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Retraction recommended for enzyme-chip paper

Reactome array study should not have been published, says ethics committee.

A chip that could provide a rapid snapshot of the total enzyme activity in a cell sounded like a dream come true for biologists. But the dream has faded fast. An investigating committee has recommended that a paper unveiling this 'reactome array' be retracted, because it does not provide experimental support for its conclusions.

The paper described a device carrying 1,676 individual enzyme substrates, tagged with fluorescent dye, that could detect enzyme activity. The project was led by scientists at the Institute of Catalysis and Petroleochemistry (ICP) in Madrid, run by the Spanish National Research Council (CSIC), and at the Helmholtz Centre for Infection Research in Braunschweig, Germany. The chip promised to be a powerful tool for monitoring, for example, how the metabolism of communities of microorganisms varies with environment.

After the paper was published (A. Beloqui et al. Science 326, 252–257; 2009), organic chemists raised concerns about the feasibility of the claim, citing errors in the general reaction scheme outlining how the chip was supposed to detect enzymes. On 17 December, Science's editor-in-chief Bruce Alberts took the unusual step of publishing an 'editorial expression of concern' about the work, and asked the authors' institutions to investigate.

The CSIC convened an ethics committee to probe the affair; it then incorporated findings from a parallel inquiry at the Helmholtz centre. The committee now concludes 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. The CSIC is considering a disciplinary investigation of the scientists involved.

The corresponding authors on the paper, Manuel Ferrer of the ICP, and Peter Golyshin, now at Bangor University, UK, were unreachable for comment on the report.

Some scientists are still convinced that the methodology used to create the array could work. "We don't know," says molecular geneticist Pere Puigdomènech of the CSIC's centre for research and development in Barcelona, who headed the CSIC ethics committee. "We only criticize how the science in this paper was conducted and reported — we'd be very happy if someone could validate it."

But David Cane, a biochemist at Brown University in Providence, Rhode Island, believes that a single chip capable of monitoring all the enzymes in a cell is not currently feasible.

He points out that enzymes are picky about the shapes of their preferred substrates. In the reactome array, substrates are attached to a dye molecule and to a linker holding them to the chip, which may change their shape enough to stop them fitting into an enzyme's active site. Cane says that the paper presents no evidence that the assay would work with choosy enzymes.

Ronald Frank of the Helmholtz centre, who coordinated the German investigation, says that a meeting will be held on 11 August to discuss whether there should be further consequences for scientists there. A spokesperson for Science says that the journal is in discussions with some of the institutions involved and will make a decision about the paper "very soon".

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Additional reporting by Daniel Cressey

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Abbott, A. Retraction recommended for enzyme-chip paper. Nature 466, 540–541 (2010). https://doi.org/10.1038/466540b

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