“I'll have a genome with chips, please”

An occasional column, in which Caveman and other troglodytes involved in cell science emerge to share their views on various aspects of life-science research. Messages for Caveman and other contributors can be left at caveman@biologists.com. Any correspondence may be published in forthcoming issues. Previous Sticky Wickets can be viewed at: www.biologists.com/JCS/caveman/index.html

A new era of science has dawned. The completion of DNA sequences of whole genomes of plants, large and small eukaryotes, bacteria and viruses is providing an unprecedented amount of information on the genes that define complex organisms. Together with this veritable tsunami of data come new words (genomics, proteomics, data mining), new types of biologists (bio-informaticians), and the appearance of (biotech) companys that specialize in the development of software to analyze and display genomic information. Perhaps the most measurable change that access to this vast quantity of genomic information is having on the average scientist is the potential to identify genes, and I mean all genes, in a given metabolic, developmental or oncogenic pathway - we are able to examine gene expression on a genome-wide level. The As Ts, Gs and Cs will be presented to us on a computer screen in an easy-to-read format; complex characterization and cross-matching of references are just a few keyboard strokes away. The equipment budget for most labs will provide faster and more powerful computers to store, access and manipulate this information. What are the potential consequences of having all the genes laid out for us like a book both for the way that we do science and for how others think that we should do science? With proteomics and consensus-sequence alignments, we may be able to identify protein functions (coiled-coil domains for protein-protein interactions, kinase domains, sites for phosphorylation, etc.) and, possibly, a representation of the encoded protein's three-dimensional structure (based on similarities to proteins with the same domain organization). No more fussing around with genetic tests; out with the suppressor screens; gone are probing complex pathways of tissue development; thank goodness we won't have to consider how to purifying protein complexes; two-hybrid analysis begone. But, as everything is laid out like a book, what need is there for an old-fashioned, bench-trained scientist who develops hypotheses (remember the old catch-phrase, “No Hypothesis, No Science!”) and performs ‘wet’ experiments (purify proteins, run gels, localize mRNA and proteins in tissues and cells). Where is the hypothesis if one scans a genome for a family of proteins and then systematically ablates the function of each of them (knockouts, RNAi) in an organism and hopes for an effect? Genome-wide analyses are also available in a ‘carry-out’ format - the seemingly ubiquitous CHIP. Here, the genome is laid out in a matrix and can be ‘read’ with an automatic analyzer (for a princely sum of money). All you need to do is supply the manipulation (heat shock, a drug, serum) and mRNA, and, ‘hey presto’, presented to you in glorious greens and reds are the ranges of changes in gene expression (up, down, no change) for all the genes in that organism. (This is a minor point, but who chose the colors? With our heightened sense of equal rights for all, what about those who are color-blind? Who is looking after their interests in this emerging area?) But, I digress. These experiments are very easy to perform, assuming that you have access to the CHIPs, a reader and have the money to buy everything ($60,000, or EU25 billion, for a full set of human CHIPs, and that's before all of the genes have been identified! However, I assume that market forces and competition will increase availability and drive down the prices.) Easy experiments are very attractive to many scientists. (ABSTRACT TRUNCATED)