Biology Reference
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jointly bring about cellular behaviour (Teusink et al., 1998). Top-down and
bottom-up systems biological studies are not mutually exclusive. Ultimately they
should be synergistic. The top-down systems biologist exhibits the pragmatism
of an engineer for which phenomenological explanations suffice, whereas the
bottom-up systems biologist is more guided by a desire to understand mechanism
or systems-theory principles (cf. O'Malley & Dupré, 2005). A recent topic on
systems biology provides more information on these two approaches to systems
biology (Alberghina & Westerhoff, 2005).
3. TOWARDS A PHILOSOPHY OF SYSTEMS BIOLOGY
3.1. The philosophy of molecular biology itself needs
no further elaboration
After the rise of biochemistry and molecular biology in the 1930s and 1950s
and their spectacular successes throughout the second half of the twentieth
century, the underlying reductionist approach has been almost beyond dispute
among practitioners of these disciplines. Studying (ensembles of) individual
(macro)molecules had become a rewarding enterprise. The reigning paradigm
became that by breaking up the system and studying the properties of the resulting
parts one should be able to understand the system fully, simply because the
parts would constitute and hence determine the whole. This reductionist mindset
provided a powerful research methodology, a clear epistemological guiding
principle for acquiring knowledge, an effective strategy for judging the quality of
manuscripts and grant applications and a consistent view of the world. Strategy
and success were so clear that no further philosophizing appeared necessary.
One should put this in the perspective of those times. It had been noted
that dissecting living organisms or even living cells to even the slightest extent
removed virtually all properties that one associated with life (as we now know
because of the interference with energy metabolism and communication, the
depletion of enzymes and coenzymes, or in fact the dependence of anything on
virtually everything in the organism). Therefore, it seemed obvious that looking
at molecules was not going to help to understand life. The alternative of the
holistic physiology that refused to look at anything other than the intact organ-
ism was also limited however. Leaving the living organism intact, one could
only describe experimental results and observed behaviour in terms of pheno-
menological models, the components of which (e.g. growth rate) had no physical/
material entity. Consequently, there was no unique dependence of behaviour
on the activity of those components, not even under well-defined experimental
conditions. An example would be the dependence of the energy state of the
cell on growth rate. On the basis of an empirical observation, a phenomeno-
logical model would describe that dependence in a certain way. According to
