Opera Buffa di Guido Kroemer a La Scala

The cancer and ageing researcher and Paris professor Guido Kroemer is absolutely THE European star scientist, his PubPeer record has absolutely zero influence on his capacity to place papers in the highest elite journals, or to bag one prestigious award after another. The France-based German native got every honour possible: the Descartes Prize in 2006 from the EU, the Grands Prix from the French Academy of Sciences in 2007, the Carus Medal from the German Academy of Sciences (Leopoldina, of which he is member) and of course also the EMBO membership. Who knows, the Karolinska Institutet foreign adjunct professor might even get the Nobel Prize next!

Kroemer’s life partner Laurence Zitvogel is also a tremendously successful scientist and just like her Guido, she is also a Photoshop expert. The elegantly dressed photogenic couple is a kind of European science royalty, and thus infallible and untouchable. This is maybe why Kroemer used his influence to host and protect his friend Carlos Lopez-Otin at his Cordeliers Research Center in Paris while the affair of fraudulent gels and murdered mice raged in Spain.

Kroemer is a star, apparently beloved by masses of dishonest scientists, and feared by the rest. This is why on 8 November 2019, this Grand Diva of European Sciences receives a €1 million award from his Italian colleagues, as main event of a festive gala at the Teatro alla Scala in Milan. One of the jury members is the infamous Carlo Croce, with 9 retractions so far and a lost lawsuit against his critic David Sanders and the New York Times. The 74 years old Croce is an Italian native, but unsackable as a litigious and obscenely rich cancer researcher at the Ohio State University in USA. Croce is also associate professor at University of Ferrara, the totalitarian rector of which is Giorgio Zauli, who himself published over 40 fraudulent papers. Zauli lauded Croce as “the most famous Italian oncologist“.

Lombardia è ricerca, premiato Guido Kroemer https://t.co/V2xoLle9VZ pic.twitter.com/Tzbbh1Jidc

— ItaliaOggi (@ItaliaOggi) November 9, 2019

The €1mn Premio Internazionale is being organised by Fondazione Umberto Veronesi and the region of Lombardy, of which Milan is the capital. Kroemer is being awarded for “Healthy Ageing”, which makes perfect sense since the jury was comprised by old and ageing males (with the exception of the Chair):

Adriano Aguzzi, Giorgio Bernardi, Paolo Calabresi, Federico Calzolari, Carlo Croce, Andrea Ferrari, Luigi Ferrucci, Carlo La Vecchia, Michele Parrinello, Silvia Priori (Chair), Giuseppe Remuzzi, Paolo Maria Rossini, Giacomo Rizzolatti, Peter J. Schwartz, Claudiu Supuran.

Not every panel member was apparently happy with sitting next to Croce (or other dishonest colleagues) while awarding Kroemer: three have resigned, a reliable source told me. One member who stayed, the Zürich professor Adriano Aguzzi, quasi-simultaneously beat his chest in Nature as champion of publication ethics. Must be a form of Italian humour. The whole award show was co-initiated by Pier Giuseppe Pelicci, the Fondazione Veronesi bigwig who should rather busy himself correcting his own papers.

And now, the collective fart by our science elite in our faces. This is YOUR public money Kroemer gets. And you won’t even get a lousy KroemerLab T-shirt.

Guido Kroemer, scienziato vincitore di @ERC_Research 🇪🇺 Advanced grant nel 2012, riceve alla Scala il premio #Lombardiaericerca per i suoi studi su invecchiamento sano #Horizon2020 pic.twitter.com/ZKEnYJ5LkH

— Massimo Gaudina (@MassimoGaudina) November 8, 2019

Now let’s do a follow-up on Kroemer’s scientific achievements, after my previous post on that topic. Stealthy gel splicing is so boringly common in his papers that I won’t bore you with it here. Although, just to prove that the technique was actually never acceptable, there was a 2015 correction for a 2008 paper from KroemerLab, Grosjean-Raillard et al Apoptosis 2008, which went like this:

“During the preparation of Fig. 3A for the final version of this manuscript, the authors have assembled immunoblots from different cell lines without clearly indicating the borders between blots.”

Mangiare di meno per vivere più a lungo, Guido Kroemer: «Ora vi spiego perché», (ha vinto il premio #Lombardia ricerche), di @StefaniaChiale https://t.co/wauP72RdAn

— daniele manca (@Daniele_Manca) November 9, 2019

Let’s start with this classic:

Hortelano, Dallaporta, Zamzami, Hirsch, Susin, Marzo, Boscá, Kroemer Nitric oxide induces apoptosis via triggering mitochondrial permeability transition FEBS Letters (1997) doi: 10.1016/s0014-5793(97)00623-6 

Do you know what happened here? Someone was too lazy to re-gate the sample by software in order to make it look different. Instead, a picture of a flow cytometry plot was copy-pasted, flipped and a white patch slapped on top to cover up a population of cells.

Another KroemerLab classic, frozen in time because neither the prestigious journal nor anyone else really wants to dig up that smelly corpse:

Susin, Lorenzo, Zamzami, Marzo, Brenner, Larochette, Prévost, Alzari, Kroemer Mitochondrial release of caspase-2 and -9 during the apoptotic process Journal of Experimental Medicine (1999) doi: 10.1084/jem.189.2.381 

Now what would be an innocent explanation as to how the gel bands from Figure 10B came to be so similar to the gel bands in Figure 10C? Too late into the paper to bother? Some student doing naughty stuff behind the boss’ back? Demanding reviewers, who kept insisting on extra experiments? Take your pick.

The following is a Zitvogel-Kroemer co-production, the evidence is 2 years old, and nobody, nobody dares to say a word. Maybe because this time someone at least bothered to re-gate the sample in FACS software before passing it off as an utterly different measurement.

Ghiringhelli, Puig, Roux, Parcellier, Schmitt, Solary, Kroemer, Martin, Chauffert, Zitvogel Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation Journal of Experimental Medicine (2005) doi: 10.1084/jem.20050463

Although in case of Figure 7C, someone got bored and just copy-pasted FACS plots without any modifications, next to each other. With different quantification numbers because really, up yours, do you know who we are? But let’s continue admiring the apoptosis and autophagy research of KroemerLab which earned him the La Scala honours of “Healthy Ageing” and €1 million pocket money.

Candé, Vahsen, Kouranti, Schmitt, Daugas, Spahr, Luban, R Kroemer, Giordanetto, Garrido, Penninger, G Kroemer AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis Oncogene (2004) doi: 10.1038/sj.onc.1207279 

Here, it seems a gel band showing CypA-/- genotype sample was rotated on its head and reused to stand for a CypA+/+ sample. A common practice in cancer research, which warrants no further attention. And so it got none at the nature Publishing Group. Now it should be mentioned that the Editor-in-Chief of Oncogene and Imperial College London professor, Justin Stebbing, himself struggles with research integrity in his own papers.

As aside, one of the coauthors, Romano Kroemer, is apparently Guido’s brother, who moved just in that year 2004 to Sanofi. The pharma giant, which now recruited as its Global R&D Head John Reed, despite or maybe actually because of his extensive Pubpeer record.

Also in the following KroemerLab paper the gel bands are strangely similar:

Boehrer, Adès, Braun, Galluzzi, Grosjean, Fabre, Le Roux, Gardin, Martin, De Botton, Fenaux, Kroemer Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study Blood (2008) doi: 10.1182/blood-2007-07-100362 

The evidence is from early 2016, back when the paper was not even 8 years old, yet the journal Blood could not be bothered. Which will surely be appreciated by all Italian supporters of Kroemer, especially the Ferrara rector Zauli, who proudly tells all and sundry how he negotiated with that same journal to leave his fraudulent papers in peace.

There are also collaborative papers, where some of the criticised figures might have been made in the Kroemer lab. To be fair, Kroemer did collaborate with some interesting characters, like the Karolinska Institutet whitewashed cheaters Helin Vakifahmetoglu-Norberg and her mentor Boris Zhivotovsky (read more about these two here). In any case, as a senior coauthor Kroemer is still co-responsible for his papers. Like this one here:

Schmitt, Parcellier, Gurbuxani, Cande, Hammann, Morales, Hunt, Dix, R Kroemer, Giordanetto, Jäättelä, Penninger, Pance, G Kroemer, Garrido Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant Cancer Research (2003) 63(23):8233-40.

The paper has quite a lot of stealth gel splicing which already renders some results unreliable. But the gel band duplication highlighted in yellow is the final evidence that this French research paper cannot be trusted.

The following was published with Kroemer’s contribution by his colleagues at INSERM Institut Gustave-Roussy in Villejuif, where he and Zitvogel are still affiliated with:

Tao, Zhang, Girdler, Frascogna, Castedo, Bourhis, Kroemer, Deutsch Enhancement of radiation response in p53-deficient cancer cells by the Aurora-B kinase inhibitor AZD1152 Oncogene (2008) doi: 10.1038/sj.onc.1210990

The probability of two neighbouring bands on the same gel to be that similar in shape to two other neighbouring bands next to them is extremely low. Might those be two different exposures of same western blot? In any case, those are just loading controls!

Kroemer is corresponding author on this other paper from Villejuif:

Massard, Zermati, Pauleau, Larochette, Métivier, Sabatier, Kroemer, Soria hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway Oncogene (2006) doi: 10.1038/sj.onc.1209487

That sloppy hack job was corrected in 2013:

“Errors were inadvertently included in Figure 3a of the article mentioned above. In particular, representative FACS profiles were a duplication of others, owing to pasting errors at figure composition. We have carefully re-analyzed our original data set and the amended version of Figure 3a is reported below. Neither quantitative determinations (Figure 3b) nor the conclusions of this article are altered. We apologize for these errors.”

Also this paper was corrected, for similar lazy FACS copy-pasting, half-heartedly and stealthily (Cell Press on principle hides corrigenda as not to confuse the readers of original papers):

Zermati, Mouhamad, Stergiou, Besse, Galluzzi, Boehrer, Pauleau, Rosselli, D’Amelio, Amendola, Castedo, Hengartner, Soria, Cecconi, Kroemer Nonapoptotic role for Apaf-1 in the DNA damage checkpoint Molecular Cell (2007) doi: 10.1016/j.molcel.2007.09.030

The 2012 correction notice went:

“errors were inadvertently introduced in Figures 2B, 4E, and S1C. In particular, some FACS profiles were duplications of others within the same figure panels due to pasting errors at figurecomposition. We have double-checked our data sets against the original FACS profiles […] Neither quantitative determinations (Figures 2C, 2D, and S1D) nor the conclusions of this article have been altered. We apologize for these errors.“

Yet nobody thought this pathetical collage passed off as Figure 4C was in any way out of order:

Did things change meanwhile? They sure did. The corrections suggest Kroemer did face some kind of gentle probing by the journals or even a benevolent investigation in France. In 2016, Kroemer was even asked to stop being Editor-in-Chief of the journal Cell Death and Disease (which he founded in 2010). Now Guido and Laurence are more careful now with western blots and FACS plots. Only that sometimes things still slip, in Science no less:

Routy, Le Chatelier, […], Kroemer, Zitvogel Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors Science (2018) doi: 10.1126/science.aan3706 

The image integrity detective Elisabeth Bik commented:

“Could the authors please check? There appears to be a duplication in Supplemental Figure S15. Two [out of 5, -LS] of the microscopy photos look very similar. They are both represented as the same treatment, alpha PD1 + Akkermansia, so it is not necessarily a problem but it is a bit confusing, since the granulomas are highlighted slightly differently between the two panels. Also, one of the panels is rotated 90 degrees.”

The Figure legend describes “Five examples of high magnification images (500μm) to visualize the presence or absence of granulomas in the different experimental settings described in the X axis of A.“. Thus apparently the images are supposed to show different experimental conditions after all, is this why the drawn granulomas have a different size, on a copied, rotated and cropped image?

You might now see a pattern how the KroemerLab functions so successfully. Exactly this is why the Carlo Croce commission in Milan was right to give the €1 million award to Kroemer at La Scala. In your face.

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