Treating the brain as a machine is not a far-fetched metaphor. In the abstract, the brain is an electrochemical computer, operating on electrical impulses and chemical signals sent between cells. Though the individual pieces may be small, on the scale of mere nanometers, drawing the wiring diagram for this machinery is theoretically possible, and has been done for very simple organisms such as the roundworm C. elegans.
But the size and complexity of the human brain create far bigger challenges. Scientists estimate that the brain contains nearly 100 billion neurons, the basic type of brain cell. Each of those neurons makes tens of thousands of contacts with other cells, bringing the number of connections into the quadrillions, or a million billion.
A complete map of these connections—sometimes called the connectome—would be nothing less than the largest dataset ever created. But within that massive inventory could lie answers to some of the most elusive scientific questions: the fundamental rules of cognition, explanations for many mental illnesses, even the biological factors that separate humans from other animals.
“It’s a huge theory of neuroscience that all of our behaviors, all of our pathologies, all of our illnesses, all of the learning that we do, is all due to changes in the connections between brain cells,” said Narayanan “Bobby” Kasthuri, assistant professor of neurobiology at the University and neuroscience researcher at Argonne. “It’s probably the equivalent of the standard model in physics, but in neuroscience.”
‘Soft, squishy things’
Since the time of Hippocrates and Herophilus, scientists have placed the location of the mind, emotions and intelligence in the brain. For centuries, this theory was explored through anatomical dissection, as the early neuroscientists named and proposed functions for the various sections of this unusual organ. It wasn’t until the late 19th century that Camillo Golgi and Santiago Ramón y Cajal developed the methods to look deeper into the brain, using a silver stain to detect the long, stringy cells now known as neurons and their connections, called synapses.
Today, neuroanatomy involves the most powerful microscopes and computers on the planet. Viewing synapses, which are only nanometers in length, requires an electron microscope imaging a slice of brain thousands of times thinner than a sheet of paper. To map an entire human brain would require 300,000 of these images, and even reconstructing a small three-dimensional brain region from these snapshots requires roughly the same supercomputing power it takes to run an astronomy simulation of the universe.
Fortunately, both of these resources exist at Argonne, where, in 2015, Kasthuri was the first neuroscientist ever hired by the U.S. Department of Energy laboratory. Peter Littlewood, the former director of Argonne who brought him in, recognized that connectome research was going to be one of the great big data challenges of the coming decades, one that UChicago and Argonne were perfectly poised to tackle.
“All real advances in science are advances in technology,” said Littlewood, professor of physics at the University. “What we were doing at Argonne with X-rays and electron microscopy was going to produce a straightforward change in the way we could process data in high resolution. We just needed somebody crazy enough to imagine this was a real possibility and who also owned the technology and understanding to do it.”