From Physiology, Genomes, Systems, and Self-Organization to Systems Biology: The Historical Roots of a Twenty-First Century Approach to Complexity - Systems Biology of Metabolic and Signaling Networks - page 5

One of the fundamental problems addressed by Systems Biology is about the
relation between the whole and its component parts in a system. This problem,
that pervades the history of “systems thinking” in biology (Haken 1978 ; Nicolis and
Prigogine 1977 ; Von Bertalanffy 1950 ), begs the central question of how macro-
scopic behavior arises from the interaction between the elementary components of a
system. It represents a connecting thread that different generations of scientists
have formulated and attempted to solve in their own conceptual and methodological
ways with the technologies available at the time (Junker 2008 ; Skyttner 2007 ;
Yates 1987 ).
The notion that variation in any element affects all the others bringing about
changes in the whole system is one of the foundations of systemic thinking.
However, interactions in a biological system are directed and selective: this result
in organization obeying certain spatial and temporal constraints. For example, in
cellular systems molecular components exist either individually or as macromolec-
ular associations or entire structures such as cytoskeleton, membranes, or
organelles. Interactions are at different degrees of organization and can be
visualized at structural or morphological levels assessed on molecular or macro-
scopic scales. However, biological interactions are not random and in organized
systems they follow certain topological properties, i.e., more or less and preferen-
tially connected to each other. For example, molecular-macromolecular functional
interactions are ruled by thermodynamics and stereo-specificity. Finally, function
in biological systems is a dynamic process resulting from interactions between
structurally arranged components under defined topological configurations.
Dynamic organization is the realm where complexity manifests as a key trait of
biological systems. As a matter of fact, biological systems are complex because
they exhibit nontrivial emergent and self-organizing behaviors (Mitchell 2009 ).
Emergent, self-organized behavior results in macroscopic structures that can be
either permanent (e.g., cytoskeleton) or transient (e.g., Ca 2+ waves), and have
functional consequences. Indeed, macroscopically self-organized structures are
dissipative [“dissipative structures”: (Nicolis and Prigogine 1977 )], i.e., they are
maintained by a continuous flow of matter and energy. Dissipative structures
emerge as complexity increases from cells to organisms and ecosystems that are
thermodynamically open, thus subjected to a constant flux of exchange of matter
(e.g., substrates in cells) and energy (e.g., sunlight in ecosystems such as forests) far
from thermodynamic equilibrium. Therefore, emergent macroscopic properties do
not result merely from static structures, but rather from dynamic interactions
occurring both within the system and between the system and its environment
(Jantsch 1980 ).
A remarkable example of the latter is given by the adaptation of an organism's
behavior to its environment that depends upon biological rhythm generation. The
role of biological clocks in adapting cyclic physiology to geophysical time was
highlighted by Sweeney and Hastings ( 1960 ). Timing exerted by oscillatory
mechanisms is foundational of autonomous periodicity, playing a pervasive role
in the timekeeping and coordination of biological rhythms (Glass 2001 ; Lloyd
1992 ). Winfree ( 1967 ) pioneered the analysis of synchronization among coupled