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Mohammed Uddin is a postdoctoral researcher at Toronto’s Hospital for Sick Children. (Chris Young For The Globe and Mail)
Mohammed Uddin is a postdoctoral researcher at Toronto’s Hospital for Sick Children. (Chris Young For The Globe and Mail)

How Canadian researchers have gained greater insight into human nature Add to ...

For a place designed to explore what makes us who we are, the Allen Institute for Brain Science could hardly be in a more fitting location.

Overlooking a canal in Seattle’s artsy Fremont district, the institute is a stone’s throw from outdoor patios and coffee shops that hum with social interaction. Everywhere, the glorious mingling of human brains – their pleasure at getting inside each other – is on display. The way our brains do this, in a manner so conspicuously different from that of other animals, has intrigued philosophers and scientists for centuries.

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What the institute brings to the table, and what may finally offer some insight into the essence of what makes humans unique, is big data.

Founded in 2003 with a $100-million donation from ex-Microsoft mogul Paul Allen, it has been on a mission to transform neuroscience by mapping the brain the way Google (coincidentally, a next-door neighbour) has been mapping the planet.

“The whole idea is to put this data in the hands of the right people,” says Ed Lein, a senior researcher at the institute. “It all goes out as we generate it.”

Dr. Lein leads a project called the Brainspan Atlas. It amounts to a three-dimensional reference for how the brain is put together and how it changes through time, revealing precisely which genes are active in different brain regions as cells grow, migrate and create the circuitry that is essential for thought and behaviour.

The scale of the project is … well, mind-blowing.

By linking the functions of genes to specific locations and moments in brain development, the atlas has effectively revealed the brain’s construction crew in action. This feature has been eagerly taken up by researchers beyond the institute who are looking for clues to a range of complex mental disorders – cases where the construction crew has taken an unexpected turn.

“Three years ago, this didn’t exist,” says Mohammed Uddin, a postdoctoral researcher at Toronto’s Hospital for Sick Children. He developed a novel way to sort the Brainspan data and compare it with other data sets, and uncovered, in one fell swoop, thousands of potential genetic links to autism spectrum disorder, a debilitating condition characterized by problems with communication and socialization.

The results, which sparked much excitement in the autism community when announced last month, suggest a new framework for thinking about the genetic basis of autism. They help to explain why the disorder manifests in some people and not others, such as siblings who share similar genetic characteristics. In a clinical setting, they may offer a surer route to identifying which children will end up on the spectrum long before behavioural symptoms appear.

But the Hospital for Sick Children study also may point to a broader discovery that includes all humans, with or without autism spectrum disorder.

Because those with autism are challenged in the way they exhibit one of the more distinct human traits – the way we interact – they also may allow us to discover where the recipe for that trait lies in our genes. In sifting out the genetic vulnerabilities underlying ASD, the study may have zeroed in on the evolutionary toolkit that makes us different from other species, compels us to mingle like the patrons of Fremont coffee shops and, tens of thousands of years ago, equipped us to take over the planet.

“I think what we’ve done, in essence, is find the minimal set of genes involved in human cognition,” says Stephen Scherer, director of the Centre for Applied Genomics at the Hospital for Sick Children.

“Natural selection has sculpted these genes by tweaking their expression in the brain.”

Scientific double threat

Dr. Uddin himself is a personal study in how the right mix of traits can go a long way.

Born in Dhaka, he still remembers the computer his sister gave him when he was in high school. The pleasure of learning to program its Pentium I processor had him dreaming of a career in Silicon Valley.

The best chance of getting there, he reasoned, lay with Memorial University in Newfoundland – the place where his family’s budget intersected with the cost of a degree in computer science.

Arriving in St. John’s in January, 2001, the boy from Bangladesh found himself smack in the middle of “the worst winter ever.” He survived it and over the next few years stuck to his plan, earning a bachelor’s, then his master’s degree.

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