{"id":621,"date":"2007-06-17T18:48:16","date_gmt":"2007-06-17T18:48:16","guid":{"rendered":"http:\/\/occamstypewriter.org\/mindthegap\/2007\/06\/17\/in_which_i_am_humbled_by_the_evolution_of_science\/"},"modified":"2007-06-17T18:48:16","modified_gmt":"2007-06-17T18:48:16","slug":"in_which_i_am_humbled_by_the_evolution_of_science","status":"publish","type":"post","link":"https:\/\/occamstypewriter.org\/mindthegap\/2007\/06\/17\/in_which_i_am_humbled_by_the_evolution_of_science\/","title":{"rendered":"In which I am humbled by the evolution of science"},"content":{"rendered":"<p>I have often thought about what it might have been like to have lived through pivotal years when scientific thinking or practice was undergoing a period of intense change. To have been a scientist in 1859 when Darwin&#8217;s <em>Origin of Species<\/em> was first published, say, and to find your frame of references turned completely upside-down, picked apart and stitched back together in some velvet-lined Victorian salon. Or to have been involved in the birth of molecular biology in the 1940s and 50s, seeing the light in a petri plate full of phage plaques and telling the world about your findings on a dusty chalkboard at Cold Spring Harbor or the Institute Pasteur. <\/p>\n<p>\n<img loading=\"lazy\" decoding=\"async\" src=\"http:\/\/www.lablit.com\/images\/Sequencing.jpg\" alt=\"\" width=\"175\" height=\"213\" \/><\/p>\n<p>\n<strong>Those were the days&#8230;<\/strong><\/p>\n<p>\nAlthough I must have always known it intuitively, it only dawned on me a few days ago that modern scientific progress is <em>always<\/em> in the midst of change. It just occurs so gradually that we realize it only in retrospect. Looking back on my career now, I recall a few moments of fumbling in the dark, working on things before the truth was revealed. As an undergraduate back in the 1980s, for example, I did a summer stint at the National Institutes of Health, trying to understand why certain strains of human papillomavirus could transform cervical epithelial cells. We knew it was down to the viral proteins E6 and E7, but nobody had a clue why. And I have a distinct memory of feeling almost overwhelmed by a black universe of ignorance \u2013 it didn&#8217;t matter how many plates of cells I forced through the FACS machine or peered at down the microscope: we would never really know what was going on. We had no purchase, no frame of reference: HPV&#8217;s transformational properties were practically magical \u2013 it might as well have been raw meat <a href=\"http:\/\/en.wikipedia.org\/wiki\/Abiogenesis\">spontaneously generating<\/a> into maggots. <\/p>\n<p>\nAnd then, of course, people worked out how the viral proteins bound to the cellular tumor suppressors p53 and Rb a few years later, and it all turned into humdrum textbook material. And now, when we discover new transforming agents, we have an arsenal of reagents to fall back upon \u2013 ignorance isn&#8217;t a universe, just a temporary and easily-remedied set-back. Thinking objectively, I honestly don&#8217;t think it was my immaturity that made me feel so lost at sea; I genuinely think that when it comes to molecular cell biology, we now know enough to be within spitting distance, at any one time, of all known pathways or effectors. We may not have the complete Google-Earth view, but we certainly have a low-resolution roadmap of how the cell works. And it just wasn&#8217;t like that in the 1980s. Hey presto \u2013 I have lived the before-and-after of the recombinant DNA era. Post-genomics, ditto. Someday, two hundred years hence, some scientist may be thinking nostalgically about the years that passed me by without their significance even registering. <\/p>\n<p>\nIt&#8217;s not just knowledge that accrues unawares. Technology, too, ticks steadily onward while you aren&#8217;t looking. On Friday, I watched a colleague prepare to do a Western blot. But instead of assembling an SDS-PAGE gel from scratch, she reached for a ready-made version sealed in foil, shelf life approximately six months. Now, this stuff was available when I last did research four years ago, but it hadn&#8217;t yet gone mainstream, and we certainly didn&#8217;t have any in our lab. Now, nobody bothers making it themselves, and all I could think was, <em>Thank god<\/em>. Yes, I&#8217;m afraid that pouring acrylamide gels is not something I can say I missed during my editorial sabbatical.<\/p>\n<p>\nMaybe the biggest change I have lived through, technologically speaking, was the transformation of DNA sequencing from do-it-yourself to outsourced. When I was a Ph.D. student in Seattle in the early 1990s, I wanted to understand how feline leukemia virus envelope genes mutated. To do this, I had to sequence the envelope gene (all 2100 base-pairs of it) of viruses I cloned from various infected cats and different time points, over and over and over again. For four years. Effectively, this meant that every day, I was pouring a big, thin acrylamide gel (remember how fiddly that was?), doing radioactive sequencing reactions via the dideoyl chain-termination method, electrophoresing the previous day&#8217;s reactions, developing the film from two days before and (worst of all) manually entering all the sequences into the computer for alignment. The G, C, A and T keys of my Mac SE were visibly more weathered than all the others, and in a few months I found I had memorized entire stretches of the wild-type FeLV envelope gene by heart. <\/p>\n<p>\nAt one point, my Ph.D. supervisor noted my passage through a momentous milestone: I, like her, was a member of the One Megabase Club. Did I pause to celebrate? No, I was too busy silanizing my plates and de-gassing my gel solution.<\/p>\n<p>\nOf course, all this should inspire us to try to guess what routine technique that we all do today might be pass\u00e9 in ten years&#8217; time, or what stubborn barriers in our knowledge will be knocked through. Stuck in the present tense, though, we can only wonder.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>I have often thought about what it might have been like to have lived through pivotal years when scientific thinking or practice was undergoing a period of intense change. To have been a scientist in 1859 when Darwin&#8217;s Origin of &hellip; <a href=\"https:\/\/occamstypewriter.org\/mindthegap\/2007\/06\/17\/in_which_i_am_humbled_by_the_evolution_of_science\/\">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-621","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/621","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=621"}],"version-history":[{"count":0,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/posts\/621\/revisions"}],"wp:attachment":[{"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/media?parent=621"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/categories?post=621"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/occamstypewriter.org\/mindthegap\/wp-json\/wp\/v2\/tags?post=621"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}