In our last installment on DNA sequencing, we brought you up to speed on the Sanger method of sequencing (named after its dual-Nobel-winning inventor, Fred Sanger), which was state-of-the-art around the time of the completion of the human genome. That was about five years ago. During a visit last month to the Broad Institute, which does genome sequencing, my hosts made it clear that, while Sanger sequencing still had its uses, the action had already moved elsewhere. The Broad had recently eliminated a number of its Sanger machines, and the remainder weren't even active on the day I was there.
The new technologies that are driving the old machines out to pasture rely on a range of tricks to shrink down the amount of DNA that's required for a sequencing reaction, in at least one case dropping it to a single molecule. Although the approaches they take are quite different, all of them rely on some combination of two key biochemical reactions: DNA ligation, and Polymerase Chain Reaction, or PCR. So, before we