Paired-read shotgun sequencing of a genome consists of randomly sampling segments of a fixed length, say 10,000 base pairs (10Kbp), and directly determining a “read” of 500 to 700bp at the two ends of each segment with an automated DNA sequencing instrument. Reconstructing or “assembling” a very large genome from such a data set was considered impossible at the time Jim Weber and I proposed it for the Human Genome (2.9Gbp) in 1996. Critics claimed that the computation would involve an impossible amount of computer time, that the size and repetitiveness of the genome would confound all attempts at assembly should sufficient computer efficiency be achieved, and that even if an assembly were produced it would be of an extremely poor quality and partial nature.