For all the talk of artificial intelligence and all the games of SimCity that have been played, no one in the world can actually simulate living things. Biology is so complex that nowhere on Earth is there a comprehensive model of even a single simple bacterial cell.
And yet, these are exciting times for "executable biology," an emerging field dedicated to creating models of organisms that run on a computer. Last year, Markus Covert's Stanford lab created the best ever molecular model of a very simple cell. To do so, they had to compile information from 900 scientific publications. An editorial that accompanied the study in the journal Cell was titled, "The Dawn of Virtual Cell Biology."
In January of this year, the one-billion euro Human Brain Project received a decade's worth of backing from the European Union to simulate a human brain in a supercomputer. It joins Blue Brain, an eight-year-old collaboration between IBM and the Swiss Federal Institute of Technology in Lausanne, in this quest. In an optimistic moment in 2009, Blue Brain's director claimed such a model was possible by 2019. And last month, President Obama unveiled a $100 million BRAIN Initiative to give "scientists the tools they need to get a dynamic picture of the brain in action." An entire field, connectomics, has emerged to create wiring diagrams of the connections between neurons ("connectomes"), which is a necessary first step in building a realistic simulation of a nervous system. In short, brains are hot, especially efforts to model them in silico.
But in between the cell-on-silicon and the brain-on-silicon simulators lies a fascinating and strange new project to create a life-like simulation of Caenohabditis elegans, a roundworm. OpenWorm isn't like these other initiatives; it's a scrappy, open-source project that began with a tweet and that's coordinated on Google Hangouts by scientists spread from San Diego to Russia. If it succeeds, it will have created a first in executable biology: a simulated animal using the principles of life to exist on a computer.
"If you're going to understand a nervous system or, more humbly, how a neural circuit works, you can look at it and stick electrodes in it and find out what kind of receptor or transmitter it has," said John White, who built the first map of C. elegans's neural anatomy, and recently started contributing to the project. "But until you can quantify and put the whole thing into a computer and simulate it and show your computer model can behave in the same way as the real one, I don't think you can say you understand it."
For example, when researchers touch a worm on the head and it responds by turning and moving backwards, what exactly is happening there? What molecular mechanisms coordinate the firing of neural networks that initiate and complete this complex behavior? This month, a paper came out in PLOS Biology describing that exact sequence as recorded in live C. elegans. But it's one of very few studies like that.
More broadly, OpenWorm raises fascinating questions about what we mean when we say something is alive. If and when this project succeeds in modeling the worm successfully, we'll be faced with a new and fascinating concept to think with: a virtual organism. Imagine downloading the worm and running it in a virtual petri dish on your computer. What, exactly, will you be looking at? Will you consider it to be alive? What would convince you?
Perhaps creations like the digital C. elegans will start to break down our binary conception of the matter in the world as either living or not living. We'll discover that we can create systems that exist in-between these two spheres, or that certain aspects of life as we know it are not required to meet our definition of being alive.
"I suspect that we'll recognize that living systems are far-from-equilibrium molecular systems that are carrying out very specific sophisticated physical patterns and have some ability to sustain themselves over time," OpenWorm's organizer Stephen Larson wrote to me. "Thinking about it that way makes me go beyond a black and white notion of 'alive' to a more functional perspective -- living systems are those which self sustain. Our goal is to aggregate more of the biological processes we know that help the worm to self-sustain than have ever been aggregated before, and to measure how close our predictions of behavior match real living behavior, more than it is to shoot for some pre-conceived notion of how much 'aliveness' we need."
* * *
It's a complex, ambitious project, to say the least. White called it "bold." Yet it all began with a tweet.
In early 2010, software engineer Giovanni Idili sent a tweet to the Twitter account for The Whole Brain Catalog, a project to bring mouse brain data together into more usable formats. He said, as if on a lark, "@braincatalog new year's resolution: simulate the whole C. Elegans brain (302 neurons)!" One of the Brain Catalog's founders, Stephen Larson, was scanning the @-replies and offered his assistance, "So, do you want any help with that? How are you going to do it?"
Beginning with a 1997 proposal at the University of Oregon, there have been several attempts to simulate worms. Some focused on the body alone. Others tried to simulate the worm's behavior through machine learning, with no attempt at a biologically realistic nervous system. Idilli and Larson wanted to go beyond these early efforts. When Larson was at MIT, he was influenced by Rodney Brooks, the director of the Computer Science and Artificial Intelligence Laboratory at the university (and the creator of the Roomba!). Brooks proposed the idea that if you want artificial intelligence, it should be situated within an environment. Is his 1990 paper, "Elephants don't play chess," he argued that "to build a system that is intelligent it is necessary to have its representations grounded in the physical world."
The great thing about C. elegans, though, is that its physical world in the laboratory is completely standardized and well known. The worms live in petri dishes with agar. If any environment can be modeled by a computer, it is a petri dish with agar. The nascent OpenWorm team could build a realistic virtual environment for a digital C. elegans.
Which meant that their little worm brain -- the target of Idili's initial suggestion -- needed a body. For that, they reached out to Christian Grove at CalTech, who donated a 3D atlas of the worm to get them started.
They had a map of the brain, a model of the body, and a pretty good idea of how to build the environment. Their artificial intelligence might not be embodied, but it would be "situated." The brain would direct the body and the body would interact with the environment, and all three pieces would be connected by the intricate feedback loops that permeate biology.