Biomedical Engineering Reference
In-Depth Information
These measurable signal surrogates can be related to some relevant fea-
ture(s) of the system that generated them. In particular, an expression of the in-
terplay between perturbation (internal/external) to system function and the
dynamic response of the regulatory processes, i.e., homeodynamic processes,
can be inferred using nonlinear time-series signal analysis techniques (12). His-
torically, the cardiovascular system (heart rate, blood pressure fluctuations) has
been the beneficiary of this approach, primarily because of the ease and accessi-
bility of system variables and the relatively well-characterized modulation of the
autonomic response. This approach has gained considerable attention, not only
in deciphering the dynamic structure that constitutes cardiovascular regulation
but also as a window onto the genesis (conception, birth, puberty) and span
(maturation, senescence, death) of human life.
The changes in physiological and functional decline accompanying aging
(see chapters 3.2 [by Winslow] and 3.3 [by Glass], Part III, this volume) are an
expression of the losses in the organizational integrity (loss of network connec-
tivity, signaling regimes). This form of organismic dysregulation of hierarchical
(feedback and feedforward circuits) organization can be conceptualized by a
complexification score that is intimately dependent on the degradation, instabil-
ity, and dropout of homeodynamic regulatory processes governing the trajectory
of life including pathologic states, aging, and death.
Reconstituting the functional integrity of a biological system is not a simple
act of replacing or putting the constituent parts back together. The main focus of
biologists for the better part of the twentieth century was the disassembly of
living systems to glean an understanding of the workings of the parts as mem-
bers of the whole. This reductionist approach started with the cell and systemati-
cally descended to the genome itself. Not surprisingly, this exuberance of effort
gave rise to a monumental amount of information that is now begging for rein-
tegration into a systematic whole. The GST concepts promulgated throughout
the 1960s have been resurrected in a reincarnated form—systems biology (16).
Indeed, the lessons of our youthful past are visited upon us again.
Mihajlo Mesarovic (17) anticipated this disconnect in 1968: "It has been
said too often, but has been really taken into account too seldom, that the theory
and applications are intimately related and none can make significant progress
without the other. Actually systems theorists tend to disregard this altogether
and take the position that all that is needed next is that the biologists learn and
apply systems theory. However, I would like to suggest that one of the many
reasons for the existing lag is that
systems theory has not been directly con-
cerned with some of the problems of vital importance in biology
."
The opportunity is ripe to revisit systems theory, its application to biology,
and the lessons that can be learned from the early developments, the goal being
to see how a more evolved perspective of living systems can provide a fresh
look in the postgenome era of the transcriptome and proteome. Interest in formal
mathematical models of biological hierarchical processes is increasing. The new
