Alfredo Fusco, a cancer researcher in Italy who is facing a criminal investigation for fraud, has had two more papers retracted.
Here’s the Cell Death & Disease notice for “High-mobility group A1 protein inhibits p53-mediated intrinsic apoptosis by interacting with Bcl-2 at mitochondria:”
The Editorial Board of Cell Death and Disease is retracting the above article (PMID 22932725).
A reader contacted the Editors about apparent duplications in Figures 1b and 2c, and possible splicing of an image in Figure 3c. Concerns were subsequently raised about the similarity of the tubulin loading controls in Figure 1b to those that appeared in Figure 1c of Cell Death and Differentiation 2006; 13: 1554–63 (PMID 16341121), a paper that was retracted by the authors on 6 December 2013.
Because the Authors were unable to provide the original source files that were used to generate the figures in question, the Editorial Board is retracting this publication.
The paper has been cited nine times, according to Thomson Scientific’s Web of Knowledge.
Here’s a notice from DNA and Cell Biology, which is unfortunately behind a paywall:
The article entitled “Targeted Disruption of the Murine Homeodomain-Interacting Protein Kinase-2 Causes Growth Deficiency In Vivo and Cell Cycle Arrest In Vitro,” by Trapasso et al., 2009;28(4);doi: 10.1089/dna.2008.0778, pp 161–167, is being officially retracted from DNA and Cell Biology.
Data presented in Figure 1 appear to have been manipulated.
We regret any inconvenience this error may have caused.
The DNA and Cell Biology paper has been cited 11 times.
Fusco’s other retractions were from the Journal of Clinical Investigation and Cell Death and Differentiation.
We’ve also obtained a letter from Ohio State University, where one of Fusco’s co-authors on the DNA and Cell Biology paper works, to pseudonymous whistleblower Clare Francis. That co-author, Carlo Croce, has written several papers with Fusco. Here’s the text, in which an administrator says OSU sees no reason to investigate, and that the Office of Research Integrity agrees:
The Ohio State University received your additional allegations against university faculty member Carlo M. Croce Ph.D., which were detailed in the emails you sent on December 12, 2013 and December 14, 2013. As noted in my letter to you dated December 12, 2013, the University reviewed the manuscripts numbered 1, 3, and 4 in your email of December 12, 2013 and determined that the manuscripts were not generated at Ohio State. Specifically, the corresponding authors for the manuscripts are not employed by the Ohio State University. Further, although Dr. Croce is a co-author on the three manuscripts, neither Dr. Croce nor any other Ohio State employee generated or provided any data for the figures in question, nor were they involved in the generation of the figures. In view of these facts, any questions regarding the figures in these papers would need to be addressed by the corresponding authors and their home institutions. Pertaining to manuscript 2 in your email of December 12, 2013, that manuscript was part of the original set of allegations (initially numbered 32) originally sent by you to the Office of Research Integrity (ORI) and then forwarded by you to Ohio State University on November 17, 2013. The manuscript was reviewed by the ORI and per the ORI there is no further action needed. As such, the Ohio State University considers this matter closed.
Of note: In the Terry Elton case, the ORI said OSU hadn’t gone far enough. OSU concluded its letter to Francis:
Please note that the Institution considers continued activities in this vein as constituting frivolous allegations and a waste of University and State resources.
Carlo Croce again? The author of the one of the silliest papers ever published
Nature. 1989 Nov 9;342(6246):195-8.
The bcl-2 gene encodes a novel G protein.
Haldar S1, Beatty C, Tsujimoto Y, Croce CM.
http://www.nature.com/nature/journal/v342/n6246/abs/342195a0.html
It should have been retracted long ago. I recommend it for a good laugh.
I’m surprised by the response from Ohio State University. Do they not adhere to the ethical principle that all authors are responsible for the whole of any scientific paper? The detached, legalistic denial does not see either adequate or appropriate given the context.
It does not seem appropriate for OSU to investigate a laboratory in Italy.
But yet the OSU professor put his name on the paper. And when it was retracted had a university lawyer right a nothing-to-do-with-me letter. That _appears_ to fall well short of the ethical ideal of scientific research.
There has been comment at Pubpeer.
https://pubpeer.com/publications/22932725
https://pubpeer.com/publications/16223882
https://pubpeer.com/publications/2FFCE9B2CED68E5A288DD34FF78ABC#fb8186
I don’t think you can punish people because their collaborators did fraud, how is that fair?
That being said, for the second pubpeer link Fusco is not a co-author, the first and last authors are from OSU, and the image looks extremely questionable. Was that the paper #2 mentioned in the letter?
“I don’t think you can punish people because their collaborators did fraud, how is that fair?”
When you take authorship you are taking responsibility for the work as a whole. No one should be looking at a paper more closely or more critically than the authors. If someone finds blatant manipulations in a paper, you as an author, are responsible.
Obviously it is everyone’s fear that a co-author could do something wrong and go unnoticed. But since your integrity has been compromised it is your duty to at least look into the problem. It is unacceptable to say “I wasn’t involved” at this point.
Sure, you are (co-)responsible. Which is why you also take the retraction onto your account.
However, when it comes down to fraud, it comes down to personal responsibility of the fraudster only. At least in the sense of criminal responsibility etc.. The fraudster deceived his co-authors as well.
Nevertheless, I agree that things like this should not happen. The co-authors should see the original raw data of every other co-author. They should make sure everything is sound. If you do it that way, deliberate fraud of one of the co-authors will be more difficult, albeit still not impossible. It would probably even help if it would work that way within one institution, but even there quite often the co-workers and even the PI don’t look to close. In biomedical research it is reality that external collaborators generally don’t get to see more than the peer reviewers and ultimately the journal readers. Like it or not, that’s the way it works in 99% of cases.
That OSU is responding as it has should not be all that surprising. Consider what has happened with the school of pharmacy:
http://www.dispatch.com/content/stories/local/2013/03/10/osu-pharmacy-college-faces-serious-issues.html
It looks to me that lanes 3, 4, and 5 in the beta-actin panel were copied into lanes 6, 7, and 8 of Figure 1B of “WWOX gene restoration prevents lung cancer growth in vitro and in vivo”
Muller Fabbri, Dimitrios Iliopoulos, Francesco Trapasso, Rami I. Aqeilan, Amelia Cimmino, Nicola Zanesi, Sai Yendamuri, Shuang-Yin Han, Dino Amadori, Kay Huebner, and Carlo M. Croce http://www.pnas.org/content/102/43/15611.long
No Fusco, but F. Trapasso and C. Croce are authors common to the DNA and Cell Biology and PNAS articles. The PNAS article should be retracted as well.
Trapasso and Croce have been coauthors on 49 Pubmed archived articles. Fusco and Croce are coauthors on 44, and the three have been coauthors on 10. Trapasso and Fusco are coauthors on 36.
Is Peter Vogt of the The Scripps Research Institute, the editor of the PNAS article, aware of these issues?
What responsibility does a principal investigator have for the obviously manipulated data emerging from his laboratory in articles with his name on them?
There is another observation at Pubpeer which is difficult to explain.
https://pubpeer.com/publications/12719539
For reference:
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5956-61. Epub 2003 Apr 28.
Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27.
Cesari R1, Martin ES, Calin GA, Pentimalli F, Bichi R, McAdams H, Trapasso F, Drusco A, Shimizu M, Masciullo V, D’Andrilli G, Scambia G, Picchio MC, Alder H, Godwin AK, Croce CM.
Author information
1Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
PMID: 12719539
The mundane, but it does dilute meaning.
https://pubpeer.com/publications/17726105
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14442-7. Epub 2007 Aug 28.
ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias.
Nakanishi H1, Nakamura T, Canaani E, Croce CM.
Author information
1Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210, USA.
PMID: 17726105
Again, the mundane, but is does dilute meaning.
https://pubpeer.com/publications/17581865
Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):10980-5. Epub 2007 Jun 20.
Oncogenic All1 fusion proteins target Drosha-mediated microRNA processing.
Nakamura T1, Canaani E, Croce CM.
Author information
1*Department of Molecular Virology, Immunology, and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210.
PMID:17581865
C.M. Croce is only a co-author, but it does dilute meaning.
https://pubpeer.com/publications/17178841
Mol Cell Biol. 2007 Mar;27(5):1889-903. Epub 2006 Dec 18.
Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth.
Issaeva I1, Zonis Y, Rozovskaia T, Orlovsky K, Croce CM, Nakamura T, Mazo A, Eisenbach L, Canaani E.
Author information
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
You get similar changes in bands, shown in Figure 1, from a cell paste if you split and warm your samples and let the Calpains do their snipping magic.
Leupeptin will inhibit Calpains, and 10-100 uM is the range used, but really 50 uM is close to your working minimum. They used on Leupeptin 2 ug/ml or 4.6 uM and only 200 uM EDTA, not even EGTA.
Sloppy work and sloppy refereeing.
Trapasso and Croce again. There can be little doubt that the beta-actin lanes in the left-hand panel of Figure 2a have been copied into the lower panel of Figure 2b.
http://www.pnas.org/content/100/10/5956.full.pdf
It appears that this practice was routine in the articles of these authors.
Another PNAS article that should be retracted.
Two recent postings at Pubpeer:-
1. https://pubpeer.com/publications/DB09C09E8DF6A785A7A2B98A81E283#fb8364
Eur J Cancer. 2011 Feb;47(3):470-8. doi: 10.1016/j.ejca.2010.09.045. Epub 2010 Oct 31.
Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice.
Fedele M1, Visone R, De Martino I, Palmieri D, Valentino T, Esposito F, Klein-Szanto A, Arra C, Ciarmiello A, Croce CM, Fusco A.
Author information
1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Università degli Studi di Napoli Federico II, 80131 Naples, Italy.
2. https://pubpeer.com/publications/13955DF2DEE158B7C685A5468CBB93#fb8307
J Pathol. 2011 May;224(1):110-20. doi: 10.1002/path.2846. Epub 2011 Mar 7.
Down-regulation of oestrogen receptor-β associates with transcriptional co-regulator PATZ1 delocalization in human testicular seminomas.
Esposito F1, Boscia F, Franco R, Tornincasa M, Fusco A, Kitazawa S, Looijenga LH, Chieffi P.
Author information
1Dipartimento di Medicina Sperimentale, II Università di Napoli, Naples, Italy.
Eur J Cancer. 2011 Feb;47(3):470-8.
Also, please compare lanes 1 and 2 GAPDH panel figure 1D.
European Journal of Cancer
Volume 47, Issue 3, February 2011, Pages 470–478
Expression of a truncated Hmga1b gene induces gigantism, lipomatosis and B-cell lymphomas in mice
Monica Fedele, , Rosa Visone , Ivana De Martino, Dario Palmieri, Teresa Valentino, Francesco Esposito, Andres Klein-Szanto, Claudio Arra, Andrea Ciarmiello, Carlo M. Croce, Alfredo Fusco http://www.sciencedirect.com/science/article/pii/S0959804910009858
Lanes 1 and 2 in the GAPDH panel of Figure 1D seem to be duplicates and lanes 3-8 of that panel seem to be longer exposures of lanes 2-7 in the Hmga1b/T panle in that figure.
Another paper that should be retracted.
Nature Medicine should take notice of this and retract rather than just correct http://www.nature.com/nm/journal/v20/n1/full/nm0114-103.html
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16570-5.
Pubpeer comment on a paper where CM Croce is one of the two corresponding authors.
https://pubpeer.com/publications/23012423
For reference:
Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16570-5. doi: 10.1073/pnas.1207917109. Epub 2012 Sep 24.
MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation.
Romano G1, Acunzo M, Garofalo M, Di Leva G, Cascione L, Zanca C, Bolon B, Condorelli G, Croce CM.
PMID: 23012423
The relationship between bands in figure 5 Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16570-5.4
has been commented on at Pubpeer.
https://pubpeer.com/publications/ABA412A220F3B7CEB35CEBA15F59C6#fb8483
Please see the image here:
http://imgur.com/Luma5Fz
A January 2014 corrigendum has been published for Nat Med. 2011 Dec 11;18(1):74-82.
http://www.nature.com/nm/journal/v20/n1/full/nm0114-103.html
“In the version of this article initially published, the actin loading control of the western blot in Figure 1a was a rotated duplicate of the actin control in Figure 1h. The authors have not been able to provide the original control data, but they have repeated the experiment and have provided new blots (Fig. 1) that are now published as part of the correction notices linked to the HTML version and attached to the PDF version of the article. The original blots remain in both online versions of the article. In addition, Figure 6g contained a spliced gel that has now been corrected in the HTML and PDF versions of the article.”
Nat Med. 2011 Dec 11;18(1):74-82. doi: 10.1038/nm.2577.
EGFR and MET receptor tyrosine kinase-altered microRNA expression induces tumorigenesis and gefitinib resistance in lung cancers.
Garofalo M1, Romano G, Di Leva G, Nuovo G, Jeon YJ, Ngankeu A, Sun J, Lovat F, Alder H, Condorelli G, Engelman JA, Ono M, Rho JK, Cascione L, Volinia S, Nephew KP, Croce CM.
Author information
1Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA.
Erratum in
Nat Med. 2014 Jan;20(1):103.
Some more Croce history–he doesn’t have a good history with supervision of collaborators.
http://books.google.com/books?id=IFqxBJNuET8C&q=croce#v=snippet&q=croce&f=false
http://articles.philly.com/2000-05-20/news/25618843_1_gene-therapy-research-gene-therapy-legal-costs
http://articles.philly.com/2000-05-20/news/25618843_1_gene-therapy-research-gene-therapy-legal-costs
Mentions a Roger J Pomerantz.
I could find 1 retraction, but that is before the 2000 newspaper article, where it is written ” Jefferson agreed to ask scientific journals to make further corrections”.
http://www.ncbi.nlm.nih.gov/pubmed/12465612
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10344.
Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody.
Duan L, Laughlin MA, Oakes JW, Pomerantz RJ.
Retraction of
Duan L, Bagasra O, Laughlin MA, Oakes JW, Pomerantz RJ. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5075-9.
PMID: 12465612
The court document on Thomas Jefferson and Croce
http://healthsci.org/USexrelYWu/2_USexrelYongWu_Settlement_Agreement.pdf
Maybe the court case helps explain the move from TJU to OSU
http://articles.philly.com/2004-07-16/news/25371565_1_cancer-researcher-carlo-croce-cancer-effort
JBC “Correction” for Croce and Fusco
POZ-, AT-hook-, and zinc finger-containing protein (PATZ) interacts with human oncogene B cell lymphoma 6 (BCL6) and is required for its negative autoregulation.
Raffaela Pero, Dario Palmieri, Tiziana Angrisano, Teresa Valentino, Antonella Federico, Renato Franco, Francesca Lembo, Andres J. Klein-Szanto, Luigi Del Vecchio, Donatella Montanaro, Simona Keller, Claudio Arra, Vasiliki Papadopoulou, Simon D. Wagner, Carlo M. Croce, Alfredo Fusco, Lorenzo Chiariotti and Monica Fedele
VOLUME 287 (2012) PAGES 18308–18317
“Western blot images representing PATZ, BCL6, and tubulin in Fig. 6C did not accurately represent the experimental results. Different lanes were erroneously duplicated. Lane 3 of the PATZ panel was duplicated in lane 7; lane 4 of the PATZ panel was duplicated in lanes 5 and 6; lane 1 of the BCL6 panel was duplicated in lane 2; lane 4 of the tubulin panel was duplicated in lane 7; and lane 5 of the tubulin panel was duplicated in lane 6. The authors have provided an image from a replicate experiment. This correction does not affect the interpretation or conclusions of this work.”
http://www.jbc.org/content/289/21/14966.full
Retractions numbers 5 and 6 Alfredo Fusco.
https://pubpeer.com/publications/23ACE37C166022FEE6E4B301AA9CD7#fb10985
https://pubpeer.com/publications/3417B0FC58836EB54C2E2D2A12D581#fb10986
So JBC has done it again. Opaque retraction notices that tell us absolutely nothing other than that the paper has been retracted.
Ivan, Adam, or Cat for that matter, it seems you need to contact them and ask why they have gone back to providing no relevant information as to why the papers were retracted. Based on the pubpeer comments it looks like another case of figure manipulation, but no one would know based on the JBC notice.
2015 Mega-correction for
Cancer Lett. 2010 May 28;291(2):230-6. doi: 10.1016/j.canlet.2009.10.017.
Fhit loss in lung preneoplasia: relation to DNA damage response checkpoint activation.
Cirombella R1, Montrone G, Stoppacciaro A, Giglio S, Volinia S, Graziano P, Huebner K, Vecchione A.
Author information
1Division of Pathology, II University of Rome La Sapienza, Ospedale Santo Andrea, Rome, Italy..
https://pubpeer.com/publications/499D4D40914B863806C7A6E10B34AE#fb38826
3rd retraction for Carlo M Croce.
2016 retraction.
http://www.jbc.org/content/291/29/14914.full
https://pubpeer.com/publications/0E3ED839EE93ED96AD45AD63AFFCEE
J Biol Chem. 2009 Oct 2;284(40):27487-99. doi: 10.1074/jbc.M109.036541. Epub 2009 Jul 29.
Unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks.
Naga Prasad SV1, Duan ZH, Gupta MK, Surampudi VS, Volinia S, Calin GA, Liu CG, Kotwal A, Moravec CS, Starling RC, Perez DM, Sen S, Wu Q, Plow EF, Croce CM, Karnik S.
Author information
1Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
The letter from Ohio State University states
“faculty member Carlo M. Croce Ph.D.”
yet according to the New York Times and his own website he does not have a Ph.D..
https://www.nytimes.com/2017/03/08/science/cancer-carlo-croce.html?_r=0
“Dr. Croce, who has a medical degree but no Ph.D.”.
https://medicine.osu.edu/cancer-biology-genetics/directory/medical-genetics/croce-carlo/pages/index.aspx
“Education & Training
1969 Doctor of Medicine, University of Rome La Sapienza”