This is a story that puzzles me: it’s a case where seemingly everyone agrees there was research fraud, but for some reason nobody wants to identify who did it. Just business as usual in the War on Cancer?
Ellie Kincaid reports:
On a Saturday last November, Philip Tsichlis of The Ohio State University received an email no researcher wants to get.
Another scientist had tried to replicate a finding in a recent paper of his, and couldn’t. “We believe that our results should lead to some revision of the model you propose,” stated the email, which was released to us by OSU following a public records request.
It turned out that was an understatement. The email eventually led Tsichlis to discover data fabrication in that paper and a related article. Within a week, he requested the retraction of both papers . . .
OK, so far so good. Here’s the background:
The email that spurred Tsichlis to reevaluate his lab’s papers came from Alexandre Maucuer of INSERM on November 13th.
It referred to an article his group had published in Nature Communications in July, titled “AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing,” and was addressed to Tsichlis and the paper’s first author, Georgios I. Laliotis. . . .
On the Friday after he received Maucuer’s email, Tsichlis emailed the editor of a related paper his group had published in October in Communications Biology, requesting to retract the article and explaining what had happened . . .
In the letter, Tsichlis referred to “evidence of data manipulation,” and here was the published retraction note:
The authors are retracting this Article as irregularities were found in the data that indicate the splicing of the U2AF2 exon 2 does not occur as reported in the Article. The irregularities call into question the conclusions and undermine our full confidence in the integrity of the study. The authors therefore wish to retract the Article.
All of the authors agree with the retraction.
My question
OK, here’s my question. If the retraction is happening because someone faked the data (that’s what “data manipulation” means, right? From the description, it doesn’t sound like a mere coding error like this), and all the authors agree with the retraction, then . . . who did the faking?
Here’s the author list:
Georgios I. Laliotis, Adam D. Kenney, Evangelia Chavdoula, Arturo Orlacchio, Abdul Kaba, Alessandro La Ferlita, Vollter Anastas, Christos Tsatsanis, Joal D. Beane, Lalit Sehgal, Vincenzo Coppola, Jacob S. Yount & Philip N. Tsichlis
That’s 13 authors. If 1 of them faked the data, then that person would have 12 very angry collaborators, right??
I just don’t understand what’s going on here. All 13 authors agreed there was data fabrication. There must be a culprit, no? So why isn’t anyone saying who did it?
OK, I get it, nobody wants to point the finger. After all, the sort of person who would fake data on a publication also could be the sort of person who would sue. But, can’t they get around it another way, by each of the non-cheaters releasing a statement saying, I didn’t do it?
If I were one of the 12 non-cheating authors on this paper, I’d be mad as hell that the cheater is getting off the hook here.
But maybe the cheater isn’t any of those people! In his letter, Tsichlis points to manipulation in Figure 1g of this other paper with an overlapping but different author list:
Georgios I. Laliotis, Evangelia Chavdoula, Maria D. Paraskevopoulou, Abdul Kaba, Alessandro La Ferlita, Satishkumar Singh, Vollter Anastas, Keith A. Nair II, Arturo Orlacchio, Vasiliki Taraslia, Ioannis Vlachos, Marina Capece, Artemis Hatzigeorgiou, Dario Palmieri, Christos Tsatsanis, Salvatore Alaimo, Lalit Sehgal, David P. Carbone, Vincenzo Coppola & Philip N. Tsichlis
The real question
Which of these 20 authors is the manipulator? Again, if I was one of the 19 honest people, I’d be furious. On the other hand, it’s possible the cheater has the power to damage co-authors’ careers. That’s the sort of thing that can make people scared to blow the whistle.
This work was funded by the National Institutes of Health:
This work was supported by the National Institute of Health grants R01CA186729 to P.N.T., and R01 CA198117 to P.N.T and V.C, and by the National Institutes of Health/National Cancer Institute P30 Grant CA016058 to the Ohio State University Comprehensive Cancer Center (OSUCCC). G.I.L was supported by a Pelotonia Post-Doctoral fellowship from OSUCCC.
I don’t think we can expect Ohio State University to look into this one too carefully, as it would be bad publicity. But the NIH, they should be really annoyed that millions of dollars have been going to research fraud. They could launch an investigation, no? This is really bad.
More evidence
The article with the problematic Figure 1g has this section:
Contributions
G.I.L. conceived and performed experiments, analyzed data, prepared figures, and contributed to the writing of the paper. E.C. designed and performed the mouse xenograft experiments, including the characterization of the tumors, performed the IHC experiments on human TMAs, and provided comments contributing to the writing of the paper. M.D.P. performed bioinformatics analyses of RNA-seq data that led to the identification of alternatively spliced targets of the IWS1 pathway. A.D.K. performed experiments, under the supervision of G.I.L. A.L.F. performed bioinformatics analyses of microarray and TCGA data. S.S. contributed to the FACS experiments. V.A. performed and analyzed the proliferation experiments. S.A. performed and supervised bioinfomatics analyses. A.O. prepared extracts of human tumors and provided comments on the paper. K.A.N. performed experiments, under the supervision of G.I.L. V.T. prepared the cells and the mRNA for the RNA-Seq experiment. I.V. Bioinformatics analyses of RNA-seq data. M.C. prepared extracts of human tumors used in this study A.H. Provided supervision for the bioinformatics analyses of the RNA-seq data. D.P. provided technical advice on several experiments in this paper and contributed to the design of these experiments. Provided comments on the paper. C.T. advised on the design of experiments. L.S. advised on the design of experiments. D.P.C. advised on the biology of lung cancer and on the design of experiments, provided cell lines, and reagents. V.C. contributed to the overall experimental design. P.N.T. conceived and initiated the project, contributed to the experimental design, supervised the work and monitored its progress, and wrote the paper, together with G.I.L.
Can this help us figure anything out? G.I.L. is the only author listed as preparing figures, so that might lead us to think that he’s the one who manipulated the data. But we can’t be sure. It could be that the Contributions statement is inaccurate and someone else made the graph. Or maybe something else went on that we don’t know about.
The Retraction Watch article has some interesting comments, including pointers to other papers by this research group that seem to have data problems, and a link to a letter by Tsichlis and the other tenured faculty in his department supporting the notorious Carlo Croce (from Wikipedia, “Croce’s research and publications have been scrutinized by the scientific community for possible scientific misconduct, including image and data manipulation. While working at Jefferson, federal investigators alleged Croce and a colleague had submitted false claims for research never undertaken. The university settled the allegations, paying $2.6 million to the government without admitting any wrongdoing. In 2007, OSU investigated Croce for misconduct after the National Institutes of Health (NIH) returned a funding application that contained major portions identical to an application submitted months earlier by Croce’s junior colleague. OSU later cleared Croce of misconduct after accusations that he had patented a researcher’s work without providing proper credit, that members of his lab had inappropriately used grant money for personal trips abroad, and that Croce improperly pressured colleagues for research attribution. Since 2013, several scientists have claimed research misconduct on the part of Croce, and as of 2020 these allegations remain under investigation by the federal Office of Research Integrity (ORI). . . . In 2013, following accusations from science critic Clare Francis of image manipulation in over 30 research papers, OSU instructed Croce to correct or retract some of his research publications; in 2015, the journal Clinical Cancer Research issued a correction after being contacted on the matter by a newspaper. In 2014, the Proceedings of the National Academy of Sciences of the United States of America dismissed a challenge that Croce’s 2005 paper on the WWOX gene contained manipulated western blots, but in 2017 the journal agreed to correct the paper after consulting with experts. In 2016, Croce was found to have plagiarized a paper he published in PLoS One from six separate sources. In 2017, the journal Cell Death and Differentiation retracted a paper Croce had published in 2010 after it learned that images had been copied from a 2008 paper published in another journal. Also in 2017, the Journal of Biological Chemistry retracted a paper Croce had published in 2008 due to image/figure irregularities. . . . In 2018, two cancer researchers at OSU, Samson T. Jacob and Ching-Shih Chen, both colleagues and co-authors with Croce on two papers each, were found to have engaged in scientific misconduct. On May 10, 2017, Croce filed a lawsuit against The New York Times and several of its writers and editors for defamation, invasion of privacy, and intentional infliction of emotional distress/ In November 2018, United States District Judge James Graham dismissed virtually all of Croce’s lawsuit. In 2017 Croce also filed a defamation lawsuit against critic David Sanders of Purdue University, who was quoted in The New York Times article. In May 2020 Croce lost the defamation lawsuit against Sanders . . .”).
Amusingly (or horrifyingly, depending on how you feel about fraud conducted at taxpayers’ expense), the letter by the 14 tenured faculty mentions that Croce is a member of the National Academy of Sciences (that’s supposed to be a good thing??? What does it take to get kicked out of that august body?) and that their department “enjoys the highest per-capita NIH funding on the entire campus.”
Also this from the Wikipedia page:
In 1994, Croce joined the Council for Tobacco Research’s scientific advisory board, where he remained until the group closed after the Tobacco Master Settlement Agreement, and during which time tobacco companies used Croce’s research into fragile histidine triad (FHIT) to argue that lung cancer was an inherited condition. . . . In 2016, Croce was paid more than $850,000 by Ohio State. In 2019, Croce was removed as chair of the Department of Cancer Biology and Genetics at OSU, and he subsequently sued OSU to be reinstated, losing his request for a temporary restraining order although retaining his salary of $804,461 per year.
And, here he is being given the full hero treatment by Smithsonian magazine:
The driver is Carlo Croce, a 64-year-old Italian scientist with a big voice, disheveled curly hair and expressive dark eyes. He heads the Human Cancer Genetics Program at Ohio State University, and his silver Scaglietti Ferrari is a fitting symbol of his approach to science: grand, high-powered and, these days especially, sizzling hot.
This was in 2009, 15 years after he did his dirty work for the Council for Tobacco Research, and 2 years after he was investigated for misconduct over an NIH application. Anyway, I guess he needed that $804,461 per year to pay for the gas for his Ferrari.
What’s going on there in Columbus, Ohio, anyway? How could it be that all 14 tenured faculty of the Department of Cancer Biology and Genetics think this is OK? Can they, like, just shut the department down and start over? What does the National Academy of Sciences think about their name being used in this way? What about the National Institutes of Health? The Ohio State University Board of Trustees? Then again, I’m still wondering what the Columbia University Board of Trustees thinks about this whole U.S. News thing.
It’s a dangerous world out there, and there’s a lot worse things going on than scientific corruption, misuse of government funds, and the trashing of the reputation of Ohio State University. Still, this all seems pretty bad.
If I were Philip N. Tsichlis, I’d be pretty angry. People keep fabricating data on papers I’m publishing but nobody ever reveals who the fabricators are, and I’m being paid less than half of the salary of a guy who’s had umpteen retractions:
At some point the dude’s gotta lose his patience, right? In the meantime, I’m kinda stunned that NIH continues to be funding these people. I guess the idea is, they might be faking their data, but they’re still curing cancer?
What’s a little fraud here and there when you’ve got disheveled hair and expressive eyes?
I was thinking that if someone’s so manifestly a crook, aren’t there more lucrative ways to go than academic fraud?
Then I read his straight up salary for one year, leaving aside the various side benefits. So maybe not.
Joshua:
Again, what stuns me is not that this guy cheated—the world is full of cheaters—but rather that he got all the tenured faculty in his department to join in on the scam. Similarly with that article with 20 coauthors—they all admit there was fraud but nobody seems to be particularly angry at whoever did the fraud. Who are these people who go into scientific research and then are OK with fraud? One or two, sure, but an entire department?? This reminds me of stories you read about police departments or school systems that are soaked in corruption (for example, here).
Andrew –
> . Who are these people who go into scientific research and then are OK with fraud?
(At least some) must have an internal narrative that leads to something other than being OK with fraud. Sure, some are consciously thinking they don’t want to kill a golden goose, or just don’t want to make waves, but I don’t think that would likely explain the behavior for such a large group.
It’s funny that when you referenced police departments or school systems, I’ll admit to a reflexive first eaction – that academic entities wouldn’t have the same self-serving behaviors as those other entities.
On second thought I realized that’s just flat out bias – probably class-based. I’ll have to work on that.
Joshua:
I’m guessing that their internal narrative is that they’re curing cancer; that they know how to do it; that their ideas are brilliant; that they deserve every one of the 369,000 dollars they were paid last year; and that designing experiments, collecting data, and analyzing data are all just a bunch of hoops to go through. From that perspective, having a colleague who fakes data is an annoyance, kinda like someone who doesn’t fill out the paperwork correctly.
My guess is that they’ve spent way too little time considering the possibility that their scientific ideas are mistaken; that their cancer cures won’t really work; that those dollars could be more effectively spent on researchers who design, gather, and analyze their data as actually reported rather than making things up.
This is really quite a contribution. About the only words I recognize as being ordinary English is “chuzpah” and “Ohio State University.” Combing through the terms totally unfamiliar to me such as
“AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing”
“bioinformatics analyses of RNA-seq data that led to the identification of alternatively spliced targets of the IWS1 pathway”
“bioinformatics analyses of microarray and TCGA data,”
I did find what I believe to be a mistake in English. “Again, if I was one of the 19 honest people, I’d be furious.” Shouldn’t that “was” be a “were”? At least, that was what was drilled into me way back in the middle of the last century. I am, however, informed that the English language has changed somewhat since then.
They’re saying that, in lung cancer cells, a mutated (overactive) EGFR overactivates AKT3. Which in turn activates IWS1 which then makes U2AF2 mRNA get spliced together differently (sometimes, depending on what stage of the cell cycle). That alternatively spliced U2AF2 then goes on to affect other stuff.
This would then explain, in part, how the mutated EGFR makes cancer cells proliferate more. The implication being that if you know the steps of this pathway*, then you can block them and cure/slow cancer.
But it seems unlikely U2AF2 could be spliced the way described in the paper, because it doesn’t have the right sequence. In the paper, they do show the required sequence but it looks photoshopped.
No one bothered to try replicating the actual experiments, but those results are probably made up.
* The premise of these pathways is implausible to begin with. Or at least so oversimplified that it causes confusion. A better conceptual model would be a network, or circuit. Something with redundancy and feedbacks.
There’s nothing strange at all in that sentence if you know introductory-level genomics at the level of the first few hundred pages of an intro cell bio textbook. If you try to expand all this into basic English, you’ll find that first sentence will be pages long. Luckily, human language is efficient and allows us to encapsulate complicated concepts in single words. Rather than saying “the sum of all the values divided by the number of values”, I say “average”, which is a word that confusingly already has a meaning in the dictionary. Then a term like “mean” is even more complex, as a mean involves integrating over the support of a random variable, none of which are basic English concepts. So rather than saying “the attachment of a phosphate group”, we say “phosphorylation”. And rather than saying “kicks off a complicated sequence of RNA and protein interactions with the DNA to initiate RNA transcription” we say “promotes”. And so on.
If you read the attached emails, there is no mystery about who took the blame.
It was the first author who they say did almost all the work then the PI (primary investigator) requested an additional of their papers be retracted. They also resigned and moved out of the country.
Indeed, this is clear from the emails. I think the bigger problem in science is actually in the excuse given, though.
“Also, I am not in contact with the first author, who was the one who did essentially all the work in these papers.”
What the hell did everyone else do to deserve to be a coauthor, and why does not a single one of them have to take any of the blame?
It reminds me of the LaCour controversy several years ago. While LaCour was obviously wrong, he pointed out that author guidelines for Science state that, “The senior author from each group is required to have examined the raw data their group has produced,” and that Green’s excuse included a claim that he hadn’t inspected the data. (https://www.science.org/content/page/science-journals-editorial-policies)
The reality is that in a very large number of cases on papers with these big teams of authors, most of them do not actually satisfy the journals’ requirements for authorship.
This also reminds me of the years long battle that Robert Trivers went through to retract one of his own papers in Nature, going so far as to self-publish a book documenting the entire situation and the problems he encountered. Nature even wrote a story about it, https://www.nature.com/articles/497170a.
You could also add the peer reviewers and perhaps editor. This is a pretty low effort falsification of the central premise of the paper.
He could have changed the underlying data rather than photoshopping, then they would need to attempt repeating the experiments. As it is, the premise fails a quick sanity check which invites closer scrutiny on the manipulated figure.
“Check WT sequence against a database” seems like it should be a standard box on the peer reviewer checklist. This could probably be largely automated.
Or just make independent replication standard, which will catch most of the fraud and errors to begin with.
The dynamic here is even a bit more suspicious given the shared nationality of the first author (fall guy) and the senior PI with the big salary.
Search the first author’s name on http://www.fcmcclerk.com/case/search .
The most likely scenario is that a postdoc/student fabricated (or severely messed up) the data; that person is no longer present and perhaps is no longer in academia; spotlighting that person serves no end and probably invites lawsuits. Put another way: what, Andrew, would you suggest the authors do, especially given that the university and funders don’t actually care?
Highlighting the eminence of the PI, by the way, serves another purpose: “bigshots” of this sort never touch data, or even figures, and have a similar relationship to their labs as my university president does to me (a fairly “normal” PI). Therefore, the astute reader knows, the bigshot’s hands are clean.
Raghu:
I guess I get it: dude’s making $369,000 so he doesn’t want to make waves. Maybe NIH should stop giving money to researchers in this department who keep getting involved in fraudulent papers. Then the university can decide whether to keep paying him $369,000?
I agree with the NIH part, and in this and so many things (like the overproduction of PhDs) I am constantly amazed and puzzled that NIH/NSF seem to care so little about the structure and incentives of the system.
> the bigshot’s hands are clean.
Yes indeed, so head here https://statmodeling.stat.columbia.edu/2022/06/19/propagation-of-responsibility/
I was in IE Business School in 2008. At the very start, the professors told us that they took plagiarism seriously. If anyone plagiarized, they’d be kicked out.
One thing you do in Business School is learn to work in teams. So, I asked, what if someone in a team plagiarized? We were told all in the team would be punished. I think we were all too terrified to ask if that meant everyone in the team would be booted out, but that’s what I thought would happen.
I don’t know what IE Business School is, but American business schools are reluctant to kick out their paying customers. Check out this story from NYU’s business school.