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 3

The French physiologist Claude Bernard in his classical: “L'introduction a
l' ´ tude de la m ´ dicine exp ´ rimentale” (1865) stated that the control of the environ-
ment in which molecules function is at least as important as the identification of the
organic molecules themselves, if not more. In an incisive essay, published almost
20 years ago, Noble and Boyd ( 1993 ) put forward the following three aims with
which Physiology should be concerned, beyond merely determining the
mechanisms of living systems: (1) integrative questions of order and control;
(2) self-organization, in order to link how such order may have emerged; and
(3) make this challenge exciting and possible. This is precisely what has happened,
and in the meantime the emergence of System Biology emphasizes interconnections
and relationships rather than component parts.
To describe a biological system we need to know the structure, the pattern of
organization, and the function (Capra 1996 ; Kitano 2002a ). The first refers to a
catalog of individual components (e.g., proteins, genes, transcriptional factors), the
second insert as to how the components are wired or linked between them (e.g.,
topological relationships, feedbacks), and third how the ensemble works (e.g.,
functional interrelationships, fluxes, response to stimuli, growth, division).
The analytical phase of biology has led to a detailed picture of the biochemistry
of living systems and produced wiring diagrams connecting chemical components
and processes such as metabolic, signaling, and genetic regulatory pathways.
Integration of those processes to understand properties arising from their interaction
(e.g., robustness, resilience, adaptation) and ensuing dynamics from collective
behavior have become a main focus of Systems Biology(Noble 2006 ; Saks
et al. 2009 ).
Systems Biology started to emerge as a distinct field with the advent of high
throughput, -omics technologies, i.e., gen-, transcript-, prote-, and metabol-omics.
Massive data gathering from -omics technologies, together with the capability for
generating computational models, have made possible the massive integration and
interpretation of information. High throughput technologies combined with the
growing facility for constructing mathematical models of complicated systems
constitute the core of Systems Biology. As such, Systems Biology has the potential
to allow us gaining insights into not only the fundamental nature of health and
disease but also with their control and regulation.
1.2 Dynamics, the Invention of Calculus, and
the Impossibility of Prediction
Newton is considered the inventor of the science of dynamics, and he shares with
Leibniz the invention of differential calculus (Gleick 2003 ; Mitchell 2009 ). Born
the year after Galileo—who had launched the scientific revolution—died, Newton
introduced the laws of motion that laid out the foundations of dynamics. These
laws—constant motion, inertial mass, and equal and opposite forces—that apply to