Industry Research integrity

WHO cures cancer in Photoshop?

The World Health Organisation (WHO) has a cancer research unit in France, IARC. Some papers from there contain impressive manipulations. The works of art are authored by Massimo Tommasino and his former junior colleague there Uzma Hasan, now tenured group leader at INSERM. Some of this research took place at the Schering-Plough Research Institute which was taken over by German pharma giant Merck.

The World Health Organisation (WHO) recently included  Traditional Chinese Medicine into its global medical compendium, thus recognising that dried and powdered bits of rare and endangered animals can cure all possible ailments and diseases. But of course Modern Medicine remains valid also, and in fact the WHO’s International Agency for Research on Cancer (IARC), with its seat in Lyon, France, uses modern technologies to find new cancer therapies. One such digital technology, applied very efficiently all very the world, is based on Photoshop, where images of western blots and other research data get artistically modified to facilitate the publishability of the postulated cancer therapy ideas in respected peer reviewed research journals. It does not really help cancer patients, but the beneficial effect on the academic and industry careers of such scientists is extremely significant and has been extensively validated and reproduced over the years.

The cancer researchers at WHO whose papers contain such impressive manipulations, are Massimo Tommasino, head of Infections and Cancer Biology Group at IARC, and his former junior colleague there Uzma Hasan, now tenured group leader at INSERM in Lyon. Some of their best or worst papers (depending how you judge it) were authored together with an industrial researcher, Jaromir Vlach, working for the Schering-Plough Research Institute which was eventually taken over by the German pharma giant Merck (known in USA as EMD).The evidence was posted on PubPeer by anonymous commenters, one of whom was the pseudonymous Clare Francis, who also alerted me to that case.

Update 3.12.2019: WHO now pronounced that their investigation:

“Found no evidence of scientific misconduct and concluded that the allegations made on PubPeer are not adequately supported and are therefore unfounded”

This was for example what Hasan, Tommasino and Vlach published on the topic of immune system responses, in the elite journal PNAS, Hasan et al 2007:

This figure contains a plethora of duplicated gel bands, so much that it is actually almost funny. Who is responsible, we do not know. The contributions say that Tommasino only contributed “new reagents/analytic tools”, while research was designed by Vlach and the two first authors. The first and corresponding author Hasan was at that time already in Tommasino’s IARC department for Infections and Cancer Biology. That PNAS paper of hers contains many other examples of Photoshop activities, like this Figure 5 here:

The industry researcher Vlach is the last author and the project designer, but it seems the work was done at IARC, since that this Photoshop tour de force was publicly funded:

“This work was supported by grants from La Ligue Contre le Cancer (Comité de Savoie) and the grant “Applied Tumour Virology” German–French cooperation, German Cancer Research Center (DKFZ), Heidelberg–Cancéropôle du Grand-Est, Besançon.”

The afore-ridiculed Figure 1A of Hasan et al PNAS 2007 contains elements which previously appeared in a different context, in a different paper and likely also in a different lab where Hasan worked until 2005, at Schering-Plough with Vlach (Hasan et al JBC 2005):

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That 2005 paper appeared in the Journal of Biological Chemistry, which is known to be tough on data manipulation, might become a problem for this paper’s three authors. Good for Tommasino that he is not one of them. There is even a duplicated flow cytometry measurement, quantified slightly differently, maybe to obscure similarities.

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Also this Hasan et al JBC 2005 study contains more of creative tricks which helped the authors elucidate the molecular pathway of Toll-signaling in immune cells. Who knew it happens through post-experimental digital data duplication?

Hasan’s work at Schering-Plough before her move to IARC with Tommasino was truly productive. Look at this interesting figure from Hasan et al J Immunology 2005:

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The framed western blot two images for Flag/HA are very similar, except the upper gel band. How can this be? Can someone accidentally reuse same image twice, while accidentally erasing the top band in one of them? There is more to find in that paper also. Tommasino is not coauthor, but is credited with having provided “invaluable advice on this manuscript”, just like in the other Hasan et al JBC 2005 paper from Schering-Plough, now part of Merck.

With Tommasino as last author, but now without Vlach and his pharma industry input, Hasan authored same year 2007 this paper, Hasan et al J Immunology 2007. Also here, Hasan is corresponding author. This IARC study helped us understand how cervical cancer develops and offered “future promise for the prevention of infectious diseases, cancer, and autoimmune diseases“. This is how this promise works, and this is just one example from that paper:

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Apparently, by re-using certain western blot bands, a potential prevention therapy for cervical cancer can be established. Amazing research, done by WHO scientists at IARC, with public support:

The study was supported by grants from La Ligue Contre le Cancer (Comité de la Savoie), “Applied Tumour Virology” German-French cooperation, and Deutsches Krebsforschungszentrum-Cancéropôle du Grand-Est.”

2007 was a particular year in Tommasino’s IARC lab, with a particularly rich harvest of Photoshopped papers in prestigious journals. Also this paper features Hasan as one of coauthors, Mansour et al, Virology 2007., Tommasino is the corresponding author. The study offers insights into mechanisms of cervix cancer progression and suggests how this cancer can be early detected. This is how the clinical approach would work:

Female patient at risk of cervical cancer will be asked to sit upon the printout of these Photoshopped western blot images, or other examples from that paper. Any resident cervical cancer cells inside the patient will be appalled by such pathetically crude data manipulations of loading controls and die in shame. In case you wonder, why some authors need to manipulate such allegedly unimportant bits of the figure like loading controls: it’s probably because the correct loading controls would have rendered the entire figure as useless or even fraudulent. Hence, cancer is being attacked not with science, but with Photoshop. This is probably exactly what EU Commission had in mind when funding this travesty :

“The study was partially supported by grants from European Union (LSHC-2005-018704) Deutsche Krebshilfe (grant N. 10-1847-To I), and Association for International Cancer Research to MT and a grant from La Ligue Contre le Cancer (Comité du Rhône)”

Tommasino never had a high opinion of loading controls anyway, it seems he saw them as nuisance and tried to make a point of this by publishing such ridiculously Photoshopped stuff. Who is interested in how much sample was loaded where, if the end picture of signal differences and its scientific message is what matters? Nobody, that’s WHO. This is why we find in older Tommasino papers figures like this, in Malanchi et al 2004 or Giarre et al 2001, both passed peer review in Journal of Virology:

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Unfortunately such attitude to research integrity in Tommasino’s department at IARC is not ancient history. The following comes from two relatively recent papers from that lab, Shahzad et al J Virology 2013 and Siouda et al PLOS Pathogens 2014:

image-1533579317454-e1539256855290.pngimage-1533985497163.png

We learn that viruses play a key role in carcinogenesis, and the correct way to clinically intervene on viral infection to prevent cancer is to reuse loading controls for various experiments, to placate some pesky peer reviewers.

Even the EMBO fellow and newly minted INSERM group leader Dr Hasan was back at publishing copy-pasted cancer therapy ideas, at Journal of Experimental Medicine, Hasan et al, JEM, 2012:

We now see how such creative approach to cancer research literally paid out for Hasan:

“This study was supported by the EMBO Fellowship Program (U.A. Hasan), La Ligue Régionale de la Loire contre le Cancer (U.A. Hasan), la Fondation pour la Recherche Médicale (U.A. Hasan), l’Association Research sur la Cancer (U.A. Hasan), and CLARA Procan Axe II innate sensors platform, Lyon (M. Tommasino)”.

The penultimate author Ruslan Medzhitov is elite HHMI-funded researcher at Yale, USA, he is also thanked for his advice in several manuscripts by Hasan, Vlach and Tommasino. What will he say of such unconventional approach which as the authors assure, “may provide a novel therapeutic strategy for cervical cancers”?

I informed Merck and WHO Ethics team about those issues in August 2018. Merck replied that they “take such inquiries seriously” and are reviewing the information on Vlach’s publications which I sent them. From WHO, a request for more information arrived, because the PubPeer information was deemed insufficient as such:

“from the links you have posted, we can see the titles of a number of publications but it is difficult to assess what may have happened. We would need to know specifically which data may have been changed, in which publications, when and by whom.”

I replied immediately with explanatory examples, but have not heard from the WHO Ethics Team ever again. My recent two requests for an update went unanswered as of yet.

Update 3.12.2019

In November 2019, I wrote to WHO again. I received a reply: WHO expects PubPeer to remove slanderous evidence against their scientists who did absolutely NOTHING wrong.

This is the statement I received:

“Thank you for bringing your concerns to the attention of WHO. We have reviewed them and an investigation was undertaken into the matter.

The investigation looked at each allegation made and a rigorous approach was adopted further to the IARC Policy on Scientific Misconduct, as publicly available on the IARC internet site.

The allegations relate entirely to gel and blot “splicing”. This was and to a large extent still is common practice to reduce the size and complexity of figures which are illustrations derived from multiple experiments, and not intended to show the results of those individual experiments. Cell Press (http://crosstalk.cell.com/blog/common-pitfalls-in-figure-prepartion) say, “it is OK to remove irrelevant or blank lanes from a gel in order to present your data in a streamlined way to readers, but when you do it, you need to mark it clearly so that there is obvious transparency about how the figure was prepared” (2015). The Journal of Cell Science have suggested that “Any grouping or consolidation of data (e.g. removal of lanes from gels and blots or cropping of images) must be made apparent (i.e. with dividing lines or white spaces) and should be explicitly indicated in the figure legends.” (see http://jcs.biologists.org/sites/default/files/Revisionattachment_JCS.pdf )

It is noted that the splicing was not hidden deliberately, though on occasion it is noted it was less obvious in the printed figure and the figure legends did not always make the splicing clear. These minor errors are common in papers and should be avoided. The authors in question have been informed of what IARC expects and a policy on gels and blots from the Journal of Cell Science has been adopted.

Noting all this, the investigation:

  1. Found no evidence of scientific misconduct and concluded that the allegations made on PubPeer are not adequately supported and are therefore unfounded,
  2. Identified a small number of individual cases where errors in the figures require corrections, and
  3. Advised the authors to provide all available original data for the papers cited on PubPeer to the journal editors for their information.

Further to the above and in line with the IARC Policy on Scientific Misconduct and the investigation, it was determined that the matter could be closed.”


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134 comments on “WHO cures cancer in Photoshop?

  1. zebedee's avatar

    “I replied immediately with explanatory examples, but have not heard from the WHO Ethics Team ever again. My recent two requests for an update went unanswered as of yet.”

    Any news from the WHO? It is dragging on. Massimo Tommasino is still publishing so is likely alive (although that is no guarantee).

    Like

  2. Morty's avatar

    I did not get any response with my expression of concern sent in October. I will send again. We should continue to put pressure.

    Like

  3. Smut Clyde's avatar
    Smut Clyde

    Guns don’t get much smokier than this:

    https://pubpeer.com/publications/D8F75DADF6C38C8D30DC530AB138A1#8

    Like

    • Smut Clyde's avatar
      Smut Clyde

      Ah, I see that Zebedee has already noted this image in a nested comment up-stream.

      Like

      • Zebedee's avatar

        That was only in the lower right corner of the full image. Not so easy to spot.

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  5. Zebedee's avatar

    2nd 2019 retraction Massimo Tommasino.
    .
    PLoS One. 2008;3(10):e3529. doi: 10.1371/journal.pone.0003529. Epub 2008 Oct 27.
    HPV16 E7-dependent transformation activates NHE1 through a PKA-RhoA-induced inhibition of p38alpha.
    Cardone RA1, Busco G, Greco MR, Bellizzi A, Accardi R, Cafarelli A, Monterisi S, Carratù P, Casavola V, Paradiso A, Tommasino M, Reshkin SJ.
    https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0003529
    Rosa A. Cardone
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Giovanni Busco
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Maria R. Greco
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Antonia Bellizzi
    AFFILIATION Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Bari, Italy

    Rosita Accardi
    AFFILIATION Infections and Cancer Biology Group, IARC-WHO, Lyon, France

    Antonella Cafarelli
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Stefania Monterisi
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Pierluigi Carratù
    AFFILIATION Department of Respiratory Medicine, University of Bari, Bari, Italy

    Valeria Casavola
    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    Angelo Paradiso
    AFFILIATION Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Bari, Italy

    Massimo Tommasino
    AFFILIATION Infections and Cancer Biology Group, IARC-WHO, Lyon, France

    Stephan J. Reshkin
    * E-mail: reshkin@biologia.uniba.it

    AFFILIATION Department of General and Environmental Physiology, University of Bari, Bari, Italy

    2019 retraction notice 2nd retraction.
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218402

    Following publication of [1], the following concerns were noted:

    Figure 1A: E7 and GAPDH panels appear to contain background irregularities;
    Figure 1B: the bands in the total p38 and total JNK panels appear similar, cropped and adjusted for brightness and contrast;
    Figure 1C: total ERK1/2 panel contains vertical discontinuities;
    Figure 1C: GAPDH panel appears similar to the Figure 1B GAPDH panel 1B;
    Figure 2A: E7 panel has a vertical change in background between the nc and +tet lanes;
    Figure 2A: GAPDH panel background appears dissimilar between bands;
    Figure 4B: Phospho-p38 panel has a vertical change in background between the middle lanes;
    Figure 5A: Phospho RhoA and total RhoA panels have been heavily adjusted for brightness/contrast;
    Figure 6A: Active RhoA panel has vertical discontinuities between the 3 and 6 hr bands.
    The corresponding author does not agree with the concerns raised and provided images in relation to Figure 1B totp38 and totJNK panels, Figure 1C total ERK panel, Figure 2A GAPDH and E7 panels, Figure 4B Phospho-p38 panel, Figure 5A phospho RhoA panel and Figure 6A Active RhoA panel, but these do not satisfactorily resolve the concerns raised for these items. The primary data underlying other figure panels has not been provided, which was attributed to the time that has passed since publication.

    In light of the unresolved concerns that question the validity of the study’s findings, the PLOS ONE Editors retract the article.

    RAC, MRG, PC, VC, MT, and SJR did not agree with retraction. GB, AB, RA, AC, SM, and AP did not respond.

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  6. Zebedee's avatar

    “I replied immediately with explanatory examples, but have not heard from the WHO Ethics Team ever again. My recent two requests for an update went unanswered as of yet.”

    Has the WHO ethics team replied since then?

    Like

    • Leonid Schneider's avatar

      Afraid not. The last communication was from 30.10.2018, where WHO Ethics Office refused to comment on the evidence. They wrote:

      “WHO is currently reviewing the matter. Please do let us know if further information becomes available”

      I presume since I had no further information beyond the available PubPeer evidence (which they explicitly declared not to understand), the matter was closed. I now sent another email though.

      Like

  7. Zebedee's avatar

    RE: “Update 3.12.2019
    In November 2019, I wrote to WHO again. I received a reply: WHO expects PubPeer to remove slanderous evidence against their scientists who did absolutely NOTHING wrong.

    This is the statement I received:

    The allegations relate entirely to gel and blot “splicing”. ”

    That is not true. The most serious problems were about duplicated images. Very difficult to explain away.

    It sounds like the WHO representive(s) who wrote the reply don’t know what they are talking about.

    Like

  8. Morty's avatar

    The answer from WHO is very worrying. I also sent an expression of concern, but dit not hear back.

    Are there any information regarding the “investigation”? Who from WHO was involved? The “investigation” report should be publicly available.

    Rune Linding suggested that this should be reported to The Office of Internal Oversight Services, the internal oversight body of the United Nations. We should! I will do that and hope that more will join.

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  9. Morty's avatar

    Answer from the Office of Internal Oversight Services:

    Dear Sir,

    Thank you for your report dated 19 December 2019 to the Investigations Division, Office of Internal Oversight Services (ID/OIOS).

    Your report has been carefully reviewed. Unfortunately, the subject of your complaint falls outside the mandate of ID/OIOS, which deals with misconduct matters involving UN staff and resources. As such, we are unable to assist in your query.

    Thank you and best regards.

    ID/OIOS

    Like

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  12. Zebedee's avatar

    https://www.iarc.who.int/news-events/dr-massimo-tommasino-27-august-1958-18-december-2022/

    “23 December 2022
    Dr Massimo Tommasino (27 August 1958–18 December 2022)
    The International Agency for Research on Cancer (IARC) is deeply saddened by the passing of Dr Massimo Tommasino at the age of 64.

    Dr Tommasino was a beloved member of the IARC community for 19 years, making indelible scientific contributions in his position as Head of the Infections and Cancer Biology Group (2002–2020) and then as Head of the Early Detection, Prevention, and Infections Branch (2020–2021) until his retirement at the end of 2021.”

    “Dr Tommasino contributed enormously to knowledge of the role of human papillomaviruses in carcinogenesis.”

    https://bari.repubblica.it/cronaca/2022/12/19/news/e_morto_a_64_anni_massimo_tommasino_era_direttore_scientifico_dellonclogico_di_bari-379785093/

    “E’ morto a 64 anni Massimo Tommasino, era direttore scientifico dell’Oncologico di Bari: “La prevenzione era la sua missione” “

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    • Leonid Schneider's avatar

      Oscar Portillo-Moreno, Domenica Altavilla, now Massimo Tommasino… My writing about their indelible scientific contributions is dangerous for health!

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      • Zebedee's avatar

        The retirement age in France is 62 years.

        The International Agency for Research on Cancer (IARC) is in Lyon, France.

        Massimo Tommasino simply retired in 2021 at the age of 62 years.

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