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.

May 21, 1999 -- Vol. 3 Number 21

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

Nature is that lovely lady to whom we owe polio,
leprosy, smallpox, syphilis, tuberculosis, and cancer.
-- Stanley Cohen

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

Contents of This Issue:

1. On Biological Terrorism
2. The Martian Meteorite Microbes Controversy: An Update
3. On the Nanoscale Science of Single Molecules
4. Population Biology, Evolution, and Infectious Disease
5. On the Functions of the Human Frontal Lobes
6. Emergence of Vancomycin Resistance in Staphylococcus Aureus

In Focus: On Superstrings

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

Please note:
On August 1, 1999 the subscription rate for ScienceWeek
will increase to $20 per year (52 issues). For substantial
savings, renew or extend your subscription now for 1 or more
years at the current rate. Subscription information is
available at URL http://scienceweek.com/subinfo.htm
or see the information in the Notices section below.

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

1. ON BIOLOGICAL TERRORISM
Although political events during the past decade have reduced
fears of biological warfare among the major powers, the pathogens
likely to be used in such warfare have not vanished, and there is
now an apparent growing concern about the use of such pathogens
in acts of biological terrorism ("bioterrorism").
... ... Donald A. Henderson (Johns Hopkins University, US)
presents a review of current views, expectations, and contingency
plans, the author making the following points concerning the
scientific fundamentals: 1) The expected scenario following
release of an aerosol cloud of a biological agent is entirely
different from that following an attack of nuclear or chemical
terrorism. A biological agent aerosol release could be silent and
would almost certainly be undetected. The cloud would be
invisible, odorless, and tasteless. It would behave much like a
gas in penetrating interior areas, and the release would not be
suspected for days or weeks later. 2) The implicit assumption has
frequently been that chemical and biological threats and the
responses to them are so generically similar that they can be
readily handled by a single "chembio" expert, usually a chemist.
This is a serious misapprehension. 3) Any of thousands of
biological agents that are capable of causing human infection
could be considered a potential biological weapon, but
realistically only a few pose serious problems. Only a very small
number of species of these pathogens can be cultivated and
dispersed effectively so as to cause cases and deaths in numbers
that would threaten the functioning of a large community. The
current consensus is that there are 11 pathogens "very likely to
be used." *Smallpox, *plague, *anthrax, and *botulism are
considered the top four candidates. The others are *tularemia,
*glanders, *typhus, *Q fever, *Venezuelan equine encephalitis,
*Marburg virus, and *influenza virus. 4) Any group with
sufficient resources could purchase prepared supplies of
aerosolizable organisms and could transport them easily, because
only small quantities are needed to inflict casualties over a
wide area. No mechanisms currently exist for screening to
intercept such materials at state or national borders. 5) Of the
potential biological weapons, smallpox and anthrax pose by far
the greatest threats, but these pathogens have different clinical
and epidemiological properties. Smallpox poses an unusually
serious threat, in part because virtually everyone is now
susceptible, vaccination having stopped worldwide 20 or more
years ago as a result of the eradication of the disease. It is
probable that no more than 20 percent of the world population is
protected; for the unprotected, fatality rates after infection
are 30 percent. Another problem is that there are no longer any
manufacturers of smallpox vaccine, which means large-scale
vaccination immediately after an outbreak is currently not
possible. 6) Concerning an inhalation anthrax epidemic, the
scenario is as dangerous as that for smallpox. After 2 to 3 days
anthrax-infected individuals would appear in emergency rooms and
doctors' offices with a variety of nonspecific symptoms such as
fever, cough, and headache. Within a day or two, patients would
become critically ill and then die within 24 to 72 hours. The
fatality rate for anthrax is 80 percent or greater. 7) The author
concludes: "Once the medical community rallied... in educating
peoples and policymakers everywhere about the dread realities of
a nuclear winter. Perhaps the same should now be done with
respect to the realities of biological weapons, which are now
considered to be a more serious threat than the nuclear ones."
-----------
Donald A. Henderson: The looming threat of bioterrorism.
(Science 26 Feb 99 283:1279)
QY: Donald A. Henderson, Johns Hopkins Center for Civilian
Biodefense Studies, Johns Hopkins Univ., Baltimore, MD 21202 US.
-----------
Text Notes:
... ... *Smallpox: This is an acute eruptive contagious disease
caused by a poxvirus (Orthopoxvirus, a member of the family
Poxviridae). The average incubation period is 8 to 14 days.
Following the incubation period, the onset symptoms are
constitutional: chills, high fever, backache, headache. In from 2
to 5 days, these symptoms subside and the skin eruptions appear.
Considering the temporal course of the disease, a smallpox
epidemic would probably not become evident until 2 to 3 weeks
after release of an aerosol.
... ... *plague: In this context, this term refers to the acute
infectious disease caused by the bacterium Yersinia pestis, the
disease marked by high fever, toxemia, and prostration. The
pathogen is usually transmitted to man by fleas that have bitten
infected rodents, and there are various forms of the disease. The
incubation period is 2 to 7 days. The fatality rate is near 50
percent, with usually 100 percent fatality for the pneumonic form
of the disease.
... ... *anthrax: This disease is caused by the bacterium
Bacillus anthracis, and is usually transmitted by infected
animals through traumatized human skin. The disease is marked by
hemorrhage and blood effusions in various organs and body
cavities, and by symptoms of extreme prostration. In the context
of this report, the disease entity of concern is "inhalation
anthrax", which is a more serious human disease than anthrax
contracted from an animal through the skin. Inhalation anthrax
produces hemorrhagic pneumonia with shock and is usually fatal
(fatality above 80 percent).
... ... *botulism: This disease is caused by toxins of the
bacterium Clostridium botulinum, an organism common in soil and
sometimes in animal feces. Symptoms appear 18 to 24 hours after
entry of the toxins, and the most severe symptoms are the result
of effects on the neuromuscular system. Death occurs from
respiratory paralysis or cardiac arrest. The fatality rate is
high. Ordinarily, botulism is not an actual human infection,
since the human disease is almost always caused by ingestion of
food contaminated with toxins produced by C. botulinum, which is
anaerobic and grows only under conditions of low or absent oxygen
(e.g., in canned foods). The botulinum toxins are among the most
highly toxic substances known: the lethal dose for a human is
estimated to be in the range 1 to 2 micrograms.
... ... *tularemia: This disease is caused by the bacterium
Francisella tularensis, a pathogen usually transmitted to humans
by biting arthropods (e.g., insects), direct contact with
infected animal tissue, ingestion of contaminated food or water,
and inhalation of aerosols. Apparently, inhalation of only 50
individual F. tularensis bacteria can result in infection.
Symptoms appear within a week. The disease can usually be
controlled with antibiotics.
... ... *glanders: A common disease of horses, mules, and
donkeys, caused by the bacterium Burkholderia mallei. The
inhalation form of the disease may lead to primary pneumonia.
The disease can usually be controlled with antibiotics.
... ... *typhus: A group of acute infectious and contagious
diseases caused by the bacterial group Rickettsaie. These
diseases are characterized by fever, headache, malaise, and
prostration.
... ... *Q fever: Also caused by a Rickettsaie bacterium, but the
symptoms resemble influenza, nonbacterial pneumonia, hepatitis,
or encephalopathy.
... ... *Venezuelan equine encephalitis: This is a viral disease
usually transmitted by mosquitoes from horses to humans. It is
caused by a togavirus, subgroup alphavirus. In humans, the
symptoms are similar to those of influenza.
... ... *Marburg virus: One of the two notorious African
Hemorrhagic Fevers (the other is Ebola virus), highly virulent,
with infections usually ending in death. These viruses have the
highest mortality rate (as much as 90 percent) of all the viral
hemorrhagic fevers. The disease was first recognized in 1967.
... ... *influenza virus: Any of a group of influenza viruses,
all of the family Orthomyxoviridae. The influenza diseases
usually have a sudden onset, are highly contagious, and easily
produce large-scale epidemics. Apparently, if only a few cells of
the respiratory *epithelium are infected by deposited virus
particles, the infection can proceed. The severity of symptoms
and the outcome depends on which strain of the virus is the
pathogen.
... ... *epithelium: In animals and humans, epithelial cells
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway passages.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21May99
-------------------
Related Background:
MONKEYPOX, SMALLPOX, AND BIOLOGICAL TERRORISM
The last case of confirmed smallpox on Earth occurred more than
20 years ago, and nearly 2 decades ago the World Health
Organization concluded the global eradication of smallpox had
been achieved. But new questions have now arisen: a) Could recent
outbreaks of human monkeypox in Africa represent the return of
another form of smallpox? b) Could smallpox virus be used as a
weapon of biological terrorism? c) What are the implications of
the decision of the World Health Organization to advise the
destruction of all isolates of the smallpox virus in June 1999?
... ... In a short review of these questions, Breman and
Henderson make following points: 1) The available data do not
support the possibility that monkeypox might soon take over the
ecological niche left vacant by smallpox. 2) All vaccination
against smallpox ceased after eradication of the disease was
affirmed. Virtually all children and many adults are now fully
susceptible to smallpox. Only limited supplies of vaccine are
available. 3) Were smallpox virus released by an act of
terrorism, the results could be catastrophic. A large proportion
of the population has no immunity. There is little available
vaccine and no effective treatment. The expected case fatality
rate would be higher than 25 percent. The authors conclude:
"Reports suggesting that monkeypox might replace smallpox as a
serious epidemic threat are unsubstantiated, but the threat posed
by the possible use of smallpox as a terrorist weapon is genuine.
Because of the gravity of this threat, all known stocks of
variola [smallpox] virus should be destroyed as soon as possible.
The deliberate deployment of this virus must be discouraged by
whatever means possible."
-----------
J.G. Breman and D.A. Henderson (2 installations, US): Poxvirus
dilemmas -- monkeypox, smallpox, and biological terrorism.
(New England J. Med. 20 Aug 98 339:556)
QY: Joel G. Breman, Nat. Inst. of Health, Bethesda, MD 20892 US
-------------------
Summary by SCIENCE-WEEK  18Sep98
-------------------
Related Background:
ALARM OVER AN OUTBREAK OF HUMAN MONKEYPOX DISEASE
The largest and most complex animal viruses are the poxviruses,
among them smallpox and a related virus called monkeypox.
Smallpox was ostensibly eradicated completely in 1979, and the
disease is more or less extinct, with debate now about whether to
completely extinguish the smallpox genome by destroying the last
of it in storage. Monkeypox, however, is far from eradicated.
Until recently the disease exhibited minor outbreaks, with the
incidence being quickly damped due to the apparent difficulty of
human to human transmission. In these outbreaks, the disease was
evidently transmitted by eating the meat of infected monkeys,
squirrels, and rats. Now, however, during the last year, there
has been a striking outbreak of 92 cases of monkeypox, all within
a few villages in the central part of the Democratic Republic of
Congo, and the most troubling aspect is the evidence that the
rate of human to human transmission may have suddenly increased
many-fold over what it has been in the past. Has the monkeypox
virus mutated to a more virulent form more easily transmitted
from one person to another? Medical epidemiologists are alarmed.
Peter Jahrling, a virologist at the U.S. Army Medical Research
Institute (MD US) says, "I hate to be accused of pushing the
alarmist button, but for practical purposes smallpox is back."
And Ali Khan, a medical epidemiologist at the U.S. Center for
Disease Control and Prevention, who recently visited the area of
the Congo in question, says, "I am personally concerned about
what would happen if this disease showed up in a major city." But
other virologists and epidemiologists, including some who
specialize in the poxviruses, are not convinced that human to
human transmission of monkeypox has actually increased
substantially. An argument can be made that the natural immunity
of the people of the Congo has been compromised by a high
incidence of HIV and the vicissitudes of armed conflict in the
area. The debate goes on, and the cases in the central Congo keep
mounting.
(Science 18 Jul 97) (Science-Week 29 Jul 97)


2. THE MARTIAN METEORITE MICROBES CONTROVERSY: AN UPDATE
In 1984, a 1.9 kilogram meteorite the size of a potato (desig-
nated ALH84001) was found in Antarctica, and because of its
chemical composition the consensus is that this meteorite (and a
dozen similar meteorites) originated from the planet Mars. The
basis for the consensus is the detailed quantitative correspond-
ence of the trapped gases in the meteorites to Martian
atmospheric gases, and the specific distributions of oxygen
isotopes. In 1996 a group of researchers, D. McKay et al
(National Aeronautics and Space Administration Johnson Space
Center, US; Stanford University, US) reported they had concluded
that unusual characteristics of the meteorite ALH84001 can be
most reasonably interpreted as vestiges of ancient Martian
bacterial life. In particular, the authors noted the presence of
tubules 20 to 40 nanometers in diameter (called by some
"nannobacteria"), and they proposed these structures were
fossilized bacteria or parts of microorganisms. The report was
first delivered at a press conference in August 1996 (published
as a paper 9 days later) and provoked considerable media
attention and controversy when it appeared. The controversy has
continued, with many biologists objecting to the interpretation
of the rock data, and in particular objecting to the idea of
"bacteria" 20 to 40 nanometers in diameter.
... ... Allan Treiman (National Aeronautics and Space
Administration, US) presents a review and update of the ALH84001
meteorite controversy, the author making the following points: 1)
Early hopes for a fast resolution of the controversy concerning
meteorite ALH84001 have evaporated: no agreement has emerged on
whether or not the meteorite ever contained Martian life. 2)
There is no disagreement that ALH84001 formed on Mars
approximately 4.5 billion years ago, that the meteorite was
probably ejected into space approximately 16 million years ago by
an asteroid impact, that the meteorite fell in Antarctica 13,000
years ago, and that the meteorite remained in Antarctica until
found on the ice in 1984. 3) ALH84001 is an igneous rock (i.e., a
rock congealed from a molten mass) that apparently crystallized
slowly from molten lava and which contains globules of carbonate
minerals scattered along fractures. All the evidence for life is
in the carbonate globules or their rims. 4) The 4 lines of
evidence originally proposed by the McKay group were a) the
presence in the meteorite of carbon compounds (polycyclic
aromatic hydrocarbons) suggestive of decayed organic matter; b)
the presence in the meteorite of unusual small crystals of
magnetite (an iron oxide) matching identical crystals believed to
be produced only by Earth bacteria; c) the presence in the
meteorite of apparently incompatible minerals (e.g., iron-sulfide
and iron-oxide) close together whose proximity would suggest
organic action if the rock were from Earth; and d) the presence
in the meteorite of bacteria-shaped formations. 5) The author
[Treiman] suggests that a) The polycyclic aromatic hydrocarbons
may or may not be Martian, and if they are, they may or may not
be related to life. b) The magnetite crystals are indeed Martian,
but there is evidence that some of these crystals formed without
life and the origin of the others remains unclear. c) The mineral
associations in the carbonate globules do not prove life, but
also do not exclude it. d) The bacteria-shaped objects in
ALH84001 are not fossil bacteria but could be fossils of bacteria
fragments. (McKay's group now agrees that the objects are too
small to be fossil microbes.) 6) The author concludes: "McKay's
original hypothesis (as expressed in the 1996 paper) depended on
all four lines of evidence working together... The evidence has
not been verified, so the hypothesis has not succeeded... Despite
world attention, significant spending, and the work of the best
laboratories on Earth, the question [of life on Mars] is
unresolved."
-----------
Allan Treiman: Microbes in a Martian meteorite?
(Sky & Telescope April 1999)
QY: Allan Treiman [treiman@lpi.jsc.nasa.gov]
-------------------
Related Background:
EVIDENCE THAT MARTIAN METEORITE AMINO ACIDS ARE CONTAMINANTS
As the subunits that compose protein polymers in living systems,
the detection of certain amino acids in a material is often
interpreted as indicating a possible biological origin. The
meteorite ALH84001, along with a number of other discovered
meteorites, has a composition that suggests it was apparently
ejected from the surface of Mars, and during the past year it has
been proposed that microanalysis of this meteorite indicates the
possible presence of bio-organics and biogenic fossils. This
proposal, however, has met with considerable controversy, and the
controversy is still in full force. ... ... Bada et al (4 authors
at 3 installations, US) now report that the amino acids present
in a sample of the ALH84001 meteorite appear to be terrestrial in
origin and similar to those found in the ice where the meteorite
was discovered, although the possibility remains that minute
amounts of endogenous amino acids are preserved in the meteorite.
The authors suggest that radiocarbon studies (cf. contiguous
report: Jull et al, Science 279:366 1998), coupled with their own
amino acid results, indicate that major and minor organic
constituents in the Martian meteorites are contaminants.
QY: Jeffrey L. Bada 
(Science 16 Jan 98) (Science-Week 30 Jan 98)
-------------------
Related Background:
AN ARGUMENT FOR RELIC LIFE ON MARS
... ... Gibson et al (National Aeronautics and Space
Administration Houston, US; University of Georgia, US), the
group including some of the authors of the 1996 McKay report, in
a review of the evidence for relic life on Mars, consider the
ALH84001 meteorite not only the strongest evidence for Martian
relic life, but also for the possibility of present Martian
microbial life. The authors are hopeful that in 2005 a "sample
return" mission will be launched to robotically collect Martian
rocks and soil and return them to Earth.
QY: Everett K. Gibson 
(Scientific American December 1997) (Science-Week 28 Nov 97)
-------------------
Related Background:
EVIDENCE AGAINST NANOFOSSILS IN MARTIAN METEORITE
The term "nanofossils" (originally spelled "nannofossils" by the
group that introduced the term) refers to elongated microscopic
forms found in the Martian meteorite ALH84001. Several groups in
the space and geology communities have proposed these forms are
fossilized bacteria, but most biologists have rejected the idea
on the basis that the forms are too small to be bacteria and
should not be classified as such. Bradley et al (3 installations,
US) now report that new analysis of material from the ALH84001
meteorite indicates the majority of the elongated microscopic
forms can be resolved as either emergent substrate layers or
magnetite whiskers, rather than biogenic nanofossils. Their
report is followed by a response from McKay et al (3 install-
ations, US CA), some of the original proponents of the nanofossil
idea, and in their response McKay et al say the artifact
possibilities mentioned by Bradley et al are already known to
them, but are not related to their own observations. They add
that living bacteria as small as 70 nanometers in diameter have
been observed in mammalian blood, and that soil bacteria as small
as 80 nanometers have also been observed. The references for
these bacterial forms are one unpublished paper and two recently
published papers in Proc. Soc. Photo-Opt. Instrum. Eng.
3111:420,429 (1997). It is evident that the nanofossil contro-
versy has not yet been resolved.
QY: J.P. Bradley, Georgia Inst. Technol. 404-894-2000; David S.
McKay 
(Nature 4 Dec 97) (Science-Week 26 Dec 97)
-------------------
Related Background:
A CONTROVERSY CONCERNING MINIMUM POSSIBLE DIMENSIONS OF BACTERIA
Apart from their heuristic significance, scientific controversies
can be either amusing or irritating. In recent months, a
controversy between some geologists and many biologists has
developed, and it is apparently irritating the biologists. The
issue concerns the minimum possible dimensions of bacteria. The
geologists are led by Robert L. Folk (University of Texas, Austin
TX US), and they have proposed that certain microscopic entities
found in the Martian meteorite ALH84001 are fossils of what they
term "nannobacteria" (their own unique spelling of the prefix
nano-), which they say are similar to those found in Earth
travertine and limestone rocks, and which have dimensions of 30
to 50 nanometers. This has caused a furor among biologists, whose
understanding of bacteria and life forms in general is that the
smallest dimensions possible for a life form with a bounding
plasma membrane is about 200 nanometers. In fact no membrane-
bound bacterium with dimensions less than 340 nanometers has ever
been identified, and one can make simple calculations that a 50
nanometer bacterium would not have enough internal volume to
sustain its chemistry. Folk published papers on the subject in
several geological journals in 1996, starting the debate, and in
the Letters section of the 20 June 1997 issue of *Science* the
debate continues, and this week it is being reported in the
popular media as a "debate about life on earth". What evidently
irritates biologists is the apparent misunderstanding by these
geologists of experimental methods in biology. Characterizations
of "living" vs. "non-living" by biologists are made on the basis
of experimental laboratory replicability of an organism, and not
on the basis of the visible structure of an entity. Which means
the geologists involved need to attempt to culture their
Earth-rock entities, and which means decisions that the Martian
meteorite's so-called "nannobacteria fossils" are actually such
will require demonstration of cultured entities with those
dimensions. Biologists are not unwilling to admit the existence
of new species of life forms, of which they have already
recognized several million entities, but they argue that one does
not classify pieces of rock as a life form on the basis of
structure alone.
(New York Times 29 Jul 97) (Science-Week 1 Aug 97)


3. 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


4. POPULATION BIOLOGY, EVOLUTION, AND INFECTIOUS DISEASE
Traditionally, the interest of population and evolutionary
biologists in infectious diseases has been almost exclusively in
the role of infectious diseases as agents of natural selection in
higher organisms. Recently, this interest has expanded to include
the genetic structure and evolution of microparasite populations,
the mechanisms of pathogenesis and the immune response, and the
population biology, ecology, and evolutionary consequences of
medical and public health interventions. ... ... B.R. Levin et al
(3 authors at 2 installations, US CH) present a review of recent
work in these research areas, with emphasis on the quantitative
population-biological approaches that have been contributing to
the understanding of infectious disease and to the design and
evaluation of interventions for treatment and prevention. The
authors make the following points: 1) The most developed research
area representing the convergence of population biology,
evolutionary biology, and infectious disease is molecular
epidemiology. The practical goals of molecular epidemiology are
to identify the microparasites (viruses, bacteria, fungi, and
protozoa) responsible for infectious diseases and determine their
physical sources, their phylogenetic relationships, their routes
of transmission, and the routes of transmission of the genes (and
accessory elements) responsible for microparasite virulence,
vaccine-relevant *antigens, and drug resistance. 2) The
"contagion school" of epidemiology was well developed before the
demonstrations by *Pasteur (1822-1895) and *Koch (1843-1910) of
bacteria as the etiologic agents of disease, and the evolutionary
implications of contagion were already evident in the writings of
Darwin (1809-1882), who used germs to bolster his argument that
the carriers of the information of inheritance and development
could be small enough to fit in the sperm of higher organisms.
Darwin also refers to infectious diseases as agents of natural
selection in higher organisms, which is the conceptual role
infectious diseases have played in the history of population and
evolutionary biology. 3) If the course of a microparasite
infection in a vertebrate host were described without jargon, the
process would be readily recognized as one of population dynamics
and evolution. For example, the replication of a virus in an
infected host can be likened to a natural ecosystem with
resources, predators, and prey. By infecting a cell, the virus
preys on its resource, the susceptible target cell, while itself
being subject to predation by the immune response of the host.
Classical virological and immunological research is mostly
concerned with uncovering the direct interactions between the
virus and different cell types as host. In contrast, population-
dynamical research aims to disentangle the complicated and often
counterintuitive dynamical behavior resulting from the web of
nonlinear interactions. 4) Population-biological models have
already played a major role in the design and targeting of
vaccination programs. They have been used, for example, to
calculate the critical fraction of a population that must be
vaccinated to eliminate a particular pathogen; to design clinical
trials of vaccines; to target vaccination programs (or other
interventions) to achieve maximum reductions in disease; to
anticipate possible "perverse" effects of vaccination; and to
predict potential outbreaks of a disease in time to take
preventive measures. 5) The conceptual and research convergence
of population biology and the biology of infectious disease is
only in its early stages, but this convergence has already led to
new fundamental insights, and has highlighted the need to
intensify the collaborative efforts of infectious disease
biologists and clinicians with population biologists. These
collaborative efforts will advance our quantitative understanding
of infectious diseases and make possible further applications to
the control and treatment of these diseases.
-----------
B.R. Levin et al: Population biology, evolution, and infectious
disease: Convergence and synthesis.
(Science 5 Feb 99 283:806)
QY: Bruce R. Levin, Biology, Emory University 800-727-6036
-----------
Text Notes:
... ... *antigens: In general, an antigen is any chemical entity
that activates an immune response, especially an entity
originating outside the body.
... ... *Pasteur: Louis Pasteur (1822-1895) discovered that
fermentation is caused by microorganisms. He developed the germ
theory of disease and created a vaccine for rabies.
... ... *Koch: Heinrich Hermann Koch (1843-1910) devised
techniques for culturing bacteria outside the body, and
formulated the rules for demonstrating whether or not a bacterium
is the cause of a disease. He identified the bacteria responsible
for tuberculosis, cholera, and other diseases. He demonstrated
that rats are vectors of bubonic plague and that sleeping
sickness is transmitted by the tsetse fly. He received the Nobel
Prize for Physiology or Medicine in 1905.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21May99


5. ON THE FUNCTIONS OF THE HUMAN FRONTAL LOBES
The human cerebral hemispheres (collectively termed the
"cerebrum") represent 85 percent of the brain by weight, and for
nearly two centuries one sustained research effort, involving a
large number of researchers, has been to identify which parts of
the cerebral hemispheres are involved with which mental
functions. Such identifications must be made carefully and in
context, since essentially every part of the brain is directly or
indirectly connected to every other part, with all parts in
principle capable of interaction. Still, for certain higher
functions, a high degree of localization is apparent. Apart from
their large size in humans, what is most evident about the human
cerebral hemispheres is the high degree of convolution, a
tortuous array of foldings of tissue, one consequence of which is
an enormous increase in surface area. This increase in surface
area is of some significance, since the entire convoluted surface
of the hemispheres comprises a laminated rind of neurons and
supporting cells approximately 2 millimeters thick, the rind
called the "cerebral cortex". The total surface area of the
cerebral cortex comprises approximately 1.6 square-meters, and it
is within this relatively thin layer of neurons that most of the
processing for the so-called "higher functions" is accomplished.
The convolutions of the cerebrum thus make it possible to have an
enormous number of neurons distributed in two dimensions in the
cerebral cortex without the necessity for an excessively large
head. Seen in toto, each cerebral hemisphere consists of 4 lobes:
frontal, parietal, temporal, and occipital (named after the bones
under which they lie), and it has been the frontal lobe, the
large fore-part of the brain, which has been the most mysterious
in terms of function. The most functionally well-defined region
of the frontal lobe is the "primary motor area", which lies at
the border between the frontal lobe and the parietal lobe, and
which is involved in the voluntary control of movement. The back
part of the frontal lobe anterior to the motor region is called
the "prefrontal region", and prefrontal cortex is apparently
involved in planning complex cognitive behaviors. In recent
years, "*functional imaging" techniques, which are essentially
non-invasive and which can be used with healthy and awake human
subjects, have become important new approaches to an old problem.
In general, the human frontal cortex apparently helps mediate
"working memory", a system that is used by the brain for
temporary storage and manipulation of information, and that is
involved in many higher cognitive functions. Working memory
apparently includes two components: short-term storage (on the
order of seconds), and executive processes that operate on the
contents of storage. ... ... E.E. Smith and J. Jonides
(University of Michigan, US) present a review of current research
concerning the functions of the human frontal lobes as revealed
by experiments using *positron emission tomography or *functional
magnetic resonance imaging to image subjects while the subjects
engage in cognitive tasks designed to reveal processes of
interest. The authors report that studies of storage indicate
that different frontal regions are activated for different kinds
of information: storage for verbal materials activates Broca's
area (an area specialized for the production of language) and
left-hemisphere prefrontal areas adjacent to primary motor
cortex; storage of spatial information activates right-hemisphere
prefrontal cortex adjacent to primary motor cortex; storage of
object information activates other areas of prefrontal cortex.
Selective attention and task management, two of the fundamental
executive processes, both activate regions of prefrontal cortex.
The authors conclude: "Neuroimaging analyses of executive
processes are quite recent, and they have yet to lead to clear
dissociations between processes. Perhaps the highest priority,
then, is to turn further attention to executive processes and
their implementation in frontal cortex."
-----------
E.E. Smith and J. Jonides: Storage and executive processes in the
frontal lobes.
(Science 12 Mar 99 283:1657)
QY: Edward E. Smith [eesmith@umich.edu]
-----------
Text Notes:
... ... *functional imaging: In general, in this context, the
term "functional imaging" refers to any technique which images
neural activity produced by specific behaviors (functions).
... ... *positron emission tomography: Positron emission
tomography is a technique for producing cross-sectional images of
the body after ingestion and systemic distribution of safely
metabolized positron-emitting agents. The images are essentially
functional or metabolic, since the ingested agents are
metabolized in various tissues. Fluorodeoxyglucose and
H(sub2)O(sup15) are common agents used for cerebral applications,
and in cerebral applications of central importance to the
technique is the fact that changes in the cellular activity of
the brains of normal, awake humans and unanesthetized laboratory
animals are invariably accompanied by changes in local blood flow
and also changes in oxygen consumption.
... ... *functional magnetic resonance: Magnetic resonance
imaging is a technique involving images produced by mobile
protons of a tissue excited by the application of a magnetic
field, and when used in functional cerebral imaging, the basis of
the technique is that it images very small metabolic, blood-flow,
and perfusion-diffusion changes in vivo, in real time, and with
no risk to the subject.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 21May99
-------------------
Related Background:
BRAIN ACTIVITY CORRELATES OF VISUAL AND VERBAL MEMORY
In contemporary human neurobiology, memory is categorized into
two types: declarative memory (available to consciousness) and
procedural memory (generally not available to consciousness).
Declarative memory includes memory for such things as daily
episodes, words and their meanings, and history. Procedural
memory includes motor skills, associations, puzzle solving
skills, and so on. Identification of the neurological correlates
of memory in humans has until recently been based on slow
advances produced primarily by clinical evidence resulting from
localized traumatic injuries and localized tissue damage caused
by various diseases (all termed "lesions"). But the pace of
research in this field has now markedly increased due to several
new imaging techniques that allow identification of brain regions
activated in normal conscious subjects during various mental
tasks. The technique called "*functional magnetic resonance
imaging" (fMRI) is now an ascendant methodology, and this is the
technique that forms the basis for this report. (fMRI technical
details are provided in the notes below.) From clinical data
involving brain damage, it has long been known that one region
essential for declarative memory is the *medial temporal lobe of
the brain: bilateral damage to this brain region produces global
amnesia, a pervasive memory deficit for all new events and new
facts. There is additional brain damage evidence that regions of
the frontal lobes also contribute to declarative memory. Memory
deficits resulting from unilateral medial temporal lobe or
frontal lobe damage are often specific, with left-side lesions
impairing verbal memory, and right-side lesions impairing
nonverbal memory. Brain lesion studies, however, cannot
distinguish whether a given brain region normally participates in
the encoding of ongoing experiences into memories, or the storage
of the memories over time, or the later retrieval of those
memories. In contrast, the newer methods of functional
neuroimaging can indeed make such distinctions.
... ... J.B. Brewer et al report the use of event-related
functional magnetic resonance imaging to identify specific brain
activations that differentiated between visual experiences that
were later remembered well, remembered less well, or forgotten.
During fMRI scanning of medial temporal lobe and frontal lobe
regions, subjects viewed complex color photographs, and subjects
later received a test of memory for the photographs. The authors
report their results indicate that the degree of activation in
right frontal lobe and bilateral *parahippocampal regions
measures how well a particular visual experience is encoded, and
that the degree of activation therefore predicts whether the
visual experience will be remembered well, remembered less well,
or forgotten by the individual. ... ... In a contiguous paper,
A.D. Wagner et al report a study of human brain activation during
word encoding, the study involving two different experimental
designs and the use of functional magnetic resonance imaging to
examine how brain activation differs for subsequently remembered
and subsequently forgotten verbal experiences. The authors report
their results indicate the ability to later remember a verbal
experience is predicted by the magnitude of activation in left
*prefrontal and temporal cortices during the experience. The
authors suggest these findings provide direct evidence that left
prefrontal and temporal regions jointly promote memory formation
for verbal experiences.
-----------
J.B. Brewer et al (5 authors at Stanford University, US): Making
memories: Brain activity that predicts how well visual experience
will be remembered.
(Science 21 Aug 98 281:1185)
QY: James B. Brewer 
A.D. Wagner et al (8 authors at Harvard University, US): Building
memories: Remembering and forgetting of verbal experiences as
predicted by brain activity.
(Science 21 Aug 98 281:1188)
QY: Anthony D. Wagner 
-----------
Text Notes:
... ... *functional magnetic resonance imaging: First, we
distinguish between magnetic resonance imaging (MRI) and
"functional" magnetic resonance imaging (fMRI) as applied to the
brain. The former is essentially a technique for examining
morphology, while the latter is a technique for examining
activity of brain tissue. Both techniques involve computerized
analysis of data. In general, MRI involves magnetic coils
producing a static magnetic field parallel to the long axis of
the patient or subject, combined with inner concentric magnetic
coils producing a static magnetic field perpendicular to the long
axis. A radio-frequency coil specifically designed for the head
perturbs the static fields to generate a magnetic resonance
image. The interaction physics in this technique is that between
the magnetic fields and atomic nuclei in brain tissue. "Sliced"
views can be obtained from any angle, and the resolution is quite
high and on the order of millimeters for current magnetic field
strengths of 1.5 tesla. Functional magnetic resonance imaging
(fMRI), the variant of MRI discussed here, is based on the fact
that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a
different magnetic resonance signal than deoxyhemoglobin, the
oxygen-depleted form of hemoglobin. Activated brain areas utilize
more oxygen, which transiently decreases the levels of
oxyhemoglobin and increases the levels of deoxyhemoglobin, and
within seconds the brain microvasculature responds to the local
change by increasing the flow of oxygen-rich blood into the
active area. This local response thus leads to an increase in the
oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for
the fMRI signal in this technique. Because of its high spatial
resolution (millimeters) and high temporal resolution (seconds)
compared to other imaging techniques, fMRI is now the technology
of choice for studies of the functional architecture of the human
brain.
... ... *medial temporal lobe: The temporal lobes are roughly the
lower sides of the brain, above the ears and behind the temporal
bones of the skull, but when the human brain is viewed from the
side, as it usually is in common gross depictions, the large and
functionally important ventral and infolded parts of the temporal
lobes are not visible. In general, the larger anatomical regions
of the human brain are best visualized as highly corrugated
lobular structures extensively folded and densely packed to fit
inside the volume-limiting protective skull. But isolated verbal
descriptions of the architecture are of limited use: anatomical
graphics are the best sources for visualization of gross brain
structures.
... ... *parahippocampal regions: These are parts of the temporal
lobes, visible only when the temporal lobes are unfolded away
from the main brain mass.
... ... *prefrontal: The portion of the frontal lobes anterior
to the motor region.
-------------------
Summary & Notes by SCIENCE-WEEK  2Oct98
-------------------
Related Background:
FUNCTIONAL ANATOMY OF HUMAN MUSIC PROCESSING
The existence of special perceptuo-motor skills in certain
individuals presents many puzzling questions for the cognitive
neurosciences. One such ability whose cerebral substrate remains
essentially unknown is absolute pitch (also called "perfect
pitch"), a relatively rare ability that refers to a long-term
internal representation for the pitch of tones in the musical
scale, typically manifested behaviorally by the ability to
identify by the name of the musical note the pitch of any sound
without reference to another sound, or by the ability to produce
a given musical tone on demand. In contrast, relative pitch,
which is well-developed among most trained musicians, refers to
the ability to make pitch judgments about the relation between
notes, such as within a musical interval...
... ... Zatorre et al (5 authors at McGill University, CA) report
a study of the neural basis of human absolute pitch using both
structural and functional brain imaging techniques (magnetic
resonance imaging and positron emission tomography). Although
there were some localization differences between absolute pitch
possessors and control non-absolute-pitch musicians when
responding to musical tones, the results as a whole bring the
authors to suggest that absolute pitch may not be associated with
a unique pattern of cerebral activity, but rather may depend on
the recruitment of a specialized network involved in the
retrieval and manipulation of verbal-tonal associations.
QY: Robert J. Zatorre [md37@musica.mcgill.ca]
(Proc. Natl. Acad. Sci. US 17 Mar 98 v95:p3172)
(Science-Week 24 Apr 98)
-------------------
Related Background:
ON DYSLEXIA AND FUNCTIONAL DISRUPTION IN BRAIN ORGANIZATION
Dyslexia is impaired reading ability when the reading competence
is below that expected from the individual's general intelligence
and there is no impairment of vision. It has been proposed that
dyslexic children and adults lack phonologic awareness, an
awareness that strings of letters (orthography) are connected to
corresponding units of speech (phonologic constituents) that they
represent. In biology, magnetic resonance imaging is a technique
involving images produced by mobile protons of a tissue excited
by the application of a magnetic field, and when used in funct-
ional cerebral imaging, the basis of the technique is that it
images very small metabolic, blood-flow, and perfusion-diffusion
changes in vivo, in real time, and with no risk to the subject,
with the essential idea of mapping activity in the brain in
response to external stimuli or during sensory, perceptual, or
cognitive events. ... ... Now Shaywitz et al (15 authors at 2
installations, US) report a study to find the location and extent
of the functional disruption in neural systems that underlies
dyslexia. Functional magnetic resonance imaging was used to
compare brain activation patterns in dyslexic and nonimpaired
subjects as they performed tasks that made progressively greater
demands on phonologic analysis. Brain activation patterns
differed significantly between the groups, with dyslexic readers
showing underactivation in certain specific brain areas and
overactivation in other specific brain areas. The authors suggest
their results support a conclusion that the impairment in
dyslexia is phonologic and that brain activation patterns may
provide a neural signature for this impairment.
QY: Sally E. Shaywitz (sally.shaywitz@yale.edu)
(Proc. Natl. Acad. Sci. US 3 Mar 98)
-------------------
Related Background:
SPATIAL WORKING MEMORY LOCALIZED IN HUMAN FRONTAL CORTEX
Magnetic resonance imaging is a technique involving images
produced by mobile protons of a tissue excited by the application
of a magnetic field, and when used in functional cerebral
imaging, the basis of the technique is that it images very small
metabolic, blood-flow, and perfusion-diffusion changes in vivo,
in real time, and with no risk to the subject, with the essential
idea of mapping activity in the brain in response to external
stimuli or during sensory, perceptual, or cognitive events. The
brain-anatomical term "superior frontal sulcus" refers to a
fissure on the superior frontal surface of each frontal lobe. In
this report, "working memory" is the process of maintaining an
active representation of information so that it is available for
use, and "spatial working memory" refers to working memory
involved with spatial memory tasks (remembering locations of
briefly displayed objects or images). ... ... Courtney et al (5
authors at National Institutes of Health, US), using functional
magnetic resonance imaging in humans, report an area in the
superior frontal sulcus specialized for spatial working memory.
The authors suggest that localization of the area in a more
superior and posterior region in the human brain than in the
monkey brain may explain why it has not been recognized
previously.
QY: Susan M. Courtney 
(Science 27 Feb 98) (Science-Week 13 Mar 98)


6. 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 mole
Penicillinium). 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 over-
whelmingly 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 Univers-
ity, US) report that 25% of bacteria sampled from infant diapers
are strains of E. coli still resistant to the antibiotic strepto-
mycin, 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 strepto-
mycin, 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 effective-
ness 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)


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
IN FOCUS: ON SUPERSTRINGS
"The name 'superstring' grew out of a historical analogy. The
greatest achievement of Einstein was his 1915 theory of gravity.
Sixty years later, a new version of Einstein's theory was
discovered, which brought gravity into closer contact with the
rest of physics. The new version of gravity was called
'supergravity'. About the same time that supergravity was
invented, another model of particle interactions was proposed.
The new particle model was called 'String Theory' because it
represented particles by one-dimensional curves or strings.
Finally, the same mathematical trick which turned gravity into
supergravity turned strings into superstrings. That is how
superstrings acquired their name. The name, like the superstring
itself, is a mathematical abstraction. Superstrings have one
striking characteristic which is easy to express in words. They
are small. They are extravagantly small. Their extravagant
smallness is one of the main reasons why we can never hope to
observe them directly. To give a quantitative idea of their
smallness, let me compare them with other things that are not so
small. Imagine, if you can, four things that have very different
sizes. First, the entire visible Universe. Second, the planet
Earth. Third, the nucleus of an atom. Fourth, a superstring. The
step in size from each of these things to the next is roughly the
same. The Earth is smaller than the visible Universe by about 20
powers of 10. An atomic nucleus is smaller than the Earth by 20
powers of 10. And a superstring is smaller than a nucleus by 20
powers of 10. That gives you a rough measure of how far we have
to go in the domain of the small before we reach superstrings."

-- Freeman J. Dyson: _Infinite in All Directions_
   (Harper & Row, New York 1988)


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

NOTICES 
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

SCIENCE-WEEK SUBSCRIPTION RENEWAL OR EXTENSION INFORMATION:
-----------------------------------------------------------

Until August 1, 1999 the subscription rate for ScienceWeek is
US$10 per year. After that the rate will be US$20 per year.
Until August 1st, renewals or extensions at the current rate will
be accepted for any number of years.

CREDIT CARD PAYMENT:

Credit card payment can be made using a secure credit card form
that can be accessed at http://scienceweek.com/subinfo.htm

As an alternative, the following information can be supplied by
Email or regular mail or voice telephone or Fax:

Your name:
Duration of renewal or extension (1 or more yrs at US$10 per yr)
Your Email address:
Type of credit card (Visa, MasterCard, or American Express):
Credit card number:
Credit card expiration date:
Zip or postal code (if any) of your home address:

Please note: The credit card charge will be by Spectrum Press,
the publisher of SCIENCE-WEEK.

For transmission of credit card information:
Email: prismx@scienceweek.com
Fax: 773-281-1419 (24 hrs.- 7 days)
Voice phone: 888-281-1419 (toll-free US) (9am-5pm M-F CST)
             773-281-1419 (outside US) (9am-5pm M-F CST)

If you use PGP Email encryption software, our public key is at
http://scienceweek.com/pgp.txt

----------------------------------------------------------------
CHECK OR MONEY ORDER:

To subscribe by check or money order (drawn in US funds on a US
bank), please provide your name, Email address, subscription 
duration, along with a check or money order for US$10.00 per year
payable to "Spectrum Press", and send it to:

SCIENCE-WEEK/Spectrum Press
3023 N. Clark Street #109
Chicago, IL 60657
USA

----------------------------------------------------------------
When we receive payment, we will confirm receipt with an Email
message to your specified Email address.

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
CHANGE OF EMAIL ADDRESS: If at any time you need to change the
Email address at which you receive SW, please send the
information to [request@scienceweek.com], and the change will be
made and confirmed the same day. 
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
been published regularly each week since that date. We welcome
comments, suggestions, and criticisms from our subscribers.
Public letters relevant to any report are also welcome.
Editorial contact: [editors@scienceweek.com].

Editor/Publisher: Dan Agin
Managing Editor: Claire Haller
Associate Editor: Joan Oliner

Copyright (c) 1997-1999 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved

---------------------------------------------
This publication is protected by U.S. and International Copyright
Laws, and no display, transmission, or duplication in any medium,
including BBS, Internet Email, website duplication, fax, or print
is permitted without the explicit consent of the holder of the
copyright. SCIENCE-WEEK is published by Spectrum Press Inc.,
3023 N. Clark St. #109, Chicago, 60657 IL, US.
---------------------------------------------