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approach. If the inseparability is so massive that effectively the entire living
cell has to be treated as a single macromolecule, the silicon cell approach does
become impractical.
This issue has been alluded to in Boogerd et al. (2005). In the philosophi-
cal sense, they have defined the generation of new properties in those systems
where macromolecules can be considered as separable from their physical-
chemical environment as weak emergence. The cases where macromolecules
are not separable from their environment would lead to strong emergence. We
would here suggest that it will be possible to make all essential properties of
living organisms emerge from silicon-cell-type models. This then implies that
all functional properties of living systems come from weak emergence. We base
this conjecture on the experience that free-energy transduction, gene expres-
sion, cell cycling and developmental biology can be generated by such models
(cf. www.siliconcell.net). However, it is a conjecture at present; although these
functional properties can be calculated, it has not been verified by experimental
testing whether the models generate the functional properties in a quantitatively
correct way and from the actual kinetic properties of the constituent macro-
molecules. And then, there are cases where function arises, where such calcula-
tions have not yet been possible, such as in the cases of epigenetic regulation of
gene expression.
4.3.4. Parameters and variables and who controls whom
An important distinction to be made in systems biology (and not only there) is
between parameters and variables. Parameters are elements set to fixed values
by the system itself or controlled externally by the experimenter, while vari-
ables are those elements that change during the course of an experiment. (Note
that the elapsed time, though in fact a variable, is normally considered an hon-
orary parameter.) In an isolated metabolic system in which protein synthesis and
degradation are not occurring, the parameters are then the concentrations, and
especially the kinetic and binding constants, of the enzymes involved, as well
as the 'fixed' concentration of 'external' substrates. The variables are then the
time-dependent concentrations of the intermediary metabolites and the flux(es)
through the pathway or network of interest. Two facts are to be noted. First, only
parameters can control variables; and variables cannot control other variables.
Parameters are controlled neither by other parameters nor by variables. Secondly,
normally it is variables that are measured experimentally, as such measurements
of changes are easier - and this statement includes all the 'omics' ('expres-
sion profiling') methods such as transcriptomics, proteomics and metabolomics.
Given these facts, it is seen that there has therefore been a very great dearth of
systematic measurements of the properties that we actually wish to measure, viz.
the binding and kinetic constants of individual proteins (and other molecules).
Such measurements were commonplace in the 1960s and early 1970s (a large
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