This is a picture of one DNA sequencing machine: the Applied Biosystems 3730xl DNA Analyzer. It costs a few hundred thousand dollars and it’s starting to show its age, but it’s still the sweetest thing on the market if you want to sequence DNA accurately and fast. Here’s another DNA sequencing machine: RNA polymerase. It’s been around for a few billion years, and you’ve got trillions of them in your body right now, most of them sequencing DNA faster than the fridge-sized 3730xl. If not, you’d be real dead.
One of the reasons I’m optimistic about our ability to understand what’s happening inside the cell is that a cell is already a sophisticated information processing engine. If we can learn how to listen to it as it’s working, we won’t need to blast it to bits and paste its little smithereens back together in a kind of glorified biotech forensics lab. The violence of the language we use is telling. Polymerase chain reactions? Shotgun sequencing? Please. Why don’t we just ask that busy little RNA polymerase to tell us what it’s doing?
Of course that’s easy for me to say, but it turns out that’s exactly what Steve Block is doing in his Stanford lab. By stringing DNA between two tiny polystyrene beads, he can effectively listen to the sound of transcription and infer the sequence. The title of his paper drives home the fact that you can’t get much smaller than this: Single-Molecule, Motion-Based DNA Sequencing Using RNA Polymerase. If you don’t have a subscription to Science (which I don’t) you can read about papers like this in places like Alex Palazzo’s Daily Transcript and then you can go directly to the publishing lab for the paper (PDF).