Mol Syst Biol. 1: 2005.0030 Large potential benefits for systems biology reside in applications to human health and identity. To develop our community's skills in these directions, ready access to highly integrated and comprehensive human genome and phenome data sets is extremely important and increasingly feasible technically. The few human 'functional genomics' data sets available today tend to be isolated from one another. Some of the tools needed to break through this impasse are addressed below in the context of a Personal Genome Project (PGP) as a natural successor to the Human Genome Project (HGP)—two recent buds in the ancient field of genetics. From my first interaction with Wally Gilbert in 1976, it seemed that a large (but appealing) leap would be to go from his new method for sequencing 30 bp segments to a method to get everyone's full genome sequenced. Six billion base pairs for six billion people had a nice ring to it. This was still merely a fantasy when we published a paper called 'Genomic Sequencing' in 1984 (Church and Gilbert, 1984) and conspired to create a 3 billion dollar HGP later that year (Cook‐Deegan, 1989). For the subsequent 16 years, radical technology development (while kept alive in a few 'back‐rooms') was clearly a minor funding priority relative to 'production' sequencing. However, by 2001, the criticisms of the old technology grew and the call for affordable personal genomes became irresistible (Jonietz, 2001). In early 2004, the NIH‐NHGRI posted a request for applications, and in October 2004 and August 2005, announced grant awards totaling $70 million for technology leading to human genome sequences for $100 000 in 5 years and $1000 in 10 years (http://www.nih.gov/news/pr/aug2005/nhgri‐08.htm). As if the motivation were not already high enough, at the recent Genome Sequencing & Analysis Conference in Hilton Head (October …