Rob.Carr@ncar.UCAR.EDU (Rob Carr) (10/02/89)
Pardon me while I think out loud for a few moments. Hopefully this will get
someone else thinking
One of the big areas in biology for the past 5 years has been chaos theory.
Stated simply, systems that are easily described may have very unpredictable
consequences. A common example is the water faucet drip. At very low drip
rates, the drops are uniform and the time between drops remains the same. When
the flow rate is speeded up, there may be differences in the drops as they
form, resulting in different time periods between the drops. While the time
periods may be random, there are patterns that may be seen if the data is
represented properly.
Biological systems, since they are non-linear, tend to be fertile grounds for
chaos theory. Already, the heart and the brain have shown that they may be
evaluated on this basis quite successfuly. What is most important is that
chaos theory allows you to examine the transition from regular to chaotic
behavior while pointing out the crucial steps in the transition. For example,
for atrial fibrillation, the behavior of the T wave, which originates in the
other part of the heart, is actually more critical for the onset of AFIB. So
now people are studying drugs that affect the ventricles to help with AFIB,
whereas before they only studied the atria.
If you've followed me so far, you've probably already guessed what's coming.
There are several chaotic periods or linear systems with chaotic regions nearby
involved in the progression of HIV. I think.
First, there is infection itself. If a person were injected with one HIV, it
is extremely doubtful that the person would become infected. Only when the
"stress" (i.e. # of viruses) is turned up does infection become more probable.
In at least some people, there is then a quiet phase where the virus is not
expressed. This would be a linear period. Yet this phase seems to progress
into a chaotic phase where antibodies become apparent and the virus replicates.
What pushes the system outside the envelope?
The course of HIV does not appear uniformly linear. There are periods of
remission and periods of catastrophic system failure. It sounds random. In
biology, there doesn't seem to be anything random, just chaotic.
If continuous p24 antigen levels, #s of infected cells, case histories, etc.
were available, it might be possible to draw the strange attractors (as they
are called) for AIDS. We might learn very quickly some important facets of the
disease. Perhaps steps we are now looking at are unimportant. Perhaps there
are ultimate times to give AZT or DDI. I think I can give an example here,
although it probably doesn't rely on chaos theory. If someone were acutely
exposed to HIV, by say a blood transfusion or needle stick from a grossly
contaminated sample, an immediate regimine of AZT may prevent the body's
leaving the initial chaotic region, giving the system sufficient time to drop
to zero. Perhaps there are "constellations" of values that indicate the
potential for future improvement or collapse which would permit the altteration
of drug dosages.
One of the stranger things about chaotic systems is that they do not always
behave as expected. For example, values of certain measurements which would be
considered "bad" may actually be indications to cut BACK on drugs.
--
Uucp: ...{gatech,ames,rutgers}!ncar!noao!asuvax!stjhmc!129!81!Rob.Carr
Internet: Rob.Carr@f81.n129.z1.fidonet.orgmandel@lll-crg.llnl.gov (Tom Mandel) (10/08/89)
Chaos theory may be useful generally to the study of how diseases spread (epidemiology) but there is no reason to think that it has any special benefits in explaining the unfolding of the HIV epidemic (over explaining the evolution of any epidemic). -- --Tom Mandel mandel@well.sf.ca.us mandel@unix.sri.com [Opinions expressed, if any, are not those of the WELL or SRI International.]
FUCHS%VCUVAX.BITNET@oac.ucla.edu (10/10/89)
Rob Carr's post did initiate many thoughts..... I too have become interested in what Chaos Theory might be able to tell us about the immune system (and in particular immune regulation.) The immune system seems to be a "nonlinear dynamic system." For example, the response you get (say amount of antibody produced) is not linearly related to the amount of antigen used to drive the system. I admit that I know little about chaos theory and this leaves me open to 'fatal flaws' in the reasoning. However, it seems like the theory of immune regulation which deals with idiotype networks may respond to this technique. In the 'Network Hypothesis' the immune system is viewed as constantly responding in positive and negative ways to various antigen receptors. The whole spectrum of antigen receptors available in the immune system act to form "internal images" of the external antigenic world. That is to say that the reason the immune system can respond to any antigen found in the world is that it is ALREADY responding to it, in the form of an internal image of its three dimensional structure represented in some cell clone's antigen receptor. This is very complicated to imagine for if a specific cell clone was induced to proliferate, it's antigen receptors would act as positive and negative signals for the proliferation or suppression of various other cell clones. When these secondary clones responded they would in turn affect the behavior of still other clones, and others, and others. Hence a 'network.' Given the vast complexity of this system it seems that it would be impossible to predict what effect the proliferation of a single clone might have on the regulation of the system as a whole. My thought is then, might there not be a "strange attractor" which constrains the operation of the above network. Within these limits the network appears to oscillate chaotically, yet not beyond the limits imposed by the attractor. Impostion of a pathogen like HIV which fundamentally alters the immune system might then alter the attractor so that the network now functions under new and dramatically different constraints. My problem is that I would not know how to set up an experiment to look for this relationship. I do not know what to "measure." Here I am probably handcuffed by the limited understanding of immune regulation (on a body wide scale and not simply in response to a single antigen) which exists today. I agree with Tom Mandel that I do not see any immediate applications of chaos theory to HIV infection IN TERMS OF disease PROGRESSION. It seems that the progression from HIV infection to seroconversion to AIDS is fairly well defined and predictable. (Although the biological basis for this slow progression is NOT well understood for AIDS or Kuru or Scrapie and other such painfully slow diseases.) If any of you have insight into the application of Chaos theory to biology I would like to hear from you.