The irony is rich. Just last month, the Swedish Karolinska Institutet (KI) announced the results of the investigation into papers by their former guest professor Paolo Macchiarini and his right-hand man Philipp Jungebluth. The two were found guilty of research misconduct and their plastic trachea transplant papers were set for retraction, where at least the journal The Lancet finally obliged (read here). Exemplary decision, but there is a snag: next to the ruthless trachea transplanters, other scientists were found guilty of misconduct, among them Karl-Henrik Grinnemo, one of the four original KI whistleblowers without whose brave actions there would have been no Macchiarini scandal. Two more whistleblowers were found “blameworthy” of negligence. Also KI professor Katarina Le Blanc was found guilty of misconduct, incidentally a whistleblower herself who reported severe ethics breaches in a different case of regenerative medicine and human research at KI two years ago. Finally, KI fingered the sacked UCL nanotechnologist Alexander Seifalian for research misconduct, using the very same shaky arguments the London university pulled off in its investigative report in 2017 (read here). The bizarre thing: back then UCL did not allow Seifalian to defend himself or to appeal against the accusations, and KI now did exactly same. He was served a misconduct verdict, but was denied by KI a right to testimony or appeal, which Macchiarini and his gang were granted generously and made ample use of.
The Macchiarini investigation was initiated in 2016 by the interim KI Vice-Chancellor (rector) Karin Dahlman-Wright and was completed this year by the newly installed Vice-Chancellor Ole Petter Ottersen. The promised irony is that several Dahlman-Wright papers were now scrutinised by the pseudonymous data integrity sleuth Clare Francis with the result that one wonders if Dahlman-Wright was the right person to supervise a research misconduct investigation. Here comes namely even more irony: that former interim rector and her successor Ottersen previously absolved the notorious KI group leader Helin Vakifahmetoglu-Norberg and her former PhD mentor, the KI professor Boris Zhivotovsky (read here), despite heavy evidence of manipulated data. Nine more professors were under misconduct investigation during Dahlman-Wright’s tenure (read here), and since we heard nothing yet, one can assume that all the duplicated and photoshopped data in their papers was also a misunderstanding which bears no relevance on the quality of their research. The Dahlman-Wright evidence I present below is heavy, but also Ottersen himself might be tainted: he is co-author on an old paper with a likely image duplication.
All this of course is per se in no way an accusation towards Dahlman-Wright and Ottersen as scientists. A group leader can never have a total oversight of what goes on in her or his lab. It is the way of how that senior author acts upon finding or receiving such evidence of data manipulation which separates honest researchers from dishonest ones. When your own papers are not kosher, it doesn’t really make a good show to accuse whistleblowers or those unable to defend themselves of research misconduct, while in a separate case to declare blatant data manipulations by your professorial colleagues to be innocent mistakes or image compression artefacts.
So here it is, the evidence for the works of the cancer researcher Dahlman-Wright. It all started with a recent PubPeer post of an Oncotarget paper.
Yichun Qiao , Chiou-Nan Shiue , Jian Zhu , Ting Zhuang , Philip Jonsson , Anthony P.H. Wright , Chunyan Zhao , Karin Dahlman-Wright
AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial-mesenchymal transition in triple-negative breast cancer
Oncotarget (2015) doi: 10.18632/oncotarget.3158
This is where Clare Francis was kind enough to check more papers from Dahlman-Wright lab. And found this:
Liu Y1, Gao H, Marstrand TT, Ström A, Valen E, Sandelin A, Gustafsson JA, Dahlman-Wright K.
The genome landscape of ERalpha- and ERbeta-binding DNA regions.
Proc Natl Acad Sci U S A. 2008 doi: 10.1073/pnas.0712085105.
Clare Francis found more, in a collaborative paper Dahlman-Wright co-authored.
Lindberg MK, Weihua Z, Andersson N, Movérare S, Gao H, Vidal O, Erlandsson M, Windahl S, Andersson G, Lubahn DB, Carlsten H, Dahlman-Wright K, Gustafsson JA, Ohlsson C.
Estrogen receptor specificity for the effects of estrogen in ovariectomized mice.
J Endocrinol. 2002. doi: 10.1677/joe.0.1740167
In the following case, Dahlman-Wright acted wisely by choosing the right journal. The Editor-in-Chief of Oncogene Justin Stebbing has his own dialectics of research integrity (read here).
Zhu J, Zhao C, Kharman-Biz A, Zhuang T, Jonsson P, Liang N, Williams C, Lin CY, Qiao Y, Zendehdel K, Strömblad S, Treuter E, Dahlman-Wright K
The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation.
Oncogene. 2014. doi: 10.1038/onc.2013.573.
Update 6.08.2018. Johan Thyberg, emeritus KI professor and chronist of KI research misconduct scandals, obtained the original gel scans, and found more.
The following paper was published at the height of the Macchiarini affair. Dahlman-Wright took over KI leadership after her predecessor Anders Hamsten and a bunch of other KI elites resigned in shame (read here), and Dahlman-Wright began investigating research misconduct by Macchiarini and others. At the same time, in her own lab somebody was doing something very, very inappropriate. No, not whistleblowing.
Jia M1, Andreassen T2, Jensen L3, Bathen TF4, Sinha I5, Gao H5, Zhao C5, Haldosen LA5, Cao Y6, Girnita L7, Moestue SA4, Dahlman-Wright K
Estrogen Receptor α Promotes Breast Cancer by Reprogramming Choline Metabolism.
Cancer Res. 2016 doi: 10.1158/0008-5472.CAN-15-2910
And here another one I received, all the evidence was afterwards posted on PubPeer. Here one might be tempted to blame Dahlman-Wright’s collaborator and last author of this paper, Sebastiano Ando from University of Calabria, given his own PubPeer record.
Update 6.08.2018. Johan Thyberg spotted more band duplications in this paper, labelled in dark blue. He also notified the institution.
Rizza P, Barone I, Zito D, Giordano F, Lanzino M, De Amicis F, Mauro L, Sisci D, Catalano S, Dahlman Wright K, Gustafsson JA, Andò S.
Estrogen receptor beta as a novel target of androgen receptor action in breast cancer cell lines.
Breast Cancer Res. 2014 doi: 10.1186/bcr3619.
Ohers joined Clare Francis in the treasure hunt. This is another recent Dahlman-Wright lab paper
Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action
Finally, this was reported on PubPeer for a paper which the current KI rector Ottersen co-authored almost 30 years ago.
M M Arroyo-Jiminez , J P Bourgeois , L M Marubio , A M Le Sourd , O P Ottersen , E Rinvik, A Fairén , J P Changeux
Ultrastructural localization of the alpha4-subunit of the neuronal acetylcholine nicotinic receptor in the rat substantia nigra
J Neurosci. 1999 Aug 1;19(15):6475-87.
People living in glass houses should not throw stones. Dahlmann-Wright and Ottersen, instead of apologising and thanking the Macchiarini whistleblowers, threw stones at them, by finding them guilty of research misconduct and negligence.
But what shall we make of their own papers? Are those apparent duplications research misconduct? Blameworthy negligence? Or maybe actually good scientific practice, when the right people do it?
Update 19.07.2018. I now obtained the whistleblowing report by Katarina Le Blanc, titled “Concerns Regarding the Clinical Use of Decidual/Foetal Membrane Stromal Cells at Karolinska University Hospital and Karolinska Institutet”. These were the concerns the report raised in 2016 (full document here):
• No prior safety or efficacy data regarding the infusion of decidual stromal cells before commencing human trials
o No animal models for safety of decidual stromal cells were published prior to
o No animal efficacy data was published for use of decidual stromal cells for any of
the indications used in humans
o No in vitro data regarding the immunogenicity of allogeneic decidual stromal cells
was published before commencing human trials
• Serious inconsistencies in local ethical approvals
o Insufficient patient information provision as per SOSFS 2009:30
o Retrieval of tissue without ethical approval or fully informed donor consent
o Consistent incorrect citation of ethical permits within scientific publications
• No regulatory permit was obtained for use of expanded decidual stromal cells in clinical trials
o Human trials of decidual stromal cells commenced in 2011
o IVO permission for procurement, isolation, storage and distribution of decidual stromal cells was only sought in November 2013. In addition to this late application, the permit was invalid as it did not cover clinical usage of manipulated cells
• Retrospective provision of information to Clinicaltrials.gov
o All clinical studies were uploaded in 2014
o This included one completed and one on going study
The main accused KI researcher was the haematologist Olle Ringdén, investigated by Dahlman-Wright and then cleared of suspicions of misconduct. The final decision by the successor Ottersen earlier this year found Ringden merely “culpable for the flaws in the implemented research”. Soon after, Le Blanc herself was found guilty of misconduct in the Macchiarini case by those same two Vice-Chancellors.
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