Allen Key

The April edition of Wired magazine carries a pretty cool article about the work of the Allen Institute for Brain Science, which is endeavouring to describe the cortex of the brain at the level of specific genes and individual neurons.

If the institute succeeds, its maps will help scientists decipher the function of the thousands of genes that help produce the human brain. (Although the Human Genome Project was completed more than five years ago, scientists still have little idea which genes are used to make the brain, let alone where in the brain they are expressed.) For the first time, it will be possible to understand how such a complex object is assembled from a basic four-letter code.

However . . .

One unexpected—even disheartening—aspect of the Allen Institute's effort is that although its scientists have barely begun their work, early data sets have already demonstrated that the flesh in our head is far more complicated than anyone previously imagined.

The brain might look homogenous to the naked eye, but it's actually filled with an array of cell types, each of which expresses a distinct set of genes depending on its precise location. Consider the neocortex, the so-called CPU of the brain: Scientists assumed for decades that most cortical circuits were essentially the same—the brain was supposed to rely on a standard set of microchips, like a typical supercomputer. But the atlas has revealed a startling genetic diversity; different slabs of cortex are defined by entirely different sets of genes. The supercomputer analogy needs to be permanently retired.

Or look at the hippocampus, the crescent-shaped center of long-term memory. Until recently, this small fold of tissue in the middle of the brain was depicted as neatly divided into four distinct areas. But data from the atlas has rendered the old maps not only obsolete but flat-out misleading. Even a single hippocampal area can actually be subdivided into at least nine discrete regions, each with its own genetic makeup.

Scientists at the institute are just starting to grapple with the seemingly infinite regress of the brain, in which every new level of detail reveals yet another level. "You can't help but be intimidated by the complexity of it all," Jones says. "Just when you think you're getting a handle on it, you realize that you haven't even scratched the surface." This is the bleak part of working at the Allen Institute: What you mostly discover is that the mind remains an immense mystery. We don't even know what we don't know.

The good news is . . .

Although the human atlas is years from completion, a theme is beginning to emerge: Every brain is profoundly unique, a landscape of cells that has never existed before and never will again. The same gene that will be highly expressed in some subjects will be completely absent in others. Important drug targets, like serotonin receptors, will exist in a disparate set of brain areas depending on the individual. This variation is even visible at a gross anatomical level—different people have differently shaped cortices, with different boundaries between anatomical regions. (This is why, for instance, neurosurgeons have to painstakingly probe the cortex during surgery.) If the human atlas is like Google Maps, then every mind is its own city.

"It can seem like there's an infinite number of variables to consider when you look at the human brain," says Elaine Shen, a manager at the institute. "We're making a genetic map, but what if the map isn't detailed enough? Or what if each brain is so different in expression patterns that we can't make sense of it?" She and her colleagues are convinced, however, that the only way to solve these unknowns is to look at the data, to break the brain apart and try to measure everything. "Once all the data is out there, someone else is going to connect the dots," Jones says. "All we want to do is make that scientific leap possible."

And it all starts here.