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Retraction Watch

Tracking retractions as a window into the scientific process

Retraction of 19-year-old Nature paper reveals hidden cameras, lab break-in, evidence tampering

with 22 comments

nature bezouskaWe’ve often found that when some authors refuse to sign retraction notices, there’s a much bigger story than terse notices let on. And a retraction in this week’s Nature of a 19-year-old paper is a shining example of that.

Here’s the brief notice for “Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity,” a 1994 paper by researchers from the UK and the Czech Republic that had already been subject to a 1996 correction:

We wish to retract this Article owing to an inability to reproduce the results. This retraction has not been signed by K.B. and A.F., and M.P. is deceased (J.O’B. cannot be traced).

K.B. is Karel Bezouska, then working in the lab of corresponding author Ten Feizi at The Glycosciences Laboratory at Northwick Park Hospital, Middlesex, UK. Bezouska, it turns out, was found by an ethics committee at Charles University (Google translation of a January 2013 press release from Czech) to have:

…most likely committed the Scientific Misconduct or “dangerous and irresponsible deviations from accepted practice how to conduct research.” This Scientific Misconduct occurred repeatedly. It’s a shame, because prof. Bezouška was considered a brilliant biochemist, one of the founders of proteomics in the Czech Republic, an excellent speaker and a devoted worker. Publication activity prof. Bezouška was high – more than 100 articles in peer-reviewed international journals. No doubt there was contained a significant amount of high-quality experimental work, unfortunately in some cases contained with high probability and non-recurrent and unprintable data.

Perhaps most astonishing is that Bezouska broke into a lab refrigerator so he could tamper with samples being used to try to replicate the experiments during the investigation:

One of the students carried out verification tests, which revealed that the experimental material stored in the fridge was handled without the knowledge of laboratory personnel. After this finding was in the room once installed camera system to track events before the refrigerator. Cameras revealed that on the night of the 19th to 20.3. twice broke into the room and 21.3 do it again broke prof. Bezouška and manipulated the experimental material in the fridge. The ethics committee after hearing all witnesses, including hearing prof. Bezouška, concluded that prof. Bezouška manipulated the samples with the highest likelihood of recurrence of artificially prepared the positive results that should confirm the binding of carbohydrates to protein NKR-P1. Positive results reported prof. Bezouška regarding custody of carbohydrates to protein NKR-P1 has repeatedly failed to replicate or reproduce more independent laboratories.

For Feizi, now at Imperial College, London, it has been a long 19 years trying to correct the scientific record. A 2011 email from her to other scientists — available on the website of Česká Pozice, a Czech newspaper that has been covering the case extensively — tells the story:

a) Re: His experiments in my lab on rat NKR-P1 published in JBC2 and Nature3 in 1994, which could not be reproduced, during the course of 4 years, with fresh proteins Karel sent us, nor with a de-novo construct5’6 generated in my lab: Karel indicated that it had been decided that he would be giving details of his protocols, to you, Vladimir, for possible attempts at repeating them.

It went on:

My response to a) was that it remained very desirable for Karel to determine why, during his time in my lab, he could repeatedly make preparations of recombinant rat NKRP-1 and get the ligand-binding data published2,3, whereas my colleagues could not reproduce them either with the very tiny mounts of the protein that he sent us after his departure, nor with recombinant protein de-novo generated in my lab during the subsequent 4 years5,6. Some of the putative ligands are commercially available and could be used in any new attempts. Complete retraction should be considered of the ligand binding data in Nature paper beyond the correction that I submitted and is on record in PubMed3.

The end of Feizi’s email suggests she has been trying hard to correct the scientific record, but that Bezouska has been a barrier:

To be honest, I doubt I would be able to interest members of my group, past and present, several of whom devoted 4 years, to what amounted to unproductive research trying to reproduce the contents of the JBC2, and Nature papers3. There were also data on human CD69 protein that were published in BBRC1 and other dramatic cell signalling data on this protein that were almost accepted for publication in Cell, but I withdrew the paper as soon as major issues of reproducibility were encountered by members of my lab. Apart from attempts in my lab, I spent several working days in Prague with Karel and an experienced post doc, Christine Galustian, working with coded samples. All results with CD69 were negative in contrast to remarkable results Karel reported and was prepared for us to submit to Cell.

I should mention that following formal investigation in 1999 by a Committee involving the Chief Executives of the Medical Research Council and of the Wellcome trust at which they interviewed Karel, who attended with support from his supervisor, the late Miloslav Pospíšil, it was suggested by the Committee that these issues of reproducibility should be resolved scientifically.

My group indeed made attempts over 4 years. In the end, all we could do was to have a retraction paper in JBC5, a partial retraction termed ‘correction’ in Nature3, and a retraction paper BBRC4 retracting the published observations1 on CD69. Karel and Miloslav declined at that time to retract the Nature paper as a whole, this is why, by rule, I could only ‘correct/retract’ the parts that my group could evaluate in the absence ofbioactive recombinant NKRP-1.

Where Feizi refers to “retraction paper,” she means follow-up studies (we’ve linked to them; one is in a different journal than the original) showing the lack of reproducibility. Bezouska’s name is not on either of those retraction papers.

Neither is his name on a 1999 correction to the 1994 JBC paper to which Feizi refers in her email. That correction begins:

As we have been unable to reproduce (1) the effects of oligosaccharides on killing by natural killer (NK) cells of the rat (2), the need has arisen to re-examine the carbohydrate-binding properties reported for recombinant soluble forms of NKR-P1A, which is a disulfide-linked homodimeric transmembrane protein of lectin type at the surface of NK cells and NK-like T cells, and is an activator of cytotoxicity (3, 4). Attempts to generate the bacterially expressed soluble forms of the monomeric carbohydrate-recognition domain (CRD)1 (5) and the dimeric full-length extracellular part (2, 5) of the rat NKR-P1A have proven unsuccessful2 in contrast to previously reported data (5).

The correction then goes on to describe other experiments.

The Nature paper has been cited 255 times, according to Thomson Scientific’s Web of Knowledge.

Update, 12:45 Eastern, 7/8/13: Feizi sent us a detailed comment:

As you will have gathered a Correction was published previously, and at that time I wanted to fully retract the Article, but the Czech co-authors did not agree as they were convinced of the validity of their data.  Nature’s policy at the time was to require that all authors agree to a formal retraction.

Members of my group and various independent scientists have never been able to reproduce the results. About a year ago I was made aware of a case of scientific misconduct against Professor Bezouska and decided to approach Nature again to reconsider the retraction.  We decided that I should wait until all investigations were complete.

The case of scientific misconduct has been proven and Prof Bezouska has been dismissed from his post.  A subsequent court case for defamation has just come to an end.

This case has been covered in the Czech press. I attach two English translations and an official statement from the Institute of Microbiology in Prague.

I informed Prof Bezouska, and Dr Anna Fiserova as well as all other contactable co-authors of the intention to retract the Article, but Bezouska and  Fiserova did not respond.

 

 

 

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22 Responses

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  1. The really worriing part here was how quickly the Czech authorities switched into damage control mode to defend one of its Old Boys Club members. The evidence for fraud (dont be mistaken by the phrase Scientific Misconduct) was lucklily too compelling. Without rock solid video evidence the whole storry would be, in my opinion, covered.

    David Biedermann

    July 4, 2013 at 10:15 am

  2. Reblogged this on The Firewall.

    forgottenman2013

    July 4, 2013 at 1:49 pm

  3. Can someone parse this sentence for me?

    Cameras revealed that on the night of the 19th to 20.3. twice broke into the room and 21.3 do it again broke prof. Bezouška and manipulated the experimental material in the fridge.

    Dave Land

    July 4, 2013 at 2:38 pm

    • (I just realized that the garbled text is likely the result of machine translation from Czech to English.)

      Dave Land

      July 4, 2013 at 2:40 pm

      • Yep, automated translation. A humanized translation would be “The video cameras revealed that on the night from 19th ot 20th of March prof. Bezouška entered the room twice
        and on the 21st of March he entered again and handled the experimental material in the fridge.”

        Further, the first paragraph says that in 1999, the Medical Research Council had informed the professor, his Head of department (now deceased) and one more worker at Microbiology Institute that they were identified for scientific misconduct by MRC ethical comittee and were requested to inform the Head of Academy of medical sciences in Prague. However, Academy of sciences nor Natural sciences faculty had no knowledge of this letter from MRC until 2012 when the ethical comittee started their trial.

        Shalmai

        July 8, 2013 at 10:14 am

  4. Ah, yes – you don’t want to mess with Professor Feizi. Old school and tough as nails. 19 years but she’s got ‘im. Thank you ma’am for persisting so hard to set the record straight.

    Scrutineer

    July 4, 2013 at 2:54 pm

    • I and colleagues have met the aforementioned Prof Feizi. For one, I am not surprised in the slightest. She was clearly frustrated at the goings on and moreso at the wasted time and energies of her staff who could have been doing something far more productive with their and her own time. Clearly, they are an honest bunch.

      Remember, there are no successful grant applications in failing to reproduce work in such highly regarded science journals.

      Science heroes come from the most unlikliest of places. Kudos to the Professor, she leads where others may only dream of following.

      Stewart

      July 4, 2013 at 3:27 pm

      • You know what would make things like less a lot less painful? If you could simply publish negative results without all this ‘reluctance’ from journals to accept them. Honestly, if you were to take a survey of how many scientists out there have been unable to replicate experiments in high profile journals, and just ended up keeping that data in a file drawer and thinking to themselves ‘I’ve proven to myself that the findings of paper X are incorrect’, I bet it would be a disturbingly high number. We desperately need to change this!

        Booker

        July 4, 2013 at 8:49 pm

        • True. A well done study that does not replicate a high profile study deserves to be published, if not for other reasons to give an idea of the roubustness of the original findings. It is possible that the original findings were real, but it is important to know how sensitive they are to small changes in parameters, for example. Usually, the high profile papers make broad claims of high impact and generality that later on turn out to be incorrect.

          Average PI

          July 5, 2013 at 5:13 am

          • I’ve been on the editorial boards of several journals for over 40 years. I can understand the reluctance to use precious journal space for a retraction. I also understand how important it is to get the word out when someone fails to replicate published results. I suggest that the space problem can be solved by putting the negative results on the Internet. It’s almost infinitely expandable. Getting word of the negative results to the people who are depending on the original article, however, is not so easily solved.

            Joseph P. Martino

            July 5, 2013 at 5:03 pm

          • And what’s in it for an academic to waste his/her time and effort on putting the negative results on the Internet, and who would fund such an experiment? All academics pursue publishable research. This is the main problem.

            aceil

            July 6, 2013 at 9:58 am

        • @Booker: here is my (double) entry into the survey (Science & Nature Materials). What is ‘funny’ is that in both cases, the argument has been that these would be ‘unlikely to be of interest to the wide audience etc’ implying that this wide audience is not really bothered by the material reality of what is published.
          http://raphazlab.wordpress.com/2012/12/20/stripy-timeline/ (scroll down to 18 sept 2009 for the Nat Materials decision)

          Raphaël Lévy

          July 5, 2013 at 8:45 am

          • It is unlikely that any funding would be provided for those scientists willing to reproduce questionable costly experiments.

            aceil

            July 6, 2013 at 10:21 am

        • I agree. I know of several authors who publish irreproducible articles with impunity. If we could publish negative results, it would spare future students and postdocs the effort of trying to reproduce those results. It might even keep those scientists from publishing their false results.

          enzo

          July 5, 2013 at 10:58 am

        • Wonderful idea!! I have about twenty notebooks worth of data that yielded negative results. Wow i bet I can get a dozen publications out of that at least. And why bother to try for experiments that work if publications about projects that did not work are just as worthwhile.

          franko

          July 5, 2013 at 3:18 pm

  5. It is very satisfying that this Nature paper finally has been retracted, this should have been done many years ago. For researchers working in this field (me included), it was clear early on after publication that the conclusions were highly dubious. If I understand the translated press release correctly, it is encouraging that this case has been followed by the Czech ethical committee and the newspaper mentioned, thanks also to Prof Feizi for eventually resolving this case.

    It remains a concern that researchers can boost their scientific career with highly dubious and even retracted publications on their CV.

    John T. Vaage

    July 4, 2013 at 4:38 pm

  6. Whatever may be the factors responsible for breaking-in, doctoring,modifying,any playful act, on the samples or evidences–certainly leads to unintelligible research results,which further lead to erratic research. And the irony is–we laymen believe such research outputs, take them very serious…change our perceptions.

    CenterPoise Inc.

    July 5, 2013 at 11:25 am

  7. Well I can’t follow either the science, part of that “wider audience” doncha know, or the translation; but there’s one thing I probably could follow. The MONEY. when in doubt always, always follow the Money. How much,from whom, to whom, and how much went missing will answer any question about why.

    ARTHUR BROGDEN

    July 5, 2013 at 2:25 pm

    • Nail, head, hammer Arthur!
      Think REF.

      Think hypothetically in the University of Somewhere composed of several schools, lets say the Dean of the Biomedical School depends on good amounts of grant money to employ the various people to get decent enough publications to be REF returnable and , hey ho….everyone wins. The Dean looks good, the school looks good, the researchers and academics look good. One grant, of course, can lead to many more.

      Now then, if the Dean of the Biomedical School at University of Somewhere happens to hear about any alleged science-fraud of one of the big grant holders that enabled REF to be returned favourably, that enabled the school to look good, and everyone in it – take a wild guess at the likelihood of anything but a verifiable squashing of any allegations.

      Always follow the money. That means grants and all associated activities, past, present and future. In todays digital age, thats not impossible.

      The only factors the Dean in question has not considered is that of integrity of reputation. And, of course, the Law. Besides, that is, the long term damage to society.

      Fraud and embezzlement are crimes and not everyone has the lack of scruples to match the Dean, and those associated with various naughty activities in question.

      Stewart

      July 5, 2013 at 5:34 pm

  8. Reblogged this on lab ant and commented:
    Well science is not always boring! but fraud is a serious issue…..indeed

    pamminge

    July 5, 2013 at 2:45 pm

  9. The MRC is pleased that this paper has been retracted, but it is very regrettable that it has taken so long. We very much endorse the comments above in support of Ten Feizi during this protracted process. The MRC funded the original research and indeed the work that Ten and her colleagues did to try to reproduce it (as part of our long term support for her research programme). Generally, the MRC recognises the importance of checking reproducibility where a strong case can be made, and will provide funding for such studies. The original allegation was one of the factors that led he MRC to formalise its scientific misconduct policy and procedure; the current version is at: http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC005820

    • I for one hope this will enable those doing honest science to contribute to our society and improve the lives of patients. Without honest science Tony, we are all losers. We need a head of a powerful and influencial organisation for Honest Research.

      All researchers applying for funding (MRC or other) MUST be a bona fide member to be eligible, and demonstrate integrity, rigor and openness with random laboratory record inspections by the respective organisation.

      If Professor Feizi could lead such an organisation I see great strides possible.

      Stewart

      July 9, 2013 at 1:26 pm


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