By Ken Reibel
Microsoft co-founder Paul Allen made his fortune helping to create the operating system used on most of the world’s personal computers. But these days his interest lies in a far more complex operating system: the 20,000 or so genes that create the self-aware tangle of neurons we call the human brain.
The team at the Allen Institute for Brain Science in Seattle has set a hugely ambitious goal: to map the human brain, and place the data sets online for scientists and the public to explore free of charge. The finished product, the Allen Human Brain Atlas, could do for neuroscience what star charts did for Columbus.
“The brain is really all about functional divisions, and it’s very important to understand how those functional divisions relate to their underlying biochemistry,” says Allan Jones, Ph.D., the institute’s chief scientific officer. “The underlying biochemistry is driven by genes.”
Comparisons to the Human Genome Project, completed just 10 years ago, are obvious but don’t speak to the scale of Allen’s vision. Whereas the HGP, which concluded in 2003, generated some 3 gigabytes of data in its 13 years, brain mapping generates over one terabyte every day.
The institute draws on the talents of computer specialists, administrators, and 30 PhD scientists whose training includes math and physics, neuroanatomy, genetics and developmental biology. And then there are the robots.
The five-year project would take decades longer without the help of dozens of robots that mount slide and scan slides. The institute has also automated the 40-step in situ hybridization process that synthetically tags RNA molecules in a process that ultimately fingers where that gene is turned on in a particular cell.
“The act of actually cover-slipping a slide, thinking back to high school biology class, is a very tedious task,” says Jones. “And you often get bubbles and other things, so we have a machine that lays down a cover slip that’s perfect every time.”
So what does all this mean for the study of autism?
Neuroscientists currently use a variety of tools to probe the brain. They can measure electrical activity of individual neurons with a microelectrode, inserted into the tissue of a live subject. Functional MRIs create images that correlate certain stimuli or mental activities to different regions of the brain. Microbiologists study enzymes, proteins, and RNA splices. But these techniques can’t explain how cells, electrical signals, and genes combine to create human consciousness.
So far, scientists have looked at autism from different angles, and even identified abnormalities in the brain’s structure. But their explanations never reach beyond the abstract – it’s like exploring Africa with a 15th century map of the coast. By identifying and labeling genes, no matter how obscure, and identifying their exact location, Allen Institute scientists can add rich detail to terra incognita that handicaps traditional brain science.
Diseases and disorders only generally associated with regions of the brain can possibly be pinpointed, even reduced to a few misfiring neurons, and linked to a known gene expression.
Though the project is two years from completion, it has already yielded significant insights into our species.
“By and large, there’s really not a whole lot of variation across human populations in the specific patterns that activate genes. It’s probably less than 5%. And so, we’ve looked at these across multiple individuals,” says Jones.
“So even though there is likely to be variation in gene expression that’s driven by population differences, it’s minor compared to the larger commonality between us. Humans are a lot more similar amongst each other than not.”
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