< New Online Game Helps Solve Medical Mysteries

Transcript

Friday, September 30, 2011

In a story that aired the weekend of September 30, Brooke Gladstone stated that an article about the game Foldit was published inScience Structural and Molecular Biology. The paper was actually published in Nature Structural and Molecular Biology. Please click on the name of the journal to follow a link to the article abstract.

BROOKE GLADSTONE:

Last New Year's we devoted the show to gaming. We wondered if all those millions of hours spent in virtual worlds could have any substantive impact on the real one.

Well, an article published in a recent issue of the journal Science Structural and Molecular Biology* may have one answer. Using a game available to anyone online called Foldit, gamers successfully built a model of an enzyme crucial to understanding how many diseases, such as AIDS, do their damage. Solving the crystal structure of the M-PMV retroviral protease has stumped scientists for more than ten years.

But the puzzle was solved by crowdsourced gamers in only ten days. Zoran Popovic is one of the conceptual designers of the game Foldit. He says it's like a very complex jigsaw puzzle, or a kind of three-dimensional Tetris. Professor Popovic, welcome to the show.

ZORAN POPOVIC:

Ah, thanks for having me.

BROOKE GLADSTONE:

Assume I am woefully ignorant of the significance of protein folding. That is what the gamers figured out, this enzyme, how it folded. Right?

ZORAN POPOVIC:

Right. If you know the shape of each one of the proteins, you more or less know the secret of life. Pretty much everything that's done in living organisms is done by proteins. This goes from digesting your food, to moving your muscles, to defending against viruses and diseases. And everything is done through the way that the shape of protein interacts with shapes of other molecules.

BROOKE GLADSTONE:

Like keys and locks?

ZORAN POPOVIC:

Yeah, very much so.

BROOKE GLADSTONE:

So figuring out how this enzyme folded, why is it a big deal?

ZORAN POPOVIC:

Each virus has a whole bunch of proteins. A lot of them are on the surface. And how these surface proteins interact with other things is exactly how a virus does its damage.

Imagine if you had another jigsaw puzzle shape that it can attach to that protein on a  virus: all of sudden you can possibly neutralize that virus and it could no longer be attacking live cells.

BROOKE GLADSTONE:

I thought that was how protease inhibitors work, that we already knew how the AIDS virus folded?

ZORAN POPOVIC:

They know how some types of AIDS virus folded, They don't know all the proteins on the entire AIDS virus. And this particular virus is different than the human virus. This is a monkey virus that they’re looking for, because the more you understand how anyone of  the HIV viruses interacts and—and does its damage, the more likely you will create a universal drug that can prevent not just the virus, but its mutations as well.

BROOKE GLADSTONE:

If I were playing this game, what would I be looking at? Some sort of 3-D model? Like one of those IQ tests I would have to try folding things in different ways or imagine how they would look when they were folded? I mean, how is this undertaking different from regular research? What are they seeing?

ZORAN POPOVIC:

Think of a necklace, and it's a necklace that instead of having beads it has a whole bunch of these strange-looking shapes on it, which are basically amino acids. And now you ask the question, what's the tightest possible way I can pack this necklace into smallest amount of space.

That turns out to be energetically the most stable shape of the protein. So what we are trying to do is move different parts of this necklace in such a way that you can pack it better. You have rubber bands and all sorts of tools with which you can do more and more of these manipulations, and then also these superpower things you can apply, like wiggle and shake, which can sort of redefine the protein even better.

BROOKE GLADSTONE:

Is this a visual spatial exercise, or do you have to understand that these are molecular structures that you are working together?

ZORAN POPOVIC:

You don't need to know any chemistry. And, in fact, what we've done is encased the relevant chemistry into the rules of the game. If you know the rules of the game, you can play and be highly effective.

BROOKE GLADSTONE:

Sometime ago we spoke to Jane McGonigal, and she says that there’s a kind of game personality that enables people to focus incredibly hard for many, many hours and fail in a game, and learn from their failures without being traumatized by them, in a way that we can’t do in real life. Are those the kinds of people who play your game?

ZORAN POPOVIC:

Many of the people that play our game have actually never really liked games, until they Foldit. And they’re – and part of the reason for that is that it has this objective of actually helping humanity, and that's what pulled them on it originally. They started playing it, and it’s like, oh wow!

BROOKE GLADSTONE:

But that's what Jane McGonigal says, that everybody has a role –

[OVERTALK]

ZORAN POPOVIC:

Yeah.

BROOKE GLADSTONE:

- and they're glad to be moving towards a common purpose.

ZORAN POPOVIC:

Yeah, yeah. So I mean basically our task was to cast the widest possible net and see how many of those people become really interested in this kind of endeavor.

BROOKE GLADSTONE:

Tell me about the incentive structure.

ZORAN POPOVIC:

Originally, we had scoring and then it became obvious that people have different types of game play. For example, some people really love to start from scratch and develop the game and just have their name singularly on that solution.

Other people were very, very good at taking other people’s solutions and evolving them into better solutions. If you play the game for a while, you've become highly ranked on the overall ranking of all protein folders.

There are also groups. You can be very good at organizing the group. For example, we have some groups that have players playing in the States, and when these guys go to sleep the Australians take on the protein and work on it.

BROOKE GLADSTONE:

What project do you have in the works that you’re most excited about right now?

ZORAN POPOVIC:

One of the key aspects of Foldit was this ability to develop experts. One thing that came to us is that well, this really is education in a nutshell. So why can we not revolutionize education in the same way? We lose so many people in elementary school and middle school that just conclude that math and science is not for them.

We can make a game that automatically adapts to every student, such that not only are they more proficient at math and science, but they actually like it and have fun it, just like they do with games.

BROOKE GLADSTONE:

You're working on a project to figure out how kids' brains fold?

ZORAN POPOVIC:

[LAUGHS] Yeah, we're trying to discover the space of all possible confusions that kids can have on these concepts and then figure out how to uniquely present material in the game that adapts to every kid and make sure that a light bulb lights up in their brain when they suddenly get it – oh, this is fun, this is easy.

BROOKE GLADSTONE:

Zoran, thank you very much.

ZORAN POPOVIC:

You’re welcome.

BROOKE GLADSTONE:

Zoran Popovic is one of the conceptual designers of the game Foldit.

 

*In a story that aired the weekend of September 30, Brooke Gladstone stated that an article about the game Foldit was published inScience Structural and Molecular Biology. The paper was actually published in Nature Structural and Molecular Biology. Please click on the name of the journal to follow a link to the article abstract.