Scientist raised serious questions about 2008 Cell study by Amy Wagers

Amy Wagers, a Harvard stem cell researcher, retracted a Nature study last week and has another published paper under scrutiny at Blood. Retraction Watch has now learned that a 2008 Cell paper she co-authored drew significant criticism from a stem cell researcher at Children’s National Medical Center.

In the paper, Wagers and her team said they were able to prepare a set of muscle cells that reversed some of the effects of muscular dystrophy in a mouse model of the disease. In a 2008 letter to the editor of Cell, however, Terence Partridge wrote

that the data presented support neither the notion that a new class of myogenic cell has been isolated nor that successful grafts of this new cell into muscles of dystrophic mdx mice leads to near normalization of muscle function.

Wagers’ team responded to the letter, saying that Partridge “seems to disregard direct evidence presented in our study that [skeletal muscle precursors] are a distinct subset of muscle satellite cells” and that the model he used to re-analyze their data was flawed:

In conclusion, although we appreciate the close consideration of our paper by Dr. Partridge, we show here that his reanalysis of our data is not based on proper statistical methods and therefore does not in fact challenge the original interpretations of our paper.

Partridge — who was well aware of Wager’s reputation for questioning the work of others — was not satisfied with the Wagers rebuttal, and he published another response online in Cell. (Scroll to the bottom of this page to see it, and thanks to Phil Score for finding the URL.) (We have not been able to find a URL, and he believes it may have just disappeared.) That response concluded:

The false claim that any of my objections involved statistical analysis leads the authors to answer criticisms I did not make, to the neglect of answering those that I did make.

Shane Mayack, who was until recently a post-doc in Wagers’ lab and is listed as an author of both the Nature and Blood papers, is not a co-author on the Cell paper. Mayack did not agree to sign the Nature retraction. The Cell paper has been cited 56 times, according to Thomson Scientific’s Web of Knowledge.

Partridge told us today that he was still not convinced that the study should have been approved by Cell‘s peer reviewers. That’s a problem, he said, in a quickly growing field with lots of methods. “It’s very difficult to see how you would end up with a coherent literature in that area,” he said. “There are too many people who don’t know the ins and outs of techniques.”

One solution, Partridge said, would be to set up a robust system of post-publication peer review — perhaps similar to what Faculty of 1000 does. He isn’t sure journals would be very enthusiastic, however.

We’ve also tried to contact Wagers for her response, and will update if we hear back.

Hat tip to @philscore44, who alerted us to the Cell correspondence between Partridge and the Wagers team.

11 thoughts on “Scientist raised serious questions about 2008 Cell study by Amy Wagers”

  1. At Nature, our articles (all of them) have been open for online comment by the community since early this year (around February, from memory). We did not expect to receive many comments, based on the experience of other journals. And so it proved, though we have had a trickle of constructive technical remarks and some debate, as well as some questions from non-specialists. Opening the full-text version of the articles for comments is one thing that journals can do to provide a platform for debate, but it does seem to be true, for several reasons, that scientists are reluctant to engage in this way. (Time, not wishing to be seen to criticise, no obvious benefit are three of the common reasons for not participating).

  2. I think you are definitely overselling this particular issue. The comments from Partridge are scientific comments suggesting that Wagers was misinterpreting or misanalyzing her data. Whenever someone writes to the editor questioning your conclusions, it’s expected that you will write back and reply to the criticism. This type of thing occurs all the time in competitive fields, often between well-respected scientists with spotless integrity (because even the best scientist interprets their data wrong from time to time). Just because someone questioned the validity of Wagers’ conclusion doesn’t mean that Wagers was falsifying anything or doing anything unethical. The issue with the Nature and Blood papers is much more serious, calling into questions whether the data is falsified.

  3. The two points at issue, dishonesty and misinterpretation, certainly carry different moral overtones and may have different effects on the career paths of those implicated. But they have very similar effects on the subsequent conduct of science in that both generate mythologies of similar pervasiveness and persistence. In neither case, save with the more startling claims, is there much incentive to reproduce the original findings and no distinction can be drawn regarding the extent to which they act to mislead subsequent research within the topic. This is especially true in the case of stem cell research where there may be financial pressure to promote and maintain strong storylines.

  4. A scientific /technical discussion of this kind may say something about the quality or competence of the editors but does not – in itself – imply any impropriety.
    But it does bring up the roles of lead author, senior author, peers and editors.
    In my opinion the initial “quality gateway” has to be the senior author when submitting for publication, and the final “guarantor” of integrity before and after a paper has been published also has to be the senior author.

    1. I agree, the senior author/PI is in a unique position to scrutinize data generated by his/her staff and is the one who has access to raw data as well as methods used to generate them. Whether or not their data can be reproducible has to happen before misleading many in the field as well as wasting vast amount of resources. There should be an accountability process rather than merely retracting and say sorry!

  5. Kudos to Partridge, ktwop, and Jey! I could not agree with you more!!!
    ….Adam,I think you are missing the point and actually several points of this issue and the discussion and therefore really the gravity of it all. First, I don’t think anyone, anywhere said anything about falsification of data regarding Wagers’ Cell, Nature or Blood papers that have been called under scrutiny. Nor, is it my understanding, that that would the only reason for a retraction. Life, science, and everything in between seems much more complicated than that wouldn’t we all agree? Given the pattern this begins to highlight, perhaps the decision to retract etc is damage control on her own part, with the modus operandi potentially being to protect her image after the fact of putting out another batch of sloppy work. We just do not know enough details and probably never will to tell. The point of this latest Retraction Watch article which highlights serious concerns raised regarding a previous paper of Wagers (Cell 2008) is that it suggests a pattern which one cannot deny would earnestly lie with the PI. Again, no one here is suggesting that the pattern is a pattern of data falsification regarding any of the issues that have been raised. Let’s think about the facts that we truly know. This is a PI who has had a lab for a very short period of time, in that short time 3 or her handful or so of publications as an independent investigator are now shrouded under some degree of serious concern. So, the details we DO know is that there is a pattern of sloppiness on her part since she has been independent and it seems reckless to me for the scientific community to ignore this. Afterall, do we only expect esteemed scientists who have made it to the towers of the ivy league to just be kings who blindly praise the tallies of their jesters or do we expect, demand, that they also be good mentors and direct and guide their underlings research and look carefully over their work , data collection, etc. as they constructively guide them? If there were mistakes, or even falsifications, the irresponsibility lies with the boss as well, period. To be giving accolades instead of holding one accountable for seemingly having done their job AFTER the fact would not fly in any other professional arena—we should expect and demand more from our leading scientists.

  6. Sally, I think you are missing the point here. There are two completely separate issues: on the one hand are the Nature and Blood papers, which are under heavy suspicion of falsification. On the other hand, there is this criticism of the Cell paper by Terence Partridge, which to me looks like a ‘normal’ scientific dispute over the interpretation of results and allegations of overselling stuff. I find it a big mistake by this blog to combine these two issues into one story – I am entirely with Adam on this one.

  7. I have to come out in agreement with the majority here. The point, I believe that many here are trying to make, goes beyond the procedural elements. Of these 3 Wagers papers being discussed, it is true that there are different levels of concerns and or questions being raised. But, even if one argues that the questions raised regarding the Wagers Cell 2008 paper, were ‘normal’ scientific inquiry and should be discounted from the discussion on this post. It still leaves a questionable mark on the very short record of this young scientist as an independent investigator that provide just cause for concern. Because as the majority here is voicing, regardless of the situation–mistakes, falsifications, sloppy math– senior authors should take accountability and be held more accountable for mentoring and quality control of their data, in the first place. (I would strongly argue against this being completely ‘normal’ scientific inquiry as such ‘normal’ does not typically get hashed out in the pages of Cell, otherwise journals would be flooded with such ‘normal’ inquiry).

    Also as others have pointed out here, no mention of falsification has been made regarding any of these 3 publications. That I believe is the only mistake being made in this blog discussion.

  8. Unfortunately, this is a clear example of “what to do”:

    1. Publish now, sort out later
    2. You can always argue your point, even the wrong one.
    3. Even if (unlikely) you are proven (caught) wrong, you are now a tenured professor.
    4. Who cares… In the end of the day, it will appear to be a mundane academic bickering. Most people will get a headache, but you got a nice job and a salary.
    5. Fools publish their statistically significant results they got after a long hard work; smart people publish what everyone wants to hear. And it is much (much!) faster.

    1. Unfortunately, Fedor Godunov’s analysis is close to the mark; I suspect that the process he describes has become unconscious. My original criticism of the Wagers’ article carried no implication of falsification, indeed the data itself, especially the large variation, carries all the hallmarks of authentic biological data. It falls from grace mainly in the under-critical evaluation of that data, which, when examined carefully, is not internally coherent. This is a common problem with cross-disciplinary studies and is routinely missed when the panel of referees does not cover the range of technologies employed. At a practical level, this issue can only be addressed by encouragement of a more discussive and less adversarial structure for post publication debate. In this instance the editorial staff of ‘Cell’ showed no enthusiasm for such a course of action. As a result, the various reviews and data-mining endeavours will treat the conclusions of the article uncritically; no major tragedy if this were an isolated case but, across the range of publications that fall into this category will certainly degrade the value of what we think of as ‘knowledge’ that we attempt to assemble into a structure of systems biology.

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