In short order, players who had never heard of Turner’s Rules proved that the underlying energy algorithm acted only on nearest neighbors. They created online charts showing all possible permutations of adjacent base pairs and their free energy contributions as measured by exhaustive in-game enumeration. Shortly thereafter, they discovered that bulges and loops could be stabilized with a dangling purine at the 3' end of a helix and that certain tetraloop sequences got a bonus. Most significantly, they concluded that strategies that worked for the canned puzzles did not work for the actual design challenges.
One might think, given the game’s emphasis on points and rankings, that players would hoard their best tricks to themselves – just as the gentleman-scientists of antiquity were loath to publish their most significant findings. But that’s not how events have unfolded. Each new insight is posted, analyzed and heatedly discussed in public online forums. Credit for ideas always is duly attributed. Massive design spreadsheets annotated with musings from the top players are freely shared. Most impressively, this cadre of elite players devotes countless hours showing the ropes to newbies so that they, too, can get synthesized and ultimately contribute fresh ideas to the fold – even if it means giving up their own coveted synthesis slots!
How many of us card-carrying scientists honestly can claim to adhere to the same ethos?
There were obstacles, however, to creating this self-sustaining ecosystem. The small, overstretched team of graduate students responsible for day-to-day operations of the game soon found themselves inundated by requests for more detailed explanations of the underlying science. What does free energy mean, anyhow, and why did designs with extremely negative free energies fail to synthesize in the lab? What is a suboptimal fold? Why is RNA only shown in 2-D? Players were getting frustrated and were quickly losing interest.
So I decided to stop being a passive observer. I linked review articles on folding algorithms, some key primary literature and other bioinformatics tools they could use to analyze their designs. I started logging in late at night to field random questions from curious players about anything and everything, from “What’s a tetraloop?” to “How can RNAs be used to treat cancer?”
It was like pouring gasoline on a fire.
The resulting flurry of activity in the forums and chat rooms proved something I had suspected all along. Ordinary citizens can read and absorb primary literature; they can formulate hypotheses, test them and analyze data. In other words, ordinary citizens can participate in science! They just need to be introduced to an interesting problem, provided with the right tools, and given access to someone willing to answer their questions. EteRNA already provided two of the three.
Providing an outreach opportunity
To be fair, EteRNA is a research project about crowdsourcing to optimize RNA folding algorithms. It was not envisioned as an outreach project, judging by the lack of educators on staff and the lengths taken to shield players from the details of the underlying science. And while such measures were necessary to appeal to casual players, the need to provide detailed explanations to sustain the interest of the most talented players initially was overlooked. This has been addressed as of late, as players now are being allowed to participate actively in improving the game itself. There even is a planned series of Q&A sessions with actual RNA researchers.