Biology Reference
In-Depth Information
was and is something to be discovered. Systems biology has led to many new
scientific insights, some of which will be reviewed below.
If essential, the paradox and the emancipation from the philosophical founda-
tions of physics may warrant the development of philosophical foundations that
are unique to systems biology - in contrast with those of molecular biology and
physics and perhaps all other disciplines mentioned above. Because systems biol-
ogy may well become main-stream biology and medicine in the coming years,
and because practicing systems biologists are often hindered by paradigm battles
with molecular biologists, we found it important that this issue be discussed
intensely and openly by experts in fields ranging from molecular and systems
biology to the philosophy of science. This topic constitutes such a discussion
and possibly some of the philosophical foundations of systems biology.
2. SYSTEMS BIOLOGY
2.1. History of systems biology
Systems biology did not come out of the blue (Westerhoff & Palsson, 2004;
Alberghina & Westerhoff, 2005). It has two roots in scientific history: a
'components' root and a 'systems' root (see also Chapter 9). The emphasis in the
former root was on individual macromolecules. Mainstream molecular biology
was strongly associated with it; recently, it culminated in a variety of new high-
throughput techniques (X-omics, bioinformatics). The latter root, with its empha-
sis on formal analysis of functional behaviour that arises when many molecules
interact simultaneously, is represented by nonequilibrium thermodynamics, math-
ematical modelling, control theory and related disciplines, and it was cherished by
a minority of systems-oriented scientists comprising control theoreticians, mathe-
matical biologists and biologists engaged in quantitative analysis of metabolism.
We would agree that these two distinct lines of inquiry in molecular biology are
converging to form the systems biology of the twenty-first century (Westerhoff &
Palsson, 2004). This convergencewas not possible any earlier, because sufficiently
large, comprehensive and precise sets of experimental data on molecules in living
cells had been lacking. The theoretical approaches to metabolism in the 1960s and
1970s involving kineticmodelling and control theory had not become part of main-
streambiology, because therewas not enough data to construct and validatemodels
comprehensively enough to explain functional phenomena completely. Because
the new methodologies are genome wide, they must comprise (virtually) all
molecules that are relevant. On the contrary, the convergence was not much
solicited before it became evident that by themselves the resulting large data
sets did not lead to the understanding of how living organisms function, explic-
iting the limitations to molecular biology to be addressed by systems biology
(cf. above).
