Switching from prokaryotic molecular biology to eukaryotic molecular biology.

In the history of biology, the early 1950s to the mid-1960s represent a period of landmark discoveries that led to the establishment of a new science named Molecular Biology. The discovery of the double helical structure of DNA byWatson and Crick in 1953 facilitated the formulation of specific questions related to the hottest questions of the time, gene replication and expression. Many ambitious and talented scientists with varied backgrounds (geneticists, biochemists, microbiologists, physicists, and others) initiated work toward similar goals. Thus, starting with the confirmation in Escherichia coli of the hypothesis that DNA replication was semiconservative and, shortly thereafter, the discovery of mRNA, the formulation of the operon model for regulation of gene expression, and finally the elucidation of the genetic code, a flood of important discoveries arrived during this period. The favorite experimental system during this time was E. coli and its bacteriophages, i.e. prokaryotic systems. But, as exemplified by the demonstration of the universality (with minor exceptions) of the genetic code as well as the earlier demonstration of the similarity in major metabolic pathways such as glycolysis and the tricarboxylic acid cycle from bacteria to humans, biologists assumed that the fundamental biological principles discovered in E. colimust be largely correct for other organisms. In fact, there was a famous saying (generally attributed to JacquesMonod), “What is true for E. coli is also true for elephants.” Thus, there was a kind of feeling among ambitious people who participated in this early development of molecular biology that most of the important questions in biology, specifically questions asked using E. coli as a model organism, had been answered. Many people thought that cellular differentiation and morphogenesis could be the next major question in molecular biology and started to switch from E. coli to other experimental organisms, mostly eukaryotes, to study the questions related to differentiation or other phenomena uniquely observed in eukaryotes. Themost extreme expression of this view came fromGunther Stent. Soon after the formal event marking the final decipherment of the genetic code, the Cold Harbor Symposium in 1966, he published an article in Science entitled “That Was the Molecular Biology That Was” (1), followed in 1969 by the publication of an expanded version as a book entitled “The Coming of the Golden Age: AView of the End of Progress” (2). After reviewing not only the history of progress in science, biology in particular, but also progress in other human activities, such asmusic and painting, Stent concluded that theremay be nomajor conceptual breakthroughs remaining to bemade in science. The exception perhapswould be in studying functions of the humanbrain, and this notion, the end of progress, might be equally true for art and other human activities. Such opinions were a strong influence on some early-day molecular biologists who had made significant contributions to the development of “classical molecular biology” using E. coli. This was exemplified by the exodus of many people from E. coli to other experimental systems at a time whenmany important problems in E. coli still remained unsolved. Like Seymour Benzer, who switched from E. coli molecular biology to Drosophila neurobiology in the late 1960s, Stent himself left E. coli molecular biology and switched to neurobiology using the leech as an experimental system.Among other earlyE. coli THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 284, NO. 15, pp. 9625–9635, April 10, 2009 © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A.