Photo: Nigel Parry
Jessica Fournier has a job that makes poor use of her talents. She spends her days stocking sneakers at a warehouse outside Grand Rapids, Michigan. A decade ago she was an astrophysics student at Michigan State University, where she coauthored a paper on RR Lyrae, a low-mass star that pulsates light. But having failed to secure long-term employment in her arcane field, today she pays her bills by cataloging shoe sizes.
She may have given up astrophysics, but Fournier still has a deep love of science. As soon as she gets home from work each night, she boots up her Asus laptop and begins what she calls “my second job”: designing molecules of ribonucleic acid—RNA—that have the power to build proteins or regulate genes. It is a job that she happens to perform better than almost anyone else on earth.
Under the fitting nickname “starryjess,” Fournier is the world’s second-ranked player of EteRNA, an online game with more than 38,000 registered users. Featuring an array of clickable candy-colored pieces, EteRNA looks a little like the popular game Bejeweled. But instead of combining jewel shapes in Tetris-like levels, EteRNA players manipulate nucleotides, the fundamental building blocks of RNA, to coax molecules into shapes specified by the game. Those shapes, which typically look like haphazardly mowed crop circles or jumbled chain-link necklaces, represent how RNA appears in nature while it goes about its work as one of life’s most essential ingredients. No self-sustaining organism gets made without the involvement of RNA.
Tweaking molecular models in this fashion is surprisingly fun—and, it turns out, useful. EteRNA was developed by scientists at Stanford and Carnegie Mellon universities, who use the designs created by players to decipher how real RNA works. The game is a direct descendant of Foldit—another science crowdsourcing tool disguised as entertainment—which gets players to help figure out the folding structures of proteins. EteRNA, though, goes much further than its predecessor.
The game’s elite players compete for a unique and wondrous prize: the chance to have RNA designs of their own making brought to life. Every two weeks, four to 16 player-designed molecules are picked to be synthesized in an RNA lab at Stanford. “It’s pretty incredible to imagine that somewhere there’s a piece of RNA that I designed that never existed anywhere in nature before,” says Robert Rogoyski, a New York City patent attorney who has had 14 of his EteRNA designs selected for synthesis. “It could encode a protein that no one has ever seen, something that’s important in the discovery of the next blockbuster glaucoma or cancer drug. Or it could be the cause of the zombie apocalypse.”
The chance to win this reward has proven highly motivating for EteRNA‘s players. They carefully study the data that the lab provides on how the synthesized molecules behave when ushered into existence, then use their observations to refine their next designs. In doing so, they—like their Foldit-playing peers—have helped scientists take advantage of the human brain’s unparalleled talent for recognizing patterns and solving puzzles. But EteRNA players have also done something much more profound: By scrutinizing their creations, learning from their triumphs and mistakes, and using their accumulated wisdom to develop new hypotheses, they aren’t just building better RNA molecules; they’re discovering fundamental aspects of biochemistry that no one—not even the world’s top RNA researchers—knew before. And in doing so, they are blurring the line that separates gamer from scientist.
At the heart of EteRNA is a small rivalry, the sort that often forms in competitive academic environments—in this case, inside the lab of David Baker, a renowned biochemist at the University of Washington. Baker has dedicated his career to figuring out and manipulating the byzantine shapes of proteins, the compounds that help form cells and make them function. Proteins consist of long chains of amino acids that fold into ornate spirals and loops as their constituent atoms push and pull on one another. Since a protein’s shape is vital to its function, researchers are constantly striving to grasp the rules that govern these contortions.
Adrien Treuille first came to Baker’s lab in January 2007 as a postdoc, having just completed a PhD in computer science. Treuille was drawn to the lab by Baker’s use of Rosetta@home, a free screensaver that doubles as a contribution to science. When a computer installed with Rosetta @home falls idle, the program can access the machine’s processing power to crunch data on protein shapes. By the time Treuille joined the lab, the screensaver had been downloaded more than 75,000 times.
There was just one problem with Rosetta@home: From the perspective of the person who installed it, it was totally inert. The screensaver did nothing but show an image of a folding protein. Treuille and a colleague named Seth Cooper were enlisted by their academic mentor, Zoran Popovíc, to add an interactive element to the program.
Within a few months, Treuille and the team had created a demo that allowed Rosetta@home users to earn points by manipulating a three-dimensional protein model into a specific shape. This interactive Rosetta was hopelessly buggy, prone to crashing twice an hour. But Treuille noticed that his testers were saving their shapes every minute—they were so absorbed in the quest for points that they didn’t want to lose their progress when the program inevitably conked out.
However, one postdoc in Baker’s lab, Rhiju Das, was a vocal critic of the game. “Rhiju was sort of this rock star, just this really smart guy,” recalls Treuille, a wiry 33-year-old New York City native who favors sagging jeans and hoodies. Das, the lab’s RNA expert, found the game pitiful. Because Das was held in such high esteem in Baker’s lab, Treuille was stung by his negative take on the new interactive elements of Rosetta. “Rhiju was a scathing critic,” Treuille says. “He basically wrote this email to the whole Baker lab where he was like, ‘I’m not sure how competent these computer science guys are, because this is a giant, steaming piece of crap.’”
But slowly the bugs were worked out, and Das was won over by the final version of the game, which was renamed Foldit prior to its release in May 2008. Tens of thousands of players flocked to Foldit that summer, drawn by the Rubik’s Cube-like challenge of twisting proteins until their most stable shape was achieved. By swapping tips, the best players quickly learned to beat the game’s most demanding challenges. Impressed, Baker urged these Foldit buffs to enter an international protein-folding competition (covered by Wired in our May 2009 issue), in which competitors—until that year always professional scientists—vie to accurately predict a protein’s shape based only on its amino acid sequence. By using the game to test the validity of their entries, a team of Foldit players outperformed many of the scientists—and scored first place in one category. Today the game continues to produce valuable data: In 2011, University of Washington researchers used insights gleaned from Foldit to crack the structure of a protein involved in the maturing of retroviruses like HIV.
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