Paul Allen’s Big Bet to ‘Uncover the Essence of What Makes Us Human’

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look deeper than the cellular level, down to the molecular level of the brain. This will be based on using high-speed/low-cost gene sequencing machines to spot DNA mutations that affect brain development and can lead to disease. The other key technology in this initiative will be the use of what scientists call “induced pluripotent stem cells” in which adult skin or blood cells are essentially re-programmed into a stem-cell like state so that they can become any type of cell in the body—including many types of neurons. By looking at DNA mutations, and then seeing how that DNA manifests itself in actual neurons from people, the scientists hope to be able to predict how brains will function. “Our ultimate goal is to generate a set of molecular tools that will empower the scientific community” to develop better understanding of how aberrant genes affect behavior and various diseases, Koch said.

There will obviously be big challenges in pulling off this kind of work, aside from the sheer technical difficulty. Jones, the institute’s CEO, said his 185 employees are spread among three buildings in Fremont, and it would be better for collaboration to be clustered under one roof (he hinted that he’s working on that one). For Koch, there’s a sociological challenge in recruiting bright scientific minds. Since top scientists tend to be independent sorts who work in narrow disciplines, and tend to follow their own latest ideas. The culture is about keeping ideas and data secret until blockbuster results get published in a peer-reviewed journal. That’s the opposite of an open-source effort, in which each individual can’t just follow whatever idea strikes them, and keep all the data and glory for themselves. “This is a team effort,” Koch says. “We have to attract the world’s best talent, and then instill in them a team spirit that we all have to work together, for common goals, common methods.”

More than once, Allen talked about the complexity involved in the work, and how daunting it is. When Koch tried to sum up what this effort is about, it’s not the kind of thing you can very easily put in a single sentence.

“We have a unique opportunity to truly push the field forward,” Koch said. “This is a large-scale, industrial-size effort to synthesize all of our genomic, anatomical, physiological, computational, and theoretical knowledge into a comprehensive picture of how the most complex piece of organized matter, the brain, develops and functions to produce perception, memory, and consciousness.”

Allen Institute for Brain Science leaders. From left, chief scientific officer Cristof Koch, founder Paul Allen, CEO Allan Jones

If you’re like me, you probably had to read that sentence more than once. It’s a big undertaking, and all the answers neuroscientists want won’t magically appear at the end of four years. Koch acknowledged that it’s likely to turn out like cosmology—once scientists learn a bit more about the universe, they realize there’s a lot more there to explore than previously thought.

But for Allen, a guy who grew up on science fiction, this is partly about exploration of new frontiers, and partly about a desire to make an impact on humanity and health.

“I’ve always been fascinated by the brain,” Allen said. “I started out as a programmer in high school, and the brain works in a completely different and unknown fashion than the way computers do. There is no greater challenge, with potentially huge impact, than understanding how brains work. For me, it’s fascinating. And as someone who’s been touched by neurodegenerative diseases—my mother has Alzheimer’s, for example—I want to see cures brought forward.”

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