[rael-science] Games for Science‏

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Source: http://www.the-scientist.com/?articles.view/articleNo/33715/title/Games-for-Science/

Games for Science

Scientists are using video games to tap the collective intelligence of people around the world, while doctors and educators are turning to games to treat and teach.

Video games designed to tackle tough scientific problems are leading to breakthroughs in RNA structure, protein folding, genetic sequence alignment, and more.

Eli Fisker has struggled to hold down a job as a librarian, largely as a result of an undiagnosed condition he describes as similar to Asperger’s. In his ample spare time, the 35-year-old from Alborg, Denmark, plays an online video game in which he arranges colored discs into two-dimensional chain-link shapes. It’s addictive, and he plays for hours on end. But EteRNA is not your typical Internet time suck: the discs represent nucleotides, and the patterns they form are blueprints for RNA molecules.

Every 2 weeks, the best designs—voted for by the players themselves—are synthesized in the lab by the Stanford University scientists who helped to create the game, and observations about how the resulting molecules behave are relayed to the players. That feedback informs the development of new playing strategies, which in turn help the scientists to better understand the rules of RNA folding and function. Although there’s no PhD after his name, Fisker, one of the best of the game’s 40,000 registered players, is helping to unravel a fundamental aspect of biochemistry that has long eluded the world’s brightest scientists—and even helping to design novel RNAs that encode proteins to fix carbon or fight disease.

RNA RUBIK’S CUBE: By switching each disc in the chain into one of four color-coded nucleotides,EteRNA players design RNA molecules, the best of which are synthesized in the lab.© ALEX SLOBODKIN/ISTOCKPHOTO.COM“Our ultimate goal is to create a platform that will enable anyone to design RNAs for anything, and have them tested via our experimental pipeline,” says Rhiju Das, a biochemist at Stanford University who helped develop EteRNA. “We call it cloud biochemistry.”

Launched in January 2011, EteRNA is one of a small stable of video games that enlist the collective intelligence of players—most with no scientific background—to solve fiendishly difficult scientific problems. It’s early days yet, but the approach has already notched some impressive achievements, including a string of widely discussed discoveries published in high-impact journals. It won’t solve every scientific problem, of course, but some argue that the recent “gamification” of science has enormous potential.

“We’re still in the proving stage, exploring how useful [gaming] can be,” says Andrew Su, who runs a bioinformatics lab at the Scripps Research Institute in La Jolla, California. “But I’m very optimistic.”

Perfecting proteins

The first and arguably most influential research game was Foldit. Created by structural biologists and computer scientists at the University of Washington in Seattle, Foldit challenges players to work out the three-dimensional structures of proteins by folding chains of virtual amino acids into optimal configurations. Results generated by online players have already accrued multiple publications in Nature journals since the game’s launch in May 2008.

The game grew out of Rosetta@Home—a project that farmed out computationally intensive protein-folding simulations to home computers. But rather than simply exploiting the spare processing power of PCs around the world, Foldit also makes use of the brainpower of computer owners by framing the problem as a competitive online game.

Players are presented with a hodgepodge of zigzags, squiggles, and loops representing the amino acids of a protein. Moving the cursor allows users to grab, bend, wiggle, and shake various parts of the molecule, with the aim of folding the messy structure into its optimal shape—the form that has the lowest energy—just as molecules tend to do in real life. The more stable the structure, the higher the score.

Foldit players quickly proved they could outperform the randomized runs of Rosetta, which simulates and tests millions of tweaks to the chain to find the shape with the lowest energy. In a challenge to work out the structures of 10 proteins that the scientists had already solved, the players got closer to the true structure than Rosetta for five of the proteins and matched it on three. Then, in September 2011, Foldit players made a breakthrough: they solved the structure of a retroviral protease of the Mason-Pfizer monkey virus, which causes an AIDS-like disease in monkeys—a problem that had stumped scientists for a decade. The study was published in Nature Structural and Molecular Biology (18:1175-77, 2011), listing the “Foldit Contenders Group” and the “Foldit Void Crushers Group” among its authors.

The achievements of the Foldit player community are really eye-opening. They’ve clearly hit on a model that is fun and scientifically productive.

—­Andrew Su, Scripps Research Institute

The game’s creators have also devised a way to extract and replicate Foldit players’ best folding strategies—which they were invited to encode and share as so-called “recipes”—in addition to their solutions. One such recipe, known as Blue Fuse, which evolved as it spread like wildfire among the game’s elite players, proved even more efficient than the algorithms that drive Rosetta (PNAS, doi:10.1073/pnas.1115898108, 2011). “It was really stunning,” says David Baker, a computational structural biologist at the University of Washington, who helped to create the game. “What they had developed, independently from us, was something better than the best current algorithm we were working on.”

MIX AND MATCH: Phylo takes a Tetris-like approach to multiple sequence alignment, challenging players to line up rows of colored blocks to help identify important DNA sequences.© FRANCKREPORTER/ISTOCKPHOTO.COMIn addition to deciphering and refining natural protein structures, the Folditcommunity is also trying its collective hand at designing better proteins. In January 2012, for example, Foldit players redesigned an enzyme in a way that sped up a reaction crucial to the production of a variety of drugs by almost 2,000 percent (Nature Biotechnology, 30:190-92, 2012). Researchers are also tasking Foldit players with designing and refining entirely new proteins, such as one to bind to and inhibit the influenza A virus, Baker says. “We’re trying to design potential protein therapeutics, and we’re enlistingFoldit players every step of the way.” Furthermore, Foldit’s designers hope to extend the drug discovery element of the game with a new toolbox of organic subcomponents that will enable the design of novel small molecules.

Foldit has helped to establish online games as a credible source of discovery in computational biology, says Su. “The achievements of [theFoldit] player community are really eye-opening,” he says. “They’ve clearly hit on a model that is fun and scientifically productive. Now a lot of people are paying attention.” 

Games for everyone

Foldit’s success has inspired other researchers to exploit the minds of gamers around the world to improve upon existing scientific methods. In comparative genomics, multiple sequence alignment (MSA) is used to identify functional elements of the genome and possible disease triggers. If a particular sequence is conserved across different species, it is likely to have an important function; and if such a sequence is mutated in people with a particular disease, it may be the cause. “MSA is probably one of the most important tools in bioinformatics today,” says Jérôme Waldispühl, a bioinformatician at McGill University in Montreal, Canada.

But the computer algorithms employed to perform MSA don’t guarantee perfect accuracy, so Waldispühl and colleagues createdPhylo—an online game that transforms the MSA problem into a simple puzzle that anyone can play. The aim of the game is to improve the sequence alignments of the promoter regions of hundreds of disease-related genes from 44 vertebrate species. The sequences are presented as several rows of blocks, color-coded to represent the four bases of DNA, and players shift the sequences left or right in order to find the best possible match for up to eight different species at a time.

Within 7 months of its November 2010 release, Phylo had more than 12,000 registered users and 3,000 regular players. And they’ve proven themselves worthy: 70 percent of the roughly 350,000 MSA solutions generated by the Phylo community are more accurate than those generated by the best computer algorithm (PLOS ONE, 7:e31362, 2012). “The results returned by the players were much better than what we hoped for,” says Waldispühl. “The human brain has evolved to be very good at recognizing visual patterns, and we can benefit from that.”

For problems where there is some quantity that defines correct answers, then I think games will be powerful.
—­David Baker, University of Washington

The game is now available on mobile devices in several different languages. And the team behind Phylo is currently developing an interface that will allow any geneticist in the world to sign in and upload sequences to be converted into puzzles and played by the community. Waldispühl says the idea is to give researchers access to the huge amount of human processing power provided by gamers. “What we want to do is make the best synergy between computer and human,” he says.

A newcomer to the scene is The Cure, a game developed at Su’s lab at the Scripps Research Institute to help find better predictive biomarkers for breast cancer prognosis. Launched last September, The Cure works like a card game in which players assemble a “hand” of five genes from a board of 25 genes pre-selected for their relevance to the disease. The gene set that wins is the one that produces the best predictive model of breast cancer prognosis, as determined by a cross-validation statistical analysis.

Research gaming has even begun to reach beyond the domain of molecular biology. Whale.fm is helping marine scientists advance their understanding of whale communication by asking players to match recordings of whale calls from different parts of the world. The exercise is designed to categorize different whale “dialects” and reveal more about the full repertoire of cetacean language.

BENDING PROTEINS: Foldit players solve protein structures by shaking, wiggling, and generally rearranging chains of amino acids into their optimal, lowest-energy configuration.© NICHOLAS MONU/ISTOCKPHOTO.COMThis burgeoning interest is a testament to the power of competitive, multiplayer online games to solve complex scientific problems, but how far will it go? Will gamification have a profound impact on the way scientific research is carried out? The answer, Baker says, is likely to depend on the type of question being asked. “For problems where there is some quantity that defines correct answers, then I think games will be powerful,” he says. “But there are other problems that just can’t be posed in that way, and those will be less surmountable with scientific games.”

At the very least, it’s a chance for dedicated gamers like Eli Fisker, most of whom have no formal scientific background, to experience the thrill of discovery. And by encouraging people to engage with complex research problems in a fun and intuitive way, such games could inspire a new type of citizen scientist, says Das—one who may find novel solutions that the professionals have missed. “Wouldn’t it be great if [anyone] could just log in from anywhere and start experimentally tackling the mysteries of life?”

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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.
 
There is nothing glorious about what our ancestors call history, 
it is simply a succession of mistakes, intolerances and violations.
 
On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.
 
Rael
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