RNA research EteRNA gets its game on

Bejeweled and Angry Birds are fun, but the computer games represent little more than a pleasant way to kill time.

Then there's EteRNA. It's a new game developed by researchers at Stanford and Carnegie Mellon in which players build strands of RNA, DNA's chemical cousin. The "winners" get to see their designs made into real RNA.

"The idea was to create games like Pong or Pac-Man, but instead of a ball, you play with living organisms," said Rhiju Das, an assistant professor of biochemistry at Stanford and one of the game designers.

EteRNA, which went live this week, is the latest in a growing field of interactive biology games, coming on the heels of a popular protein-based game called FoldIt.

Players aren't scientists, and, more often than not, they don't know much about the biology they're playing with. Still, researchers are hoping that their gaming skills will prove useful in the lab.

"My sense is there are people out there in the world who can look at these games and do them much better than I can," Das said. "This project has a chance of uncovering principles of RNA design that have been missed by me and experts in the field."

Not for children

EteRNA isn't a game for schoolchildren, and it's not designed to teach people all about RNA. There are brief lessons along the way, mostly to help players understand the rules of building RNA, and, therefore, the rules of the game.

RNA is one of the "holy trinity" of biology, along with DNA and protein. They're the three molecular building blocks of life. DNA carries the basic instructions for building protein, and RNA is responsible for making sure those instructions are carried out.

For decades, scientists assigned RNA a minor role as the "messenger," but, in the past 10 years, they've come to appreciate its subtle power. Now RNA is considered a possible key to solving a wide variety of human ailments, from HIV and polio to genetic diseases.

"It was thought to be scrap paper, this carbon copy of DNA," Das said. "But it's not just scrap paper. It can cut and paste itself, it can be scissors and tape, and it all gets remixed after it's made. It's more like an operating system for DNA."

Whereas DNA is known for its famous double-helix design, RNA is made up of single strands that fold and loop into intricate, "beautiful" designs, Das said. Those shapes are essential to RNA's performance, and scientists have spent 30 years in labs trying to develop an algorithm that will define how and why RNA folds the way it does so they can learn to replicate it in the lab.

But there are gaps in the algorithms. And that's where EteRNA comes in.

Researchers developed the game based on the best algorithm available. The schematics allow players to create computerized RNA according to that algorithm. But because the algorithm isn't perfect, what works for computerized RNA might not work in real life.

That's where the fun starts, says Adrien Treuille, an assistant professor of computer science at Carnegie Mellon, who worked with Das on the game. Every week, EteRNA players will be given a target RNA shape, one that's actually found in nature.

Players will make computerized designs that create that RNA shape, then they'll vote on the design that they think is most viable, based on the stability of the structure and how closely it matches the organic shape. The scientists will try to produce the winning design in the lab.

Scientists hope that EteRNA will utilize "crowd sourcing," an online phenomenon that allows thousands of minds to come together and solve a problem - or answer a question - that would take a team of individuals years or decades to figure out.

"We're trying to get as many players as possible," said Treuille, who noted that the game already has about 7,000 players since first going public last week. "One of the things we're trying to study is how big of a community can we scale to so that meaningful advances are made."

'Silly exercises'

Das noted that players aren't designing RNA for new life forms, or even existing forms such as HIV or other viruses. Most of the RNA designs in the game are from monkeys or insects or plants. They're "silly exercises," Das said. "They're not RNA that would glow in the dark when they sense food. We might do that in a few months."

But Jackie Gu, who was one of the game's original testers, said it's still a lot of fun. She was just 14 and a freshman at Saratoga High School when she tried out some of the early designs in May - and surprised the researchers by solving a few tough challenges. She ended up working in Das' lab over the summer and getting the chance to manufacture the RNA she designed.

"For my first one, it was just a test run, and they didn't expect me to succeed. But to everyone's surprise, I did," said Gu, who has since designed several RNA samples. "After designing them online, I synthesized them in the lab. That was really, really cool."

E-mail Erin Allday at eallday@sfchronicle.com.

This article appeared on page C - 1 of the San Francisco Chronicle