Biomedical Engineering Reference
In-Depth Information
modeling them, and learning the tricks for reducing their
complexity to attain computability, are in the engineering domain,
and bioengineering-trained investigators will be the integrators of
the future.
Of course, all models are incomplete. They come in a variety of
forms, such as sketches of concepts, diagrams of relationships,
schemas of interactions, mathematical models defined by sets
of equations, and computational models (from analytical
mathematical solutions or from numerical solutions to differential
or algebraic equations). The behavior of a well developed, well
documented computer model can give us some insight into the
behavior of the real system.
We must do our utmost to predict well, not just the direct results
of a proposed intervention, but also the secondary and long-term
effects. Thus, databasing, the development, archiving, and
dissemination of simple and complex systems models, and the
evaluation (and rejection or improvement) of data and of models -
are all part of the moral imperative. They are the tools necessary to
thinking in depth about the problems that accompany, or are
created by, interventions in human systems or ecosystems.
properties. These models are part of the tool kit for the ''reverse
engineering'' of biology. The scale of the models, like the scale
of models for weather prediction, presents computational
grand challenges.
The Physiome Project is not likely to result in a virtual human
being as a single computational entity. Instead, small models
linked together will form large integrative systems for analyzing
data. There is a growing appreciation of the importance, indeed
the necessity, of modeling for analysis and for prediction in
biological systems as much as in physical and chemical
systems.
The hierarchical nature of biological systems is being used
as a guide to the development of hierarchies of models. Models
at the molecular level can be based on biophysics, chemistry,
energetics, and molecular dynamics, but it is obviously not
practical to use molecular dynamics in describing the fluxes
through sets of biochemical pathways, just as it is not practical
to use the full set of biochemical reactions when describing
force-velocity relationships in muscle, or to use the details of
myofilament crossbridge reactions when describing limb
movement and athletic performance. One cannot build a truck
out of quarks.
Biological models can be defined at many hierarchical levels
from gene to protein to cell to organ to intact organism.
Practical models comprised of sets of linked component
models, each somewhat simplified, represent one level of the
hierarchy. The strategy is to avoid computing the details of
underlying events and to capture, at the higher level, the
essence of their dynamic behavior. But monohierarchical
models are not necessarily built to adapt to changes in
conditions. Handling transients is like using adjustable time
steps in systems of stiff equations, but more complicated; the
lower level model must be used to correct the higher level
representation. Once we have very good models that extend
from gene regulation to the functions of the organism, they can
be used to predict the short-term and long-term efficacy and
side effects of various therapies.
Questions:
1. Like genomic information, should biological information
and models be put in the public domain?
2. What types of risks and benefits can be expected from
this project?
As a step toward providing these tools, Bassingthwaighte
has initiated the Physiome and the Physiome Project:
A physiome can be defined as the quantitative description of the
functional state of an organism. A quantitative model is a way of
removing contradictions among observations and concepts and
creating a consistent, reproducible representation of a system.
Like the genome, the physiome can be defined for each species
and for each individual within the species. The composite and
integrated system behavior of the living organism is described
quantitatively in hierarchical sets of mathematical models defining
the behavior of the system. The models will be linked to databases
of information from a multitude of studies. Without data, there is
nothing to model; and without models, there is no source of deep
predictive understanding.
The Physiome Project provides one response to the
macroethical imperative to minimize risk while advancing medical
science and therapy. The project is an effort to define the
physiome, through databasing and modeling, of individual species,
from bacteria to man. The project began with collaborations
among groups of scientists in a few fields and is developing
spontaneously as a multinational collaborative effort. Investigators
first defined goals and then proceeded to put pieces together into
impressive edifices. Via iteration with new experimentation,
models can remove contradictions and demonstrate emergent
3.
Is this amodel for medical and engineering collaboration?
Why or why not?
in spite of the doctor's beliefs, he or she agrees to arrange
the termination of pregnancy, then the patient might
not be able to infer that the doctor has a pro-life attitude,
and a knowledgeable observer might conclude that the
doctor's pro-life attitude is not strongly held compared
with competing pressures to act in a counter-attitude
manner.
Attitude affects empathy, which is central to justice.
Justice is the virtue that enables us to give others what is
due to them as our fellow human beings. This means we
must not only avoid hurting others by our actions, but we
[A] psychological tendency that is expressed by
evaluating a particular entity {the object of the
attitude} with some degree of favour or disfavour.
50
Attitudes are inferred by observing an individual's re-
sponse to a situation (a stimulus); but they cannot be
measured directly (
Figure 8.2-1
)
51
. For example,
a doctor holding a pro-life attitude, when confronted by
a patient requesting a termination of pregnancy, might
respond by refusing to act as the patient wishes, or by
explaining his or her beliefs to the patient, or both. But if,
