The genomics revolution that reached its climax in 2000 owes its very existence to two men. The first is Frederick Sanger who in 1977 developed the method for DNA sequencing that now bears his name. The second is Leroy Hood, who (with colleagues Michael Hunkapiller and Lloyd Smith) in 1986 took Sanger's method and made it better.
Sanger's enzymatic approach relies on specially modified reagents (2',3'-dideoxynucleotide triphosphates) whose incorporation into a growing DNA strand terminates the extension reaction (see related story, p. 44). The method calls for extending a primer-template pair in the presence of a radioactive marker and, in four parallel reactions, either dideoxy-A, dideoxy-C, dideoxy-G, or dideoxy-T. The resulting products can then be resolved on a high-resolution polyacry-lamide gel to produce a four-lane-wide "ladder" that reveals the template's sequence. Brilliantly inventive, the technique is also painfully laborious, producing a few hundred or perhaps a thousand bases at a ...
