||Technology of this sort, or something equivalent, is essential for success of the genome project. In fact, I contend that the new technology is the most important outcome of the genome project because it is enabling for future application of genome sequences to all the interesting biological and medical questions that will occupy the future for many decades. Methods based on sequence ladders of the kind that I have shown you will be the only game in town for at least the next five years of large-scale sequence accumulation. Other, experimental technologies are in the wings and may become the future technology. These technologies include use of mass spectrometry, single molecule sequencing, micro-machines, and sequencing by hybridization on silicone chips. The last technique mentioned is likely to be of great utility for checking known sequences for accuracy or mutations. Here arrays of very large numbers of short DN As of known sequence are laid out in a defined pattern on microchips. Affimetrix, Inc., has made arrays of the sequences complementary to all the known variants of HIV virus. A DNA sample representing an unknown HIV strain is tagged with a fluorescent compound and applied to the chip. It binds wherever it finds a complementary sequence, producing a bright spot. From the known pattern of the arrayed short molecules, the particular sequence of the unknown can be deduced. This is a cheap, fast and powerful technology but you have to have a predicted sequence first. It will be great for diagnoses and sequence checking but will not work for initial sequence determinations. Other clever approaches that will increase accessibility to genomes are likely to mature. What Do We Learn from Qenome Sequences? Although the Human Genome Project will end in 2005, genome science will still be in its infancy. After the first round of genomes is sequenced for human and model organisms, there will be an overwhelming appetite for more genome sequences: chimp, orangutan, lemur, albatross, leak, liverwort, etc. Each new genome will betray another set of nature's secrets. The clamor has already started with respect to microorganisms which have small enough genomes to sequence with current technology. Hemophilus influenzae and Mycoplasma genitalia have been finished. The Utah center is sequencing Pyococcus furiosus, TIGR is doing Methanococcus jannaschii and Archaeoglobus fulgidus. Genome Theraputics is sequencing Methanobacterium thermoautotrophicum. Ford Doolittle in Canada is sequencing Sulfolobus. Another long list is waiting. Why are these small, primitive organisms of such great interest? They reveal wonders of evolutionary information.