Path: utzoo!utgpu!watmath!iuvax!bionet!prc.unisys.com!overt
From: overt@PRC.UNISYS.COM
Newsgroups: bionet.molbio.bio-matrix
Subject: Re: the bio-matrix IS model-based reasoning!
Message-ID: <8905240139.AA06394@caesar>
Date: 24 May 89 01:39:04 GMT
References: <8905232332.AA00269@benden>
Sender: daemon@NET.BIO.NET
Lines: 78


I wasn't going to respond to any of this now, although I find it very
interesting, because I am working on a grant proposal due June 1, but
after reading Dan's message I feel like putting my 2 cents worth in.

I take "reasoning from first principles" to mean the capability of
making strong predictions about the behavior of a system based on the
knowledge of a set of rules which embody a theory about the system.
In the physical sciences, these rules usually are stated concisely in
the form of mathematical equations.  With few exceptions, no set of
simple rules and no equally powerful formal language is available to
describe or support reasoning in the biological sciences.  One strong
rule in biology is the central dogma, but then it, like everything
else in biology, has an exception.  [In fact, the only good rule in
biology is that there aren't any unbreakable rules.]  In general,
biological disciplines have only weak theories and little predictive
power as compared to the physical sciences.  This is why "reasoning
from first principles" has not proven especially successful in
biology.  But I keep hoping that some day, just maybe, we can have a 
reasonable set of rules to describe biological system.

The biological sciences encompass disciplines from the molecular level
to the eco-systemic level.  I prefer to think of each level in the
hierarchy of organization as having its own rules and formal language,
and that the lower levels in the hierarchy impose constraints on the
higher levels.  Of course, interactions take place across widely
separate levels, but that too can be taken into account.  Then each
level would have its own first principles from which to reason, rather
than as Jon Sticklen suggests, the lowest level (whatever that is)
having the "first principles" which manifest themselves at the higher
levels.

It's certainly not the case that there aren't first principles to be
found in biology (sorry for the double negative), it's just that their
character and their complexity will be different from those in the
physical sciences.  And it will require a different approach to
uncovering them then that used in the physical sciences.  [In part,
this is the justification for the bioMatrix project.]  This is because
biological systems are extraordinarily complex self-regulating systems
and because the existing examples are historical accidents.  So what's
this got to do with reasoning from first principles?  Well, the fact
that the systems are complex implies that the number of rules needed
to describe them is going to be large.  We're not going to see
something like e=mc^2 as a description of vertebrate development.
Second, while all biological systems are related through evolution,
the fact that the systems are historical accidents means that if you
tell me exactly how a drosophila works, I've still got a long way to
go before I understand how a mouse works.  I like to think about this
by analogy to natural languages---another group of complex, historical
systems.  For example, given a complete formal description of Chinese,
what predictions could you make from first principles about the syntax
and semantics of English if all you have to work with are as many
examples of spoken English sentences as you care to hear?  Not many.
On the other hand, when parallels can be identified between mouse and
fly systems, for example by functional or sequence similarity, then
strong inferences can be made.  This forms the basis for reasoning by
analogy in biology.

Peter Karp and Jon Sticklen would like a clearer statement of the
goals of the bioMatrix.  Peter has been involved in this as long as I
have so he should be able to articulate his own perspective on the
goals of the bioMatrix.  Let me say though that there seem to be as
many views of what the bioMatrix is as there are people involved in
it.  Biologists in general perceive it as a grand tool to give them
better database access.  Computer scientists see it as an opportunity
to test out whatever system they are building in an interesting
domain.  My personal view is that the point of the bio-matrix is to
try to aid in the development of appropriate theories of biology at
each level of the hierarchy of organization.  The general approach
advocated is an information intensive one which requires multiple
components to make it work.  The components include a means to access
the ever growing body of information in biological databases, a means
to properly organize and represent the ground data as well as higher
level abstract concepts (ie laws and generalizations of biology), and,
of major importance, methodologies for reasoning about the
information.  Reasoning by analogy is one especially powerful method
in biology, but other potentially important reasoning methods, such as
qualitative reasoning, may also prove important.