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.

ole-karin-6_web
Some funny stuff in our papers they found! Ole Petter Ottersen and Karin Dahlman Wright. Photo: Gustav Mårtenson/KI

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

file

image-1531691510854.jpg
Above: A duplicated image of cells. Maybe a mistake, maybe the authors only took one single photograph for controls, which is not really good research practice. Below: a western blot loading control was reused, in a different experimental context. This can’t really be a mistake, because the image was flipped. So, what was wrong with the proper loading control then?

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.

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What have we got? An apparent gel image duplication in Figure 1A. Might be an honest mistake. But what looks like duplicated patches of background in Figure 1B is (if confirmed) deliberate photoshopping to hide something. In Figure 1C, the square shapes around the gel bands suggest those might have been inserted in Photoshop, probably because the authors didn’t like what the gel originally showed.

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

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This looks like duplicated gel bands. There is no excuse for that.

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.

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Somehow the western blot for ERalpha apparently became also the loading control for GAPDH. All was needed was some shrinking, brightness enhancing and cropping. Must have been an accident, right?

Update 6.08.2018. Johan Thyberg, emeritus KI professor and chronist of KI research misconduct scandals, obtained the original gel scans, and found more.

image 2

oncogene2014

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

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Definitely honest mistakes, all those copy-pasted gel bands, right? In any case, no research misconduct of the horrible kind the KI whistle-blowers committed, especially by talking to media

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.

screenshot-mail.google.com-2018-08-06-10-19-04

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.

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The bands are quite similar, especially certain tell-tale features highlighted by arrows

Ohers joined Clare Francis in the treasure hunt. This is another recent Dahlman-Wright lab paper

Marko Matic , Galyna Bryzgalova , Hui Gao , Per Antonson , Patricia Humire , Yoko Omoto , Neil Portwood , Camilla Pramfalk , Suad Efendic , Per-Olof Berggren , Jan-Åke Gustafsson , Karin Dahlman-Wright

Estrogen signalling and the metabolic syndrome: targeting the hepatic estrogen receptor alpha action

PLoS ONE (2013)  doi: 10.1371/journal.pone.0057458

image-1531978042217
Apparently, parts of same photograph were used to stand in for two different experimental conditions

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.

The last 3 lanes looks strangely similar. Are they maybe the same?

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
human trials
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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17 thoughts on “Former KI rector Dahlman-Wright: stones in a glass house

  1. That is the point: before accusing others we should make sure our own work is irreproachable and totally transparent and humbly accept fair criticism

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  2. How could you think again that rectors have time to do research or to read own papers?
    Macchiarini did not remembered code for entrance to his lab and he had much less administrative duties.

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    1. If Rectors don’t have time for research or to read papers they shouldn’t sign and assume those publications as if they had revised it

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      1. That is the point. Current system demands that rectors continue research. They can’t honestly admit that their administrative duties leave 1 hour per month for research on weekends. I suspect most of rectors work much over 8 hours a day and still can’t make all work. Why to demand from them to do research and force into gray zone of signing papers made by others? Make them pure administrstors and admit reality. Rectors must be officially forbidden to be PI’s.

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  3. One underlying issue is that scientists are trying to distance themselves, and differentiate themselves from “managers”. It is up to scientists to root out as many “managers” as possible.

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    1. I think Rectors can keep working in research, I think we can both a scientist and a business person, many pharmacists like me to this
      I think the secret is how to be able to manage all of your activities and we can do it very honestly
      Because a Rector is a Rector and is obligated to conduct research that is no excuse they don’t read the papers they sign

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  4. With this article as submitted evidence, KI has opened an official misconduct investigation, case number Dnr 2-4145/2018
    Rector Pettersen issued an offiical comment after Swedish daily Dagens Nyheter reported about the manipulated data in his paper.
    https://www.dn.se/nyheter/kritiken-vaxer-mot-kis-rektor-efter-macchiarini-granskningen/
    https://ki.se/nyheter/kommentar-angaende-dn-artikel-publicerad-19-juli-2018
    The whistleblower Grinnemo and others now brought a complaint against KI in administrative court against the misconduct findings.
    https://www.dagensmedicin.se/artiklar/2018/07/20/medforfattare-overklagar-ki-beslut-i-domstol/

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    1. KI Chairman Mikael Odenbrg now published this official blog post as response to a newspaper article and my reporting above of which I notified KI.
      http://blog.ki.se/chairman/jag-delar-de-resonemang-som-uttrycks-i-rektors-beslut-2/
      He also sent me and Johan Thyberg confrimations of our notifications (here and here)
      Translation:

      I agree with the reasoning expressed in the President’s decision
      published 20 July, 2018, updatedJuly 21, 2018 by President

      By midsummer, we completed an important chapter in the Macchiarini scandal when the headmaster made his decision in the large fraud case concerning six scientific articles by 43 authors including Macchiarini himself.

      This decision as it was became controversial. Personally, I can easily share the values ​​and the reasoning expressed in the President’s decision. I have obviously not been involved in the handling of the case, yet from the distance I could understand with the precision and care and sometimes anguish with which that work has been conducted.

      The decision is well written and as far as I can see, very solid. But that is not appreciated by everyone. Especially the whistleblowers convicted or accused are obviously disappointed. I can understand that. Yet one must keep things separate.

      I listened to a radio feature in Studio Ett on P1 in which the president discussed the decision with one of the so-called whistle-blowers. In the radio segment he expressed much criticism of KI’s handling of the matter:

      “We whistleblowers made a valid notification, but KI and KS [Karolinska University Hospital] ignored it. This is a continuation of the repressions whicht we were always exposed to. It was our notification that allowed for the fraud to be revealed. We took responsibility, and more, in contrast to KI and KS which did not take any responsibility at all. Yet they blame us while Anders Hamsten avoids both scrutiny and accountability. Why not review him, the rector, instead” .

      Individual assessment

      Yes, much of this is in some sense true. KI and KS have much to be ashamed of. But the rector – in this context – did not have to assess individuals’ motives. He did not have to assess intent or benefit. He did not have to assess the KI previous shortcomings. He did not have to assess the whistleblowing effort. He did not have to assess Anders Hamsten’s actions.

      He had to assess the cheating in six scientific articles. He has done that. And he did not choose the easy way to make a collective judgment on the authors, like when the expert group at CEPN proposed to accuse all 43 of research misconduct.

      KI’s rector instead chose the more difficult and longer route and decided on a more individual basis. This led to five co-authors being freed. Seven of the researchers were convicted of research misconduct, while 31 were considered blameworthy, without being guilty of misconduct.

      I’m happy to repeat my heartfelt thanks to the whistleblowers for their effort. But I refuse to accept an approach which would mean reducing – or even influencing – their responsibility for the content of scientific articles on which they have chosen to put their name.

      The criticism is based on erroneous grounds

      Today a full-page article about the Rector’s Macchiarini investigation appeared in Dagens Nyheter. It describes the criticism of whistleblowers that they could not comment on the rector’s decision before it was taken, and a professor of administrative law is interviewed. The problem is that the criticism is based on a completely false assumption.

      It goes without saying that whistleblowers were consulted during the preparation and before the rector made his decision. They have in fact been heard a number of times. But whistleblowers seems to think that they should have had a draft of the decision itself for some sort of final comments. However, this is not custom or supported by any requirements of the Administrative Procedure.

      A point is also an accusation of bias in the DN article. The issue of bias was brought, however, by the person in question and there was also a proper consultation of our lawyers.

      In the sad aftermath there are now attempts to finger the university management – the Rector Ole Petter Ottersen and Vice Rector Karin Dahlman-Wright – with accusations that they certainly are also guilty of research fraud.

      Notifications are collected and handled

      We learned yesterday of two similar complaints, and particularly in the one it became abundantly clear that the issue is really about the whistleblowers. The idea seems to be that if the rector did wrong him- or herself, and if they can be convicted of this, they have also forfeited their right to judge others.

      Yes, complainants’ motives, of course, play no role now. Notification shall obviously be received and dealt with in due course. It will be done in the following way.

      Complaint against the rector will not be taken up by KI. The article questioned was published long before Ole Petter Ottersen began his work at KI and is about experiments mainly carried out at the Pasteur Institute in Paris. Consequently, I will refer the notifier there.

      Regarding the complaints against the Vice Rector Karin Dahlman-Wright I conclude that – although there is no direct disqualification – it would be inappropriate to deal with inside the KI, that is to say that the Rector should be forced to investigate one of his closest associates.

      We will therefore request this fraud case to be dealt with at another university.

      I have been in contact with the the Governor Cecilia Schelin Seidegård who is my chair colleague at the University of Gothenburg, where the Rector Eva Wiberg has declared herself prepared to take over the proceedings.

      Finally, I regret that the Macchiarini case indirectly continues to blight our lives. Fraud case surrounding the six articles is in any case now a closed chapter, as far as KI is concerned. KI’s journey continues and I can not emphasize enough how safe I feel to have Ole Petter and Karin as rector and vice-rector on this journey.

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  5. The letter from the chairman is directed torrwards the organisation. It says be quite or we will crush you. The Karolinska Institutet is rapidly moving closer to North Korea and one can really ask “who would want to accept a Nobel Price from this organisation”.

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  6. The Chairmans blogg is a travisty. There has now been reports in Swedish media of multipel errors in the vice-chansellors report in the Macchiarini case. Following the usual logic at the Karolinska the leadership are now trying to cover-up The Dahlman-Wright scandal reported by you. It is like Karolinska learned nothing from the Macchiarini scandal. Internally there has now been reports of students that have been ordered to destroy lab-books inorder to cover-up fraud. The entire Institue is sadly collapsing

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  7. I can accept cold and logic as used in the verdict of the whistle-blowers. But if cold and logic is the (new?) KI strategy, why does the chairman declare loyalty (“I can not emphasize enough how safe I feel”) to KDW at a time he has her “fraud case” investigated. That does not send a message of neutrality.

    Fraud investigation at another university is not a guarantee for neutrality. Certainly not if that other university is chosen within a single day after the fraud was revealed, and by the person who feels deep loyalty to the accused.

    Passivity (“t would be inappropriate to deal with inside the KI”) at the KI itself will delay the investigation, and allow the fraudsters to remove tracks.

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  8. KI should never have handled the Macchiarini case either. There are to many people involved in this Cover-up at the Karolinska to objectively handle this case. For many years the leadership at the Karolinska have actively encourage research fraud and punished whistleblowers and organisation have lost the ethical and moral compass needed in research a long time ago.

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  9. You are correct in your analaysis of Anders Hamsten. Karolinskas problem of coruption is deeply rooted and therefore less capable people is promoted to higher level positions. In crisis this quickly leads to the collapse of the institution since the entire upper level management are incompetent and can not handle the crisis. This is what has happened at the Karolinska and we are only in the early phases of this collapse. This will get much worse

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