Introduction: From Physiology to DNA and Back

Abstract

It all began with physiology. A century ago we learned that microbes can adapt to their environment by expressing new enzymatic activities. One of the earliest findings was in yeast, where the enzymes for galactose metabolism were found to appear only when cells are exposed to lactose or galactose as carbon and energy sources. Similar findings were made subsequently with bacteria. However, in a sense, the focus on regulatory mechanisms as a major scientific problem began only in the 1930s when Karstrom coined the term “enzyme adaptation.” Giving a name to the phenomenon focused greater attention on it and sparked debate about the nature of the process. In 1944, Jacques Monod, working by night with the French Resistance and by day at the Institut Pasteur in Paris, initiated his studies on “adaptation” to lactose by E. coli. Over the next decade, Monod and his coworkers described fundamental properties of this system that were ultimately to have a profound generative effect on the evolution of studies on gene regulation. First, he described diauxie, a phenomenon in which growth on glucose as carbon source prevents lactose from inducing the appearance of β-galactosidase activity (which is ordinarily induced by lactose).