Silvia Bulfone-Paus

Silvia Bulfone-Paus (born Silvia Bulfone) is an Italian immunologist, who gained widespread attention in mainstream media for rampant scientific misconduct.

She is the chair of the Research Center Borstel's Department of Immunology and Cell Biology^[1][2] and also serves as professor of Immunobiology at the University of Manchester School of Medicine.^[3] Her position at the Board of Directors of the Research Centre Borstel is currently in “abeyance”.^[4]

Personal life

Bulfone-Paus is married to Ralf Paus, a professor in Dermatology at the University of Münster in Germany.^[5] Paus also holds a position as Professor of Cutaneous Medicine at the University of Manchester.^[5] Bulfone-Paus and Paus have three children.^[5]

Work and fraud investigations

Bulfone-Paus specializes her research in the biology of the immune response, especially cytokines and mast cells.^[3] Mast cells secrete a substance known as histamine, which produces inflammation.^[6] Cytokines are small molecules made of amino acids.^[7] These cell-signaling molecules play a role in the immune response and include interferons and interleukins.^[7]

Formal investigation

In the fall of 2009, Bulfone-Paus was alerted to potential misconduct in her lab at the Research Centre Borstel by a biologist and one-time post-doctoral student in Paus’ lab.^[8] Bulfone-Paus delayed three months before alerting her institution to the allegations in February 2010.^[9] A formal investigation was begun in June of the same year.^[10]

In July 2010, an anonymous whistleblower(s) began what Nature called a “libelous” “trial-by-internet”.^[11] The informer(s) commenced emailing the investigators, other scientists, and politicians, alerting them to instances of fraud in Bulfone-Paus’ laboratory.^[12] The anonymous instigator(s) went by several pseudonyms, including Marco Berns, David Hardman, and Fernando Pessoa.^[12] Blogs with information regarding the case and the alleged misinformation were posted on a website, hosted in Panama, under the name of Martin Frost.^[12] Many expressed their dismay that a colleague would be subjected to such a “smear-campaign”.^[11][13] However, in an editorial in the Lab-Times, the writers express, “Ultimately, we have been left to question whether the ‘Bulfone-Paus stone’ would have actually started rolling without the ‘smear campaign’. To be honest, we doubt it."^[12]

The formal investigation committee found evidence of image manipulation in six papers written between 2001 and 2009.^[10] The blame was placed upon the shoulders of two post-doctoral students in the lab, Russians Elena Bulanova and Vadim Budagian.^[10] The investigators also stated they found no conclusive evidence regarding falsification of data and cleared the six papers on that charge. Bulfone-Paus was listed as either the senior or corresponding author on all six of the publications.^[10]

DFG and Internal Investigation

DFG, the German Research Foundation, a major supplier of research funding in Germany, also initiated an investigation into Bulfone-Paus’ laboratory in 2010.^[10] At the culmination of the formal investigation, the director of the Research Centre Borstel indicated that an internal investigation of the lab was forthcoming, as officials at the center believed a more extensive investigation was warranted.^[10] The center commenced its own internal investigation.^[10] In December, 2010, officials at the research center made it known they were asking for the retraction of six further papers, written between 1999 and 2005, all authored or co-authored by Silvia Bulfone-Paus.^[13][14] According to a press release from Research Centre Borstel, "manipulation" was admitted in four of the new retractions.^[14][15] The center found two other publications for which they felt retraction was necessary as well.^[14][15] In response to the findings of their investigation, the Research Centre Borstel downsized Bulfone-Paus’ laboratory and decreased the funding of the lab.^[16]

In the retraction statement for one of the articles, “A promiscuous liaison between IL-15 and Axl receptor tyrosine kinase in cell death control”, the authors of the paper, minus the two Russian researchers, alleged Bulanova and Budagian performed both the experiments and the data manipulation.^[17][18][19] The researchers went on to say they believed the results of the experiment were in no way compromised by the fraud.^[20]

Retraction notices for all twelve papers continued to appear throughout the months of February and March of 2011.^[21]

Reaction of the Scientific Community

On March 16, 2011, an open letter, written to the Board of Directors at the Research Centre Borstel and signed by twenty-five scientists hailing from all parts of the globe, was published.^[22] In this letter, the scientists repeatedly expressed their admiration and respect for Bulfone-Paus and her contributions to scientific research.^[23] The writers also lamented that their esteemed colleague was being held as much responsible for the incidents as the two post-doctoral students.^[13]

One month later, the Board of Directors of the Research Centre Borstel wrote a reply to the outraged scientists.^[13] The letter issues their dismay with the way Bulfone-Paus handled the accusations and her considerable delay before alerting officials at the centre.^[13] The letter also states Bulfone-Paus knew of the possibility of misconduct in her laboratory since 2004, when Dr. Wiebauer first brought the issue to her attention.^[13] In response to the scientists’ claims that Bulfone-Paus’ considerable and extensive contributions in her field should influence how she was affected by the incident, officials at Borstel said, “Severe failure in one area (as supervisor and responsible senior, corresponding and first author) can hardly be compensated by merits in other areas.”^[13]

Further Investigation and Retractions

In June of 2011, Retraction Watch blog reported Blood had made known to them that they were conducting a review of a paper written by Bulfone-Paus in 1999.^[24] The article in question listed Bulfone-Paus as senior author and did not list either of the two previously implicated Russian post-doctoral students as contributor to the paper.^[13][25]

Also in June, the University of Lubeck, in Germany, began investigations into six papers authored by Bulfone-Paus’ husband, Ralf Paus.^[16] Of the six articles in question, Bulfone-Paus was listed as co-author on five of them.^[16] Neither of the Russian post-doctoral students were listed as co-authors.^[16]

In December of the same year, the journal Transplantation stated they were retracting another of Bulfone-Paus’ papers.^[21][26] The article, published in 2000, was retracted because of “inaccurate information” for two figures contained in the paper.^[26] As with the article in Blood, Elena Bulanova and Vadim Budagian were not listed as contributing authors.^[26]

Retracted Articles

1. ATP induces P2X7 receptor-independent cytokine and chemokine expression through P2X1 and P2X3 receptors in murine mast cells- Journal of Leukocyte Biology
2. Retraction Notice
3. The IL-15Rα Chain Signals Through Association with Syk in Human B Cells- Journal of Immunology
4. Retraction Notice
5. Mast Cells Express Novel Functional IL-15 Receptor α Isoforms- Journal of Immunology
6. Retraction Notice
7. Extracellular ATP Induces Cytokine Expression and Apoptosis through P2X7 Receptor in Murine Mast Cells- Journal of Immunology Retraction Notice
8. A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control- The EMBO Journal Retraction Notice
9. Enhanced Inhibition of Tumour Growth and Metastasis, and Induction of Antitumour Immunity by IL-2-IgG2b Fusion Protein- Scandinavian Journal of Immunology Retraction Notice
10. Soluble Interleukin (IL)-15Rα Is Generated by Alternative Splicing or Proteolytic Cleavage and Forms Functional Complexes with IL-15- Journal of Biological Chemistry Retraction Notice
11. Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum- Molecular and Cell Biology Retraction Notice
12. Death deflected: IL-15 inhibits TNF-α-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Rα chain- The FASEB Journal Retraction Notice
13. Signaling through P2X7 receptor in human T cells involves p56LCK, MAP kinases, and transcription factors AP-1 and NF-kB- Journal of Biological Chemistry Retraction Notice
14. Natural Soluble Interleukin-15Rα Is Generated by Cleavage That Involves the Tumor Necrosis Factor-α-converting Enzyme (TACE/ADAM17)- Journal of Biological Chemistry Retraction Notice
15. Reverse Signaling through Membrane-bound Interleukin-15- Journal of Biological Chemistry Retraction Notice
16. An Interleukin-2-IgG-Fas Ligand Fusion Protein Suppresses Delayed-Type Hypersensitivity in Mice by Triggering Apoptosis in Activated T Cells as a Novel Strategy for Immunosuppression- Transplantation Retraction Notice

See also

• List of scientific misconduct incidents

References

1. "Professor Silvia Bulfone-Paus, research profile". University of Manchester. University of Manchester. Retrieved 15 January 2012.
2. "Leibniz-Zentrum Borstel: Department of Immunology and Cell Biology". Leibniz-Zentrum Borstel. Leibniz-Zentrum Borstel. Retrieved 15 January 2012.
3. "Professor Silvia Bulfone-Paus - personal details". University of Manchester. University of Manchester. Retrieved 15 January 2012.
4. "Leibniz-Zentrum Borstel: Board of Directors". Leibniz-Zentrum Borstel. Leibniz-Zentrum Borstel. Retrieved 15 January 2012.
5. "Professor Ralf Paus - personal details". University of Manchester. University of Manchester. Retrieved 15 January 2012.
6. "Mastocytosis: What It Is and How It's Diagnosed and Treated". American Family Physician. 59 (11): 3059–3060. June 1999. Retrieved 19 January 2012.
7. "Cytokine Definition". Medicine Net. Medicine Net. Retrieved 17 January 2012.
8. Marcus, Adam (2011-05-19). "Retraction Watch Tracking retractions as a window into the scientific process Bulfone-Paus saga continues: Her supporters and home institution exchange sharp letters". Retraction Watch. Retraction Watch. Retrieved 15 January 2012.
9. Marcus, Adam (2011-05-19). "Bulfone-Paus saga continues: Her supporters and home institution exchange sharp letters". Retraction Watch. Retraction Watch. Retrieved 15 January 2012.
10. Schiermeier, Quirin (December 2010). "German research centre widens misconduct probe". Nature. doi:10.1038/news.2010.671. Retrieved 17 January 2012.
11. "A destabilizing force". Nature. 467 (7312): 133. 9 September 2010. doi:10.1038/467133b. PMID 20829751.
12. "'Smear Campaign'..." (PDF). Lab Times (1): 3. February 2011. Retrieved 17 January 2012.
13. "Response to Open Letter" (PDF). Research Centre Borstel. Research Centre Borstel. Retrieved 17 January 2012.
14. Oransky, Ivan (2011-01-18). "Four more Bulfone-Paus paper retractions accepted". Retraction Watch Blog. Retraction Watch Blog. Retrieved 13 January 2012.
15. "Status Quo zum Sachstand wissenschaftlichen Fehlverhaltens am FZB". Forschungszentrum Borstel - Medizinische Klink. Research Centre Borstel. Retrieved 18 January 2012.
16. Jump, Paul (2 June 2011). "Husband and wife in data duplication papers probe". Times Higher Education. Retrieved 17 January 2012.
17. Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Thon, Lutz; Mamat, Uwe; Bellosta, Paola; Basilico, Claudio; Adam, Dieter; Paus, Ralf; Bulfone-Paus, Silvia (2005). "A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control". The EMBO Journal. 24 (24): 4260–4270. doi:10.1038/sj.emboj.7600874. PMC 1356322. PMID 16308569.
18. Marcus, Adam (2011-02-02). "In retraction notice, Bulfone-Paus "declares" data and conclusions confirmed; journals accept six more retractions". Retraction Watch. Retraction Watch. Retrieved 17 January 2012.
19. Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Thon, Lutz; Mamat, Uwe; Bellosta, Paola; Basilico, Claudio; Adam, Dieter; Paus, Ralf; Bulfone-Paus, Silvia (February 2011). "A promiscuous liaison between IL-15 receptor and Axl receptor tyrosine kinase in cell death control". The EMBO Journal. 30 (3): 627. doi:10.1038/emboj.2011.7. PMC 3034024. PMID 21285977.
20. "In retraction notice, Bulfone-Paus "declares" data and conclusions confirmed; journals accept six more retractions". Retraction Watch Blog. Retraction Watch. 2011-02-02. Retrieved 19 January 2012.
21. Marcus, Adam (2011-12-13). "Bulfone-Paus retraction count grows to 13 with one in Transplantation". Retraction Watch. Retraction Watch. Retrieved 17 January 2012.
22. "OPEN LETTER - TO WHOM IT MAY CONCERN March 16, 2011" (PDF). Signotories. Retraction Watch. Retrieved 17 January 2012.
23. "RESPONSE - TO WHOM IT MAY CONCERN April 6, 2011" (PDF). Board of Directors of the Research Center Borste. Research Center Borste. Retrieved 17 January 2012.
24. Marcus, Adam (2011-06-02). "Another Bulfone-Paus paper under review, this one in Blood". Retraction Watch. Retraction Watch. Retrieved 17 January 2012.
25. Verfassen, Kommentar. "Blowing the whistle on Blood 93, 1999, page 3531". Abnormal Science. Abnormal Science. Retrieved 17 January 2012.
26. Jump, Paul (13 December 2011). "New retraction of paper by husband and wife research team". Times Higher Education. Retrieved 17 January 2012.