Is that realistic? Not really. But it made it possible to start experimenting. "We still don't know enough about the living organisms," Ellison told me. "50 percent of E. coli is still a blackbox."
That figure might be even larger for C. elegans, but it's still the best characterized animal that researchers have got. It remains the only organism for which a complete connectome actually exists. Working in Nobel laureate Sydney Brenner's Laboratory of Molecular Biology in Cambridge during the 1970s, White and his team spent 13 years creating the wiring diagram. Electron microscopist Nichol Thomson cut the one-milimeter worms into 20,000 very thin slices, which -- because the worms are transparent -- he could then image with his microscope. "The thing that gave [Thomson] the biggest pleasure of all was to cut a long series of quality images," White told me.
Then, with White's direction, a technician named Eileen Southgate painstakingly labeled each nerve cell and connection in the micrographs. Through their work, they discovered C. elegans has 302 neurons that form approximately 10,000 connections. And Southgate traced each and every one. "I found out several years into her collaboration that as a hobby, she put huge jigsaw puzzles together," White recalled. "She has a wonderful visual memory." She began work at the lab when she was 16 years old and stayed until she retired.
The brain map was only one of several scientific feats accomplished with C. elegans. The worm was also the first multicellular organism to have its genome sequenced. And scientists precisely tracked its development from embryo to adulthood. There's even a database (WormBase) that contains more complete data about the organism's functioning at the molecular level than one could find for any other animal. Dozens of labs work with this little species.
Brenner handpicked the organism precisely for its amenability to study, calling the worm "nature's gift to science." University of Kansas worm biologist, Brian Ackley, likes to joke that Brenner created C. elegans in a lab "because he was tired of working on things that didn't have perfect biological criteria." They're tiny, transparent, reproduce quickly, have a small number of neurons, and each body is composed of exactly 959 total cells.
"Brenner planned to use the worm to discover how genes made bodies and then behavior," wrote Andrew Brown in a book on C. elegans. "And this was in 1965, before anyone had found and analysed a single gene for anything." It is only today, in 2013, that his disciples' disciples' are beginning to fulfill that original vision.
In a 1974 paper quoted in the talk he gave accepting the Nobel Prize for Medicine, Brenner put it like this, "Behavior is the result of a complex ill-understood set of computations performed by nervous systems and it seems essential to decompose the question into two," he wrote, "one concerned with the question of the genetic speciﬁcation of nervous systems and the other with the way nervous systems work to produce behaviour." In other words, how do genes build brains and how do brains direct bodies?
Now, finally, OpenWorm may be able to integrate the strains of research that began with Brenner into one simulation that, as it wiggles along in its digital petri dish, might be the first realistic virtual animal, a boon to research, and a Kurzweilian foreshadowing of the challenges humans face when we begin running life on silicon chips.
I asked several researchers whether simulating the worm was possible. "It's really a difficult thing to say whether it's possible," said Steven Cook, a graduate student at Yale who has worked on C. elegans connectomics. But, he admitted, "I'm optimistic that if we're starting with 302 neurons and 10,000 synapses we'll be able to understand its behavior from a modeling perspective." And, in any case, "If we can't model a worm, I don't know how we can model a human, monkey, or cat brain."
Ellison echoed that thought. "They stand a much better chance of success than the people working on mammalian brains," he said. White, who led the creation of the worm connectome, said OpenWorm "seemed appropriate really" as a way of integrating all the data that biologists were producing. And the Kansas worm scientist Ackley figured that even if OpenWorm didn't work, something like it would. "C. elegans is probably going to be the first or very close to the first [multicellular organism] to be simulated," he said
David Dalrymple, an MIT graduate student who has contributed to OpenWorm and is working on a worm brain modeling project of his own, pointed out what he sees as a limitation to the effort. OpenWorm has incorporated a lot of anatomical data -- the structures of the worm's nervous system and musculature -- described by scientists like White. But these studies were carried out with dead worms. They can't tell scientists about the relative importance of connections between neurons within the worm's neural system, only that a connection exists. Very little data from living animals' cells exist in the published literature, and it may be required to develop a good simulation.
"I believe that an accurate model requires a great deal of functional data that has not yet been collected, because it requires a kind of experiment that has only become feasible in the last year or two," Dalrymple told me in an email. His own research is to build an automated experimental apparatus that can gather up that functional data, which can then be fed into these models. "We're coming at the problem from different directions," he said. "Hopefully, at some point in the future, we'll meet in the middle and save each other a couple years of extra work to complete the story."