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.

October 29, 1999 -- Vol. 3 Number 44

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If the Lord Almighty had consulted me before
embarking on the Creation, I should have
recommended something simpler.
-- Alfonso X, King of Castile (1226-1284)

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Contents of This Issue:

1. Kansas, Evolution, and Ignorance in America
2. On Scanning Probe Microscopy
3. Fermi Degeneracy in a Trapped Atomic Gas
4. On Prospects for Gene Therapy In Utero
5. Activity-Induced Potentiation of Developing Synapses
6. Implications of Antibiotic Resistance in Wild Rodents

In Focus: On General Relativity

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

1. KANSAS, EVOLUTION, AND IGNORANCE IN AMERICA
Concerning the recent decision by the Kansas (US) State Board of
Education to purge evolution and cosmology from the science
curricula of all Kansas public schools, R.B. Hanson and F.E.
Bloom (_Science_) present an editorial, with the authors making
the following points:
     1) The authors suggest that two aspects of "this
intellectual cleansing atrocity" are most troubling: a) No
political leaders from either party have as yet elected to step
forward and challenge the lunacy of removing from the educational
opportunities of the future voters of Kansas two of the best
established theories of our era. "Such reluctance emphasizes a
growing public ignorance of the methods by which scientific
observations are formulated into testable hypotheses and, when
sufficiently strongly supported, are elevated into... theories."
b) Second, and more troubling, is the shrewdness of the strategy
used by the creationists in achieving their ends. No longer are
they attempting to overturn the series of court decisions that
have banned the teaching of creationism as a science. The new
strategy, representing a far more threatening menace to future
generations, is not only not to teach evolution and cosmology,
but to undermine the solidity of their scientific acceptance.
     2) The authors point out that evolution is the unifying
concept of biology and the basis for all modern biological
research, including much research that affects our daily lives
and national welfare. It is as fundamental in vaccine and health
research as it is in agriculture. "Incomprehensibly, Kansas has
now decided to stop teaching about the basis of its current and
future economy..." The attack on evolution is unequivocally an
attack on all of scientific knowledge.
     3) The authors suggest that in the past, US political
leaders understood the connection between scientific research,
education, and economic competitiveness. Funding of biological,
agricultural, and space research, and of energy exploration --
wholly reliant on evolution and cosmology -- has fostered the US
economy. The authors ask: Where are these leaders now?
     4) The authors conclude: "The Kansas decision is not an
isolated action but the tip of an iceberg of ignorance that is
growing, not melting. Unless these new strategies are directly
defied, the United States will not for long remain a leader in
science and technology."
-----------
R.B. Hanson and F.E. Bloom: Fending off furtive strategists.
(Science 17 Sep 99 285:1847)
QY: R.B. Hanson [science_editors@aaas.org]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
-------------------
Related Background:
MORE REACTION TO KANSAS DECISION ON EVOLUTION TEACHING
What is sometimes not emphasized enough in discussions of the
conflict between science and creationism is that the logical
foundations of these two ways of viewing the world are quite
different. Now, in an unsigned editorial, one of the leading
science journals (_Nature_) discusses the difference between
science and dogma, suggesting that scientists and science
teachers can draw useful lessons from the efforts in Kansas to
expel Charles Darwin from the state's schools. The editorial
states: "In removing the teaching of evolution, as well as
aspects of cosmology, from its curriculum guidance for school
students, the Kansas Board of Education has done no favors to the
schoolchildren of Kansas or to the national and international
reputation of their state." Further: "If more children were
taught science as a means of interrogating nature, rather than as
a toolbox of rules, the 'debate' between creationism and
Darwinism would come to be seen in a clearer light. Darwin's
theory will continue to be attacked and will develop on the
strength of new information established by geneticists,
paleontologists and others. The idea of divine creation is
unlikely to benefit from such further investigation because it is
not scientific theory, but a dogma." (NAT)
(Science-Week Bulletin 25 Aug 99)
-------------------
Related Background:
EVOLUTIONARY BIOLOGY AND THE WIZARD OF KANSAS
What is most disturbing about the news out of Kansas this week is
that Kansas is the US heartland, the place from where Judy
Garland was blown by a tornado into the Land of Oz. Now,
apparently, the Wizard of Oz is behind the curtain controlling
the state: the Kansas Board of Education this week effectively
removed the teaching of evolution from the curriculum of every
Kansas public school, with one prominent board member stating:
"It is not good science to teach evolution as fact." Apparently,
the reality that evolution has broad acceptance in the science
community does not matter; what matters are mental comforts
promoted by Biblical conceptions, including the lunatic idea that
life on Earth is less than 10,000 years old. Many scientists feel
a great sadness about this development in Kansas; it is always a
sad thing when children with the potential for achievement are
denied that achievement by their elders. For that, undoubtedly,
will be the outcome: with a continuing and increasing effect,
Kansas will be shunned by thinking people as a backward place,
heartland or no heartland, a place unsuited for the education of
children with potential, and a place whose children will find it
more and more difficult to attend the top-rank out-of-state
universities. And the two major universities in Kansas, the
University of Kansas and Kansas State University, will themselves
suffer by the attrition of productive science faculty and the
reluctance of new science faculty to bring their children to such
a place. Kansas has, in effect, voted itself into intellectual
and economic decline. And the issue is evidently not a local one:
Tom DeLay, a prominent controlling member of the US Congress,
recently excoriated the teaching of evolution, stating: "Our
school systems teach the children that they are nothing but
glorified apes who are evolutionized out of some primordial soup
of mud." The Board of Education of Kansas apparently agrees.
(Science-Week Bulletin 13 Aug 99)
-------------------
Related Background:
SCIENCE, EVOLUTION, AND CONTEMPORARY AMERICA
Despite a flurry of media bugle blowing during the past several
years, a flurry purporting to demonstrate that religion and
science in the US are "merging", the reality is perhaps that any
such merging is a myth. A large and politically influential group
of Americans continues to refuse acceptance of the facts of
biological evolution on Earth provided by science, even if they
do accept, implicitly at least, the medical care, communication
systems, transportation systems, defense systems, etc. of the
technology produced by that same science. It is apparently not
yet understood that if biological and human evolution is denied,
all of science must be denied and the human species returns to
darkness -- to ignorance, hardship, and the decimation of infants
and children by disease. Stephen Jay Gould, paleobiologist and
current President of the American Association for the Advancement
of Science, confronts the issue in a recent editorial in the
journal _Science_, the author making the following points:
     1) The author poses the question: "What strange set of
historical circumstances, what odd disconnect between science and
society, can explain the paradox that organic evolution -- the
central operating concept of an entire discipline and one of the
firmest facts ever validated by science -- remains such a focus
of controversy, even of widespread disbelief, in contemporary
America?"
     2) Concerning the conflict, the author states: "Denigration
and disrespect will never win the minds (not to mention the
hearts) of these people. But the right combination of education
and humility might extend a hand of fellowship and eventually end
the embarrassing paradox of a technological nation entering a new
millennium with nearly half its people actively denying the
greatest biological discovery ever made."
     3) The author suggests three principles "to guide our
pastoral efforts": a) Evolution is true, and the truth can only
make us free. b) Evolution liberates the human spirit. c) For
sheer excitement, evolution, as an empirical reality, "beats any
myth of human origins by light-years. A genealogical nexus
stretching back nearly 4 billion years and now ranging from
bacteria in rocks several miles under the Earth's surface to the
tip of the highest redwood tree, to human footprints on the Moon.
Can any tale of Zeus or Wotan top this?"
     4) The author concludes: "Let us praise this evolutionary
nexus -- a far more stately mansion for the human soul than any
pretty or parochial comfort ever conjured by our swollen
neurology to obscure the source of our physical being, or to deny
the natural substrate for our separate and complementary
spiritual quest."
-----------
Stephen Jay Gould: Darwin's more stately mansion.
(Science 25 Jun 99 284:2087)
QY: Stephen Jay Gould, Dept. of Zoology, Harvard University 617-
495-1000.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 9Jul99


2. ON SCANNING PROBE MICROSCOPY
The new technology of scanning probe microscopy has created a
revolution in microscopy, with applications ranging from
condensed matter physics to biology. The first scanning probe
microscope, the scanning tunneling microscope, was invented by G.
Binnig and H. Rohrer in the 1980s (they received the Nobel Prize
in Physics in 1986), and the invention has been the catalyst of a
technological revolution. Scanning probe microscopes have no
lenses. Instead, a "probe" tip is brought very close to the
specimen surface, and the interaction of the tip with the region
of the specimen immediately below it is measured. The type of
interaction measured essentially defines the type of scanning
probe microscopy. When the interaction measured is the force
between atoms at the end of the tip and atoms in the specimen,
the technique is called "atomic force microscopy". When the
*quantum mechanical tunneling current is measured, the technique
is called "scanning tunneling microscopy". These two techniques,
atomic force microscopy (AFM) and scanning tunneling microscopy
(STM) have been the parents of a variety of scanning probe
microscopy techniques investigating a number of physical
properties. ... ... A. Yazdani and C.M. Lieber (2 installations,
US) present a review of recent developments in scanning probe
microscopy, the authors making the following points:
     1) The invention and development of scanning probe
microscopy has taken the ability to image matter to the atomic
scale and opened fresh perspectives on everything from
semiconductors to biomolecules, and new methods are being devised
to modify and measure the microscopic landscape in order to
explore its physical, chemical, and biological features.
     2) In scanning tunneling microscopy, electrons quantum
mechanically "tunnel" between the tip and the surface of the
sample. This tunneling process is sensitive to any overlap
between the electronic wave functions of the tip and sample, and
depends exponentially on their separation. The scanning tunneling
microscope makes of this extreme sensitivity to distance. In
practice, the tip is scanned across the surface, while a feedback
circuit continuously adjusts the height of the tip above the
sample to maintain a constant tunneling current. The recorded
trajectory of the tip creates an image that maps the electronic
wave functions at the surface, revealing the atomic landscape in
fine detail.
     2) The most widely used scanning probe microscopy technique,
one which can operate in air and liquids, is atomic force
microscopy. In this technique, a tip is mounted at the end of a
soft cantilever that bends when the sample exerts a force on the
tip. By optically monitoring the cantilever motion it is possible
to detect extremely small chemical, electrostatic, or magnetic
forces which are only a fraction of those required to break a
single chemical bond or to change the direction of magnetization
of a small magnetic grain. Applications of atomic force
microscopy have included in vitro imaging of biological
processes.
     3) In general, the various techniques of scanning probe
microscopy have now been applied to high-resolution spectroscopy,
the probing of nanostructures, measurements of forces in
chemistry and biology, the production of deliberate movements of
small numbers of atoms, and the use of precision lithography as a
tool for making nanometric-sized electronic devices.
     4) The authors conclude: The scanning probe microscope has
evolved from a passive imaging tool into a sophisticated probe of
the nanometer scale. These advances point to exciting
opportunities in many areas of physics and biology, where
scanning probe microscopes can complement macroscopically
averaged measurement techniques and enable more direct
investigations. More importantly, these tools should inspire new
approaches to experiments in which controlled measurements of
individual molecules, molecular assemblies, and nanostructures
are possible."
-----------
A. Yazdani and C.M. Lieber: Up close and personal to atoms.
(Nature 16 Sep 99 401:227)
QY: Ali Yazdani [ayazdani@uiuc.edu]
-----------
Text Notes:

... ... *quantum mechanical tunneling current: In general,
quantum mechanical tunneling is a quantum mechanical phenomenon
involving an effective penetration of an energy barrier resulting
from the width of the barrier being less than the wavelength of
the particle.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
MEASUREMENT OF THE RUPTURE FORCE OF SINGLE COVALENT BONDS
From an elementary standpoint, what we call a "chemical bond" is
something that ties two or more atoms together to form a
molecular entity with sufficient stability for us to measure or
describe some of the entity's properties. The idea of the
chemical bond, including the notion of valence and the way we
draw the connections between atoms in a molecule, is usually
ascribed to Friedrich Kekule (1829-1896), but in fact it was
Edward Frankland (1825-1899) who first suggested the idea of
valence, and Archibald Couper (1831-1892) who first suggested the
depiction of the bond between 2 atoms by a dash. The use of
Couper's dashes to depict bonds was made popular by a chemist
well-known at the time for various discoveries in synthetic
chemistry, Richard Erlenmeyer (1825-1909). So today we have the
irony that Erlenmeyer is known primarily for the name of a glass
flask that he designed, Cooper and Frankland are hardly known at
all, and Kekule is often described to students as having
concocted these beginnings of structural chemistry in a dream.
Kekule may have indeed dreamt of the resonating benzene ring, but
his dream had the intimate help of his generation of chemists.
Putting aside the personal history of the concept of the chemical
bond, during its relatively short 150-year-old existence, this
concept has without any doubt been one of the most important
ideas in modern science. During this century, the focus has been
to understand the chemical bond in terms of quantum physics, but
certain classical aspects remain of great practical interest,
particularly the question of the relative strengths of the bonds
between different types of atoms. There are various ways to
approach this question of "bond strength", including actual
determinations of the mechanical force necessary to rupture
bonds. The mechanical stabilities of covalent bonds, bonds that
involve sharing of electrons, have in the past been investigated 
indirectly in ensemble measurements or by flow-induced chain
fracture in liquids. The recent development of nanoscale
manipulation techniques has made it possible to directly address
single atoms or molecules and probe their mechanical properties.
... ... M. Grandbois et al (5 authors at 3 installations, DE US)
now report a study of the rupture force of single covalent bonds
under an external load measured with an *atomic force microscope.
Single polysaccharide molecules were covalently anchored between
a surface and an atomic force microscope tip and then stretched
until the molecule became detached. The authors report that by
using different surface chemistries for the attachment, it was
found that the silicon-carbon bond ruptured at 2.0 +- 0.3
nanonewtons, whereas the sulfur-gold anchor ruptured at 1.4 +-
0.3 nanonewtons, at force-loading rates of 10 nanonewtons per
second. The authors report these results agree with bond rupture
probability calculations based on *density functional theory. The
authors conclude: "Although chemical compounds play a dominant
role in material sciences, the forces that chemical bonds can
withstand could previously not be directly measured in
experiments. The experiments reported here demonstrate that the
individual chemical bonds can be probed in mechanical
experiments. An important feature of such experiments is the
mechanical activation of chemical bonds (here in the simplest
form as bond rupture), which can now be studied on an individual
basis."
-----------
M. Grandbois: How strong is a chemical bond?
(Science 12 Mar 99 283:1727)
QY: Hermann E. Gaug, Lehrstuhl fur Angewandte Physik, Ludwig-
Maximillians-Universitat, Amalienstrasse 54, D-80799 Munich, DE.
-----------
Text Notes:
... ... *atomic force microscope: In general, in atomic force
microscopy, a tip is fixed to a cantilever whose position is
monitored while the tip scans a surface. The force between the
tip and the surface determines the position of the cantilever.
When recorded in atomic resolution, the image represents a map of
atomic forces at the surface. In the present study, the active
polymer molecule was first coupled to the substrate surface. The
tip was then slowly brought into contact with the surface,
allowing the polymer to bind to the tip (which occurred in
approximately 30 percent of the cases). The tip and the substrate
where then gradually separated while the force was recorded. The
polymer was repeatedly stretched and relaxed through one or more
conformational transitions. After analysis confirmed that a
single molecule was bound, the force was gradually increased
until the molecular bridge ruptured.
... ... *density functional theory: For atomic force calculations
on solids, the current method of choice is density functional
theory, due to Kohn, Hohenberg, and Sham. Its name comes from its
predicted connection between the total ground state electronic
energy of a system and the electronic charge density. The theory
was first proposed in 1964, and has since been useful as a
simplifying alternative to more rigorous but intractable many-
electron wavefunction calculations. In general, in density
functional theory, it is the electron density which is the
fundamental variable: the ground state of a system is defined by
that electron density distribution which minimizes the total
energy. In this approach, once the ground state electron density
is known, all other ground state properties (lattice constants,
cohesive energies, etc.) follow, at least in principle. In
mathematics, a "functional" is a function whose value depends on
the set of all values of another function. In density functional
theory, the ground state properties of a system are functionals
of the ground state electron density function.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 4Jun99
ON THE NANOSCALE SCIENCE OF SINGLE MOLECULES
In recent years, experiments on individual molecules using
scanning probe microscopies [*Note #1] have demonstrated a
diversity of physical, chemical, mechanical, and electronic
phenomena. These techniques have permitted deeper insight into
the quantum electronics of molecular systems and have provided
unique information about the conformational and mechanical
properties of these systems. Concomitant developments in
experimentation and theory have allowed a diverse range of
molecules to be studied, molecules varying in complexity from
simple diatomic systems to biological macromolecular systems.
... ... J.K. Gimzewski and C. Joachim (2 installations, CH FR)
present an extensive review of current single-molecule research,
the authors making the following points: 1) The very nature of
proximal probe methods encourages exploration of the nanoworld
beyond conventional microscopic imaging. Scanning probes now
allow us to perform "engineering" operations on single molecules,
atoms, and bonds, thereby providing a tool that operates at the
ultimate limits of fabrication. These techniques have also
enabled explorations of molecular properties on an individual
basis as opposed to explorations restricted to the statistical
properties of large populations of molecules. 2) The
nanomechanical properties of individual molecules take the form
of vibrations, rotations, conformational changes, and
translations. *Inelastic tunneling processes, probe-tip-induced
forces, and Brownian motion have been found to drive mechanical
responses in individual molecules, and these aspects are the
focus of current research. The important role of thermal noise at
room temperature in nanoscale systems suggests that future
technologies for building small energy-efficient devices will
need to use ambient temperature fluctuations rather than fight
against them. 3) Future developments in single-molecule nanoscale
science call for a close integration of chemistry, biology,
physics, and technology in terms of synthesis, theoretical
modeling, and advanced scanning probe microscope techniques.
Although scanning probe microscopy has been shown to be an
ultimate probe for investigating the properties of individual
molecules, it is still an open question whether these techniques
have the intrinsic capabilities to be useful fabrication tools in
technology. The recent development of massive micromechanical
arrays of thousands of scanning probe microscopy probes suggests
that such a possibility is becoming more real each day.
-----------
J.K. Gimzewski and C. Joachim: Nanoscale science of single
molecules using local probes.
(Science 12 Mar 99 283:1683)
QY: James K. Gimzewski [gim@zurich.ibm.com]
-----------
Text Notes:
... ... *Note #1: The general approach in scanning probe
microscopy research is illustrated by consideration of two major
techniques, scanning tunneling microscopy (STM) and atomic force
microscopy (AFM). In scanning tunneling microscopy, an atomically
sharp metal tip is brought in atomic proximity (e.g., 0.5 to 1
nanometer) to a flat surface so that electrons can *tunnel
between the two systems. The probe is slowly moved across the
surface and raised and lowered so as to keep the tunneling
current constant. A computer-generated contour map of the surface
is thus produced. The technique can resolve individual atoms, but
requires electrically conducting materials. In atomic force
microscopy, a tip is fixed to a cantilever whose position is
monitored while the tip scans the surface. The force between the
tip and the surface determines the position of the cantilever.
When recorded in atomic resolution, the image represents a map of
atomic forces at the surface. The advantage of atomic force
microscopy is that the probed surface does not need to be
electrically conducting.
... ... *tunnel: "Tunneling" is a quantum mechanical
phenomenon involving an effective penetration of an energy
barrier resulting from the width of the barrier being less than
the wavelength of the particle.
... ... *Inelastic tunneling processes: In general, an
"inelastic" process is a process which results in a permanent
change in the properties of a system. In this context, the term
"inelastic tunneling process" refers to a technique involving the
input of energy into a single-molecule system to selectively
excite chemical bonds or to perform spectroscopic studies of the
system.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21May99
-------------------
Related Background:
ON REACTIONS ON SEMICONDUCTOR SURFACES
Chemical reactions on surfaces are important in many areas of
science and technology. On metal surfaces, the electronic states
of the surface atoms are spatially extended and can therefore be
easily shared with those of reactive species, the result a
dramatic influence on the structure of these species as they
approach the surface. In contrast, bonding on semiconductor
surfaces is largely covalent, and surface electronic states tend
to be spatially localized. ... ... Harry E. Ruda (University of
Toronto, CA) presents a short review of current research
concerning reactions on semiconductor surfaces, the author making
the following points: 1) Understanding of the interactions of
species with semiconductor surfaces has been considerably
advanced by the widespread use of *scanning tunneling microscopy
(STM), which can probe, with atomic resolution, the spatial
extent of electron density on a surface. 2) Bias-dependent
scanning tunneling microscopy studies, in which images are taken
at different voltages between the STM tip and the sample, allow
the determination of the energy spectra of surface electronic
states, and in special cases enable discrimination between
different chemical species. 3) Coupled with computer modeling,
which can provide increasingly realistic descriptions of the
pertinent underlying physics, scanning tunneling microscopy
studies are providing  the information needed to understand and
control the interactions of chemical species on semiconductor
surfaces. The author concludes: "This research will have a
profound influence on nanotechnology, slated to become the
cornerstone of coming generations of semiconductor devices and
circuitry."
-----------
Harry E. Ruda: Reactions on semiconductor surfaces.
(Science 29 Jan 99 283:646)
QY: Harry E. Ruda [ruda@edf.utoronto.ca]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 9Apr99
[For more information: http://scienceweek.com/search/search.htm]


3. FERMI DEGENERACY IN A TRAPPED ATOMIC GAS
In quantum mechanics, electrons, protons, and neutrons have an
intrinsic angular momentum known as "spin", and a *magnetic
moment parallel or antiparallel to that angular momentum. When
electrons are combined together to form an atom or ion, there is
a resultant angular momentum which is a combination of the
intrinsic spin of the electrons and the angular momentum due to
their motion about the nucleus, and this is the "spin" of the
atom or ion. Atoms or ions with non-zero spin are magnetic atoms
or ions [*Note #1]. Elementary particle spin involves a virtual
rotation about the axis of the particle, which means only two
spin states are possible, one clockwise and one counterclockwise.
According to quantum theory, spin is quantized and restricted to
multiples of h/2ã, where (h) is the Planck constant. Only integer
or half-integer multiples are allowed. The multiple factor is the
"spin number" or "spin state": e.g., for spin number of + 1/2,
the actual spin is + 1/2 x h/2ã. Elementary particles (e.g.,
electrons, protons, neutrons) that have half-integer spin are
called fermions, and such particles obey the Pauli exclusion
principle: i.e., no two fermions of the same kind can occupy the
same quantum state in a system. Because of their quantized energy
constraints, fermions obey a special statistics (Fermi-Dirac
statistics). In general, an atomic or molecular system is said to
exhibit "quantum degeneracy" when the system has a number of
possible quantized states and two or more distinct states of the
set of possible states have the same energy. A "degenerate gas"
is a gas in which the concentration of particles is sufficiently
high for classical distribution statistics (Maxwell-Boltzmann
statistics) not to hold, with the behavior of the gas controlled
by quantum statistics (e.g., Fermi statistics). In a Fermi-Dirac
system, the "Fermi level" is the energy level at which there is
an 0.5 probability of finding an electron, and the "Fermi
temperature" is defined by T(subF) = E(subF)/k, where E(subF) is
the Fermi level energy and k is the Boltzmann constant. In
general, Fermi-Dirac systems (Fermi systems) are dense and
strongly interacting. Until now the only realization of a low-
density Fermi system has been a dilute solution of liquid
(sup3)He dissolved in superfluid (sup4)He.
... ... B. DeMarco and D.S. Jin (University of Colorado, US) now
report the creation of a nearly ideal Fermi gas composed of atoms
[(sup40)K] cooled to the regime where the effects of quantum
statistics can be observed. The authors used an evaporative
cooling strategy in which a two-component Fermi gas was used to
cool a magnetically trapped gas of 7 x 10^(5) (sup40)K atoms to
0.5 of the Fermi temperature. The authors report that in this
temperature regime quantum degeneracy was observed as a barrier
to evaporative cooling and as a modification of the
thermodynamics, and that measurements of the momentum
distribution and the total energy of the confined Fermi gas
directly revealed the quantum statistics. The authors conclude:
"Reaching this quantum regime in the dilute Fermi gas extends the
field of quantum degenerate gases and sets the stage for further
experimental probes of a Fermi sea of atoms."
-----------
B. DeMarco and D.S. Jin: Onset of Fermi degeneracy in a trapped
atomic gas.
(Science 10 Sep 99 285:1703)
QY: D.S. Jin [jin@jilau1.colorado.edu]
-----------
Text Notes:
... ... *magnetic moment: (magnetic dipole moment) The intrinsic
spins of the electrons in an atom, together with the motion of
the electrons around the nucleus, give rise to a magnetic field
around the atom, and the magnitude of this field is related to
the magnetic dipole moment of the atom or ion.
... ... *Note #1: The idea of electron spin was first proposed by
Goudsmit and Uhlenbeck in 1925 to explain the splitting of atomic
spectroscopic emission lines in the presence of a magnetic field.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
[For more information: http://scienceweek.com/search/search.htm]


4. ON PROSPECTS FOR GENE THERAPY IN UTERO
The term "gene therapy" refers to the treatment of disease by the
transfer and appropriate expression of an exogenous normal gene
into somatic cells of a patient, and gene therapy for the
treatment of disease in children and adults is being actively
pursued at many medical centers [*Note #1]. However, a number of
genetic disorders result in irreversible damage to the fetus
before birth. In these cases, as well as for those with genetic
diseases who may benefit from therapy before symptoms are
manifested, in utero gene therapy could be beneficial. Although
some successes with in utero gene transfer have been reported in
animals, significant questions remain to be answered before in
utero gene transfer would be an acceptable clinical procedure.
... ... E.D. Zanjani and W.F. Anderson (2 installations, US)
present a review of current research in this field, the authors
making the following points:
     1) In general, clinical success in gene therapy has been
limited by low efficiency of gene transfer into the appropriate
target cells and poor in vivo expression of the gene once
transferred. All of the more than 400 approved clinical gene
therapy protocols worldwide describe attempts to treat pediatric
and adult patients after birth.
     2) The rationale for human in utero gene therapy is that it
may allow the correction of some types of genetic diseases before
the appearance of any clinical manifestations. In addition, gene
transfer in the fetus offers a number of potential advantages
over postnatal gene transfer, since gene transfer in the fetus is
apparently more efficient than in the mature organism, so that
gene therapy should be easier to accomplish prenatally than
postnatally.
     3) Long-term persistence and expression of vector-encoded
genes after in utero transfer in small and large animal studies
have provided evidence that in utero gene therapy might present a
viable approach for the treatment of genetic disorders. Two in
utero gene therapy approaches have been evaluated in small and
large animals: a) gene-engineered cell transfer has been examined
in sheep and monkeys, and b) direct injection of vector into the
fetus has been studied in rodents and sheep.
     4) At the present time, it is not clear which genetic
diseases would be the best initial candidates for in utero gene
therapy. As a minimum, the disease should be life-threatening or
cause significant disability either during gestation or in early
infancy. Also, based on the pathophysiology of the disease, it
should be probable that treatment in utero would be both
beneficial and free of significant risks to the fetus or the
mother.
     5) The primary question is whether in utero gene therapy can
successfully treat a disease. Several factors are involved: a)
Can enough genes be transferred into the appropriate target cells
by any approach? b) Will expression of the transferred gene be at
the correct level, and for an adequate duration, and will it be
regulated appropriately for the disease treated? c) Will the gene
product be eliminated by the immune system or by some other
mechanism?
     6) In summary, the authors suggest that in utero gene
therapy approach is promising not only for the treatment of
genetic diseases that produce fetal damage before birth, but also
as an additional treatment procedure that may offer advantages
over postnatal therapy. However, despite the existence of
encouraging data in small and large animals, the question remains
whether an in utero gene therapy protocol can be developed that
will provide sufficient gene transfer in vivo to be effective in
the treatment of a genetic disease. Once questions concerning the
appropriate disease, the gene delivery procedure, efficacy,
safety, and germ-line transmission are resolved by further animal
experiments, then it would be appropriate to conduct human
clinical trials of in utero gene therapy procedures.
-----------
E.D. Zanjani and W.F. Anderson: Prospects for in utero human gene
therapy.
(Science 24 Sep 99 285:2084)
QY: E.D. Zanjani [zanjani@scs.unr.edu]
-----------
Text Notes:
... ... *Note #1: Essential in this context are the following
considerations: 1) Once genetic material in the form of a piece
of DNA gets into a cell, it will usually be taken up by the cell
nucleus and incorporated into the cell genome. 2) When this
happens, the new genetic material (new gene or genes) can be
"expressed", i.e., result in the production of a specific protein
or proteins. 3) One problem is how to achieve delivery of genetic
material to the cell. The delivery vehicle is called a "vector",
and certain natural or engineered non-pathogenic viruses are good
candidates for a vector, if the virus possesses those viral
attributes that allow viruses to penetrate cells and deliver
their genetic material to the genome of the cell. What is done is
to splice the delivered gene (or its RNA precursor in an RNA
virus) into the viral genome, so that when the virus penetrates
the cell, the genetic material directly or ultimately delivered
to the cell contains the corrective genetic material that one
desires to be incorporated into the cell genome for therapeutic
purposes. Non-viral vectors are also possible, for example
laboratory-created vesicles (liposomes) carrying DNA material and
which are taken up by cells by translocation through the cell
membrane. 4) Another important problem concerns "regulation" of
the new gene or genes once incorporated into the cell genome. In
a living cell, the various steps involved in the production of a
specific protein based on the code carried by a specific gene are
regulated by other genes. What this means is that the mere
incorporation of new genetic material into a genome is not enough
to ensure a desired therapeutic consequence: the new genetic
material (and the synthesis of its protein) must be appropriately
regulated if the outcome is to be clinically useful.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON GENE THERAPY
At the present time, more than 200 clinical trials of gene
therapy are apparently in place worldwide, with hundreds of
patients enrolled, but there is still not a single case of gene
therapy that can be called an unequivocal success. The major
problem is evidently gene delivery, getting the therapeutic gene
or genes or bits of DNA into cells in a way such that the new
genetic materials will be allowed to express their proteins in an
enduring cellular environment. There are basically two methods
for gene delivery, viral and non-viral, and neither method has
yet proved satisfactory. Success with either method, absent some
serendipitous laboratory or clinical discovery, will most likely
depend on further basic research. ... ... Eric B. Kmiec (Thomas
Jefferson University, US) presents a review of current
difficulties in gene therapy strategies, the author making the
following points:
     1) Most of the gene therapy techniques developed so far are
of the gene-addition variety, an attempt to provide a good copy
of a gene to cells that harbor bad copies of the gene. To date,
the results of clinical trials involving these techniques have
been disappointing. Even the most successful clinical trials has
fallen short of therapeutic efficacy.
     2) Many of these clinical trials may have been conducted
before the technology was fully mature, driven in part by
investor demands on biotechnology companies to rush products to
market. Such clinical trials were almost certainly destined to
fall short of the mark.
     3) Making gene therapy a successful endeavor will require
careful research to understand why traditional approaches have
not produced the hoped for results and, in turn, to improve them,
while exploring new ways to deal with genetic defects.
     4) In spite of increased government scrutiny of previous
gene-therapy protocols, the pressures to bring gene therapy to
the clinic do not seem to abate. This is in part because of the
formation of ventures aimed at commercializing products and
techniques. Financial pressures and constraints often force
biotechnology companies to forgo basic research in favor of
application-driven development. Unfortunately, the result is that
promising but technically difficult approaches may never be
adequately developed for lack of research funding.
     5) Increases in public funds for research may be part of the
answer to improving the technology. What is clearly needed is the
development of molecular analysis and rigorous testing at the
level of basic science, with an eye towards application in
clinically appropriate targets. Only then will gene therapy have
a hope of fulfilling its promise.
     6) The author suggests that pronouncements of gene therapy's
imminent demise are as premature as were the overly optimistic
pronouncements of its imminent success. At its core, the notion
of gene therapy or gene correction is scientifically sound and
commitment to programs of research must be maintained.
-----------
Eric B. Kmiec: Gene therapy.
(American Scientist May/Jun 1999 87:240)
QY: Eric B. Kmiec [kmiec@lac.jci.tju.edu]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 25Jun99
-------------------
Related Background:
ON HUMAN GENE THERAPY
... W. Anderson (University of Southern California, US) reviews
the status of the field and the difficulties that have delayed
advances, the author making the following points: 1) Gene therapy
is a powerful new technology that will require several years
before it will make a noticeable impact on the treatment of
disease. 2) Several major problems still exist, including poor
delivery systems, both viral and non-viral, and poor gene
expression after genes are delivered. 3) The reason for the low
efficiency of gene transfer and expression in human patients is
that we still lack a basic understanding of how vectors should be
constructed, what regulatory sequences are appropriate for which
cell types, how in vivo immune defenses can be overcome, and how
to manufacture efficiently the vectors that we do make. 4)
Although it not surprising that we have not yet had notable
clinical successes, the lessons we are learning in the clinic are
invaluable in illuminating the problems that future research must
solve. 5) Despite our present lack of knowledge, gene therapy
will almost certainly revolutionize the practice of medicine over
the next 25 years. In every field of medicine, the ability to
give the patient therapeutic genes offers extraordinary
opportunities to treat, cure, and ultimately prevent a vast range
of diseases that now plague mankind.
QY: W. French Anderson, Univ. of Southern California 213-740-2311
(Nature 30 Apr 98 392/supp:25) (Science-Week 29 May 98)
[For more information: http://scienceweek.com/search/search.htm]


5. ACTIVITY-INDUCED POTENTIATION OF DEVELOPING SYNAPSES
In general, the nervous system of an animal consists of a large
number of active entities (neurons) receiving input from a
variety of sensory cells, the active entities integrating and
performing various operations on this input via interactions
between the entities, and the entities ultimately producing an
output that controls groups of "effector cells" (e.g., muscle
cells). Of critical importance in this scheme are the junctions
between neurons, between receptor cells and neurons, and between
neurons and effector cells, the so-called "synapses". For many
decades now, the consensus view among neurobiologists has been
that the psychological functions that we call "learning and
memory" are somehow dependent on short-term or long-term changes
in these synapses, but progress in elucidating precisely what is
occurring at synapses that relates to learning and memory has
been difficult and frustrating. At the present time, two key
experimental concepts at the cellular level in this field are
"long-term potentiation" (LTP) and "long-term depression" (LTD). 
Long-term potentiation is an experimentally observed persistent
strengthening (facilitation of activity) of synapses based on
past patterns of activity, the strengthening lasting hours or
days or weeks. Long-term depression is the converse, a persistent
weakening (damping of activity) of synapses based on past
patterns of activity, the weakening also lasting hours or days or
weeks. These are experimentally observed phenomena in a wide
variety of nervous systems, both relatively simple and complex,
and the central questions are what are the cellular controls, the
molecular controls, and the relevance of these phenomena to
learning and memory behaviors?
... ... J. Wan and M. Poo (University of California San Diego,
US) now report that in African clawed toad (Xenopus) nerve-muscle
cultures, a brief burst of *action potentials in the presynaptic
neuron induced a persistent potentiation of neuromuscular
synapses that exhibit immature synaptic functions. Until now,
long-term potentiation has not been reported in any neuromuscular
system, although long-term depression in such systems is well
known. In the experiments of the authors, induction of
potentiation required an elevation of *postsynaptic calcium ion
concentration and expression of potentiation appeared to involve
an increased probability of *transmitter secretion from the
*presynaptic terminal. The authors suggest that activity-
dependent persistent synaptic enhancement may reflect properties
characteristic of immature synaptic connections, and that
bursting activity in developing spinal neurons may promote
functional maturation of the neuromuscular synapse.
-----------
J. Wan and M. Poo: Activity-induced potentiation of developing
neuromuscular synapses.
(Science 10 Sep 99 285:1725)
QY: Mu-ming Poo [mpoo@ucsd.edu]
-----------
Text Notes:
... ... *action potentials: (nerve impulses) In general,
transient pulses (e.g., 1 millisecond) of reversed membrane
potential propagated over the long extensions of neurons (axons),
in some cases over relatively large distances (e.g., 1 meter
between spinal motorneurons and peripheral muscle cells). The
physical characteristics of the action potentials in the nervous
systems of diverse animal forms are often quite similar. Also
often similar across diverse animal forms are events at various
synapses. The nervous system of the African clawed toad (Xenopus
laevis) has been a common laboratory model in neurophysiology for
the past half century.
... ... *postsynaptic: Considering a 2-unit junction (synapse)
between two cellular entities, entity A transmitting activity to
entity B, events on the entity-B side of the junction are called
"postsynaptic", and events on the entity-A side of the junction
are called "presynaptic".
... ... *transmitter secretion: (neurotransmitter secretion)
Neurotransmitters are chemical substances released at the
terminals of nerve axons in response to the propagation of an
impulse (action potential) to the end of that axon. The
neurotransmitter substance diffuses into the synapse, the
junction between the presynaptic nerve ending and the
postsynaptic neuron, and at the membrane of the postsynaptic
neuron the transmitter substance interacts with a receptor.
Depending on the type of receptor, the result may be an
excitatory or an inhibitory effect on the postsynaptic nerve
cell.
... ... *presynaptic terminal: See above: *postsynaptic.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
TARGET-SPECIFIC PRESYNAPTIC PLASTICITY IN NEURONS
The term "mossy fibers" refers to a type of nerve fiber in the
brain with large axon terminal endings, and their synapses
(connections to other nerve cells) are among the largest in the
mammalian central nervous system. The term "synaptic
transmission" refers to the transmission of electrical activity
from one nerve cell to another via the synapse -- the connection
between them. The hippocampus is a deep region of the brain
involved with many fundamental activities, including memory
storage. The term "interneurons" refers to nerve cells localized
in a succinct region (population of nerve cells), with the
primary function of these nerve cells an involvement with
information processing in the region, rather than with input to
the region or output from the region: interneurons are therefore
involved in "local circuitry". "Rat brain slices" are exactly
that, the rat brain removed from the animal and a thin slice of a
particular region prepared in an appropriate solution for
electrophysiological recording of nerve cell activity. The term
"tetanic stimulation" refers to repetitive stimulation.
"Long-term potentiation" is an apparent facilitation of synaptic
transmission following repetitive stimulation under certain
conditions. In this context, the term "depression" refers to a
long-term reduction in efficacy of synaptic transmission. Cyclic
adenosine monophosphate (cAMP) is an important postsynaptic
intracellular substance activated by incoming synaptic activity,
a "messenger" involved in various aspects of cell regulation and
protein synthesis. In general, the term "afferent pathway" refers
to any input pathway, as opposed to an output pathway (efferent).
... ... Maccaferri et al (3 authors at National Institutes of
Health, US) report a comparison of mossy fiber synaptic
transmission at hippocampal pyramidal cells and interneurons in
rat brain slices, finding that tetanic stimulation of mossy
fibers induces long-term potentiation in pyramidal neurons, but
is either without effect or induces depression at synapses with
interneurons. Furthermore, unlike transmission onto pyramidal
neurons, transmission onto interneurons was not potentiated after
cAMP activation. The authors suggest their results indicate that
synaptic terminals arising from a common afferent pathway do not
behave as a single computational unit, but are functionally
specialized with effects depending on the postsynaptic target.
QY: Chris J. McBain [crismcb@codon.nih.gov]
(Science 27 Feb 98) (Science-Week 13 Mar 98)
-------------------
Related Background:
A NEW TYPE OF SYNAPTIC PLASTICITY OF NEOCORTICAL NEURONS
The term "synaptic plasticity" refers to a changeability of
synaptic connections and/or the efficacy of particular connect-
ions. "Cultured neurons" are embryological neurons separated from
the animal and growing and making connections in a suitable
experimental chamber. Glutamate is a major excitatory amino acid
neurotransmitter (transmitter substance at synapses) in the
brain, involved in about 40% of all brain activity. The term
"Hebbian modification" (named after the neuropsychologist Donald
Hebb) refers to the Hebbian "rule" that essentially states that
when one nerve cell repeatedly activates another nerve cell,
changes involving growth or metabolism occur in one or both nerve
cells that increase the efficiency of the activation.
... ... Turrigiano et al (5 authors at Brandeis University, US)
report a new form of synaptic plasticity in cultured neurons that
increases or decreases the strength of all of a neuron's synaptic
inputs as a function of activity, the changes partly due to
postsynaptic alterations in the response to glutamate. The
authors suggest that such "synaptic scaling" may help prevent
saturation of firing rates during developmental changes in the
number and strength of synaptic inputs, may stabilize synaptic
strengths during Hebbian modification, and may facilitate
competition between synapses and associated elimination of
synapses during development.
QY: Gina G. Turrigiano [turrigiano@binah.cc.brandeis.edu]
(Nature 26 Feb 98) (Science-Week 13 Mar 98)
-------------------
Related Background:
POSTSYNAPTIC MEMBRANE FUSION AND LONG-TERM POTENTIATION
The anatomical connections between nerve cells are called
"synapses", and in mammalian nervous systems the most important
type of connection involves the axon terminals of one neuron
(presynaptic endings) terminating on various parts of the second
neuron (postsynaptic loci). In general, electrical activity of
the first neuron causes secretion of a "neurotransmitter"
substance at its presynaptic terminals, and this neurotransmitter
may excite or inhibit the electrical activity of the second
neuron, the effect often mediated by inputs to the second neuron
from hundreds of other neurons. Prior to its release, the neuro-
transmitter substance is contained in vesicles in the presynaptic
terminals, and one of the significant events associated with
release of the neurotransmitter substance is the fusion of the
vesicle with the presynaptic membrane -- a "membrane" fusion,
since the shell of the vesicle itself is also a bilayer membrane.
In general, long-lasting enhancement of the postsynaptic response
of a neuron as a result of repetitive incoming synaptic activity
is called "long-term potentiation", and there are many varieties
of this phenomenon observed in different kinds of nerve cells,
and it is considered an example of synaptic plasticity. Since
long-term potentiation involves the behavior of a neuron relating
to its past history, the phenomenon is naturally of great
interest to neurobiologists seeking to understand neuronal
information storage. ... ... Lledo et al (5 authors at 2
installations, US) report that introducing substances that block
membrane fusion into the postsynaptic cell reduces long term
potentiation. Introducing a protein (SNAP) that promotes membrane
fusion enhances synaptic transmission, but at a reduced level in
already potentiated synapses. The authors suggest that fusion
events, in addition to being important for the presynaptic
release of neurotransmitters, are also involved in some mechanism
at the postsynaptic membrane, and thus contribute to long term
potentiation.
QY: Roger A. Nicoll [nicoll@phy.ucsf.edu]
(Science 16 Jan 98) (Science-Week 30 Jan 98)
[For more information: http://scienceweek.com/search/search.htm]


6. IMPLICATIONS OF ANTIBIOTIC RESISTANCE IN WILD RODENTS
During this century, the use of antibiotics profoundly changed
the face of clinical medicine and saved many thousands of lives
worldwide. A variety of infections that were considered dangerous
during the early decades of the century, when antibiotics were
unknown, are now routinely and successfully treated by various
antibiotics or "antimicrobial" agents [*Note #1]. In general, the
term "antibiotic" refers to a chemical substance, produced by one
kind of microorganism, which has the capacity in low
concentrations to inhibit the growth of or to destroy
microorganisms of another kind. The first antibiotic to receive
widespread attention was penicillin, which was developed to meet
the need for an effective anti-infectious agent during World War
II. Penicillin and certain other classes of antibiotics are
secreted by strains of various molds, but in recent decades
pharmaceutical chemical synthesis has produced a wide variety of
substances with antibiotic action, and the availability of
antibiotics is no longer completely dependent on natural sources.
That progress, however, has been tempered by the appearance of a
potentially serious problem -- the evolution, presumably by
conventional evolutionary selection pressures, of pathological
bacterial strains resistant to antibiotics currently in use. For
some time, the consensus view concerning microbial resistance to
antibiotics has been that the clinical overuse of antibiotics is
the cause of the problem, and that a reduction in antibiotic
usage will reduce or even reverse such resistance. Unfortunately,
as the present report and other reports indicate, the problem may
be more intractable than expected. ... ... M.A. Gilliver et al
(University of Liverpool, UK) now report that antibiotic
resistance is prevalent in populations of wild rodents that have
not been exposed to antibiotics, indicating that approaches to
control of resistance based on the over-use assumption may be
overly optimistic. The study reported by the authors involved a
survey of *commensal enteric Enterobacteriaceae isolated from two
wild populations of small rodents (bank voles and wood mice). The
antibiotics whose effectiveness was examined were tetracycline,
trimethoprim, naladixic acid, chloramphenicol,
amoxycillin/clavulanic acid, amoxycillin, and cefuroxime. The
authors suggest their results indicate that resistance to
antibiotics is widespread in at least some wild populations, even
though these populations have never to their knowledge been
exposed to antibiotics, and that these results undermine the
presumption that resistance will decline in the absence of
antibiotic treatment. The authors suggest that the origin of the
resistance and the selection mechanisms ("if indeed such
mechanisms are necessary") responsible for maintaining a high
prevalence of resistance are unknown. Finally, the authors
suggest that "it is important to address these questions, not
least because similar mechanisms may operate in farm animals and
humans, in which case the management of antibiotic resistance may
need to be reconsidered."
-----------
M.A. Gilliver et al: Antibiotic resistance found in wild rodents.
(Nature 16 Sep 99 401:233)
QY: C. Anthony Hart [c.a.hart@liverpool.ac.uk]
-----------
Text Notes:
... ... *Note #1: In general, biologists recognize a variety of
categories of "microbes" (microorganisms): e.g., yeasts, molds
(fungi), streptomycetes, protozoa, bacteria, rickettsiae,
viruses, etc. A large proportion of the infectious diseases of
animals and humans is caused by 3 of these groups: bacteria,
rickettsiae, and viruses. Antibiotics are most effective against
bacteria and rickettsiae, and with no direct effect on viruses.
"Streptomycetes" (Streptomycetaceae; actinobacteria) is a family
of oxygen-utilizing (aerobic) bacteria that form chains or
filaments with occasional branches, the form giving the
appearance of microscopic fungi. They mostly live in soil, and
they are responsible for several types of human infections. Some
species produce antibiotics. "Rickettsiae" are a type of small
bacteria that usually occur in the cytoplasm of cells of lice,
fleas, ticks, and mites. Some species of rickettsiae are
parasitic in humans, causing epidemic typhus, murine typhus,
Rocky Mountain spotted fever, and other diseases.
... ... *commensal enteric Enterobacteriaceae: In general, the
term "commensal" refers to a symbiotic relationship in which one
species derives benefit and the other is unharmed. The term
"enteric" means relating to the intestine. The term "enteric
Enterobacteriaceae", in this context, refers to a type of
bacteria that occurs in the intestines and feces of man and
animals. The so-called "type genus" of the large family
Enterobacteriaceae is the familiar species Escherichia coli, a
common inhabitant of the human intestinal tract, with most
varieties of E. coli commensal in the intestinal tract. [Note:
Certain varieties of E. coli which are not pathogenic in the
intestine can be virulently pathogenic in other tissues of the
body. Conversely, there are varieties of E. coli which are
usually pathogenic _inside_ the intestinal tract and cause
serious diseases (e.g., various diarrheal diseases). The notion
that E. coli is a harmless human symbiont is inexact.]
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 29Oct99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
EMERGENCE OF VANCOMYCIN RESISTANCE IN STAPHYLOCOCCUS AUREUS
The bacterial genus Staphylococcus has at least 30 different
species. The organisms are spherical cells approximately 1 micron
in diameter. They are nonmotile, they do not form *spores, and
they are ordinarily destroyed by *penicillin. One of the
staphylococcus species of clinical importance in humans is
Staphylococcus aureus, which is a major pathogen. The other two
staphylococcus species of clinical importance are *S. epidermidis
and *S. saprophyticus. S. aureus produces the enzyme coagulase,
which clots oxalated or citrated plasma, and the "coagulase test"
is a common test to differentiate S. aureus from other
staphylococcal infections: S. aureus is "coagulase-positive".
Almost every person will have some type of S. aureus infection
during a lifetime, ranging in severity from food poisoning or
minor skin infections to severe life-threatening infections. S.
aureus is one of the most common causes of community-acquired
infections and infections acquired in hospitals (*nosocomial
infections). S. aureus is also the most common cause of surgical
wound infections, and a major cause of nosocomial bloodstream
infection. After the initial success of penicillin in treating S.
aureus infections during and immediately after World War II,
bacterial resistance to penicillin began to emerge, and at the
present time, 70 to 80 percent of S. aureus isolates are
resistant to this antibiotic. *Methicillin and other
semisynthetic penicillins were successful in treating penicillin-
resistant S. aureus infections until the 1980s, when methicillin-
resistant S. aureus became *endemic in many hospitals. Since the
emergence of methicillin-resistant S. aureus, the *glycopeptide
vancomycin has been the only uniformly effective treatment for
staphylococcal infections. The recent emergence of glycopeptide
resistance in coagulase-negative staphylococci has heightened
concern about whether S. aureus could acquire glycopeptide
resistance. In May 1996, the world's first documented clinical
infection due to S. aureus with intermediate resistance to
glycopeptides (denoted as "glycopeptide-intermediate S. aureus")
was diagnosed in a patient in Japan [*Note #1].
... ... T.L. Smith et al (11 authors at 3 installations, US) now
report the first documented glycopeptide-intermediate S. aureus
infections in the US, two cases at two different installations in
Michigan and New Jersey. The authors conclude: "The emergence of
S. aureus with intermediate glycopeptide resistance threatens to
return us to the era before the development of antibiotics. To
prevent further emergence of S. aureus strains with intermediate
glycopeptide resistance, and the emergence of S. aureus with full
vancomycin resistance, the use of vancomycin must be optimized,
laboratory methods for the detection of resistant pathogens must
be enhanced, and infection-control precautions must be strictly
followed for infected or colonized patients."
-----------
Editor's note: In addition to the background material below, see
the SW Focus Report "Microbial Drug Resistance" available at URL
http://scienceweek.com/swfr013.htm
-----------
T.L. Smith et al: Emergence of vancomycin resistance in
Staphylococcus aureus.
(New England J. Med. 18 Feb 99 340:493)
QY: Michele L. Pearson, Hospital Infections Program, Centers for
Disease Control and Prevention, Atlanta, GA 30333 US.
-----------
Text Notes:
... ... *spores: Certain types of bacteria form spores,
specialized structures that may allow survival in extreme
environments and facilitate dissemination. The spore remains
dormant, nonreplicating, until appropriate environmental
conditions cause a transformation back to a viable replicating
organism.
... ... *penicillin: (penicillins) The penicillin antibiotics are
derived from molds of the genus Penicillium and obtained by
extraction of submerged cultures grown in special media. The most
widely used natural penicillin is Penicillin G. In general, with
6-aminopenicillanic acid as the fundamental chemical entity, an
almost unlimited variety of penicillin compounds can be
synthesized by coupling different radical carboxyl groups to the
free amino group.
... ... *S. epidermidis: This species of staphylococcus is the
primary cause of infections due to implanted appliances and
devices.
... ... *S. saprophyticus: This species of staphylococcus is a
relatively common cause of urinary tract infections in young
women.
... ... *nosocomial infections: In general, a nosocomial
infection is any infection acquired by a patient as a result of
entrance into a hospital. It is estimated that some 15 to 20
percent of all hospital workers carry S. aureus on the skin of
their hands, and that 60 to 70 percent of all hospital workers
carry S. aureus in their nostrils.
... ... *Methicillin: A "semisynthetic" penicillin antibiotic
(i.e., the basic penicillin structure is derived from the mold
Penicillium). It is less potent than Penicillin G.
... ... *endemic: (enzootic) An "endemic" disease is a disease
that prevails continually in a region, as opposed to an
"epidemic" disease, which is a disease with a relatively abrupt
sporadic outbreak.
... ... *glycopeptide: Any compound containing sugar(s) linked to
amino acids (or peptides), with the peptides preponderant. Such
compounds are an important component of bacterial cell walls.
The glycopeptide vancomycin, which is markedly bactericidal for
staphylococci, has a molecular weight of 1450 and is produced by
the bacterium Streptomyces orientalis.
... ... *Note #1: There are a number of different mechanisms that
can be evolved by microorganisms to cause resistance to drugs: 1)
Production of enzymes that destroy the active drug. 2) A change
in cell wall and/or membrane permeability to the drug. 3)
Development of an altered structured target for the drug. 4)
Development of an altered metabolic pathway that bypasses the
reaction inhibited by the drug. 5) Development of an altered
enzyme that can still perform its metabolic function but is much
less affected by the drug. Staphylococci resistant to Penicillin
G produce an enzyme (a beta-lactamase) that destroys the
antibiotic.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21May99
-------------------
Related Background:
ON THE RESISTANCE OF BACTERIA TO ANTIBIOTICS
S. Levy (Tufts University, US), in a review of recent
developments in antibiotic resistance, notes that strains of at
least 3 pathogenic bacterial species -- Enterococcus faecalis,
Mycobacterium tuberculosis, Pseudomonas aeruginosa -- have
already developed resistance to every one of the 100 antibiotic
drugs in use by clinicians. Levy says a change in attitudes of
the public and clinicians concerning the overuse of antibiotics
is badly needed, and that a reversal of increasing bacterial
resistance to antibiotics, as well as increasing resistance of
parasites, fungi, and viruses to antimicrobials and antivirals,
will require a new global awareness of the broad consequences of
anti-pathogen drug usage.
QY: Stuart B. Levy, Tufts Univ. School of Medicine 617-636-6571
(Scientific American March 1998) (Science-Week 20 Feb 98)
-------------------
Related Background:
STUDIES SHOW MARKED INCREASE IN DRUG RESISTANCE OF MICROBES
Widespread use of antibiotics continues to force the evolution of
strains of pathogens resistant to the drugs. For example, the
incidence in the U.S. of microbes resistant to penicillin has
increased fourfold since 1994. At the May 19th International
Conference of the American Lung Association and American Thoracic
Society in San Francisco, researchers from the State University
of New York (Buffalo NY US) and the University of Iowa College of
Medicine (Iowa City IA US) found the increase in resistance of
Streptococcus pneumoniae, a common cause of respiratory
infections, to be dramatic. 10.5% of the samples were highly
resistant to antibiotics and 24.9% moderately resistant. In 1994,
those figures stood at only 3.2% and 14.1%, respectively. In the
Southeastern part of the U.S., 41% of the samples were found to
be resistant. The researchers suggest that the medical community
must be on the watch for rapidly developing epidemics caused by
antibiotic resistant strains of pathogens, and that antibiotics
themselves should be administered only when necessary if we are
to slow down the evolution of these resistant microbes.
(UPI 19 May 97) (Science-Week 22 May 97)
-------------------
Related Background:
APPEARANCE OF A STAPHYLOCOCCUS STRAIN RESISTANT TO VANCOMYCIN
Staphylococcus aureus is a common pathogenic bacterium in
hospitals, and causes thousands of often fatal infections each
year. Vancomycin is an antibiotic of last resort, which is used
when all other antibiotics fail. Now the first case has appeared
in Japan of a 4 year old boy infected with a strain of
Staphylococcus aureus resistant to vancomycin. Health experts
say it is only a matter of time before the pathogen reaches U.S.
hospitals. Fred Tenover, laboratory chief of the U.S. Center for
Disease Control Hospital Infections Branch says, "The strain is
marching up the ladder of resistance... It is not a cause for
panic, but it is a cause for concern."
(UPI 28 May 97) (Science-Week 29 May 97)
-------------------
Related Background:
REDUCED ANTIBIOTIC USAGE LOWERS BACTERIAL RESISTANCE
To understand the mechanism of the worldwide increase in
bacterial resistance to antibiotics one need only consider that
for all biological organisms most chemical aspects are more or
less displayed as a Gaussian distribution, the so-called "normal"
or "bell-shaped" curve. What this means in the context of
applying an antibiotic to a population of a particular bacterial
species is that something like 10% or 15% of the population will
show much lower than average resistance to the drug, about 60%
will have close to the average resistance to the drug, and about
10% to 15% will show above average resistance to the drug, all
because of the way the chemistry responsible for resistance to
the drug is distributed in the population. These numbers are
variable from one species of bacteria to another, and they also
vary with the antibiotic used, but the general idea is the same.
The result of all of this is that if we use an antibiotic against
a specific bacterial population, those members of the population
that have superior resistance to the antibiotic will survive to
reproduce their genome, most of the others will be killed, and
before long we will have on our hands populations of that species
which are more or less totally resistant to the antibiotic. This
is nothing more than a concrete instance of the idea of
"selection pressure" in evolution. In 1946 about 90% of
Staphylococcus aureus (a common and dangerous pathogen bacterium)
in hospitals were killed by the antibiotic penicillin, which
first became widely available at about that time. By only 6 years
later, 75% of S. aureus caught and cultured in hospitals were
resistant to penicillin, and by the 1970s, 90% of S. aureus,
whether in hospitals or in the community, were resistant to the
drug. There are similar stories concerning other bacterial
species and other drugs, the worst scenarios evidently occurring
in hospitals; but one cannot fault hospitals, because in both
hospitals and the community antibiotics have been routinely
needlessly administered and/or over-administered, with a
consequent selection pressure that produces antibiotic-resistant
pathogens. Can the process be reversed? There may still be some
hope against bacterial species which are not already
overwhelmingly resistant. This week Helena Seppala et al (about
100 authors in FI) report that in Finland, after an organized
nationwide reduction in the use of macrolide antibiotics
(macrolides are large-ring molecules with many functional side
groups) for outpatient therapy, the resistance of group A
streptococci to the common antibiotic erythromycin dropped by
half from 16.5 per cent in 1992 to 8.5 per cent in 1996. In an
editorial in the New England Journal of Medicine, Morton N.
Swartz (Massachusetts General Hospital, Boston US) calls this "an
impressive example of how an enlightened national policy on
antibiotic use can become an effective public health measure."
QY: H. S. Seppala, Antimicrobial Research Laboratory, PO Box 57,
20521 Turku, FI.
(New England J. Med. 14 Aug 97) (Science-Week 15 Aug 97)
-------------------
NEW MULTI-DRUG RESISTANCE OF PLAGUE PATHOGEN
Plague, also called bubonic plague or "Black Death", is a disease
with a notorious history. It is caused by the bacillus Yersinia
pestis, which infects wild rodents. The bubonic variant of the
disease is transmitted to humans from rodents by the bite of an
infected flea. Human to human transmission occurs by inhalation
of respiratory droplets spread by the cough of patients with
plague who have developed pulmonary lesions, and the result of
this is "primary pneumonic plague", which differs from "bubonic
plague" in that bubonic plague affects the lymph nodes, among
other tissues (producing "buboes", lymph node swellings). The
last plague pandemic began in Hong Kong in 1894 and spread
throughout the world. Plague still exists as an endemic disease
in many parts of the world, including the southwestern U.S.
Prevention of plague is based on rodent control, and the use of
insect repellents to minimize flea bites. Early treatment after
infection with the antibiotics streptomycin, chloramphenicol, or
tetracycline reduces mortality to less than 5%. Nevertheless,
plague is now considered a reemerging disease, with recent
epidemics in a number of countries after an absence of as much as
3 decades. The incidence of the disease has also been spreading
in the U.S. Now Marc Galimand et al (World Health Organization
and the Pasteur Institute, FR) report high-level resistance of Y.
pestis in a clinical isolate in Madagascar to multiple
antibiotics, including resistance to all the drugs recommended
for plague prophylaxis and therapy. The resistant genes are
apparently carried by a plasmid that can conjugate to other Y.
pestis isolates. So this pathogen species, heretofore considered
universally susceptible to antibiotics, is now exhibiting high
and spreadable resistance to these drugs. Epidemiologists are
alarmed and are urging an international effort to deal with the
problem.
QY: Elisabeth Carniel, Institut Pasteur, 28 rue du Dr.
Roux, 75724 Paris CEDEX 15, FR.
(New England J. Med. 4 Sep 97) (Science-Week 12 Sep 97)
-------------------
APPARENT IRREVERSIBILITY OF BACTERIAL ANTIBIOTIC RESISTANCE
At a recent meeting of the European Society for Evolutionary
Biology (Arnhem NL), several research groups have apparently
independently confirmed the unhappy news that bacteria that have
mutated to exhibit resistance to specific antibiotics do not
evolve susceptible strains when they are no longer exposed to
these antibiotics. Bruce Levin and Bassam Tomah (Emory
University, US) report that 25% of bacteria sampled from infant
diapers are strains of E. coli still resistant to the antibiotic
streptomycin, which has been rarely used during the past 30
years. Richard Lenski (Michigan State University, US) has
independently shown that after 20,000 generations in the absence
of streptomycin, E. coli still carries the gene that confers
resistance to the antibiotic. The consensus is apparently that a
compensatory mutation has occurred, a mutation that compensates
for the loss of fitness produced by the gene that confers
antibiotic resistance, and which results in long-term survival of
the resistant strain. Levin suggests the same kind of
compensatory mutations "will almost certainly be found in other
resistant bacteria." The implication is that the evolutionary
development of bacterial resistance to antibiotics will not be
reversed by reducing the use of these antibiotics, which means
the effectiveness of these antibiotics is essentially
irreversibly lost.
QY: B. Levin, Emory Univ., Population Genetics (404) 727-5660
(Science 24 Oct 97) (Science-Week 14 Nov 97)
[For more information: http://scienceweek.com/search/search.htm]


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IN FOCUS: ON GENERAL RELATIVITY
"During the two decades 1960-80, the subject of general
relativity experienced a rebirth. Despite its enormous influence
on scientific thought in its early years, by the late 1950s
general relativity had become a sterile, formalistic subject, cut
off from the mainstream of physics. It was thought to have very
little observational contact, outside of cosmology and a few
tests. It was believed to be an extremely difficult subject to
learn and comprehend. It was also viewed as a field that was full
of ambiguities and unanswerable questions... One of the
outgrowths of the renaissance of general relativity that occurred
between 1960 and 1980 has been a change in attitude about the
importance and use of the theory. Its importance as a fundamental
theory of the nature of spacetime and gravitation has not been
diminished in the least: if anything it has been enhanced by the
flowering of research in the subject that has taken place. Its
importance as a foundation for other theories of physics has been
strengthened by current searches for unified and grand unified
quantum theories of nature that incorporate gravity along with
other interactions. But the real change in attitude about general
relativity has been its use as a tool in the real world. [In
astrophysics, for example] the general relativistic bending of
light in gravitational lenses can help astrophysicists probe the
structure of galaxies. General relativistic effects in the binary
pulsar gave a high-precision determination of the mass of the
pulsar. Had the result been very different from 1.4 solar masses
it could have affected our understanding of supernovae in close
binary systems. Neutron-star mass limits from general relativity
are important in the observational search for black holes.
Finally, gravitational radiation may one day provide a completely
new tool for exploring and examining the universe. Relativity
even plays a role in everyday life. For example, the
gravitational redshift effect on clocks _must_ be taken into
account in satellite-based navigation systems, such as the US
Global Positioning System, in order to achieve the required
positional accuracy of a few meters or time transfer accuracy of
a few nanoseconds."
-----------
Clifford Will: The Renaissance of General Relativity.
in: Paul Davies (ed.): _The New Physics_
(Cambridge University Press, Cambridge UK 1989, p.7,33)


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