“Permissive Culture of Data Manipulation” in Cancer Research Lab

A university investigation found an emeritus professor had committed research misconduct after reviewing dozens of allegations, culminating in a recommendation to retract 10 papers and revoke his emeritus status.

The Ohio State University investigated 20 manuscripts by the cancer research group of Samson Jacob after the university received allegations in 2017 of image manipulation stretching over years of work, according to a misconduct investigation report we obtained via a public records request.

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

After determining that Jacob had committed research misconduct, the investigation committee recommended sanctions and asked for the immediate retraction of 10 papers in addition to the 10 that had already been addressed (nine retracted and one corrected) prior to the close of the inquiry. The school revoked Jacob’s emeritus position in May 2021, the OSU Lantern reported at the time.

The investigation committee reviewed 67 allegations, but declined to probe many more concerns that surfaced for the sake of time, according to the report.

The committee found that 14 of these allegations met at least one of two evidence standards for research misconduct—clear and convincing evidence or a preponderance of evidence. But the committee noted that its conclusion that the other 53 allegations did not constitute research misconduct does not mean that the data in the work were sound.

For the most part, the committee didn’t have access to original data. This meant they saw frequent signs of image manipulation in figures but lacked explicit evidence for misconduct and couldn’t contrast figures with the original data. The image issues were frequently severe enough for the committee to recommend retraction of the manuscripts in question. The allegations mainly involved figures that appeared spliced together from various experimental runs without noting that fact.

Jacob and other witnesses argued that no one had challenged their data until OSU received allegations in November 2017. They stated that splicing different experimental runs together in such a way had at the times of publication been an acceptable practice in the field.

As for the former point, after reviewing email records, the committee found that as early as March 23, 2017 and June 30, 2017, Jacob had “received formal notifications” from the Proceedings of the National Academy of Sciences and the Journal of Biological Chemistry, respectively, about concerns with his papers. For the latter point, the committee decided that the standard in the field that required explicit labeling of splicing was still emerging and “not yet a mandatory practice” when some of the publications were written, so the unlabeled splicing alone did not constitute misconduct.

The sheer number of apparently manipulated images in manuscripts published from 2002 to 2014, with the manipulation mostly of the control lanes of figures, convinced the committee “that there was a permissive culture of data manipulation in the lab, with emphasis on the control lanes to minimize detection, and that this was not due to inadvertent error.”

The report states that during the investigation, the committee suspected members of Jacob’s lab “were not truthful” about communicating with each other and were in frequent contact. They provided “remarkably similar, if not identical response statements, and mounted a ‘circle the wagons’ defense to any allegations,” the report said.

When first confronted with the fact that the committee had evidence of possible image manipulation, Kalpana Ghoshal, a senior member of the lab, “purposely obfuscated and lied to the Inquiry committee, explaining away the files as irrelevant” and saying they were not “generated for the purpose of using or publishing,” the report said. “[A]s far as anyone can tell, these images were never published or used in any way,” the report quotes her saying. “Such statements epitomize dishonesty in the opinion of the Committee and damage the credibility of arguments made by Dr. Ghoshal as a witness.”

For the six papers which had some original data available, the data didn’t absolve the authors. Two of the data sets provided did not mirror the published results, the report said.

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

In another case, Jacob had informed a journal investigating one of his papers that a figure was “a composite” and provided a new figure with the original data. The committee found another falsification after looking at the original data.

The committee wrote that “the brazen use and later acknowledgement of creating a composite figure from multiple sources of data because there had been a problem detecting bands during experimentation falls well outside the established practices and standards of the field.”

They continued: “Further, providing original data that allows the committee to identify an additional falsification reinforces the conclusion that Dr. Jacob shows a disregard for the accepted practices and rigors of scientific inquiry and an intention to manipulate and deceive the reader.”

The report states that Jacob “staunchly objected to any and all allegations; however, as the evidence mounted against the laboratory, Dr. Jacob vacillated between positioning himself as a victim of the dubious actions of members of his laboratory and aligning himself with them and relying on their responses to the allegations.”

In an interview with the committee, Jacob insisted that if there had been any data manipulation in his lab, he “was not aware of this, never orchestrated it, and would consider himself a victim of such activity.” However, later, in a letter to the committee dated Nov.15, 2019, “Jacob back-tracked to his previous arguments and placed trust in and reliance on Dr. Ghoshal’s responses,” the report said.

Another fact limited the committee’s willingness to trust members of Jacob’s lab: The investigation found that most of the alleged manipulations appeared to be in the control lanes of figures, as opposed to being randomly distributed between control and experimental lanes, as one would expect of accidental errors. The fact that researchers and reviewers “primarily focus on the experimental data lanes,” the report said, makes accidental error a less credible explanation.

Investigators noted that Jacob and his co-authors often used nearly identical language in their communications with the committee and repeatedly said that image duplication couldn’t have occurred without visible splice lines.

The committee didn’t find evidence that Jacob created any of the final published figures in question because he didn’t typically have any role in producing figures. However, in one publication, the committee found that Jacob was involved directly or at least knew who was responsible for the falsification.

The committee concluded that as senior author “it was arguably irresponsible, and at times reckless for Dr. Jacob to assume, and not take any action to verify, that figures…were reliable and accurately represented the experimental results.”

The committee recommended that Jacob be prohibited from all research, overseeing graduate students or other trainees, and submitting applications for federal funding for three years. They also asked that his emeritus and distinguished faculty statuses be revoked, and that he lose his “PI/Co-PI” status for three years from the date of the report. The report then lists the manuscripts the committee recommends for retraction or correction:

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

  2. “5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal,” Molecular and Cellular Biology, 2005 (Retracted April 2022)

  3. “DNA Methyltransferase 3b Regulates Nerve Growth Factor-Induced Differentiation of PC12 Cells by Recruiting Histone Deacetylase 2,” Molecular and Cellular Biology, 2005 (Retracted April 2022)

  4. “Physical and Functional Interaction of DNA Methyltransferase 3A with Mbd3 and Brg1 in Mouse Lymphosarcoma Cells,” Cancer Research, 2005

  5. “A Folate- and Methyl-Deficient Diet Alters the Expression of DNA Methyltransferases and Methyl CpG Binding Proteins Involved in Epigenetic Gene Silencing in Livers of F344 Rats,” The Journal of Nutrition, 2006

  6. “Methylation Mediated Silencing of MicroRNA-1 Gene 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 inducing its degradation,” Cancer Research, 2009

  8. “Estrogen-mediated suppression 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 of DNMT3B, Is Methylated at an Upstream CpG Island, and Functions as a Tumor Suppressor in Primary Colorectal Tumors,” PLOS ONE, 2010

  10. “Novel Insights into the Molecular Mechanism of Action of DNA Hypomethylating Agents: Role of Protein Kinase C δ in Decitabine-Induced Degradation of DNA Methyltransferase 1,” Genes & Cancer, 2012

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

Benjamin Johnson, Senior Director of Media and Public Relations at OSU, told us: “The board of trustees revoked Jacob’s emeritus status in May 2021” and that he has “no current affiliation with the university.” Ghoshal resigned from the university effective June 4, 2021, Johnson said.

Our efforts to reach Jacob and Ghoshal for comment were unsuccessful. Their OSU contact info no longer works.

As for the 10 publications recommended for retraction and one for correction, Johnson told Retraction Watch: “The university worked with the authors and contacted the relevant journals in October 2021. The university continues to work with the journals and the authors to correct the research record.”

We contacted those journal editors and one got back to us. Teresa Davis, editor in chief of the Journal of Nutrition, wrote that a representative from OSU’s Office of Research Compliance reached out with concerns about the paper and the journal launched its own investigation.

“The Journal of Nutrition investigated the concern according to COPE guidelines and has determined that a retraction is not warranted,” Davis wrote, despite OSU’s recommendation. “The Ohio State [University] has been notified of the results of our investigation.”

Davis did not respond to follow up questions about why the journal decided not to retract the paper.

We didn’t hear back from Molecular and Cellular Biology, which hosts another two of Jacob’s papers recommended for retraction, but both articles were retracted 11 days after our email in early April 2022. The retraction notices say OSU contacted the journal claiming to have found falsified data and note an “unsatisfactory response” from the authors.

The eight other manuscripts recommended for retraction or correction remain unchanged.

Source: Read Full Article