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First Ever Brain "Atlas" Completed

Aalok Mehta
National Geographic News
September 26, 2006
 
Scientists have made a complete "atlas" of the mouse brain, which they hope will spark a new era of insight into how the brain works and what happens when it breaks down.

The Allen Brain Atlas, launched with a hundred million U.S. dollars from Microsoft co-founder Paul Allen, provides an online, three-dimensional map showing where each of more than 21,000 genes is activated in the mouse brain.

Members of the Allen Institute for Brain Science in Seattle, Washington, announced the completion of the project this morning.

"It's an extraordinary achievement," said Allan Jones, the Allen Institute's chief scientific officer.

"The atlas provides a comprehensive understanding of the genetic underpinnings of the brain."

"No one has ever done anything like this before," Arthur Toga, a professor of neurology at the University of California at Los Angeles's School of Medicine, told National Geographic News.

"It tells us not just what genes are there, but where they are," added Toga, who is a member of the brain atlas's scientific advisory panel.

Such detailed mapping allows scientists to develop a more integrated understanding of the connection between genes and anatomy, he explains.

"This is an enormously important and innovative accomplishment," Toga said, "and will likely form the foundation for many other investigations into fundamental questions of the brain."

Making a Difference

Microsoft's Allen, a noted philanthropist who helped fund SpaceShipOne, the first privately built craft to reach space, initiated the atlas project because of his longstanding fascination with neuroscience.

"For someone coming up in the commercial side of things, the more you learn about computers, the more you wonder how the brain works … in ways that no computer today can," Allen said.

(See National Geographic magazine's "Beyond the Brain.")

He met with some of the field's top experts, who suggested that a three-dimensional map of gene expression in the mouse brain would revolutionize neuroscience.

The detailed mouse map holds a number of surprises, confirming just how complex an organ the brain really is.

About 80 percent of all genes are expressed in some form in the brain, says Jones, the Allen Institute's chief scientist—much higher than the 60 to 70 percent previous studies had indicated.

Almost none of these genes are expressed in only one region of the brain, he adds, providing insights into how drugs might affect different parts of the brain.

Massive Database

Jones led the team of scientists that began the brain atlas project three years ago.

They chose a mouse as their first subject, because it's easy to obtain genetically similar mice, simplifying the mapping process.

In addition, more than 90 percent of the genes in a mouse brain have a direct counterpart in humans, making mice brains powerful tools for modeling human brain function and diseases.

(See related: "Mice With Human Brain Cells Created" [December 2005].)

The researchers developed an automated process for creating extremely thin brain slices and marked these samples with chemical stains unique to each mouse gene.

In total, the team snapped more than 85 million images, containing a total of 600 terabytes of data—the equivalent of 20,000 iPods—Jones says. The resulting map is extremely precise, providing detail down to the cellular level.

A vital part of the project—taking up some one-third of the total budget, Jones estimates—was developing software that allows scientists to rapidly search and analyze the massive database.

Using these programs, all freely available on the brain map Web site, scientists can make a few mouse clicks to achieve what used to take months of experimentation.

More than 250 researchers are already using the Web site on a daily basis, Jones says.

The Next Step

The project's scope is analogous to flying above the Earth and seeing not just the surface but the locations of all the world's mineral and oil deposits below ground, says David Anderson, a biologist at the California Institute of Technology and another member of the project's scientific advisory panel.

"All the resources are mapped out for you—all the prospecting is done," he said, allowing researchers to focus on unraveling the mysteries of the brain instead of on laborious, time-consuming background work.

"That's the gift Allen has given me and my students and my colleagues."

For example, researchers working on new drugs can now quickly screen for genes expressed in regions of the brain associated with diseases such as autism or depression. Or they can see how drugs targeting one gene will affect various regions of the brain.

Scientists can also compare diseased brain tissue against the brain atlas to see how illnesses affect gene expression.

Maps of the human brain are also on the way, the Allen Institute's Jones says.

His research team next plans to take on the human neocortex, the outer, "wrinkly" part of the brain associated with higher functions such as consciousness, language, and sensory perception.

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