The Triple Helix model of university-industry-government relations can be generalized from a neo-institutional model of networks of relations to a neo-evolutionary model of how three selection environments operate upon one another. Two selection mechanisms operating upon each other can mutually shape a trajectory, while three selection environments can be expected to generate a regime. The neo-evolutionary model enables us to appreciate both organizational integration in university-industry-government relations and differentiation among functions like wealth creation, knowledge production, and legislation. The specification of systems of innovations in terms of nations, sectors, and regions can then be formulated as empirical questions: is synergy generated among functions in a network of relations? Thus, this Triple Helix model enables us to study the knowledge base of an economy in terms of a trade-off between locally stabilized and (potentially locked-in) trajectories versus techno-economic regimes at the global level.