Spanish elites rally in support of data manipulation

A horrible, horrible conspiracy befell Spain. Worse than anything you can imagine: Carlos Lopez-Otin, a star of cancer and ageing research from the University of Oviedo, was forced to retract EIGHT papers in the Journal of Biological Chemistry (JBC), right after he retracted a very important paper in Nature Cell Biology. Spanish elites cry foul, and point accusing fingers at the evil deed by JBC, and of course also at yours truly, without naming me, for my “virulent and libellous attacks” on poor Carlos. A letter signed by 50 Spanish researchers was sent to JBC trying to dissuade the journal from retracting the 8 papers. The ringleader here appears to be a certain Juan Valcarcel of CRG in Barcelona, and I shall use this occasion to release the 3 incompetent investigative reports Valcarcel commissioned in 2015 to whitewash his CRG colleague, the Italian zombie scientist Maria Pia Cosma.

All 8 Lopez-Otin retractions in the JBC issue from January 25th 2019 are similarly worded: some image data was found inappropriately manipulated or duplicated, after the journal used the occasion to scrutinise all the papers the Oviedo lab published there. Original data was not available, so the authors were asked to withdraw their papers. After which Lopez-Otin and his friends took to Spanish media to decry the injustice perpetrated by JBC.

Whitewashing Inc

The whole circus is somewhat similar to what happened in France, in the Catherine Jessus case, where another top-rank biologist became victim of my reporting and of PubPeer data analysis campaign instigated by my readers. Also in France, there was a whitewashing investigation, and a signature campaign in support (read here). The differences are: French newspaper Le Monde played a key part in uncovering the affair (and got huge flak for it), while Spanish media chose to leave the podium to Lopez-Otin and his supporters, largely unchallenged. Main difference however is: Jessus never hat to retract anything, the journals blinked and issued passive-aggressively worded corrections only.

JBC however has a different stance on data manipulation, and is unafraid to do mass-retraction if they see either excessive fraud or a pattern of recurrent data manipulation from the same lab. This happened to several other researchers, Rony Seger, Yehiel Zick or Samson T Jacob. When only one paper is found manipulated, it may be bad luck, a rogue student, the journal will issue a correction. Otherwise, it gets progressively more and more suspicious, especially if the only common name on these 8 papers is that of principal investigator, here Lopez-Otin. 

Apparently in Spain (similarly to France), the elites of science are either too crooked or too incompetent to understand this. So here comes a statement from the University of Oviedo, via its president, Santiago García Granda, from 28.01.2019, as announced in the local newspaper Asturias Mondial:

“Given the press reports about the recent withdrawal of several articles by the group of Professor at the University of Oviedo, Carlos López Otín, we as the institution express our full support for this research, his team and his work. The group of Professor López Otín has collaborated with publishers by providing all required information and kept the academic authorities informed at all times. Our support is based on the findings from an investigation conducted by the Ethics Committee of the University of Oviedo, and the analysis of the articles retracted from the Journal of Biological Chemistry by an expert group of Spanish scientists which sent its conclusions to the University.

These findings support the scientific validity of the published results despite the deficiencies found in some of these studies. The evidence analysed confirms the reliability of this research, as multiple studies by independent laboratories later corroborated it, based on the cited work. As mentioned in the statement of the Institute of Oncology, “reagents generated in these works, including plasmids, recombinant proteins, antibodies, etc., as well as the valuable animal models developed in this laboratory, have always been shared with dozens groups worldwide, allowing validation of the results described in numerous publications by international laboratories. In fact, many of the work done by this group has opened up new lines of research, up to now.”

In any case, the University of Oviedo reserves the right to take legal action to preserve the good name and reputation of our institution as well as to defend the honour and the reputation of the members of our university community, and to allow them to practice their scientific investigations, teaching and management”.

I am not sure whom the University of Oviedo meant to threaten here with legal action? Myself? I had this before, from another fake clown of a rector in Italy, Giorgio Zauli, and again from France, and that time it was the Government itself, on behalf of minister Frederique Vidal and her Ministry of Research and Innovation. 

If only Spanish biomedical elites could be interested in doing something about real injustice. Like, to call for an investigation of patient abuse and deaths caused by Paolo Macchiarini in Barcelona. This was where I actually was sentenced in court for, so maybe Lopez-Otin’s university and his Instituto Universitario de Oncología in Oviedo did speak of Macchiarini as another victim of mine, when their present and two past directors wrote in this press release (which was already quoted above):

“There have been very virulent and libellous attacks in some social networks, whose goals are completely away from constructive criticism and scientific debate. “We are facing a very complex media situation where attacks which compromise the activity of several research groups are carried out with impunity and whose main victims are leaders of groups with high research activity”.

Save-Our-Carlos Letter

Now even the regional Government of Asturia expressed support for Lopez-Otin, because in Spain they do not separate between scientific and state issues. If this gets out of control, Spain might even send war ships to bomb the offices of JBC and the American Society for Biochemistry and Molecular Biology:

“Also, the Minister Fernando Lastra, who spoke at the press conference as spokesman of the Governing Council, pointed personal relationship of the Asturian President, Javier Fernández, with the researcher so their support is even a “little beyond “the expression of recognition of their work by the Governing Council.”

Before that, we had the Ethics Committee at University of Oviedo whitewash Carlos-Otin, assisted by some unnamed external investigation, and finally, there was a letter to JBC signed by 50 scientists, as reported by El Mundo.:

“Fifty Spanish scientists also asked the journal not retract the papers completely, but to allow the correction of errors. But they found a ‘no’ for an answer.

“Mistakes must be corrected, but the retraction of the articles does a disservice to science,” says geneticist Juan Valcarcel, one of the scientists who has defended the work of Otín and coordinated the appeal to the journal.

“The detected errors do not affect in any way the research findings, which have been validated independently on multiple occasions and have served as a basis for further work as the development of animal models for understanding cancer progression. Nobody doubts its validity, ” says the researcher.

Beside him, the letter was signed by first class personalities in the field of science such as Margarita Salas, professor Ad Honorem Center Severo Ochoa Molecular Biology; Manuel Serrano, researcher at IRB Barcelona; Elias Campo, scientist at the Institute of Biomedical Research Pi i Sunyer Augus Barcelona; Cristina Garmendia, former Minister of Science; López-Barneo José, Institute of Biomedicine of Seville and Juan Bueren, Center for Energy, Environment and Technology in Madrid, among others.”

It is actually an exorcise in nepotism. Margarita Salas, the grand dame of Spanish biology, trained by the revered Nobelist Severo Ochoa, is herself the doctorate mentor of Lopez-Otin. Manuel Serrano is another star of Spanish life science, who also did PhD with Salas. His ex-wife is Maria Blasco, who is a regular coauthor of Lopez-Otin and another graduate of Salas. So is the signatory politician Cristina Garmendia, who is also a personal friend of Lopez-Otin since their common time in university. Elias Campo is Lopez-Otin’s co-author and has his own PubPeer record. Elsewhere Juan Bueren is mentioned,  another newspaper names Jesús Ávila as a signatory, guess under whom he did his PhD? Exactly, Salas.

Salas is appalled by my and my readers’ behaviour: “I do not know who or how many are behind this, but have done unnecessary damage“, she also explained how to think properly of her Carlos and his data manipulations:

“For me he is, if not the best, one of the best researchers we have in Spain. Without a doubt, one of the most brilliant scientists. He has all my confidence, my support and my respect. His career is absolutely flawless”

 

The Maria Pia Cosma affair

But I would like to go back to Juan Valcarcel of CRG in Barcelona, the instigator of that letter to JBC. It is not the first time Valcarcel engages in whitewashing activities to help a colleague caught with manipulated data. I interacted with Valcarcel in 2015, on the affair of the CRG group leader Maria Pia Cosma, who story I later presented in this article. The issue was an “investigation” Valcarcel commissioned to declare that all those obviously duplicated bands in Cosma’s papers from her previous stints as PhD student at the infamous Università di Napoli “Federico II” in Italy and as postdoc at the Institute for Molecular Pathology (IMP) in Vienna, Austria, were actually never ever duplicated.

These were the three papers:

Cosma MP, Cardone M, Charlemagne F, and Colantuoni V. (1998). Mutations in the extracellular domain cause RET loss of function by a dominant negative mechanism. Mol Cell Biol , Vol. 18 (6) :3321-9

Cosma MP, Panizza S and Nasmyth K (2001) Cdk1 triggers association of RNA
polymerase to cell cycle promoters only after recruitment of the mediator by
SBF. Molecular Cell, Vol. 7 (6): 1213-1220

Cosma MP, Tanaka T and Nasmyth K (1999) Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle and developmentally regulated promoter. Cell ,Vol. 97 (3) : 299-311

These are the three investigative reports, here, here and here. Back then, I presented the excerpts on PubPeer for debate, see thread here.

The expert was in all three cases Josep Manel Rodríguez Sánchez, Senior Engineer in Computer Science from the Universitat Politècnica de Catalunya. In the nutshell: whenever the expert found one single pixel difference between two bands, he used it as evidence to declare them as utterly unrelated. In detail, this was his methodology:

“Steps I followed:
1. Obtaining the original images published in the different articles with the highest possible quality. To do this, I downloaded the published article PDFs.

2. Visual Analysis: the first step was to determine visually if there was cause for a more
detailed examination. For this I used the best possible images that can be obtained. Specifically, I obtained the digital images contained in the cell.com website where the article was published.

3. Forensic Analysis: If necessary, the second step involved the forensic analysis of the
images to determine if the reasons of the comments were valid or not, or whether there
were additional evidences that might be detected.
This forensic analysis was performed with computer tools for the treatment of images,
basically the Adobe Photoshop version 2014 of which I have the corresponding
authorization for use. “

This is an embarrassing approach from an IT expert, who should know how compression works. If a gel band is digitally duplicated in an image, and the image is then compressed into a pdf, tiny pixel differences are bound to be discovered if you only search long enough. But these papers were done actually in pre-Photoshop days, and the bands are not likely to have been digitally duplicated. Back then, thermoprinter images from the gel camera were printed out, re-photographed and sent to the journal as figures. Another scientist, Heike Lange, recently had together with her former PhD advisor Roland Lill to correct a paper from around same time, after she admitted to having inadvertently printed out too many copies of the same band and collaged them together into one continuous western blot image. With such “analogue” duplication with print-outs, scissors and glue, there are bound to be even more pixel dissimilarities, even if otherwise bands look identical and neatly superimpose.

Valcarcel explained to me in May 2015:

“While we are not ourselves experts in forensic analysis, the expert, who as you know was designated by the Official College of Computer Engineers of Catalonia, and whose reports are legally recognized (e.g. in a court of law), has stated that he took into account possible compression artifacts and used the best images available. Unfortunately records of original data are not available for the majority of the claims.”

I approached Sanchez with some of the criticisms his methodology met on PubPeer. This was how he replied back then:

” in deference to you and to CGR I have no objection to clarify that the images they use for the issuance of the report, as indicated in the are of the highest possible quality, in the following order:
* Original picture extracted from the documentation hanging on the web ( powerpoints and images )
* Extracted image of the PDF.The majority of the images were of the original powerpoint and in very few cases use images extracted from the pdf.
All it is known that the extracted image of the PDF may suffer some variation in the conversion process. I followed the recommendations of Dr. John Krueger from ORI ( The Office of Research Integrity ) in this aspect and perform the appropriate actions at the time of the analysis. I recommend the reading of a report published by Dr. Krueger (https://www.aclu.org/sites/default/files/assets/krueger_affidavit.pdf) for more details on the subject as well as tools and techniques that I have gleaned from the website of the ORI (http://ori.hhs.gov/advanced-forensic-actions ). In any case, try at all times avoid the effects of compression and compare images among themselves to the extent possible. “

In July 2015, Valcarcel wrote to me:

“The forensic analysis of the expert assigned by the Official College of Computer Engineers of Catalonia is considered professionally and legally valid. Given this report, the absence of primary data and the corrections issued or in process in various Journals, we have decided to close the case.”

Just days after this email, Cell issued this editorial note (which I covered in my article at that time):

“Concerns about duplicated images in Cosma et al. (Cell, 1999) and Cosma et al. (2001, Mol. Cell 7, 1213–1220) were brought to our attention by a reader. We, the editors of Cell and Molecular Cell, have investigated the matter, communicating with the corresponding author, Dr. Kim Nasmyth; the first author, Dr. Pia Cosma; The Research Institute of Molecular Pathology (IMP), where the research in question was conducted; and the Center for Genomic Regulation, Dr. Cosma’s current institute, which conducted its own investigation. The IMP located Dr. Cosma’s notebooks and provided her with high-resolution copies. As part of our investigation, Dr. Cosma brought those copies to the Cell Press office, where we went through them with her, identifying data for the figures in the paper. The notebooks contained original images, alternate exposures, and/or replicate data for most of the figures in the papers, providing support for the reported findings. In a few instances, original data could not be located, making it difficult to assess the concerns raised about those specific data panels.

While we understand the reasons that the figures in the paper were flagged by the community, in our judgment the burden of proof for determining inappropriate data handling or image duplication has not been met. Furthermore, the available original data support the findings of the papers. With these things in mind, based on the information available to us at this time, we have decided not to take any further action. This statement is to notify the community of our investigation and findings”.

Valcarcel’s bullshittery, combined with the impressive fraud tolerance of Cell editor at that time, Emilie Marcus, as well as IMP’s obvious reluctance to damage their former director Kim Nasmyth, proved successful. The gel bands which most obviously look duplicated where proven to be not duplicated exactly because original data was available, though not specifically for these questioned figures.

Again, these are the three investigative reports, here, here and here.

Such a success story apparently prompted Valcarcel to try it once again (he even compares Lopez-Otin to Christopher Columbus here). Only that JBC is exactly the opposite of Cell in research ethics,  and apparently unafraid of bullshitting bullies like Valcarcel. He now looks very silly now. Serves him right.

And his friend Carlos? Hiding in Paris, with another dishonest elite scientist Guido Kroemer; one wonders if the “sabbatical” is paid from Lopez-Otin’s ERC grant. Maybe his wife Gloria Velasco (professor at the same department) continues supervising his research in the Oviedo lab. Soon the convalescing Spanish victim of persecution will be visiting the Galapagos islands, as his son tweeted. Not sure if Kroemer and/or his charming co-author, Laurence Zitvogel, will be joining Carlos there.

---

 

 

Update 4.02.2019.  Events happen quite fast, if you want to keep track, follow my comment section and tweets. In particular:

• Some months ago, almost 6000 of Lopez-Otin’s transgenic mice had to be culled due to a mysterious infection.
• Right-wing newspaper El Comercio and the rector of Oviedo fingered certain Oviedo scientists as masterminds behind my reporting, these claims are made up, I never had any sources in Spain

---