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SEQUENCING Nature Knows Best

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Eugene Chan was a first-year med student when he began brainstorming better ways to sequence DNA. He tried to find an example in nature that would improve upon the decades-old technologies of PCR and Sanger’s sequencing. “The most obvious is in cell division,” he says. “During that process you get faithful replication and reading of the genome in less than 30 minutes.”

Chan, now 28, figured if nature had spent billions of years perfecting the technique, he was hardly one to argue with it. “The most appealing part was, ‘Geez, nature can do it, it’s possible,’” he says.

So he dropped out of Harvard’s medical school and in 1997 started rounding up investors for US Genomics, a company based on his sequencing concept: instead of shearing the DNA, he would uncoil it and read it straight off the strand the way one reads a ticker tape. “That was the question investors asked: Can you even uncoil DNA and make it behave the way you need?” he recalls. He teamed up with his brother Ian and spent almost 11 months bringing his idea to fruition. In the end, it worked — and he wound up with an invention that reads up to 30 million base pairs per second. The minutes-long run of Chan’s system is measured in hundreds of megabases, and the brothers are working on fully sequencing small genomes.

Let’s say you’re standing on a train platform in the dark, and you shine a flashlight on a passing train. According to Chan, this is the basic idea for the technology. A nanochip uncoils the DNA, and then a small-scale laser is aimed at the resulting linear strand. As the DNA moves past, the laser enables a reader to pick up the different fluorescent tags of each base.

“A large part of what drives me is this desire to learn as much as I can,” says Chan, who has studied engineering, molecular biology, and chemistry. He believes his technology still has a long way to go before it reaches his goal of being robust enough to do broad-based sequencing of human genomes.

“We call it post-genomics, but we’re really just at the very beginning of it,” he says. “Beyond [industrial-scale sequencing], that’s where the fun really begins.”

— Meredith Salisbury

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