{"id":176,"date":"2012-09-06T15:09:21","date_gmt":"2012-09-06T15:09:21","guid":{"rendered":"http:\/\/genotopia.peachpuff-wolverine-566518.hostingersite.com\/?p=176"},"modified":"2012-09-06T15:10:23","modified_gmt":"2012-09-06T15:10:23","slug":"decoding-encode","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/genotopia\/176\/decoding-encode\/","title":{"rendered":"Decoding ENCODE"},"content":{"rendered":"

When I was a science writer at Cold Spring Harbor Laboratory<\/a>, back in the early 1990s, I attended the annual genome meeting and heard Sydney Brenner make his pitch for the fugu genome. The puffer fish\u2014known to sushi aficionados and neurobiologists for its tiny gland that produces the neurotoxin tetrodotoxin\u2014Brenner, said, has a marvelously condensed genome, free of \u201cjunk DNA.\u201d<\/p>\n

The standard dogma of the day was that the human genome was 99% junk\u2014an evolutionary midden-heap, strewn with the discarded wrecks of past experiments, genes that had mutated out of all functionality, mind-numbing repetitive sequences where the polymerase got stuck and churned out the nucleotide version of Nebraska, and spare parts that might be used in assembling some future genetic component. The Human Genome Project would take far longer and be far more expensive if we tried to sequence all of it, Brenner said. By studying the fugu genome, he argued, we could cut to the chase, learning about the genes without sifting through all this trash; perhaps then we could use fugu genes to identify the functional sequences in the human genome. But Brenner\u2019s Fugu Genome Project went into science\u2019s own scrapheap. Not long after this meeting, Craig Venter\u2019s shotgun sequencing techniques began to accelerate the Human Genome Project, shortening the projected finish time and slashing budget projections. The Fugu Genome Project <\/a>continued, but it had nothing like the impact Brenner envisioned.<\/p>\n

\"\"
Barbara McClintock, from CSHL Archives<\/figcaption><\/figure>\n

Then I went back to grad school, studied the history of science, and began my dissertation research on Barbara McClintock<\/a>, the maize geneticist who worked at Cold Spring Harbor for half a century and who won a Nobel prize in 1983 for her discovery of mobile genetic elements. Late in her career, McClintock became deeply interested in all forms of gene regulation. Development and evolution were united in her mind by means, dimly understood, of turning genes on and off and modulating their activity. She was convinced there was a higher-order organization that controlled the genes; phenotypes resulted from patterns<\/em> of gene action. Most people think that McClintock\u2019s discovery of transposable elements was ignored or dismissed by the scientific community. I found that wasn\u2019t true. They believed that McClintock had found movable elements. They just didn\u2019t believe those elements controlled evolution. McClintock\u2019s late work continued her theme of gene regulation and interaction. The genome, she wrote, was a \u201csensitive organ of the cell,\u201d dynamic and responsive\u2014not a blueprint or an instruction manual.<\/p>\n

Study of the human and other genomes has revealed that \u201cjunk DNA\u201d is itself junk\u2014much of that noncoding sequence is involved in gene regulation. Some of it is of the sort that McClintock envisioned; some is beyond even her imagination. The genome is now understood in terms much closer to McClintock\u2019s mystical-sounding notion. As I wrote in my book, The Tangled Field<\/a>, <\/em>she deserves more credit as an early proponent of the complex, dynamic genome.<\/p>\n

This week, the genome community has been all aflutter with news of the ENCODE project<\/a>, a sophisticated genome database that catalogs patterns of gene activity. It turns out that most of Brenner\u2019s junk DNA, isn\u2019t. Much of that non-gene sequence is deeply important to gene function: it\u2019s full of regulatory sequences, what the press are calling \u201cswitches,\u201d that determine how and when and in what context the genes act. Had the National Institutes of Health invested as heavily in fugu as Brenner had hoped, it would likely have taken much longer to reach this level of subtle understanding. As Michael Eisen points out in a nice critique of the science media machine<\/a>, none of this is actually news. The junk DNA model has been out of style in science for years, and the ENCODE project has not identified \u201cmillions of switches\u201d that regulate the genome. More accurate to say, it has identified millions of potential<\/em> switches\u2014all the science of those switches still has to be done. Many of the science writers who have plumped this story simply dressed up the ENCODE project\u2019s press release<\/a>, dumbing down a lot of complex science into an easily digestible but historically misleading narrative.<\/p>\n

Oversimplification is endemic in both science and science journalism. The former is a set of methods for making the complex simple\u2014and the latter is a set of methods for making science simple. I did both before studying history, which is a set of methods for making the simple complex\u2014or, rather, for decoding the complexity in what we oversimplify. Addressing subjects as massively complex and integrated as the genome\u2014or the brain, or the immune system, or an ecological community\u2014requires both approaches.<\/p>\n","protected":false},"excerpt":{"rendered":"

When I was a science writer at Cold Spring Harbor Laboratory, back in the early 1990s, I attended the annual genome meeting and heard Sydney Brenner make his pitch for the fugu genome. The puffer fish\u2014known to sushi aficionados and neurobiologists for its tiny gland that produces the neurotoxin tetrodotoxin\u2014Brenner, said, has a marvelously condensed … Read more<\/a><\/p>\n","protected":false},"author":19,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_post_was_ever_published":false,"_links_to":"","_links_to_target":""},"categories":[1],"tags":[9,177,173,174,54,176,175],"class_list":["post-176","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-barbara-mcclintock","tag-complexity","tag-encode","tag-fugu","tag-history","tag-journalism","tag-sydney-brenner"],"yoast_head":"\nDecoding ENCODE - Genotopia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/genotopia\/176\/decoding-encode\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Decoding ENCODE\" \/>\n<meta property=\"og:description\" content=\"When I was a science writer at Cold Spring Harbor Laboratory, back in the early 1990s, I attended the annual genome meeting and heard Sydney Brenner make his pitch for the fugu genome. 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From 1997 to 2002, he was on the history faculty at The George Washington University, where he also served as Deputy Director of the Center for History of Recent Science. The Center\u2019s director and founder was Horace Freeland Judson (The Eighth Day of Creation), who, along with John McPhee and Monty Python, Comfort considers among his biggest writing influences. Comfort\u2019s books include The Science of Human Perfection: How Genes Became the Heart of American Medicine (Yale, 2012), The Tangled Field: Barbara McClintock\u2019s Search for the Patterns of Genetic Control (Harvard, 2001), and the edited volume, The Panda\u2019s Black Box: Opening Up the Intelligent Design Debate (Johns Hopkins, 2007). In addition to scholarly articles, he has written for Natural History, the New York Times Book Review, National Public Radio, Nature, Science, New Scientist, The Believer, and other publications. 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