From systems biology to synthetic biology

If each of us conveys our idiosyncratic view of the elephant, then we, in communion, can imagine its wholeness (Ireland, 1997). An analogous process elucidates Molecular Systems Biology (MSB) and this journal is dedicated to it. The work of a scientist/engineer (seer for short) consists of discovery, modeling, perturbation, and invention. Cycling through these is a key practice of biology. Adding high-throughput analyses (Ideker et al, 2001) gives one view of MSB. Systems Engineering (Wiener, 1948; Chestnut, 1967) adds a great deal more. For the next step, we recognize five unalienable rights— to search, check, design, merge, and share (in electronic media). Exercise of these is exemplary in the realms of genetics, crystallography, and sequencing. Few who use Google or Blast will doubt that text-searching is a killerapplication. With computer searches, we can check if a discovery or design is truly new or alignable with other facts. If alignable, merging can produce a more comprehensive map of the elephant. Without these five rights, seers fall to politics, opinions, and fads. But even the most meager search presupposes a means to share and to decide on alignments. Journals and granting agencies encourage sharing promptly and unambiguously via accession numbers. We generally share models, not raw data. Aligned protein models are far beyond raw DNA electrophoresis data; aligned 3D structures are far from diffraction spots; and genetic linkages are far from DNA-polymorphism-chip intensities. For each of these, we have useful (and jargon-laden) metrics of goodness of fit and completion (Selinger et al, 2003), for example, Blast E-values, R-factors/RMSDS, and LOD scores, respectively.