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Q&A: Why the reactome is real

Over the last several months, biochemists have linkurl:questioned the validity;http://www.the-scientist.com/blog/display/56266/ of a new technique heralded as a "breakthrough" technology when it was linkurl:published in Science;http://www.sciencemag.org/cgi/content/abstract/sci;326/5950/252 in October 2009 -- a reactome array of nearly 2,500 metabolites and other substrate compounds tethered to a glass slide that would allow scientists to assess the functionality of hundreds of active proteins s

By | August 9, 2010

Over the last several months, biochemists have linkurl:questioned the validity;http://www.the-scientist.com/blog/display/56266/ of a new technique heralded as a "breakthrough" technology when it was linkurl:published in Science;http://www.sciencemag.org/cgi/content/abstract/sci;326/5950/252 in October 2009 -- a reactome array of nearly 2,500 metabolites and other substrate compounds tethered to a glass slide that would allow scientists to assess the functionality of hundreds of active proteins simultaneously. Indeed, last week, Science decided to retract the paper, upon the recommendation of an ethics committee at the Spanish National Research Council (CSIC), where several of the authors (including last author Manuel Ferrer) are based, and two other affiliated institutions.
A biochip
Image: Flickr,
linkurl:Argonne Laboratory;http://www.flickr.com/photos/argonne/3397932229/
Some researchers, however, including Nobel Laureate linkurl:Richard Roberts,;http://www.neb.com/nebecomm/researchScientist.asp?id=RRoberts chief scientific officer of New England Biolabs, continue to defend the technique and the potential it holds for studying the metabolic activities of cells. Roberts spoke with The Scientist about why he believes the decision to retract the paper was a big mistake. The Scientist: First of all, what is the importance of this new tool, if it proves successful? Richard Roberts: At the moment, trying to understand the function of the genes in an organism after you've got its complete DNA sequence is a bit of a problem because there are no really good high throughput methods. This is potentially a high throughput method, and so it could actually make functional annotation of genomes very much easier than it is at present. TS: What was your reaction when you first read the original paper? RR: Disbelief. It just seemed too good to be true. TS: So you, like so many others, were initially skeptical of these results, but you saw the potential benefit of such a tool. Did you believe, for example, that it could help your linkurl:Combrex project,;http://www.the-scientist.com/toc/2010/6/1/ which aims to assign functions to the thousands of unannotated genes in the sequenced microbial genomes? RR: If it was true, I would want to collaborate with these guys, and if it wasn't true, I would like to know about that before I started any sort of collaboration. So I made an arrangement to visit Dr. Ferrer in Madrid during a conference that I was at last December. I spent about three hours or so with him, met with all the people in his group, [who] showed me how they did everything, [and even] went over and met with one of his local collaborators, who was doing some of the identification work. And everything that I saw while I was there gave me complete confidence that everything was above board. So I was a convert; I converted from my initial skepticism to being a believer. TS: So then what did you think of the concerns that were later raised? RR: Well, my reaction was that what they were saying, which was that the methods were not well documented in the paper, was absolutely true. I mean, this was one of the reasons for some skepticism in the first place. From my perspective, that alone was not enough to say this must be fraudulent. Because that was not what the paper was about. The paper wasn't about the chemistry; the paper was about what great biology you could do if you have this tool available to you. TS: So you think a reactome array is feasible. How have you gone about proving that? RR: I said, 'Why don't we just set up a test?' So that's what we did. Basically, we set up 10 compounds, of which 8 [Ferrer] should be able to detect and know what they were, one should not have been detectable at all by his system, and the other one was a complete unknown. And the bottom line was that he got the correct results on everything. TS: What do you think about the CSIC committee's report that concluded that the paper should not have been published? RR: I thought it was a rather superficial view of everything. It was pretty wishy-washy. It basically said that the original paper had not had all the methodology in it, which is basically what the chemists had said to start out with. TS: So the fact that the original paper lacked the detailed methodology in your mind isn't a justification for retraction. What do you see as the repercussions of such a retraction? RR: All this does is cast some severe shadows on the scientific integrity of Dr. Ferrer, and [no one knows] at this point whether they're justified or not.
**__Related stories:__***linkurl:Wiki-annotating;http://www.the-scientist.com/toc/2010/6/1/
[June 2010]*linkurl:Why we need a reactome;http://www.the-scientist.com/blog/display/56266/
[12th January 2010]*linkurl:Bring Me Your Genomes;http://www.the-scientist.com/article/display/15531/
[6th June 2005]
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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 85

August 9, 2010

Dr. Roberts' comments about the importance of the reactome tool would only be valid if the piece had been published as a theoretical "gedanken" piece, which is the way he decided to interpret it. But from what I can gather from this article, the original paper was not published as a "gedanken" piece, rather, it was published as an experimental research article. Thus, his comments seem to be largely irrelevant to the question of the validity of the research paper. He himself admits that he had concerns about the article as an experimental research article, and these appear (from what I can tell from this article) to be the same concerns that led to the retraction.\n\nThe scientific enterprise comprises a complex set of activities, which include observations of nature, generation of ideas about how nature works, generation of ideas about how humans can adapt natural phenomena for pragmatic purposes, logical experimental testing of ideas about how nature works, and empirical experimental testing of ideas about adapting nature for practical purposes. It is important for scientists to understand the distinctions between these activities as well as the interdependence among them (e.g., experimental results often turn out to be new observations that in turn inspire new ideas).
Avatar of: anonymous poster

anonymous poster

Posts: 2

August 10, 2010

Almost all papers in Science are lacking in sufficient detail compared to what is required by more specialized journals. Detail gets in the way of newsworthiness, it seems. This causes problems. If people try to publish the details of a Science paper in a longer and better documented form elsewhere, editors and/or reviewers typically say the work is already published ,and reject it- thus, the important details are kept from the community. \n\nIf people try to include detail in Science papers, they are usually told (in the successful cases) to resubmit as a brief communication, and these, if accepted, are just too short to be much more than a pretty snapshot instead of a hearty, reproducible document. Whose fault? More the editors' than the authors' in many cases. Why? The Science papers often encompass multiple scientific fields, e.g. from analytical chemistry to biology. Publishing the results separately takes away from (and may completely obscure) the overall impact and can even lead to charges that too many papers are being written on the same topic, so the authors can have dilemmas no matter what they do. \n\nI'm not defending the authors in this specific case, I don't know enough about it, but I am attacking Science's editorial policies, which seem to me to result in many fancy pictures or impressions being published without the data or details to back them up completely. \n\nOf course, I'm not attacking every paper in Science, and I'm sure that most are fine, but, if there is controversy, I'm more likely to believe the results in other journals, "lesser" journals where sufficient space is allowed for a full presentation of materials and methods and results in the body of every paper. Replace "Science" with "Nature" and the same comments hold.
Avatar of: anonymous poster

anonymous poster

Posts: 182

August 13, 2010

Another interpretation is that what Roberts is saying is that the group has come up with a very interesting and useful tool of potential application to many areas of biomedical research. The authors might have failed to document their research properly but what Roberts did is an extraordinary example of scientific vision other than collegiality. He turned his disbelief into a direct open question to the authors and opportunity for them to document and VALIDATE their methodology. They did it. Thank you Dr Roberts.

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