Science wants “reactome array” enzyme chip authors to retract paper

Following an investigation into an October 2009 study in Science that claimed to have proven the ability of a device to measure all of the enzyme activity in a cell at a particular time, the journal has asked the study’s authors to retract the paper, Science‘s news blog, ScienceInsider, reported on Friday.

The move comes after Bruce Alberts, Science‘s editor in chief, issued an Editorial Expression of Concern in December in response to concerns raised by other scientists

to alert our readers to thefact that serious questions have been raised about the methodsand data presented in this article. The questions focus in particularon the synthesis of the dye-labeled metabolites that are centralto the microarray technique. In addition, the spectroscopicdata the authors cite in support of their claim were not postedto the Bangor University School of Biological Sciences Web siteat the time of publication, despite the authors’ indicationin the Supporting Online Material that the data would be soposted. In response to inquiries from Science, the authors haveprovided new descriptions of the synthetic methods that differsubstantially from those in their published article. Based onour original concerns and the authors’ response, Science hasrequested evaluation of the original data and records by officialsat the authors’ institutions: These officials have agreed toundertake this task.

That evaluation, reported late last month by Nature, concluded

that the paper should not have been submitted or published, noting, among other things, that experiments in the paper lacked proper controls.

Their report says that all of the scientists who signed the paper must share responsibility for its content, and expresses concern about the peer-review process — potentially challenging for interdisciplinary research — that the paper underwent.

As recently as last week, some scientists, including a Nobel laureate, still supported the paper and its findings. Nobelist Richard Roberts, of New England Biolabs, was satisfied with the results of a blind test he had the original authors perform, according to ScienceInsider, and submitted those results to Science for review.

The method in question, if it holds up, would be an advance because it could help scientists figure out the inner workings of cells when it’s not clear how already-discovered genes — many of which code for enzymes — act. We turned again to our molecular biology guru, Jeff Perkel, for more of an explanation.

Perkel said that the reactome array basically provides a set of substances that a cell might break down, and asks which ones it actually can break down. What that does is allow researchers to link those breakdown products to the enzymes that act on them, and at the same time describes those enzymes at a molecular level.

All of that means scientists can check the guesses they often make about a gene’s function — many of them wrong — with data that allow them to determine what genes actually do. They can then predict, with great accuracy, whether a group of cells, or an organ, or a whole organism can process a given substance — and if so, with what enzyme.

The authors suggest, for example, that their array “would provide a measureof pollutant-metabolizing enzymes and thus a measure of theconcentration of bioavailable pollutant.” It could therefore theoretically help researchers develop diagnostic tests and discover unknown enzymes that could serve as drug targets.

The paper has been cited 11 times, according to the Thomson Reuters Web of Knowledge (disclosure: Reuters Health, where Ivan works, is obviously also part of Thomson Reuters). That’s a good number for a study published less than a year ago.

So what happens now? The authors can of course do what Science has asked, and withdraw the paper. Or Science could decide to retract it without permission. Retraction Watch has emailed corresponding authors Peter Golyshin, of Bangor University (UK) and Manuel Ferrer, of the CSIC, for comment, and will update if we hear back.

The possibility of a retraction worries Victor de Lorenzo, of the Spanish National Research Council  (CSIC)’s National Center of Biotechnology in Madrid, who told ScienceInsider by email:

If the paper is just withdrawn or retracted, I am afraid of two consequences [i] the wider scientific community will be deprived of the use of an incredibly powerful tool, further amendments and improvements notwithstanding and [ii] any smart cookie (maybe some of those who raised the most venomous criticism) may now rush, if they have not done it yet, to replicate the work, produce a publication and claim credit for themselves.

Nature reported that the Helmholtz Centre for Infection Research, where some of the study’s authors were based, will hold a meeting this Wednesday (August 11) “to discuss whether there should be further consequences for scientists there.”

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