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.

July 23, 1999 -- Vol. 3 Number 30

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"Our biology has made us into creatures who are constantly
recreating our psychic and material environments, and whose
individual lives are the outcomes of an extraordinary
multiplicity of intersecting causal pathways. Thus, it is our
biology that makes us free." -- Richard Lewontin

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Contents of This Issue:

1. On Health Impacts of Domestic Coal Use in China
2. Mathematics: On Kurt Godel and the Limits of Logic
3. On the Birth of Binary Stars
4. Molecular Biology: On the Phylogeny of Innate Immunity
5. Ion Channel Genes and Human Neurological Disease
6. Medical Biology: The Search for Unrecognized Pathogens

Addendum:
AAAS in Surprise Opposition to NIH Electronic Journal Plan

In Focus: On Homeobox Genes

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1. ON HEALTH IMPACTS OF DOMESTIC COAL USE IN CHINA
The coals burned in the US generally contain low to modest
concentrations of hazardous air pollutant elements, and many
coal-burning utilities use sophisticated pollution control
systems that efficiently reduce the emissions. Such is not the
case in many developing countries, especially in homes where coal
is used for heating and cooking. Domestic use of coal can present
serious human health problems because the coals generally are
mined locally with little regard to their composition, and the
coals are commonly burned in poorly vented or unvented stoves,
directly exposing residents to the emissions. Thus, domestic coal
combustion has had profound adverse effects on the health of
millions of people worldwide. In China alone, several hundred
millions of people commonly burn raw coal in unvented stoves that
permeate their homes with high levels of toxic metals and organic
compounds. ... ... R.B. Finkelman et al (2 installations, US CN)
present a review of the health impacts of domestic coal use in
China, the authors making the following points:
     1) At least 3000 people in Guizhou Province in southwest
China are suffering from severe *arsenic poisoning. The primary
source of the arsenic appears to be consumption of chili peppers
dried over fires fueled with high-arsenic coal. Coal samples in
the region were found to contain up to 35,000 parts per million
(ppm) arsenic. Chili peppers dried over high-arsenic coal fires
adsorb 500 ppm arsenic on average.
     2) More than 10 million people in Guizhou Province and
surrounding areas suffer from dental and skeletal *fluorosis. The
excess fluorine is caused by eating corn dried over burning
briquettes made from high-fluorine coals and high-fluorine clay
binders.
     3) Polycyclic aromatic hydrocarbons formed during coal
combustion are believed to cause or contribute to the high
incidence of esophageal and lung cancers in parts of China.
Esophageal cancer is a fatal cancer and the fourth-leading cause
of cancer death in China. Parts of Henan Province in north-
central China have some of the highest rates of esophageal cancer
in the world, with cumulative death rates of over 20 percent by
age 75 for both sexes.
     4) Domestic coal consumption also has caused selenium
poisoning and possibly mercury poisoning. Nearly 500 cases of
human selenosis (excess selenium) have been reported in southwest
China, the disease attributed to the use of selenium-rich
carbonaceous shales. The use of combustion ash as a soil
amendment results in selenium uptake by crops. Concerning
mercury, chemical analysis of a coal sample used in Guizhou
Province indicates a mercury concentration of 55 ppm, which is
approximately 200 times the average mercury concentration in US
coals.
     5) The authors suggest that better knowledge of coal quality
parameters may help to reduce some of these health problems.
Information on concentrations and distributions of potentially
toxic elements in coal may help delineate areas of coal deposit
to be avoided. Information on the modes of occurrence of toxic
elements and the textural relations of the minerals and *macerals
in coal may help predict the behavior of the potentially toxic
components during coal combustion.
-----------
R.B. Finkelman et al: Health impacts of domestic coal use in
China.
(Proc. Natl. Acad. Sci. US 30 Mar 99 96:3427)
QY: Robert B. Finkelman [rbf@usgs.gov]
-----------
Text Notes:
... ... *arsenic poisoning: Typical consequences of chronic
arsenic poisoning are hyperpigmentation (flushed appearance,
freckles), hyperkeratosis (scaly lesions on the skin), Bowen's
disease (dark precancerous lesions of the skin), and squamous
cell carcinoma.
... ... *fluorosis: Typical consequences of fluorosis (excess
fluorine) include mottling of tooth enamel, osteosclerosis,
limited movement of the joints, severe bone deformations of the
limbs, spinal curvature.
... ... *macerals: In general, "macerals" are the microscopic
organic constituents found in coal.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99


2. MATHEMATICS: ON KURT GODEL AND THE LIMITS OF LOGIC
The mathematician Kurt Godel (1906-1978), brilliant and
individualistic and psychiatrically self-destructive, appears in
the history of 20th century science like some character invented
by a novelist. Godel was a Viennese physics student who switched
to mathematics; participated as a youth in the famous *Vienna
Circle of philosophers; met and became bonded to an older
nightclub dancer when he was a student; published at the age of
25 a thesis that forever changed the field of mathematics;
escaped from Nazi Germany in 1940 by travelling across Asia with
the nightclub dancer (whom he had now married); settled at the
Institute for Advanced Study at Princeton, where apparently
everyone agreed that Godel was brilliant but slightly crazy; was
chaperoned by Einstein in daily walks apparently designed by
Einstein to calm Godel and keep him working; and then, finally,
in 1978, refusing to eat because he believed people were trying
to poison him, Godel died of starvation. Science, after all, is a
human enterprise, and every human enterprise has its human
stories. Concerning the contributions of Godel to mathematics,
John W. Dawson Jr (Pennsylvania State University, US) presents a
biographical essay on Godel, the author making the following
points:
     1) The story of Godel's life and work is that of a
persistent quest for rationality in all things, pursued against a
background of recurrent mental instability.
     2) Godel proved that the mathematical methods in place since
the time of Euclid were inadequate for discovering all that is
true about the natural numbers. His discovery undercut the
foundations on which mathematics had been built through the ages
up to the 20th century, stimulated thinkers to seek alternatives,
and generated a lively philosophical debate about the nature of
truth. Godel's innovative techniques, which could readily be
applied to algorithms for computation, also laid the foundation
for modern computer science.
     3) In his famous 1931 "incompleteness theorem" paper, Godel
demonstrated that there exists some statement that is true of the
natural numbers that must fail to be provable. That is, objects
that obey the axioms of number theory, but fail to behave like
the natural numbers in some other respects, do exist.
     4) The concepts and methods Godel introduced in his
"incompleteness" paper are central to the discipline of
*recursion theory, which underlies all of modern computer
science. Extensions of his ideas have allowed the derivation of
several other results concerning the limits of computational
procedures. One result is the unsolvability of the so-called
"halting problem" -- that of deciding, for an arbitrary computer
with an arbitrary input, whether the computer will eventually
halt and produce an output rather than becoming stuck in infinite
loop. Another result is the demonstration that no computer
program that does not alter a computer's operating system can
detect all programs (e.g., computer viruses) that do.
     5) Godel published remarkably few papers during his lifetime
-- fewer than any other great mathematician except *Bernhard
Riemann -- but the impact of Godel's papers has been enormous,
and his work has affected virtually every branch of modern logic.
-----------
John W. Dawson Jr.: Godel and the limits of logic.
(Scientific American June 1999)
QY: John W. Dawson Jr., Dept. of Mathematics, Pennsylvania State
University York 814-863-8461.
-----------
Text Notes:
... ... *Vienna Circle of philosophers: (Vienna School) A
philosophical school of philosophers in Vienna in the 1920s,
inspired by the physicist-philosopher Ernst Mach (1838-1916). The
group is considered responsible for the branch of philosophy
called "logical positivism", and included Ludwig Wittgenstein
(1889-1951) and Rudolf Carnap (1891-1970). The essential approach
of logical positivism was to dismiss most "metaphysics" as
meaningless answers to pseudoproblems, and to focus on the
foundations of knowledge, scientific method, logic, and
semantics. Although Godel is often considered a member of the
Vienna Circle, from a philosophical standpoint he was a Platonist
rather than a logical positivist: Godel believed the objects of
true knowledge are ideas, particularly universals.
... ... *recursion theory: In this context, the theory of
iterative processes in computation.
... ... *Bernhard Riemann: Georg Friedrich Bernhard Riemann
(1826-1866). Many mathematicians consider Riemann's influence on
the course of modern mathematics to be unparalleled. Almost all
of his short number of papers were and remain important. He died
of tuberculosis before his 40th birthday.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99


3. ON THE BIRTH OF BINARY STARS
Binary stars are a pair of stars revolving around a common
center of mass under the influence of their mutual gravitational
attraction, and apparently the majority of stars in the universe
are binaries and not singlets. In some cases the binary system is
resolvable into two components, and in other cases the presence
of a second star is inferred by perturbations in the motion or
perturbations in the emitted radiation of the first star. If the
binaries are close enough, they may share stellar material, and
this results in a particular kind of stellar evolution.
... ... Alan P. Boss (Carnegie Institution of Washington, US),
presents a review of current research concerning the origin of
binary star systems, the author making the following points:
     1) Astrophysicists have reached a point where both 
observations and theory apparently yield the same answer: binary
star systems appear to form at the very same time that the stars
themselves form -- during the gravitational collapse of
*interstellar clouds. Thus, stars are paired from the outset, and
this has profound consequences for the long-term viability of any
planets created in these same systems.
     2) Binary stars have been discovered with orbital periods
that range from a few hours for the closest pairs to millions of
years for the most distant and barely bound systems. Separations
thus vary from a few stellar radii to almost a light year, and
different observational methods are required to find binary stars
over this extended range.
     3) Because of continuing advances in instrumentation,
extremely small companion objects -- either planets or *brown
dwarf stars --  can now be detected around *main-sequence stars.
Brown dwarfs are particularly difficult to detect, so many nearby
stars previously thought to be single stars may actually be
binary. There is indeed evidence that low mass objects accompany
approximately 10 percent of main-sequence stars.
     4) There is no longer any doubt that binary *protostars are
prevalent and that pairing occur with approximately the same
frequency for old stars, clusters of young stars, and newly
formed stars. The formation of a binary system apparently occurs
prior to the protostar phase, during the gravitational
contraction of dense interstellar clouds. The culmination of this
process is a rapid collapse lasting approximately 100,000 years
or less.
     5) The breakup or division that can occur during the
collapse of a cloud is called "fragmentation", and various models
of dense-cloud-core fragmentation have been designed. The success
of any of these theoretical models depends on an understanding of
the properties of dense interstellar clouds on the verge of
collapse. According to current views, such clouds rotate at
different rates, are centrally condensed, and have prolate
shapes. The structure of the cloud is determined in part by
magnetic fields and in part by pressure from hot gases. Magnetic
fields control the early phases of the contraction of a cloud,
but once the fields begin to leak out of the cloud by *ambipolar
diffusion, a rapid collapse follows. Given these initial
conditions, theoretical models of collapsing magnetic clouds
indicate that fragmentation into binary protostars is possible
provided that the systems rotate relatively fast, with a rotation
period of approximately 2 million years or less. Slower rotating
clouds lead only to single protostars. Approximately half of the
observed dense cloud cores rotate faster than the theoretical
critical rate, and so will eventually form binary protostars. In
addition, current models indicate that binary protostars formed
by fragmentation inevitably begin their lives in eccentric
orbits, and indeed observations confirm orbital eccentricities in
binary systems.
-----------
Alan P. Boss: The birth of binary stars.
(Sky & Telescope June 1999)
QY: Alan P. Boss [boss@dtm.ciw.edu]
-----------
Text Notes:
... ... *interstellar clouds: These are mainly hydrogen gas, some
helium, and approximately 1 percent dust grains. The temperatures
of these clouds vary, with hot clouds having temperatures of
10^(6) degrees kelvin.
... ... *brown dwarf stars: Brown dwarf stars are formed by the
contraction of a lump of gas with a mass too small for nuclear
reactions to begin in the core. Such a star has a relatively
short-lived luminosity (approximately 100 million years) as the
result of conversion of gravitational energy to radiation. The
surface temperature of a brown dwarf is below 2500 degrees
kelvin. As recently as 1994, brown dwarfs were only "theoretical"
stars, with no brown dwarfs considered to be unambiguously
identified.
... ... *main-sequence stars: The Hertzsprung-Russell diagram is
a plot of stellar absolute magnitude against spectral type, and
is one of the most useful diagrammatic aids in astrophysics. The
Main Sequence is a region on the Hertzsprung-Russell diagram
where most stars, including our own Sun, are situated. The course
of a star's evolution can be traced as a particular path in the
H-R diagram, with the paths of various types of stars showing
significant differences.
... ... *protostars: A star in the earliest phase of its life,
before the onset of nuclear burning. Protostars are visible at
infrared wavelengths, but not at visible wavelengths due to
obscuration by infalling material.
... ... *ambipolar diffusion: In general, this refers to a
diffusion regime in which more than one type of gradient drives
diffusion, e.g., the diffusion of charged particles. In a charged
particle diffusion regime, both particle density gradients and
electric charge density gradients interact and drive the
diffusion process. Interstellar clouds are mostly plasmas (i.e.,
ionized gases) exhibiting ambipolar diffusion.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99
-------------------
Related Background:
A MILLISECOND PULSAR IN AN X-RAY BINARY SYSTEM
A pulsar is a regularly pulsating source of radiation, the
pulsations believed to involve the magnetic field of a rotating
*neutron star. Pulsars were originally discovered at radio
wavelengths, but they have also been detected at optical and
gamma-ray wavelengths. They can be powerful gamma-ray emitters
(gamma-ray pulsars), and there is also a class of x-ray pulsars.
The periods of pulsars range from approximately 1.5 milliseconds
to 4 seconds and can typically be measured to accuracies of one
part in 10^(10). Pulsars with periods shorter than approximately
0.01 seconds constitute the distinct class of millisecond
pulsars. Most pulsars are single stars, but binary pulsars are
known, about half of which are millisecond pulsars. The
millisecond-pulsar neutron star is believed to be rotating
hundreds of times per second, and a large number of millisecond
binary pulsars have been discovered in globular clusters. The
origin and evolution of pulsars has not been clear, but it has
been thought that millisecond radio pulsars, which are often
found in binary systems, start as ordinary pulsars, then lose
most of their magnetic field and "spin up" to millisecond periods
by the accretion of matter (and transfer of angular momentum)
from a companion star in an x-ray binary system. Until now, there
has been no direct proof of this idea in the form of predicted
coherent millisecond x-ray pulsations in the flux of an x-ray
binary. ... ... Wijnands and van der Klis (2 installations, NL
US) now report the discovery of such a pulsar, confirming
theoretical expectations. The authors suggest the source will
probably become a millisecond radio pulsar when the accretion
turns off completely. ... ... In a contiguous paper, Chakrabarty
and Morgan (Massachusetts Institute of Technology, US) report
that the orbital period of this binary system is 2 hours, and
that the system seems closely related to "black-widow"
millisecond radio pulsars, a class of pulsars that completely
consume their binary companions.
QY: Michiel van der Klis 
QY: Deepto Chakrabarty 
(Nature 23 Jul 98 394:344,346) (Science-Week 14 Aug 98)
-------------------
Related Background:
... ... *neutron star: If, following the terminal stages of its
evolution, the remnant mass of a star is between 1.4 and 2 to 3
solar-masses, the star will collapse into a neutron star, a body
with a radius of 10 to 15 kilometers, with a core so dense that
its component protons and electrons have merged into neutrons.
The average density of a neutron star is 10^(15) grams per cubic
centimeter, and the weight of an object on the surface of a
neutron star would be 10^(11) its weight on the surface of the
Earth. Neutron stars apparently have an outer shell of iron, but
it is iron like no Earth iron, an iron of 4 orders of magnitude
greater density. Theory predicts that a neutron star should
rotate very rapidly, be extremely hot, and have an intense
magnetic field.
-------------------
Related Background:
ON THE LIVES OF BINARY STARS
... A Roche-lobe (named after Edouard A. Roche 1820-1883, the
astronomer who first presented the mathematical analysis) is an
equipotential surface produced by the coalescence of the
gravitational fields of two relatively close stars in a binary
system. When the stars are relatively far apart, the
equipotential surfaces of their gravitational fields are
spherical shells. At lesser distances between the stars, the
equipotential shells may be coalesced to form bi-lobate surfaces.
As seen in a two-dimensional field mapping, the Roche-lobes are
essentially the lobes of a "figure-eight", with each star at the
center of one of the lobes. The major significance of the Roche-
lobe surfaces is that they define a surface in space where
stellar material is communal, belonging to neither star, the
stellar material therefore moving without energy barriers from
one star to another. The evolution of such a stellar system will
differ markedly from the evolution of a singlet star. Iben and
Tutukov (Univ. of Illinois, US; Institute for Astronomy, RU)
review what is known of the birth and death of binary stars,
especially Roche-lobe material transfer mechanisms, and outline
how the theory of the gravitational geometry of binary star
systems is in apparent agreement with observations. The authors
suggest it is not unreasonable to believe we have now deduced the
correct evolutionary path for most stars, either isolated stars
or those in close binary systems.
QY: Icko Iben Jr., Univ. of Illinois 217-333-3090
(Sky & Telescope January 1998) (Science-Week 5 Dec 97)


4. MOLECULAR BIOLOGY: ON THE PHYLOGENY OF INNATE IMMUNITY
All biological organisms are subject to invasive attack by
microbial pathogens, and the survivability of biological
organisms depends on the activation of various protective
mechanisms (immune responses) when a microbial invasion occurs.
In biology, the "immunity" of organisms to infection by various
pathogens is functionally characterized into 2 types: The term
"innate immunity" refers to non-specific antimicrobial systems of
response (e.g., phagocytosis: engulfment and digestion of
microbes by "killer" cells) that are innate and not intrinsically
affected by prior contact with the infectious agent; the term
"adaptive immunity" refers to immune responses which involve an
enhanced ability to respond to specific molecular *antigens
presented by the invading pathogenic entity, the enhancement
dependent on prior contact with the same pathogen. In addition,
the concept of innate immunity generally refers to the first-line
host defense that serves to limit infection in the early hours
after exposure to microorganisms. Recent data have highlighted
similarities between pathogen recognition, signaling pathways,
and *effector mechanisms of innate immunity in both the fruit fly
Drosophila and in mammals, pointing to a common ancestry of these
defenses. In addition to its role in the early phase of defense,
innate immunity in mammals appears to play a key role in
stimulating the subsequent *clonal response of adaptive immunity.
... ...  J.A. Hoffmann et al (4 authors at 4 installations, FR DE
US) present an extensive review of innate immunity in Drosophila,
the essential characteristics of mammalian innate immunity, and
the links between innate and adaptive immunity. The authors make
the following points:
     1) The fruit fly Drosophila is particularly resistant to
microbial infections, and 3 mechanisms contribute to this
resistance: a) phagocytosis of invading microorganisms by blood
cells; b) *proteolytic cascades leading to localized blood
clotting, *melanin formation, and *opsonization; c) transient
synthesis of potent antimicrobial peptides. These reactions all
take place within a short period after pathogenic injury.
     2) Drosophila is capable of discriminating between classes
of invading microorganisms, for instance, between bacteria and
fungi, and of responding by preferentially producing peptides
that target destruction of the recognized pathogen.
     3) A key feature of innate immunity in mammals is the
ability to rapidly limit the infectious challenge. This is based
on the capacity to discriminate species self from infectious
nonself. Microbes display molecular arrays or patterns that are
apparently recognized by pattern recognition molecules or
receptors, and these patterns are evidently shared among groups
of pathogens, e.g.: lipopolysaccharides of *gram-negative
bacteria; lipotechoic acids of *gram-positive bacteria; mannans
of *yeast; double-stranded RNA of viruses. To limit infection,
the mammalian host uses a wide variety of pattern recognition
molecules, including *complement, *collectins, and a battery of
antimicrobial peptides that act together with effector cells to
combat the infectious challenge.
     4) The adaptive immune system apparently appeared
approximately 450 million years ago when a *transposon that
carried the forerunners of certain *recombinase-activating genes
was inserted into the germ-line of early jawed vertebrates. The
ability to mount an adaptive immune response allowed organisms to
"remember" the pathogens they had already encountered, and
natural selection made the adaptive immune response a virtually
universal characteristic of vertebrates. But the innate immune
system was not discarded, and indeed the innate immune system has
been coopted in vertebrates to serve a second function, that of
stimulating and orienting the primary adaptive immune response by
controlling the expression of "*costimulatory molecules".
     5) Concerning innate immunity, it is a provocative thought
that innate immunity in both plants and animals may have evolved
from common ancestral modules that have been used to protect
against infection for more than 1 billion years of evolution.
-----------
J.A. Hoffmann et al: Phylogenetic perspectives in innate
immunity.
(Science 21 May 99 284: 1313)
QY: Jules A. Hoffmann [jhoff@ibmc.u-strasbg.fr]
-----------
Text Notes:
... ... *antigens: In general, any chemical entity that activates
an immune response, especially an entity originating outside the
body. Antibodies are specific proteins synthesized by the immune
system which interact with specific antigens.
... ... *effector mechanisms: In this context, an "effector
mechanism" is any process which is part of the response of the
biological system to microbial invasion.
... ... *clonal response: In this context, the term "clonal
response" refers to an immune system effector mechanism involving
proliferation of a single line of cells producing a single
antibody to a single specific antigen.
... ... *proteolytic cascades: In general, "proteolysis" is the
enzyme-catalyzed degradation of protein by hydrolysis of one or
more peptide bonds. A "proteolytic cascade" is a sequence of
proteolytic reactions involving a series of enzymes, with each
reaction serving to activate the next reaction in the sequence.
... ... *melanin: A dark brown pigment product of tyrosine
metabolism, usually bound to proteins.
... ... *opsonization: (opsonification) Opsonin is a blood
protein that when combined with microorganisms or other
particulate matter renders them more susceptible to phagocytosis.
The term "opsonization" refers to the coating of microorganisms
or other particulate matter with opsonin.
... ... *gram-negative/gram positive bacteria: Most bacteria can
be classified into two types, depending on the chemistry of their
outer coat, which chemistry determines whether a bacterium will
admit certain dyes into the interior. The classification,
according to the differential staining technique, is
gram-negative vs. gram-positive, named after the bacteriologist
H.C. Gram (1853-1938). Gram-positive bacteria take up a crystal
violet stain and turn purple, while gram-negative bacteria
exclude the crystal violet and counterstain instead with stains
such as safranin, eosin red, or brilliant green. As might be
expected, since the technique differentiates the outer coats of
bacteria, some antibiotics are effective against one type and not
the other type, and vice versa.
... ... *complement: A group of 9 interacting serum proteins,
mostly enzymes, which are activated during the immune response,
and which participate in bacterial lysis (destruction of bacteria
by disruption of cell membrane) and macrophage chemotaxis
(chemical attraction of macrophages, immune system amoeba-like
cells active in phagocytosis of bacteria and other particulates.)
... ... *collectins: A family of plasma lectins (a group of
antibody-like proteins which agglutinate cells and particulates).
... ... *transposon: A transposon is a limited DNA sequence that
under the proper dynamic conditions can effectively translocate
from one DNA system to another, either in the same cell, or
between cells, or between cells of different organisms of the
same or different species, and remain functional.
... ... *recombinase: In general, an enzyme that plays a specific
role in recombining DNA sequences into genes that encode for
antibodies.
... ... *costimulatory molecules: An alternative name for the
interleukins, a heterogeneous group of *cytokines that act as
signaling molecules between different populations of immune
system white blood cells (leukocytes).
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. As a promoter of cell growth and
division, a cytokine acts as a messenger to cells, and the
transmission of the message requires a binding of the cytokine 
molecule to a cytokine-specific receptor on the cell surface.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99
-------------------
Related Background:
NEW EVIDENCE CONCERNING EVOLUTION OF THE IMMUNE SYSTEM
*Lymphocytes of the *vertebrate adaptive immune system rely on an
array of variable *immunoglobulin (antibody) and *T-cell *antigen
*receptors for specific recognition of antigens. In the genome,
the genes encoding the variable portions of these receptors are
typically split into variable components (V), joining components
(J), and in some cases, diversity gene components (D). One of
each type of each component or gene segment is joined together in
a site-specific *recombination reaction to form the *exon that
encodes the antigen-binding portion of the polypeptide that forms
the antibody or T-cell receptor. This reaction, known as V(D)J
recombination, occurs only in lymphocytes, and in some vertebrate
species is responsible for generating much of the diversity seen
in antigen receptors. It is known that the two proteins encoded
by the recombination-activating genes  and  are
essential to the V(D)J recombination reaction, the proteins
mediating sequence-specific DNA recognition of recombination
"signals" (specific short base-pair sequences involved in this
particular recombination process) and DNA cleavage next to these
signals. ... ... Agrawal et al report that in vitro the proteins
RAG1 and RAG2 together form a *transposase capable of excising a
piece of DNA containing recombination signals from a donor site
and inserting the excised piece into a target DNA molecule. The
products formed contain a structure similar to that created by
*retroviral integration and by all known *transposition
reactions. The authors point out that all jawed vertebrates
studied thus far possess adjacent  and  genes as well
as immunoglobulin and T-cell receptor genes, which usually must
be assembled by *somatic recombination before they can be
expressed. There is no evidence that any of these molecules, or
antigen-specific lymphocytes, are found in jawless vertebrates
(hagfish and lamprey) or invertebrates. This indicates that split
antigen-receptor genes and the enzymatic machinery necessary for
their assembly into functional units arose in the approximately
100 million years between the divergence of jawless and jawed
vertebrates and the divergence of cartilaginous and bony fishes.
The authors suggest their results are evidence in favor of the
theory that a pivotal event in the evolution of the antigen-
specific immune system was the insertion of a "RAG *transposon"
into the genome of a vertebrate ancestor.
-----------
A. Agrawal et al (Yale University, US): Transposition mediated by
RAG1 and RAG2 and its implications for the evolution of the
immune system. (Nature 20 Aug 98 394:744)
QY: David G. Schatz [david.schatz@yale.edu]
-----------
Text Notes:
... ... *Lymphocytes: These are a type of leukocyte responsible
for the immune response. There are two classes of lymphocytes: 1)
the B-cells, which when presented with an activating chemical
entity (antigen) change into antibody producing plasma cells;
and, 2) the T-cells, which interact directly with foreign
invaders such as bacteria and viruses. There are also forms of T-
cells that are involved with B-cell activation.
... ... *vertebrate adaptive immune system: The term "adaptive"
here refers to those parts of the immune system that are capable
of adaptation to chemical experience.
... ... *immunoglobulin (antibody): In general, antibodies are
immunoglobulin proteins.
... ... *T-cell: see *Lymphocyte note above.
... ... *antigen: Any chemical entity that activates an immune
response, especially an entity originating outside the body.
... ... *receptors: In this context, cell surface macromolecules
that bind antigens.
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *exon: In general, any DNA sequence encoding and giving
rise to a translated polypeptide sequence.
... ... *transposase: Any enzyme required for the transposition
of DNA segments (see below, *transposition reactions).
... ... *retroviral integration: Retroviruses are single-stranded
RNA viruses that have an enzyme called reverse transcriptase, and
with this enzyme the viral RNA is used as a template to produce
viral DNA from cellular material. This DNA is then incorporated
(integrated) into the host cell's genome, where it codes for the
synthesis of viral components.
... ... *transposition reactions: In general, any reactions that
insert or excise DNA fragments into or from a genome.
... ... *somatic recombination: Somatic cells are any cells other
than germ cells (gametes). Somatic recombination, where it
occurs, involves the transposition of DNA fragments from one DNA
molecule to another, or within the same DNA molecule. Somatic
recombination theory is one of the theories proposed to explain
the enormous variety of antibodies produced by the immune system.
... ... *transposon: A large transposable genetic element having
at least the genes necessary for its own transposition to the
same or another genome.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 18Sep98
-------------------
Related Background:
AN ANALYSIS OF HYPERMUTATION ANTIBODY GENE TARGETS
In vertebrates, the immune system provides protection against
foreign agents, for the most part by recognizing molecular
entities (antigens) that are interpreted by the immune system as
of foreign origin. Many types of cells are involved in the immune
response, with 3 primary types the so-called B-cells, cytotoxic
T-cells, and helper T-cells. In general, cytotoxic T-cells
recognize and kill host cells that are infected, while B-cells
are cells that secrete antibodies, protein molecules that bind to
antigens. Helper T-cells (and other immune system cells) are
involved in both processes, provoking particular steps in the
immune response. The ability of the immune system to recognize
and respond to the enormous number of antigens encountered by an
individual in a lifetime is due in large part to the diversity of
antibodies (also called *immunoglobulins) produced by B-cells.
Each B-cell produces only a single species of antibody, and
during the systemic immune response, the presence of a specific
antigen results in the proliferation by *clonal selection of
B-cells producing antibody specific for that antigen. All
antibody molecules are proteins consisting of two light
polypeptide chains and two heavy polypeptide chains that are
joined together by disulfide bonds. Each polypeptide chain
contains regions of variable amino acid sequence and regions of
constant amino acid sequence, resulting in an antigen-binding
locus with a variable specific affinity for particular ligands.
Further antibody variability arises from a variability in the way
the particular segments of the antibody are joined. The ability
of antibodies to recognize a large variety of antigens is thus
controlled, in part, by the variability of the variable segments
of the amino acid sequences of the antibody polypeptide chains.
This amino acid variability in the light and heavy chains is the
result of a variability in B-cell DNA generated by somatic
recombination, an alteration and reassembly of genes. During the
past 15 years, it has become evident that in immune system B-
cells, the part of the genome coding for the variable parts of
antibodies is involved in a process of "hypermutation", a
substantial increase in mutation rate, the effect of which is to
provide the immune system with a rapidly changing enormous
library of possible antibodies. This hypermutation process is
highly specific to the immune system, and it occurs only within a
DNA segment of approximately 1000 to 2000 DNA bases, the segment
that encodes the bulk of the variable regions of the antibody
polypeptides. The mechanism of the hypermutation process remains
unknown. ... ... Milstein et al (3 authors at Medical Research
Council, UK) report an analysis of the average frequency of
mutations of each of the 3 bases of all *nucleotide triplets in
the relevant DNA segment. Their focus was the question of whether
the B-cell hypermutation process involves one strand or both
strands of the DNA double helix. Many hypermutation models
propose that only one of the strands of DNA is involved in
hypermutation. The Milstein et al analysis used large databases
of mutations involving both variable and non-variable mutation
targets. The essential idea is that by using large databases of
such mutations, one can contrast the mutation distributions
observed with what would be expected if either one or both DNA
strands are hypermutation targets. The authors report their
analysis indicates there are two aspects of the hypermutation
process, one aspect that is DNA strand-dependent and the other
aspect that is not. The strand-independent aspect is sensitive to
local DNA sequences (i.e., mutation hot spots correlate with
local sequence environments), but without strand preference. The
authors report a similar conclusion has been reached by a
separate research group (Dorner et al, Immunol. Rev. 162:161
1998).
QY: Cesar Milstein, Medical Research Council Laboratory of
Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.
(Proc. Natl. Acad. Sci. US 21 Jul 98 95:8791)
(Science-Week 21 Aug 98)
-------------------
Related Background:
... ... *immunoglobulins: The immunoglobulins are a large
glycoprotein category that includes antibodies as a subset.
... ... *clonal selection: In this context, the process by which
an antigen selectively stimulates the proliferation of those
B-cells that possess antigen receptors targeted against the
stimulating antigen.
... ... *nucleotide triplets: Nucleotides are molecules
consisting a purine or pyrimidine base joined to a 5-carbon sugar
(ribose or deoxyribose) containing an attached phosphate group.
Nucleotides are the fundamental building blocks of nucleic acids,
and nucleotide triplets of 3 contiguous nucleotides are the
fundamental coding units of the genome.
-------------------
Related Background:
HUMAN IMMUNE SYSTEM LINKAGE TO A PLANT DEFENSE SYSTEM
Interstitial tissue is a general term for tissue forming
interstices in an organ or tissue, and "glioma" is a general term
for any neoplasm deriving from one of the various types of cells
that form the interstitial tissue of brain, spinal cord, pineal
gland, posterior pituitary gland, or retina. Glioblastoma
multiforme is a type of glioma that occurs most frequently in the
adult brain. ... ... Szyperski et al (4 authors at Institute for
Molecular Biology and Biophysics Zurich, CH) report that a human
glioma pathogenesis-related protein (GliPR), which is highly
expressed in the brain tumor glioblastoma multiforme (which
arises from brain immune cells), shows 35% amino acid sequence
identity with a tomato pathogenesis-related protein (P14a), which
has an important role for the plant defense system. The authors
compared the molecular structure of both proteins in the folded
state and identified a common partially solvent-exposed spatial
cluster of 4 amino acid residues, this cluster apparently
conserved in all known plant pathogenesis related proteins of a
particular type (called Type 1). The authors suggest their data
indicate a common active site for the human and plant proteins
and a functional link between the human immune system and a plant
defense system. In an analysis of possible evolutionary linkages,
the authors further suggest that the human immune and plant
defensive proteins considered here arose from a common ancestor
that evolved into a large pathogenesis-related protein
superfamily that includes the human protein (GliPR), plant
pathogenesis-related proteins of Type 1, mammalian sperm-coating
proteins, allergens of insect venoms, and snake or lizard
toxins -- the superfamily thus appearing in the 3 kingdoms of
animals, plants, and fungi. Although all these proteins exhibit
alignment of their amino acid sequences with the human glioma
protein, the underlying mechanism for the action of these
proteins is unknown. The authors suggest it is possible all the
proteins of this superfamily operate according to the same
molecular mechanism.
QY: K. Wuethrich, Institut fur Molekularbiologie und Biophysik,
Eidgenoessische Technische Hochschule-Hoenggerberg, CH-8093
Zurich, CH (Proc. Natl. Acad. Sci. US 3 Mar 98)
(Science-Week 27 Mar 98)


5. ION CHANNEL GENES AND HUMAN NEUROLOGICAL DISEASE
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 involve a number of
different associated protein subunits forming a discrete pore in
the cell surface. Most ion channels are selective, allowing only
certain ions to pass, and an individual cell has ion channels
with various ion selectivities. The selectivity of an ion channel
can be "gated", the channel effectively opened or closed, and ion
channels are said to "*voltage-gated" or "*ligand-gated",
depending on how the change in selectivity is provoked. Progress
in the study of ion channels has made it possible to analyze the
effects of human neurological disease-causing channel mutations
at various levels: the single channel, the subcellular domain,
the neuronal network, and the behaving organism.
... ... E.C. Cooper and L.Y. Jan present a review of recent
research relating ion channel genes to human neurological
disease, the authors making the following points:
     1) Clinicians and geneticists seeking the causes of
neurological disorders have mapped chromosomal loci for
hereditary diseases and have found at these loci both previously
unknown channel genes and pathogenic mutations in known channel
genes. This work has proceeded rapidly. The first ion channel
disease mutations, those associated with *hyperkalemic periodic
paralysis, were identified in 1991. Now the list includes
hundreds of disease-causing gene entities responsible for more
than 20 nerve and muscle disorders. Meanwhile, advances in many
disciplines, including electrophysiology, cell biology, genomics,
neuroanatomy, and structural biology have deepened our
understanding of how ion channels function at the molecular and
cellular level, so that it is now possible to approach the
question of how channel gene mutations cause particular types of
neurological symptoms.
     2) Molecular cloning has revealed a large number of channel
genes, and apparently this expansion began early in evolution.
The genome of the *nematode worm Caenorhabditis elegans contains
approximately 80 potassium channel genes, 90 ligand-gated channel
genes, 5 voltage-gated calcium-channel genes, 6 cyclic
nucleotide-gated channel genes, and 6 chloride channel genes.
These numbers do not include the many and variable channel
auxiliary subunits that make important contributions to channel
function. Homologues of a large portion of the C. elegans channel
genes have already been found in mammals.
     3) The characterization of the expressed products of ion
channel genes in general, and of the channel mutations that cause
neurological diseases, is a relatively new research effort. A
large variety of disease phenotypes apparently may result from
mutations in channels functioning together at a single anatomical
site such as the *neuromuscular synapse. In the brain, a far
greater variety of channels are expressed, and the roles played
by specific channels are for the most part poorly understood. But
studies of several brain channel disorders indicate that subtle
changes in the electrophysiological properties of a single
channel type can have important effects on behavior.
     4) In the future, while neurobiologists illuminate the links
between individual genes and behavior, structural biologists and
pharmacologists will characterize in new detail the molecular
character of the different channel proteins and identify
compounds that modify the activity of individual channel types.
In 1998, this effort entered a period of accelerating progress,
as in that year the structure of a bacterial potassium channel
was solved by x-ray crystallography, and the structures of
components of eukaryotic channels involved in gating, subunit
association, and ligand binding also were determined.
-----------
E.C. Cooper and L.Y. Jan: Ion channel genes and human
neurological disease: Recent progress, prospects, and challenges.
(Proc. Natl. Acad. Sci. US 27 Apr 99 96:4759)
QY: Lily Yeh Jan [gkw@itsa.ucsf.edu]
-----------
Text Notes:
... ... *voltage-gated: Refers to the opening or closing of an
ion channel by changes in the electrical potential across the
cell membrane.
... ... *ligand-gated: Refers to the opening and closing of an
ion channel by interactions between ligands and membrane
receptors. 
... ... *hyperkalemic periodic paralysis: A disease characterized
by defective voltage-gated calcium channels producing sustained
membrane depolarization.
... ... *nematode worm Caenorhabditis elegans:  A nematode worm
is a member of an abundant and ubiquitous phylum of
unsegmented roundworms. Caenorhabditis elegans is a small (1 mm)
nematode worm. It is transparent, hermaphroditic, free-living,
and found in soil. It has a relatively small genome
(approximately 3000 genes), and only a few types of cells in its
body. It has a 16-hr embryogenesis that can be achieved in a
petri dish, and is thus highly suitable for the study of
developmental and behavioral genetics.
... ... *neuromuscular synapse: (neuromuscular junction;
myoneural junction) The neuromuscular junction is an anatomically
specialized area of contact between the axon terminal of a motor
neuron and the surface membrane of a muscle fiber (muscle cell).
In general, a "motor" neuron is a neuron that conveys nerve
impulses (action potentials) from the central nervous system to
either muscles or glands. The axon of nerve cell is the usually
long extension along which action potentials are propagated.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99


6. MEDICAL BIOLOGY: THE SEARCH FOR UNRECOGNIZED PATHOGENS
Molecular biology is the "New Biology" of the 20th century, and
it has impacted virtually every field in biology and applied
biological science. Two important research areas whose character
has completely changed in recent decades are microbiology, the
study of microorganisms, and medical microbiology, the study of
pathogenic microorganisms. ... ... David A. Relman (Stanford
University, US) presents a review of current strategies in
molecular medical microbiology, with a focus on the search for
unrecognized pathogens. The author makes the following points:
     1) Considering only human parasitic and *symbiotic microbes
that have been successfully cultivated in the laboratory --
bacteria, viruses, and unicellular *eukaryotes that inhabit the
human body -- the number and variety of relations between microbe
and host are enormous. Yet more than 99 percent of microorganisms
resist cultivation in the laboratory and can only be identified
or characterized by the use of molecular approaches. Since nearly
all available information concerning the composition of microbes
normally resident in the human body (endogenous microbes) and the
role of microbes in infectious human disease has been based on
laboratory cultivation, one must conclude that unrecognized
pathogens may be the cause of many serious diseases that
currently are without convincing etiology.
     2) During the past 15 years, the pathogens for the following
infectious diseases were revealed for the first time:
... ... *Peptic ulcer disease: Helicobacter pylori (1984)
... ... *Non-A, Non-B Hepatitis: Hepatitis C virus (1989)
... ... *Bacillary angiomatosis: Bartonella henselae (1990)
... ... *Whipple's disease: Tropheryma whippelii (1991)
... ... *Hantavirus pulmonary syndrome: Sin Nombre virus (1993)
... ... *Kaposi's sarcoma: KS-associated herpesvirus (1994)
With the exception of Helicobacter pylori, all of the above
infectious agents were first identified directly from clinical
specimens using *molecular genotyping.
     3) In the detection and identification of human microbial
pathogens, a reliance on laboratory cultivation of the microbe
poses potential pitfalls: a) we are largely ignorant of the
environmental conditions required by some microorganisms for
growth, and we are thus unable to replicate them in the
laboratory; b) *phenotypic traits are difficult to quantitate,
and they can be misleading. In contrast, genotypic traits
generally provide reliable and quantifiable information and
characterization of infectious agents.
     4) There are acute and chronic diseases and syndromes over a
wide range of characteristics that deserve to be the focus of
broad cultivation-independent searches for microbial pathogens.
In short, a substantial amount of unexplained illness resembles
infectious disease. Most clinicians, for example, are familiar
with a scenario in which a previously healthy individual develops
an acute life-threatening illness with signs of infection but
with negative diagnostic test results. Evidence indicates that a)
unexplained death or unexplained critical illness occurs in 0.5
to 2.0 persons per 100,000 population in the US per year; b)
broad-range bacterial *ribosomal DNA *PCR analysis has revealed
known disease-causing agents as a probable or definite pathogen
in certain cases; and c) little thought or attention has been
directed at the selection and processing of clinical specimens
appropriate for molecular pathogen discovery.
     5) The application of new pathogen discovery methods is
certain to alter our perspective on microbial disease causation.
For example, improvements in microbial detection and
discrimination may generate data that challenge the traditional
association of one microorganism with one diseased host. We
currently accept the concept of polymicrobial disease causation
in the setting of abscess formation; however, the same concept
may apply to other types of disease, including rheumatic or
"autoimmune" disease, and cancer.
-----------
David A. Relman: The search for unrecognized pathogens.
(Science 21 May 99 284:1308)
QY: David A. Relman [relman@cmgm.stanford.edu]
-----------
Text Notes:
... ... *symbiotic microbes: In biology, symbiosis is an intimate
and protracted association of individuals of different species.
The term is ordinarily used for mutualistic symbiosis, i.e.,
symbiosis of mutual benefit to the organisms involved. In this
context, the bacteria that normally inhabit the human intestine
and which aid in digestion are symbiotic microbes.
... ... *eukaryotes: Eukaryotes are cells containing membrane-
bound organelles such as a nucleus.
... ... *Peptic ulcer disease: Helicobacter pylori: H. pylori is
an actively motile rod-shaped bacterium with multiple flagella
(whip-like extensions involved in locomotion) at one pole.
... ... *Non-A, Non-B Hepatitis: Hepatitis C virus: The hepatitis
C pathogen is a 30 to 60 nanometer spherical virus with a single-
stranded RNA genome containing approximately 10,000 nucleotide
bases.
... ... *Bacillary angiomatosis: Bartonella henselae: The
bacterium B. henselae is the pathogen that causes "cat-scratch"
disease, and is also involved in bacillary angiomatosis, a
disease predominantly of immunosuppressed individuals,
particularly of AIDS patients. Bacillary angiomatosis is
characterized by circumscribed lesions in almost every organ.
... ... *Whipple's disease: Tropheryma whippelii: The bacterial
organism T. whippelii is only tentatively named, since cultures
to isolate the organism have been unsuccessful. The organism is a
bacillus. Whipple's disease is characterized by fever, abdominal
pain, diarrhea, weight loss, and migratory severe pain in the
joints. A unique bacterial ribosomal RNA sequence has been
identified by *PCR from the lesions.
... ... *Hantavirus pulmonary syndrome: Sin Nombre virus:
Hantavirus is classified as a subtype of bunyavirus, which are
spherical particles containing a single-stranded RNA genome 11 to
21 kilobases in size. In general, the bunyaviruses are one of
several pathogens involved in rodent-borne hemorrhagic fevers
worldwide. The virus measures 80 to 120 nanometers. Hantavirus
pulmonary syndrome is newly recognized in the US, the pathogen
transmitted by deer mice, the disease apparently 60 percent
fatal.
... ... *Kaposi's sarcoma: KS-associated herpesvirus: Kaposi's
sarcoma is an ordinarily rare cancer that can be common in humans
with compromised immune systems (for example, in AIDS). KS-
associated herpesvirus has been detected in over 90 percent of
Kaposi's sarcomas. All herpesviruses have a core of double-
stranded DNA, and range from 100 to 200 nanometers in diameter,
depending on the life cycle stage.
... ... *molecular genotyping: In general, the term "genotyping"
refers to the determination of genetic constitution, as
distinguished from determination of physical appearance
(phenotyping). Molecular genotyping refers to determination of
all or part of the genome.
... ... *phenotypic traits: In general, the observed properties
of an organism. Phenotypic traits are produced by the interaction
of the genotype with the environment. In general, categorization
of an organism on the basis of shape and size is phenotyping;
categorization of an organism on the basis of genome analysis is
genotyping.
... ... *ribosomal DNA: A ribosome (not to be confused with
riboZYME) is a small particle, a complex of various ribonucleic
acid (RNA) component subunits and proteins, that functions as the
site of protein synthesis. There is no DNA in ribosomes. The term
"ribosomal DNA" refers to any DNA sequence that codes for
ribosomal RNA.
... ... *PCR analysis: Polymerase chain reaction (PCR): A
technique for isolating and amplifying any specifically desired
DNA sequence. The reaction is facilitated by a heat-stable DNA
polymerase (e.g., Taq, which is obtained from a thermophilic
bacterium) that can withstand the many cycles of heating and
cooling involved in the technique. PCR is considered by many
molecular biologists to be the most important technical advance
in molecular biology in the second half of the 20th century. The
inventor of the technique, Kary Mullis, received the Nobel Prize
for Chemistry in 1993 for his discovery.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Jul99

-----------------------------------------------------------------

Addendum:

AAAS IN SURPRISE OPPOSITION TO NIH ELECTRONIC JOURNAL PLAN
Although the evolution of the application of information
technology to problems concerning access to scientific data and
educational information is still not clear, one would expect the
scientific societies to welcome any means that improves the
dissemination of science at less cost to the end-user. That,
apparently, is an optimistic expectation. The American
Association for the Advancement of Science (AAAS) exists for
several reasons, but certainly one reason is to promote the
dissemination of scientific information among working scientists.
Many people believe that one way to accomplish that objective is
to reduce the cost of scientific journals to libraries and
individual scientists by using the Internet and information
technology to change the character of current scientific journal
publishing. Harold Varmus, head of the US National Institutes of
Health, has recently put forth a plan to create an all-
encompassing archive for biomedical research data, called "E-
Biomed", the system modeled on the already functioning Los Alamos
National Laboratory ePrint Server used by the physics community.
In general, the idea of the Varmus plan is to make access to life
science research journals completely free to end-users. One can
understand why certain huge profit-making multiple-journal
publishers would be opposed to this plan, but the apparent
opposition of some scientific societies to this plan is perhaps a
surprise. The American Association for the Advancement of
Science, via its publishing organ, the journal _Science_, and the
editor of that journal, Floyd E. Bloom, is one scientific society
evidently opposed to the Varmus idea. In an editorial in the
journal, Editor-in-Chief Bloom, cites a 40-year old quote from a
US Senate advisory panel considering the need for an information
system similar to that existing at that time in the Soviet Union.
The US Senate panel said: "The case for a Government-operated
highly centralized type of center can be no better defended for
scientific information services than it could be for automobile
agencies, delicatessens, or barber shops." _Science_ journal
Editor-in-Chief Bloom adds: "Surely, other creative solutions can
be found to what NIH considers problems. Are they prepared to
listen, or is this a done deal?" Perhaps another question (not
posed by Bloom) is whether we have reached a stage where the
information needs of working scientists have become less
important than the revenue needs of established scientific
journal publishers and editors. For the journal _Science_
(individual subscriber rate US$110 per year), the estimated
current annual revenues from all subscriptions is in excess of
US$25 million, and the estimated annual revenues from advertising
in excess of US$10 million.
(Science 9 Jul 99) (SW Bulletin 16 Jul 99)
-----------
The above report is from the SW Bulletin 16 July 1999.
The SW Bulletin, consisting of brief reports of general interest,
is delivered via Email 3 times per week and subscription is free.
To subscribe, send SUB BULLETIN as the subject of an Email
message to request@scienceweek.com
-------------------
Related Background:
ON FREE INTERNET ACCESS TO TRADITIONAL JOURNALS
Thomas J. Walker (University of Florida, US) presents an analysis
of current problems involving the production costs and
subscription prices of scientific journals, the author making the
following points: 1) On the Web, publishers are now beginning to
charge for access to journal articles online through
subscriptions, site licenses, and "pay-per-view" plans. These
toll-gate approaches are an extension of the current economic
structure of scientific publishing and are being developed
largely by the organizations that benefit most from that economic
structure. On the other hand, many of those who do the research
and write the articles do not share these economic interests, nor
do many of the scientific societies to which they belong. 2) Some
scientific societies currently finance publishing through per-
page charges that are paid by authors or their grants or
institutions. Such charges now help hold down subscription
prices, and in the future similar charges might finance free
access. 3) The 1970s witnessed the beginning of extraordinary
increases in the real prices of science journals. Whereas the
costs of scholarly publishing in general closely followed the
Consumer Price Index, the average prices of science and technical
journals markedly diverged upward, so that by 1996 the relative
increase in the prices of scientific journals was an order of
magnitude greater than the relative increase in the prices of
scientific books. 4) In the past decade, research libraries have
spent more than twice what they spent in 1986 to purchase 7
percent fewer titles. Every year libraries must cancel journal
subscriptions in order to continue to receive other journals that
are increasingly costly. And publishers often raise subscription
prices as their subscriber base shrinks, creating a feedback loop
that worsens the situation. 5) Unfortunately, rather than ending
the journals crisis for libraries, the beginning of Web access to
traditional journals may have intensified it. Publishers now
offer licenses to electronic versions as add-ons to regular
subscriptions, in most cases with a substantial increase in
subscription price. 6) The author suggests that the economics of
electronic publication are so favorable that scientific societies
should be able to finance free access to all their articles from
page charges to authors who want their articles immediately
posted, and that the Florida Entomological Society is now doing
just that. 7) The author further suggests that if scientific
societies acknowledge that their mission is to serve members,
they should realize that restricting access to refereed research
results, when free access has finally become affordable, is
counter to that mission. The author concludes: "Free access to
traditional journals is affordable and achievable... Taking
action now can secure an information highway where toll gates do
not limit access to the literature of science."
QY: Thomas J. Walker [tjw@ufl.edu]
(American Scientist Sep/Oct 1998) (Science-Week 11 Sep 98)
[Editor's note: A collection of other previous SW reports on this
subject can be found at URL (http://scienceweek.com/swfr023.htm)]


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

IN FOCUS: ON HOMEOBOX GENES
"In the 1980s, the door to incorporating developmental insights
into evolutionary theory was finally opened with the discovery of
a class of highly conserved regulatory genes, called homeobox
genes. Homeobox genes control an organism's development by means
of sending signals from one to another in the form of the
proteins they produce. As demonstrated in the fruit fly, the cell
that eventually gives rise to the egg cell receives the messages
that determine what will be the head and tail and up, down,
right, and left sides of a potential offspring by a back-and-
forth signaling, carried by proteins, between homeobox genes in
this cell and the cells of the ovary around it. The animal that
then emerges from the egg that derives from this predetermined,
pre-egg cell obtains its specific features through the process of
turning on and off certain homeobox genes at different times in
different regions of its developing body. All animals, from
unsegmented worms to fruit flies, starfish, tunicates, zebra
fish, chickens, mice, and humans, share essentially the same
basic homeobox genes. Since all of an organism's genes are
contained in each and every one of its cells, the striking
morphological difference between animals lies basically in which 
cells and when during development one or more homeobox genes are
active... It is mind-boggling to realize that, for all intents
and purposes, many differences between a fruit fly and a human
may lie pretty much in where and when certain homeobox genes are
activated. To be sure, there are some other differences between a
fruit fly and a human at the molecular level. But, fundamentally,
the main difference between organisms lies in alterations in
development that result from differences in the timing of
homeobox gene activity."

-- Jeffrey H. Schwartz: _Sudden Origins: Fossils, Genes, and the
Emergence of Species_ (John Wiley & Sons, New York 1999, p.12)
[QY: Jeffrey H. Schwartz, Department of Anthropology, University
of Pittsburgh, US]

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