Allen Institute for Brain Science

By Ellen Kuwana Neuroscience for Kids Staff Writer September 26, 2003 A Man, His Money, and a Mouse Map Paul Allen, co-founder (with Bill Gates) of the software giant Microsoft, is a man with money and a man with a mission: a $100 million mission. As the fourth-richest person in the world, Allen is directing a large portion of his $22 billion fortune towards illuminating the mysteries of the most complex organ, the brain. Long a supporter of arts and entertainment, as well as medical research, Allen is creating the private, nonprofit Allen Institute for Brain Science in Seattle. The Allen Institute's first project will be a detailed atlas of the mouse brain. What makes the Allen Brain Atlas unique is the information it will contain: a three-dimensional anatomical representation of the brain, complete with gene expression (locations and functions of active genes) and circuitry (the network of nerve cells, and how they link to create pathways to convey information) details. The Human Genome Project, completed this year, identified all the genes, but didn't determine the function of each gene. As Mark Boguski, Director of the Allen Institute, explains with an analogy: "It's like opening a box filled with parts to build two tables and there are 30,000 parts and no instructions. There is no map. We have to figure out which are for the brain, and then we have to figure out how they are put together or what they do." Humans have approximately 30,000 genes that provide the instructions for the developing embryo. The numbers are astounding. About two-thirds (20,000 genes) are thought to be involved in brain development and function. From these genes, a brain is formed with billions of nerve cells, each capable of making a thousand different connections each. Humans and mice have almost identical sets of genes, differing by as few as 300. (The mouse genome map was published in December of 2002.) This means that humans share 99% of their genes with mice. So although the Allen Brain Atlas will be of a mouse brain, the information housed within the atlas will also advance human medicine. By focusing on which genes are active in which areas of the brain, researchers will gather clues about normal brain development and gain insight into what happens when brain development goes awry. This is especially important and timely, as people are living longer, and thus more people are living with neurodegenerative disorders such as Alzheimer's disease. Marc Tessier-Lavigne, an expert on brain development and nerve regeneration and a board member of the Allen Institute for Brain Science, described the atlas as a "source of information...to address which...genes control the development of nerve cells and thus can be exploited for brain repair and regeneration."

The altas will be made by mapping gene expression patterns using a technique developed in 1969 called in situ hybridization. ISH is a method for detecting specific nucleic acid sequences. Mouse brains will be preserved and cut into sections that are thinner than a human hair. These sections are placed onto microscope slides, and processed with a genetic "probe." A probe is a specially labelled piece of nucleic acid that results in visualization of the desired gene expression pattern in the tissue section. Thus, bit by bit, the pattern (expression pattern) of a gene can be determined. Hundreds of sections will then be reassembled using computers, creating a 3-D representation of a specific gene pattern within the brain. This will be repeated for many genes, some of which have known functions, others with functions that are mysteries.

Gene expression pattern in mouse embryo. Photo by Ellen Kuwana.

This new project, which is expected to take five years, will generate an unprecedented amount of information, most of which will be made available on the Internet. To put this amount of information in perspective, the Web now houses about eight petabytes of information; this brain mapping project is expected to generate several petabytes of data. (One petabyte is equal to one thousand trillion bytes.) The Allen Institute predicts that they will publish initial results by early 2004. "The fact that from only 30,000 genes, you can build the brain--something with a trillion nerve cells in it--that's a fascinating thing. When you think about the medical treatment and disease implications of having a better understanding of the genes in the brain, it's just such a fertile area. To have a chance to accelerate that--it's a fantastic opportunity." - Paul Allen (Seattle Times) Did You Know? There is disagreement about where to draw boundaries in the brain, and what to call regions. By mapping the brain using gene pattern to set the boundaries, the Allen Institute will create one map for all brain researchers to use. Special thanks to Jason E. Long, PhD, for his contributions to this article.

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