353 INTRODUCTION - BACKGROUND Systems, Biology and Systems Biology In recent years, there has been a rebirth of systems approaches to biological research, collectively known as “systems biology” (Ideker et al., 2001). Despite certain difficulties associated with the definition of this field (Cowley, 2004) or process (Naylor & Ca- vanagh, 2004), the goals of systems biology are high- ly ambitious: to represent, perturb and manipulate biological systems so that the functional roles of the individual components can be unveiled and ultimate- ly understood in their entire context (Ideker et al., 2001). There has been a general agreement and a precipitous realization that the function of molecular components in cells is context-dependent (Burgess, 2004), and methods that specifically address this issue have been developed, for example the computation- al detection of functional modules in protein interac- tion networks (Spirin & Mirny, 2003; Pereira-Leal et al., 2004). Where opinions differ is the limit of this wider context. Typically, most of systems biology has ini- tially focused on molecular systems, but nothing in the original definition precludes the expansion of that scope towards organisms, populations, species or ecosystems: “A growing wave of biological research aims at systems - from networks of proteins in signal transduction pathways to communities of species” (May, 2005). In fact, it could be argued that the roots of systems biology arise from the pioneering work of von Neumann, Wiener, von Bertalanffy, Rosen and others (Cornish-Bowden & Cardenas, 2005). The earliest reference to a systems approach appears to be the definitive work of Lotka on physical biology, which dealt with species equilibria and ecological modeling on a grand scale, among other things (Lot- ka, 1925). The quest for an upper limit in systems biology Christos A. OUZOUNIS 1,2,3* , Vasilis J. PROMPONAS 1 and Ioannis ILIOPOULOS 4 1 Bioinformatics Research Laboratory, Department of Biological Sciences, University of Cyprus, PO Box 20537, CY-1678 Nicosia, Cyprus 2 Institute of Agrobiotechnology, Centre for Research & Technology Hellas (CERTH), GR-57001 Thessaloniki, Greece 3 Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada 4 Division of Medical Sciences, Medical School, University of Crete, GR-71110 Heraklion, Greece Received: 27 May 2012 Accepted: 29 May 2012 We discuss order-of-magnitude formulations for molecular systems biology, in order to derive estimates for the upper limit of the number of unique gene families and their ensuing potential interactions. A useful equation in the field of the Search for ExtraTerrestrial Intelligence (SETI), known as the Drake equation, can be mapped precisely to the problem of estimating the total number of unique gene families. Despite the fact that the parameter values cannot be accurate- ly estimated at present, this semantic mapping provides a basis upon which a novel research agenda might be established, delimiting the scope of our technological capabilities in systems bi- ology and appreciating the complexity of our scientific aspirations. Key words: systems biology, gene families, Drake equation, protein interactions. * Corresponding author: tel.: +30 2310 498473, e-mail: ouzounis@certh.gr Journal of Biological Research-Thessaloniki 18: 353 – 358, 2012 J. Biol. Res.-Thessalon. is available online at http://www.jbr.gr Indexed in: WoS (Web of Science, ISI Thomson), SCOPUS, CAS (Chemical Abstracts Service) and DOAJ (Directory of Open Access Journals)