{"id":628,"date":"2007-10-03T22:35:18","date_gmt":"2007-10-03T22:35:18","guid":{"rendered":"http:\/\/occamstypewriter.org\/mindthegap\/2007\/10\/03\/in_which_i_ponder_the_pros_and_cons_of_skepticism\/"},"modified":"2007-10-03T22:35:18","modified_gmt":"2007-10-03T22:35:18","slug":"in_which_i_ponder_the_pros_and_cons_of_skepticism","status":"publish","type":"post","link":"https:\/\/occamstypewriter.org\/mindthegap\/2007\/10\/03\/in_which_i_ponder_the_pros_and_cons_of_skepticism\/","title":{"rendered":"In which I ponder the pros and cons of skepticism"},"content":{"rendered":"<p>There&#8217;s a thread running on the <a href=\"http:\/\/forums.lablit.com\/\">LabLit forums<\/a> inspired by a recent news article in <em>Nature<\/em> about two young scientists who have been facing an uphill battle to get their unconventional work published. Have a look at Erika Check&#8217;s <a href=\"http:\/\/www.nature.com\/nature\/journal\/v448\/n7156\/full\/448855a.html\">piece<\/a> for the details, but briefly, two youngish researchers have been compiling evidence that miRNAs can occasionally activate genes instead of knocking them down. After a lot of experiments and numerous rejections, they finally managed to get some of the findings <a href=\"http:\/\/www.pnas.org\/cgi\/content\/abstract\/103\/46\/17337\">published<\/a> in <em>PNAS<\/em>. But despite a few additional supporting papers from independent labs, apparently most of the RNA interference community still doesn&#8217;t believe them. (Interestingly, one of the researchers says he&#8217;s been scanning through archives of biology message forums and found that &#8220;other scientists \u2013 often graduate students \u2013 have also seen evidence of RNA activation. But they have been encouraged to discount it&#8221;.)<\/p>\n<p>\nNow, I haven&#8217;t had a chance to read the <em>PNAS<\/em> paper yet, but clearly, if the work is true, it&#8217;s an important piece of information for researchers to know about. Not just those who study the biology of small RNAs, either, but the even larger proportion of folks, like me, who use siRNA as crucial knock-down tools. The big journals say they can&#8217;t publish without a &#8216;mechanism&#8217;, but I suspect that if an RNAi luminary like Greg Hannon, Craig Mello or Thomas Tuschl had submitted this work to a top-tier journal, the referees and editors might have been a bit more receptive. In short, the inexperience of the authors was probably one of the main sticking point. <\/p>\n<p>\nIn some ways, I suspect it&#8217;s healthy to have your skepticism dial turned up to eleven when faced with inexperienced researchers. Not only are they more error-prone but, let&#8217;s face it, they are also packed full of youthful excitability. I can still recall in vivid detail during my first year of graduate school, on several occasions, racing from the darkroom to my boss&#8217;s office, so flushed with a good result that I didn&#8217;t even bother to check the precise order in which I&#8217;d loaded my samples onto the gel. And <a href=\"http:\/\/myprofile.cos.com\/overbauj89\">Julie<\/a> would give me that look, frogmarch me back to my notebook \u2013 and I&#8217;d belatedly realize the whopping dark band I was celebrating was actually just the positive control. <\/p>\n<p>\nHow times have changed. These days, I&#8217;m treating cells with siRNAs targeted to novel genes and looking for phenotypes. I&#8217;ve had a beautiful phenotype staring me in the face for weeks; I&#8217;ve repeated it five times using different conditions, made cautious scribbles and sketches in my notebook about how there &#8220;appears&#8221; to be an effect \u2013 the images are annotated with circles and arrows and everything. I&#8217;m camped out by the microscope. But somehow, I just haven&#8217;t been able to truly believe it. And here&#8217;s the crux: I think it&#8217;s also about age, but this time the other side. We might be hyper-gullible about our results when we first start, but as we get wiser and more cynical, it gets harder to convince ourselves that our own data is real, let alone that of some green newbie fresh out of grad school. (Disclaimer: I am speaking generally. Some of my best friends are green newbies fresh out of grad school.)<\/p>\n<p>\nOf course, thanks to hearing about this weird new activation role of small RNAs, my scepticism feels entirely justified. Just as I was feeling comfortable with my phenotype, I suppose I am now obliged to suspect that it was an artefact all along.<\/p>\n<p>\nBut no, it&#8217;s too late \u2013 I&#8217;ve already given it a name! <\/p>\n<p>\n(See, I knew reading <em>Nature<\/em> was dangerous. Cheers, Erika.)<\/p>\n","protected":false},"excerpt":{"rendered":"<p>There&#8217;s a thread running on the LabLit forums inspired by a recent news article in Nature about two young scientists who have been facing an uphill battle to get their unconventional work published. Have a look at Erika Check&#8217;s piece &hellip; <a href=\"https:\/\/occamstypewriter.org\/mindthegap\/2007\/10\/03\/in_which_i_ponder_the_pros_and_cons_of_skepticism\/\">Continue reading <span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":6,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-628","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/628","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/comments?post=628"}],"version-history":[{"count":0,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/628\/revisions"}],"wp:attachment":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/media?parent=628"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/categories?post=628"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/tags?post=628"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}