Mapping the Brain

I've got a new feature in Wired Magazine on the Allen Brain Institute and their heroic attempts to construct a gene expression map of the human brain. I was most impressed by the way the Institute has "industrialized" the scientific process, as it transforms the artisan model of lab benchwork - post docs playing with micropipettes - into a high-throughput model, in which massive robots execute most of the actual "science".

The article is now online, but the photographs are pretty stunning (in a gruesome sort of way), so be sure to pick up a copy of the magazine.

The human brain is surprisingly bloody. I've worked in neuroscience labs, and I'm used to seeing brains that are stored in glass jars filled with formaldehyde, the preserved tissue a lifeless gray. But this brain--removed from a warm body just a few hours ago--looks bruised, its folds stained purple. Blood drips from the severed stem, forming puddles on the stainless steel table.

I'm in the dissection room of the Allen Institute for Brain Science in Seattle, and the scientist next to me is in a hurry: His specimen--this fragile cortex--is falling apart. Dying, the gray matter turns acidic and begins to eat away at itself; nucleic acids unravel, cell membranes dissolve. He takes a thin, sterilized knife and slices into the tissue with disconcerting ease. I'm reminded of Jell-O and guillotines and the meat counter at the supermarket. He saws repeatedly until the brain is reduced to a series of thin slabs, which are then photographed and rushed to a freezer. All that remains is a pool of blood, like the scene of a crime.

Behind all the gore there's a profound purpose: The scientists here are mapping the brain. And while conventional brain maps describe distinct anatomical areas, like the frontal lobes and the hippocampus--many of which were first outlined in the 19th century--the Allen Brain Atlas seeks to describe the cortex at the level of specific genes and individual neurons. Slices of tissue containing billions of brain cells will be analyzed to see which snippets of DNA are turned on in each cell.

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.