Research integrity

Data integrity conspiracy against German research senator Roland Lill?

Roland Lill is the quiet star of German molecular biology. The 63-year old professor works at the University of Marburg, on mitochondria, using yeast as a model organism. Lill is also since 2014 member of the Senate at the German Research Foundation (DFG), re-elected just recently, where he represents the interests of German molecular biologists and decides on federal funding distribution and research policies. Since 2016, the Marburg professor is also Senator for Biochemistry and Biophysics at the Leopoldina, which is the German Academy of Sciences. Furthermore, Lill is EMBO member since 2013 and he also used to be Fellow of the Max Planck Society.

Lill’s research focus is on iron-sulfur biogenesis, and his achievements for German science are indeed strong as iron, as evident by his awards and medals (including the Leibniz Prize of €1.55 Mn in 2003), his impressive funding acquisition success and publication record. Recently however, a sulfuric smell of rotten eggs emitted from the whistleblowing platform PubPeer, tainting his legacy. Currently 9 Lill papers are affected, the evidence looks worrisome, and might indicate possible data manipulations. Mostly it is about apparently duplicated gel bands. Luckily however, most papers are 13 and more years old, nobody would expect Professor Lill to have stored the original data for so long, even if it was ever available. The despicable attack on Professor’s Lill research record will be surely thwarted by the journals’ reluctance of dealing with problems in old papers, and of course by the tremendous respect and influence this Senator enjoys in German academia. In fact, both DFG and the two research integrity Ombudspersons of the University of Marburg refused to comment on the PubPeer evidence. Leopoldina announced to me to have the “accusations” addressed by their Ombudsman; DFG mentioned to have had the PubPeer information “forwarded inside the house”.

 

 

 

There can be only one explanation. Someone, or a group of someones, have been trying to damage Professor Lill for decades by sneaking suspicious-looking data into his publications. One might be tempted to blame Lill’s past PhD student, Heike Lange, who is now a tenured researcher at The Olivier Voinnet Institute for Research Integrity in Plant Sciencesalso known as the CNRS Institut de Biologie Moléculaire des Plantes (IBMP) in Strasbourg, France. After leaving the Lill lab in Marburg, Lange apparently kept on accidentally duplicating gel bands in her publications, as evident in this IBMP paper Lange et al 2011. These are Lange’s disputed papers with Lill:

H Lange, A Kaut, G Kispal, R Lill

A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins.
Proceedings of the National Academy of Sciences of the United States of America (2000) doi: 10.1073/pnas.97.3.1050 

 

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From Lange et a, PNAS 2000, gel bands appear duplicated (highlights colour coded); source: PubPeer

Anita Kaut, Heike Lange, Kerstin Diekert, Gyula Kispal, Roland Lill

Isa1p is a component of the mitochondrial machinery for maturation of cellular iron-sulfur proteins and requires conserved cysteine residues for function.
The Journal of biological chemistry (2000) doi: 10.1074/jbc.M909502199

luf7h3w.png
From Kraut et al, JBC 2000. A gel panel appears duplicated (red frames), a gel section appears digitally erased (purple highlight). Source: PubPeer

Heike Lange, Thomas Lisowsky, Jana Gerber, Ulrich Mühlenhoff, Gyula Kispal, Roland Lill

An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins.
EMBO reports (2001) doi: 10.1093/embo-reports/kve161 

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From Lange et al EMBO Reports 2000, gel bands appear duplicated. Source: PubPeer. Lill is member of advisory editorial board at EMBO Reports

Comment on PubPeer regarding above image:

Dear Madam/Sir,
We have inspected the claim that several bands in Fig. 4 of our EMBO Rep paper from 2001 “are duplicates (red, blue) or flipped duplicates (green)”. Especially in larger magnification, it easily becomes clear that the criticized couples are NOT identical. We further note that the result of this figure (i.e. Erv1 is a protein of the mitochondrial intermembrane space) has been verified by other labs many times since our publication.
Sincerely,
Heike Lange and Roland Lill

Heike Lange, Ulrich Mühlenhoff, Martin Denzel, Gyula Kispal, Roland Lill

The heme synthesis defect of mutants impaired in mitochondrial iron-sulfur protein biogenesis is caused by reversible inhibition of ferrochelatase.
The Journal of biological chemistry (2004) doi: 10.1074/jbc.M403721200 

rtb4ear.png
From Lange et al JBC 2004. Western blot bands seem to have been re-used in different context. Source: PubPeer

 

 

Problem is, Lange is not co-author on a number of other papers from Lill lab. One wonders, which sinister powers might be then behind that attempt to rust the iron legacy of professor Lill:

Jana Gerber, Ulrich Mühlenhoff, Roland Lill

An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO reports (2003) doi: 10.1038/sj.embor.embor918 

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From Gerber et al, EMBO Rep 2003. Irregular splicing brings doubt into validity of this figure, source PubPeer. Lill is member of advisory editorial board at EMBO Reports

Janneke Balk, Antonio J Pierik, Daili J Aguilar Netz, Ulrich Mühlenhoff, Roland Lill

The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron–sulphur proteins
The EMBO Journal (2004) doi: 10.1038/sj.emboj.7600216

image-1497545949800
From Balk et al, EMBO J 2004. Gel bands in panel Sec61p have suspicious borders, suggesting they might have been digitally copy-pasted into the background of panel Aac2p. Source: PubPeer

Jana Gerber, Karina Neumann, Corinna Prohl, Ulrich Mühlenhoff, Roland Lill

The Yeast Scaffold Proteins Isu1p and Isu2p Are Required inside Mitochondria for Maturation of Cytosolic Fe/S Proteins
Molecular and Cellular Biology (2004) doi: 10.1128/MCB.24.11.4848-4857.2004

image-1499363671400
From Gerber et al, MCB 2004. The highlighted gel band has suspicious borders, indicating being possibly digitally pasted into the gel image. Source: PubPeer

So what happened in the Lill lab in early noughties? Luckily, those secretive misdeeds of parties unknown did not damage the authors’ careers. Janneke Balk is now group leader at John Innes Centre in Norwich, UK; Heike Lange is respected tenured researcher at IBMP in Strasbourg, where she occasionally marches for science (5th from right on tweeted photo below). Also Professor Lill is listed as official supporter of March for Science Germany.

https://twitter.com/DaujatMag/status/855788118930272256

There is only one recent Lill paper flagged on PubPeer so far, featuring as corresponding author Lill’s long-term junior associate and regular co-author on above papers, Ulrich Mühlenhoff:

Stefan Christ, Lars I. Leichert, Anna Willms, Roland Lill, Ulrich Mühlenhoff

Defects in Mitochondrial Iron–Sulfur Cluster Assembly Induce Cysteine S-Polythiolation on Iron–Sulfur Apoproteins
Antioxidants & Redox Signaling (2016) doi: 10.1089/ars.2015.6599

image-1500328387900.png
From Christ et al 2016. A panel is apparently duplicated in different context, highlighted in red. Source: PubPeer

Finally, a reader of my site sent me another possible image duplication, from a very ancient Lill publication (Csere et al 1998, below). It indicates that the conspiracy against Professor Lill probably started long ago. But what if the busy Senator was actually tricked to agree to function as lead author on manipulated publications he had scientifically no influence over? Only recently DFG saved an ophthalmology professor and Berlin university clinic director, Antonia Joussen, by uncovering just such a constellation. Joussen was cleared of all suspicion and advised by the DFG to be careful in the future on where she agrees to function as corresponding author, since those papers might contain manipulated data. Did the same happen inadvertently to Lill? Will DFG provide their senator with the similar advice?

Csere P1, Lill R, Kispal G.

Identification of a human mitochondrial ABC transporter, the functional orthologue of yeast Atm1p. FEBS Lett. 1998 DOI: 10.1016/S0014-5793(98)01560-9

mzgtcys.jpg
From Csere et al 1998. The highlighted blot sections appear very similar, the rest is different. Source: reader communication

Update 26.07.2017, 21:00. This evidence was just forwarded to me by a reader:

Janneke Balk, Daili J. Aguilar Netz, Katharina Tepper, Antonio J. Pierik, and Roland Lill

The Essential WD40 Protein Cia1 Is Involved in a Late Step of Cytosolic and Nuclear Iron-Sulfur Protein Assembly Mol Cell Biol. 2005 doi:  10.1128/MCB.25.24.10833-10841.2005

8d40afd9-7f34-4ca5-900c-e79f587c5da9
From Balk et al MCB 2005. Bands appear duplicated and re-used (colour-coded). Source: reader of my site

Update 12.08.2017. Balk now commented on PubPeer, and admitted intentional gel band duplications shown above, which were performed with knowledge and approval from Lill:

“This response is from Janneke Balk, with input from Roland Lill.

After being alerted to our paper on PubPeer, we needed a bit of time to find my notebooks from 2004, which turned out to be still in Marburg. Roland then scanned the relevant pages and emailed those to me in Norwich. Everything was clearly described.

The immuno-labelling signals for Cfd1-HA in Figure 6C (Balk et al. 2005 Mol Cell Biol) are indeed duplicated. However, this stems from the design of the experiment and how we chose to present the data in a figure”.

Then follows a lengthy explanation about the experimental details which supposedly justified duplicating bands in a Photoshop-like software to generate what was then published as seemingly independent western blots. Balk concludes:

“Looking back at the results after so many years and now with knowledge of the helpful guidance on digital image manipulation from Rossner & Yamada 2005 (J Cell Biol. 166, 1 – 11), the ‘wt’ signals in C should have been separated from the ‘up’ lanes. Or I should have loaded the samples twice on the gel, in anticipation of the figure layout.

Scans of the films from Janneke Balk’s laboratory notebook are attached. Annotations in colour have been added for the benefit of PubPeer readers”.


 

 

 

 

 

 

 

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13 comments on “Data integrity conspiracy against German research senator Roland Lill?

  1. Hi Leonid
    I admire your writing style.
    The sarcasm drips heavy from each sentence in this piece
    Cheers Oliver

    Like

  2. Ana Pedro

    A few thoughts:
    1.WB, always the WB!
    2.research misconduct is like an octopus: the head are the mentors, people with access to funding the arms the undergraduate students PhD students post docs new PIs. Mentors are responsible to educate research integrity if they don’t teach their undergraduates research misconduct will spread. Like the Bahai’s mention we need since people is small
    3. Research misconduct is an huge social problem resulting in the deviation of money supposed to be applied for the good of humanity
    4. Raw, original data needs to be published as well and be available to public

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  4. As mentioned above, my first email to the Ombudspersons of the Philipps University Marburg, Helmut Remschmidt, and Rita Engenhart-Cabillic, cc-ed to the press office, listing the PubPeer evidence, went completely unanswered.
    On August 12th I made another attempt, linkign to my article and involving the university’s president and its leadership as further addressees. Yesterday I then received a reply, which I translate here:

    “Dear Mr Schneider
    I regret that you have not been informed of the state of the matter so far, and I can inform you that such cases are being carefully investigated in our university, as is the case with Prof. Lill. The investigation is in full progress and we will inform you of the results, of course. I must, however, ask you for your understanding that a careful review of 9 publications, which are based on experimental research, can not be completed in 14 days. You will receive notifications upon completion of the investigation without having to ask. Please confirm the receipt of this mail.
    Best regards,
    Prof.Dr.med.Dr.phil Dr.h.c. Helmut Remschmidt,
    Ombudsmann der Philipps-Universität”

    Like

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  7. The very first paper mentioned above, Lange et al PNAS 2000 has been corrected:

    The Correction notice mentions:

    “the first author cut the thermoprinter paper printout into pieces and reassembled them. Unfortunately, the published version contained an unintentional data duplication (mirrored bands for the 64 h data points), but the overall results were not impacted”

    Research integrity Watchdogs at Retraction Watch explain to lay people that nothing untoward or sinister indeed has happened:

    “It turns out, the first author had cut the paper into pieces and reassembled them to present the blots in the “desired order,” and some had become duplicated by mistake. The overall results were unaffected, so the journal swapped the image with a corrected version”

    Still, some ill-informed RW readers chose to keep pointing accusatory fingers, so here Heike Langer herself comments on Retraction Watch:

    “It was a honest mistake that nobody spotted in time.
    The originals that do not contain any duplicated (or triplicated band if you think that this really matters in this context) are shown in the corrected figure, and prove that we did not observe any significant changes in Leu1 protein levels in this experiment. Personally, I do not see any need for further actions from my side, and consider the case as closed: i made a mistake, I have no problems to admit it, I corrected it. However, you’re totally free to continue commenting it for the next 18 years”

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