Just when you think that “any further audacious FRAUD (in publishing scientific papers) cannot be possible” (because all possible forms of corruption have already been invented) — along comes something new and even more dishonest. ☹
Research integrity investigators (16 authors — from several locations in Australia, United States, and France; see attached pdf)) have apparently found a new red flag for identifying fraudulent papers, at least in cancer research: discovery of human cell lines that apparently do not exist. That’s the conclusion of a recent study investigating eight cell lines that are consistently misspelled across 420 papers published from 2004 to 2023, including some in highly ranked cancer research journals. Some of the misspellings may have been inadvertent errors, but a subset of 235 papers provided details involving seven of the eight lines that “indicate the reported experiments were not actually conducted,” the sleuths say.
“Unfortunately, this looks like a massive invention of data and experiments that probably never happened,” said study lead author Jennifer Byrne, a cancer researcher and data detective at the University of Sydney. Some of the nonexistent cell lines have already been cited in literature reviews and could confuse and mislead other scientists conducting similar studies, she adds. “It’s a hell of a mess.”
Chao Shen, a cell biologist at Wuhan University and deputy director of the China Center for Type Culture Collection, a suppository of human cell lines, hopes the findings gain attention. “These revelations underline the urgent need for concerted efforts to address the challenges posed by these cell lines to research integrity and reproducibility,” such as standardized reporting of cell lines, he says.
Problems with human cell culture lines had already drawn attention in recent years, because scientists discovered that many have been contaminated by other, more robust cell lines that corrupted the results. But the new study reveals a different kind of flaw, stemming not from the misidentification of a known cell line, but from possible fabrication. ☹
The survey study, published recently in the International Journal of Cancer, began as an examination of misspelled cell lines in papers about cancer research — to determine whether the lines were contaminated or misidentified. Some of the misspellings may have begun as mistakes by inexperienced authors, Byrne said. But the team became suspicious about a subset of these papers that, in various ways, referred to the same seven cell lines as if they were not the same as similarly spelled, known cell lines. For example, some reported separate, different results from experiments that used the incorrectly and correctly spelled names of the same cell line.
These papers also had other red flags: They lacked a description of how the suspicious cell line was derived and did not provide its unique genetic fingerprint commonly used by researchers, which is based on short specific DNA sequences known as short tandem repeats (STRs). What’s more, several papers identified three repositories from which researchers could purchase many of the seven cell lines, including the largest such resource, the American Type Culture Collection. But when the research team searched for the lines in their directories, none appeared.
The team eventually identified 235 such papers in 150 journals, including high-impact publications such as Cancer Letters and Oncogene. Most of the suspect publications list authors in China, who are affiliated with hospitals — a group previously identified as a source of customers for paper mills, businesses that sell authorship on papers that are often fake or shoddy, because they may lack research experience and have faced publish-or-perish pressure to gain professional promotion (this topic has been previously discussed in our GEITP email blog).
“It’s difficult to prove unequivocally that something doesn’t exist,” Byrne stated, “but, from our analyses, we’re pretty confident.”
She speculated that paper mill writers may have copied the misspelled names from otherwise legitimate papers, unaware of the correct spellings, instead of fabricating new names, because those might have attracted greater scrutiny from knowledgeable readers. The suspect characteristics are “really very unlikely to be made by a genuine researcher,” she said. “I worked with numerous cell lines as long as 30 years ago, and I can still recite their names correctly.”
And these papers may be the tip of the iceberg, Byrne warned. Since January 2023, more than 50,000 scholarly articles about human cancer cell lines have been published. Byrne’s team identified a total of 23 misspelled lines, but limited its analysis to eight mentioned in 420 papers to keep the workload manageable. Her team plans further examinations, and she hopes others will as well. “We’re a small group, and going through these papers is very tedious.”
Obviously, reproducible laboratory research relies on correctly identified reagents, which can be used by any future laboratory to confirm or extend reported findings. Many of these previously described gene research papers with wrongly identified nucleotide sequence(s) — involved experiments in papers studying the microRNA, miR-145. Authors [see attached pdf file] manually verified the reagent identities in 36 “recent miR-145 papers” and found that 56%, and 17%, of papers described misidentified nucleotide sequences and cell lines, respectively. Authors also found five cell line identifiers in miR-145 papers having misidentified nucleotide sequences and cell lines, and 18 cell line identifiers published elsewhere, which could not be found in any list of officially indexed human cell lines. These 23 identifiers were described as non-verifiable (NV), because their identities were uncertain.
Furthermore, studying 420 papers that mentioned eight NV identifier(s), authors discovered 235 papers (56%) that referred to seven identifiers (BGC-803, BSG-803, BSG-823, GSE-1,HGC-7901, HGC-803, and MGC-823) as independent cell lines. Authors [see attached] could not find any publications or other information as to how these cell lines were established. Six cell lines were described as “sourced from cell line repositories with externally accessible online catalogs,” but these cell lines could not found, as claimed. Some papers also stated that STR profiles had been generated for three cell lines, yet no STR profiles could be identified. In summary, because non-verifiable (NV) cell lines represent new challenges to research integrity, reproducibility, and success of future studies with such human cancer cell lines — further investigations are required to clarify their status and identities. ☹
DWN
COMMENTS:
Kirsi,
Over the past six decades of reviewing thousands of manuscripts — I, too, have ALWAYS asked the authors to verify the name, the origin, and the accuracy of spelling of every cell line involved in every publication. ☹
Thank you Olavi, for forwarding to me this important and very interesting paper! I am sure you won’t mind if I forward it to several colleagues.
I am so glad someone is willing to take the time and effort to go through reagents, backgrounds and financing of research etc. to reveal some of the difficulties in research — but also to uncover intentional unethical misinformation and disinformation of researchers.
As to cell lines in papers, I think that the original source of the cell line, how and from whom it was purchased/received, and its main characteristics should always be mentioned in all manuscripts submitted for publication — and not just a reference (which may or may not be correct, as pointed out in this paper). When I review a paper for any journal, these are the things I ask the authors to include. Naturally, testing that the cell line is still in its original condition and has the claimed characteristics would even be better, but is there anyone, who actually does that?
Best regards, Kirsi
COMMENTS:
Really no surprise here, Liars lie, and Cheaters cheat. But this sentence caught my eye, and will be enshrined in my phantom archive of great malapropisms.
Chao Shen, a cell biologist at Wuhan University and deputy director of the China Center for Type Culture Collection, a suppository of human cell lines, hopes the findings gain attention.
From your comments, many of these papers and cell lines, and perhaps the Chinese repository, were in need of a suppository.