Bench Press

A few years ago, I blogged about an ingenious crowdsourced game called Fold.It. The concept was pretty simple:

• Use human intuition to help solve complicated three-dimensional protein folding challenges which is oftentimes as effective but significantly faster & cheaper than computational algorithms
• Pool together lots of human volunteers
• Turn the whole experience into a game to get more volunteers to spend more time

The result was a nifty little game which contributed findings which have made it, to date, into a number of peer-reviewed publications (see PNAS paper here and Nature Structure & Molecular Biology paper here)!

Well some researchers at McGill University in Canada want to take a page out of this playbook with a game they built called Phylo (HT: MedGadget) to help deal with another challenging issue in bioinformatics: multiple sequence alignment. In a nutshell, to better understand DNA and how it impacts life, we need to see how stretches of DNA line up with one another. Now, computers are extremely good at taking care of this problem for short stretches of DNA and for “roughly” aligning longer stretches of DNA – but its fairly difficult and costly to do it accurately for long stretches using computer algorithms.

People, however, are curiously intuitive about patterns and shapes. So, the researchers turned the multiple sequence alignment problem into a puzzle game they’ve called Phylo (see image below) where the goal is to line up multiple colored blocks. Players tackle the individual puzzles (in a browser or even on their mobile phone) and the researchers aggregate all of this into improved sequence alignments which help them better understand the underlying genetics of disease.

And how has it been doing? According to the McGill University press release:

So far, it has been working very well. Since the game was launched in November 2010, the researchers have received more than 350,000 solutions to alignment sequence problems. “Phylo has contributed to improving our understanding of the regulation of 521 genes involved in a variety of diseases. It also confirms that difficult computational problems can be embedded in a casual game that can easily be played by people without any scientific training,” Waldispuhl said. “What we’re doing here is different from classical citizen science approaches. We aren’t substituting humans for computers or asking them to compete with the machines. They are working together. It’s a synergy of humans and machines that helps to solve one of the most fundamental biological problems.”

With the new games and platforms, the researchers are hoping to encourage even more gamers to join the fun and contribute to a better understanding of genetically-based diseases at the same time.

Try it out – I have to admit I’m not especially good with puzzle games, so I haven’t been doing particularly well, but the researchers have done a pretty good job with the design of the game (esp. relative to many other academic-inspired gaming programs that I’ve seen) – and who knows, you might be a key contributor to the next big drug treatment!

We’ve posted before on the Federation of American Scientist’s Immune Attack computer game as a great example of the use of games in science education. But, science “edutainment” isn’t limited just to computer games. Fans of Wizard’s Magic the Gathering and Konami’s Yu-Gi-Oh trading card games will immediately recognize The Healing Blade, a trading card game designed in the spirit of Magic and Yu-Gi-Oh but designed around the battle between antibiotics and bacteria (HT: AMEDNEWS)

The game was designed by two self-admitted “mega-geek” physicians, Dr. Arun Mathews and Dr. Francis Kong, who met in medical school and created the company Nerdcore Learning to promote The Healing Blade and other medicine-related “edutainment” paraphernalia. As to why they created the concept, Dr. Mathews notes:

I was struck upon the complexity and yet innate nature of gaming within the choice I would make for putting some of my sick patients on particular antibiotics … Essentially, in a similar way, when you are playing a complex multi-tiered video game, we are making similar choices by obtaining data from our cultures [and] making risk-management decisions.

Truer words were never spoken.

Amazingly, while Mathews and Kong had only intended to bring 30 copies of the game to launch at the American Medical Students Association annual meeting, a printing error turned that into over 100 copies, 90% of which sold! Mathews describes the sight:

We had this gaggle of students just sitting down, spreading out on a bunch of tables, all playing the game. That is one memory that will take a while to fade, because it was such a neat thing to see students getting super excited about infectious disease and therapies.

As an unabashed former-Magic-and-Yu-gi-oh player, I can definitely see the appeal. There is something very compelling about the mix of chance and strategy in trading card gameplay. Sadly, at the time of the writing of this blog post, The Healing Blade’s online purchase form shows that the game is sold out. So, in the meantime, I will have to leave you with some pictures of some very nice-looking game card art:

(Images and video from Healing Blade website)

In a world with flashy distractions like YouTube and Modern Warfare 2, how the heck do you get students to be interested in monocyte recruitment?

One idea that the Federation of American Scientists is proof-of-concept-ing is the use of video games as tools for science education. To that end, the FAS developed, in conjunction with game studio Escape Hatch Entertainment, a game called Immune Attack (trailer below):

The premise of the game is pretty creative. A patient who suffers from a non-functioning immune system needs the player’s help to train her immune cells on how to fight off a bacterial infection. More detail can be found in the lesson plan on the Immune Attack website, but the game itself covers multiple phases showing:

• how leukocytes move from bloodstream to infection site
• how leukocytes are recruited by chemical signals
• how the immune system can recognize pathogen-associated molecular patterns
• phagocytosis (how white blood cells devour pathogens that they find)
• how white blood cells can recruit additional immune cells with chemokines
• how natural killers and MHC molecules can identify cells infected by viruses

While the game’s concept is original, the production value of the game is not quite up to a full-fledged professional studio. Although, to be fair, for only a ~500MB download and from an effort that wasn’t backed by a major game company, the quality was fairly impressive. The problem, though, is that the game mechanics are oriented around maneuvering about the 3D world to train the patient’s immune system how to respond to infection. The game is thus very dependent on the quality of the controls and the graphics. As I was playing on a Thinkpad T400 using a Trackpoint, it was actually fairly difficult at times to do the maneuvers necessary to move on to the next level.

The interface was also somewhat klunky – being similar enough to a standard first-person shooter controls but with enough variations to make the controls a little awkward (the need to hold down the right mouse button while steering with the mouse and the inability of the keyboard to change the pitch of motion were annoying). The software also didn’t feel complete bug-free. Just to see what would happen, I deliberately failed a mission requiring me to identify and destroy 5 infected cells before a viral infection destroyed 5 healthy cells. When I re-started the mission, the count of destroyed healthy cells began at 5 – is it any wonder that I failed the mission, again?

With all that said, I do believe that this was a very impressive effort that just needs a little polishing. The music and graphics were a little hokey, and the lesson plan materials need to be fleshed out a bit better, but the game mechanics were designed very well to ingrain visually and physically how monocyte transmigration worked, how white blood cells are recruited, and how basic viral and bacterial pathogens spread infection. While I wouldn’t say I’m yet fully convinced that this approach will work, I am optimistic that this is a good method to help scientists convey very complicated phenomena to students.

We’ve written before about the ability of scientists to use distributed computing to pool the computing power of millions of users over the internet to solve sophisticated mathematical problems. But imagine if we could actually pool the brainpower of volunteers — but in a way which doesn’t involve jacking our brains into the Matrix.

Now, imagine if it could be fun for the volunteers.

Imagine no longer. Fold.It was created less than a year ago at the University of Washington to do just that. Instead of pooling the computational power of millions of machines, it seeks to pool the “human intuition” of volunteers to solve challenging protein folding problems.

The basic scientific concept behind Fold.It is that nature will “push” chains of amino acids to adopt a folded structure which minimizes free energy. But, while free energy calculations can be done relatively easily, finding the structure that minimizes free energy is not so easy to do and requires immense computational power (which is why Folding@Home uses distributed computing).

But, humans have a gift which computers do not: the gift of intuition. While we may not be able to compute the free energies in our head, we have the ability to make logical jumps and do complex reasoning. While we might not necessarily understand how to calculate the strength of a hydrophobic interaction, we know enough that we should place two hydrophobic (non-polar) leucine amino acids near one another. While we may not be able to write a mathematical equation to describe the arc of a polypeptide chain, we can conceptualize and visualize that a chain should be more “scrunched up” or “stretched out”.

And that type of “soft reasoning” is the processing power Fold.It seeks to capture. Fold.It created a game which literally depicts a “raw” protein chain in all its unfolded glory and asks human players to fold it. And, by deploying another unique characteristic of human beings, our competitiveness, the game encourages users to try to aim for the protein structure with the lowest free energy. The current aim is to see if the gift of human logic and competition is enough to solve complicated protein folding problems which currently require massive brute force calculations by supercomputers/distributed systems, and if so, if human 3D intuition can be “taught” to computers.

A quick overview of the game:

The novelty of this approach is striking. Interestingly, if Fold.It is successful, it will have done three very impressive (and very difficult) things:

• Successfully used crowdsourcing by pooling the wisdom of volunteers to solve problems which traditional brute-force computation finds nearly intractable
• Successfully use machine learning to copy the pooled wisdom of the volunteers to create smarter machines capable of solving the important protein folding questions which may underlie disease processes like cancer and Alzheimer’s
• Developed a new avenue with which to mobilize the public – by giving the public a tangible way to actively connect with and help an important scientific endeavor in a fun and easy-to-understand way

Check it out!