Biomedical Engineering Reference
In-Depth Information
namic (14) regulation) via the neural, endocrine, and immune communicative
feedback/feedforward subsystems. From the thermodynamic perspective, if one
follows the path that leads to system disorganization, the outcome is inevitable.
The terminal state (death) is reached when a critical breakdown in the signaling
network and in the connectivity of interacting organs, tissue, and cellular proc-
esses is breached. In the realm of scientific superstition, the observed changes in
regulatory nets commit causation to a sure death.
5.
SYSTEMS BIOLOGY AND MATHEMATICAL MODELING
The construction of mathematical models that realistically simulate whole-
organ function, or a signaling pathway that regulates cell processes such as cell
replication, would be extremely complex and computationally intractable. The
time scales of life events range from microseconds (molecular motion) to years
(life span). The needed spatial resolution is equally enormous (1 nm ion channel
pore size to 1 m body dimension). Clearly, a large assembly of models would be
needed to cover the full span of biological hierarchy and order, each in turn able
to couple to respective levels of known association (e.g., Human Physiome Pro-
ject).
For example, it would seem straightforward that a simplified model system
(e.g., myocardial tissue) that is restricted to only three cell types (neurocytes,
endothelial, myocytes) can be fractionated into various two- and one-cell sys-
tems, each of which is suitably simplified to be understood in isolation. On
closer examination (see Figures 7 and 8), it becomes obvious that the crucial
integrity (stability) and information are completely lost. The simplest explana-
tion offered by system theory is that the fractionation methodologies and analy-
sis techniques used do not commute (see Figure 11) with the dynamic properties
of the system as a whole. Moreover, the participation of the environment (local
milieu) complicates the fractionation aftermath, destroying the dynamics of the
system and its function, thereby preserving mutual information (e.g., genetic
mutations and environment contribute to disease manifestation). It may interest
the reader to know that this classic three-body problem is universally difficult to
reconcile and that the acronym for the neural, endothelial, and muscle (NEM)
cell arrangement means "No" in Hungarian. Surely, this is precisely what Ervin
Laszlo (born in Budapest, 1932) would have said with regard to fractionation
and coarse reductionism. The building of predicative models of cells, organs,
and ultimately organisms need not be the sole course or salvation of reduction-
ism. Acquiring analytical data and methods for integrating the network of genes
with cells and whole organism remains an important endeavor of systems biol-
ogy. Importantly, the quantitative understanding of the entire subcellular, cellu-
lar, or multicellular systems would dramatically alter the approach to and course
of drug discovery and personalized medicine.
