In 1968, Case Institute of Technology launched Systems Biology research and education at the International Symposium "Systems Theory and Biology" with participation from leading biology and systems sciences researchers. Mihajlo Mesarovic of Case declared at the meeting that "The real advance [...] will come about only when biologists start asking questions which are based on systems-theoretic concepts [...] then we will [...] have [...] a field of Systems Biology".

Science, proclaimed that "A field of systems biology with its own identity and its own right" has been launched. (see "A Means Towards a New Holistic", Science 161(3836), July 1968).

To coincide with the 35th anniversary of the discipline at the University, Case Systems Biology Initiative has been launched based on two cornerstones:

  • Integration of Biology and health.
  • Human body and pathologies viewed as 'organized complexity' via multilevel/hierarchical architecture.


  1. System: a relation on 'items'
  2. Complex System: system of systems, or alternately, a relation on systems such that
    • the 'overall' system has a distinct behavior and
    • the subsystems preserve their own identity
    A complex system is different from a complicated system i.e. it is not characterized solely by the number of items but by the architecture of 'organized complexity' as a system of systems.
  3. Subsystems (items in a complex system)
    • preserve their own identity,
    • have their own recognizable boundary and existence
    • ,
    • their behavior is conditioned by mutual interaction and being within the overall system.


Two of the most common concepts used extensively in present day research in Systems Biology are dynamics and feedback. However, there are Systems Science concepts that are relevant to understanding and explaining Complex Biological Phenomena. Systems Concepts that we use are:
  1. Multilevelnesss
    • From conceptual to mathematical and computer based
    • Identification of the roles and functioning of levels
    • Space and time scaling
  2. Domain of Autonomy
  3. Coordination and use of Interaction Balance Principle
  4. Robustness and Resilience - Omnipresent in biological phenomena, the coordinated behavior of the overall systems does not need absolute balance. Rather the system is able to tolerate imbalances within certain bounds, and these bounds can evolve over time.
Examples from our research: