RNA Game Lets Players Help Find a Biological Prize - Center for Technology Transfer and Enterprise Creation - Carnegie Mellon University

Monday, January 10, 2011

RNA Game Lets Players Help Find a Biological Prize

Scientists at Carnegie Mellon University and Stanford University are attempting to harness the wisdom of crowds with the creation of an online video game that challenges players to design new ways to fold RNA molecules.

The scientists hope to uncover fundamental principles underlying one of life’s building blocks, and they believe that the free game will also serve as a training ground for a cadre of citizen-experts who will help generate a new storehouse of biological knowledge. The process may also aid researchers in building more powerful automated algorithms for biological discovery.

The game, EteRNA, is accessible at eterna.cmu.edu/content/EteRNA. It allows non-biologists to design complex new ribonucleic acid (RNA) molecules, as well as to receive quick feedback on the biological function of their designs.

In a way, EteRNA is a successor to Foldit, a popular Internet-based video game that proved that the pattern matching skills of amateurs could outperform some of the best protein-folding algorithms designed by scientists.

Designed by some of the same researchers as Foldit, EteRNA is similar in that it is basically a two-dimensional puzzle-solving exercise performed in this case with the four bases — adenine, guanine, uracil and cytosine — that make up RNA molecules. Players can design elaborate structures including knots, lattices and switches. Unlike earlier efforts at crowd-sourced science, EteRNA will cross over from simulation to biology. Each week the best designs created by game players and chosen by the gaming community will be synthesized at Stanford, according to the scientists.

Synthesizing the designs created by game players will make it possible for researchers to see if their models fold correctly, yielding predicted shapes that are biologically active. Beyond better biological understanding, the scientists believe they will be able to employ new RNA molecules as a basic toolkit to help explore new avenues in nanoengineering.

“The dream is that within a year or so we will be able to create RNA that is functional and that we can transcribe into cells to do things such as sense light or even deactivate a virus,” said Rhiju Das, a physicist who teaches in the Stanford biochemistry department and who is one of the designers of the game.

During the last half decade there has been a rapidly growing interest in the role of RNA as a messenger and a regulator of cell functions. But there is still a tremendous amount that biologists have yet to learn about its purpose. And it is possible that RNA could be used to build a powerful biological computer, Dr. Das said.

EteRNA is the joint effort of a group of scientists led by Dr. Das, and Adrien Treuille, an assistant professor of computer science at Carnegie Mellon. They met as postgraduate researchers at the University of Washington, where they were part of the team that created Foldit.

The new game may be more user-friendly in some ways. “I do think EteRNA will be easier to play,” said Jeehyung Lee, a computer science graduate student at Carnegie Mellon, who led the programming effort to design the game.

But mastering the molecule construction kit requires players working individually and in groups to become adept in some aspects of biochemistry. “We’re the leading edge in asking nonexperts to do really complicated things online,” said Dr. Treuille. “RNA are these beautiful molecules. They are very simple and they self-assemble into complex shapes. From the scientific side there is a RNA revolution going on. The complexity of life may be due to RNA signaling.”

The scientists hope to tap the Internet’s ability to harness what is described as “collective intelligence,” the collaborative potential of hundreds or thousands of human minds linked together. Using games to harvest participation from amateurs exploits a resource which the social scientist Clay Shirky recently described as the “cognitive surplus.” It was recently estimated by the software developer Rovio, for example, that its iPhone game Angry Birds consumes roughly 200 million minutes of human attention each day.

“This is like putting a molecular chess game in people’s hands at a massive level,” said Dr. Treuille. “I think of this as opening up science. I think we are democratizing science.”

Whether what the researchers describe as “social computation” will have a significant impact on scientific research has yet to be seen. Foldit, in which players competed to predict protein folding, attracted more than 50,000 participants. Significantly, not only were the humans able to outperform software protein algorithms, but the scientists determined that the human strategies developed in the course of the game were significantly more flexible and adaptable than the computer-only software programs they competed against.

Another effort, Galaxy Zoo, developed to help classify deep sky objects by a broad community of astronomers, has so far enlisted more than 250,000 people in an Internet system that employs the pattern recognition skills of Web surfers. The designers initially thought that it would take a year to classify the one million galaxy images collected by the Sloan Digital Sky Survey. But within a day of the project’s start, eager users were classifying more than 70,000 objects an hour, and 50 million classifications were entered in the first year from almost 150,000 people.

The early experience with both Foldit and Galaxy Zoo is just a hint of the power inherent in digitally weaving together humans, Mr. Shirky said.

“We’re still in the world of special cases,” he said, “but there are bunches of places where people are being harnessed for their native cognitive abilities.”

For the moment, Dr. Treuille said the development of new forms of RNA would not pose safety issues because the components are being created in such small quantities and are isolated in test tubes. In the future, real ethical and legal questions may confront the game players.

“We want to modify little bits of cellular machinery that do real things,” he said. “There is the question of not just safety but also the question of who owns it.”


Article courtesy of
NYTimes