{"id":380,"date":"2009-03-27T21:58:14","date_gmt":"2009-03-27T21:58:14","guid":{"rendered":"http:\/\/occamstypewriter.org\/scurry\/2009\/03\/27\/eye_opening_access\/"},"modified":"2012-01-31T08:20:11","modified_gmt":"2012-01-31T08:20:11","slug":"eye_opening_access","status":"publish","type":"post","link":"https:\/\/occamstypewriter.org\/scurry\/2009\/03\/27\/eye_opening_access\/","title":{"rendered":"Eye-opening access"},"content":{"rendered":"

If this paper<\/a> is the future of open access publishing, then we are in for an interesting ride. And it’s a journey that will reveal a great deal more about the process of science than most outsiders will have seen hitherto.<\/p>\n

\tThe article by Kinch and Grishin, published in a recent issue of the very<\/em> open access journal Biology Direct<\/em><\/a>, provides a great example of the self-correcting nature of science by refuting a finding from Kiriakidou et al.<\/a> that was reported two years earlier in one of the life science giants, Cell<\/em>. What adds a particular frisson of excitement to all this is that the reviewers\u2019 comments and the authors\u2019 responses are appended to the end of the Biology Direct<\/em> paper for all to see. I\u2019ve not come across this level of openness before, but I think it could be a very good thing<\/em>.<\/p>\n

\tThe scientific nub of the matter is of considerable interest since it touches on an exciting topic\u2014translational repression by RNA interference (RNAi)\u2014but the public nature of the dispute is even more gripping.<\/p>\n

\tKiriakidou and colleagues looked at the amino acid sequence of human Argonaute, a protein crucial to the mechanism of gene silencing by RNA interference. Curiously, they found a segment of Argonaute that resembles another protein, eIF4E, the mRNA cap-binding protein that controls the initiation of protein synthesis. The inference from this observation, that Argonaute might also bind the mRNA cap, appeared to be borne out by experiment and led to the formulation of a plausible mechanism to explain how the synthesis of proteins from mRNAs targeted by Argonaute might be repressed. Here was an important new finding in a hot area of science. No surprise then that it ended up being reported in Cell<\/em>. The paper was even flagged up by the Faculty of 1000<\/a>.<\/p>\n

\tBut there\u2019s a problem: the Kiriakidou paper is based on an error. Kinch and Grishin looked again at the protein sequences of Argonaute and eIF4E\u2014using more sophisticated methods\u2014and detected no similarity. None.<\/p>\n

\tMore compellingly still, they compared their three-dimensional structures of the two proteins (which, curiously, were both available in 2007) and showed that they were not the same. At all. As a result, the title of their paper in Biology Direct<\/em> reads like an inversion of the earlier work: Argonaute \u2018does not<\/em> contain an eIF4E-like mRNA cap binding motif\u2019. We are a long way here from the linear progression model of scientific development, but somewhat closer to reality.<\/p>\n

\tAnd what brings us closer still is the publication alongside the paper of the correspondence between the reviewers and the authors, which gives some great insights into the messy and disputatious business of science.<\/p>\n

\tIn their comments the authors reveal that the paper was originally submitted to \u201cthe high-profile journal that published the Kiriakidou et al paper\u201d (tellingly, Kinch and Grishin can\u2019t even bring themselves to write the name<\/em> of the journal) but was rejected after a six-month wait \u201con the basis of lacking experimental evidence\u201d, even though the reviewers for Biology Direct<\/em> are unanimous in their praise for the thorough-going nature of the work. It does rather look as if Cell<\/em> has dodged a dose of medicine that might have done the journal and their readers (and authors?) some good.<\/p>\n

\tWhile the referees are generally very positive in their comments, there is a request to shorten some of the sections describing the methodology of the paper, but Kinch and Grishin defend the inclusion of such details as necessary to convince their peers of the utility of computational analyses of sequence and structure. Again a certain frustration is evident: \u201cWithout a certain detailed familiarity with the methods, sequence similarity search results are easy to misinterpret\u201d and go on to complain that many life scientists are simply too ready to discount \u201ccomputational experiments\u201d. Could they be referring to prejudice<\/em>? My favourite remark is their parting shot: \u201cAlthough convincing researchers with pre-formed opinions is particularly difficult, we think our description contains an educational component that could help developing minds.\u201d Ouch.<\/p>\n

\tNot every paper is so controversial but this sort of episode is common enough in science. It\u2019s a business that is messy, incomplete, contradictory and suffused with human feeling. Often things have to be thrashed out in several labs before a consistent and plausible story emerges. Not every experiment is perfectly insightful or free from error. And day-to-day battles may occasionally be won on the strength of feelings<\/em> about this or that piece of data. But the process is nevertheless a sound one; in the long run, through repeated experiments and thorough discussion, the data will speak and well-founded skepticism will suck out the traces of personal venom. It\u2019s still the best way we have to fight the war of discovery.<\/p>\n

\tAnd it’s good that this messiness should be made known, so that the public get a much better understanding of what science is really like. This seems to be a growing movement; just recently we have seen Alom Shaha’s brilliant film<\/a> on the importance of science and, as Ryan<\/a> and<\/em> Heather<\/a> have pointed out, a great new web-site at Berkeley<\/a> that aims to present the warts’n’all view of what scientists do. The movie mentioned recently by Caryn<\/a> looks to be in the same vein.<\/p>\n

\tThe publication of the reviewers\u2019 comments also strikes me as a good way to make sure that they do a professional job of their critique. Biology Direct<\/em> even goes one step further in publishing the names of the reviewers (all members of the Editorial Board). As a sometime reviewer myself I would be happy to live with publication of my comments on someone else’s manuscript but I’m not sure I’d want to have my name printed alongside. I guess I would be apprehensive about repercussions on my own manuscripts and grant applications from aggrieved authors, concerns that are shared by others<\/a>.<\/p>\n

\tKiriakidou and colleagues will no doubt have been stung by the correction \u2014 no-one likes to be proved wrong (I know I don’t). But they\u2019ll get over it. I\u2019m sure they know they made a mistake and will be determined not to repeat it. In any case their experimental observation that Argonaute can bind mRNA caps still stands and may be significant, though it is likely to come under renewed scrutiny. But this is good; it will generate new data and new insights into how the protein works.<\/p>\n

\tThat’s the funny, amazing thing about science: it always wins.<\/p>\n

\t\"\"<\/a><\/p>\n

\t\"ResearchBlogging.org\"<\/a><\/span><\/p>\n

\tKinch, L., & Grishin, N. (2009). The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif Biology Direct, 4<\/span> (1) DOI: 10.1186\/1745-6150-4-2<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

If this paper is the future of open access publishing, then we are in for an interesting ride. And it’s a journey that will reveal a great deal more about the process of science than most outsiders will have seen … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[152,1],"tags":[],"class_list":["post-380","post","type-post","status-publish","format-standard","hentry","category-open-access-2","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/posts\/380","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/comments?post=380"}],"version-history":[{"count":0,"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/posts\/380\/revisions"}],"wp:attachment":[{"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/media?parent=380"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/categories?post=380"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/occamstypewriter.org\/scurry\/wp-json\/wp\/v2\/tags?post=380"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}