A prominent diabetes researcher based at Harvard Medical School has retracted a third paper, citing manipulation of multiple figures.
Late last year, Carl Ronald Kahn—also chief academic officer at Joslin Diabetes Center—retracted two papers for similar reasons. In November, Kahn pulled a 2005 paper from The Journal of Clinical Investigation (JCI) and a month later, he retracted a 2003 paper from The Journal of Biological Chemistry (JBC), both times citing duplications that the authors said were introduced while assembling the figures.
Last month, Kahn retracted his third paper, also published in JBC in 2003, because the authors omitted data when constructing the images. Still, the authors remain confident in their findings, given that data from other labs “have confirmed and extended the conclusions of the manuscript.”
Here’s the retraction notice:
This article has been withdrawn by the authors. In many of the experiments reported in this study, cells from mice of four genotypes were used (wild-type, p85α−/−, p85α+/−, and p85β−/−), but data from only three of the genotypes (wild-type, p85α−/−, and p85β−/−) were included in the final paper. As a result, there was splicing of the figures of several autoradiograms, which led to several duplicated or mislabeled lanes in the Western blots in Figs. 2B, 3C, and 5B. Although the experimental data generated in the lab from the same time period support the original conclusions of the study, and the studies by this lab and others have confirmed and extended the conclusions of the manuscript, in the interest of maintaining accuracy in the published scientific literature and because the initial figures were not up to the standards of JBC, the authors wish to withdraw this article. The authors apologize for these errors.
“Positive and negative roles of p85α and p85β regulatory subunits of phosphoinositide 3-kinase in insulin signaling” has been cited 146 times, according to Clarivate Analytics’ Web of Science, formerly part of Thomson Reuters.
We reached out to Kahn for further details on how the duplication occurred.
Kaoru Sakabe—data integrity manager at the American Society for Biochemistry and Molecular Biology (which publishes JBC)—told us that a reader alerted them to the issues.
In 2015, a user on PubPeer flagged potential issues with several figures in this paper.
Other papers by Kahn have received corrections and many have been questioned on PubPeer. We’ve covered eight corrections for Kahn (1, 2, 3, 4, 5, 6, 7, 8). We’ve noted two other errata for Kahn (9, 10). Kahn and co-authors received a 2009 erratum for a 2009 study in Cell Metabolism because of “several errors in the figure labeling” as well as a 2007 corrigendum for a study in JCI, published that year, citing figure manipulation.
One of the co-authors on the latest retraction is Lewis C. Cantley, a cancer biologist based at Weill Cornell Medical College. Cantley is credited with the discovery of a signaling pathway essential for the growth and survival of normal and cancerous cells, research which won him the coveted $3 million inaugural Breakthrough Prize in Life Sciences in 2013.
Like Retraction Watch? Consider making a tax-deductible contribution to support our growth. You can also follow us on Twitter, like us on Facebook, add us to your RSS reader, sign up on our homepage for an email every time there’s a new post, or subscribe to our daily digest. Click here to review our Comments Policy. For a sneak peek at what we’re working on, click here.
RE: erratum number 10.
http://www.jci.org/articles/view/31408C1
For figure 4. There are other problematic figures. Please see below.
J Clin Invest. 2007 Aug;117(8):2289-301.
Muscle-specific knockout of PKC-lambda impairs glucose transport and induces metabolic and diabetic syndromes.
Robert V. Farese,1,2,3 Mini P. Sajan,1,2,3 Hong Yang,1,2,3 Pengfei Li,1,3 Steven Mastorides,1 William R. Gower, Jr.,1,3 Sonali Nimal,1,2,3 Cheol Soo Choi,4 Sheene Kim,4 Gerald I. Shulman,4 C. Ronald Kahn,5 Ursula Braun,6,7 and Michael Leitges6,7
1James A. Haley Veterans Medical Center, Tampa, Florida, USA. 2Roskamp Institute, Sarasota, Florida, USA. 3Department of Internal Medicine and Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, Florida, USA. 4Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. 5Joslin Research Foundation and Harvard Medical School, Boston, Massachusetts, USA. 6Division of Nephrology, Department of Medicine, Hannover Medical School, Hannover, Germany. 7Biotechnology Centre of Oslo, Oslo, Norway.
https://pubpeer.com/publications/CA9B7DEC7599BD29593D4192E3209C
Figure 2A.
http://i.imgur.com/QjHvhdT.jpg
Figure 2B.
http://i.imgur.com/rGgWOTV.jpg
Figure 1F.
http://imgur.com/C0t0j0u
J Clin Invest. 2001 Oct 15; 108(8): 1205–1213.
doi: 10.1172/JCI13103
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.
https://pubpeer.com/publications/11602628
Figure 3c.
http://i.imgur.com/uv8Q3DB.jpg
Figure 4b.
http://i.imgur.com/AGq0DK7.jpg
J Clin Invest. 2001 Oct 15; 108(8): 1205–1213.
Additional problematic data figure 4b.
https://imgur.com/JV1CXqv
Mol Cell Biol. 2001 Apr; 21(7): 2269–2280.
doi: 10.1128/MCB.21.7.2269-2280.2001
PMCID: PMC86861
Association of Insulin Receptor Substrate 1 (IRS-1) Y895 with Grb-2 Mediates the Insulin Signaling Involved in IRS-1-Deficient Brown Adipocyte Mitogenesis
Angela M. Valverde,1 Cecilia Mur,1 Sebastián Pons,2,† Alberto M. Alvarez,3 Morris F. White,2 C. Ronald Kahn,2 and Manuel Benito1,*
Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia,1 and Centro de Citometría de Flujo y Microscopía Confocal,3 Universidad Complutense, 28040 Madrid, Spain, and Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts2
*Corresponding author. Mailing address: Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Ciudad Universitaria, 28040 Madrid, Spain. Phone: 34-91-3941777. Fax: 34-91-3941779. E-mail: se.mcu.mis.xamcue@otineb.
†Present address: Instituto de Neurobiología Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain.
https://pubpeer.com/publications/D9076FBE55AD0C0EE56CED7264D4F3
Figure 5B.
http://i.imgur.com/LuEyJb1.jpg
J Biol Chem. 2003 Mar 21;278(12):10221-31. doi: 10.1074/jbc.M209363200
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*
Angela M. Valverde‡, Mónica Arribas‡, Cecilia Mur‡, Paloma Navarro‡, Sebastián Pons§, Anne-Marie Cassard-Doulcier¶, C. Ronald Kahn§ and Manuel Benito‡‖
– Author Affiliations
From the ‡Departamento de Bioquı́mica y Biologı́a Molecular, Centro Mixto Consejo Superior de Investigaciones Cientı́ficas/Universidad Complutense de Madrid, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain, §Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, and ¶Centre de Recherches sur l’Endocrinologie Moléculaire et le Dévelopment, CNRS, 92190 Meudon, France.
https://pubpeer.com/publications/12525499
Figure 7C.
http://i.imgur.com/NzQisfm.jpg
J Biol Chem. 2003 Mar 21;278(12):10221-31.
Additional problematic data coming to light.
https://imgur.com/5GqtG14
Diabetes. 2002 Mar;51(3):743-54.
Increased insulin sensitivity in IGF-I receptor–deficient brown adipocytes.
Cecilia Mur1, Angela M. Valverde1, C. Ronald Kahn2 and Manuel Benito1
– Author Affiliations
1Departamento de Bioquímica y Biología Molecular, Centro Mixto CSIC/UCM, Facultad de Farmacia, Universidad Complutense, Madrid, Spain
2Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.
https://pubpeer.com/publications/11872675
Figure 8.
http://i.imgur.com/xlPNXpE.jpg
Figure 4.
http://i.imgur.com/MkwWAWT.jpg
Diabetes. 1999 Nov;48(11):2122-31. https://doi.org/10.2337/diabetes.48.11.2122
Insulin signaling in insulin receptor substrate (IRS)-1-deficient brown adipocytes: requirement of IRS-1 for lipid synthesis.
A M Valverde, C R Kahn and M Benito.
Figure 1B.
http://i.imgur.com/nFdybdG.jpg
Will Harvard be forced to return the NIH and other agencies grants’ money?
Mol Cell Biol. 2004 Jun;24(11):5080-7.
Increased insulin sensitivity and reduced adiposity in phosphatidylinositol 5-phosphate 4-kinase beta-/- mice.
Lamia KA1, Peroni OD, Kim YB, Rameh LE, Kahn BB, Cantley LC.
Author information
1
Beth Israel Hospital, Harvard Institutes of Medicine, Division of Signal Transduction, 10th Floor, 330 Brookline, MA 02215, USA.
Figure 2.
http://i.imgur.com/EnnOOFA.jpg
Did you highlight this one because of Cantley, or because of Kahn? In case of the latter, note this is a different Kahn.
J Biol Chem. 1995 Mar 3;270(9):4805-12.
Characterization of Rad, a new member of Ras/GTPase superfamily, and its regulation by a unique GTPase-activating protein (GAP)-like activity.
Zhu J1, Reynet C, Caldwell JS, Kahn CR.
Author information
1
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215.
https://pubpeer.com/publications/44542AB505779F4EE31CF38ED690DE#fb121039
Figure 5.
http://i.imgur.com/7IQRI1G.jpg
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12490-5.
Cross-talk between the insulin and angiotensin signaling systems.
Velloso LA1, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR.
Author information
1
Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil.
https://pubpeer.com/publications/8901609
Figure 5. http://i.imgur.com/3GtKLte.jpg
Penultimate author: http://retractionwatch.com/2017/05/18/journal-flags-two-papers-diabetes-researcher-sued-stop-retractions-now-12/
Nat Genet. 2002 May;31(1):111-5. Epub 2002 Apr 1.
beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass.
Kulkarni RN1, Holzenberger M, Shih DQ, Ozcan U, Stoffel M, Magnuson MA, Kahn CR.
Author information
1
Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston Massachusetts 02215, USA.
Figure 4. https://imgur.com/6ILCFqk
Anversa left his post at Harvard for less than this.
http://retractionwatch.com/2015/11/20/stem-cell-researcher-who-sued-harvard-brigham-womens-is-leaving-his-post/
Why is Harvard standing by its man (C Ronald Kahn)?
2019 Expression of Concern for C Ronald Kahn paper.
https://www.jci.org/articles/view/126191
Original citation: J Clin Invest. 2001;108(8):1205–1213. https://doi.org/10.1172/JCI13103
Citation for this Expression of Concern: J Clin Invest. 2019;129(1):437. https://doi.org/10.1172/JCI126191
A reader recently contacted the Editors regarding possible duplication of portions of the images presented in Figure 3, A–C, and Figure 4, A and B, that were used to represent distinct samples. The Editors have requested that the corresponding author provide the original data supporting these figures; however, these data are no longer available. As we are unable to evaluate the integrity of these figures, we are publishing this notice to alert readers to the concern.
The corresponding author dissents from the JCI’s decision to issue this Expression of Concern.
https://pubpeer.com/publications/6FDF6B730030E5398CF394523FD5EE
2019 prize.
https://www.jci.org/articles/view/133156
“2019 Kober Medal to Professor C. Ronald Kahn”
J Biol Chem. 2004 Aug 20;279(34):35950-7. doi: 10.1074/jbc.M405842200. Epub 2004 Jun 15.
Problematic data figure 4. Figure 4. Rightmost 2 lanes much more similar than expected. See: https://imgur.com/ljhNa38
A multi-enzyme cascade of hemoglobin proteolysis in the intestine of blood-feeding hookworms
Angela L Williamson 1, Paolo Lecchi, Benjamin E Turk, Youngchool Choe, Peter J Hotez, James H McKerrow, Lewis C Cantley, Mohammed Sajid, Charles S Craik, Alex Loukas.
Affiliation
1
Department of Microbiology and Tropical Medicine, The George Washington University, Washington, DC 20037, USA.
PMID: 15199048 DOI: 10.1074/jbc.M405842200
Cancer Cell. 2004 Jul;6(1):91-9. doi: 10.1016/j.ccr.2004.06.007.
Problematic data figure 2D. Vertical, straight changes in signal between lanes in P-S6K1 panel, but not in the other panels. See: https://imgur.com/66TWYBd
The LKB1 tumor suppressor negatively regulates mTOR signalingReuben J Shaw 1, Nabeel Bardeesy, Brendan D Manning, Lyle Lopez, Monica Kosmatka, Ronald A DePinho, Lewis C CantleyAffiliation1Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Mol Endocrinol. 2006 Dec;20(12):3389-99. doi: 10.1210/me.2006-0092. Epub 2006 Aug 17.
The reciprocal stability of FOXO1 and IRS2 creates a regulatory circuit that controls insulin signaling
Shaodong Guo 1, Sarah L Dunn, Morris F White
Affiliation
Howard Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Harvard Medical School, Karp Family Research Laboratories, Room 04210, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
PMID: 16916938 DOI: 10.1210/me.2006-0092
Figure 3. Much more similar and different than expected.
See: https://imgur.com/rCVnqeM
https://pubpeer.com/publications/EBC3AF137EDC6DB3AEA625BCC6994C#4
The Actin band in Figure 1C appears to have been reused in Figure 3H as a Tsc2 band. It appears to have been placed differently, contrast adjusted and the dimensions have been adjusted. It is difficult to understand how these transformations could occur by accident.
This issue was not addressed in the previous correction.
2021 erratum for:
FASEB J . 2014 Oct;28(10):4408-19. doi: 10.1096/fj.14-253971. Epub 2014 Jul 8.
Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications
Cecile Vernochet 1, Federico Damilano 2, Arnaud Mourier 3, Olivier Bezy 1, Marcelo A Mori 1, Graham Smyth 1, Anthony Rosenzweig 2, Nils-Göran Larsson 3, C Ronald Kahn 4
Affiliations
1 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA;
2 Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; and.
3 Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, Cologne, Germany.
4Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, Massachusetts, USA; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA; [email protected]
https://pubpeer.com/publications/57CEB9AB62EF9CEAF3678F73DA0A51
2021 erratum.
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fsb2.21633
The authors report that in Figure 1B, the western blots labeled inguinal white adipose tissue (iWAT) tubulin and brown adipose tissue (BAT) mitochondrial transcription factor A (TFAM) contain duplicated images. Note, in this series of experiments, tubulin served as a loading control for TFAM and was used for quantitation. After careful re‐examination of the original data, it appears that this was a duplication; while the BAT TFAM blot is correct, a copy of the same blot was incorrectly inserted in the position of the iWAT tubulin blot. After identification of the correct blot and revision of the figure, recalculation of the quantitation shown in the right panel of Figure 1B revealed no change from the original, indicating that the mistake was solely an image duplication error. Thus, this error did not affect the validity of the research or the conclusions drawn in the paper. The authors thank the reader who brought this mistake to their attention and apologize for any confusion that this error may have caused.