Research integrity

Another dead scientist framed with manipulated data?

On 7 April 2010 the Spanish diabetes researcher Margarita Lorenzo died of metastatic melanoma, aged only 51. Two months after her death, Lorenzo's colleagues submitted a paper to the journal Diabetes. The paper, which studies the mechanisms of obesity and insulin resistance, seems to be full of manipulated western blot data. While Lorenzo was dying of cancer, her colleagues advanced their careers using her reputation, using their own disreputable Photoshop skills.

On 7 April 2010 the Spanish diabetes researcher Margarita Lorenzo, Professor of Biochemistry at the Complutense University in Madrid, died of metastatic melanoma, aged only 51. Two months after her death, Lorenzo’s colleagues submitted a paper to the journal Diabetes (published by American Diabetes Association), which was accepted for publication 4 weeks later. These colleagues, primarily the corresponding authors Sonia Fernandez-Veledo (now research group leader at IISPV in Tarragona) and Cristina Murga (now deputy director at CBMSO in Madrid), wrote in the paper’s acknowledgements:

“This work is dedicated to the memory of Prof. Margarita Lorenzo, who passed away April 7, 2010, at the age of 51”.

The paper, which studies the mechanisms of obesity and insulin resistance, seems to be full of manipulated western blot data. The only thing which is rather clear: the late Margarita Lorenzo didn’t do it. While she was dying of cancer, her colleagues advanced their careers using her reputation, using their own disreputable Photoshop skills. This shows too many uncanny parallels with another case in diabetology research, where some unscrupulous scientists at Weizmann Institute in Israel urinated on the grave of their dying colleague, by placing manipulated western blots into his last papers. That scientist was Ofer Lider, and he died of cancer (leukaemia) at 49, a similar age as Margarita Lorenzo. Obituaries were written by those responsible for the publishing of rigged research, in both cases.

hilda 3

This is the publication dedicated to the memory of Margarita Lorenzo:

 

Several of the co-authors were established members of Lorenzo lab. Shared co-first-authors Garcia-Guerra and Nieto-Vasquez joined as PhD student in 2006 and as postdoc in 2003, respectively. The corresponding author Fernandez-Veledo arrived in 2004 and took over the lab leadership after her PI’s death. The other corresponding author, Murga, was at the time already professor at Universidad Autónoma de Madrid.

And here is what data integrity sleuths Clare Francis and others found in that paper, namely duplicated western blot bands:

khdjdfs
Coloured boxes show evidence of gel band duplication, arrows indicate traces of digital splicing. This splicing means that the bands may have been run on physically separate gels and that loading controls (which are apparently photoshopped anyway) don’t match. If confirmed, this data manipulation amounts to research misconduct.

Not just in one figure. Also the Figure 6G contains evidence of duplicated gel bands and inappropriate splicing, while same loading control was apparently used trice, for 3 utterly unrelated sets of samples. Without correct loading controls, but with duplicated bands the entire paper loses credibility.

image-1530219298628

There is even more (visit the relevant PubPeer site), even lazy careless duplications like in Figure 1 or in Figure 3:

Just before Lorenzo’s death, the corresponding author Fernadez-Veledo published this paper:

Rocio Vila-Bedmar , Margarita Lorenzo , Sonia Fernández-Veledo
Adenosine 5′-monophosphate-activated protein kinase-mammalian target of rapamycin cross talk regulates brown adipocyte differentiation
Endocrinology (2010) doi: 10.1210/en.2009-0810

Also there we find some apparent microscopy image and gel band duplications, as discussed on PubPeer. For example:

Little colour boxes indicated apparently duplicated bands. They do show same antibody signal (P-mTOR or GAPDH). but certainly not same samples. A classic case of Photoshop cloning.

In 2008, two years before Margarita Lorenzo died of melanoma, this paper was published:

Sonia Fernández-Veledo , Iria Nieto-Vazquez , Javier De Castro , M. Pilar Ramos , Silke Brüderlein , Peter Möller, Margarita Lorenzo
Hyperinsulinemia Induces Insulin Resistance on Glucose and Lipid Metabolism in a Human Adipocytic Cell Line: Paracrine Interaction with Myocytes
The Journal of Clinical Endocrinology & Metabolism (2008) doi: 10.1210/jc.2007-2472

Among other issues, it contains what looks like a set of meticulously duplicated gel bands, hidden by rearrangement, mirroring and stretching. Who did that?

image-1530481180617Same names keep popping up, and the only thing certain is that the legacy of the late scientist Margarita Lorenzo is tainted by such evidence of data manipulation.

The successor Fernandez-Veledo authored an obituary on her former PI, which was published by the journal Archives of Physiology and Biochemistry where Lorenzo used to be editorial board member of:

“All of those who had the chance to meet and interact with Margarita along her brilliant scientific career (as member of the COST and other collaborative research networks or as an active participant in international meetings) were impressed by her rigorous and talented scientific contributions in the field of insulin resistance, her contagious energy and enthusiasm and the way she enjoyed both science and life. In addition to her scientific legacy, we will always remember Margarita’s courage during her final months”.

Also the Spanish main daily El Pais published an obituary. Its first author was Manuel Benito, professor at the same Complutense University as his late colleague Lorenzo. Benito has his own lengthy PubPeer record of duplicated gel bands, some of his flagged papers were co-authored by one in this respect even more notorious US researcher: C Roland Kahn. An example from the Benito lab, Valverde et al Diabetes 2003, which happened without any input from Kahn:

Another co-author of the El Pais obituary and the Garcia-Guerra et al Diabetes 2010 paper dedicated to the memory of Margerita Lorenzo, is Federico Mayor, professor at Universidad Autónoma de Madrid and former director of Centro de Biología Molecular “Severo Ochoa” (CBMSO), where Cristina Murgas is now deputy director. Would you like to see a sample of the kind of science Mayor and Murgas published together?

Here you go. This is just one example from Peregrin et al, Current Biology 2006. Murga is last author, Mayor penultimate and corresponding author. The coloured boxes show where the images of cells in a dish were accidentally duplicated, while zoomed out, to stand in for utterly separate cells populations.

image-1530130048813

After having been informed how Ofer Lider’s name was besmirched with manipulated data his co-authored placed in his papers, Weizmann Institute quickly performed a misconduct investigation. Two papers have already been retracted for data manipulation, more might follow. Maybe the Complutense University in Madrid will now do the same to clear Margarita Lorenzo’s name?


 

 

Donate!

If you are interested to support my work, you can leave here a small tip of $5. Or several of small tips, just increase the amount as you like. Your generous patronage of my journalism, however small it appears to you, will greatly help me with my legal costs.

€5,00

23 comments on “Another dead scientist framed with manipulated data?

  1. Zebedee

    “Cristina Murga (now deputy director at CBMSO in Madrid)”.

    http://www.jbc.org/content/275/16/12069.long
    doi: 10.1074/jbc.275.16.12069 April 21, 2000
    The Journal of Biological Chemistry 275, 12069-12073.
    A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt.
    Cristina Murga, Shigetomo Fukuhara and J. Silvio Gutkind‡
    Author information

    From the Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4330.

    Figure 3A.

    Like

    • Smut Clyde

      You don’t often see the Crab Canon in gel electrophoresis!

      Like

    • Zebedee

      Also brought to you by the lab that brought you the Crab Canon.
      J Biol Chem. 2000 Dec 29;275(52):41227-33.
      Signaling from E-cadherins to the MAPK pathway by the recruitment and activation of epidermal growth factor receptors upon cell-cell contact formation.
      Pece S1, Gutkind JS.
      Author information
      1 Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4330, USA.

      Figure 3B.

      Like

    • Zebedee

      Also brought to you by the lab that brought you the Crab Canon.
      Cancer Res. 2000 May 1;60(9):2464-72.
      A role for the p38 mitogen-acitvated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents.
      Sanchez-Prieto R1, Rojas JM, Taya Y, Gutkind JS.
      Author information
      1 Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892-4330, USA.

      Figure 1.

      Like

  2. Zebedee

    2 years before the senior author’s death.
    Nuclear Exclusion of Forkhead Box O and Elk1 and Activation of Nuclear Factor-κB Are Required for C2C12-RasV12C40 Myoblast Differentiation
    Cristina De Alvaro Iria Nieto-Vazquez Jose Maria Rojas Margarita Lorenzo
    Endocrinology, Volume 149, Issue 2, 1 February 2008, Pages 793–801, https://doi.org/10.1210/en.2007-0657

    See: https://pubpeer.com/publications/A18472472618ADF24C65BD6BF010DC

    The penultimate author has a style much like that of Piet Mondriaan, which seems to have spilled over.

    J Biol Chem. 2002 Nov 15;277(46):44171-9. Epub 2002 Sep 9.
    HSos1 contains a new amino-terminal regulatory motif with specific binding affinity for its pleckstrin homology domain.
    Jorge R1, Zarich N, Oliva JL, Azañedo M, Martínez N, de la Cruz X, Rojas JM.
    Author information
    1 Unidad de Biologia Celular, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain.

    See: https://pubpeer.com/publications/89582C2164A1D9F4764540B7A83E2B

    J Biol Chem. 2004 Aug 6;279(32):33480-91. Epub 2004 Jun 4.
    The P34G mutation reduces the transforming activity of K-Ras and N-Ras in NIH 3T3 cells but not of H-Ras.
    Oliva JL1, Zarich N, Martínez N, Jorge R, Castrillo A, Azañedo M, García-Vargas S, Gutiérrez-Eisman S, Juarranz A, Boscá L, Gutkind JS, Rojas JM.
    Author information

    1Unidad de Biología Celular, Centro Nacional de Microbiología, Instituto de Salud Carlos III (ISCIII), 28220 Majadahonda, Madrid, Spain.

    See: https://pubpeer.com/publications/C20FE9AAE2120DFC44CFCB7DFDB6F2

    Mol Biol Cell. 2006 Aug;17(8):3591-7. Epub 2006 Jun 7.
    Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1.
    Zarich N1, Oliva JL, Martínez N, Jorge R, Ballester A, Gutiérrez-Eisman S, García-Vargas S, Rojas JM.
    Author information
    1 Unidad de Biología Celular, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain.

    See: https://pubpeer.com/publications/D6ABBDA2D87FF215C2083F2C9EC576

    Like

    • J Biol Chem. 2002 Nov 15;277(46):44171-9.
      hSos1 contains a new amino-terminal regulatory motif with specific binding affinity for its pleckstrin homology domain. Rocío Jorge, Natasha Zarich, José Luis Oliva, Marta Azañedo, Natalia Martínez, Xavier de la Cruz and José M. Rojas
      VOLUME 277 (2002) PAGES 44171–44179

      2018 retraction.
      http://www.jbc.org/content/293/29/11650.short

      This article has been withdrawn by the authors (although Rocío Jorge could not be reached and Natalia Martínez passed away). The authors have become aware of errors in the preparation of Figs. 2A, 3A, 4A, and 5A, where some lanes appear to be duplicated. The authors state that although replicated experiments performed at the time of the article as well as subsequent data published by other groups (Sondermann, H., Nagar, B., Bar-Sagi, D., and Kuriyan, J. (2005) Computational docking and solution x-ray scattering predict a membrane-interacting role for the histone domain of the Ras activator son of sevenless. Proc. Natl. Acad. Sci. U.S.A. 102, 16632–16637; Yadav, K. K., and Bar-Sagi, D. (2010) Allosteric gating of Son of sevenless activity by the histone domain. Proc. Natl. Acad. Sci. U.S.A. 107, 3436–3440; and Tartaglia, M., Pennacchio, L. A., Zhao, C., Yadav, K. K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., Bristow, J., Carta, C., Lepri, F., Neri, C., Vasta, I., Gibson, K., Curry, C. J., Siguero, J. P., Digilio, M. C., Zampino, G., Dallapiccola, B., Bar-Sagi, D., and Gelb, B. D. (2007) Nat. Genet. 39, 75–79) support the results and conclusions presented in this published paper, they consider that the responsible course of action is to withdraw the article in the interests of maintaining the publication standards of the journal. The authors apologize for any inconvenience they may have caused. The paper with the corrected figures can be obtained by contacting the authors.

      Like

    • J Biol Chem. 2004 Aug 6;279(32):33480-91. Epub 2004 Jun 4.
      The P34G mutation reduces the transforming activity of K-Ras and N-Ras in NIH 3T3 cells but not of H-Ras.
      Oliva JL1, Zarich N, Martínez N, Jorge R, Castrillo A, Azañedo M, García-Vargas S, Gutiérrez-Eisman S, Juarranz A, Boscá L, Gutkind JS, Rojas JM.

      2018 retraction.
      http://www.jbc.org/content/293/29/11651.short

      This article has been withdrawn by the authors (although Rocío Jorge, Susana García-Vargas, and Silvia Gutiérrez-Eisman could not be reached, and Natalia Martínez passed away). The authors have become aware of errors in the preparation of Figs. 2A and 3C, where some lanes were erroneously cropped, as well as the Figs. 6A and 8A where some images appear duplicated. The authors state that although replicated experiments performed at the time of the article support the results and conclusions presented in this published paper, they consider that the responsible course of action is to withdraw the article in the interests of maintaining the publication standards of the journal. The authors apologize for any inconvenience they may have caused. The paper with the corrected figures can be obtained by contacting the authors.

      Like

  3. In iberian peninsula, people study photoshop biology… Reminding the case of Carlos Lopez-Otin, a giant of photoshopper. Nicely uncovered the hidden legacy of dead scientist.

    Like

    • Ana Pedro

      You are totally right
      Photoshop biology distortion is a fundamental PhD course in Spain

      Like

  4. Zebedee

    https://www.nature.com/articles/1201778
    Oncogene volume 16, pages 2435–2445 (14 May 1998)
    Signalling of the Ret receptor tyrosine kinase through the c-Jun NH2-terminal protein kinases (JNKs): evidence for a divergence of the ERKs and JNKs pathways induced by Ret
    Mario Chiariello, Roberta Visconti, Francesca Carlomagno, Rosa Marina Melillo, Cecilia Bucci, Vittorio de Franciscis, Gary M Fox, Shuqian Jing, Omar A Coso, J Silvio Gutkind, Alfredo Fusco & Massimo Santoro.

    Affiliations
    Centro di Endocrinologia ed Oncologia Sperimentale del CNR, c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università di Napoli `Federico II’, via S Pansini 5, 80131 Naples, Italy
    Mario Chiariello, Roberta Visconti, Francesca Carlomagno, Rosa Marina Melillo, Cecilia Bucci, Vittorio de Franciscis & Massimo Santoro
    Amgen, 1840 DeHavilland Drive, Thousand Oaks, California 91320-1789, USA
    Gary M Fox & Shuqian Jing
    Oral and Pharyngeal Cancer Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA
    Omar A Coso & J Silvio Gutkind
    Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgia di Catanzaro, Università di Reggio Calabria, via T Campanella 5, 88100 Catanzaro, Italy
    Alfredo Fusco.

    Figure 8.

    Like

  5. Zebedee

    Senior author dead for a year when this one was published.
    Diabetologia. 2011 May;54(5):1157-68. doi: 10.1007/s00125-011-2057-0. Epub 2011 Feb 12.
    New emerging role of protein-tyrosine phosphatase 1B in the regulation of glycogen metabolism in basal and TNF-α-induced insulin-resistant conditions in an immortalised muscle cell line isolated from mice.
    Alonso-Chamorro M1, Nieto-Vazquez I, Montori-Grau M, Gomez-Foix AM, Fernandez-Veledo S, Lorenzo M.
    Author information
    1 Department of Biochemistry and Molecular Biology II, Faculty of Pharmacy, Universidad Complutense de Madrid, 28040 Madrid, Spain.

    Figure 6b.

    Like

  6. Is there any connection between Lorenzo and Lopez-Otin? One taught the other? 2 of most influential photoshop scientists in Spain. Or photoshop biology is just normal thing among big PIs there…?

    Like

  7. Zebedee

    Manuel Benito with help from C Ronald Kahn (Harvard) and Michael White (Harvard).
    More comes to light.

    Mol Cell Biol. 2001 Apr;21(7):2269-80.
    Association of insulin receptor substrate 1 (IRS-1) y895 with Grb-2 mediates the insulin signaling involved in IRS-1-deficient brown adipocyte mitogenesis.
    Valverde AM1, Mur C, Pons S, Alvarez AM, White MF, Kahn CR, Benito M.
    Author information
    1 Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.

    Figure 5B.

    Like

  8. Amazing… I see the same pattern of reusing blots as Lopez-Otin has been doing. I have to say it is tradition of Spain.

    Like

  9. Zebedee

    J Clin Invest. 2001 Oct 15; 108(8): 1205–1213 continued.

    Figure 2d.

    Like

  10. Zebedee

    Manuel Benito with help from C Ronald Kahn (Harvard).

    J Clin Invest. 2001 Oct 15; 108(8): 1205–1213.
    doi: 10.1172/JCI13103
    PMCID: PMC209529
    PMID: 11602628
    Brown adipose tissue–specific insulin receptor knockout shows diabetic phenotype without insulin resistance
    Carmen Guerra,1 Paloma Navarro,2 Angela M. Valverde,2 Monica Arribas,2 Jens Brüning,3 Leslie P. Kozak,1 C. Ronald Kahn,3 and Manuel Benito2
    1Jackson Laboratory, Bar Harbor, Minnesota, USA2Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain3Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA
    Address correspondence to: Manuel Benito, Departamento de Bioquímica y Biologia Molecular, Facultad de Farmacia, Universidad Complutense, Madrid 28040, Spain.

    Figure 3c.

    Figure 4b.

    Like

  11. Fernando

    2 JBC papers from Jose Rojas were retracted.
    http://www.jbc.org/content/293/29/11650.short
    http://www.jbc.org/content/293/29/11651.short
    Right move!!
    Clean out the residue of past fascism in spain.

    Like

  12. J Biol Chem. 2003 Mar 21;278(12):10221-31. Epub 2003 Jan 13.
    Insulin-induced up-regulated uncoupling protein-1 expression is mediated by insulin receptor substrate 1 through the phosphatidylinositol 3-kinase/Akt signaling pathway in fetal brown adipocytes.
    Valverde AM1, Arribas M, Mur C, Navarro P, Pons S, Cassard-Doulcier AM, Kahn CR, Benito M.
    Author information
    1
    Departamento de Bioquímica y Biología Molecular, Centro Mixto Consejo Superior de Investigaciones Cientificas/Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, Spain.

    Figure 5D.

    https://imgur.com/5GqtG14

    Figure 7D.

    https://imgur.com/911popk

    Like

  13. Mol Biol Cell. 2004 Nov; 15(11): 5101–5117.
    doi: 10.1091/mbc.E03-11-0853
    PMCID: PMC524782
    PMID: 15356271
    Susceptibility to Apoptosis in Insulin-like Growth Factor-I Receptor-deficient Brown Adipocytes
    Angela M. Valverde,† Cecilia Mur, Michael Brownlee,‡ and Manuel Benito*
    Carl-Henrik Heldin, Monitoring Editor
    * Instituto de Bioquímica/Departamento de Bioquímica y Biología Molecular II, Centro Mixto Consejo Superior de Investigaciones Cientificas/Universidad Complutense de Madrid, Facultad de Farmacia, Ciudad Universitaria, 28040-Madrid, Spain
    ‡ Diabetes Research Center, Albert Einstein College of Medicine, New York, NY 10461

    Figure 2B.

    Figure 5B.

    Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: