientist.”

With the field wide open again, he relishes the idea of going back to basics “to find the right answers:”

I find these things even more fascinating than before. 

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