Silvia Bulfone-Paus, the Borstel Institute researcher who was forced to step down as institute director and has already retracted 12 papers, has retracted another, this one in Transplantation. Here’s the text of the notice:
The Editors and Publisher retract the article by Bulfone-Paus et al. published in Transplantation (Vol. 69, pp. 1386–1391, April 15, 2000) because of the inaccurate information provided for Figures 4 and 5.
The paper has been cited five times, according to Thomson Scientific’s Web of Knowledge. It’s the first retraction by Bulfone-Paus that doesn’t include two post-docs, Vadim Budagian and Elena Bulanova, who were blamed for the manipulations in the other 12 retracted papers. Blood is also reviewing a paper co-authored by Bulfone-Paus that doesn’t include Budagian and Bulanova, and BioEssays has issued an Expression of Concern about one that does include them.
Bulfone-Paus was not yet working at Borstel when she published the paper. She was at the Free University in Berlin, and her co-authors were at Friedrich Alexander University and Humboldt University.
We’ve asked the editor of Transplantation for more details, and will update with anything we hear back. In the meantime, Joerg Zwirner, who runs the Abnormal Science blog, raised questions about figure 5 in June.
Hat tip: “Clare Francis”
May I refer the German readers to our post on that issue at Laborjournal Blog: http://www.laborjournal.de/wordpress/?p=3978?
Times Higher Education picking up on story:
http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&storycode=418431&c=1
So, it looks like this misconduct is still a family business, but within the family of Paus and Bulfone-Paus rather than the family of Budagian and Bulanova. I am wondering at what stage will the former couple be put the etire responsibility and blame on and the latter couple be apologized to and restored in their scientific merit.
Dear “A scientific family member”,
In the real world they blame downwards. It is called management.
It is very difficult to deal with because it does not appear as “party political”, but is everywhere.
If you say anything about one manager the managers on the other side of the world will take the manager’s side. I don’t believe that institute directors actually work in the lab. They are managers.
It must have taken a lot of shenanigans by one manager to get the other managers to become critical of one of their fellows.
You have fine aspirations, but the apology will never happen.
I completely agree with David Hartman that “In the real world they blame downwards.”
and that “If you say anything about one manager the managers on the other side of the world will take the manager’s side.”
There is a proverb in some countries which can be translated in English as: “A crow never assaults other fellow crows.”
As illustration of this, I came across two cases where, since the allegations come from external to the academic institution party, the above mentioned proverb applies to the extent that even the Integrity Officers of the academic institutions brake their own Codes and Guidelines in order to cover up the misconduct!
In reply to “A scientific family member” originally posted December 14, 2011 at 5:56 am
Would it be unfair to include professor U Kunzendorf in the Paus/Bulfone-Paus family, say as an uncle figure?
http://www.uni-kiel.de/ps/cgi-bin/exp.php?eid=73
I say this because he is the senior author of the present Transplantation 2000 retraction.
The original paper:
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.
Bulfone-Paus S, Rückert R, Krause H, von Bernuth H, Notter M, Pohl T, Tran TH, Paus R, Kunzendorf U.
Transplantation. 2000 Apr 15;69(7):1386-91.
PMID:10798759
and because he is also an author on the earliest retraction we know about by this group.
Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain.
Bulfone-Paus S, Bulanova E, Pohl T, Budagian V, Durkop H, Ruckert R, Kunzendorf U, Paus R, Krause H.
FASEB J. 1999 Sep;13(12):1575-85. Retraction in: FASEB J. 2011 Mar;25(3):1118.
PMID: 10463949
That is just my opinion, the picture is a bit fuzzy, but may come into clearer view soon.
Bulfone-Paus will need to find other postdocs to blame for this set of retractions. There are two possibilities, either she attracts a wrong kind of postdoc or there is a global postdoc conspiracy hell-bent on ruining her reputation. She, of course, is beyond reproach.
This story is reported on in “The Scientist” under “Immune system fraud”.
http://the-scientist.com/2011/12/19/top-science-scandals-of-2011/
One question is: which interleukins are real?
There are so many, and they are quite confusing. The kind of thing that are stuffed into the heads of medical students.
We know that IL-4A does not exist. Such an old story probably very few are old enough to remember it.
http://articles.chicagotribune.com/1986-11-23/news/8603270927_1_claudio-milanese-interleukin-retraction
The present problems with IL-15 are throwing it into doubt.
IL-33 is one of the things that Alirio Melendez has been working on.
http://www.retractionwatch.com/2011/10/10/70-papers-by-alirio-melendez-under-investigation-report/
If you look at the comment posted : Clare Francis on November 23, 2011 at 4:53 pm it looks like the co-author, F.Y. Liew, does not believe the IL-33 work.
Is just this paper, or is the IL-33 field in trouble?
IL-33 is a nuclear, chromation protein by all acounts, but is also thought to act as an interleukin.
Does anybody know how reliable this work is?
From the literature IL-33 was first discovered by a group led by JP Girard when it was
called NF-HEV (standing for nuclear factor expressed high endothelial venules).
Am J Pathol. 2003 Jul;163(1):69-79.
http://www.ncbi.nlm.nih.gov/pubmed/12819012
“Rediscovered” as a cytokine and named IL-33 by a group led by RA Kastelein
Immunity. 2005 Nov;23(5):479-90.
http://www.ncbi.nlm.nih.gov/pubmed/16286016
When charaterized further by the group that discovered it
Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7.
http://www.ncbi.nlm.nih.gov/pubmed/17185418
the authors conclude that “IL-33 is a heterochromatin-associated nuclear factor in vivo”.
They made a GFP:IL-33 fusion and find it has similar cellular distribution to what they find sing 3 antibodies.
Then in 2009 comes the publication with the title:
“The cytokine interleukin-33 mediates anaphylactic shock”, which is being invetgated by PNAS, and which FY Liew no loniger believes.
Pushparaj PN, Tay HK, H’ng SC, Pitman N, Xu D, McKenzie A, Liew FY, Melendez AJ.
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9773-8.
Since that time JP Girard has published
J Immunol. 2009 Sep 15;183(6):3591-7. and Eur J Immunol. 2011 Feb;41(2):299-305. doi: 10.1002/eji.201040647.
where he is second from last author. One might imagine that he is no longer enthused by IL-33.
The field is too dense for me to make much sense of it. I would appreciate some help.
This is a good review.
The degree of detail in your post and the amazing fact that you posted it at 2am on the 25th December demonstrate how much you are involved with this case.
In reply to: A scientific family member February 10, 2012 at 5:19 am
I am not a Christian. What has the 25th of December got to do with it? Please do not be emotive.
I think that the work by JP Girard is good. Were you referring to Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7. It is a good piece of work. “They made a GFP:IL-33 fusion and find it has similar cellular distribution to what they find (u)sing 3 antibodies”, was written to show that they had taken some care.
In reply to: A scientific family member February 10, 2012 at 5:19 am
I think that my questions about the veracity of interleukines 4A, 15 and 33 are important questions.
I do not know the answers to the latter 2, i.e. IL-15 and IL-33.
From reading this blog you get the impression that IL-15 is in doubt. From my own questions to professor F.Y Liew, and his reply, I start to think that IL-33 (as an interleukin) may also be in doubt.
Reading and writing enables us to gather information outside our immediate environment. You sound aginst this. That is your opinion.
University of Lübeck report on Bulfone-Paus/Paus under wraps:
http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&storycode=418973&c=1
Article in German:
http://www.aerzteblatt-sh.de/nachrichten/abschlussberichte-zum-vermeintlichen-wissenschaftlichen-fehlverhalten-liegen-vor
Thank you for letting us know of that report, Bernard.
Really, as the people above noted, the bosses will cover each other, and it looks like we (the scientific community and the community at large) will never know the truth.
But how about the right of those whom she blamed (the same or other postdocs) to defend themselves?
Status of IL-14 as an interleukin in doubt.
People may be interested that on the issue of the veracity of individual interleukines
Roitt’s Essential Immunology. 12th edition. 2011. Wiley-Blackwell.
http://books.google.de/books?id=UegBn_GT3fkC&pg=PA229&lpg=PA229&dq=interleukin+14+doubt&source=bl&ots=WdhyJmcnpI&sig=Oz9NflFnWBjWLXmkHWip_61fD4Q&hl=de#v=onepage&q=interleukin%2014%20doubt&f=false
page 229, has this to say.
“Approximately 34 interluekines have been described to date (IL-1 to IL-35) with the status of IL-14 as an interleukin in doubt”.
See also table legend 9.1 same page.
Please let’s take care with that. Many cytokines are well studied, well characterized. Proteins with certain functions, receptors and intracell pathways. IL-33 is studied by many other groups, with different actions in different systems. IL-15 is not, and the problem, sometimes, is not the cytokine. The problem is: IL-33 or any other IL will not work as you want, will not be produced when you want and will not be important as you might expect. JP Girard came with a Nature and a PNAS just now. He seems to be serious and consistent in his work. Liew seems to be much more “shot’n go” but with universally accepted data in the field. Alirio’s problems start when he described a role for IL-33 that is definetely not well explained and not consistent at all. It is easy to show how a protein work in different cells and tissues (and some effects are rather limited, already published and represents the end of the line), but not to force them to act as a Nobel prize machine. Let’s not treat Immunology as a chocolate box.
In reply to Deus ex Machina February 27, 2012 at 4:23
Thanks for your measured contribution. I was playing the devil’s advocate. I do take your points.
When there are problems you simply do not know if it is a “one off”, or if something deeper is awry.
You do need to ask the questions. I always liked it when at university the teacher would ask “what is the evidence for?”. Many knew all the lists in the textbooks, but few could give one or two pieces of evidence, or even what sort of thing they would take as evidence.
I do take your point that many cytokines are well studied. My view was, and is, that JP Girard is serious and consistent. I agrre with your assessment of F.Y. Liew, “shot’n go”.
One day it should be possible to have a list of which cytokines are real and which ones are not.
Some may not be real was my point. Sometimes the problem may not be with the cytokine, but sometimes the problem may be with the “cytokine”. There is immunology, and also “immunology”.
From what I read would it be fair to say that IL-4A, and IL-14 are not cytokines, that IL-15 is in doubt as a cytokine, but that IL-33 is most likely a cytokine?
I do get the feeling that “immunology” does not like scrutiny.
Fully agree with you.
Many Immunologists will not just leave people touch their chocolate boxes… This feeling of immunology and its findings as a precious child is often beyond the concept of scientific value: it is an obsession. But it finally works for many other fields of research as well.
Regarding cytokines, I am pretty sure they will change names, functions and sources in the next 10 years. This is not a problem IF this transition is well explained, tested and published. And there is also the “potential therapeutic target”, often wrongly used in many concluding remarks troughout Immunology’s top journals. IL-5, TNF-alpha, IL-1B and many others are REAL therapeutic targets with real and consistent references that might be used in the future for real clinical advances. The huge number of cytokines doesn’t mean they are “overrated”. To force a result or a phenomenum is the crime of the century here. Don’t know what else should we expect from this IL-15-Bulfone-Paus history…
Before the 2012 retraction in Transplantation particular Indians (postdocs), as opposed to the chief (senior and corresponding author) could be blamed for all the retractions. Now this is no longer the case.
Managers blame downwards, but the evidence seems to be that those higher up (the “haves”) or more likely to likely to cheat. It is only one study, but it does make you think.
http://articles.latimes.com/2012/feb/27/science/la-sci-0228-greed-20120228