Bringing a Virtual Brain to Life

For months, Henry Markram and his team had been feeding data into a supercomputer, four vending-machine-size black boxes whirring quietly in the basement of the Swiss Federal Institute of Technology in Lausanne.
The boxes housed thousands of microchips, each programmed to act like a brain cell. Cables carried signals from microchip to microchip, just as cells do in a real brain.
In 2006, Dr. Markram flipped the switch. Blue Brain, a tangled web of nearly 10,000 virtual neurons, crackled to life. As millions of signals raced along the cables, electrical activity resembling real brain waves emerged.
“That was an incredible moment,” he said, comparing the simulation to what goes on in real brain tissue. “It didn’t match perfectly, but it was pretty good. As a biologist, I was amazed.”
Deciding then that simulating the entire brain on a supercomputer would be possible within his lifetime, Dr. Markram, now 50, set out to prove it.
That is no small feat. The brain contains nearly 100 billion neurons organized into networks with 100 trillion total connections, all firing split-second spikes of voltage in a broth of complex biological molecules in constant flux.
In 2009, Dr. Markram conceived of the Human Brain Project, a sprawling and controversial initiative of more than 150 institutions around the world that he hopes will bring scientists together to realize his dream.
In January, the European Union raised the stakes by awarding the project a 10-year grant of up to $1.3 billion — an unheard-of sum in neuroscience.
“A meticulous virtual copy of the human brain,” Dr. Markram wrote in Scientific American, “would enable basic research on brain cells and circuits or computer-based drug trials.”
An equally ambitious “big brain” idea is in the works in the United States: The Obama administration is expected to propose its own project, with up to $3 billion allocated over a decade to develop technologies to track the electrical activity of every neuron in the brain.
But just as many obstacles stand in the way of the American project, a number of scientists have expressed serious reservations about Dr. Markram’s project.
Some say we don’t know enough about the brain to simulate it on a supercomputer. And even if we did, these critics ask, what would be the value of building such a complicated “virtual brain”?
Henry Markram traces his fascination with the brain to a school assignment in his native South Africa. He was 14, and as he sat in the library reading about depression, he was astonished to discover there might be “molecular explanations to mental illness” that could be treated with drugs.
That set him on a path to medical school, where he planned to become a psychiatrist. But as a medical student, he realized that we know next to nothing about what prescription drugs really do to the brain.
To understand mental illness, he reasoned, we need to understand the brain first. “So I dropped out of medical school,” he said, “and got on a plane to do some real neuroscience.”
He went to the Weizmann Institute of Science in Israel to earn a Ph.D., followed by a stint at the National Institutes of Health in the United States on a Fulbright scholarship. That work led to a position with the Nobel Prize-winning neurophysiologist Bert Sakmann at the Max Planck Institute in Germany.
At Dr. Sakmann’s lab, Dr. Markram made his most famous discovery.
He was pondering how the brain learns cause and effect. He set up an experiment to record the electrical activity from two connected neurons in a slice from a rat’s brain, and discovered that the neurons required a precise sequence of voltage spikes to change the strength of their connections. He speculated that the mechanism might be at the root of our notion of causality.
That work has now been cited thousands of times. Yet as Dr. Markram’s reputation grew, so did his impatience.
Neurons are organized into interconnected circuits that can number in the millions. Dr. Markram realized that to make real progress linking neurons to behavior, experimenting on two neurons at a time “just wasn’t enough.”
In his first faculty position, at the Weizmann Institute, he set up a wildly ambitious new experimental rig that could record data not just from 2 neurons in a rat’s brain but also from 12.
“His rig made NASA look tame,” recalled Dr. Markram’s postdoctoral adviser at the N.I.H., Elise F. Stanley, who visited him at the Weizmann in 1995. “There was so much equipment that you couldn’t even see the brain tissue.”
Soon Dr. Markram would learn that his son, Kai, had autism. “You know how powerless you feel,” he said. “You have this child with autism, and you, even as a neuroscientist, really don’t know what to do.”
By Tim Requarth
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