The Cardiff University in UK is now investigating two cancer researchers, both senior professors, for suspected scientific misconduct. The evidence was submitted by pseudonymous Clare Francis, I publish below the results of preliminary investigations. One of these two professors is Robert Nicholson, specialist in breast cancer, former director of Tenovus Centre for Cancer Research, now professor of Cardiff School of Pharmacy & Pharmaceutical Sciences, celebrated on BBC in 2008 for discovering a therapy target for tamoxifen-resistant tumours. The other is Wen Jiang, professor of Surgery and Tumour Biology at Cardiff University School of Medicine specialising in metastatic solid tumours, Fellow of Royal Society of Medicine and chair of Cardiff China Medical Research Collaborative. Jiang also made it into BBC news in 2013, when he announced to have discovered a “formula”, “consisting of 14 herbs” from traditional Chinese medicine, to stop cancer metastasis.

The two great doctors Jiang and Nicholson made great promises to cancer patients. A preliminary investigation by Cardiff University now determined that those promises were based on duplicated images and cloned gel bands. Importantly, the committee also saw irregular splicing of gels as a problem, an issue many tend to dismiss. The traditional excuse goes that gel splicing was allegedly permitted until 2008 or so. In fact, irregular splicing of gels, where bits of different gels are assembled to look as it were one intact physical gel, was never permitted and always considered to be data manipulation. Especially where due to splicing the gel loading controls are proven not to match the analytic gels, the entire figure becomes meaningless. Or worse, it indicates research misconduct. This is not the first case of research misconduct Cardiff University and its School of Medicine have to deal with. In 2013, the School’s dean Paul Morgan stepped down after a misconduct investigation which acquitted him, but found his postdoc guilty of falsifying data in 4 papers. Clare Francis commented to me on the reasons for scrutinising papers by Nicholson and Jiang:

“My finding the present 2 was prompted by the 5th anniversary of my first complaints, i.e. last summer was 5 years after first complaining about Dean BP Morgan. I looked at who published in a similar field to BP Morgan in Cardiff, found RI Nicholson. I also looked at a person who published over 500 papers in Cardiff, found WG Jiang”.

The preliminary investigation was chaired by cell biologist Adrian Harwood, professor for neuroscience at School of Biosciences, and assisted by Alastair Sloan, Head of School of Dentistry. The two Cardiff academics were engaged tfor this task in late summer/early autumn 2017. Some of the analysed papers were quite old, around 15 years. Still, the committee determined them to contain duplicated data and referred the evidence to the main investigation. The results of all analysed papers were communicated to Clare Francis on February 5th 2018 in a transparent manner, which indicates that Cardiff University takes the issue very seriously.

After suspected image and gel band duplications as well as irregular gel splicing were confirmed in many instances for both Jiang and Nicholson, an external investigative committee was set up in Cardiff consisting of:

Judge Ray Singh (Independent Chair)

Professor Gavin Brooks (Pro Vice Chancellor Teaching and Learning, Reading University)

Professor Jeremy Guggenheim (School of Optometry & Vision Sciences, Cardiff University).

The full reports by the Harwood and Sloan preliminary investigation are here and here, below main excerpts, which I illustrate with annotated PubPeer evidence.

ARM 17/01: Report of Screening Panel Meeting held on 10 November 2017

5.1       Identification of Respondents

It was clarified that at this stage the allegations raised were levelled at all co-authors of each of the journal articles under scrutiny, and that the correspondence researchers for each publication had been asked to respond to the allegations. Professor Robert Nicholson had also his capacity as Head of the Research Group provided a context overview as a response to the allegations.

[…]

8. Summary of Screening Panel’s Findings

Article 1 – Breast Cancer Res. 2011 Sep 22;13(5):R93. doi: 10.1186/bcr3018

Details of Allegations       A number of issues raised with images including:

• Image duplication(the same data cannot represent two things)
• Image Compression
• Vertical stretch
• Degree rotation

Panel Finding                   The Panel found that there was evidence of non-attributed or unacknowledged image manipulation and splicing. The respondent acknowledged they have done this in their response but fail to acknowledge it is falsification of data. Some manipulation has inaccuracies. This is identified as poor lab practice.

Recommendation:          Progress to Investigation Panel to determine if this was deliberate and the impact on the scientific argument

Article 2 – Insulin-Like Growth Factor-I Receptor Signaling in Tamoxifen-Resistant Breast Cancer: A Supporting Role to the Epidermal Growth Factor Receptor

Details of Allegation       Inappropriate splicing

Panel Findings:               The panel upheld the allegation on the grounds of clear evidence of splicing

Recommendation           Progress to Investigation Panel.

Article 3 – Endocrinology. 2003 Mar;144(3):1032-44.

Details of Allegations     (a) Inappropriate splicing

(b) Vertical flipping of image (It cannot be paired with two different sets of data).

Panel Findings:               (a) The Panel noted that it has been acknowledged by the corresponding author that image slicing had taken place. It was noted by the corresponding author that they did not feel that splicing was inappropriate and that this was standard practice in a lab. The Panel disagreed with that assertion feeling that splicing represented poor lab practice.

(b) The panel noted that there was insufficient evidence to uphold the allegation of vertical flipping

Recommendations         1.      Progress to Investigation Panel to determine impact on the scientific argument (allegation (a))

2. No further action was recommended with regard to allegation (b)

Article 4 – Fulvestrant-induced expression of ErbB3 and ErbB4 receptors sensitizes oestrogen receptor-positive breast cancer cells to heregulin β1

Details of Allegation         Examples of inappropriate splicing

Same panels used to represent different cell types

Panel Findings:               The Panel found that there was evidence of non-attributed or unacknowledged image manipulation and splicing. The respondent acknowledged they have done this in their response but fail to acknowledge it is falsification of data. Some manipulation has inaccuracies. This is identified as poor lab practice.

Recommendations         Progress to Investigation Panel to determine impact on the scientific argument

Article 5 – Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells

Details of Allegations     (a)    Inappropriate splicing, vertical stretch

Panel Findings:               (a)    The Panel found that there was evidence of non-attributed or unacknowledged image manipulation and splicing. It was noted that reassembling spliced images in different orders means that not all findings can be accurate and it is therefore an Illustration of what the results should be rather than the accurate result.

Recommendations                       (a)       Progress to Investigation Panel

Details of Allegations     (b)         Two very similar reviews

Panel Findings                 (b)         No sufficient evidence to uphold this allegation

Recommendations         (b)         No further action was recommended

Article 6 – Endocrinology. 2003 Nov;144(11):5105-17. Epub 2003 Aug 7.

Details of Allegations       Illogical pairing of images.

Panel Finding                      The Panel felt that there was evidence of misleading data due to pairing of images.

Recommendation:             Progress to Investigation Panel

Article 7 –Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8.  Epub 2009 Mar 15.

Details of Allegations       Double use of a Western blot

Panel Finding                      The Panel felt that there was evidence of duplication of an image. It was noted however that this could have been done in error with no intent to deceive and the figure was not central to the scientific case being promoted.

Recommendations         1.      that tightening up of the scrutiny of manuscripts prior to submission should be recommended.

2. that the University could issue an error item to the journal to address this.
3. that no further action was required with regard to the allegation.
   

Article 8 – Endocr Relat Cancer. 2006 Dec;13(4):1085-99.

Details of Allegations       Unidentifiable mark in gel

Panel Finding                      No sufficient evidence to uphold this allegation as there was no evidence to suggest intent to deceive and the figure was not central to the scientific case being promoted.

Recommendation:             No further action was recommended

Article 9 – Breast Cancer Res Treat. 2006 Mar;96(2):131-46. Epub 2005 Oct 27.Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth.

Details of Allegations       Splicing of images

Panel Finding                      The panel found that there was evidence of splicing in this image and while this was not deliberately misleading it represented poor practice and rendered the figure represented as meaningless.

Recommendation:             Warrants further investigation into impact of misleading representation of data – Progress to Investigation Panel

Article 10 – Endocrinology. 2008 Oct;149(10):4912-20. doi: 10.1210/en.2008-0351. Epub 2008 Jun 26.

Details of Allegations       Reuse of image – Horizontal flip and vertical stretch

Panel Finding                      The panel found that there was evidence of re-use of image and horizontal flip. This was indetified as poor practice and representation of misleading data.

Recommendation:             Warrants further investigation into impact of misleading representation of data – Progress to Investigation Panel

Article 11 – Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004 Dec;11(4):793-814.

Details of Allegations       Vertical change in background   

Panel Finding                     No sufficient evidence to uphold this allegation

Recommendation:             No further action was recommended 

9. Conclusion

The Panel recommends to the Named Person:

1. That a Formal Investigation Panel under section 6 of the Procedure be established to consider the relevant articles identified above [Articles 1, 2, 3a, 4, 5a, 6, 9 and 10];

2. The screening panel recommends that in the scope of the investigation the quality assurance practices across the research group are investigated by the formal panel as the articles all relate to one research group;

3. The Panel recorded its concern over the nature, volume and proliferation in the public domain of the allegations.

 

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ARM 17/02: Report of Screening Panel Meeting held on 10 November 2017

5.1 Identification of Respondents

It was clarified that at this stage the allegations raised were levelled at Professor Wen Jiang who has been asked to respond to the allegations.

5.2       Allegations

It was confirmed that allegations in relation to 19 articles would be considered by the Panel;

The Panel was cognisant of the differences in practice across and within academic disciplines regarding the attribution of authorship rights; the role and responsibilities of lead, corresponding authors and the variability of the peer review process between different journals.

[…]

8. Summary of Screening Panel’s Findings

Article 1 – Br J Surg. 2005 Mar;92(3):305-10.Interleukin 7 upregulates vascular endothelial growth factor D in breast cancer cells and induces lymphangiogenesis in vivo.

Details of Allegations        Similarity of images – duplication

Panel Finding                      The Panel found that there was sufficient suspicion surrounding the similarity of the two highlighted images, and that further expert opinion would be required to determine if this was deliberate and the impact on the scientific argument.

Recommendations                       Warrants further investigation; progress to Investigation Panel. 

Article 2- Oncogene advance online publication 10 July 2017; doi: 10.1038/ onc.2017.199 PDZK1 inhibits the development and progression of renal cell carcinoma by suppression of SHP-1 phosphorylation

Details of Allegations       Similarity of images – duplication

Panel Finding                      The Panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action was recommended

Article 3- Oncol Rep. 2011 Jul;26(1):237-45. doi: 10.3892/or.2011.1271. Epub 2011 Apr 18. Knockdown of human antigen R reduces the growth and invasion of breast cancer cells in vitro and affects expression of cyclin D1 and MMP-9.

Details of Allegations       (a) Vertical Stretch

(b) Unexpected similarity of images

Panel Finding                      (a) The panel found that there was insufficient evidence to support this allegation

                                                (b)The panel found that there was insufficient evidence of duplication in figure 5C however, there was sufficient evidence of duplication for figure 5A 

Recommendation:             (a) No further action recommended

(b) Warrants further investigation; progress to Investigation Panel.

Article 4 – Oncotarget 2016 Mar 29;7(13):15378-89. Doi: 10.18632/ oncotarget.7463 Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer.

Details of Allegations       Splicing of image

Panel Finding                      The panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action recommended

Article 5 – Oncology Report, 2010, 24: 1653-9 Growth and differentiation factor-9 promotes adhesive and motile capacity of prostate cancer cells by up-regulating FAK and Paxillin via Smad dependent pathway.

Details of Allegations       Similarity of images and over exposure

Panel Finding                      The panel found that there was evidence of manipulation of the images that supported the allegation

Recommendation:             Warrants further investigation; progress to Investigation Panel. 

Article 6 –  J Urol, 2009, 181:2749, Fig 10C and 10D Epub 2009 Apr Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway. 

Details of Allegations       No images (figure 10C and 10D)

Panel Finding                      The panel found that there was sufficient evidence to support the allegation

Recommendation:             Warrants further investigation; progress to Investigation Panel. 

Article 7- IJO, 2013, 42: 1249-56, Fig 5. Candidate of metastasis 1 regulates in vitro growth and invasion of bladder cancer cells.

Details of Allegations       Unexpected similarity of highlighted images

Panel Finding                      The panel found that there was sufficient evidence to support the allegation

Recommendation:             Warrants further investigation; progress to Investigation Panel.

Article 8 – Lin Ye, BMP7, JUrol 2007 and Lin Ye HGF BMPR, IJO, 2007 Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells.

Details of Allegations       Sharing of some of the same data (double-dipping).

Panel Finding                      The Panel felt there was sufficient evidence to support the allegation raising a concern about the article being published without the journal’s permission.

Recommendation:             Warrants further investigation; progress to Investigation Panel.

Article 9 – 2015 May 10;15:51. doi: 10.1186/s12935-015-0203-3. eCollection 2015. Knockdown of WAVE3 impairs HGF induced migration and invasion of prostate cancer cells.

Details of Allegations       Unexpected similarity of images

Panel Finding                      The panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action recommended

Article 10 – Cancer Sci. 2010 Oct;101(10):2137-44. doi: 10.1111/j.1349-7006.2010.01648.x. Epub 2010 Jul 1.Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer.

Details of Allegations       Spliced Image

Panel Finding                      The panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action recommended

Article 11 –BMC Cancer. 2014 Sep 27;14:723. doi: 10.1186/1471-2407-14-723. Implication of metastasis suppressor gene, Kiss-1 and its receptor Kiss-1R in colorectal cancer.

Details of Allegations       Unexpected similarity between highlighted images

Panel Finding                      The respondent has identified the images were duplicated in error in the publication. The Panel upheld that there had been duplication.

Recommendation:             Progress to Investigation Panel to determine impact on the scientific argument and consider action required to address this issue.

Aricle 12 – Urol Oncol. 2008 Jul-Aug;26(4):386-91. doi: 10.1016/j.urolonc.2007.06.003. Epub 2008 Jan 14. Phospholipase-C gamma-1 (PLCgamma-1) is critical in hepatocyte growth factor induced in vitro invasion and migration without affecting the growth of prostate cancer cells.

Details of Allegations       Similarity of highlighted images

Panel Finding                      The panel found that there evidence to suggest that there was likely duplication of this image

Recommendation:             Warrants further investigation; progress to Investigation Panel.

Article 13– Oncol Rep. 2015 Oct;34(4):1977-87. doi: 10.3892/or.2015.4162. Epub 2015 Jul 30. Inhibition of sphingosine-1-phosphate phosphatase 1 promotes cancer cells migration in gastric cancer: Clinical implications.

Details of Allegations       Similarity of images

Panel Finding                      The respondent has identified the images were duplicated in error in the publication. The Panel upheld that there had been duplication.

Recommendation:          Progress to Investigation Panel to determine impact on the scientific argument and consider action required to address this issue. 

Article 14 – Int J Oncol. 2016 Mar;48(3):919-28. doi: 10.3892/ijo.2016.3339. Epub 2016 Jan 15. Importance of osteoprotegrin and receptor activator of nuclear factor κB in breast cancer response to hepatocyte growth factor and the bone microenvironment in vitro. 

Details of Allegations       Similarity of images

Panel Finding                      The panel found that there evidence to suggest that there was likely duplication of this image

 

Recommendation:             Warrants further investigation; progress to Investigation Panel.

Article 15- Int J Mol Med. 2016 Nov;38(5):1349-1358. doi: 10.3892/ijmm .2016.2733. Epub 2016 Sep 13. Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing.

Details of Allegations       Similarity of images

Panel Finding                      The panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action recommended 

Article 16 – Eur J Cancer. 2004 Dec;40(18):2717-25. Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer. 

Details of Allegations       Similarity of images/Horizontal Flip

Panel Finding                      The panel found that there was sufficient evidence to support the allegation

 

Recommendation:             Warrants further investigation; progress to Investigation Panel.

Articles 17 &18 – Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3510-7. Decreased pigment epithelium-derived factor expression in human breast cancer progression.

Shares data with:

Eur J Cancer. 2005 Dec;41(18):2819-27. Epub 2005 Nov 4. Placenta growth factor is over-expressed and has prognostic value in human breast cancer.

Details of Allegations       Sharing data (double-dipping)

Panel Finding                      The panel found that there was insufficient evidence to support this allegation

Recommendation:             No further action recommended

Article 19 – British Journal of Cancer (2014) 110, 421–429. doi:10.1038/bjc.2013.712 www.bjcancer.com.  Published online 3 December 2013. Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy

Details of Allegations     Similarity of images some differences in the intensity and gaps between bands

Panel Finding                      The panel found that there was sufficient evidence to support the allegation

Recommendation:             Warrants further investigation; progress to Investigation Panel.

9. Conclusion

The Panel recommends to the Named Person:

1. That a Formal Investigation Panel under section 6 of the Procedure be established to consider the relevant articles identified above [Articles 1, 3b, 4, 5 6, 7, 8, 11, 12, 13, 14,16,19 ];

2. The Panel recorded its concern over the nature, volume and proliferation in the public domain of the allegations.

 

Update 24.04.2018. The Cardiff University now issued a press release, where it declared the above evidence for Wen Jiang publications to be false allegations:

Allegations relating to research misconduct – 19/04/2018

“In recent months a number of allegations have emerged on social media and blog posts about research conducted by Professor Wen G. Jiang, notably on https://forbetterscience.com/2018/02/14/fried-divine-comedy-featuring-anti-cancer-cockroach-and-phallic-fungus/#more-23091

Some of these allegations, relating to research misconduct, were formally submitted to Cardiff University by an anonymous whistleblower.

Cases of research misconduct are rare at Cardiff University. However, when allegations are made they are considered in accordance with the University’s Procedure for Dealing with Allegations of Misconduct in Academic Research.

The University’s procedure is in line with guidance issued by the UK Research Integrity Office, to which the University subscribes.

The University has conducted a formal investigation into the allegations.

In all it reviewed allegations relating to 19 publications and has not upheld the allegations of misconduct.

Cardiff University reviews the research quality of all its academic staff as part of performance development reviews and ongoing preparations for the next national Research Excellence Framework (REF). Professor Jiang has been assessed by independent review as having research outputs of a standard eligible for submission to the next REF.

[…]”

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