Citizen science just went next level: Video gamers have made a biological discovery, and it’s now been published by a peer-reviewed scientific journal.

Published this week in the Journal of Molecular Biology, a series of intuitively developed rules for how difficult a particular shape will be to achieve through RNA design. They found, for example, that the more symmetrical a shape is, the harder it will be to design a strand of RNA to match it.

The collective of video-gamers made the discovery by playing, EteRNA, a game that challenges players to take strands of RNA and fold them into a desired shape by altering their chemical makeup. The scientific problem of folding RNA into a particular shape is complex, but the game is not — no understanding of biochemistry is required to start playing.

The gamers took up the research question on their own initiative, as a way of giving newer players tools to judge the relative difficulty of different puzzles. The findings will help guide future biomedical research, since the new set of rules gives scientists a better sense of whether or not trying to fold RNA into a given shape is a futile exercise.

“This research suggests that the standard paradigm of scientific crowdsourcing can be flipped,” Rhiju Das, a professor of biochemistry at Stanford, tells Inverse in an email. EteRNA was launched in 2011 by Das and Adrien Treuille, an assistant professor of computer science at Carnegie Mellon University. “EteRNA players can devise their own research questions and can write up their own papers. In this research, there was a little guidance and independent testing from experts in my lab.”

Synthesized RNA holds an incredible potential for a new generation of drugs and medical therapies. If it can be folded into the right shape, RNA can be built to target specific viruses, cancers, and even genetic disorders. CRISPR, a gene editing process that could dramatically alter the future of human existence, uses RNA to guide the DNA-cutting enzyme, Cas9, to the undesirable section of DNA.

EteRNA started out as a forum for expert scientists to present puzzles to the gamers, but it’s since grown beyond that. The game and its 100,000 registered players now exist in a symbiotic and evolving relationship with professional scientists and computer models built to design and test RNA structure.

“Computer modeling and EteRNA are not exclusive,” says Das. “EteRNA brings together lots of people, some of whom are writing their own computer models.”

In the current paper, the players collaboratively wrote scripts to test their ideas for what makes RNA structures difficult to design. Das says that some players told him they are particularly excited to automate their ideas into computer models because they want to go on and solve harder problems.

Problems built by EteRNA players actually go on to be synthesized in Das’ lab — so far 86,459 player-generated sequences have been built IRL.

The lead authors of the paper were EteRNA gamers Jeff Anderson-Lee, Eli Fisker, Vineet Kosaraju, and Michelle Wu. Wu is also a Ph.D. student in biomedical informatics at Stanford.

In the future, it could be that citizen experts begin publishing scientific discoveries completely independently.

“This ‘flipped crowdsourcing’ template for citizen science might be useful for other projects and fields of science, such as astronomy (Galaxy Zoo) or crowd-sourced species identification (Barcode of Life),” says Das. “Especially if they, like EteRNA, are seeing bottlenecks at the stage of paper writing.”


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