ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.

February 25, 2000 -- Vol. 4 Number 8

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No one of us really will ever know very much.
This is why we shall have to find comfort in the
fact that taken together we know more and more.
-- J. Robert Oppenheimer (1904-1967)

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Contents of This Issue:

1. Theoretical Physics: On the Theory of Everything and
Reductionism in Physics, Chemistry, and Biology.

2. Evolutionary Biology: The Quality of the Fossil Record

3. Animal Behavior: Nongenomic Transmission of Maternal Behavior

4. Medical Biology: Ethanol-Induced Neurodegeneration and Fetal
Alcohol Syndrome

5. Medical Biology: On the Present World Epidemic of Allergic
Diseases
 
In Focus: On Gravitational Waves

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1. THEORETICAL PHYSICS: ON THE THEORY OF EVERYTHING
In a recent issue of SW (11 Feb 00/Report #1; appended below), we
discussed a call by several biologists for a phenomenological
approach to dynamic processes inside biological cells. In this
issue we discuss a similar call by two physicists concerning
"emergent behavior" in physical systems, i.e., behavior
apparently not predictable from first principles but dependent on
new principles emerging only at higher levels of complexity. In
both cases, the essential question is the same: To what extent
are reductionist approaches to phenomena limited, and where
limits exist, what is to be done?
... ... R.B. Laughlin and D. Pines (2 installations, US) present
a provocative commentary on current fundamental theory in
physics, the authors making the following points:
     1) The term "Theory of Everything" refers to the ultimate
theory of the Universe, a set of equations capable of describing
all phenomena that have been observed, or that will ever be
observed. It is the modern incarnation of the reductionist idea
of the ancient Greeks, an approach to the natural world that has
been extremely successful and which for many people is the
central paradigm of physics. A special case of this idea is the
general wavefunction equation of nonrelativistic quantum
mechanics, which describes the everyday world in terms of known
quantities: the charge and mass of the electron, the charges and
masses of the atomic nuclei, and Planck's constant. Less
immediate things in the Universe, such as the planet Jupiter,
nuclear fission, the Sun, or the isotopic abundances of elements
in space are not described by this equation, because important
variables such as gravity and nuclear interactions are missing.
But concerning everyday people-scale phenomena, this equation is
for all practical purposes the Theory of Everything for our
everyday world.
     2) The authors suggest, however, that examining the Theory
of Everything, it becomes obvious that it is not even remotely a
theory of every thing. We know the equation is correct because it
has been solved accurately for small numbers of particles
(isolated atoms and small molecules) and found to agree in minute
detail with experiment. But it cannot be solved accurately when
the number of particles exceeds approximately 10. The authors
suggest that no computer existing, or that will ever exist, can
break this barrier -- it is a "catastrophe of dimension": If the
amount of computer memory required to represent the quantum
wavefunction of one particle is N, then the amount of computer
memory required to represent the wavefunction of k particles is
N^(k). Although it is possible to perform approximate
calculations for larger systems, and such calculations have in
many cases been valuable, the schemes for approximating are not
first-principles deductions, they are rather art keyed to
experiment. These approximate approaches thus tend to be the
least reliable precisely when reliability is most needed, i.e.,
when experimental information is scarce, the physical behavior
has no precedent, and the key questions have not yet been
identified.
     3) A variety of physical phenomena easily observed in the
laboratory (e.g., the *quantum Hall effect, *superfluid helium,
*Josephson effect) permit measurements of exact quantities that
cannot be deduced by direct calculation from the present Theory
of Everything, for exact results cannot be predicted by
approximate calculations. The authors suggest this point is still
not understood by many professional physicists, who find it
easier to believe that a deductive link exists, and has only to
be discovered, than to face the truth that there is no link. But
the absence of a link is true nonetheless, and not denied by the
reliability of such experiments: The important consideration is
that experiments concerning these physical phenomena work because
there are higher organizing principles in nature that make them
work.
     4) Concerning Big Bang cosmology and attempts to develop
fundamental theory from considerations and observations of the
early Universe, the authors suggest that no one familiar with
violent high-temperature phenomena would dare to infer anything
about the equations of quantum mechanics by studying explosions,
for explosions are unstable and quite unpredictable from one
experiment to the next. The authors suggest that the assumption
that the early Universe should be exempt from this problem, and
that a Theory of Everything can be inferred from observations of
the early Universe, is not justified by anything except wishful
thinking. It could very well turn out that the Big Bang is the
ultimate emergent phenomenon, "for it is impossible to miss the
similarity between the large-scale structure recently discovered
in the density of galaxies and the structure of styrofoam,
popcorn, or puffed cereals."
     5) The authors suggest that the fact that the essential role
played by higher organizing principles in determining emergent
behavior continues to be disavowed by so many physical scientists
is a poignant comment on the nature of modern science. To solid-
state physicists and chemists, who are schooled in quantum
mechanics and deal with it every day in the context of
unpredictable electronic phenomena such as that exhibited by
*Kondo insulators or *cuprate superconductivity, the existence of
these organizing principles in emergent behavior is so obvious
that it is a commonplace not discussed in polite company. But to
other scientists, the idea is considered dangerous and ludicrous,
since it is fundamentally at odds with the reductionist beliefs
central to much of physics. But, the authors suggest, the safety
that comes from acknowledging only the facts one likes is
fundamentally incompatible with science, and sooner or later this
attitude "must be swept away by the forces of history".
     6) The authors point out that for the biologist, evolution
and emergence are part of daily life. For many physicists, on the
other hand, the transition from a reductionist approach may not
be easy, but should, in the long run, prove highly satisfying.
Living with emergence means, among other things, focusing on what
experiment tells us about candidate scenarios for the way a given
system might behave before attempting to explore the consequences
of any specific model. This contrasts sharply with the imperative
of reductionism, which requires us never to use experimental
observations in the formulation of theory, as the objective of
reductionism is to construct a deductive path from the ultimate
equations to the experiment without "cheating". But this is
unreasonable when the behavior in question is emergent, for the
higher organizing principles -- the core physical ideas on which
the model is based -- would have to be deduced from the
underlying equations, and in general this is impossible.
Repudiation of this physically unreasonable constraint is the
first step down the road to fundamental discovery.
     7) The authors conclude: "The central task of theoretical
physics in our time is no longer to write down the ultimate
equations but rather to catalogue and understand emergent
behavior in its many guises, including potentially life itself.
We call this physics of the next century the study of complex
adaptive matter. For better or worse we are now witnessing a
transition from the science of the past, so intimately linked to
reductionism, to the study of complex adaptive matter, firmly
based in experiment, with its hope for providing a jumping-off
point for new discoveries, new concepts, and new wisdom."
-----------
Editor's note: Contrast with the above views the reports on
complexity in chemistry and biology appended below.
-----------
R.B. Laughlin and D. Pines: The Theory of Everything.
(Proc. Natl. Acad. Sci. US 4 Jan 00 97:28)
QY: R.B. Laughlin, Dept. of Physics, Stanford Univ. 415-723-3058.
-----------
Text Notes:
... ... *quantum Hall effect: In classical physics, the Hall
effect is the development of a transverse voltage across a
current-carrying conductor in a magnetic field, the voltage being
perpendicular to both the  direction of the current and the
direction of the magnetic field. In quantum physics, there are
two other Hall effects, an integer charge quantum Hall effect,
and a fractional charge quantum Hall effect, these quantum Hall
effects being observed at extremely low temperatures (a few
degrees Kelvin) and extremely intense magnetic fields (at least
several tesla). Both quantum Hall effects were first noted in the
1980s, and the fractional quantum Hall effect, although
experimentally observed, has not been theoretically resolved. In
1982, R.B. Laughlin (one of the authors of the paper reviewed in
the present report) postulated the theoretical existence of
quasi-particle excitations with fractional charge e/3, where e is
the conventional electronic charge, the quasi-particle being the
statistical result of the collective motion of many electrons. R.
de-Picciotto et al (1997) apparently demonstrated unambiguously
the existence of quasi-particles with fractional charge as
predicted by Laughlin's theory. 
... ... *superfluid helium: In general, a "superfluid" is a fluid
that flows without any resistance. "Superconductivity" is
sometimes considered as a special case of superfluidity in which
the "fluid" components (electrons) are charged. But more
conventionally, superfluidity is considered a property of liquid
helium at extremely low temperatures, a property that enables
liquid helium to flow without friction. Both helium isotopes
(sup4)He (the common isotope, often denoted as helium-4) and
(sup3)He (the rare isotope, often denoted as helium-3) possess
superfluidity under special circumstances.
... ... *Josephson effect: In general, any of the phenomena that
occur at sufficiently low temperatures when a current flows
through a thin insulating layer between two superconducting
substances. Such phenomena were predicted theoretically by B.D.
Josephson in 1962. Josephson was 22 years of age when he made his
theoretical discovery; he received the Nobel Prize in Physics in
1973.
... ... *Kondo insulators: An insulator exhibiting the Kondo
effect. The Kondo effect is a large anomalous increase in the
resistance of certain dilute alloys of magnetic materials in
nonmagnetic hosts as the temperature is lowered. In general, the
Kondo effect occurs when an impurity atom with an unpaired
electron is placed in a metal, producing an interaction of
localized electrons with delocalized electrons.
... ... *cuprate superconductivity: In general, high-temperature
superconductivity exhibited by certain copper alloys. The
accepted theory of ordinary low-temperature superconductivity
is the Bardeen-Cooper-Schrieffer theory (1957). At the present
time, a successful theory of high-temperature superconductivity
has not been developed, in spite of a great deal of effort. J.G.
Bednorz and K.A. Mueller shared the Nobel Prize in Physics in
1987 for their discovery of high-temperature superconductivity in
a ceramic oxide (lanthanum-barium-copper) alloy at 30 degrees
kelvin, at that time the highest superconductivity temperature
ever observed.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 25Feb00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON COMPLEXITY IN CHEMISTRY
The term "complexity" is fashionable in science these days, the
interest presumed to indicate a movement away from reductionism,
away from the idea that the behavior of a system is best
understood in terms of how the components of the system behave
and interact. A focus on "complexity", however, is not perforce
anti-reductionist. Indeed, in practice, with real systems, the
behavior of a system is often not predictable from knowledge of
the behavior of its components, but most often this is simply
because that knowledge is incomplete, and not because of any
_principle_ barring prediction of the behavior of the system from
knowledge of its parts. Even systems exhibiting *chaotic
fluctuations are not necessarily non-reductionist, since such
systems are mathematically deterministic. In any case, faced with
an apparent unpredictability of a system given available
information about its parts, one looks for predictive global
methods to understand the system, methods that do not depend upon
a detailed knowledge of the behavior of the components of the
system. Thermodynamics is exactly such a global method of great
utility in chemistry and physics, and since thermodynamics is a
method of analysis that goes back to its originator Carnot in
1824, one can safely say that the idea of special methods to deal
with "complexity" is quite old. In our time, at least for ideal
systems, we can derive the equations of thermodynamics from
statistical mechanics, i.e., derive the global equations from
equations for the behavior of components. But Nicolas Sadi Carnot
(1796-1832) never heard of statistical mechanics, which was
introduced by Boltzmann (1844-1906) in 1871; Carnot founded
thermodynamics as a predictive global method to deal with an
important "complex" system of his time -- the steam engine.
... ... G.M. Whitesides and R.F. Ismagilov (Harvard University,
US) present a review of current ideas in chemistry concerning
"complexity", the authors making the following points:
     1) Chemistry has its own understandings of the term
"complexity". In one characterization, a complex system is one
whose evolution is very sensitive to initial conditions or to
small perturbations, one in which the number of independent
interacting components is large, or one in which there are
multiple pathways by which the system can evolve. Analytical
descriptions of such systems typically require nonlinear
differential equations. A second characterization is more
informal; that is, the system is "complicated" by some subjective
judgment and is not amenable to exact description, analytical or
otherwise.
     2) Faced with the impossibility of handling many real
systems exactly, chemists have evolved a series of approaches to
the treatment of complex systems. These treatments include
reasoning by analogy, averaging, linearization, drastic
approximation, pure empiricism, and detailed analytical solution.
The emphasis in thinking about complicated systems has been to
find methods that are predictive, even if they are non-
analytical. "Complexity" per se, the study of nonlinear processes
with high sensitivity to conditions, has not been the focus of
major effort.
     3) Chemistry has relied heavily on the ability of ensemble
properties that are obtained through thermodynamics and
statistical mechanics to make it unnecessary to consider the
behavior of individual molecules. However, single-molecule
chemistry is now making it possible to inquire about individual
molecular behaviors, and the behavior of macromolecules is a
promising area of research because of the existence of many
possible molecular conformations, each with different properties.
     4) At the core of chemical interest in complexity are the
two fundamental problems concerning life: a) how collections of
molecules give rise to the varieties of behaviors that
characterize cells and organisms; and 2) how individual molecules
might have originally assembled into collections that had the
characteristics of life (energy dissipation, self-replication,
and adaptation). Whether the understanding of complexity at the
molecular level will reveal important elements of the structure
of life is unclear.
     5) One of the opportunities in fundamental chemical research
is to learn from biology and to use what is learned to design
non-biological systems that dissipate energy, replicate, and
adapt. Whether such systems would model life is not critical;
they would unquestionably be interesting and probably important.
-----------
G.M. Whitesides and R.F. Ismagilov: Complexity in chemistry.
(Science 2 Apr 99 284:89)
QY: George M. Whitesides [gwhitesides@gmwgroup.harvard.edu]
-----------
Text Notes:
... ... *chaotic fluctuations: The term "chaotic", in this
context, is specific. In the study of physical systems, the
term "chaotic behavior" has a specific meaning: the behavior of a
system is said to be "chaotic" if its final state is so sensitive
to the system's precise initial conditions that the behavior of
the system is in effect unpredictable and cannot be distinguished
from a random process, even though the behavior of the system is
strictly determinate in a mathematical sense. In other words, a
deterministic system characterized by extremely sensitive
instabilities, despite the system being determinate, can exhibit
behavior that is unpredictable, and the system is then called
"chaotic". During the past several decades, the analysis of such
chaotic systems has intrigued both physicists and mathematicians.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 2Jul99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
CELL BIOLOGY: FUNCTIONAL MODULES IN BIOLOGICAL ORGANIZATION
     The term "phenomenology" has a variety of meanings, but in
this report we are concerned with only one meaning of the term:
we take the term "phenomenology" to refer to a scientific
approach that focuses on explanations based on formal
relationships among observed entities or processes, as opposed to
an approach ("reductionist") that focuses on explanations based
on analysis of the fundamental constituents of such entities or
processes. Using the terms in this way, we have the following
examples: a) Thermodynamics is a phenomenological approach to the
behavior of a gas; statistical mechanics is a reductionist
approach to the behavior of a gas. b) Mendelian genetics is a
phenomenological approach to the inheritance of traits; molecular
genetics is a reductionist approach to the inheritance of traits.
One can think of similar dichotomies in almost every field in
science.
     The term "reductionist" has had an unfortunate history in
biology, where it has been used to characterize the idea that any
biological entity or process can be "explained" in terms of the
laws of physics and chemistry. Certainly, the behavior of every
entity or process in the natural world is ultimately totally
dependent on the laws of physics and chemistry (which leads to
the idea that the behavior can "in principle" be derived
["explained"] from such laws), but the actual practical
possibility of any explanations of the behavior of observable
entities or processes in terms of the laws of physics and
chemistry depends on the current state of our knowledge
concerning both the observables and the fundamental laws. In the
practice of science, it can be argued that it does not matter
much which approach is used, phenomenological or reductionist,
provided the approach produces results that are useful, or which
help in understanding the behavior of the entity or process, or
which suggest new and intriguing questions. Beyond this, the
discussion properly belongs in the domain of philosophy and not
science.
     The above preamble is necessary in the context of the
present report, since the report concerns a recent article in
which a group of authors (2 molecular biologists, a biophysicist,
and a physiologist) call for a more "phenomenological" approach
to cell biology, an interesting idea, since cell biology is not
one of those areas of biology where such appeals are common.
During the last 50 years, in fact, cell biology has experienced a
remarkable flowering based on the application of fundamental
biochemistry, biophysics, and molecular biology to entities and
processes recognizable at the cellular level (i.e., micron-scale
objects).
... ... L.H. Hartwell et al (4 authors at 3 installations, US)
present an essay calling for a transition from molecular to
"modular" cell biology, the authors making the following points:
     1) The authors begin their essay with the following
statement: "Although living systems obey the laws of physics and
chemistry, the notion of function or purpose differentiates
biology from other natural sciences. Organisms exist to
reproduce, whereas, outside religious belief, rocks and stars
have no purpose. Selection for function has produced the living
cell, with a unique set of properties that distinguish it from
inanimate systems of interacting molecules." [Editor's note:
Contrast with this the remarks in the relevant background
material below.]
     2) The authors propose that a major challenge for science in
the 21st century is to develop an integrated understanding of how
biological cells and organisms survive and reproduce. The authors
suggest that cell biology is in transition from a science that
was preoccupied with assigning functions to individual proteins
or genes, to a science that is now attempting to cope with the
complex sets of molecules that interact to form "functional
modules".
     3) The authors define a "functional module" as a discrete
entity whose function is separable from those of other modules.
This separation depends on chemical isolation, which can
originate from spatial localization or from chemical specificity.
For example, a ribosome, the module that synthesizes proteins,
concentrates the reactions involved in making a polypeptide into
a single particle, thus spatially isolating its function. Modules
can be insulated from or connected to each other. The authors
suggest that in the future, the higher-level properties of cells,
such as their ability to integrate information from multiple
sources, will be described by the pattern of connections among
their functional modules.
     4) The authors point out that the number of cellular
functional modules that have been analyzed in detail is very
small, and each of these efforts has required intensive study.
The authors suggest that biologists need to study more functions
at the modular level and develop methods that make it easier to
determine the relationship of inputs to outputs of modules, their
biochemical connectivity, and the states of key intermediates
within them.
     5) The authors suggest that the best test of our
understanding of cells will be to make quantitative predictions
about their behavior and test them. This will require detailed
simulations of the biochemical processes occurring within the
modules. "But making predictions is not synonymous with
understanding. We need to develop simplifying, higher-level
models and find general principles that will allow us to grasp
and manipulate the functions of biological modules."
     6) The authors summarize their essay: "Cellular functions,
such as signal transmission, are carried out by 'modules' made up
of many species of interacting molecules. Understanding how
modules work has depended on combining phenomenological analysis
with molecular studies. General principles that govern the
structure and behavior of modules may be discovered with help
from synthetic sciences such as engineering and computer science,
from stronger interactions between experiment and theory in cell
biology, and from an appreciation of evolutionary constraints."
-----------
Editor's note: The essential idea here can be presented as
follows: Consider a computer, a machine with a "purpose" -- to
compute. A computer operates on its inputs in specific ways to
produce specific outputs. A "flow diagram" of computer dynamics
is a phenomenological description of the behavior of the machine.
A complete "wiring diagram" of electrical entities and events in
the machine is a reductionist description of the behavior of the
machine. (Of course, from the perspective of quantum mechanics,
the wiring diagram is itself phenomenological.) Suppose we are
given a machine and know nothing about it except that it operates
on inputs to produce outputs. If our problem is to predict the
behavior of the machine in response to particular inputs, there
will come a time when a flow diagram, albeit "phenomenological",
will be of immense value in understanding how the machine works.
What the authors propose is that much of the future of cell
biology will lie in the construction of the equivalent of
detailed and predictive flow diagrams for the internal operations
of biological cells.
-----------
L.H. Hartwell: From molecular to modular cell biology.
(Nature 2 Dec 99 402supp:C47)
QY: Leland H. Hartwell, Fred Hutchinson Cancer Center, Seattle,
WA 98109 US.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 11Feb00
-------------------
Related Background:
IN FOCUS: ON FUNCTION AND TELEOLOGY IN BIOLOGY
"Biology, and especially evolutionary biology, is rife with
claims concerning what various characteristics are "for". The
heart exists for the purpose of pumping blood. Bears have fur in
order to ward off the cold. Functional claims of this sort have
quite disappeared from physics. Whereas Aristotle thought that
planets, no less than living things, have goals, this
teleological conception of the physical world is now a relic of a
bygone age. Planets move as they do because of the laws of
motion; they do not act as they do for the good of anything.
Darwin is rightly famous for having introduced an important
materialist element into the science of life. But rather than
banishing functional notions from biology, he showed how they can
be domesticated within a materialist framework. Organisms are
goal-directed systems because they have evolved. Their behaviors
are suited to the tasks of survival and reproduction because
natural selection has allowed some traits, but not others, to be
passed from ancestors to descendants. Even if Darwinism
legitimates talk of goal and purpose within biology, the question
of what such talk means remains to be addressed. The heart does
many things. It pumps blood, but it also makes noise and takes up
space in our chests. Why are we inclined to say that pumping
blood is part of the heart's function, but making noise and
taking up space are not?"
-----------
Elliott Sober: _Conceptual Issues in Evolutionary Biology_
(MIT Press, Cambridge 1995, p.x)
(Science-Week 9 Jul 99)


2. EVOLUTIONARY BIOLOGY: THE QUALITY OF THE FOSSIL RECORD
One of the important questions debated by evolutionary biologists
during the past few decades is whether the fossil record presents
a true picture of the diversification of living systems, since it
is evident that the quality of the fossil record becomes more and
more reduced as we go backwards in time: fossils in ancient rocks
are more likely to have been eroded, crushed, melted, *subducted,
not collected, or misunderstood than younger fossils. For
example, molecular studies suggest that multicellular animals
(metazoans) and modern bird and mammal orders apparently
originated much earlier than expected from the fossil evidence.
Thus, the question is whether the older fossil records are
adequate to recount important events in the history of life.
... ... M.J. Benton et al (3 authors at 2 installations, UK)
present a study of the question, the authors reporting new
assessment methods in which the order of fossils in the rocks
(stratigraphy) is compared with the order inherent in
evolutionary trees (phylogeny). The authors report that such
assessments of congruence between stratigraphy and phylogeny for
a sample of 1000 published phylogenies show no evidence of
diminution of quality backwards in time. Ancient rocks clearly
preserve less information, on average, than more recent rocks.
However, if scaled to the stratigraphic level of the stage and
the taxonomic level of the family, the past 540 million years of
the fossil record provide uniformly good documentation of the
life of the past. [Editor's note: The essential point of the
authors is that although the ancient parts of the fossil record
are indeed incomplete, the record is adequate to illustrate broad
patterns.]
-----------
M.J. Benton et al: Quality of the fossil record through time.
(Nature 3 Feb 00 403:534)
QY: M.J. Benton [mike.benton@bris.ac.uk]
-----------
Text Notes:
... ... *subducted: The term "subduction" refers to the process
of underthrusting of the edge of an oceanic plate into the mantle
underlying an adjacent plate. In this context, the term "plate"
derives from "plate tectonics", the current consensus theory that
the Earth's lithosphere is broken into fairly rigid plates, seven
major plates and many smaller plates, and that convection within
the underlying less rigid "asthenosphere" causes the plates (and
the associated continents and crust) to move relative to each
other.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 25Feb00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
EARLY ANIMAL EVOLUTION
The geological period known as the Cambrian is the time frame
from about 505 million years ago to 545 million years ago. Its
most outstanding aspect is the rather sudden appearance of
numerous invertebrate fossils, so numerous that some have termed
it an explosion of evolutionary processes. Many of the life forms
that existed during the Cambrian are long extinct, but their
fossils are numerous, and through their fossils the various
Cambrian species have been the subject of much study by
paleobiologists. The Cambrian explosion of life forms has been a
long-standing puzzle for paleobiologists, and at present there is
apparently no single generally accepted explanation. Among the
ideas proposed have been, 1) that the explosion of new forms
resulted from a sudden increase in atmospheric oxygen; 2) that
the explosion is only apparent, and the Precambrian, the period
previous to the Cambrian, lacks fossils because of heat and
pressure associated with important geological changes; 3) that
living forms evolved mostly in freshwater areas, and are
therefore absent in Precambrian sediments, which are primarily
marine; 4) that changes in the shape and extent of shorelines
produced by continental drift dramatically transformed climate
and environment; 5) that the previous evolution of DNA
recombination and regulatory genes culminated in and sparked the
diversity and anatomical complexity manifested in the explosion;
6) that an exponential increase of species could become
significant only after attaining a threshold value at the start
of the Cambrian; and 7) that once multicellular organisms
appeared, the intrinsic possibilities for variation increased
enormously with a resultant explosion of evolved forms.
Unfortunately, there is no evidence to suggest a selection of one
of these proposals, although some of them are less convincing
than others. And of course the truth may be that more than one
factor was involved. No matter the origin, the Cambrian explosion
is apparently accepted by most paleobiologists as a real
discontinuity, a period that saw the sudden emergence of dozens
of new orders and phyla, including sponges, *annelids,
*crustaceans, *hemichordates, *brachiopods, and *mollusks.
... ... A.H. Knoll and S.B. Carroll (2 installations, US) present
a review of recent fossil, phylogenetic, embryological, and
paleo-environmental discoveries that are provoking new ideas
about early animal evolution. The authors make the following
points:
     1) The debate about Cambrian evolution may be old, but only
in the past decade have the data necessary to weigh conflicting
hypotheses begun to emerge. The new information has come from a
broad range of disciplines that includes not only paleontology
and stratigraphy, but also geochemistry, molecular systematics,
and developmental genetics.
     2) It is becoming increasingly clear that understanding the
Cambrian explosion requires that considerations of the Cambrian
fauna and the environments that shaped it be complemented by new
perspectives on the late *Proterozoic world. To understand what
actually transpired during the Cambrian explosion, or what may
have enabled the Cambrian explosion, we must consider what
animals, what developmental and genetic mechanisms, and what
ecosystems were in place before it.
     3) We cannot yet claim to have solved the major questions of
early animal evolution. But we have reached a point where
pathways to understanding are becoming clearer. Testing
hypotheses concerning the identity, age, complexity, and
diversity of early animals and the environments in which they
lived has become an interdisciplinary exercise.
     4) We can see clearly now that intrinsic and extrinsic
hypotheses are not really alternative ways of explaining animal
diversification. There were certainly intrinsic catalysts of
early animal evolution. The assembly and regulatory
diversification of the genetic "toolkit" for animal development
undoubtedly underpin Proterozoic and Cambrian evolution. And the
evolution of complex appendages, organs, and sophisticated
nervous and musculo-skeletal structures must have facilitated
diversification. But extrinsic events also helped to shape early
animal evolution by altering environments in ways that doomed
some *clades and created opportunity for others.
     5) The authors conclude: "Discipline-bound intrinsic or
extrinsic explanations of early animal history fail not so much
because they are wrong as because they are incomplete. The
Cambrian explosion... is the historical product of the interplay
between genetic possibility and environmental opportunity,
amplified by ecological interactions to extend across all of
biology."
-----------
A.H. Knoll and S.B. Carroll: Early animal evolution: Emerging
views from comparative biology and geology.
(Science 25 Jun 99 284:2129)
QY: Andrew H. Knoll, Harvard University 617-495-1000.
-----------
Text Notes:
... ... *annelids: Soft-bodied, metamerically segmented coelomate
worms, e.g., earthworms. The term "coelomate" refers to the
possession of a body cavity.
... ... *crustaceans: A class of Arthropods, including shrimps,
crabs, water fleas, etc.
... ... *hemichordates: A group of marine invertebrates,
including the acorn worms.
... ... *brachiopods: Bivalve coelomate invertebrates that live
attached to the sea-bed (e.g., lamp shells).
... ... *mollusks: (Mollusca) A phylum of bilaterally symmetrical
unsegmented invertebrates. Includes aquatic bivalves such as
mussels and clams, terrestrial slugs and snails, octupi and
squids.
... ... *Proterozoic: The Proterozoic eon is the time-frame 2600
million years ago to 600 million years ago.
... ... *clades:  A "clade" is a cluster of taxa derived from a
single common ancestor.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 24Sep99
-------------------
Related Background:
A MOLECULAR DATING TEST OF THE CAMBRIAN EXPLOSION HYPOTHESIS
The early history of the *Metazoa, whether the Metazoa originated
as part of a *Cambrian "explosion" or with an extended
*Precambrian "phylogenetic fuse", remains controversial in
evolutionary biology. The Cambrian explosion hypothesis -- that
the phyla and even classes of the animal kingdom originated in a
rapid evolutionary radiation at the base of the Cambrian at 545
to 560 million years ago -- rests on the sudden appearance of a
diverse range of animals in the fossil record. Although recent
discoveries of *Ediacaran metazoans have extended the record of
sponges and bilateral animals to 570 million years ago, the
biological affinities of many Ediacaran organisms remains
controversial, and the earliest paleontological evidence of
metazoan life is no more than 600 million years ago. However, the
absence of earlier metazoan fossils could have been caused by
systematic biases in preservation that left the Precambrian
history of recognized phyla unrecorded in fossils. Molecular
studies have the potential to shed light on the origin of the
animal phyla by providing independent estimates of the divergence
times, but molecular studies have been criticized for failing to
account adequately for variations in rate of evolution.
... ... L. Bromham et al now present a study involving a method
of dating divergence times from molecular data (both
*mitochondrial DNA and nuclear DNA) which addresses the
criticisms of earlier studies, and which the authors state
provides more realistic but wider confidence intervals. The
authors report their data are not compatible with the Cambrian
explosion hypothesis as an explanation for the origin of metazoan
phyla, and they suggest their data provide additional support for
an extended period of Precambrian metazoan diversification. The
authors conclude: "Although we cannot provide precise estimates
of the origin of metazoan phyla, we can use our results to
confidently reject the Cambrian explosion hypothesis, which rests
on a literal interpretation of the fossil record and assumes that
special evolutionary phenomena, capable of producing profound
differentiation in a short period, operated in the Cambrian but
not before or since. By contrast, the Precambrian phylogenetic
fuse hypothesis assumes no more than we already know to be
reasonable: that lineages can diverge gradually over time and
that the fossil record contains gaps that can greatly reduce the
chances of finding fossils for certain periods or particular
types of organisms.
-----------
L. Bromham et al (3 installations, UK NZ)
Testing the Cambrian explosion hypothesis by using a molecular
dating technique.
(Proc. Natl. Acad. Sci. US 13 Oct 98 95:12386)
QY: Lindell Bromham [LBromham@zoology.uq.edu.au]
-----------
Text Notes:
... ... *Metazoa: In general, the term "metazoa" refers to all
multicellular animals. Among important distinguishing
characteristics of metazoa are cell differentiation and
intercellular communication. For certain multicellular colonial
entities such as sponges, some biologists prefer the term
"parazoa".
... ... *Cambrian "explosion": See notes in main report.
... ... *Precambrian "phylogenetic fuse": The term "fuse" here is
a metaphor for a proposed long series of precursor events leading
to the apparent "explosion" in the fossil record. The essential
question is whether the apparent explosion in the fossil record
was the result of relatively sudden changes in preservation
constraints (e.g., hard-body vs. soft-body forms), or whether a
set of special conditions (e.g., climate change or atmospheric
oxygen availability) provoked an actual rapid diversification of
forms.
... ... *Ediacaran metazoans: The term "Ediacaran" refers to an
assemblage (until recently the oldest) of soft-bodied marine
animals, the assemblage first discovered in the Ediacara Hills in
Australia.
... ... *mitochondrial DNA: Mitochondrial DNA (sometimes denoted
as mtDNA), found in the mitochondria of all eukaryotes, is
believed to evolve in parallel with nuclear DNA, but since sperm
lose their mitochondria, it is inherited only in the maternal
lineage in animals.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 24Sep98
[For more information: http://scienceweek.com/search/search.htm]


3. ANIMAL BEHAVIOR: NONGENOMIC TRANSMISSION OF MATERNAL BEHAVIOR
The question of genetic vs. non-genetic determinants of behavior
is an area of controversy in several branches of science, and as
can be seen from the background material attached to this report,
discussion of the question is on occasion contentious. In humans,
individual differences in personality traits often appear to be
transmitted from parents to offspring, and a critical question
concerns the mode of transmission of such traits. Studies of
identical (monozygotic) and non-identical (dizygotic) twins have
provided some evidence for a genetic mechanism of transmission of
even complex personality traits. In contrast to genomic
transmission, parental behavior influences the development of
offspring and could therefore serve as a mechanism for a non-
genomic behavioral mode of transmission of traits. In rats, for
example, it has been known for 50 years that variations in
maternal care are associated with the development of individual
differences in behavioral and endocrine responses to stress in
the offspring, and this species has served as an animal model in
many studies of the effects of variations in maternal care on the
behavior of offspring.
... ... D. Francis et al (4 authors at McGill University, CA) 
now present cross-fostering studies examining the possibility
that variations in rat maternal care might be the mechanism for a
behavioral transmission of individual differences across multiple
generations. In the experimental and control protocols, no more
than 2 of 12 rat pups were fostered into or from any one litter.
The authors report their results provide evidence for 1) a causal
relationship between maternal behavior and stress reactivity in
the offspring; and 2) the transmission of such individual
differences in maternal behavior from one generation of females
to the next. In addition, the authors report that an
environmental manipulation imposed during early development that
alters maternal behavior can affect the pattern of transmission
in subsequent generations. The authors suggest that taken
together, these results indicate that variations in maternal care
can serve as the basis for a non-genomic behavioral transmission
of individual differences in stress reactivity across
generations. The authors conclude: "In humans, social, emotional,
and economic contexts influence the quality of the relationship
between parent and child and can show continuity across
generations. Our findings in rats may thus be relevant in
understanding the importance of early intervention programs in
humans."
-----------
D. Francis et al: Nongenomic transmission across generations of
maternal behavior and stress responses in the rat.
(Science 5 Nov 99 286:1155)
QY: Michael J. Meaney [mdmm@musica.mcgill.ca]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 25Feb00
-------------------
Related Background:
GENETIC CONTROL OF SOCIAL ORGANIZATION IN ANTS
Biological evolution is marked by a number of major transitions,
one of which is the evolution of complex social behavior. Animal
social life can take a variety of forms, each distinguished by
features such as group size and the reproductive roles of group
members. One focus in evolutionary biology is to identify the
causes of social behavior and its conspicuous variation, and to
determine the extent to which social organization is under
genetic control. Such information is useful for reconstructing
pathways of animal social evolution. Current views on insect
social evolution stress the importance of ecological and
behavioral environments in molding what are largely plastic
social behaviors.
... ... K.G. Ross and L. Keller (2 installations, US CH) report
evidence that major variation in the social organization of fire
ant colonies is under simple genetic control, providing a
demonstration of an apparent strong genetic component to complex
social behavior. The authors report that a single genomic element
(the gene [Gp-9]) is responsible for the existence of two
distinct forms of social organization in the fire ant *Solenopsis
invicta. This genetic factor apparently influences the
reproductive *phenotypes and behavioral strategies of ant queens
and determines whether workers tolerate a single fertile queen or
multiple queens per colony. The authors suggest "these findings
reveal how a single genetic factor can have major effects on
complex social behavior and influence the nature of social
organization."
-----------
K.G. Ross and L. Keller: Genetic control of social organization
in an ant.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14232)
QY: Kenneth G. Ross [kenross@arches.uga.edu]
-----------
Text Notes:
... ... *Solenopsis invicta: The fire ant S. invicta is an
introduced pest species in the southern US, the species existing
in two distinct social forms. The "monogyne" form features
colonies with a single fertile (egg-laying) queen, whereas the
"polygyne" form features colonies with multiple fertile queens.
The two social forms differ in other major aspects of their
reproductive biology.
... ... *phenotypes: The term "phenotype" refers to the total
appearance of an organism as determined by the interaction during
development between its genetic constitution (genotype) and the
environment.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 15Jan99
-------------------
Related Background:
ON HONEYBEE SOCIAL BEHAVIOR, GENES, AND THE ENVIRONMENT
The so-called social insects live in societies that rival human
societies in complexity and internal cohesion. Honey bees, for
example, apparently always follow 3 rules: a) they live in
colonies with overlapping generations; b) they care cooperatively
for offspring other than their own; and, c) they maintain a
reproductive division of labor. ... ... In a review of research
(much of it from the author's own laboratory) concerning the
genetic and environmental factors responsible for honey bee
behavior, Gene E. Robinson (University of Illinois Urbana-
Champaign, US) makes the following points: 1) Genes do not play
an exclusive role in regulating behavior: biologists have long
realized that behavior is influenced by genes, the environment,
and interactions between the two. 2) Genes never act alone. They
must operate in an environment where they code for proteins that
participate in many systems in an organism, with these systems in
turn influencing the expression of genes. Consequently,
biologists must take a broad approach in assessing the impact of
any gene. 3) The research group of the author uses the Western
honey bee, Apis mellifera. Honey bees pass through different life
stages as they age, and their behavioral responses to
environmental and social stimuli change in predictable ways.
Although worker bees go through a consistent path of behavioral
development, this path is not rigidly determined. Bees can
accelerate, retard, or even reverse their behavioral development
in response to changing environmental and colony conditions. 4)
Experimental evidence indicates that juvenile hormone, one of
the most important hormones influencing insect development, helps
time the pace of behavioral maturation in honey bees. The rate of
endocrine-mediated behavioral development is influenced by
inhibitory social interactions. Older bees inhibit the behavioral
development of younger bees: the rate of behavioral development
is negatively correlated with the proportion of older bees in a
colony. Inhibitory social interactions that influence the rate of
behavioral development involve chemical communication between
colony members. 5) Evidence from the laboratory of the author in
1993 indicated the so-called mushroom bodies in the bee brain are
involved in the behavioral changes occurring during maturation,
the volume of the bodies increasing, and the volume increase
associated with an increase in synapses with neurons from brain
regions devoted to sensory input. The author suggests this was
the first report of brain plasticity in an invertebrate. 6) The
author suggests that, in general, two-way interactions between
the nervous system and the genome contribute fundamentally to the
control of social behavior. Information about social conditions
that is acquired by the nervous system is likely to induce
changes in genomic function that in turn produce adaptive
modifications of the structure and function of the nervous
system. 7) The author proposes a new research initiative called
"sociogenomics", defined as a "wide-ranging approach to identify
genes that influence social behavior, determining the influence
of these genes on underlying neural and endocrine mechanisms, and
exploring the effects of the environment -- particularly the
social environment --  on gene action."
QY: Gene E. Robinson, Dept. of Entomology, Univ. of Illinois
Urbana-Champaign 217-333-3090.
(American Scientist Sep/Oct 1998 86:456)
(Science-Week 11 Sep 98)
-------------------
Related Background:
IN FOCUS: ON SOCIOBIOLOGY
"Evolutionary theory itself has an appropriately zoocentric
core... But the zoocentric view can be extended too far into a
caricature often called the "nothing but" fallacy (humans are
"nothing but" animals). The simplistic accounts of human
sociobiology now flooding popular literature embody this
overextended version of zoocentrism. Sociobiology is not just any
statement that biology, genetics, and evolutionary theory have
something to do with human behavior. Sociobiology is a specific
theory about the nature of genetic and evolutionary input into
human behavior. It rests upon the view that natural selection is
a virtually omnipotent architect, constructing organisms part by
part as best solutions to problems of life in local environments.
It fragments organisms into "traits", explains their existence as
a set of best solutions, and argues that each trait is a product
of natural selection operating "for" the form or behavior in
question. Applied to humans, it must view _specific_ behaviors
(not just general potentials) as adaptations built by natural
selection and rooted in genetic determinants, for natural
selection is a theory of genetic change. Thus, we are presented
with unproved and unprovable speculations about the adaptive and
genetic basis of specific human behaviors: why some (or all)
people are aggressive, xenophobic, religious, acquisitive, or
homosexual. Zoocentrism is the primary fallacy of human
sociobiology, for this view of human behavior rests on the
argument that if the actions of "lower" animals with simple
nervous systems arise as genetic products of natural selection,
then human behavior should have a similar basis."
-----------
Stephen Jay Gould: _Hen's Teeth and Horse's Toes_
(W.W. Norton, New York 1983, p.243)
[Editor's note: Stephen Jay Gould (Harvard University, US) is the
current president of the American Association for the Advancement
of Science.]


4. MEDICAL BIOLOGY: ETHANOL-INDUCED NEURODEGENERATION AND FETAL
ALCOHOL SYNDROME
The term "fetal alcohol syndrome" refers to fetal dysfunction due
to maternal alcohol abuse during pregnancy, and it is the most
common cause of drug-induced fetal dysfunction and fetal
malformations (teratogenesis). The most severe dysfunction
consequence is severe mental retardation due to impaired brain
development. In general, alcohol ingested during pregnancy can
produce a wide spectrum of defects, ranging from spontaneous
abortion to severe behavioral defects without apparent physical
anomalies. The US incidence of fetal alcohol syndrome is
approximately 2.2 per 1000 live births, which exceeds that of
Down syndrome and cerebral palsy. The critical volume of ingested
alcohol that results in fetal alcohol syndrome is unknown.
... ... C. Ikonomidou et al (12 authors at 3 installations, DE JP
US) now report that ethanol, acting by a dual mechanism involving
both blockade of *NMDA receptors and excessive activation of
*GABA(subA) receptors, triggers widespread neurodegenerative
programmed cell death (apoptosis) in the developing rat
forebrain. Vulnerability coincides with the period of active
developmental synapse formation (synaptogenesis), which in humans
extends from the sixth month of gestation to several years after
birth. The authors suggest that during this period transient
ethanol exposure can delete millions of neurons from the
developing brain, and that this can explain the reduced brain
mass and neurobehavioral disturbances associated with human fetal
alcohol syndrome. In addition, the authors point out the
following:
     1) If a pregnant mother imbibes ethanolic beverages for
several hours in a single drinking episode, she could expose her
3rd-trimester fetus to blood ethanol levels equivalent to those
required to trigger apoptotic neurodegeneration in the immature
rat brain (200 milligrams per deciliter lasting 4 hours or more.)
     2) The authors point out that from a clinical perspective it
is important to recognize that both NMDA antagonists and
GABA(subA) agonists are frequently used as sedatives,
tranquilizers, anticonvulsants, or anesthetics in pediatric
and/or obstetric medicine. These agents are also drugs of abuse.
Because the human brain growth spurt spans not only the last
trimester of pregnancy but also several years after birth, the
developing human brain may be exposed to these agents by medical
professionals or by drug-abusing pregnant mothers.
     3) The authors also report that within the synaptogenesis
period, different neuronal populations have different temporal
patterns of response to the apoptosis-inducing effects of these
drugs. The authors conclude: "Thus, depending on the timing of
exposure, different combinations of neuronal groups will be
deleted, which signifies that this is a neurodevelopmental
mechanism that can contribute to a wide spectrum of
neuropsychiatric disturbances."
-----------
C. Ikonomidou et al: Ethanol-induced apoptotic neurodegeneration
and fetal alcohol syndrome.
(Science 11 Feb 00 287:)
QY: John W. Olney, Dept. of Psychiatry, Washington University St.
Louis, 4940 Children's Place, St. Louis, MO 63110 US.
-----------
Text Notes:
... ... *NMDA receptors: (N-methyl-D-aspartate receptor) This is
a type of "glutamate receptor", a receptor protein present in
nerve cell membranes. Glutamate is a major excitatory amino acid
neurotransmitter, accounting for an estimated 40 percent of all
nerve signals in the mammalian brain, and involved in phenomena
such as neural development, learning, and memory
formation. In general, a "glutamate receptor" is a molecular site
that mediates the actions of glutamate *neurotransmitters.
... ... *neurotransmitters: Neurotransmitters are chemical
substances released at the terminals of nerve axons in response
to the propagation of an impulse to the end of that axon. The
released neurotransmitter diffuses into the junction between the
source neuron and the target neuron, and in general the
neurotransmitter exerts either an excitatory or inhibitory effect
on the target neuron, depending on the chemical identity of the
neurotransmitter.
... ... *GABA(subA) receptors: GABA is gamma-amino butyric acid.
The term "GABA receptor" refers to any of several membrane
proteins that bind GABA and mediate its effects as an inhibitory
neurotransmitter. GABA(subA) receptors (GABA-gated channels) are
a type of GABA receptor that function as chloride *ion channels.
... ... *ion channels: Ion channels are protein channels
in cell membranes that allow ions to pass from extracellular
solution to intracellular solution and vice versa. Most ion
channels are selective, allowing only certain ions to pass, and
an individual cell has ion channels with various ion
selectivities. From an electrical standpoint, each ion channel is
effectively a specific parallel conductance pathway through the
cell membrane, and the dynamic electrical behavior of nerve cells
is essentially directly determined by the opening and closing of
its ion channels.
-------------------
Related Background:
FETAL EFFECTS OF EXPOSURE TO ORGANIC SOLVENTS DURING PREGNANCY
Biological membranes are essentially lipid barriers with a
secondary population of attached or embedded proteins. Organic
solvents are particularly potent in their chemical action on
biological systems because they readily and quickly pass through
lipid domains such as biological membranes, including membranes
of the skin, the digestive tract, and the respiratory system.
Many women of child-bearing age are occupationally exposed to
organic solvents, and since fetal tissue is even more vulnerable
to such solvents than adult tissue, the question of the effects
on the fetus of occupational exposure of the mother to organic
solvents is of some significance. The most important women-
dominated occupations with potential chemical exposures are
health care professions and work tasks in the clothing and
textile industries, all of which involve exposures to organic
solvents. Many industrial solvents are teratogenic (i.e., capable
of producing a malformed fetus) in laboratory animals, and there
are reports of limb and central nervous system defects in mice,
marked developmental toxic effects and retardation of skeletal
growth in rats, and congenital malformations in rabbits. However,
the animal studies typically use high doses of single solvents
and a variety of routes of administration. In the human
occupational setting, exposure usually occurs to a multitude of
solvents at much lower doses by inhalation, making extrapolations
from animals to humans problematic.
... ... S. Khattak et al (6 authors at University of Toronto, CA)
now report a study to evaluate pregnancy and fetal outcome
following maternal occupational exposure to organic solvents. The
study involved 125 pregnant women who were exposed occupationally
to organic solvents and seen during the first trimester between
1987 and 1996, and 125 matched controls. The organic solvents to
which the women were occupationally exposed included aliphatic
and aromatic hydrocarbons, phenols, trichloroethylene, xylene,
vinyl chloride, acetone, and related compounds. These women
worked in the following occupations (number of women): factory
worker (37), laboratory technician (21), artist (16), printing
industry (14), chemist (13), painter (8), office worker (4), car
cleaning service (3), veterinary technician (3), orthotist (2),
funeral home service (2), carpenter (1), social worker (1). Only
women known individually to be exposed to organic solvents were
in the above groupings. The authors tabulated the occurrence of
major congenital malformations in the infants delivered by these
women. The authors report that significantly more major
malformations occurred among fetuses of women exposed to organic
solvents than matched controls (13 vs. 1). In other words, 10.4
percent of the women in the organic-solvent-exposed group
produced a malformed fetus, as opposed to 0.8 percent of the
women in the control group. 12 of the 13 malformations occurred
among the 75 women who had symptoms of exposure during their
exposure, while no malformations occurred among the exposed women
who did not exhibit symptoms during their exposure. The authors
conclude that occupational exposure to organic solvents during
pregnancy is associated with an increased risk of major fetal
malformations, and that this risk appears to be increased among
women who report symptoms associated with organic solvent
exposure. The authors suggest that exposure of women to organic
solvents should be minimized during pregnancy, and that "health
care professionals who counsel families of reproductive age
should inform their patients that some types of employment may
influence reproductive outcomes."
-----------
S. Khattak et al: Pregnancy outcome following gestational
exposure to organic solvents.
(J. Amer. Med. Assoc. 24/31 Mar 99 281:1106)
QY: Gideon Koren, The Hospital for Sick Children, 555 University
Avenue, Toronto, Ontario CA M5G 1X8.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 30Jul99


5. MEDICAL BIOLOGY: ON THE PRESENT WORLD EPIDEMIC OF ALLERGIC
DISEASES
     The term "antigen" refers to any substance that elicits an
immune response, and an individual who is overreactive to an
antigen that is tolerated by most others is said to be "allergic"
(hypersensitive). When an allergic reaction occurs, there is
usually some tissue injury, and the antigens that induce an
allergic reaction are called "allergens". Common allergens
include certain foods, antibiotics, vitamins, drugs, vaccines,
insect and snake venoms, cosmetics, plant chemicals, pollens,
dust, molds, iodine-containing dyes, etc. 
     Asthma is a chronic *inflammatory disorder that produces
*sporadic narrowing of the airways. Attacks are brought on by
spasms of *smooth muscle in the walls of the smaller *bronchi and
bronchioles, causing the passageways to close partially or
completely (bronchoconstriction). Symptoms include periods of
coughing, difficult breathing, and wheezing that may abate
spontaneously or with treatment. The patient has trouble
inhaling, and air may be trapped in the *alveoli during
expiration. The airways of people with asthma are hypersensitive
to a variety of stimuli that normally do not trigger
bronchoconstriction in people without asthma. Sometimes the
trigger is an allergen, such as pollen, house dust mites,, molds,
or a particular food.
     In the US, approximately 12 million people have asthma. From
1982 to 1992, the US prevalence of asthma increased from 34.7 to
49.4 per 1000. The death rate due to asthma increased by 40
percent, from 13.4 to 18.8 per million, with the death rate 5
times higher for blacks than for whites. Asthma is currently the
leading cause of hospitalization for children, and the primary
chronic condition causing school absenteeism.
... ... A recent journal supplement presents 6 papers reviewing
current research concerning allergy and asthma. Stephen T.
Holgate (University of Southampton, UK) reviews the current
epidemic of allergy and asthma, the author making the following
points:
     1) Our knowledge of allergy has evolved slowly, beginning
with the description by John Bostock of catarrus aestivus (hay
fever) (1819), the recognition by Charles Blackley of pollen
grains as causative agents (1873), the discovery of a
transferable tissue-sensitizing factor in the serum by Frausnitz
and Kuestner (1921), and the identification of this factor as an
*immunoglobulin subclass (immunoglobulin E; IgE) by two separate
laboratories (Johanssen and Ishizaka) in 1967.
     2) The past 30 years have witnessed a spectacular increase
in our knowledge of the cellular and molecular mechanisms of
allergic disease, and this has been paralleled by the rising
trends in the incidence and health impacts of these diseases
worldwide. Whereas in Bostock's and Blakeley's time hay fever was
a rare disorder restricted to the privileged class, at present
almost half the population of the West exhibits sensitization to
one or more environmental allergens. In countries such as the UK
and Australia, this translates to 1 in 4 children under the age
of 14 years having asthma, and 1 in 5 children under the age of
14 years having *eczema. Added to this is the occurrence of
serious allergic disorders caused by new allergens such as nuts,
soya, and latex.
     3) The author suggests that allergic diseases, such as
asthma, *rhinitis, eczema, and food allergies, are reaching
epidemic proportions in both the developed and developing world,
and that key factors driving these rising trends are apparently
increased exposure to sensitizing allergens and reduced
stimulation of the immune system during the critical periods of
development. In allergic disease, there is a polarization of *T-
lymphocyte responses, and enhanced secretion of *cytokines
involved in regulation of various immune system cells, and this
ultimately leads to inflammation and disease.
     4) The author suggests that although genetic factors may
explain at least part of the wide intercountry differences in
allergic disease incidence, they do not explain the rising
disease trends. The current consensus hypothesis is that higher
standards of hygiene deprive the developing immune response of
important signals during the period from the fetus to up to 5
years after birth, signals important for immune system
development. This hygiene hypothesis "best accommodates the link
between allergy and social class, the urban to rural gradient,
infant diet, over-use of antibiotics and the East to West
gradient of disease."
     5) The author concludes: "The recognition that most atopic
disorders [allergic disorders] have their origins in childhood,
are increasing in incidence in developed and developing countries
and have strong links to the environment suggests that solutions
to stop the epidemic are more likely to come from public health
than pharmacological interventions."
-----------
Stephen T. Holgate: The epidemic of allergy and asthma.
(Nature 25 Nov 99 402supp:B2)
QY: Stephen T. Holgate [sth@soton.ac.uk]
-----------
Text Notes:
... ... *inflammatory disorder: In general, inflammation is a
fundamental pathologic process consisting of a dynamic complex of
cellular and chemical reactions occurring in affected blood
vessels and adjacent tissues in response to an injury or abnormal
stimulation caused by physical, chemical, or biological agents.
... ... *sporadic: In this context, the term "sporadic" refers to
a reversible phenomenon (e.g., asthmatic attack) that occurs
irregularly.

... ... *smooth muscle: Smooth muscle was originally
differentiated from striated muscle on the basis of microscopic
appearance, but there are important other differences both
functional and molecular. In general smooth muscle is
specialized for slow sustained contractions such as those
involved in the control of the diameters of blood vessels.
... ... *bronchi and bronchioles: A "bronchus" is one of the two
subdivisions of the trachea that serve as airways to and from the
lungs, and a "bronchiole" is one of the approximately 6
generations of linear branches of the bronchi.
... ... *alveoli: In general, an "alveolus" is a small cavity or
socket, and in this context, a [pulmonary] alveolus is one of the
thin-walled sac-like terminal dilations of the respiratory
bronchioles and alveolar ducts across which gas exchange occurs
between alveolar air and the pulmonary capillaries.
... ... *immunoglobulin: The immunoglobulins are a large
glycoprotein category that includes antibodies as a subset. In
general, an "antibody" is a protein molecule produced by the
immune system of vertebrate organisms, the molecule designed to
specifically interact with a particular antigen.
... ... *eczema: In general, an inflammatory conditions of the
skin.
... ... *rhinitis: (nasal catarrh) In general, inflammation of
the nasal mucous membranes.
... ... *T-lymphocyte: (T-cells) Lymphocytes (lymph cells,
lympho-leukocytes) are a type of leukocyte (white blood cell)
involved in the immune response. T-lymphocytes are lymphocytes
that mature in the thymus gland.
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Cytokines mediate many functions
of the immune system.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 25Feb00
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
LEUKOTRIENES AND THE TREATMENT OF ASTHMA
... In 1990 in the US, hospital care of asthmatics cost in excess
of US$2 billion, and the total cost of asthma care was US$6.21
billion. The airway obstruction in asthma is due to a combination
of factors, including spasm of airway *smooth muscle, *edema of
airway *mucosa, increased mucus secretion, cellular infiltration
of the airway walls (especially by *eosinophils and *leukocytes),
and injury of the airway *epithelium. Recently, a group of drugs
called "leukotriene modifiers" was introduced for the treatment
of asthma, but the role of these drugs in treatment has not yet
been established. In general, a "leukotriene" is a member of a
family of pharmacologically active substances derived from
polyunsaturated fatty acids (especially from arachidonic acid),
some of which contain a peptide moiety based on cysteine. The
leukotrienes are classified as "local hormones", i.e., hormones
that are not stored, but which are synthesized in response to
specific stimuli. They are formally derived from eicosanoic acid
and contain a set of 3 conjugated double bonds (thus the suffix
"triene"). The story of the drugs called "leukotriene modifiers"
is a classic example of the interaction of basic science, medical
science, and pharmaceutical industry research and development
leading to the availability of specific drug therapy against an
important human disease. ... ... J.M. Drazen et al (3 authors at
2 installations, US CA) present a review of the use of
leukotrienes in the treatment of asthma, the authors making the
following points: 1) In 1940, Kellaway and Trethewie discovered a
slow-reacting *anaphylaxis-related substance or substances that
stimulated smooth muscle contraction. In 1979, Murphy et al
identified the chemical structures of the chemical entities, the
substances now called the "leukotrienes". The molecules received
the prefix "leuco" because the parent molecule was originally
isolated from leukocytes. The new structural information provided
the key to elaborating the oxidative pathway of lipid metabolism
known as the "*5-lipoxygenase pathway". 2) Respiratory physicians
and scientists had been interested in the classical slow-reacting
substance of anaphylaxis because of the observation that the
substance or substances stimulated airway smooth muscle by a
mechanism that apparently did not involve *histamine. After the
leukotriene structures had been elucidated, the leukotrienes
proved to be potent stimulators of smooth muscle in animal and
human tissues in vitro and in vivo. For example, in normal
subjects, inhalation of one type of leukotriene (D(sub4)) results
in the same degree of airway obstruction as inhalation of
solutions of histamine or *methacholine that are 10,000 times as
concentrated. 3) In addition to their potent *bronchoconstrictor
properties, leukotrienes and other products of the 5-lipoxygenase
pathway induce pathophysiologic responses similar to those
associated with asthma. Specifically, 5-lipoxygenase products can
cause tissue edema and migration of eosinophils, and can
stimulate airway secretions. The leukotrienes also stimulate
*cell cycling and proliferation of both smooth muscle and various
*hematopoietic cells. Since all these responses contribute to
asthma, the pharmaceutical industry initiated research programs
to identify substances that could inhibit the action or synthesis
of the leukotrienes. By early 1998, three chemically distinct
cysteinyl leukotriene-receptor antagonists (Montelukast,
Pranlukast, Zafirlukast) and an inhibitor of leukotriene
synthesis (Zileuton) were available by prescription in more than
a dozen countries. 4) The leukotrienes apparently exert their
biologic actions by binding to and activating specific receptors.
In humans, these receptors are of two types: one type of receptor
mediates constriction of pulmonary vascular smooth muscle, and
the other type of receptor mediates *chemotaxis. Leukotrienes are
apparently produced during asthmatic reactions by cells involved
in the pathogenesis of asthma. The most convincing evidence of a
causative role of leukotrienes in asthma comes from studies of
the effectiveness against asthma of drugs that inhibit the action
or formation of leukotrienes. These so-called "leukotriene
modifiers" are effective in preventing many types of specifically
provoked asthmatic responses. 5) The leukotriene modifiers are
the first new drugs for the treatment of asthma to be introduced
in more than 20 years. Despite their novelty, and the fact that
their exact role remains to be determined, the authors suggest
there are data to support their use in patients with persistent
asthma, whether the asthma is mild, moderate, or severe. 6) The
authors conclude: "Because the leukotriene modifiers are the
first treatment for asthma to result from a search for an
inhibitor of a specific biologic process, these new drugs should
teach us about the pathobiology of asthma while providing orally
available, safe, and effective therapy."
-----------
J.M. Drazen et al: Treatment of asthma with drugs modifying the
leukotriene pathway.
(New England J. Med. 21 Jan 99 340:197)
QY: Jeffrey M. Drazen, Respiratory Disease Division, Brigham and
Women's Hospital, 75 Francis St., Boston, MA 02115 US.
-----------
Text Notes:
... ... *smooth muscle: See main report.
... ... *edema: In general, an accumulation of an excessive
amount of watery fluid in cells and tissues.
... ... *mucosa: In general, a multilayer tissue lining various
tubular structures in the body.
... ... *eosinophils: A type *leukocyte that stains readily with
eosin dye.
... ... *leukocytes: This is a synonym for "white blood cells",
of which there are many types.
... ... *epithelium: In animals, epithelial cells (epithelium)
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway passages.
... ... *anaphylaxis: This term has a number of historical
different meanings. In current usage (and especially in the
context of this report), it refers to an immediate and transient
allergic reaction characterized by contraction of smooth muscle
and dilation of capillaries due to the release of
pharmacologically active substances, including *histamine and the
so-called slow-reacting substances (i.e., the leukotrienes).
... ... *5-lipoxygenase pathway: Lipoxygenase (carotene oxidase,
lipoxidase) is an enzyme that catalyzes the oxidation of
unsaturated fatty acids to yield hydroperoxides of the fatty
acids. 5-lipoxygenase catalyzes the first step in leukotriene
biosynthesis, acting on arichodonate.
... ... *histamine: A local hormone that acts as a powerful
stimulant of gastric secretion, constriction of bronchial smooth
muscle, and dilation of blood vessels.
... ... *methacholine: (Provocholine) A substance with potent
*bronchoconstrictor properties sometimes administered as an
inhalant to test for bronchial hyperreactivity.
... ... *bronchoconstrictor: In general, any agent that causes a
reduction in the caliber of a bronchus or bronchial tube.
... ... *cell cycling: The "cell cycle" is the name given to the
ordered sequence of phases through which a cell passes from one
mitotic cell division to the next.
... ... *hematopoietic cells: (hemopoietic cells) The term
"hematopoiesis" refers to the formation and development of the
various types of blood cells, and "hematopoietic cells" are the
precursor cells of these various types.
... ... *chemotaxis: In general, a movement of cells (or
organisms) in response to chemicals.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 14May99
-------------------
Related Background:
DETAILS OF DISCOVERY OF ASTHMA GENE REMAIN A CORPORATE SECRET
Difficulties in the mingling of corporate interests with
scientific research continue to grow in number, perhaps because
the financial stakes are growing. This week Sequana Therapeutics
Inc. (San Diego CA US), in conjunction with collaborators at the
University of Toronto (CA), issued a press release declaring they
had "discovered a gene responsible for asthma", while at the same
time stating that the scientific paper reporting the research was
in the "very early stages" of preparation and might be published
within a year. Sequana is in a financial arrangement with the
pharmaceutical firm Boehringer Ingelheim, and the CEO of Sequana
says no scientific details of the discovery will be revealed
until his company has filed for a patent, the purpose of this to
give Boehringer Ingelheim some "lead time" in commercial
development. The academic collaborators in the project are Arthur
Slutsky and Noe Zamel (University of Toronto CA). Slutsky points
out that the Sequana investment of more than $10 million to find
the gene is more than the Canadian government has spent on the
entire human genome project in the last two years. The price for
the Sequana financial support of the research was apparently
secrecy. (Science 30 May) (Science-Week 5 Jun 97)
[For more information: http://scienceweek.com/search/search.htm]


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

IN FOCUS: ON GRAVITATIONAL WAVES
"The idea of gravitational waves was already implicit in the 1905
special theory of relativity, with its finite limiting speed for
information transfer. The explicit formulation for gravitational
waves in general relativity was put forward by Einstein in 1916
and 1918. He showed that the acceleration of masses generates
time-dependent gravitational fields that propagate away from
their source at the speed of light as warpages of spacetime. Such
a propagating warpage is called a gravitational wave. The best
empirical evidence we have of the existence of gravitational
radiation is indirect. It comes from the 1974 discovery and
beautiful observations, by Russell Hulse and Joseph Taylor, of
the first binary pulsar ever found. Exploiting the clockwork
pulsar signal from the neutron star, they were able to monitor
the orbital period of the binary star system with exquisite
precision and confirm that it was indeed gradually speeding up at
just the rate predicted for the general-relativistic emission of
gravitational waves. The _direct_ detection of gravitational
waves will mark the opening of a new window on the near and far
reaches of the cosmos. For physics, its most important promise is
the direct observation of gravitation in highly relativistic
settings, so that one can test general relativity in the strong-
field limit, where it is not merely a small correction to
Newtonian gravity. In that limit, the strong curvature of the
spacetime geometry should show us fundamentally new physics."
-----------
B.C. Barish and R. Weiss: LIGO and the Detection of Gravitational
Waves.
(Physics Today October 1999)


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