(Fwd) James Shapiro Article (fwd)

Pattle Pun (Pattle.P.Pun@wheaton.edu)
Thu, 3 Sep 1998 10:47:47 -0500 (CDT)

Dear Keith and fellow ASAers,

You may be interested in the following article by James Shapiro, a non
Christian molecular biologist who is open to the Intelligent Design
movement. Please notice the empirical data he is presenting that cannot be
accounted for the traditional Neo-Darwinian model.

Dr. Pattle Pun
Professor of Biology
Wheaton College, Wheaton, IL 60187
eMail: Pattle.P.Pun@wheaton.edu
Phone: (630)752-5303
FAX: (630)752-5996


James A. Shapiro, Professor of Microbiology, Department of Biochemistry and
Molecular Biology, University of Chicago

The recent reviews in your columns of books by Dennet, Dawkins and
Behe is testimony to the unflagging interest in controversies about
evolution. Although purists like Dennet and Dawkins repeatedly assert that
the scientific issues surrounding evolution are basically solved by
conventional neo-Darwinism, the ongoing public fascination reveals a deeper
wisdom. There are far more unresolved questions than answers about
evolutionary processes, and contemporary science continues to provide us
with new conceptual possibilities. Unfortunately, readers of the Boston
Review may remain unaware of this intellectual ferment because the
evolution debate so often assumes the quality of an abstract and
philosophical "dialogue of the deaf" between Creationists and Darwinists.
Although our knowledge of the molecular details of biological organization
is undergoing a revolutionary expansion, serious open-minded discussions of
the impact of discoveries in molecular biology are all too rare. The
possibility of non-Darwinian scientific viewpoints is virtually never
considered. The main argument of this essay, therefore, will be that
developments in contemporary life science reveal many shortcomings in
orthodox evolutionary theory and open the door to very different ways of
formulating questions about the evolutionary process. After a discussion of
technical advances in our views about genome organization and the
mechanisms of genetic change, I will focus on a growing convergence between
biology and information science which offers the potential for scientific
investigation of possible intelligent cellular action in evolution.
The past five decades of research in genetics and molecular
biology have brought us revolutionary discoveries. Rather than confirm the
oversimplified views of cellular organization and function held at
mid-century, the molecular revolution has revealed an unanticipated realm
of complexity and interaction more consistent with computer technology than
with the mechanical viewpoint which dominated when the neo-Darwinian Modern
Synthesis was formulated. The conceptual changes in biology are comparable
in magnitude to the transition from classical physics to relativistic and
quantum physics. I would like to single out four categories of molecular
discoveries that open up exciting, new ways of thinking about the
biological processes that underlie evolutionary change.
(1) GENOME ORGANIZATION. Our current ideas of genome organization
are completely different from the "beads on a string" view that dominated
genetics in the 1940s and 1950s. At that time genes were "units" which
corresponded to individual organismal traits, and the "one gene-one enzyme"
hypothesis told us that the essential business of each gene was to encode a
specific protein molecule linked to a particular phenotype. We have now
deconstructed each genetic locus into a modular assembly of regulatory and
coding motifs. Most of these motifs are shared between many loci,
suggesting that genomes are assembled in Lego-like fashion from a
repertoire of more basic sequence elements, many of which do not encode
proteins but determine other important functions (transcription,
translation, RNA processing, DNA replication, chromatin condensation,
etc.). As we analyze genome expression during cellular proliferation and
multicellular development, we have learned that diverse genetic loci are
organized hierarchically into interconnected genome-wide networks which
function dynamically. Not confined to a single pathway, many genetic loci
are active at different times, participating in the expression of more than
one phenotypic trait. Comparisons of genomes in different organisms have
revealed unexpected patterns of evolutionary conservation across large
taxonomic distances, while closely-related genomes frequently differ
significantly in the arrangement of repetitive DNA elements which do not
encode proteins.
How all of this modularity, complexity and integration arose and
changed during the history of life on earth is a central evolutionary
question. Localized random mutation, selection operating "one gene at a
time" (John Maynard Smith's formulation), and gradual modification of
individual functions are unable to provide satisfactory explanations for
the molecular data, no matter how much time for change is assumed. There
are simply too many potential degrees of freedom for random variability and
too many interconnections to account for.
(2) CELLULAR REPAIR CAPABILITIES. Studies of the molecular sources
of genetic variability have taught us two major lessons. The first of these
lessons is that all cells from bacteria to man possess a truly astonishing
array of repair systems which serve to remove accidental and stochastic
sources of mutation. There are multiple levels of proofreading mechanisms
which recognize and remove errors that inevitably occur during DNA
replication. These proofreading systems are capable of distinguishing
between newly synthesized and parental strands of the DNA double helix, so
they operate efficiently to rectify rather than fix the results of
accidental misincorporations of the wrong nucleotide. Other systems scan
non-replicating DNA for chemical changes that could lead to miscoding and
remove modified nucleotides, while additional functions monitor the pools
of precursors and remove potentially mutagenic contaminants. In
anticipation of chemical and physical insults to the genome, such as
alkylating agents and ultraviolet radiation, additional repair systems are
encoded in the genome and can be induced to correct damage when it occurs.
It has been a surprise to learn how thoroughly cells protect themselves
against the kinds of accidental genetic change that, according to
conventional theory, are the sources of evolutionary variability. By virtue
of their proofreading and repair systems, living cells are not passive
victims of the random forces of chemistry and physics. They devote large
resources to suppressing random genetic variation and have the capacity to
set the level of background localized mutability by adjusting the activity
of their repair systems.
other major lesson of molecular studies into the origins of genetic change
is that all cells possess multiple biochemical agents for natural genetic
engineering -- processes that include the cutting and splicing of DNA
molecules into new sequence arrangements. Most frequently, natural genetic
engineering capabilities reveal themselves through the activities of mobile
genetic elements -- DNA structures found in all genomes that can move from
one position to another. Mobile genetic elements comprise the most fluid
components of the genome and are also the most taxonomically specific. In
human cells, mobile elements include retrotransposons, like the half
million or more Alu sequences dispersed over all our chromosomes, as well
as the inherited gene fragments which our lymphocytes assemble daily to
form active genetic loci encoding the key antigen recognition molecules of
our immune system. The biochemical agents of DNA restructuring include the
enzymes used in our own genetic engineering for research and biotechnology
(nucleases, ligases, reverse transcriptases and polymerases) as well as
other proteins that combine to form molecular machines capable of
mobilizing different genomic components.
The existence of cellular biochemical activities capable of
rearranging DNA molecules means that genetic change can be specific (these
activities can recognize particular sequence motifs) and need not be
limited to one genetic locus (the same activity can operate at multiple
sites in the genome). In other words, genetic change can be massive and
non-random. Some organisms, such as the ciliated protozooan Oxytricha,
completely reorganize their genetic apparatus within a single cell
generation, fragmenting the germ-line chromosomes into thousands of pieces
and then reassembling a particular subset of them into a distinct kind of
functional genome. Furthermore, natural genetic engineering systems can
operate premeiotically during the somatic development of tissues that will
ultimately produce gametes. This means that major chromosome
reorganizations can be present in multiple gametes. Consequently, the
appearance of new genome architectures during evolution is not necessarily
limited to isolated individuals.
The discovery that genome reorganization is largely a biological
process traces back to Barbara McClintock's pioneering studies of mutation
and chromosome rearrangement in maize from the 1940s through the 1960s. She
linked these genetic events to changes in the regulation of gene expression
programs during plant development. We can now appreciate her tremendous
wisdom and foresight by seeing how the Lego-like patterns of integrated
genome organization mentioned above could be created by the activity of
cellular natural genetic engineering systems. Because, like all cellular
functions, natural genetic engineering systems are subject to control
circuits, they can be held in abeyance for long periods and then called
into action at certain key times. Sometimes these activations can be
regularly programmed, as in the development of our immune systems, and
sometimes activations can occur in response to crisis, as McClintock
documented in maize.
The point of this discussion is that our current knowledge of
genetic change is fundamentally at variance with postulates held by
neo-Darwinists. We have progressed from the Constant Genome, subject only
to random, localized changes at a more or less constant mutation rate, to
the Fluid Genome, subject to episodic, massive and non-random
reorganizations capable of producing new functional architectures. It is
inevitable that such a profound advance in awareness of genetic
capabilities will dramatically alter our understanding of the evolutionary
process. Nonetheless, neo-Darwinist writers like Dawkins continue to ignore
or trivialize the new knowledge and insist on gradualism as the only path
for evolutionary change.
(4) CELLULAR INFORMATION PROCESSING. While it is easy to see how
advances in our understanding of genome organization and genetic change
will impact theories of evolutionary processes, there is another
development in contemporary biology whose relevance to evolution is less
obvious but more basic. This is the growing realization that cells have
molecular computing networks which process information about internal
operations and about the external environment to make decisions controlling
growth, movement and differentiation. This realization has come, in large
measure, from detailed genetic analysis of cellular processes and
multicellular development. The inducible repair systems mentioned above
provide a relatively simple, well-studied example. Bacterial and yeast
cells have molecules that monitor the status of the genome and activate
cellular responses when damaged DNA accumulates. The surveillance molecules
do this by modifying transcription factors so that appropriate repair
functions are synthesized. These inducible DNA damage response systems are
sophisticated and include so-called "checkpoint" functions that act to
arrest cell division until the repair process has been completed. When the
checkpoints do not function, cell division proceeds before repair is
completed, and the damaged cells die or produce inviable progeny. One can
characterize this surveillance/inducible repair/checkpoint system as a
molecular computation network demonstrating biologically useful properties
of self-awareness and decision-making.
There are many other cellular systems that display comparable
information processing capabilties. It is now common among molecular
biologists who study the cell cycle to speak of various checkpoints (is DNA
replication complete? are the chromosomes properly condensed and aligned on
the metaphase plate?) and decision points (e.g. when to initiate chromosome
movement and cytokinesis). A recent special issue of ScientificAmerican
describes beautifully how cancer is now seen as a disease of the molecular
information processing routines that ensure orderly cell growth and
behavior in the healthy organism. Aberrant tumor cell growth appears to
result from at least two kinds of malfunction: (a) the loss of checkpoint
controls, or (b) the failure of decision-making routines that dictate
programmed cell death (apoptosis) for cells in inappropriate surroundings.
During embryonic development, cells make decisions about differentiation
based on multiple molecular signals picked up from their environment and
from their neighbors by means of surface receptors. These receptors are
linked to intercellular molecular cascades called "signal transduction
pathways" which integrate the inputs from the receptors to generate
appropriate patterns of differential gene expression and morphogenesis of
specialized cell structures.
Signal transduction is not limited to multicellular development. We
are learning that virtually every aspect of cellular function is influenced
by chemical messages detected, transmitted and interpreted by molecular
relays. To a remarkable extent, therefore, contemporary biology has become
a science of sensitivity, inter- and intra-cellular communication, and
control. Given the enormous complexity of living cells and the need to
coordinate literally millions of biochemical events, it would be surprising
if powerful cellular capacities for information processing did not manifest
themselves. In an important way, biology has returned to questions debated
during the mechanism-vitalism controversy earlier this century. This time
around, however, there are two new factors. One is that the techniques of
molecular and cell biology allow us to examine the detailed operation of
the hardware responsible for cellular responsiveness and decision-making.
The second new factor is the existence of computers and information
networks, physical entities endowed with computational and decision-making
capabilities. Their existence means that discussing the potential for
similar activities by living organisms is neither vague nor mystical.
What significance does an emerging interface between biology and
information science hold for thinking about evolution? It opens up the
possibility of addressing scientifically rather than ideologically the
central issue so hotly contested by fundamentalists on both sides of the
Creationist-Darwinist debate: Is there any guiding intelligence at work in
the origin of species displaying exquisite adaptations that range from
lambda prophage repression and the Krebs cycle through the mitotic
apparatus and the eye to the immune system, mimicry and social
organization? Borrowing concepts from information science, new schools of
evolutionists can begin to rephrase virtually intractable global questions
in terms amenable to computer modelling and experimentation. We can
speculate what some of these more manageable questions might be: How can
molecular control circuits be combined to direct the expression of novel
traits? Do genomes display characteristic system architectures that allow
us to predict phenotypic consequences when we rearrange DNA sequence
components? Are molecular heuristics at work as signal transduction
networks regulate the action of natural genetic engineering hardware?
Questions like those above will certainly prove to be naive because
we are just on the threshold of a new way of thinking about living
organisms and their variations. Nonetheless, these questions serve to
illustrate the potential for addressing the deep issues of evolution from a
radically different scientific perspective. Novel ways of looking at
longstanding problems have historically been the chief motors of scientific
progress. However, the potential for new science is hard to find in the
Creationist-Darwinist debate. Both sides appear to have a common interest
in presenting a static view of the scientific enterprise. This is to be
expected from the Creationists, who naturally refuse to recognize science's
remarkable record of making more and more seemingly miraculous aspects of
our world comprehensible to our understanding and accessible to our
technology. But the neo-Darwinian advocates claim to be scientists, and we
can legitimately expect of them a more open spirit of inquiry. Instead,
they assume a defensive posture of outraged orthodoxy and assert an
unassailable claim to truth, which only serves to validate the
Creationists' criticism that Darwinism has become more of a faith than a
A sounder perspective on the history of science would be very
helpful to all concerned. For example, a parallel has been drawn in your
columns and elsewhere between criticisms of Darwinian orthodoxy and
assaults on the Law of Gravity, presenting them as equally deplorable
examples of anti-science obscurantism. Yet, if truth be told, gravity is
far from a settled matter. The relativistic Law of Gravity at the end of
the 20th Century is not the same as the classical Law of Gravity at the end
of the 19th Century, and discovering how the continuous descriptions of
general relativity can be integrated into a single theory with the discrete
accounts of quantum physics is still an active field of research. From a
scientific point of view, then, the Law of Gravity has quite properly been
under continuous challenge. Dogmas and taboos may be suitable for religion,
but they have no place in science. No theory or viewpoint should ever
become sacrosanct because experience tells us that even the most elegant
Laws of Nature ultimately succumb to the inexorable progress of scientific
thinking and technological innovation. The present debate over Darwinism
will be more productive if it takes place in recognition of the fact that
scientific advances are made not by canonizing our predecessors but by
creating intellectual and technical opportunities for our successors.

James A. Shapiro is a bacterial geneticist. For three decades, his research
has analyzed how mobile genetic elements rearrange the bacterial genome and
how cellular control circuits regulate the activities of these natural
genetic engineering systems. In addition, he studies the processes of
multicellular self-organization as bacterial populations grow into

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James A. Shapiro
920 E. 58TH STREET, CHICAGO, ILL. 60637-4931
773-702-1625/Fax 773-702-0439/Email jsha@midway.uchicago.edu


Stanton L. Jones
Office of the Provost
Wheaton College
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