Online commentary on papers allows scooped authors to argue their priority?

A fascinating vignette into the glorious future of online commenting on papers was passed along to me by a reader.

Laurén and colleagues published a paper in Nature in February 2009 describing a phenomenon related to understanding the process of Alzheimer's disease and a possible role for prion. From the Abstract we can glean the essentials.

Here we identify the cellular prion protein (PrPC) as an amyloid-β-oligomer receptor by expression cloning. Amyloid-β oligomers bind with nanomolar affinity to PrPC, but the interaction does not require the infectious PrPSc conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-β oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-β-oligomer binding to PrPC and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-β. Thus, PrPC is a mediator of amyloid-β-oligomer-induced synaptic dysfunction, and PrPC-specific pharmaceuticals may have therapeutic potential for Alzheimer’s disease.

This is grand stuff. Treatment for AD continues to be a holding/rearguard action to slow progression and maintain cognitive function as long as possible. Our treatments are not so great, even at that limited role. So any new therapeutic targets, particularly ones that interfere with the pathological processes (as opposed to treating the symptoms of such unrelenting processes), are a BigDeal (or BFD as the US Vice President would have it).

However, a "brief communication arising" which has just been published in Nature says "uh-uh, not so fast". Kessel et al (2010) conclude the following from their results:

Laurén et al. suggested that binding between oligomeric amyloid-β ... and the cellular prion protein (PrPC)8 is necessary for synaptic perturbations. Here we show that PrPC is not required for amyloid-β-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-β-mediated synaptic defects do not require PrPc.

Laurén et al provided a response, in Nature, to possibly explain the different outcomes.

Great, right? Big new idea/finding, some people jump on it and either confirm or question the results. These get published, and a dialog results. Happy, happy, amirite?

Well, somebody isn't too thrilled and has offered a comment on the Kessels et al paper. A. Aguzzi congratulated the group on their study and then points out that they scooped him. Not by getting their first in offering a counterpoint to Laurén et al

on May 19th, 2009, I have reported my lab's finding indicating that the Prnp genotype (Prnp+/+ vs +/-, /, and overexpressors) exerts no influence on LTP degradation in APPPS1 transgenic mice at the CDD conference in Rome.

but by being the first to be able to publish a counterpoint in Nature.

Marie-Therese Heemels, Nature editor, attended the talk and asked me (during the lunch break) to send her my findings to be considered for publication as ?brief matters arising? in Nature. (3) Following Dr. Heemels? request, we rapidly submitted our paper (Calella et al.). The paper was rejected on August 21, 2009 despite largely positive referees? comments (which I shall be happy to post separately if the blog editor allows for sufficient space). (4) because of the favorable, encouraging comments we opted to perform additional experimentation and to resubmit a further version of our paper, which was again rejected on May 5th, 2010 despite additional commendatory comments by the referees.

Our manuscript was then submitted to EMBO Molecular Medicine, where it received a rather enthusiastic reception and was finally published on July 21st, 2010

Yowsa! Now, I will admit right up front that I am unable to reasonably judge the quality of the papers of Kessels et al and of A. Aguzzi (Calella et al, 2010; EMBO Mol Med) so as to be able to determine why the one was worthy of Nature publication (as correspondence arising) and the other was not. Nor am I able to determine if one is a "better" criticism, counterpoint or elucidation of Laurén et al. But one thing does seem obvious to me. If the publication of Kessels et al in Nature was driven mostly by the mere fact it questioned or pared back the claims of Laurén et al then it would seem that Aguzzi's work was similarly meritorious on this criterion.

I will be fascinated to see if Nature responds to this in any way, including deleting the comment. Clearly they are going to have to take the view that Aguzzi's description of the reviews as largely positive and commendatory is a bit inaccurate. Right? Because beyond the scientific view of the reviewers, the only possible role for nonscientific professional editors is to judge hotness, relevance, impact and all that. And clearly since they published Kessels et al (which Nature received 22 Feb 2010 and accepted 01 Apr 2010), they think critique of Laurén et al is sufficient justification. If Aguzzi's contention that Nature rejected his second submission 05 May 2010 is valid, obviously the journal had both of these criticisms of Laurén et al in hand at the same time and chose to publish one but not the other.

I'd be interested to hear their thinking on that one.

22 responses so far

  • juniorprof says:

    This is going to be quite interesting to watch unfold!

  • Nat says:

    Getcha popcorn!

  • Odyssey says:

    Got my lawnchair, cooler full of beer and big bag of chips. I'm ready.

  • bill says:

    Editor Heemels appears to have trained in the lab of one Hidde L Pleogh, who has published thirteen papers with Ton Schumacher (several of those with Heemels as co-author), who in turn has published nine papers with Helmut Kessels (whose total output to date is around 17 papers).

    Just sayin'.

    • DrugMonkey says:

      You have to be joking bill. Tell me you are just funning! No? ....oh this is gonna get good.

      (and where's the Neurotree.org training/collaboration chart on these folks? that'd be a nice little visual aid, wouldn't it?)

    • DrugMonkey says:

      just because I was curious, the Kessels/Schumacher pubs run from 2000-2006 and the Heemels/Schumacher/Pleogh pubs run from 1990-1994.

  • DrugMonkey says:

    Hey, I wonder who got the A. Aguzzi paper to review back in August 2009 when he originally submitted it?

  • DrugMonkey says:

    Yeah, they might have been bad reviews or at least damned with faint praise.

  • DrugMonkey says:

    As some dude was reminding me today, we have to leave open the possibility that Aguzzi's work wasn't as good until the EMBO submission...Kessels and crew may have presented a better manuscript at the start. So if Nature went with better over first on this one I have to credit them.

  • Alteredstory says:

    I would love to see a list of titles rejected and why, some time.

    Really, I think such a list wouldn't be very nice for the people on it (and sometimes it's because there's no more room in an issue or something like that maybe, I don't know) but I AM curious to see what it is that doesn't make it into daylight.

  • tideliar says:

    Hopefully this will be resolved with element of transparency, but considering the brand damage that could happen IF (<- big if, no accusations here) it turns out an editor was biased then this might well be hushed up and hidden from sight... If it turns out Nature editors are skewing towards their old labs and collaborators then there will be a lot of noise.

    Funnily enough, when word got out at work that I was interviewing at Nature Neuroscience (back in 2008) every PI in the neuro-group suddenly wanted to be my bosombuddyandpal...

  • DrugMonkey says:

    of course they are "skewing" to their old labs and collaborators, particularly if they are already big GlamorMag operations. It is only natural. It is en-worsened by the fact that GlamorMag professional editors are quite open about the fact they think it is a significant part of their job to go out to labs and meetings to get schmoozed by the in-crowd. of course this has an effect. is it *specifically* biased though?

    the question for today is how often do you have a genuine head-to-head situation in which the work is clearly of similar importance, quality and scope? *Do* we have that here (and my rumor mill is already saying yes)? Does the quality and scope of the EMBO publication reflect the quality and scope of the last version that Nature rejected? Were the reviews as good as the senior author A.A. is suggesting? Who reviewed the respective submissions anyway?

  • tideliar says:

    Just read the papers and was interested to note that Malinow is the corresponding author on the Kessels Brief Communication. Anything with Malinow's name on it is a big deal because he's a big hitter. I'll bet a shiny internet sixpence that had something to do with it... if I had the choice of two communications and one was from a big hitter (not that AA isn't, he has a hell of publication record too, but RM has 'status') I know which one I would choose.

    (funnily enough when I interviewed at NN one of the prep papers I had to cover was one of RMs and I said I would have rejected it as not NN-worthy (good work, but nothing super new). The askance looks told me they had just published it and I had stepped in the shit).

    Re your question, "Does the quality and scope of the EMBO publication reflect the quality and scope of the last version that Nature rejected? Were the reviews as good as the senior author A.A. is suggesting? Who reviewed the respective submissions anyway?"

    I wonder too. I'm leaning towards them being equally good papers from a science-practice standpoint, but one having a head start in impact and readability maybe? It has to be that or else this is just shear bloody-minded bias with malice aforethought and that troubles me.

    Unless Howie Jacobs or Marie Hemmel joins in, or AA published his critiques we'll never know I fear (at least until SfN when we can have a good gossip with the primaries involved here...like they'd deign to talk to me...)

  • Nat says:

    Damn this is getting juicy. *spurts butter all over popcorn*

    Thanks bill and tideliar for digging deeper.

  • DrugMonkey says:

    if I had the choice of two communications and one was from a big hitter (not that AA isn’t, he has a hell of publication record too, but RM has ‘status’) I know which one I would choose.

    but why "choose"?

    These GlamourMags have been known to co-publish under dubious and suspicious timelines you know. Wouldn't having both of the papers really draw the eye? of course, that might mean some theoretical dilution of the eventual citations- can't have that, can we? (Did I mention I hate GlamourScience and all that this does to actual, lower case, science?)

  • Nat says:

    paper was rejected on August 21, 2009 despite largely positive referees? comments (which I shall be happy to post separately if the blog editor allows for sufficient space)

    The dude did say he'd post the reviewers' comments. Maybe he could post them here? Whaddya say DM?

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  • Adriano Aguzzi says:

    According to Nature, our paper was rejected because we did not exactly reproduce Lauren's experiment (throwing A-beta at slices) but chose to perform a different, more involved (and - I maintain - more valid) experiment, namely to cross PrP-deficient and PrP-overexpressing mice to A-beta overexpressors.

    One may have different opinions on this issue - mine is that we went one step further than both Malinow and Strittmatter! The flurry of subsequent papers reproducing our findings seems to confirm my view.

    One poster said that I may have a hell of a publication record but Roberto Malinow has "status". Whatever that may mean, our paper is being quoted like crazy (already 18 times in 9 months since its publication, according to Google Scholar), and therefore I am rather relaxed about the whole affair.

  • drugmonkey says:

    While I am happy this is all working out great for your work, AA, the fact is that if you are correct that your paper was "more valid" and subsequent progress of science shows that...then Nature screwed up. One might think they would be interested in why that happened for their own purposes so as to improve their future selection.

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