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“Permissive Culture of Data Manipulation” in Cancer Research Lab

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A university investigation found the professor emeritus engaged in research misconduct after considering dozens of allegations, culminating in a recommendation that 10 papers be retracted and his honorary status removed.

Ohio State University investigated 20 manuscripts from the Samson Jacob Research Group after the university received allegations of image manipulation over years of operation in 2017, according to a misconduct investigation report we obtained upon request for public records.

The 209-page report, dated February 9, 2021, tells the story of an investigation spanning more than a decade in Jacob’s lab that ran into “dishonesty” from interviewed lab staff.

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Finding that Jacob had committed misconduct during the course of the investigation, the investigation committee recommended sanctions and demanded the immediate retraction of 10 articles in addition to the 10 that had already been considered (nine retracted and one amended) before the investigation was closed. As OSU Lantern reported at the time, the school canceled Jacob’s honorary position in May 2021.

According to the report, the investigative committee considered 67 allegations but declined to investigate many other concerns that were raised in order to save time.

The Committee found that 14 of these allegations met at least one of the two standards of evidence for research misconduct – clear and conclusive evidence or preponderance of evidence. But the committee noted that its conclusion that the other 53 claims were not in breach of research discipline does not mean that the data in the paper were reliable.

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For the most part, the committee did not have access to the original data. This meant that they saw frequent signs of image manipulation in the numbers, but had no clear evidence of misconduct and could not match the numbers to the original data. Image problems were often severe enough for the committee to recommend retraction of the manuscripts in question. The accusations were mainly about numbers that were glued together from various experimental runs without considering this fact.

Jacob and other witnesses claimed that no one disputed their data until OSU received the allegations in November 2017. They stated that combining various experimental runs in this manner was, at the time of publication, acceptable practice in the field.

Regarding the first point, after reviewing the email records, the committee found that as early as March 23, 2017 and June 30, 2017, Jacob “received legal notices” from the Proceedings of the National Academy of Sciences and the Journal of Biological Chemistry. , respectively, about problems with his papers. Regarding the last point, the committee decided that the standard in the field requiring explicit splicing labeling was still emerging and “not yet a mandatory practice” when some publications were written, so unlabeled splicing itself is not a violation.

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The sheer number of apparently altered images in manuscripts published from 2002 to 2014, with manipulation of mostly digit control tracks, convinced the committee “that there is a permissive culture in the lab of data manipulation with an emphasis on control tracks to minimize detection, and that this is not happened due to an unintentional error.

The report states that during the investigation, the committee suspected that members of Jacob’s lab “were not truthful” in communicating with each other and were in frequent contact. They presented “remarkably similar, if not identical, responses and organized a van circle defense against any allegations,” the report said.

First confronted with the fact that the committee had evidence of possible image manipulation, Kalpana Ghoshal, a senior lab official, “deliberately confused and lied to the investigation committee by explaining the files as irrelevant” and claiming they were not “generated.” for the purpose of use or publication, ”the message says. “[A]as far as can be determined, these images have never been published or used in any way,” she was quoted as saying by the report. .”

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For the six articles for which raw data were available, the data did not exonerate the authors. The report states that the two datasets provided do not reflect published results.

In investigating one allegation, members of the committee looked through files on Ghoshal’s computer and found a set of images that appeared to be in the process of being manipulated into a merged image.

On another occasion, Jacob told a magazine researching one of his articles that the figure was “composite” and provided a new figure with the original data. The commission found another falsification after reviewing the original data.

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The committee wrote that “the brazen use and then acceptance of creating a composite figure from multiple data sources due to a problem with detecting bands during experiments goes far beyond established practices and standards in the field.”

They continued, “Furthermore, providing background data that allows the committee to identify additional falsification supports the conclusion that Dr. Jacob demonstrates a disregard for accepted practice and scientific rigor, and an intent to manipulate and deceive the reader.”

The report states that Jacob “strongly objected to any and all allegations; however, as the evidence against the lab piled up, Dr. Jacob vacillated between positioning himself as a victim of the dubious practices of his lab staff and joining and relying on them.” about their responses to the allegations.

In an interview with the committee, Jacob insisted that if there was any data manipulation in his lab, he “didn’t know about it, never orchestrated it, and would consider himself a victim of such activity.” However, later, in a letter to the committee dated November 15, 2019, “Jacob returned to his previous arguments and trusted and relied on Dr. Ghoshal’s answers,” the report said.

Another fact limited the committee’s willingness to trust Jacob’s lab staff: the investigation showed that most of the alleged manipulations appeared to occur on the control lanes of the figures, rather than being randomly distributed between the control and experimental lanes, as one would expect from random manipulations. errors. The fact that researchers and reviewers “mainly focus on bands of experimental data,” the report says, makes random error a less plausible explanation.

Investigators noted that Jacob and his co-authors often used nearly the same language when communicating with the committee and repeatedly stated that the duplication of the image could not have occurred without visible glue lines.

The committee found no evidence that Jacob created any of the final published figures in question because he usually played no part in the creation of the figures. However, in one publication, the committee found that Jacob was directly involved, or at least knew who was responsible for the fabrication.

The committee concluded that, as senior author, “it may have been irresponsible and sometimes reckless on the part of Dr. Jacob to assume and take no action to verify that the figures … were reliable and accurately represented the experimental results.”

The committee recommended that Jacob be banned from doing any research, supervising graduate students or other interns, or applying for federal funding for three years. They also requested that his honorary and distinguished teaching status be revoked, and that he be stripped of his “PI/Co-PI” status for three years from the date of the report. The report then lists the manuscripts that the committee recommends for retraction or correction:

  1. “Protein tyrosine phosphatase type O receptor (PTPRO) exhibits characteristics of a tumor suppressor candidate in human lung cancer”, Proceedings of the National Academy of Sciences, 2004 (withdrawn, May 2022)

  2. “5-aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 in a proteasome pathway that requires a KEN block, a bromine contiguous homology domain, and a nuclear localization signal”, Molecular and Cellular Biology, 2005 (withdrawn April 2022)

  3. “DNA methyltransferase 3b regulates nerve growth factor-induced PC12 cell differentiation by recruiting histone deacetylase 2”, Molecular and Cell Biology, 2005 (withdrawn April 2022)

  4. “Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells”, Cancer Research, 2005.

  5. “Folate and methyl-deficient diet alters the expression of DNA methyltransferases and methyl-binding CpG proteins involved in epigenetic gene silencing in the liver of F344 rats”, The Journal of Nutrition, 2006.

  6. “Methylation mediated miRNA-1 gene silencing and its role in hepatocellular carcinogenesis”, Cancer Research, 2008.

  7. “A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and causing its degradation”, Cancer Research, 2009.

  8. “Estrogen-mediated downregulation of the gene encoding protein tyrosine phosphatase PTPRO in human breast cancer: mechanism and role in tamoxifen sensitivity”, Molecular Endocrinology, 2009

  9. “HOXB13, a target for DNMT3B, is methylated at the upstream CpG island and acts as a tumor suppressor in primary colorectal tumors”, PLOS ONE, 2010.

  10. “New insights into the molecular mechanism of action of DNA hypomethylating agents: the role of protein kinase C δ in decitabine-induced degradation of DNA methyltransferase 1”, Genes & Cancer, 2012.

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According to Clarivate’s Web of Science, the papers have been cited nearly 1,400 times in total.

Benjamin Johnson, senior director of media and public affairs at OSU, told us, “Jacob’s honorary status was revoked by the board of trustees in May 2021” and that he “is not currently affiliated with the university.” According to Johnson, Ghoshal retired from the university as of June 4, 2021.

Our attempts to contact Jacob and Ghoshal for comment were unsuccessful. Their OSU contact information no longer works.

Regarding the 10 publications recommended for retraction and one publication for correction, Johnson told Retraction Watch, “The university has been working with the authors and contacted the relevant journals in October 2021. The university continues to work with journals and authors to correct the study report. .”

We contacted the editors of these journals and one of them responded to us. Teresa Davis, editor-in-chief of the Journal of Nutrition, wrote that a spokesperson for OSU’s Research Compliance Office had reached out with concerns about the paper, and the journal launched its own investigation.

“Nutrition Journal investigated the issue in accordance with COPE guidelines and determined that a retraction is not warranted,” Davis wrote, despite OSU’s recommendation. “Ohio State [University] been informed of the results of our investigation.”

Davis did not respond to additional questions about why the journal chose not to withdraw the article.

We have not received a response from Molecular and Cellular Biology, where two of Jacob’s papers are recommended for retraction, but both papers were retracted 11 days after our email in early April 2022. The retraction notices state that OSU contacted the journal, claiming to have found fraudulent data, and note the authors’ “unsatisfactory response”.

Eight other manuscripts recommended for refutation or correction remain unchanged.

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