Gray Matter

  • When Microsoft billionaire Paul Allen heard about the plan to map the entire human genome—all 3 billion base pairs—he was duly impressed. And inspired. What if the same approach were applied to the most daunting frontier in biology—the human brain? "It's incredibly fascinating," says Allen. "We know so little about how the brain really works."

    So in 2002 he gathered together some of the nation's leading brain experts and asked them what they needed to accelerate their research. An atlas, they said, would be very helpful, one that detailed all the genes that are active in the human brain.

    A problem immediately arose. Making such a map would require a dependable source of fresh human brain tissue, something even Paul Allen's money couldn't buy. Mice, however, are plentiful. And because mice and men share 90% of their genes, the mouse brain made a pretty good stand-in. So in 2003, Allen created the Allen Institute for Brain Science with $141 million of his own money and launched the mouse-brain genome as its first project.

    That project was completed last week, and a digitized index of the more than 21,000 genes active in the brain of a mouse was posted on the Web. Available at no charge to researchers—and anyone else who wants to see it, at brainatlas.org—it provides detailed cellular and molecular descriptions of the genes and their products as well as interactive, three-dimensional views that allow scientists to see where in the brain certain genes are active.

    The atlas is the start of what neuroscientists see as the future of brain science, and it already has revealed something new about how the brain works. Researchers had always thought that the neurons in the brain were pretty much the same, distinguished mainly by how they were wired up to one another. It turns out, however, that brain cells, like other cells in the body, show a diverse array of gene expression patterns, meaning that different cells use different genes at different times to perform their complex functions.

    With the mouse map up and running, the next challenge for the institute is to start mapping the human neocortex—the outer blanket of the brain—using samples of brain tissue from cadavers and biopsies from recent brain surgeries. It's the beginning of what neuroscientists hope will be a long-term effort to understand both how the brain works and what happens when things go awry. The more they learn, the sooner they can come up with new ways to treat neurological disorders.