From: <complex-science@necsi.org> (Sungchul Ji)
Sender: <y3list1@necsi.org> (Yaneer Bar-Yam)
To: complex-science
Date: Wed, 06 Aug 2008 23:27:43 -0400
Message-ID: <redirect-22520612@necsi.org>
Subject: Paradigm shift in biology: From structure to structure-process 
     duality
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Structure (e.g., DNA) and processes (e.g., gene expression) are both
essential to account for life on the molecular level.  In other words,
structure (S) and processes (P) are fundamental to life on an equal
footing, and yet contemporary biologists have been emphasizing structures
over processes (especially since the discovery of the elegant DNA double
helix in 1953), most likely because of the experimental constraints
favoring the study of stable structures over transient, dynamic processes.

Perhaps biologists can learn from a similar experience that physicists
went through between the 17th and 20th centuries in the form of the
wave-particle duality debate on the nature of light.  As is well known,
the Huygens, Bohr and their followers thought that light was a wave (on
the basis of interference phenomena, for example), while Newton, Einstein
and their followers firmly believed that light was a stream of particles
(as evidenced by the photoelectric effect).  The wave-particle duality
problem was not solved until the early decades of the 20th century when
the new science of quantum mechanics was established in the hands of
Planck, Einstein, de Broglie, Heisenberg, Dirac, Schroedinger, Pauli, and
Born.

Available evidence indicates to me that the 21st century biology is faced
with the structure-process duality problem that may be analogous to the
wave-particle duality pardox in physics in the past century.  One major
difference may be that, while physicists were equally familiar with both
of the competing concepts, i.e., waves and particles, contemporary
biologists are familiar almost exclusively with one of them, namely,
the concept of structures and have only a vague idea about the importance
of processes in living systems.

I offer the following three examples as evidence for the necessity to
invoke the structure-process duality in biology:

   1) Microarray experiments
With the invention of the DNA microarray technique in the mid-1990's,
biologists have been able to measure RNA levels of tens of thousands of
genes simultaneously. The mistake (in my opinion [1]) that many biologists
have been making in this field unwittingly over the past decade or more is
this: When the microarray technique is used to measure the so-called gene
expression profiles and ascribe to the genes encoding these RNAs the role
for regulating their levels, biologists are measuring P (i.e., gene
expression, which is a process) and reducing it to S (i.e., DNA
sequences).  It is analogous to physicists who measure the wave property
of light (e.g.,  interference patterns) and interpreting them in terms of
particles (as in photoelectric effects). For convenience, we may
refer to such mis-interpretations in biology as the 'P-to-S reduction
error'. To correct such an error, all we need to do is to treat S and P on
an equal footing (S-P democracy ?), without reducing one to the other, an
error committed not only by biologists but also by process philosophers in
the Whiteheadian tradition, in my opinion.  (Here they commit the error of
eliminating S in favor of P, at least when applied to biology!)

   2)  The definition of a gene
Prior to 2007 when the results of an international research effort known
as the ENCODE (Encyclopedia of DNA Elements) Project was anounced, the
defintion of gene was simple: DNA segments encoding RNAs leading to
protein synthesis [2].  But the ENCODE project has unearthed about a dozen
new findings that cannot be readily accommodated by this simple conception
of a gene and a new definition of a gene is called for. The failure of the
pre-ENCODE conception of a gene can be traced ultimately to the following
fact:  Biologists have been measuring the functions of genes (i.e., P) and
reduced the results to nucleotide sequences of DNA (i.e., S). The 'P-to-S
reducton error agian. One way to resolve the problems revealed by the
ENCODE project is to postulate that there are two equally important
classes of genes -- the S-genes and P-genes.  The former is identified
with the pre-ENCODE conception of genes (also called the Watson-Crick
genes [3]) and the latter is a new class of genes called the Prigoginian
genes [3]).  S-genes are analogous to sheet music (or written language)
and P-genes are analogous to audio music (or spoken language) [4, 5]. 
Just as the sheet music is converted into audio music by a pianist, so the
Watson-Crick genes are postulated to be transduced into Prigoginain genes
by conformons, the conformational strains of enzymes [3].

   3)  Free radicals and human diseases
Free radicals are defined as any chemical species carrying one or more
unpaired electrons.  Examples include the superoxide anion free radicals (
an oxygen molecule with one extra electron), nitric oxide (NO), and
carbon-centered free radicals generated during air oxidation of
phospholipids constituting cell membranes.

Many free radicals are generated in cells as the results of normal
metabolism as during mitochondrial respiration responsible for generating
ATP but do not cause any harm because their concentrations are strictly
controlled not to exceed beyond certain critical levels (reminiscent of
nuclear reactors).  They cause cell damages only when such control
mechanisms malfunction or go awry due to environmental toxicants or
pathogens.  Therefore it seems reasonable to postulate that there are two
kinds of free radicals in cells and tissues -- "good" and "bad" free
radicals, depending on how much of them is produced where, when and for
how long [6].  In other words, not all free radicals are bad (as many
biologists have been assuming), since it is not the chemical structures of
free radicals (i.e., S) but rather their spatiotemporally organized
concentration distribtuions in living cells and tissues (i.e., related to
P) that determine whether they are good or bad for human health. To remedy
the shortcomings of the traditional paradigm in biomedical research,
therefore, it appears necessary to make the transition from the
traditional 'equilibrium structure-based' paradigm to the 'dissipative
structure-based' one.  The drugs developed under the new paradigm may be
referred to as the "dissipative structure-targeting drugs (DSTDs)" as
compared to the traditional "equilibrium structure-targeting drugs
(ESTDs)" [7].  If this speculation turns out to be valid, the DSTDs would
turn out to be the drugs of the 21st century just as ESTDs would be
considered to be the drugs of the 20th century.

With all the best.

Sung

____________________________________________
Sungchul Ji, Ph.D.
Department of Pharmacology and Toxicology
Rutgers University
Piscaraway, N.J. 08855


references:

   [1]  Ji, S., Chaovalitwongse, A., Fefferman, N., Yoo, W., and
Perez-Ortin, J. E. (2008).  Mechanism-based Clustering of Genome-wide
RNA Levels in Budding Yeast: Roles of Transcription and Transcript
Degradation. In: Clustering Challenges in Biological Networks
(Chaovalitwongse, A., ed.) (in press).
   [2]  Gerstein, M. B., et al (2007).  What is a gene, post-ENCODE?
History and updated definition.  Genome Research 17:669-681.
   [3] Ji, S. (1988).  Watson-Crick and Prigoginaina Forms of Genetic
Informaton. J. theoret. Biol. 130: 239-245.
   [4] Ji, S. (2008).  Molecular Theory of the Living Cell: Conceptual
Foundations, Molecular Mechanisms, and Applications.  Springer, New
York (to appear)
   [5] Ji, S. (2009).  Words, Sounds, and Meanings of DNA.  Imperial
Co9lleger Press, London (in preparation under invitation from the
publisher).
   [6] Ji, S. (1991).  Biocybernetics: A Machine Theory of Biology.  In:
Molecular Theories of Cell Life and Death (Ji, S., ed.), Rutgers
Univeristy Press, New Brunswick.  Pp. 1-237. See the section on FSDM
Hypothesis of Disease Development on pp. 191-194, available at
http://www.rci.rutgers.edu/~sji, under Publications.
   [7] Ji, S. (2010).  Cell Model-Based Pharmacotherapeutics and
Toxicology (in preparation).