An Australian university has put a hold on trials of an experimental drug for skin cancer whose main developer has been dogged by charges of research misconduct for several years.
The Australian Broadcasting Corporation is reporting that the University of New South Wales has suspended trials of the drug, DZ13, while it investigates the work of Levon Khachigian, who is leading the studies.
According to the news organization, Khachigian and his group were cleared by the school in two prior inquiries. However, additional accusations of misconduct — specifically involving image manipulation and misuse — prompted a third investigation.
We’ve found four retractions of Khachigian’s studies, from the Journal of Biological Chemistry and Biochemical and Biophysical Research Communications, between 2009 and 2010 (before the launch of Retraction Watch).
They are:
1. Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1beta and forms a cytokine-inducible gene-silencing complex with NF-kappab p65 and interferon regulatory factor-1. (cited five times, according to Thomson Scientific’s Web of Knowledge)
Liu MY, Khachigian LM.
J Biol Chem. 2009 Dec 11;284(50):35101-12. doi: 10.1074/jbc.M109.061903. Epub 2009 Oct 20. Erratum in: J Biol Chem. 2010 Feb 5;285(6):4263. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
Zhang N, Khachigian LM.
J Biol Chem. 2009 Oct 9;284(41):27933-43. doi: 10.1074/jbc.M109.025742. Epub 2009 Jul 31. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
Zhang C, Song QH, Khachigian LM, Lubenec I, Shie JL, Yang B, Li J, Tian Y.
Biochem Biophys Res Commun. 2009 Mar 13;380(3):689-94. doi: 10.1016/j.bbrc.2009.01.151. Epub 2009 Jan 29. Retraction in: Biochem Biophys Res Commun. 2009 Oct 16;388(2):464.
4. Ets-1 positively regulates Fas ligand transcription via cooperative interactions with Sp1. (cited 49 times)
Kavurma MM, Bobryshev Y, Khachigian LM.
J Biol Chem. 2002 Sep 27;277(39):36244-52. Epub 2002 Apr 22. Retraction in: J Biol Chem. 2010 Jul 9;285(28):21902.
The retraction notices in the JBC are, well, uninformative, as they’ve unfortunately been in the past. Consider:
This article has been withdrawn by the authors.
But there was this earlier errata for “Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1β and forms a cytokine-inducible gene-silencing complex with NF-κB p65 and interferon regulatory factor-1”:
The published version of the left panel of Fig. 4C inadvertently duplicated the first five lanes from the right panel of Fig. 2A. The correct version of Fig. 4C is shown below.
PAGE 35110:
In the published version of Fig. 6B, the fourth panel was inadvertently duplicated as the sixth panel. The correct version of Fig. 6B is shown below.
These additions and corrections do not result in any change in the conclusions of the article.
Researchers — including David Vaux — have raised questions about another 2010 article in the JBC. That paper’s not identified, but we think it might be “c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins,” which appeared that year.
The ABC quotes Kachigian saying:
the research was not flawed. The independent inquiry panel found no case of research misconduct, nor any evidence of falsification, fabrication or misrepresentation of data.
The story gets pretty gnarly, so it’s worth reading ABC’s coverage.
I am curious as to how research misconduct with serious and perhaps life threatening consequences is remedied?
OK, there are several blots that need examination.
For starters:
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0039811&representation=PDF
Fig 3A, EGFR, lane 2 (2.5). Under the band there is a unusual clear background on the left, but normal on the right. Has the image been digitally smoothened?
The background on many of the blots is very even. Most of the B-actin bands are all saturated, and therefore cannot be quantitated reliably.
Unfortunately, I feel a deeper story about to unfold on this one.
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0039811&representation=PDF
If you look at Fig 5 the PD153035 treatment image looks like the AG1478 treatment image upside down. I wonder how that could have happened….
…inadvertently?
This paper (PLoS One, pointed out by Stewart August 12, 2013) has now been corrected:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0039811
“There was an inadvertent error in the assembly of panels ‘AG1478, IL-1b’ and ‘PD153035, IL-1b’ in Figure 5 of this article; as a result, the panels were duplicated in error. A new figure from separate experiments is provided herewith:…”
“Inadvertent error” strikes again!
In the “correct version of Fig. 4C” above, lanes 4 and 5 look similar to lanes 6 and 7.
totally agree, ! the same observation struck me, and this is supposed to be the ‘corrected ‘ version ?
How can misconduct happen when there are so many people around you.
Don’t you just love the phrasing “inadvertently duplicated”in the errata? How is anyone supposed to believe that?
Great news!
Some issues with Khacigian’s papers have been discussed in the comments section of previous blog posts:
http://www.retractionwatch.com/2012/12/27/stem-cell-retraction-leaves-grad-student-in-limbo-reveals-tangled-web-of-industry-academic-ties/
http://www.retractionwatch.com/2013/06/07/a-mega-correction-for-rui-curi-whose-lawyers-threated-to-sue-science-fraud-org/
Thanks for the interesting further details when I last mentioned this to you guys on twitter there was no further description of what was wrong with published images. UNSW has had a number of scandals in recent years so this is going to look awfully bad.
The PDF linked to in ABC’s coverage with the statements from Khacigian’s lawyer (btw, the usual stuff with this is just a personal vendetta case by a dismissed employee, so it is very important that David Vaux once again has stepped up) makes it pretty clear, that it is the JBC paper you guys have linked to in the RW post:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823545/figure/F1/
Fig 1C, Elastin panels, the treatment Dz13 and control Dz13scr are identical, just different magnification.
Hmmm, I agree, especially when you consider that of the four retracted papers by the lab, the only name common to all of them is Kachigians. Hard to point the finger at a disgruntled employee when it is ultimately his responsibility (and that of his peer reviewers) to ensure that the data is correct. Bravo to Professor Vaux for picking up on it, and having the courage to take it further, in particular because Australia has no easy recourse to do so, ie no proper independent panels to deal with these things, it takes someone with clout to make themselves heard.
UNSW has for too long been judge and jury to itself ( I’m thinking Bruce Hall here and I know of at least one name who will soon follow Kachigians, he is unfortunatley not alone). When attractive industry money grows research projects the temptation for the researcher is to bring in the results that our sponsor is asking for, to justify the next milestone payment. The successful head of the lab is then touted by UNSW as being the gold standard that his or her colleagues should all aim for, and then when the results come in and are less than exciting, it is difficult to bite the hand that feeds you, leading to corruption of results.
There is alot of pressure to produce the next wonderdrug, when the pressure becomes too much the head of the lab starts to ask his/or her team to bring in the next milestone payment, rather than ask them to validate the drug candidate correctly – and have the courage to accept the negative results for what they are. We need more courage shown by the scientists who witness this sort of behaviour, and more support shown to them by the institutions responsible for creating the pressure to succeed, instead of the stock standard reply we just got from UNSW…we’d like to point out that the whistleblower in question did not have their contract renewed…discredit, discredit ..come on UNSW – lets try to do better this time!
Kangaroofrog – would really like to talk to you – how can I reach you?
Ugly splicing, especially since the control (Coomassie) is not spliced:
http://jnci.oxfordjournals.org/content/96/9/683/F2.large.jpg
More ugly splicing:
http://www.jbc.org/content/279/39/40289/F2.large.jpg
http://bloodjournal.hematologylibrary.org/content/107/6/2322/F3.large.jpg
And a funny correction:
http://mcr.aacrjournals.org/content/7/9/1594
Thank you!
As a student of the same university, I find it disappointing that this can go unnoticed for so long. This bloke has an apparently mint CV, and any student would have previously loved to research in his team.
Of course, one wonders how much of his ‘mint CV’ is due to fraudulent work…
Can research not be celebrated purely by virtue of the fact you’re contributing to scientific knowledge, without a bias for positive results?
I know Levon’s former PhD/Postdoc who worked for me as RA. I did not trust any results she was generating. She could not even troubleshoot western blot nor realtime PCR. And in her CV and interview she claimed she was an expert in these techniques. Anytime the questions were raised regarding her results she got physically and verbally abusive. Eventually I had to call security.
Levon gave her a good reference.
The professor of my department supported her because they were getting result for publication by hook or by crook. Most students/postdoc under pressure of publication or getting grant are making up results at UNSW. The person who raises voice against them is fired on the spot…..I am glad the truth is out…..
A correction to has been published-
http://www.jbc.org/content/288/44/31918.full
c-Jun regulates shear- and injury-inducible Egr-1 expression, vein graft stenosis after autologous end-to-side transplantation in rabbits, and intimal hyperplasia in human saphenous veins.
Jun Ni, Alla Waldman and Levon M. Khachigian
VOLUME 285 (2010) PAGES 4038–4048
“The original versions of Figs. 1, 5, and 6 contained incorrect micrographs.”
Corrections have been provided for Fig. 1C, 5D,F, 6B.
– That means the only duplicate image that remains to be corrected is in Fig. 6G (unless there are more…).
Fresh concerns over research conducted by University of New South Wales professor Levon Khachigian
http://www.abc.net.au/news/2013-10-22/fresh-concerns-over-prof-levon-khacigian-research/5038644
It’s very noble for Vaux to call for an immediate commission into such mishaps in scientific reporting, but in a country where funding is already low due to the fed govt, and where universities cannot support their researchers at all, with a public who would rather support their kids doing sports and not academia in general, I do not see how this is going to happen. AT LEAST, now funding by NHMRC may be shared by all, and not the elitists, especially those working out of Royal Pde in Melbourne. I know, because I was one of them.