Even though systems biology is a new approach, it draws on theoretical and methodological approaches with a long and complex history. One of the important roots of systems biology is the earlier systems theoretic approaches that emerged in the mid-20th century. The concept of systems biology was used to describe a systems theoretic approach to biology already in the 60ies, but the ideas associated with the approaches did not initially become a part of mainstream biology. What makes them relevant for contemporary biology is that they in recent years have gained new thrust as a consequence of other developments such as the birth of functional genomics. A common goal for the earlier approaches and the new system theoretic stream of “new systems biology” is the search for organizing principles. These are general principles that apply to a class of systems despite the apparent differences of these systems, e.g. between artificial and biological networks, different species or different levels of organization. Organizing principles can thus be understood as robust generalizations that provide a deeper and more fundamental understanding of the behavior of a class of systems. Finding such principles remains a major challenge to contemporary systems biology and several systems biologists have called for new theoretical tools to focus the search for such robust generalizations.

In this paper I investigate the historical trajectories of the search for general principles of biological organization. I argue that more knowledge on the early systems approaches not only has the potential to improve our understanding of the current notion of organizing principles, but also can be important for future scientific developments within systems biology. Looking back can guide the development of new theoretical and methodological frameworks that draw on early systems approaches whose potential has not yet been fully explored. Furthermore, scientists may benefit from reflecting on the problems faced by earlier systems approaches in order to discuss the implications of the current modeling strategies. The talk will reflect on the heuristic value of the strategic search for organizing principles in general and the potential of earlier systems theoretical approaches in particular.