The pre-omics era: the early days of two-dimensional gels

I present a personal view of the beginning of two-dimensional gels and unsanctioned proteomics. I was still a young graduate student in the early 1970s when I developed methods for two-dimensional gel electrophoresis that became widely used. Though the method gave us the capacity to do things that had never been done, the value of global enumeration of proteins was not appreciated, and we were still two decades away from the invention of the term proteomics. I describe a period of exploration where, by exercising our new capability, we conducted the first proteomic type expression experiments, and made unforeseen contributions to advances in biology. Detection of single-amino acid substitutions validated genetic selections in cultured cells, and revealed a regulatory system that maintains the accuracy of protein synthesis by assuring an unbiased supply of its substrates. We documented biologic control with a dynamic range >10(8) fold, and, in a surprising turn, we identified an approach that provided a major breakthrough in recombinant DNA technology, the ability to express cloned sequences in Escherichia coli. The challenge then and now is to use a capability for global analysis to produce new insights into fundamental aspects of biology and to drive substantive technical advances.