Tuesday, March 04, 2008

The Blue Brain project

A computer simulation of the upper layer of a rat brain neocortical column.
Here neurons light up in a "global excitatory state" of blues and yellows.
Courtesy of Alain Herzog/EPFL

In the basement of a university in Lausanne, Switzerland sit four black boxes, each about the size of a refrigerator, and filled with 2,000 IBM microchips stacked in repeating rows. Together they form the processing core of a machine that can handle 22.8 trillion operations per second. It contains no moving parts and is eerily silent. When the computer is turned on, the only thing you can hear is the continuous sigh of the massive air conditioner. This is Blue Brain.

The name of the supercomputer is literal: Each of its microchips has been programmed to act just like a real neuron in a real brain. The behavior of the computer replicates, with shocking precision, the cellular events unfolding inside a mind. "This is the first model of the brain that has been built from the bottom-up," says Henry Markram, a neuroscientist at Ecole Polytechnique Fédérale de Lausanne (EPFL) and the director of the Blue Brain project. "There are lots of models out there, but this is the only one that is totally biologically accurate. We began with the most basic facts about the brain and just worked from there."

Before the Blue Brain project launched, Markram had likened it to the Human Genome Project, a comparison that some found ridiculous and others dismissed as mere self-promotion. When he launched the project in the summer of 2005, as a joint venture with IBM, there was still no shortage of skepticism.
Scientists criticized the project as an expensive pipedream, a blatant waste of money and talent. Neuroscience didn't need a supercomputer, they argued; it needed more molecular biologists. Terry Sejnowski, an eminent computational neuroscientist at the Salk Institute, declared that Blue Brain was "bound to fail," for the mind remained too mysterious to model. But Markram's attitude was very different. "I wanted to model the brain because we didn't understand it," he says. "The best way to figure out how something works is to try to build it from scratch."

The Blue Brain project is now at a crucial juncture. The first phase of the project—"the feasibility phase"—is coming to a close. The skeptics, for the most part, have been proven wrong. It took less than two years for the Blue Brain supercomputer to accurately simulate a neocortical column, which is a tiny slice of brain containing approximately 10,000 neurons, with about 30 million synaptic connections between them.
"The column has been built and it runs," Markram says. "Now we just have to scale it up." Blue Brain scientists are confident that, at some point in the next few years, they will be able to start simulating an entire brain. "If we build this brain right, it will do everything," Markram says. I ask him if that includes
selfconsciousness: Is it really possible to put a ghost into a machine? "When I say everything, I mean everything," he says, and a mischievous smile spreads across his face.

Henry Markram is tall and slim. He wears jeans and tailored shirts. He has an aquiline nose and a lustrous mop of dirty blond hair that he likes to run his hands through when contemplating a difficult problem. He has a talent for speaking in eloquent soundbites, so that the most grandiose conjectures ("In ten years, this computer will be talking to us.") are tossed off with a casual air. If it weren't for his bloodshot, blue eyes—"I don't sleep much,"
he admits—Markram could pass for a European playboy.

But the playboy is actually a lab rat. Markram starts working around nine in the morning, and usually doesn't leave his office until the campus is deserted and the lab doors are locked. Before he began developing Blue Brain, Markram was best known for his painstaking studies of cellular connectivity, which one scientist described to me as "beautiful stuff...and yet it must have been experimental hell." He trained under Dr. Bert Sakmann, who won a Nobel Prize for pioneering the patch clamp technique, allowing scientists to monitor the flux of voltage within an individual brain cell, or neuron, for the first time. (This involves piercing the membrane of a neuron with an invisibly sharp glass pipette.) Markram's technical innovation was "patching" multiple neurons at the same time, so that he could eavesdrop on their interactions. This experimental breakthrough promised to shed light on one of the enduring mysteries of the brain, which is how billions of discrete cells weave themselves into functional networks. In a series of elegant papers published in the late 1990s, Markram was able to show that these electrical conversations were incredibly precise. If, for example, he delayed a neuron's natural firing time by just a few milliseconds, the entire sequence of events was disrupted. The connected cells became strangers to one another.

When Markram looked closer at the electrical language of neurons, he realized that he was staring at a code he couldn't break. "I would observe the cells and I would think, 'We are never going to understand the brain.' Here is the simplest possible circuit—just two neurons connected to each other—and I still couldn't make sense of it. It was still too complicated."

Neuroscience is a reductionist science. It describes the brain in terms of its physical details, dissecting the mind into the smallest possible parts.
This process has been phenomenally successful. Over the last 50 years, scientists have managed to uncover a seemingly endless list of molecules, enzymes, pathways, and genes. The mind has been revealed as a Byzantine machine. According to Markram, however, this scientific approach has exhausted itself. "I think that reductionism peaked five years ago," he says.
"This doesn't mean we've completed the reductionist project, far from it.
There is still so much that we don't know about the brain. But now we have a different, and perhaps even harder, problem. We're literally drowning in data. We have lots of scientists who spend their life working out important details, but we have virtually no idea how all these details connect together. Blue Brain is about showing people the whole."

In other words, the Blue Brain project isn't just a model of a neural circuit. Markram hopes that it represents a whole new kind of neuroscience.
"You need to look at the history of physics," he says. "From Copernicus to Einstein, the big breakthroughs always came from conceptual models.
They are what integrated all the facts so that they made sense. You can have all the data in the world, but without a model the data will never be enough."
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