The Nobel Assembly at the Karolinska Institutet (KI) in Sweden awarded this week the Nobel Prize in Physiology or Medicine 2016 to the Japanese scientist Yoshinori Ohsumi “for his discoveries of mechanisms for autophagy”. Autophagy is a physiologically highly relevant intracellular process of protein and organelle recycling, when these are misfolded or damaged or when the cell lacks nutrients. Possibly, KI Nobel Assembly’s decision might have been inspired by the success of their own excellent young autophagy researcher: Helin Vakifahmetoglu-Norberg, see also this press release. The following is to raise concerns about hers and KI’s achievements in the Nobel-awarded research field of autophagy, which are somewhat marred by recurrent image duplications. The copious new evidence I was given by a certain sleuth team suggests a possibly bigger problem than KI previously decreed.

The young group leader started her career in the field of apoptosis (cell death) research and authored many publications in highly respectable journals, both as PhD student of Karolinska in the lab of cell biologist Boris Zhivotovsky, as well as postdoctoral scientist in Harvard, with another apoptosis specialist, Junying Yian. Vakifahmetoglu-Norberg then returned to KI to start her own cell biology research group, not on apoptosis, but on autophagy. At her institutional website she lists research funding from top-sources like the Swedish Research Council (VR), the Ragnar Söderberg Foundation, the Swedish Society for Medical Research and several others. “Highly enthusiastic and hardworking postdocs and undergraduate students” are invited to join the “protein degradation pathways“ lab, while also discretely asked to bring their own financial support. Funding money plays a big role at KI, as we all recently learned during the Paolo Macchiarini scandal.

One year ago, concerns were raised on PubPeer about image reuse in a Vakifahmetoglu-Norberg publication on autophagy in the Journal of Cell Biology (JCB), namely Xia et al 2015. Normally, JCB editorial team screens all manuscript submissions for internal image duplications and other irregularities. The problem in that case was: the reused images came from two different publications, namely from her earlier papers as junior researcher with Zhivotovsky and Yian (Vakifahmetoglu-Norberg et al, Cell Death and Disease, 2013 and Vakifahmetoglu-Norberg et al, Genes & Development 2013, respectively). JCB corrected the publication on August 31st 2015 with a note:

“It recently came to the authors’ attention that the tubulin loading control panels shown in Figs. 2 Gand S2 F were incorrect as a result of errors introduced during figure preparation. The authors apologize for these mistakes. The conclusions of the experiments shown in these figures are not affected”.

Also the Genes & Development 2013 paper was corrected on April 1st 2016, again with the caveat:

“Neither the quantitative determinations nor the conclusions of this article are altered”.

Unfortunately, it seems there was another western blot image from the 2013 Genes & Development paper which somehow was erroneously introduced during figure preparation:

In July 2016, Tomas Ahlbeck, Press secretary at the KI Communications and Public Relations Office informed me:

“Regarding Helin Vakifahmetoglu-Norberg: the three allegations are investigated and have been written off”.

I asked him to clarify this, but he remained silent. Yesterday I requested from KI registrar the investigative report (dated May 31st 2016) and here it now is, in assisted Google- translation (Swedish original here):

Decision The case is removed from the register. The case In view of the information on the Pubpeer.com about the three publications by Helin VakifahmetogluNorberg a case on suspicion of research misconduct was initiated The three publications referred to are “Degradation of HK2 by chaperone-mediated autophagy promotes metabolic catastrophe and cell death“,“Chaperone-mediated autophagy degrades mutant p53“and “Chromosomal breaks during mitotic catastrophe trigger γH2AX–ATM–p53-mediated apoptosis“. Helin Vakifahmetoglu-Norberg spoke about the case on April 18 and April 29, 2016. On April 5, 2016 Professor Junying Yuan forwarded a letter to Karolinska Institutet in cases 21646/2016 and 21647/2016 that corrections have been made in Genes and Development and Joumal of Cell Biology. Professor Boris Zhivotovsky explained on April 29, 2016 regarding the publication 21648/2016 that he was asked by the publisher to provide high resolutions of all images. On this occasion, the blot was duplicated by a technical mistake. It was not Helin VakifahmetogluNorberg who was responsible for these images. The correct version has been accepted by the publisher and errata has recently become published. Reason for the decision It emerged from the investigation of the cases that these do not constitute dishonest research, this is why the case is terminated. This decision was made by the Acting President Karin Dahlman-Wright in presence of University Director Per Bengtsson after a presentation by lawyer Lisen Samuelsson. Present were Deputy Vice Chancellor Professor Grönberg, as well as University Director Marie Tell and the Chairman of Medical Society Frida Hellström.

It is possible though that KI knew about more than just three allegations. Not only there were more papers by Vakifahmetoglu-Norberg flagged on PubPeer, there were also further corrections.

Journal of Cell Science, which prides itself of their publishing ethics, corrected on May 1st 2016 the above mentioned paper from Zhivotovsky’s KI lab, featuring Vakifahmetoglu-Norberg as co-author (Imreh et al, 2011). A western blot was replaced, with the correction note warning off all potential sceptics:

“There are no changes to the figure legend, which is accurate. This error does not affect the conclusions of the study”.

Unfortunately, the editors missed evidence for image duplication inside same figure (or maybe they were simply not really looking). All one had to do to detect it was to boost contrast:

On July 4th 2016, a collaborative paper in Oncogene featuring Vakifahmetoglu-Norberg and Zhivotovsky as co-authors, was corrected. Some western blot duplication issues in Shen et al 2008 were corrected, with experiments repeated. The correction note made clear:

“All data are in agreement with previous findings described in the original article, and the main conclusion remains unchanged”.

There was just one small problem with those allegedly reproduced experiments: one new western blot looks strangely similar to another already appearing in the same 8 year old paper, in a different context. Meanwhile, it seems to have grown an additional lane in between. Another corrected western blot, also allegedly freshly made for the purpose of correction, seems to be very similar to its old place-holder, aside of having lost a lane instead.

The evidence I was provided shows even more. Another couple of eight year old papers from Zhivotovsky lab in the journal Cell Death Differentiation, namely the research paper Vakifahmetoglu et al 2008 and the review paper Vakifahmetoglu et al 2008 seem to share not just some accidentally copied images as duplication. Instead, some individual cells inside certain microscopy images look very similar to cells from utterly different microscopy images. Their neighbours however are different, one wonders how authors would explain that peculiarity.

Yet another Cell Death Differentiation paper, Vakifahmetoglu-Norberg et al 2013, authored by Zhivotovsky together with his former star PhD student and now close colleague at KI, contains evidence of western blot reuse as well:

In summary, maybe KI and the journals should have another look. Just to be absolutely sure, that despite many duplications, all the main conclusions in papers authored by this star autophagy researcher are still absolutely solid and beyond any doubt. With the Nobel Prize just awarded to this field, the reputation of KI’s own autophagy researchers should be beyond reproach.

The dossier I made from the evidence I was forwarded to, is available here.