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.

December 3, 1999 -- Vol. 3 Number 49

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Science gains reality when it is viewed not as an abstraction,
but as the concrete sum of work of scientists, past and present,
living and dead. Not a statement in science, not an observation,
not a thought exists in itself. Each was ground out of the harsh
effort of some man, and unless you know the man and the world in
which he worked; the assumptions he accepted as truths; the
concepts he considered untenable; you cannot fully understand the
statement or observation or thought.
-- Isaac Azimov (1920-1992)

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Contents of This Issue:

1. An Ethical Debate Concerning Sham Human Surgery
2. On Statistical Evolutionary Biology
3. Regeneration of a Germinal Layer in the Adult Mammalian Brain
4. Planetary Science: The Ocean of the Jovian Moon Europa
5. On Single Molecule Physics and Chemistry
6. On the Discovery of High Temperature Superconductivity
7. In Brief: Hazards in Zoos: Multiple Human Exposures to Rabies

In Focus: History of Biology: On 19th Century Vitalism

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1. AN ETHICAL DEBATE CONCERNING SHAM HUMAN SURGERY
One of the fundamental ethical dilemmas in clinical medicine
arises whenever a simple contradiction occurs between two axioms.
The first axiom is, "Do not harm the patient." The second axiom
is, "Do not use bogus medicine -- subject every treatment to
scientific validation." Consider, for example, surgical
procedures. Such procedures are frequently introduced into
general medical practice on the basis of uncontrolled studies
that are less rigorous than those generally required for the
approval of medical interventions. The standard for the
evaluation of surgical therapy is lower because of the complexity
of designing and conducting scientifically valid and ethically
acceptable clinical trials of surgical procedures. As a result,
many surgical trials fail to control for investigator bias and/or
placebo effects. The list of inadequate invasive or surgical
procedures that became part of standard medical practice in this
century only to be abandoned after closer scrutiny includes
bloodletting, routine tonsillectomy, routine circumcision,
repeated cesarean delivery, internal thoracic-artery ligation,
gastric freezing, jejuno-ilial bypass for morbid obesity,
glomectomy for asthma, adrenalectomy for essential hypertension,
and so on. In this century, millions of patients have been
subjected to surgical procedures without those procedures
validated by controlled experiments. The dilemma is clear: How do
we test a surgical procedure and at the same time obey the axiom
not to harm the patient? Recently, this dilemma was clearly
articulated by two contiguous articles devoted to the problem of
experimental human surgery in the treatment of Parkinson's
disease. This disease is a disorder of motor function
characterized by tremor, rigidity, decrease in spontaneity of
movement (bradykinesia), gait disturbance, and postural
instability. The main pathological features are a loss of
dopamine-secreting neurons (dopaminergic neurons) in a specific
brain region (substantia nigra) and a consequent reduction in
local levels of dopamine. One of many developed therapies is
fetal-tissue transplantation, a treatment of Parkinson's disease
based on research demonstrating that implanted embryonic
dopaminergic neurons can survive, reinnervate the deficient brain
region, and reverse motor abnormalities in animal models of
parkinsonism. At least 18 centers throughout the world have
introduced clinical transplantation programs for the treatment of
human Parkinson's disease, but the results have been variable and
so far clinicians cannot exclude the possibility that the
observed benefits are due to a placebo effect or investigator
bias.
... ... T.B. Freeman et al (7 authors at 4 installations, US)
present the case in favor of placebo-controlled surgical trials,
the authors having designed a study to test the efficacy of fetal
tissue transplantation in Parkinson's disease. According to the
experimental protocol, each placebo procedure includes the
placement of a *stereotactic frame, target localization on
*magnetic resonance imaging, the administration of general
anesthesia with a laryngeal-mask airway, and a skin incision with
a partial burr hole that does not penetrate the inner cortex of
the skull; in the placebo group, there are no needle penetrations
into the brain, and no fetal tissue is implanted. All patients
receive a low-dose immunosuppressant (cyclosporine) to inhibit
transplant rejection for 6 months, and the care before, during,
and after surgery is identical in all groups. All subjects are
aware of the existence of a placebo group. The authors present
the following argument:
     1) Randomized, double-blind, placebo-controlled trials are
the gold standard for evaluating new interventions, and are
routinely used to assess new medical therapies. Surgeons have
been reluctant to use imitation surgery as a placebo control in
the evaluation of new procedures, and it is estimated that only 7
percent of surgical investigators use a randomized study design
of any type. Cellular-based surgical therapies have much in
common with pharmacologic treatments and lend themselves to
evaluation in randomized, double-blind, placebo-controlled
trials.
     2) The authors conclude: "The inclusion of a placebo group
in our study of 36 subjects will permit us to establish whether
the benefit observed to date can be attributed to an effect of
treatment apart from a placebo effect. If fetal tissue
transplants are found to be safe and effective, thousands of
patients with Parkinson's disease stand to benefit, and further
research will be encouraged. If the transplants are found to be
unsafe or ineffective, or if they offer nothing more than a
placebo effect, hundreds or even thousands of patients will be
spared the risks and financial burdens of an unproved operation."
... ... In a contiguous article, Ruth Macklin (Albert Einstein
College of Medicine, US) presents a counter-argument, the author
making the following points:
     1) At first glance, the recent studies involving patients
with Parkinson's disease, in which sham surgery is used as a
control and real surgery is used to implant fetal cells, appear
to fulfill the conditions that would make placebo controls
ethically acceptable. Existing treatments for Parkinson's disease
are ineffective in helping patients regain lost motor function,
which is one of the hoped for results of surgical implantation of
fetal cells in the brain... Why should the use of sham surgery be
questioned when the conditions for the ethical acceptability of a
placebo-controlled study appear to be met? The chief reason is
that performing a surgical procedure that has no expected benefit
other than the placebo effect violates the ethical and regulatory
principle that the risk of harm to subjects must be minimized in
the conduct of research.
     2) The author concludes: "Sham surgery is ethically
unacceptable as a placebo control in trials of fetal-cell
transplantation in patients with Parkinson's disease. Sham
surgery, with accompanying anesthesia, poses the risks of any
surgical intervention that would not be used alone for
therapeutic purposes. In trials that use antibiotics to protect
subjects against infection, there are the added risks associated
with antibiotic treatment. In trials that forego the use of
antibiotics in the sham-surgery group, there are the added risks
of infection... The placebo-controlled trial may well be the gold
standard of research design, but unlike pure gold, it can be
tarnished by unethical applications."
-----------
Editor's note: This is a complex subject of considerable
importance, and our brief review here (and even the published
articles in question) cannot do the subject full justice. We
present the material here as a cogent example of a sharply drawn
ethical conflict in the fundamentals of scientific research.
-----------
T.B. Freeman et al: Use of placebo surgery in controlled trials
of a cellular-based therapy for Parkinson's disease.
(New England J. Med. 23 Sep 99 341:988)
QY: Thomas B. Freeman, University of South Florida, Tampa FL
33606 US.
-----------
Ruth Macklin: The ethical problems with sham surgery in clinical
research.
(New England J. Med. 23 Sep 99 341:992)
QY: Ruth Macklin, Albert Einstein College of Medicine, Bronx NY
10461 US.
-----------
Text Notes:
... ... *stereotactic frame: A stereotaxic device is a rigid
metal coordinate frame into which the head of a patient is fixed
so that microscale positioning of electrodes or cannulae at any
particular coordinate position can be effected without
displacement caused by movement of the patient.
... ... *magnetic resonance imaging: Magnetic resonance imaging
(MRI) is essentially a technique for examining morphology (as
opposed to _functional_ magnetic resonance imaging, which is a
technique for examining anatomical correlates of function). 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 magnetic field strengths of 1.5 tesla.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON NEW SURGICAL APPROACHES TO PARKINSON'S DISEASE
Parkinson's disease (also called Parkinson disease) is a slowly
progressive degenerative central nervous system disorder,
characterized by decreased movement, muscular rigidity, resting
tremor, and postural instability. The disease was first described
by James Parkinson (1817) and is now known to be associated with
degeneration of one or more specific regions of the brain
(dopaminergic neuron groups such as the *substantia nigra) and
resultant loss of *neural projections to several important brain
centers. Dopaminergic neurons are nerve cells that use dopamine
as a *neurotransmitter substance. Dopamine is found in several
major areas of the brain, and it is the degeneration of so-called
dopamine neurons that is apparently involved in Parkinson's
disease. One must distinguish "parkinsonism" from Parkinson's
disease. Parkinsonism is a syndrome (a complex of symptoms; in
this context, a complex of various movement symptoms) that may be
caused by Parkinson's disease, but which may also be caused by
infectious, vascular, pharmacological, toxic, metabolic,
structural, and various degenerative disorders. In other words,
not every individual with parkinsonism has Parkinson's disease.
The major differentiating characteristic is the response to the
drug "*levodopa", which is converted by the body into dopamine.
Individuals with parkinsonism who respond to levodopa treatment
receive a diagnosis of Parkinson's disease. At the present time,
Parkinson's disease is the 4th most common neurodegenerative
disease of the elderly. It affects approximately 1 percent of
people older than 65 years, and 0.4 percent of people between 40
and 65 years. ... ... Pat Phillips (_J. Amer. Med. Assoc._)
reviews current work on surgical approaches to the disease
presented at a recent (July 1999) international congress, the
author making the following points:
     1) Deep brain stimulation and cell transplantation are new
techniques of great interest to clinicians involved in the
surgical treatment of patients with Parkinson's disease,
particularly in the treatment of those patients in more advanced
stages of the disease. Apparently, one factor responsible for the
resurgence of interest in surgical treatment is the limited
success of medical therapy with the drug levodopa. Other factors
are safer and more accurate surgical techniques, improvements in
microelectrode recording techniques during surgery, and advances
in neuroimaging (i.e., imaging of gross brain structures), all of
which combine to allow surgeons to reach their targets with
greater accuracy and less likelihood of adverse effects.
     2) Concerning deep brain stimulation, at specialized centers
in Europe and North America, high-frequency deep brain
stimulation of 3 different targets in the brain has been the
focus of an apparently promising surgical approach. The targets
are the *subthalamic nucleus, the globus pallidus internus, and
the ventral intermediate nucleus. The procedure involves
implanting an electrode deep into one of the 3 target areas using
a *stereotactic technique and microelectrode guidance. The
microelectrodes provide recordings of local neuron activity that
enable the neurosurgeon to detect typical electrical activity
patterns of cell group targets or of adjacent structures to be
avoided.
     3) Concerning *cell transplantation, fetal cell
transplantation has been performed worldwide on approximately 360
patients in 17 clinical centers, and preliminary evidence
apparently indicates that the procedure can be done safely,
reliably, and reproducibly. However, this approach has been
limited because of societal concern about the use of fetal
tissue, and because of technical surgical issues, including
identification of the best target area for transplantation. Some
neurosurgeons believe it is unlikely that fetal tissue
transplantation will ever by performed outside of a small number
of clinical installations, and that instead fetal tissue
transplantation is likely to serve as the standard for assessment
of protocols using non-fetal tissue transplantation. Researchers
are currently experimenting with a variety of non-fetal cells for
use in transplantation. Retinal cells, for example, secrete
dopamine and neurotrophic factors, and are candidates for
transplantation research.
-----------
Pat Phillips: New surgical approaches to Parkinson disease.
(J. Amer. Med. Assoc. 22/29 Sep 99 282:1117)
QY: QY: Pat Phillips [jama@ama-assn.org]
-----------
Text Notes:
... ... *substantia nigra: A large cell mass at the base of the
brain that receives input from a number of cortical and
subcortical structures ("cortical" refers to cerebral cortex).
... ... *neural projections: In this context, the term
"projection" refers to arrays of nerve fibers originating in one
location and transmitting activity to one or more other
locations.
... ... *neurotransmitter substance: Neurotransmitters are
chemical substances released at the terminals of nerve axons in
response to the propagation of an impulse to the end of that
axon. The 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.
... ... *levodopa: (L-dopa) The biologically active form
of "dopa", which is converted into dopamine. Dopamine = 3,4-
dihydroxyphenylethylamine. Dopa = 3,4-dihydroxypheynylalanine.
... ... *subthalamic nucleus, the globus pallidus internus, and
the ventral intermediate nucleus: In this context, a "nucleus" is
a cluster of nerve cells in the brain. The term "basal ganglia"
refers to a group of nuclei lying deep in the subcortical white
matter of the frontal lobes, these nuclei involved in the
organization of motor behavior. The globus pallidus is one of the
major components of the basal ganglia, and the subthalamic
nucleus is often considered to be part of this group. The ventral
intermediate nucleus is a nucleus in the thalamus, a major
subcortical assembly of nuclei, and the ventral intermediate
nucleus is also involved in the modulation of motor control. In
general, the "modulation" of motor control in the nervous system,
like the modulation of the motions of a complex machine, depends
in a major way on feedback control circuits. In the human nervous
system, the motor control feedback loops are widespread in the
brain, involving a number of major structures, and dysfunctions
in any local parts of the various loops can have serious
consequences.
... ... *stereotactic technique: A stereotaxic device is a rigid
metal coordinate frame into which the head of a patient is fixed
so that microscale positioning of electrodes at any particular
coordinate position can be effected without displacement caused
by movement of the patient.
... ... *cell transplantation: In general, the cell
transplantation procedures in this context are at the present
time concerned with the transplantation of cells that secrete
dopamine, the objective to increase the working concentration of
dopamine in relevant structures. The transplanted cells are thus
drug delivery vehicles rather than replacements for dysfunctional
neurons. Fetal cell transplantation, however, offers the
possibility of transplantation of primitive cells (stem cells)
that will differentiate into working new neurons that supplant
defective adult neurons.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 22Oct99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON PARKINSON'S DISEASE
Parkinson's disease, first described by James Parkinson more than
180 years ago, is a major neurodegenerative disease of unknown
cause. ... ... A.E. Lang and A.M. Lozano present the first of a
2-part extensive review of the disease and make the following
points: 1) The disease effects over 1 million people in North
America. Age is the single most consistent risk factor, and the
prevalence of the disease is expected to rise steadily in the
future with the increasing age of the general population.
Mortality is 2 to 5 times as high among affected persons as among
age-matched controls, resulting in a marked reduction in life
expectancy. In general, neurodegenerative diseases (Parkinson's
disease, motor neuron disease, and dementia) are projected to
surpass cancer by the year 2040 as the second most common cause
of death among the elderly. 2) Parkinson's disease occurs
throughout the world, in all ethnic groups, and affects both
sexes approximately equally or with a slight predominance among
males. The prevalence increases exponentially with age between 65
and 90 years. Approximately 0.3 percent of the general population
and 3 percent of people over the age of 65 have the disease. 5 to
10 percent of patients have symptoms before the age of 40. The
lowest reported incidence is among Asians and African blacks,
whereas the highest reported incidence is among whites. 3) The
classic triad of major signs of Parkinson's disease consists of
tremor, rigidity, and akinesia (absence or loss of the power of
voluntary movement). The diagnosis is made on the basis of
clinical criteria, and underdiagnosis is common. Misdiagnosis is
also common, because the syndrome may be produced by different
causes such as drugs, *Wilson's disease, and other
neurodegenerative diseases. Although the neuropathological
examination is the standard for diagnosis of Parkinson's disease,
there is still no biological marker that unequivocally confirms
the diagnosis. 4) At the cellular level, Parkinson's disease is
characterized by the progressive death of specific but
heterogeneous populations of neurons, including *dopaminergic
neurons in the *substantia nigra, *aminergic *brainstem nuclei,
the *cholinergic *nucleus basalis of Meynert, *hypothalamic
neurons, and small *cortical neurons. In addition, degeneration
of nerve cells in the *olfactory bulb, *sympathetic ganglia, and
*parasympathetic neurons in the gut may also be involved in the
disease. 5) The mechanisms responsible for cell death in
Parkinson's disease are largely unknown. Evidence suggests that
neuronal death in the substantia nigra may involve *apoptosis,
but this idea is not universally accepted. Among the factors that
have been implicated in neuronal degeneration in this disease are
*mitochondrial dysfunction, *oxidative stress, the actions of
*excitotoxins, deficient *neurotrophic support, and immune
mechanisms. A critical question is why specific neurons are
selectively vulnerable to the disease.
-----------
A.E. Lang and A.M. Lozano (2 installations, CA)
Parkinson's disease.
(New England J. Med. 8 Oct 98 339:1044)
QY: Anthony E. Lang, Toronto Hospital, 399 Bathurst St., MP 11,
Toronto, ON M5T 2S8 CA.
-----------
Text Notes:
... ... *Wilson's disease:  A rare genetic disease involving
copper metabolism dysfunction.
... ... *dopaminergic neurons: Nerve cells that use dopamine as a
*neurotransmitter substance. "Levodopa", which is used in the
treatment of Parkinson's disease, is the biologically active form
of "dopa", which is converted into dopamine. Dopamine = 3,4-
dihydroxyphenylethylamine. Dopa = 3,4-dihydroxypheynylalanine.
... ... *neurotransmitter substance: See main report.
... ... *substantia nigra: A large cell mass at the base of the
brain that receives input from a number of cortical and
subcortical structures ("cortical" refers to cerebral cortex).
... ... *aminergic: In this context, the term refers in general
to neurons whose neurotransmitters are amines.
... ... *brainstem nuclei: Clusters of nerve cells in the
brainstem, which is a phylogenetically old region of the central
nervous system that among other things contains control centers
for fundamental physiological processes such as breathing and
heart rate. Anatomically, the brainstem is the connecting region
between the brain above it and spinal cord below it.
... ... *cholinergic: Refers to synaptic transmission mediated by
the release of acetylcholine.
... ... *nucleus basalis of Meynert: One of the basal nuclei
(neuron clusters) lying deep in the subcortical white matter of
the frontal lobes and involved in the organization of motor
behavior.
... ... *hypothalamic neurons: A deep brain structure with
various clusters of nerve cells controlling several important
homeostatic functions such as temperature regulation and food
intake, and in addition the sex drive, aggressive emotions,
psychosomatic effects, etc. The hypothalamus essentially
integrates the activity of the autonomic nervous system, and it
acts as an intermediary between the endocrine (hormone) system
and the nervous system, with various hypothalamic neuron types
secreting hormones themselves. In general, the term "hormones"
refers to chemical messengers which are distributed systemically
via the bloodstream. 
... ... *cortical neurons: In general, neurons of the cerebral
cortex, the phylogenetically newer part of the brain that
controls the higher analysis of sensory data and most non-
automatic activities.
... ... *olfactory bulb: Olfactory relay station that receives
axons from the olfactory cranial nerve and transmits the
information via the olfactory tract to higher centers.
... ... *sympathetic ganglia: Nerve cell clusters in the
sympathetic nervous system, which is a division of the peripheral
autonomic nervous system in vertebrates comprising, for the most
part, adrenergic neurons (nerve cells that secrete norepinephrine
or epinephrine as neurotransmitters) located relatively distant
from target organs.
... ... *parasympathetic neurons: The parasympathetic nervous
system is a division of the autonomic nervous system comprising
cholinergic nerve cells clusters located near target organs.
... ... *apoptosis: Programmed cell death produced by control
mechanisms designed to destroy defective cells.
... ... *mitochondrial dysfunction: Mitochondria are organelles
of the cell cytoplasm, and they are the principal energy source
of the cell, containing various enzymes involved in electron
transport and metabolic cycles.
... ... *oxidative stress: In this context, the term "oxidative"
refers to oxidative metabolism, a set of biochemical pathways
dependent on the utilization of supplied oxygen.
... ... *excitotoxins: Toxins that bind to certain neuron
receptors and which may be involved in neuron cell death. Certain
amino acids (e.g., glutamic acid) can act as excitotoxins, and
their study has given rise to the "excitotoxicity hypothesis",
which proposes that the effects produced by these amino acids are
caused by a prolonged depolarization of receptive neurons, the
process leading somehow to the eventual damage or death of these
nerve cells.
... ... *neurotrophic support: In general, neurons in the central
nervous system apparently depend for their survival on a number
of secreted substances called neurotrophins (neurotrophic
factors).
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 6Nov98
[For more information: http://scienceweek.com/search/search.htm]


2. ON STATISTICAL EVOLUTIONARY BIOLOGY
*Phylogenetic "trees" describe the pattern of descent amongst a
group of species. With the rapid accumulation of DNA sequence
data, an increasing number of phylogenies are being constructed
based upon sequence comparisons. The combination of these
phylogenies with new statistical approaches for the analysis of
biological evolution is challenging some widely held beliefs
concerning the history and evolution of life on Earth.
... ... Mark Pagel (University of Reading, UK) presents a review
of recent work in statistical evolutionary biology, the author
making the following points:
     1) Since 1981, the number of articles reporting phylogenies
based on gene sequence information has been increasing
exponentially, with more than half appearing since 1996. The
phylogenies span taxonomic groups ranging from viruses to
bacteria, fungi, plants, and animals. The prospect of describing
in detail the patterns of descent within many of the major groups
of organisms, seen as fanciful just 10 years ago, is now
realistic.
     2) But the influence of these new phylogenies extends beyond
cataloguing the relatedness of species. Since all the events of
biological evolution are played out somewhere along the branches
of phylogenetic trees, these phylogenetic trees preserve traces
of the historical evolutionary processes that gave rise to the
diversity of contemporary species. This raises the intriguing
possibility that the combination of a phylogeny and information
on species can be used to infer what the past was like and how
the present came about.
     3) Recent advances in statistical modelling of evolution on
phylogenetic trees, particularly the use of "*maximum-likelihood
techniques", are providing researchers with new ways to
investigate the evolution of life on Earth. What sets the new
statistical techniques apart from conventional non-statistical
methods or paleontological approaches is the range of
characteristics that can be investigated and the nuances of
historical trends of evolution that can be characterized. The
result is that a new era of biological studies is emerging in
which statistical approaches applied to phylogenies and
information about species form an independent branch of
historical inquiry.
     4) Four areas of historical evolutionary inquiry have
benefitted most from the new statistical approaches:
... ... a) Reconstruction of ancestral character states, using a
phylogeny in combination with a statistical description of how
the traits or organisms evolve, to discover the most probable
characteristics of ancestral species.
... ... b) Estimations of the timings of historical evolutionary
events.
... ... c) Assessment of the tempo of evolution, which in turn
allows the testing of *punctuational or gradual models of
evolution.
... ... d) Comparative studies, using correlation and regression
to investigate which features of organisms change with which
other features or with aspects of their environment, which can
provide evidence for the temporal order of changes in two traits,
suggesting possible causal pathways.
     5) The author concludes: "The growth of statistical
inference techniques brings a new and independent point of view
to debates about the history of life... Statistical techniques
for inferring the history and pattern of evolution will prove
invaluable for looking into the past in ways, and for kinds of
traits, that are out of reach to other approaches."
-----------
Mark Pagel: Inferring the historical patterns of biological
evolution.
(Nature 28 Oct 99 401:877)
QY: Mark Pagel, School of Animal and Microbial Sciences,
University of Reading, UK.
-----------
Text Notes:
... ... *Phylogenetic "trees": The term "phylogeny" refers to the
evolutionary history of a species or group of species in terms of
their derivation and relationships. A "phylogenetic tree" is a
schematic diagram that represents that evolution.
... ... "*maximum-likelihood techniques: The author provides the
following definition: "A set of techniques for choosing the
parameters of a statistical model in such a way as to provide the
most probable description of the observed data, given the model."
In general, in statistical analysis, the "maximum likelihood
method" is a procedure of finding the value of one or more
parameters for a given statistic which makes the known likelihood
distribution a maximum. The "likelihood" is the hypothetical
probability that an event which has already occurred would yield
a specific outcome. The concept of "likelihood" differs from that
of probability in that a probability refers to the occurrence of
future events, while a likelihood refers to past events with a
known outcome.
... ... *punctuational or gradual models of evolution: In recent
years, considerable debate in evolutionary biology has focused on
the rate of evolutionary change. Some biologists propose that
evolution largely occurs by gradual change; other biologists take
the view that species persist unchanged for considerable periods
of time, with relatively rapid speciation events "punctuating"
the fossil record.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON MODELS OF MOLECULAR EVOLUTION AND PHYLOGENY
The term "phylogeny" refers to the evolutionary history of a
group of organisms, and the term "molecular phylogenetic
relationships" refers especially to relationships between the DNA
and proteins of one species and the DNA and proteins of other
species, such relationships evidently derived from evolutionary
relationships. Reconstructing evolutionary relationships is
called "phylogenetic reconstruction", and this is a fast-growing
field involving various statistical approaches and applications
of findings in a broad range of biological specialties.
Fundamental to the statistical approaches are mathematical models
used to describe the patterns of DNA base substitution and
protein amino acid replacement, and such models have potential as
a basis for comparative genome research. ... ... P. Lio and N.
Goldman present a review of current work on models of molecular
evolution and phylogeny, the authors making the following points:
1) A geneticist reconstructs molecular phylogenetic relationships
by proceeding hierarchically. The first step comprises DNA
sequence selection and alignment to determine site-by-site
homologies and to detect DNA (or amino acid) differences. 2) The
second step is to build a mathematical model describing the
evolution in time of the sequences. A model can be built
empirically, using properties calculated through comparisons of
observed sequences, or parametrically, using chemical or
biological properties of DNA and amino acids (e.g., the
*hydrophobicity values of each amino acid). Such models permit
estimation of the genetic distance between two *homologous
sequences, the distance measured by the expected number of
nucleotide substitutions per site that have occurred between the
genome of a species and the genome of its most recent common
ancestor. Such distances may be represented as branch lengths in
a phylogenetic tree: the extant sequences form the tips of the
tree, whereas the ancestral sequences form the internal nodes and
are generally not known. 3) The third step in molecular
phylogenetic reconstruction involves applying an appropriate
statistical method to find the tree topology and branch lengths
that best describe the phylogenetic relationships of the
sequences. The authors suggest that the modeling of processes of
sequence evolution is a thriving field of research with two
immediate and important benefits: a) an improved understanding of
the biological processes that shape evolution at the molecular
level, and b) an improved ability to infer from sequence data the
story of the evolution of life on Earth.
-----------
P. Lio and N. Goldman: Models of molecular evolution and
phylogeny.
(Genome Research December 1998 8:1233)
QY: Nick Goldman [N.Goldman@gen.cam.ac.uk]
-----------
Text Notes:
... ... *hydrophobicity: In general, the term "hydrophobic"
refers to a tendency not to dissolve in water, to have a low
affinity for water, etc. In chemistry, a "hydrophobic
interaction" is an association of nonpolar molecules or groups in
aqueous media, the interaction resulting from the tendency of
water molecules to exclude nonpolar species.
... ... *homologous sequences: In this context, the term
"homologous" refers to DNA or protein macromolecules having the
same or similar residues at corresponding positions.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 12Mar99
-------------------
[For more information: http://scienceweek.com/search/search.htm]


3. REGENERATION OF A GERMINAL LAYER IN THE ADULT MAMMALIAN BRAIN
Until recently, one of the dogmas of neurobiology was that the
adult mammalian brain is incapable of regeneration: after injury,
neurons in the central nervous system do not spontaneously
reestablish their connections. During the past decade, however,
progress has been made in identifying various factors and types
of cells that can promote a degree of *axonal regeneration, and
an unanticipated form of *neuroplasticity in the adult mammalian
brain has been demonstrated  -- the continued production of new
neurons in certain brain regions. For example, proliferating
cells apparently persist throughout adult life along the length
of the lateral wall of the internal brain fluid space known as
the "lateral *ventricles". This germinal region, called the
"subventricular zone", generates new neurons destined for the
part of the brain receiving olfactory sensory information
(olfactory bulb). The olfactory bulb is a major mammalian brain
structure, considerably reduced in size in man, but still of
physiological importance [*Note #1]. The subventricular zone is
organized as an extensive network of chains of migrating cells
destined to become neurons (neuroblasts). The newly generated
neuroblasts migrate through the subventricular zone to join a
migrating stream of precursor neurons that leads to the olfactory
bulb, and in the olfactory bulb, the new neurons differentiate
into various types of nerve cells
... ... F. Doetsch et al (3 authors at 2 installations, US ES)
now report that after treatment of the adult mouse brain with an
antimitotic agent (cytosine-beta-D-arabinofuranoside) (i.e., an
agent that stops cell mitosis), subventricular zone neuroblasts
are eliminated, but the subventricular zone network then rapidly
regenerates. In 2 days, precursor cells reappear, followed at 4.5
days by migrating neuroblasts. By 10 days, the subventricular
zone network is fully regenerated, and the orientation and
organization of chains of migrating neuroblasts resemble that of
normal mice. The authors suggest this regeneration reveals an
unexpected plasticity in the adult central nervous system and
should provide a model system to study the early stages of
neurogenesis in the adult brain.
-----------
F. Doetsch et al: Regeneration of a germinal layer in the adult
mammalian brain.
(Proc. Natl. Acad. Sci. US 28 Sep 99 96:11619)
QY: Arturo Alavarz-Buylla [alvarez@rockvax.rockefeller.edu]
-----------
Text Notes:
... ... *axonal regeneration: In general, nerve cells have a
single long extension (the "axon") that propagates the electrical
output (the action potential) of the cell. In some types of nerve
cells, axons are extensively branched into a multitude of fine
fibers that make contact (synapses) with other nerve cells. 
... ... *neuroplasticity: In neurobiology, the term "plasticity"
is the name given to the capacity of neural tissue to adjust to
change. One variant of this concerns the dependence of the
"wiring" of the nervous system on its input. Another variant
concerns the degree to which one region can under certain
conditions assume the function of another region. A 3rd meaning,
used in this report, refers to the ability of the nervous system
to repair itself after damage, i.e., to regenerate both cells and
connections between cells.
... ... *ventricles: The ventricles are spaces in the vertebrate
brain that comprise the remnants of the embryonic neural tube.
These spaces are filled with cerebrospinal fluid (CSF), a clear
colorless fluid that flows continuously in the brain and spinal
cord, the fluid containing proteins, glucose, and various
electrolytes.
... ... **Note #1: The olfactory sensory tissue system (olfactory
epithelium) comprises approximately 10 square centimeters in a
70-kilogram human and 20 square centimeters in a 3-kilogram cat.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
ON NEW NERVE CELLS IN THE ADULT HUMAN BRAIN
During most of this century, one of the dogmas in neurobiology
was that in the adult human brain new connections between neurons
may arise, but never new neurons. The dogma, in other words, was
that in the adult human brain new nerve cells are not produced,
and the neurons present at birth are the neurons present in the
adult, albeit a maximum number of nerve cells at birth, since a)
the number of neurons in the healthy adult human brain apparently
decreases with age beginning at about age 35; and b) various
neurodegenerative diseases can markedly reduce the population of
neurons in either specific regions of the brain or globally
nearly everywhere in the brain. In recent years, this dogma, the
idea that new nerve cells are not produced in the adult human
brain, has effectively crumbled for at least one specific and
important brain locus called the "hippocampus", which is a region
of the cerebral cortex in the *medial part of the temporal lobe.
In humans, among other functions, the hippocampus is apparently
involved in short-term memory, and analysis of the neurological
correlates of learning behavior in animals indicates that the
hippocampus is also involved in memory in other species.
... ... G. Kempermann and F.H. Gage (2 installations, DE US)
present a review of past and current research in adult
neurogenesis in humans, the authors making the following points:
     1) In 1965, Altman and Das reported neurogenesis in the
hippocampus of rats, in a subregion of the hippocampus called the
"dentate gyrus". But this data was not viewed as evidence of
significant neurogenesis in adult mammals, primarily because the
methods available then could not accurately estimate the number
of new neurons nor demonstrate definitively that the new cells
were indeed nerve cells. In addition, the concept of *stem cells
in the brain had not yet been introduced, and the belief was that
for new neurons to appear, the only source would be replication
(i.e., mitosis) of adult neurons. There was also no evidence that
neurogenesis occurred in non-human primates, and so the relevance
of the rat data for the human brain seemed remote.
     2) In the mid 1980s, Nottebohm discovered that neurogenesis
occurred in adult canaries in brain centers responsible for song
learning, and that the process accelerated during the seasons in
which the adult birds acquired their songs. Nottebohm and his co-
workers then demonstrated that neurogenesis also occurred in the
hippocampus of adult chickadees, particularly during seasons when
the birds had to keep track of dispersed food storage sites.
     3) In 1997, Gould and McEwan reported that some neurogenesis
occurs in the hippocampus of the primate-like tree shrew, and in
1998, these authors found the same phenomenon in marmoset
monkeys, which are classified as actual primates.
     4) Because of research difficulties, demonstration of
neurogenesis in the adult human brain had to await special
techniques. In 1998, Peter S. Eriksson reported the use of
bromodeoxyruridine as a marker for neurogenesis and the first
evidence for neurogenesis in the hippocampus of adult humans. The
use of this marker depended on its already established use as a
tumor marker in cancer patients. Bromodeoxyuridine is a marker
that becomes integrated only into the DNA of cells preparing to
divide, and the marker was in use with terminally ill patients
with cancer of the tongue or larynx. Eriksson obtained consent
from a number of patients to investigate their brains after
death, and when 5 patients died, all 5 brains displayed new
neurons in the dentate gyrus subregion of the hippocampus. At the
same time as this study was reported, other research groups
reported nerve cell production in the hippocampus of adult rhesus
monkeys, which are primates closer to humans than marmoset
monkeys.
     5) In their review, the authors refer to their own work,
noting that beginning in 1997, they have demonstrated that adult
mice given enriched living conditions generate substantial
increases in dentate gyrus hippocampal neurons over that found in
genetically identical control animals.
     6) The authors suggest that studies of neurogenesis in the
adult human brain, while difficult, may lead to better treatments
for a variety of neurological diseases. The authors conclude:
"The expected benefits of unlocking the brain's regenerative
potential justify all the effort that will be required."
-----------
G. Kempermann and F.H. Gage: New nerve cells in the adult brain.
(Scientific American May 1999)
QY: Gerd Kempermann, University of Regensburg, DE.
-----------
Text Notes: 
... ... *medial part of the 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. Isolated verbal descriptions of the
architecture are of limited use: anatomical graphics are the best
sources for visualization of gross brain structures.
... ... *stem cells: In general, the term "stem" cells
refers to undifferentiated cells that upon differentiation can
give rise to various specialized cell lines such as blood cells,
skin cells, nerve cells, etc. Adult bone marrow, for example,
contains stem cells that are the precursors of the various
specialized types of blood cells.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 18Jun99
-------------------
Related Background:
REGENERATION OF AXONS IN CENTRAL NERVOUS SYSTEM WHITE MATTER
When examining the gross anatomy of the mammalian brain and
spinal cord, a striking feature is the presence of large regions
with an opalescent ivory color. The color is due to myelin, the
substance that sheaths many nerve fibers in the central nervous
system. In the vertebrate central nervous system, the axons of
nerve cells involved in physiological functions that require
rapid signaling (for example, the neural control of voluntary
muscle) are wrapped in myelin with a special consequence. The
myelin sheath consists of concentric layers of electrically
insulating lipid material, but the sheath is periodically
interrupted, and at the points where the sheath is interrupted so
is the electrical insulation interrupted. The result, predictable
from the classical physics of electrical transmission lines and
the electrical parameters of nerve fibers, is that the propagat-
ion of an electrical pulse along such nerve fibers occurs at a
velocity much higher than that found in unmyelinated fibers.
Glial cells are cells of the central and peripheral nervous
system that metabolically support neurons and produce the
multiple membrane layers called myelin and enfold nerve cell
axons with it. The glial cells are found everywhere in the brain
and spinal cord, and one result of a localized injury to the
central nervous system is a local proliferation of glial cells to
form a scar matrix. Concerning brain and spinal cord injury, it
has always been a canon of neurobiology that adult central
nervous system neurons cannot regenerate after injury to re-
establish the connections to other cells necessary for proper
functioning. Davies et al (6 authors at 2 installations, US UK),
using microtransplantation techniques, now report that adult
central nervous system white matter can support long-distance
regeneration of adult axons provided the reactive glial
extracellular matrix at the site of the lesion can be bypassed.
The authors suggest this is the first time this glial barrier to
axon regeneration has been noted.
QY: Jerry Silver [jsx10@po.cwru.edu]
(Nature 18/25 Dec 97) (Science-Week 9 Jan 98)
-------------------
Related Background:
REGENERATION OF MOTOR NEURONS: IDENTIFICATION OF A MITOGEN
Motor neurons are nerve cells that transmit nerve signals from
the brain or spinal cord to muscle or gland tissue, and sensory
neurons are nerve cells that carry signals from various parts of
the body to the brain or spinal cord. High signal propagation
velocities in motor and sensory neurons in vertebrates are
achieved by association of the nerve fiber with an enfolding
sheath called myelin. The myelin sheath consists of concentric
layers of electrically insulating lipid material, but the sheath
is periodically interrupted, and at the points where the sheath
is interrupted so is the electrical insulation interrupted. The
result, predictable from the classical physics of electrical
transmission lines and the electrical parameters of nerve fibers,
is that the propagation of an electrical pulse along such nerve
fibers occurs at a velocity much higher than that found in
unmyelinated fibers. Glial cells are the cells of the central and
peripheral nervous system that produce the multiple membrane
layers called myelin and enfold nerve cell axons with it, and
Schwann cells are a particular type of glial cell. A mitogen is
any compound that stimulates mitotic cell division. Livesey et al
(6 authors at 3 installations, UK CA) report the identification
of an extracellular signaling molecule, previously described as
the pancreatic secreted protein Reg-2, that is expressed solely
in regenerating and developing rat motor and sensory neurons,
with Reg-2 a potent Schwann cell mitogen in vitro. In vivo, Reg-2
is apparently transported along regrowing axons, and inhibition
of Reg-2 significantly retards the regeneration of axons
containing the protein. The authors suggest that Reg-2 is an
essential component of the neuron-glia interactions underlying
development and regeneration of mammalian motor neurons.
QY: Frederick J. Livesey [rlivesey@mail.tcd.ie]
(Nature 11 Dec 97) (Science-Week 2 Jan 98)
[For more information: http://scienceweek.com/search/search.htm]


4. PLANETARY SCIENCE: THE OCEAN OF THE JOVIAN MOON EUROPA
Jupiter's satellite system consists of at least 16 moons, the
four largest of which are called the Galilean moons, since they
were discovered by Galileo. They are Io, Europa, Ganymede, and
Callisto, in order of their orbital distance from Jupiter.
Europa, which is slightly smaller than Earth's moon, has a thick
icy crust, and may also have a liquid water mantle beneath this
crust. Very few craters are present on Europa, which suggests an
active surface that renews itself and thus erases craters as fast
as they form from impacts. The surface also shows numerous lines
about 30 kilometers wide and 1000 kilometers long, and these have
been interpreted to be breaks in the crust where water from below
has refrozen. The possible existence of a liquid water mantle
beneath the ice on Europa is of great interest to planetary
scientists, since such a mantle might contain life forms.
... ... R.T. Pappalardo et al (3 authors 2 installations, US)
present a review of current research on Europa's apparent
subsurface ocean, the authors making the following points:
     1) In the 1960s, spectroscopic data indicated that the
Jovian satellite Europa, like many others in the outer Solar
System, is covered with ice. With surface temperatures of 110
degrees kelvin near the equator and 50 degrees kelvin near the
poles, the ice on Europa must form a rock-hard skin. Recently,
spectacular images radioed from visiting spacecraft have revealed
a young and tremendously deformed surface. Apparently, somewhere
under the icy shell must be a warm mobile interior. Is it glacial
ice? Or are the innards of Europa warm enough to sustain an ocean
of liquid water?
     2) Theory and observation have combined to provide a strong
self-consistent case for a global ocean within Europa. But the
existence of this ocean is not unequivocally proved. Warm
subsurface ice could mimic many of the effects of an internal
ocean. Although the surface of the satellite is sparsely cratered
and probably geologically young, searches for definitive evidence
of ongoing geological activity have been fruitless. Europa might
have had an ocean in the recent past that is now frozen solid.
The only way to be certain is to return a spacecraft to Europa
and this time go into orbit.
     3) Such a mission is being planned by the US National
Aeronautics and Space Administration (NASA). The Europa Orbiter
Mission could be launched as early as November 2003 and would
enter Jupiter's orbit 3 years later. Approximately 2 years after
that, the spacecraft would go into orbit around Europa at an
average altitude of just 200 kilometers. Precise tracking of the
position and altitude of the spacecraft would map the
gravitational field and shape of Europa in enough detail to track
the ebb and flow of tides as the moon trundles around Jupiter. If
Europa does have a subsurface sea, the surface of the moon should
rise and fall 30 meters every 3.6-day orbit. In this way, the
Europa Orbiter will provide the definitive test for an ocean.
-----------
R.T. Pappalardo et al: The hidden ocean of Europa.
(Scientific American October 1999)
QY: Robert T. Pappalardo, Brown University, US.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
NEW EVIDENCE FOR SUBSURFACE OCEANS IN EUROPA AND CALLISTO
The 4 largest of Jupiter's moons are called the Galilean moons,
and in order from outermost inward they are Callisto, Ganymede,
Europa, and Io. Callisto is a low-density moon 44 percent larger
than Earth's moon. Europa is denser than Callisto and slightly
smaller than Earth's moon, and it apparently contains a liquid
water mantle and a thick icy crust. Because of the presence of
large amounts of liquid water, Europa has been considered a
possible abode of life. Since 7 December 1995, the Galileo
spacecraft has been orbiting Jupiter and transmitting data
concerning the Jovian moons, and initial results from the
spacecraft's *magnetometer have indicated that neither Europa nor
Callisto have an appreciable internal magnetic field, in contrast
to Ganymede and possibly Io. ... ... K.K. Khurana et al now
report perturbations of the external magnetic fields (associated
with Jupiter's inner *magnetosphere) in the vicinity of both
Europa and Callisto. The authors interpret these perturbations as
arising from induced magnetic fields generated by the moons in
response to the periodically varying *plasma environment. The
authors suggest that *electromagnetic induction requires *eddy
currents to flow within the moons, and that their calculations
indicate that the most probable explanation is that there are
layers of significant electrical conductivity just beneath the
surfaces of both moons. The authors propose that these conducting
layers may be best be explained by the presence of salty liquid-
water oceans, for which there is already indirect geological
evidence in the case of Europa.
-----------
K.K. Khurana et al (7 authors at 3 installations, US)
Induced magnetic fields as evidence for subsurface oceans in
Europa and Callisto.
QY: K.K. Khurana [kkhurana@igpp.ucla.edu]
(Nature 22 Oct 98 395:777)
-----------
Text Notes:
... ... *magnetometer: In general, any instrument used to measure
the strength and direction of a magnetic field.
... ... *magnetosphere: In general, a region surrounding a planet
in which charged particles are controlled by the magnetic field
of the planet rather than by the magnetic field of the Sun. The
charged particles originate in the *solar wind (or stellar wind,
if the planet is extrasolar), and they form a tenuous ionized gas
(*plasma) surrounding the planet.
... ... *plasma: In general, a fully ionized gas consisting of
ions and electrons moving freely. 
... ... *solar wind: The solar wind is the steady flow of charged
particles, consisting primarily of protons and electrons, from
the solar corona into interplanetary space. The solar wind
particles have energies high enough so they can escape the Sun's
gravitational field, but the wind is influenced by the Sun's
magnetic field, and the particles can be trapped by planetary
magnetic fields.
... ... *electromagnetic induction: In general, this refers to
the production of an electromotive force either by motion of a
conductor through a magnetic field so as to cut across the
magnetic flux (magnetic "lines of force") or by a change in the
magnetic flux that threads a conductor.
... ... *eddy currents: (Foucault currents) In general, an eddy
current is an electrical current induced within the body of a
conductor when that conductor either moves through a nonuniform
magnetic field or is in a region where there is a change in
magnetic flux.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 13Nov98
-------------------
Related Background:
MOUNTING EVIDENCE FOR A SUB-SURFACE OCEAN ON JUPITER'S EUROPA
Europa is the smallest of Jupiter's so-called Galilean
satellites, with a diameter of 3138 kilometers. It has a smooth
crust of water-ice, criss-crossed by a network of light and dark
linear markings. It has been thought that beneath the crust there
may be an ocean of water, and a variety of ice tectonics has been
proposed to be operating on the surface. The Galileo spacecraft
is a US National Aeronautics and Space Administration mission to
Jupiter launched in 1989. ... ... Now Carr et al (22 authors at
12 installations, US DE) report high-resolution (54 meters per
pixel) Galileo spacecraft images of Europa that provide evidence
for mobile "icebergs", the detailed morphology of the terrain
strongly supporting the presence of liquid water at shallow
depths below the surface either at present or at some time in the
past. In a contiguous report, Pappalardo et al (11 authors at 7
installations, US) report an analysis of certain surface features
of Europa also revealed by high-resolution images from the same
spacecraft, and conclude the features are surface manifestations
of localized relatively warm ice masses that have risen through
the subsurface, and are consistent with a subsurface liquid water
ocean. Results from 2 other contiguous reports are also
interpreted as consistent with the idea of a subsurface liquid
water ocean on Europa.
QY: Michael H. Carr [carr@astmnl.wr.usgs.gov]; R.T. Pappalardo
[robert_pappalardo@brown.edu]; Robert Sullivan
[sullivan@cuspif.tn.cornell.edu]
(Nature 22 Jan 98) (Science-Week 6 Feb 98)
-------------------
Related Background:
NEW DETERMINATIONS OF INTERNAL STRUCTURE OF JUPITER'S MOON EUROPA
Data from the December 19, 1996 Galileo spacecraft encounter
with the Jovian moon Europa have now been published, and the
consensus is that Europa has a water ice-liquid outer shell
about 100 to 200 kilometers thick. Gravitational effects on the
spacecraft are consistent with two models of Europa. In one the
core is a mixture of rock and metal, and in the other it is
purely metallic. Further data concerning Europa's intrinsic
magnetic field is needed to distinguish between the two models.
Reports were provided by J. D. Anderson et al (California
Institute of Technology, Pasadena CA US; University of
California Los Angeles, CA US) and M. G. Kivelson et al
(University of California Los Angeles, CA US; Imperial College of
London UK; California Institute of Technology, Pasadena CA US).
(Science 23 May 97) (Science-Week 29 May 97)
-------------------
Related Background:
POSSIBILITY OF A DEEP OCEAN ON JUPITER'S MOON EUROPA
...Until recently, most planetary scientists apparently doubted
any contemporary existence of a liquid water mantle on Europa.
But new analyses have been appearing, and at the meeting last
week of the Division for Planetary Sciences of the American
Astronomical Society in Boston, a consensus appears to have
formed that a water mantle probably existed in the recent past,
and may even exist today. In December, the Galileo spacecraft, as
part of its extended mission, will take an even closer look at
Europa, with the resolution of its best images expected to
improve from 70 meters to 10 meters, and planetary scientists are
hopeful the question of the state of water on Europa will be
answered.
(Science 8 Aug 97) (Science-Week 15 Aug 97)
[For more information: http://scienceweek.com/search/search.htm]


5. ON SINGLE MOLECULE PHYSICS AND CHEMISTRY
Only a few decades ago, most scientists believed that individual
molecules would not come within the domain of experimental
observations within their lifetime, if ever, and that the
statistical ensemble properties of molecules were therefore the
only properties of relevance. That view has now undergone a
dramatic alteration as a consequence of technological advances,
and there is much excitement evident in many laboratories over
the prospects of single-molecule explorations in physics,
chemistry, and biology.
... ... C. Bai et al (4 authors at 3 installations, CN US)
present a short review of recent work in single-molecule physics
and chemistry, the authors making the following points:
     1) The authors point out that when Richard Feynman (1918-
1988) was bothered while looking through one of the first
*scanning tunneling microscopes, he was upset to have been
interrupted because seeing the images of singe atoms was a
"religious experience". For many generations of scientists, the
molecule was both the concrete ultimate entity upon which our
understanding of the everyday world was based, and at the same
time an elusive intellectual construct whose very existence could
only be inferred circumstantially by experiments on macroscopic
samples. Thus, seeing an individual atom or molecule in motion
brings immediate emotional impact to this central concept of
modern thought.
     2) The authors ask: "When is molecular individuality
important?" The new possibility of studying single molecules is
important because molecular individuality does finally come into
play when the molecule is a complex entity. This may occur
because the molecule itself may have an intricate internal
structure -- e.g., a biomolecule -- resulting in a complex energy
landscape. Alternatively, the molecule may be part of a complex
environment that substantially changes the behavior of the
molecule. Here, distinguishing different molecules at different
locales is crucial for understanding the system as a whole.
Biomolecules in living cells are examples of this. Even simple
inorganic molecules on structured surfaces or in disordered
systems such as viscous liquids or glasses provide situations in
which molecular individuality matters. In all of these cases, the
capability of studying an individual molecule over time can
provide new insights unavailable by straightforward experiments
on macroscopic populations of molecules.
     3) With the aid of *scanning probe microscopy, direct
observations of entire arrays of atoms, molecules, and the fine
structures of molecular aggregates have become possible. The
ability to precisely control probes permits the study of long-
range structures made by molecules lying on surfaces. However,
although pretty pictures of such systems are easy to construct,
obtaining quantitative characteristics of surface-bound molecules
is not entirely straightforward, and the rigorous interpretation
of scanning probe microscopy images requires substantial
theoretical as well as experimental effort.
     4) The authors conclude: "We are only at the beginning, but
it is clear there is much to be discovered of a fundamental
nature about complex molecules viewed as individuals. Perhaps
equally important will be the idea of single molecule control.
Now that experiments interact with molecules at an individual
level, we can try to control them as individuals, not as
populations. A molecule under active control by an adaptive
environment will be a new beast. Such tamed molecules may well
resemble much more the elegant engineered machinery of everyday
experience than the unruly, wild molecules we are used to
studying today."
-----------
C. Bai et al: Single molecule physics and chemistry.
(Proc. Natl. Acad. Sci. US 28 Sep 99 96:11075)
QY: Chunli Bai, Institute of Chemistry, The Chinese Academy of
Sciences, Beijing 100080 CN.
-----------
Text Notes:
... ... *scanning tunneling microscopes: First available in the
early 1980s, this technique involves an atomically sharp metal
tip brought in atomic proximity (e.g., 0.5 to 1 nanometer) to a
flat surface so that electrons can *tunnel between the two
systems. Recording the atomic modulation of the atomic structure
which scanning the tip across the surface allows one to image
adsorbed species and surface morphologies.
... ... 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.
... ... *scanning probe microscopy: A general term comprising all
atomic-level probe techniques. See background material below.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]
-------------------
Related Background:
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]


6. ON THE DISCOVERY OF HIGH TEMPERATURE SUPERCONDUCTIVITY
One of the operating tenets of 20th century "big science" is that
important breakthroughs in science can be more or less engineered
if appropriate conditions are constructed and appropriate
individual researchers placed in those conditions. When this
approach produces a success, the various bureaucrats who support
the idea feel reaffirmed; when various counter-examples to the
approach occur, it is the turn of the doubters to feel
reaffirmed. A cogent instance of a counter-example was provided
in 1986 by the Bednorz-Mueller discovery of high-temperature
superconductivity -- a discovery of signal importance in
experimental physics made by two relatively unknown researchers
working in what can be characterized as a backwater and poorly-
equipped laboratory. Not only was the discovery of high-
temperature superconductivity totally unexpected by the
international physics community, but the discovery of the
phenomenon by outsiders under "little science" conditions caused
a degree of shock in the science policy system. Ordinary
superconductivity is a property of many metals, alloys, and
chemical compounds at temperatures near absolute zero, at which
temperatures (their "critical temperatures") their electrical
resistivity vanishes and they become strongly diamagnetic.
(Diamagnetic substances such as the alkalis and alkaline earth
metals, the halogens, and the noble gases are repelled by magnets
and tend to position themselves at right angles to the magnetic
lines of force.) High-temperature superconductors were unknown
until 1986, but at present there are some known high-temperature
superconductors with critical temperatures greater than 100
degrees kelvin. The accepted theory of ordinary superconductivity
is the Bardeen-Cooper-Schrieffer theory (BCS theory) (1957). At
the present time, a successful theory of high-temperature
superconductivity has not been developed, in spite of a great
deal of effort. Johannes Georg Bednorz (1950- ) and K. Alexander
Mueller (1927- ) shared the Nobel Prize in Physics in 1987 for
their discovery of high-temperature superconductivity in a
ceramic oxide (lanthanum-barium-copper) alloy at 30 degrees
kelvin, at that time the highest superconductivity temperature
ever observed, the work having been carried out at the IBM Zurich
Research Laboratories at Rueschlikon.
... ... Helga Nowotny (Swiss Federal Institute of Technology, CH)
presents an essay on innovation in research and the modern
partnership between basic research and applied science, the
author making the following points:
     1) One of the most exciting recent success stories of
science began in September 1986 with the appearance in the
_Zeitschrift fur Physik_ of an article with the cautious title,
"Possible high-T(subc) superconductivity in the Ba-La-Cu-O
system." A few weeks later, the names of the two authors,
Alexander Mueller and Georg Bednorz, and their discovery hit the
front pages of _The New York Times_ and researchers around the
world were caught in an unprecedented frenzy, attempting to
replicate and surpass the findings of the initial breakthrough.
The race for high-temperature superconducting systems was on.
     2) The discovery of high-temperature superconductivity was
unexpected in terms of its discoverers, the place of its
discovery, and the scientific ideas involved. It contradicted
conventional wisdom and the expectations of peers and research
administrators. Mueller and Bednorz were outsiders, Mueller a
specialist on perovskites (a type of oxide mineral) and Bednorz a
crystallographer. They benefitted from the novice effect, but
they also enjoyed a degree of autonomy that allowed them to
prepare for the unpredictable. Of the 3 superconductivity
laboratories of IBM, the Rueschlikon laboratory where the two
researchers were based was by far the most modestly equipped. And
the discovery contradicted long-held views, not only overturning
certain established empirical rules concerning superconductivity,
but also unveiling previously unknown phenomena not accounted for
by the classic Bardeen-Cooper-Schrieffer theory.
     3) The author points out that even if we knew how to create
conditions under which creativity can flourish, and how to favor
the occurrence of what cannot be planned, the problem remains of
how to turn highly individualistic bursts of scientific
creativity into socially desired techno-scientific outcomes. "For
the most disturbing paradox is this: there has been a relative
decline in the importance of the individual creative act, while
its proliferation is encouraged. Individual scientific creativity
has become a necessary, but no longer sufficient, precondition in
a long, branching sequence of possibilities."
-----------
Helga Nowotny: Innovation machine on the boil.
(Nature 28 Oct 99 401:859)
QY: Helga Nowotny, Swiss Federal Institute of Technology, ETH-
Zentrum, CH-8092 Zurich, CH.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]


7. IN BRIEF: HAZARDS IN ZOOS: MULTIPLE HUMAN EXPOSURES TO RABIES
Rabies (hydrophobia) is an acute infectious disease of mammals,
especially of carnivores, the disease characterized by central
nervous system pathology leading to paralysis and death. The
disease is caused by a neurotropic virus (i.e., a virus with an
affinity for the nervous system), the virus present in the saliva
of rabid animals. The rabies virus is classified as a
"rhabdovirus", and is a rod- or bullet-shaped particle 75 x 180
nanometers, the particle surrounded by a membranous envelope with
protruding spikes 10 nanometers long. The spikes are composed of
a viral glycoprotein. The genome is a single-stranded RNA
molecule of 12 kilobases. The virus attaches to cells via its
glycoprotein spikes, and the neurotropic character of the virus
is manifested by nerve cell nicotinic acetylcholine receptors
apparently serving as cellular receptors for the virus particle.
Rabid animals transmit the infection by biting other animals or
humans. Worldwide, rabid dogs present the highest risk to humans.
In the US, where vaccination has largely eliminated canine
rabies, bites of infected wild animals, especially bats, have
caused most of the infrequent cases of human rabies since 1960.
In humans, the incubation period of rabies varies from 10 days to
more than 1 year, with an average incubation period of 30 to 50
days, and the possible long incubation period makes this disease
especially insidious. In a recent report, the US Centers for
Disease Control and Prevention presents the details of a case of
multiple human exposures to a rabid bear cub at a petting zoo and
"barnwarming" that occurred in Iowa in August 1999. According to
the report, on August 27, 1999, a black bear cub, approximately 5
to 6 months old, died after several hours of acute central
nervous system symptoms. Preliminary test results available the
next day indicated the bear had rabies. The bear was part of the
Swenson's Wild Midwest Exotic Petting Zoo in northeastern Iowa.
At the petting zoo, visitors fed, wrestled, and may have been
nipped by the bear. The bear was also taken to an August 14th
barnwarming in eastern Iowa, where it reportedly nipped people.
An estimated 400 people from 10 states and Australia had contact
with the bear cub at either the petting zoo or the barnwarming
during the 28 days before its death, during which time the bear
may have transmitted rabies virus. On the basis of telephone
calls to petting zoo visitors who signed the guest book and
provided contact information, approximately 150 of the 400
persons who were exposed to the saliva of the bear need to obtain
vaccine and rabies immune globulin. Public health authorities are
continuing to attempt to contact petting zoo visitors by
telephone and the Internet, but not every visitor signed the
register and provided sufficient information. The Iowa Department
of Public Health is maintaining an emergency telephone number at
(515) 323-4360.
-----------
US Centers for Disease Control and Prevention: Multiple human
exposures to a rabid bear cub at a petting zoo and barnwarming --
Iowa, August 1999.
(Morbidity and Mortality Weekly Report 1999 48:761)
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Dec99
[For more information: http://scienceweek.com/search/search.htm]

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

IN FOCUS: HISTORY OF BIOLOGY: ON 19TH CENTURY VITALISM
"The term 'vitalism' can be applied in one form or another to the
thinking of the majority of the scientists concerned with any
biological subject during most of the nineteenth century.
However, this does not mean that all held the same theory. Rather
it signifies that sooner or later each scientist reached a level
of speculation as to the mechanisms of the living organism at
which he could no longer explain these mechanisms with the facts
at his disposal. The point at which this level was reached
differed in individual cases, but the fact seemingly could not be
denied that there was a distinction between the inorganic and the
organic worlds; the unorganized and the organized as the
distinction was often expressed. After the popularization of the
idea of a vital force by Barthez (1734-1806), the term came to
cover a multitude of concepts. To some it represented an actual
substance characteristic of life, to others it was a force which
operated on the inorganic elements to give them unique properties
when it acted. Probably the best statement of the general
situation was the remark of Berzelius (1779-1848): 'We make use
of a _word_ to which we can affix no idea.'... After Liebig
(1803-1873), the structural theory of organic chemistry made
possible the synthesis of thousands of new compounds and an
understanding of mechanisms of their reactions. Chemists no
longer saw the need for a vital force. The German school of
physiologists, Temkin's 'mechanical materialists', discarded
vitalism completely and turned to the rapidly advancing science
of physics for an explanation of vital mechanisms. For them man
became 'but a passing constellation of lifeless particles of
matter.' It cannot be said that vitalism was completely
extinguished. Even in the twentieth century Hans Driesch (1867-
1941) continued to insist that the function of protoplasm could
not be explained mechanically. However, with the accumulating
mass of chemical and physiological information, vitalism did
gradually disappear from biological thought."
-----------
Henry M. Leicester: _Development of Biochemical Concepts from
Ancient to Modern Times_
(Harvard University Press, Cambridge MA 1974, p.150,159)


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