Retraction Watch

Tracking retractions as a window into the scientific process

Aftermath: Gut-wrenching misstep leads to retraction, frayed feelings and a paperless postdoc

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Graham Ellis-Davies says January 25th was one of the worst days of his life. That was when the journal ChemBioChem retracted an article, published barely two weeks earlier, for a mistake Ellis-Davies blames squarely on himself.

The fallout has been nearly two months of painful self-recrimination, a tattered friendship and, perhaps most significant, he adds, the wasted effort of a postdoc who poured months of research into a now worthless publication.

The tale begins in the early 2000s, when Ellis-Davies, a renowned chemical biologist at Mount Sinai School of Medicine, first hooked up with Jeff Magee, then a promising neuroscientist at Louisiana State University. The two spent a week together at Magee’s New Orleans lab, collaborating on what would become a 2003 publication in the Journal of Physiology.

The researchers remained friends, and had a chance to work together again not long ago when Ellis-Davies and a few of his colleagues, including his postdoc Srinivas Kantevari, went to visit Magee at his new digs in Ashburn, Va., at the Janelia Farm campus of the Howard Hughes Medical Institute.

The two groups were interested in exploiting a technique that Ellis-Davies helped discover to get over the serious hurdle of solubility of molecules, such as drugs, in the body.

Ellis-Davies explains:

Solubility is really a fundamental problem, particularly for the central nervous system and peripheral nervous system. About 50% of a drug, by weight, is non-clinical material that promotes solubilization in plasma or other buffer.

For drugs that have to cross the blood-brain barrier — a membrane that acts as a filter to protect the brain from large, potentially toxic molecules — all that extra matter is like a sign that screams “don’t let me in,” making the development of effective neuroactive medications difficult.

A solution to the solubility problem would be to dispense with the chaperoning substance entirely. That, of course, raises a second issue: that the drug would become immediately active in the body, and thus far less useful, if useful at all.

Ellis-Davies has been working on ways of avoiding the solubility problem by keeping potentially therapeutic molecules inert until they can be activated by a signal. Ellis-Davies and his colleagues graft fat-loving molecules onto the end of neurotransmitters, rendering them inert. But by shining a finely tuned laser onto the fatty chain — which he describes as a kind of chemical antenna — they can activate the neurotransmitter.

The laser is so precise that it can stimulate the firing of a single synapse, thus releasing the same amount of a neurotransmitter as would be spit forth from a lone neuron.

The beam becomes like a conductor’s baton, a magic wand.

At least, that’s the theory. In fact, what Ellis-Davies discovered was that the idea is much harder to implement in practice.

The product of the one-day site visit (at which Magee agreed to provide the Mount Sinai team with tracers to conduct their experiments) was the hard-won realization that the creating a reliable “photochemical scaffold” for releasing neurotransmitters is maddeningly difficult, Ellis-Davies says.

Not wanting to squander the leg work, he and Kantevari wrote up a paper, “Development of Anionically Decorated 2-(ortho-Nitrophenyl)-Propyl-Caged Neurotransmitters for Photolysis in vitro and in vivo,” describing the effort. The article was not a boast about success, Ellis-Davies insists, but an effort highlight for other scientists the pitfalls of  making the best possible scaffolds. Indeed, the discussion section carries a “cautionary note” for the field about how the problem is “not trivial” to solve.

It’s an account of how we didn’t solve the problem. We wrote it in a way to say we didn’t succeed.

Ellis-Davies says he showed the manuscript to collaborators at the University of Pennsylvania, who okayed the paper, but that he neglected to send a copy to Magee prior to submitting it to ChemBioChem. Although the journal asked Ellis-Davies to complete an electronic form vouching for the data and authorship, it did not require him to collect signatures from every author — a step, he says, that doubtless would have prevented what followed.

The article appeared on January 10. The retraction notice came 15 days later:

The article Srinivas Kantevari, Judit K. Makara, Attila Losonczy,Tommaso Fellin, Philip G. Haydon, Jeffrey C. Magee, and Graham C. R. Ellis-Davies, published online on 10th January 2011 in Wiley Online Library (www.onlinelibrary.wiley.com, 10.1002/cbic.201000254) has been retracted (25th January 2011) by the journal editor-in-chief, Dr. Peter Gölitz, and Wiley-VCH, in accordance with the “EUCheMS Ethical Guidelines for Publication in Journals and Re­views” adhered to by the journal (EUCheMS Ethical Guidelines for Publication in Jour­nals and Reviews, 2006, http://www.euchems.org/Publications/index.asp). J.K.M., A.L. and J.C.M. were not informed about the manuscript prior to its publication and hold that the data presented in Figure 3 and related text are too preliminary for publica­tion.

Magee, who has not responded to a Retraction Watch request for comment on the paper, contacted Ellis-Davies and said he had regarded the research as “anecdotal” and not for publication — at least, not with his name on it. A “very surprised” Ellis-Davies responded that he regarded the work “as proof of concept” and thus worth reporting. Such experiments are very common in his field, he told us.

In the end, Ellis-Davies realized that the group at Janelia would not consent to be part of the paper, and he agreed to retract it.

The paper couldn’t really exist without the work done in his lab. It has no meaning.

A contrite Ellis-Davies says the episode has been the worst of his career — indeed, of his entire life. “I made a huge mistake,” he says, insisting that Magee and his Janelia colleagues were “perfectly correct” to seek the retraction. And he feels especially for Kantevari, who is now back in India.

The first author has put a huge amount of work into it, he’s the one that’s most affected by it.

But he’s not ready to throw away the idea.

I hope to revisit the biology with another friend of mine, when the dust settles. In a way, I actually quite like the paper. I think the core of it is correct.

The next time he has a cross-lab collaboration, though, he’ll be sure to vet whatever manuscript that emerges with all of his co-authors:

I’m 53. Why am I still learning things the hard way?

Written by amarcus41

March 9th, 2011 at 2:00 pm

Posted in Uncategorized

Comments
  • elaine newman March 9, 2011 at 2:49 pm

    Is there anyone in any walk of life who thinks they can sign someone else’s name to any statement of any kind without their consent? Ellis-Davies SHOUL be sorry for the postdoc.Maybe he should consider not hiring any more postdocs.

  • elaine newman March 9, 2011 at 2:50 pm

    forgotto askforfollowup

  • Ph Starck March 9, 2011 at 3:25 pm

    >I’m 53. Why am I still learning things the hard way?

    Well, I guess that if you are 53 and think that sending a manuscript without the authors knowing of it is the way to go, then you might deserve to learn that way.

    Btw, the first author of the retracted study, Dr. Kantevari, has a Nature Protocols first author paper in 2011 plus another 3 papers with Prof. Ellis-Davies, so I guess you cannot say he is paperless.

    As reported from a previous commenter, you do not have lots of pictures of american researchers linked to your posts, so here is the picture of Prof. Ellis-Davies in case you are willing to modify the trend: http://www.med.upenn.edu/ins/faculty/ellis_davies.htm

    • Srinivas June 16, 2011 at 5:24 am

      Btw, the first author of the retracted study, Dr. Kantevari, has a Nature Protocols first author paper in 2011 plus another 3 papers with Prof. Ellis-Davies, so I guess you cannot say he is paperless.

      The statement of “he is paperless” is wrong. I know how hard the research presented here came out. You must know from the above write up before writing comment.
      Please donot post such messages

      • amarcus41 June 16, 2011 at 10:42 am

        I think there’s something of a misunderstanding here, or at least too literal a reading of what we wrote in that post. The point was not that Dr. Kantevari never published anything. Rather, it was that he lost a publication through no fault of his own after spending a substantial amount of time on a project–something Dr. Ellis-Davies lamented.
        Thanks for reading!
        AM

  • ok now I am sure March 9, 2011 at 3:36 pm

    I would be happy to know the reason why all my comments are awaiting moderation. I guess it has to do with the never published comment to your post on the German minister? cmon guys, this is silly.

    • ivanoransky March 9, 2011 at 3:46 pm

      I tried to send this to you by email, but you’ve left a fake email address, which makes it difficult:

      The way we have the site set up, your first comment always requires moderation. Once we approve one, all of them will go straight through — unless we then decline to post one. That’s the case with yours because you chose to attempt to post a libelous statement about zu Guttenberg. Libel is not “silly.” We are happy to approve future comments that are not libelous.

      As far as your comment about not having any pictures of American researchers, please see our response to the last baseless comment to which you refer: http://www.retractionwatch.com/2011/03/02/nejm-retracts-potti-paper/#comment-1842

      We have of course used photos of American researchers; here’s an example: http://www.retractionwatch.com/2011/01/05/why-was-that-paper-retracted-editor-to-retraction-watch-its-none-of-your-damn-business/

      The fact is, we don’t usually use photos, we use journal covers, as I’m sure you’ve realized given your careful attention to Retraction Watch — which we appreciate.

  • William Raillant-Clark March 9, 2011 at 5:09 pm

    Wow, I don’t even send out a *press release* without the researchers approving it first…

  • D. Marcus March 9, 2011 at 9:44 pm

    I appreciate empathy and applaud the writers of retraction watch for not taking pleasure from the mistakes and worse of others.

    • William Raillant-Clark March 10, 2011 at 9:41 am

      I certainly hope that my own comment does not reek of schadenfreude – as Neuroskeptic and Clare Francis point out below, mistakes are human.

      • clare francis March 10, 2011 at 10:18 am

        I didn’t mean to appear “soft”, just reasonable.

        I like this quote:

        “Science and pseudoscience differs not in that one contains fraud and bad practices and the other does not, but in that in science there is at least a willingness to clear up the mess sometimes.
        Retraction Watch is a brilliant idea to present this effort for self correction and openness of science.”

        which was posted on Retraction by

        Gabor Hrasko
        President – Hungarian Skeptic Society

        Gabor Hrasko

        October 17, 2010 at 4:22 am

        What I do not like is when you point out things that do not make sense to the authorities, journal editors and suchlike, but this is met with either obfuscation, or no willingness to clear up the mess, even when they can see something is wrong. That’s when things get serious and people are entitled to complain.

  • Neuroskeptic March 10, 2011 at 3:43 am

    I think commentators are being too harsh here. This was clearly an honest mistake, Ellis-Davies stood to gain nothing from it, and I’m sure he thought he was being helpful by putting Magee’s name on the paper. Naive maybe but if that’s a crime in science the prisons would be overflowing.

  • clare francis March 10, 2011 at 7:28 am

    It looks like an honest mistake, if not a bit naive. Sad, maybe should be published as a short story (in fact it has by Retraction Watch).

    Surely the essence of Retraction Watch is to raise the ethical standards by making things public and open for public discussion? I hope that science is about being honest, not about being pernickety. You show your colleagues your results, see if they can repeat them. Let them do the experiment blind. That’s what I feel it should be about. Perhaps I am mistaken.

    I believe that real fraudsters play on the genuine fear that many scientists have of having to retract their work at some future data. If the data has been collected and recorded in a true and accurate way that is the best you can expect. Interpretations will change until the end of time as we get to know more.

    Single “slips” should be corrected as soon as possible. Multiple “slips” should make you start to wonder. If people do these things systematically they should be removed from the pool.

  • Barbara March 12, 2011 at 10:08 pm

    This kind of mistake happens. It shouldn’t. Simple politeness suggests that it shouldn’t.

    I am co-author on a recent paper with a different kind of error. The first author wrote the paper, sent it to all of us, we sent back edits, and we agreed on a manuscript for submission to the journal. Then the first author added data that, shall we say, we disagree about how to interpret. He also changed the article title to reflect this data. I knew nothing about it until it showed up in print.

    I’m being polite about it — we have reason to work together in the future. However, I’ll be very careful about co-authoring anything with him.

    And the most frustrating thing is this: The first author wasn’t really happy about working with me in the first place, and if he’d told us about the changes (and insisted on making them), I would have withdrawn as co-author. He could have published without me. (The discovery was definitely his, though I was involved in studying it and helped prepare it for publication.)

    On the other hand . . . One day I found out by accident that I was co-author on a different paper, already published. I had done important work on an early part of the study, then left the lab. Ethically, the other authors really should have shown me a late draft (at least) before submitting the article. In this case, though, the paper is very nice and I don’t object to the results, though the process should have been better.

    I do feel badly for the post-doc in the case reported here.

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