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 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]