Jacob and Monod: From Operons to EvoDevo

As Francois Jacob tells it, one afternoon in September 1958, just back from New York, he walked into Jacque Monod’s office at the Pasteur Institute in Paris; he believed he had something exciting to discuss. But he found an unimpressed Monod brusquely dismissive. Tired from his flight, Jacob quickly gave up and went home to bed. The next day he returned re-energized and found an altogether more receptive Monod. Although the two had worked at the Pasteur for a number of years, their conversation that day launched an intense period of collaboration that resulted in one of the true intellectual and experimental triumphs of molecular biology. Jacob had been in New York to deliver the Harvey Lecture at Rockefeller University and in the weeks leading up to this prestigious event, while pondering what he might say, something rather remarkable had occurred to him: perhaps the two unrelated biological systems studied at the Pasteur were controlled in the same way. The two systems in question were lysogeny by bacteriophage lambda, and the ability of Escherichia coli to make an enzyme that digests lactose only when the cell encounters that sugar. Jacob’s idea was that the mechanisms underlying the regulation of these two otherwise distinct phenomena were identical. Below I give an overview of how Jacob and Monod came to work together, and of the historic experiments they completed 50 years ago this year. This is not for mere arcane amusement on this important anniversary, but because their work remains relevant. Many observations reported since in studies of gene regulation and developmental biology are in essence re-runs of their experiments, in different ways and in a variety of systems. They also provide the context for what follows in this special issue on the evolution of gene expression. Jacob and Monod’s model of gene regulation is essential for an understanding of the emerging fields of EvoDevo and the evolution of gene circuitry.