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 by Watson 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. coli must be largely correct for other organisms. In fact, there was a famous saying (generally attributed to Jacques Monod), “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. The most extreme expression of this view came from Gunther 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: A View 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 as music and painting, Stent concluded that there may be no major conceptual breakthroughs remaining to be made in science. The exception perhaps would be in studying functions of the human brain, 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 when many 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 early E. coli molecular biologists who switched their fields/systems, notably successful persons were, for example, George Streisinger, who initiated zebrafish research, and Sydney Brenner, who initiated research using the nematode worm Caenorhabditis elegans.