When bacteria are grown in the presence of both glucose and another sugar like lactose, they use first glucose. When glucose is depleted, they start using the second sugar after a short lag. This phenomenon is called adaptation. Lactose metabolizing enzymes are essentially absent during the first phase of the diauxic growth and they are induced in the presence of lactose. There are mutants, called lactose constitutive mutants that always express β-galactosidase. Monod and his colleagues used conjugation to determine the mechanism of enzyme synthesis and of its induction. They showed that conjugation only involves the transfer of genetic material from the donor to the recipient, with no detectable transfer of the cytoplasm. Upon transfer of a wild type lactose region into a recipient that is constitutive but lacks the lacZ gene, the recipient start to express β-galactosidase constitutively. After two hours, the accumulation of enzyme stops in the absence of inducer but continues in its presence, indicating that the cells have now acquired the wild type inducible phenotype. Recombination does occur in these cells, but its contribution to the lactose phenotypes is not relevant. The similarity between the control of lac genes and that of lysogeny with phage λ was instrumental in convincing the authors of the general significance of their findings. In the short note by Jacob et al., the authors were able to use stable partial diploids. They isolate another class of constitutive mutants, in the operator. Most constitutive mutations map to the i gene that controls the synthesis of a repressor, a regulatory gene, and they are recessive. In contrast, mutants in the operator are dominant in cis. Although the existence of a promoter could have explained the phenotype of “physiological deletions”, these were later shown to be polar lacZ mutants that prevent the expression of the adjacent lacY gene. In the short time span of two years, the authors construct an extensive theory of the negative regulation of gene expression. Study of the lactose system was greatly facilitated by a number of lactose analogs that allow the separation of induction from substrate utilization. The property of the lactose repressor led to the concept of allostery.