Nature yanks controversial genetics paper whose co-author was found dead in lab in 2012

naturecover1113Nature has retracted a controversial 2012 paper by a group from Johns Hopkins University which has been the subject of a protracted public dispute.

The article, “Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK,” came from the lab of Jef Boeke,  a celebrated biochemist. But a former lab member, Daniel Yuan, who was fired by Hopkins in late 2011 after 10 years at the institution, had repeatedly raised questions about the validity of the findings. Those concerns eventually made their way into the Washington Post, prompting this response from the university.

The Post’s Peter Whoriskey reported that, once he began asking questions about the article, both Hopkins and Nature said that a correction to the article would be forthcoming. But that didn’t happen. Instead, today Nature has issued the following retraction notice:

In response to a concern raised by a reader about inconsistencies in our Letter between the results from the primary microarray screen and cell growth validation studies (Supplementary Table 2), we reviewed the methods described, and the subsequent analytical and validation work. We conclude that the Methods section in our Letter is inaccurate, and that for 38% of the interactions found by the primary screen there was a discordance in sign when validated (for example, an interaction might be called ‘synthetic lethal’ by the primary screen but ‘synthetic rescue’ in the cell growth validation assay, or vice versa). Although the results from the reanalysis did not contradict our key conclusions, we also re-evaluated the experiments in Figs 2–4 that indicate that p300 acetylates PRKAA1 and HDAC1 deacetylates it. We sequence-verified and spot-checked many of the plasmids and cell lines described, which are available on request. The biological materials were found to be as we described, and certain aspects, such as p300 acetylation of PRKAA1 protein in vitro, could be reproduced. However, despite several attempts, we were unable to obtain results definitively supporting the major claims of the Letter, namely that p300 is the acetyltransferase and HDAC1 is the deacetylase for PRKAA1 in cells. The batch of polyclonal antibody against acetyl-lysine originally used is no longer available. More definitive experiments require antibodies that specifically recognize acetylated sites on PRKAA1, which we are developing. Although our inability to reproduce these results does not mean our conclusions are incorrect, we cannot say with confidence that they are correct. Given the time that has elapsed, and our inability to reproduce the main conclusions of the Letter, we feel obliged to retract it. All the authors have signed this retraction with the exception of Y.-Y.L., who is deceased. Correspondence should be addressed to J.D.B.

The deceased author is Yu-yi Lin, a collaborator on the article who was found dead in August 2012, possibly of suicide, in his Taiwan office.

The study has been cited 24 times, according to Thomson Scientific’s Web of Knowledge. Hopkins took the time to promote the study in a press release upon publication, so we hope they’ll do the same for the retraction. Also noteworthy: Boeke had what we’d consider a mega-correction in Cell earlier this year, of a paper cited 319 times.

14 thoughts on “Nature yanks controversial genetics paper whose co-author was found dead in lab in 2012”

  1. I hope the readers will assess what is termed a “mega-correction” RE: the Cell paper noted above. My reading is that the correction added details of experimental procedure that were opaque in the original paper. This certainly is qualitatively different from any number of other “mega-corrections” that have been detailed here. I also note that Dr. Boeke has been a major contributor to the field of yeast genetics in terms if seminal methods and analyses. He is highly respected for a number of reasons due to his contributions.

    1. Lets get this into perspective – the only concern here is the loss of life. The life of a dignified and honest researcher who dedicated himself to the search for truth that is science. That search was perhaps not shared by all those he worked for which is disappointing.

      The researcher who took his own life needs to be remembered by the University he worked at. Is there a memorial plaque? I would hope his former PI would be dignified to, at the very least, dedicate a wall in his laboratory or his office to the work of Dr Yuan.

      A remeberance wall and plaque would show a great deal of respect for Dr Yuans family and is entirely appropriate.

      1. Considering it was not Dr. Yuan who passed away, I think you would be hard pressed to convince anyone of a reason to dedicate a wall to him.

    1. And at great personal cost to Yu-yi Lin. Its a cruel system, unreproducible work is rampant – if everyone committed suicide, the hospitals and universities would be charnel houses with academics dangling from every lamp-post. I am sure that Dr Yuan will have felt personal distress at the outcome.

      I know when I was attempting to whistle-blow on a cheating Institute head, there was always the nagging concern what if I am successful and he commits suicide as a result? Luckily for me, the scientific and medical fraternity showed a united front and covered up and suppressed furiously.
      Psychologically difficult for me, of course, instead – but I am made of tougher stuff than academics.

      1. I agree that Dr. Yuan should likely be employed. If he couldn’t get a grant in two years that’s tough, but no well funded researcher can float an unsupported semi-independent senior researcher indefinitely. Soft money is a tough life, and getting tougher.

        Given the outcome and the ultimate retraction by Hopkins, I feel that the readers of RW should be giving Hopkins a little more in the way of kudos.

        2012 to now to get a retraction seems a long time, but considering it was based on failure to reproduce and not obvious misconduct IF ANY, not so long at all.

        I say other research institutions need to look at this case carefully and not go into full scale cover-up mode at the first sign of a misconduct allegation.

        1. I don’t think Hopkins came out so good. Check out their letter to the editor after the Post story. They slimed Yuan and bided time while experiments were rerun. They have not gotten a press release out to correct the original plug. And the disappeared their earlier press release. Pretty much classic institutional weasel behavior. Yuan was right and Hopkins was full of it.

  2. The “mega correction” appears to be an expansion of the methods portion of the paper and a reanalysis of some of the data that slightly reduces the statistical strength of one of the arguments in their paper. It looks pretty minor. Maybe it’s considered “mega” because of the word count?

    1. It seems a little more serious than you state. They state “We regret the omission and note that the subset of interactions whose identification was not based directly on the dSLAM screen
      cannot be used to support the efficacy of the dSLAM method itself.”

      I assume this means that they used known interactions to support the argument that dSLAM works. When you exclude these known interactors is the dSLAM method able to detect any other interactions? Maybe there are a lot of false positives – the bane of high throughput screens. Perhaps the dSLAM method might not be that effective in finding new interactions? I think this is why there was a correction, people were trying to use the method and it didn’t work as well as published. But who knows?

  3. A few statements in the retraction notice are unclear to me.
    “However, despite several attempts, we were unable to obtain results definitively supporting the major claims of the Letter, namely that p300 is the acetyltransferase and HDAC1 is the deacetylase for PRKAA1 in cells. The batch of polyclonal antibody against acetyl-lysine originally used is no longer available.”
    So this means that no fraud was involved, but the results are not reproducible because the commercially available anti acetyl-lysine antibodies sometimes work and sometimes don’t work? And just in the retracted paper it happened to work?
    “Given the time that has elapsed, and our inability to reproduce the main conclusions of the Letter, we feel obliged to retract it.”
    The paper is just one year old, so the time that has elapsed is not relevant to the retraction.

      1. According with The Washington Post article, “Lin, Boeke and their co-
        authors reported discovering 878 genetic interactions, or “hits.” But Yuan, who was familiar with the data and the statistics, reanalyzed the data in the paper and concluded that there was essentially no evidence for any more than a handful of the 878 genetic interactions.”
        I don’t think that the retraction note properly addresses the concern raised by the “reader”.
        This reminds me of the discrepancies between the engineers and NASA management during the Challenger disaster, where the engineers calculated a chance of failure of 1/100 and NASA management calculated chance of failure of 1/100000. Maybe Richard Feynman’s conclusions can be applied to this discrepancy too?

        If a reasonable launch schedule is to be maintained, engineering often cannot be done fast enough to keep up with the expectations of originally conservative certification criteria designed to guarantee a very safe vehicle. …..
        They therefore fly in a relatively unsafe condition, with a chance of failure of the order of a percent (it is difficult to be more accurate).
        Official management, on the other hand, claims to believe the probability of failure is a thousand times less. One reason for this may be an attempt to assure the government of NASA perfection and success in order to ensure the supply of funds. The other may be that they sincerely believed it to be true, demonstrating an almost incredible lack of communication between themselves and their working engineers………..
        Let us make recommendations to ensure that NASA officials deal in a world of reality in understanding technological weaknesses and imperfections well enough to be actively trying to eliminate them………
        NASA owes it to the citizens from whom it asks support to be frank, honest, and informative, so that these citizens can make the wisest decisions for the use of their limited resources.
        For a successful technology, reality must take precedence over public relations, for nature cannot be fooled.”

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