Online Games Help Fight Disease

Video games can serve the higher public good when players work alone or with a team to solve genetic and biochemical puzzles

Article Highlights:
  • Several new online games offer players a chance to perform useful scientific tasks, such as aligning portions of genetic code, folding proteins and designing molecules, at the same time as they compete for high scores.
  • The games are designed to harness the collective brain power of computer users to take on important but time-consuming jobs that computers can't readily do by themselves.
  • Researchers hope that, by helping solve these puzzles, “citizen scientists” at home can speed up the process of scientific discovery, hastening development of cures and treatments for diseases like ALS and muscular dystrophy.
by Miriam Davidson on March 31, 2011 - 11:57am

QUEST Vol. 18, No. 2

Note: This article was updated Sept. 19, 2011.

Video games have a reputation for being big time-wasters. But what if you could help solve scientific mysteries — such as unraveling the origins of a genetic disease — at the same time as you’re having fun?

That’s the idea behind several new online games designed to harness the collective brain power of computer users — a process known as “distributive computing” — for purposes greater than killing zombies.

One game, called Phylo, invites people to align colored squares that represent regions of genetic code (DNA) that are similar among different species.

Another, Foldit, asks users to figure out the best way to fold proteins, a basic activity of cells that, when gone awry, is thought to cause disease.

And a third game that just started in 2011, EteRNA, asks players to come up with new designs for molecules of RNA (the chemical messengers of the cell) — designs that someday could be used to combat disease.

Although all of these games are meant to be played by nonscientists, figuring out how to play and score them can be a challenge. Designers are still working on the scoring systems and other details to make the games more user friendly.

The games’ creators insist, however, that patience and practice will pay off. They say players get satisfaction not only from attaining high scores and beating rivals, but from knowing that they’re contributing to deeper scientific understanding of genetics, biochemistry, and — perhaps someday — diseases like muscular dystrophy and ALS.

The wisdom of crowd sourcing

There are some things that humans still can do better than computers. Such talents include recognizing subtle differences in shapes, determining patterns, making intuitive leaps, sacrificing short-term gain for long-term benefit, foreseeing dead-ends and knowing when to quit (at least when it comes to video games).

The first distributive computing (a form of crowd sourcing) game to take advantage of these unique human abilities was Galaxy Zoo. This astronomy project, launched in England in 2007, asked computer users to categorize galaxies as spiral or elliptical — a simple task that computers are simply incapable of doing. The project took off. Thanks to thousands of volunteer citizen-scientists looking at pictures of outer space on their computers, more than 1.25 million galaxies have been classified so far.

Cell biology computer games

Phylo: Building on the success of Galaxy Zoo, this game, developed by biologists and computer scientists at McGill University in Montreal, seeks to capitalize on human prowess in pattern recognition. It takes pieces of the human genome that have been pre-aligned by a computer, sorts out the alignments the computer had trouble with, and asks players to improve on them.

Screenshot of the game Phylo
In the game of Phylo, players align colored squares representing pieces of genetic code (DNA) that are similar among different species.

According to lead designer Jerome Waldispuhl, a professor in bioinformatics and computational biology at McGill, there are about 10,000 regular Phylo players. He said the game has the potential to aid research into genetic diseases because it focuses on sections of DNA that control expression (activity) of the gene, where mutations are likely to cause the most damage.

“We are doing a service,” Waldispuhl said. “Once the players have improved the alignment, we give the information back to the scientific community for analysis. The idea is to provide high-quality data to biologists.”

Waldispuhl said his team is currently working on simple versions of Phylo that would be available on Facebook or other social media. He said that at some point, researchers hope to re-annotate the human genome so people would know which part they helped align.

Foldit: This game tackles one of the most complex problems in biology: the question of how chains of amino acids fold themselves up into protein structures within cells. Even a small protein can consist of 100 amino acids, and some human ones are more than 10 times that large, with hundreds of chemical “side chains” sticking off the main chain.

Depending on the protein’s purpose in the cell, each chain folds itself into a complex, three-dimensional structure. When the chain is misfolded, the protein can’t do its work and/or can cause harm. Several diseases, including Alzheimer’s and possibly ALS, are thought to result at least in part from misfolded proteins.

Screenshot of the game Foldit
The game Foldit asks players to come up with the best way to fold proteins, an essential function of cells. Because the protein-structure puzzles are three-dimensional, this game is extremely difficult.

Foldit was initially designed by researchers at the University of Washington at Seattle as a screen saver called Rosetta@home, which enabled otherwise-idle computers to work on protein folding by themselves. But people who watched their computers slowly struggle with the puzzles began contacting the program’s developers to say they could see ways to improve on the computer’s performance.

The scientists then created the game of Foldit, which they used to test human players against the computer. They found that, in most cases, humans were able to do a better job. Foldit allows players to compete against each other for points as they work on finding solutions to these extremely complicated puzzles. If players are any good, they may have the satisfaction of seeing their methods incorporated into new computer programs with superior protein-folding abilities.

Firas Khatib, a postdoctoral researcher in biochemistry at UW who helped develop Foldit, concedes that, “It’s not as exciting as some of the games out there.” More than 200,000 people have registered to play, but most (employing another one of their human talents) have given up because protein folding is just too hard. Khatib says the Foldit team is studying ways to make the game more accessible, yet still useful to scientists.

Update, Sept. 19, 2011: In just three weeks, Foldit gamers produced an accurate model of a protein-cutting enzyme from an AIDS-like virus, solving a problem that had stymied scientists for more than a decade, reports a paper appearing Sept. 18 in the journal Nature Structural & Molecular Biology. The model provides “exciting opportunities for the design of retroviral drugs, including AIDS drugs,”  says the paper, which lists both scientists and gamers as co-authors.

Screenshot of the game EteRNA
In the game EteRNA, players can create new designs for molecules of RNA (chemical messengers of the cell) that may someday be used to combat disease.

EteRNA: Pronounced “e-tern-a,” this newest addition to the online cell biology game roster is much like Foldit, except easier, because the puzzle exists in two dimensions instead of three. It was designed by researchers at Stanford and Carnegie Mellon University, some of whom previously worked on Foldit.

RNA, or ribonucleic acid, consists of long chains of chemical compounds called nucleotides that perform a variety of functions in cells, such as providing a template for protein synthesis from DNA instructions, delivering amino acids to the place where they will be synthesized into protein molecules, and influencing gene expression levels.

Scientists are still discovering all their functions and roles in causing (and preventing) disease.

In this game, using colored circles that represent the four nucleotides that make up RNA, players are invited to form RNA chains and other structures.

EteRNA players compete against computer programs to find the fastest way to solve known RNA designs. They also are given the opportunity to design new RNA molecules that could someday be used as switches or nanomachines to fight disease.

The game’s website encourages originality. It says, “By playing EteRNA, you will participate in creating the first large-scale library of synthetic RNA designs.” It also offers a more immediate incentive: Players who come up with the best design each week will be awarded by having their new RNA molecules synthesized in the lab at Stanford.

How to play

In all of these games, players work either individually or as part of a team. Players can compete for the best score against the computer, or against other individuals or teams from all over the world.

The sites offer tutorials and practice puzzles to get started, increasing levels of difficulty, links and other information to help players understand the science behind what they’re doing. Playing is free — and the science is priceless.

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