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.

November 3, 2000 -- Vol. 4 Number 44

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The reason why we are on a higher imaginative level
is not because we have finer imagination, but because
we have better instruments.
-- Alfred North Whitehead (1861-1947)

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Section 1
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Contents of this Issue (Full reports in Section 2):

1. IMMUNOLOGY:
ON DIRECT DESTRUCTION OF ANTIGENS BY ANTIBODIES
A central idea in vertebrate immunology has been that antibodies
themselves do not in general possess destructive ability, but
instead mark antigens for removal by various immune system
processes (e.g., specific binding by other entities and/or actual
digestion [phagocytosis] by specialized immune system cells). In
recent years, however, it has become evident that antibodies may
do more than merely mark antigens for destruction, and there is
now evidence that antibodies may indeed play a direct role in
destroying antigens.
(Proc. Natl. Acad. Sci. US 26 Sep 00 97:10930)

2. MEDICAL BIOLOGY:
ENTRAINMENT OF FREE-RUNNING CIRCADIAN RHYTHMS BY MELATONIN IN
BLIND PEOPLE
Most totally blind people have circadian rhythms that are "free-
running", i.e., that are not synchronized to environmental time
cues and that oscillate on a cycle slightly longer than 24 hours.
This condition causes recurrent insomnia and daytime sleepiness
when the rhythms drift out of phase with the normal 24-hour
cycle. There is now evidence that free-running circadian rhythms
in blind people can be entrained to a 24-hour cycle with a daily
dose of melatonin, thereby preventing a burdensome sleep
disorder. It is also possible that the phase-shifting effects of
melatonin in blind people may also be relevant to the treatment
of sighted people who have symptoms of disordered sleep as a
result of circadian disturbances.
(New England J. Med. 12 Oct 00 343:1070)

3. BIOPHYSICS:
MEASUREMENTS OF BIOLOGICAL CELLS VIA CAPACITANCE CYTOMETRY
Classical electrical studies of biological cells have focused on
external macroscopic properties, such as cell membrane response
or volume, and have reflected primarily the properties of large
ensembles of cells. Researchers now report a new technique that
allows investigation of some of the internal properties of
individual cells, the technique called "capacitance cytometry".
This technique can apparently quantify the DNA content of single
eukaryotic cells from a diverse set of organisms ranging from
yeast to mammals. In addition, capacitance cytometry can be used
as an assay for abnormal changes in DNA content, such as are
frequently encountered in neoplastic cells.
(Proc. Natl. Acad. Sci. US 26 Sep 00 97:10687)

4. ASTROPHYSICS:
A NEW CALIBRATION OF CEPHEID-BASED DISTANCES
Cepheids are a class of variable (pulsating) stars whose absolute
luminosities are related in a simple manner to their pulsational
periods. By measuring the period and using the "period-
luminosity" relationship, astronomers can use the observed visual
brightness to determine the distance to the star. Because these
stars are very luminous, they can be observed in other galaxies,
and therefore can be used to help determine the expansion rate of
the Universe (the Hubble constant). Calibration of the period-
luminosity relation is a necessary first step, but the small
number of sufficiently nearby Cepheids has forced the use of
indirect techniques, with associated systematic uncertainties.
Researchers now report the first unambiguous detection of the
pulsating diameter of a Cepheid variable star, and the prospect
is a substantial refinement of the Cepheid period-luminosity
relation. (Nature 28 Sep 00 407:485)

5. PLANETARY SCIENCE:
DETECTION OF DAILY CLOUDS ON SATURN'S MOON TITAN
The atmosphere of Saturn's moon Titan has often been compared to
that of Earth, and it has been speculated that Titan may support
a methane cycle (resembling Earth's hydrologic cycle), with
clouds, rain, and seas. Astronomers now report the discovery of
frequent variations in the near-infrared spectrum of Titan,
variations which are indicative of the daily presence of sparse
clouds covering less than 1 percent of the area of the moon. The
thermodynamics of Titan's atmosphere and the apparent altitude of
the clouds suggest that convection governs the evolution of these
clouds. It is suggested that the short lives of these clouds
point to the presence of rain, and that Titan's atmosphere
resembles Earth's, with clouds, rain, and an active weather
cycle. (Science 20 Oct 00 290:509)

6. CHEMISTRY: A FIRST NOBLE GAS-NOBLE METAL COMPOUND
According to the valence shell model of atoms, the atoms of the
noble gases all have valence shells that are closed octets
(except helium, where there is a duet). These closed shells are
quite stable, consistent with their high ionization potentials.
The noble gases, however, can indeed engage in chemical
interactions. Since the creation of the first noble gas compound,
XePtF(sub6), in 1962, xenon compounds with direct bonds to
fluorine, oxygen, nitrogen, carbon, xenon itself, and most
recently, chlorine, have been established, with the list for
krypton-bonded elements much shorter. All these bonded atoms are
electronegative main-group elements, and noble gas chemistry
would be greatly enhanced if xenon (or other noble gases) could
be bonded directly to metal atoms or ions. Researchers now report
the first metal-xenon compound with direct metal-xenon (in this
case, gold-xenon) bonds. (Science 6 Oct 00 290:117)

7. IN FOCUS: ON SIZE AND EVOLUTION

8. FROM THE SCIENCEWEEK ARCHIVE:
A CRITIQUE OF THE NOBEL PRIZE

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Section 2
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1. IMMUNOLOGY:
ON DIRECT DESTRUCTION OF ANTIGENS BY ANTIBODIES
     In general, an antigen is any entity that provokes an immune
response, and this may include, in certain disease states,
entities that are not "foreign" to the body. The term "antibody"
refers to a protein molecule produced by the immune system of
vertebrate organisms, the molecule designed to specifically
interact with a particular antigen. In the laboratory, antibodies
specific to a variety of substances can be easily produced in an
appropriate experimental animal, and the antibodies then
separated from animal blood and used as binding agents in
biochemical and biophysical experiments. The immunoglobulins are
a large glycoprotein category that includes antibodies as a
subset.
     A central idea in vertebrate immunology has been that
antibodies themselves do not in general possess destructive
ability, but instead mark antigens for removal by various immune
system processes (e.g., specific binding by other entities and/or
actual digestion [phagocytosis] by specialized immune system
cells). In recent years, however, it has become evident that
antibodies may do more than merely mark antigens for destruction.
... ... A.D. Wentworth et al (5 authors at Scripps Research
Institute, US) present new evidence that antibodies may indeed
play a direct role in destroying antigens, the authors making the
following points:
     1) The authors point out that the existence of antibody
catalysis [see related background material below] demonstrates
that antibodies are capable of much more complex chemistry than
simple binding of antibody to antigen, and that this has led to
the question of whether more sophisticated chemical mechanisms
are part of the strategy of the antibody molecule. But thus far,
there has been no evidence to support this idea, and the
consensus has been that just because antibodies are capable of
complex chemistry does not mean they use such chemistry in host
defense. The authors now report a previously unremarked capacity
of antibodies to convert molecular oxygen into hydrogen peroxide,
and that since hydrogen peroxide is capable of generating a
variety of toxic products in biological cells, there is thereby
an effective link between antibody recognition of an antigen and
killing events.
     2) The authors found a universal ability of antibodies to
generate hydrogen peroxide from molecular oxygen, the function
apparently shared across a range of species and independent of
antibody composition of antigen specificity. The authors
investigated 39 different immunoglobulins from mouse, human, rat,
hamster, sheep, horse, rabbit, and goat immune systems.
     3) The authors point out that throughout nature, organisms
have defended themselves by production of relatively simple
chemicals. At the level of single molecules, this mechanism has
been thought to have been largely abandoned with the appearance
in evolution of the vertebrate immune system. The idea has been
that once an immune system targeting device (antibodies) had
evolved, the killing mechanism moved elsewhere. The authors
suggest their studies realign recognition with killing within the
same molecule, and that in a certain sense this chemical immune
system parallels the purely chemical defense mechanism of lower
organisms, with the exception that a more sophisticated and
diverse targeting entity is added.
     4) The authors also suggest their findings raise questions
as to how the immune system may have evolved. It is possible that
the immune system began as a single protein with killing
capacity, and that the diversity and recognition components
evolved later. Thus, the ability of certain other proteins to
perform this process, although usually at a lower rate, offers
the idea that antibodies evolved by coupling this specific
property of some proteins with a diversity-generated targeting
device. The authors suggest that from an evolutionary
perspective, the key issue is that this ability seems to be
conserved in all antibodies.
-----------
A.D. Wentworth et al: Antibodies have the intrinsic capacity to
destroy antigens.
(Proc. Natl. Acad. Sci. US 26 Sep 00 97:10930)
QY: Richard A. Lerner: Scripps Research Institute 619-784-1000.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON THE USE OF ANTIBODY CATALYSIS IN ORGANIC CHEMISTRY
An antibody is a protein molecule (immunoglobulin) produced by
vertebrates that binds with high specificity to a "foreign"
entity (*antigen) that has entered the system by one means or
another (for example, via bacteria, tissue grafts, or blood
transfusions). Antibodies are therefore key elements in all
vertebrate immune systems. That is the first point. The second
point is that we now know that enzymes work the way they do
mostly because they bind *transition state entities in chemical
reactions, this binding lowering the energy barrier to the
transition state, and thereby increasing the reaction rate
many-fold. Which provokes the notion that it might somehow be
possible to use the high specificity of antibodies in catalysis.
And the notion is correct. A catalytic antibody, sometimes called
an "abzyme", is an antibody capable of catalyzing specific
chemical reactions. The general strategy in producing catalytic
antibodies has been to 1) design and synthesize a molecule whose
charge and shape closely resemble those of the transition state
of the reaction to be catalyzed; 2) attach this molecule to a
larger molecule and provoke an immune response in a living system
to this complex; and 3) isolate the resultant antibodies for
catalytic activity of the type desired. These resultant
antibodies are highly specific for binding to the transition
state, and they will be potentially capable of catalyzing the
reaction. Antibody catalysis has become a multifaceted field of
research involving many bridges between the biological and
chemical sciences. ... ... Peter G. Schultz (University of
California Berkeley, US) presents a short review of past and
recent research in the field, the author making the following
points: 1) The use of catalytic antibodies in organic chemistry
began with the idea that chemists should be able to use the
complex machinery of the immune system, which is capable of
generating enormous chemical diversity through the processes of
*recombination and *somatic mutation, to create new molecular
functions, specifically highly selective catalysts. 2) The
earliest examples involved the use of transition state analogues
to select antibodies with maximal binding affinity toward the
rate-limiting transition state for a given reaction. Other
strategies then emerged, strategies in which many of the basic
concepts of biological catalysis (e.g., strain, proximity,
general acid/base catalysis) were used in the design of molecules
that could guide the generation of catalytic antibodies for a
wide variety of reactions. 3) More recently, efforts have focused
on detailed studies of catalytic antibodies to gain new insights
into the molecular mechanisms of biological catalysis and of the
immune response itself. For example, structural studies of
catalytic antibodies have resulted in important new perspectives
concerning the *combinatorial processes involved in the immune
response. 4) Another direction the field has taken involves
efforts to recapitulate the combinatorial processes of the immune
system in vitro. For example, strategies are now being developed
to directly select *bacteriophage mutants with enhanced catalytic
activities from large libraries of such mutants. Such strategies
are designed to provide a direct linkage between catalysis and
biological amplification in order to produce protein catalysts
for a broad range of chemical reactions. 5) A new strategy for
generating antibody catalysis involves "reactive immunization" --
a designed covalent interaction between immunogen and antibody,
and this technique has now been used to carry out the synthesis
of key intermediates that in turn simplify the synthesis of the
natural product epothilone, a powerful cytotoxic agent of
considerable biomedical interest [*Note #1].
-----------
Peter G. Schultz: Bringing biological solutions to chemical
problems.
(Proc. Natl. Acad. Sci. US 8 Dec 98 95:14590)
QY: Peter G. Schultz, Univ. of Calif. Berkeley 510-642-6000.
-----------
Text Notes:
... ... *antigen: In general, an antigen is any substance or
moiety that produces an immune response.
... ... *transition state: (activated state) In general, in any
chemical reaction, the "transition state" is the high energy
configuration through which the reactants must pass before
becoming products.
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *somatic mutation: In general, a mutation occurring in
non-germ cells, which means the mutation is not transmitted to
the next generation.
... ... *combinatorial processes: Certain aspects of the immune
response and its production of antibodies apparently mimic a
"combinatorial process" in the sense that many factors are
involved in various combinations, rather than one factor involved
as a predominant determinant. (Combinatorial analysis is a branch
of mathematics involving analysis by means of combinations,
permutations, etc.) Combinatorial chemistry is a recent
technology involving the automated rapid production and screening
of thousands of compounds for specific properties, the population
of compounds consisting of a large number of possible
permutations of chemical constituents. One method, for example,
produces thin-film "libraries" of up to 25,000 different
substances on a 3-inch diameter substrate. The methods are
increasingly used in molecular biology for the production and
screening of large libraries of antibodies, peptides, DNA
ligands, and so on. A random peptide library synthesis may
involve as many as 100 million different peptides, with
subsequent screening of the library for the purposes of drug
discovery.
... ... *bacteriophage: Bacteriophage is a virus that
infects bacteria, the virus essentially consisting of a naked
strand of DNA surrounded by a complex polyhedral shell ("capsid")
composed mainly of glycoproteins.
... ... *Note #1: The Schultz review is a commentary on a
research report appearing in the same issue of the journal: S.C.
Sinha et al: The antibody catalysis route to the total synthesis
of epothilones. ((Proc. Natl. Acad. Sci. US 8 Dec 98 95:14603)
Epothilones are powerful cytotoxic agents isolated from
*myxobacteria (Sorangium cellulosum), the substances exhibiting a
*taxol-like effect on cellular *microtubules.
... ... *myxobacteria: An order of bacteria bearing extracellular
slime.
... ... *taxol: An anti-tumor and anti-leukemic agent isolated
from the bark of the yew tree.
... ... *microtubules: Microtubules are part of the cytoskeleton
of biological cells, the quasi-rigid matrix that among other
things determines cell shape. The microtubules are 25 nanometers
in diameter, and composed of the protein tubulin. They occur in
regular arrays in cilia, flagella, the mitotic spindle, and in
the cytoplasm in general, and they contribute not only to cell
shape, but also to cell motility. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 29Jan99
-------------------
Related Background:
SELECTION OF BROAD-SCOPE ENZYMES BY ANTIBODY CATALYSIS
... "Reactive immunization" is a new term to describe a synthetic
antibody specificity that involves a covalent chemical reaction
with an antigen rather than weaker affinity bonds, and new
antigens specifically synthesized or selected for this reactive
process are called "reactive immunogens". In biological systems,
glycolysis (also known as Embden-Meyerhof pathway), involving the
breakdown of glucose, is one of the main energy producing
pathways in the cell, and anaerobic glycolysis is glycolysis in
the absence of oxygen. Decarboxylation is the removal of CO(2)
from organic compounds, and in biological systems often involves
the conversion of amino acids to amines. Lysine is one of the
amino acids found in biological systems. ... ... Barbas et al (11
authors at Scripps Res. Inst., US) report the preparation of
catalytic antibodies by reactive immunization, the process
yielding aldolase catalytic antibodies that approximate the rate
acceleration of the natural enzyme used in glycolysis. But unlike
the natural enzyme, the antibody aldolases catalyze a variety of
aldol reactions and decarboxylations. Crystal structure analysis
of one of the antibodies identified the lysine residue selected
in the immunization process, and the lysine residue is apparently
deeply buried in a hydrophobic pocket at the base of the binding
site. The authors suggest that an early defining event in the
evolution of some natural enzymes was an interaction with
reactive materials such as toxins in a process similar to the
induction of catalytic antibodies with a reactive immunogen.
QY: Richard A. Lerner, Scripps Research Institute 619-784-1000
(Science 19 Dec 97) (Science-Week 9 Jan 98)
-------------------
Related Background:
RELATING BOND ENERGY TO CATALYSIS IN CATALYTIC ANTIBODIES
A catalytic antibody, sometimes called an "abzyme", is an
antibody capable of catalyzing specific chemical reactions. 
These antibodies, which can be immunologically engineered, are
highly specific for binding to the transition states of react-
ions, and they are potentially capable of catalyzing such
reactions. Helle D. Ulrich et al (University of California
Berkeley, US) recently reported a study of the relationship
between binding energy and catalysis by catalytic antibodies, the
study involving the antibody AZ-28, which catalyzes a well-known
reaction in organic chemistry called an oxy-Cope rearrangement.
They found the catalytic rate depends on a complex balance of
several subtle stereo-electronic effects, so that increasing the
affinity for a catalytic antibody with its ligand may actually
reduce the reaction rate rather than increase it. The authors
suggest that catalytic antibodies can be useful to explore the
complex relationships between binding energy and catalysis in
biological enzymes.
QY: Peter G. Schultz, Univ. Calif., Chemistry (510) 642-5883
(Nature 18 Sep 97) (Science-Week 3 Oct 97)
-------------------
Related Background:
FIRST COMMERCIAL CATALYTIC ANTIBODY FOR CHEMICAL SYNTHESIS
... Now there has been announced the first catalytic antibody to
enter the marketplace, produced by Richard A. Lerner et al
(Scripps Research Institute, La Jolla CA US), and available to
anyone who wants it at a modest charge. The new entity, called
38C2, catalyzes a wide range of aldol condensation reactions at
high efficiency (accelerating the reaction by a factor of 3.6
million). Aldol condensations are among the reactions widely used
for the synthesis of steroids, terpenoids, and other natural
products, so this new catalytic antibody molecule will be of
great interest to organic chemists.
QY: R. Lerner, Scripps Research Institute 619-784-1000
(J. Amer. Chem. Soc. 119:8131 1997) (Science-Week 12 Sep 97)
-------------------
Related Background:
NEW EVIDENCE CONCERNING EVOLUTION OF THE IMMUNE SYSTEM
*Lymphocytes of the *vertebrate adaptive immune system rely on an
array of variable *immunoglobulin (antibody) and *T-cell *antigen
*receptors for specific recognition of antigens. In the genome,
the genes encoding the variable portions of these receptors are
typically split into variable components (V), joining components
(J), and in some cases, diversity gene components (D). One of
each type of each component or gene segment is joined together in
a site-specific *recombination reaction to form the *exon that
encodes the antigen-binding portion of the polypeptide that forms
the antibody or T-cell receptor. This reaction, known as V(D)J
recombination, occurs only in lymphocytes, and in some vertebrate
species is responsible for generating much of the diversity seen
in antigen receptors. It is known that the two proteins encoded
by the recombination-activating genes _RAG1_ and _RAG2_ are
essential to the V(D)J recombination reaction, the proteins
mediating sequence-specific DNA recognition of recombination
"signals" (specific short base-pair sequences involved in this
particular recombination process) and DNA cleavage next to these
signals. ... ... Agrawal et al report that in vitro the proteins
RAG1 and RAG2 together form a *transposase capable of excising a
piece of DNA containing recombination signals from a donor site
and inserting the excised piece into a target DNA molecule. The
products formed contain a structure similar to that created by
*retroviral integration and by all known *transposition
reactions. The authors point out that all jawed vertebrates
studied thus far possess adjacent _RAG1_ and _RAG2_ genes as well
as immunoglobulin and T-cell receptor genes, which usually must
be assembled by *somatic recombination before they can be
expressed. There is no evidence that any of these molecules, or
antigen-specific lymphocytes, are found in jawless vertebrates
(hagfish and lamprey) or invertebrates. This indicates that split
antigen-receptor genes and the enzymatic machinery necessary for
their assembly into functional units arose in the approximately
100 million years between the divergence of jawless and jawed
vertebrates and the divergence of cartilaginous and bony fishes.
The authors suggest their results are evidence in favor of the
theory that a pivotal event in the evolution of the antigen-
specific immune system was the insertion of a "RAG *transposon"
into the genome of a vertebrate ancestor.
-----------
A. Agrawal et al (Yale University, US): Transposition mediated by
RAG1 and RAG2 and its implications for the evolution of the
immune system. (Nature 20 Aug 98 394:744)
QY: David G. Schatz: david.schatz@yale.edu
-----------
Text Notes:
... ... *Lymphocytes: These are a type of leukocyte responsible
for the immune response. There are two classes of lymphocytes: 1)
the B-cells, which when presented with an activating chemical
entity (antigen) change into antibody producing plasma cells;
and, 2) the T-cells, which interact directly with foreign
invaders such as bacteria and viruses. There are also forms of T-
cells that are involved with B-cell activation.
... ... *vertebrate adaptive immune system: The term "adaptive"
here refers to those parts of the immune system that are capable
of adaptation to chemical experience.
... ... *immunoglobulin (antibody): In general, antibodies are
immunoglobulin proteins.
... ... *T-cell: see *Lymphocyte note above.
... ... *antigen: Any chemical entity that activates an immune
response, especially an entity originating outside the body.
... ... *receptors: In this context, cell surface macromolecules
that bind antigens.
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *exon: In general, any DNA sequence encoding and giving
rise to a translated polypeptide sequence.
... ... *transposase: Any enzyme required for the transposition
of DNA segments (see below, *transposition reactions).
... ... *retroviral integration: Retroviruses are single-stranded
RNA viruses that have an enzyme called reverse transcriptase, and
with this enzyme the viral RNA is used as a template to produce
viral DNA from cellular material. This DNA is then incorporated
(integrated) into the host cell's genome, where it codes for the
synthesis of viral components.
... ... *transposition reactions: In general, any reactions that
insert or excise DNA fragments into or from a genome.
... ... *somatic recombination: Somatic cells are any cells other
than germ cells (gametes). Somatic recombination, where it
occurs, involves the transposition of DNA fragments from one DNA
molecule to another, or within the same DNA molecule. Somatic
recombination theory is one of the theories proposed to explain
the enormous variety of antibodies produced by the immune system.
... ... *transposon: A large transposable genetic element having
at least the genes necessary for its own transposition to the
same or another genome.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 18Sep98
For more information: http://scienceweek.com/swfr.htm

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2. MEDICAL BIOLOGY:
ENTRAINMENT OF FREE-RUNNING CIRCADIAN RHYTHMS BY MELATONIN IN
BLIND PEOPLE
     In biology, a "circadian rhythm" is a daily cyclical
process, be it biochemical, or physiological, or behavioral. The
human sleep-wake cycle is the most familiar example. Circadian
rhythms are often described in terms of endogenous "biological
clocks", with the thrust of research to reduce some particular
behavioral or physiological circadian rhythm to biochemical
events. These clocks are usually set by environmental cues such
as the light-dark cycle, and what is characteristic of an
endogenous clock is that if one removes the environmental cue,
keeps the organism in constant light or darkness, for example,
the endogenous rhythm will continue, but will tend to drift out
of phase with the outdoors environmental light-dark cycle.
Restoring the external light-dark cue will reset the clock to its
normal intrinsic rhythm.
     In humans, the endogenous circadian pacemaker oscillates
with a period that is slightly longer than 24 hours, and the
pacemaker therefore requires synchronization ("entrainment") to
the 24-hour day.
     In mammals, including humans, the biological clock
apparently resides in a group of neuron clusters in a part of the
brain called the hypothalamus, a region that responds to many
chemical inputs, including the hormone melatonin, an indole
derived from the metabolism of serotonin. Melatonin is secreted
by another hypothalamic brain structure, the pineal gland, which
in turn is stimulated by neurons in a nearby cluster (the
suprachiasmatic nucleus) that receives input from the retina of
the eye. So this is the apparent pathway of light-induced
secretion of melatonin and action in mammals: light on the
retina, electrical activity in the retino-hypothalamic tract,
activity in a hypothalamic region called the suprachiasmatic
nucleus, electrical signals to the pineal gland, secretion of the
hormone melatonin, action of melatonin on other neural structures
in the hypothalamus and elsewhere.
     In totally blind people, light cues are unavailable, and
disturbances of circadian rhythms are common.
... ... R.L. Sack et al (4 authors at Oregon Health Sciences
University Portland, US) report a study of the effects of
melatonin administration on the circadian rhythms of totally
blind people, the authors making the following points:
     1) Most totally blind people have circadian rhythms that are
"free-running", i.e., that are not synchronized to environmental
time cues and that oscillate on a cycle slightly longer than 24
hours. This condition causes recurrent insomnia and daytime
sleepiness when the rhythms drift out of phase with the normal
24-hour cycle. The authors investigated whether a daily dose of
melatonin could entrain the circadian rhythms of totally blind
people to a normal 24-hour cycle.
     2) A crossover study was performed on 7 totally blind
subjects who had free-running circadian rhythms. The subjects
were given 10 milligrams of melatonin or a placebo daily, one
hour before their preferred bedtime, for 3 to 9 weeks. They were
then given the other treatment. The timing of the production of
endogenous melatonin was measured as a marker of the circadian
time (phase), and sleep was monitored by *polysomnography.
     3) At base line, the subjects had free-running circadian
rhythms with distinct and predictable cycles averaging 24.5 hours
(range: 24.2 to 24.9). These rhythms were unaffected by the
administration of placebo. In 6 of the 7 subjects, the rhythm was
entrained to a 24.0 hour cycle during melatonin treatment.
     4) The authors point out that there are approximately 1
million blind people in the US, of whom approximately 20 percent
are totally blind, and it is estimated that at least half of this
20 percent (approximately 100,000 people) probably have free-
running circadian rhythms, with a high proportion having
circadian sleep-wake disorders. The authors suggest melatonin may
prove to be a safe and effective treatment for many of these
people.
     5) The authors also suggest that the phase-shifting effects
of melatonin observed in their study of circadian rhythms in
blind people may be relevant to the treatment of sighted people
as well. "People who fly across multiple time zones or who work
nighttime or early-morning shifts routinely have symptoms of
disordered sleep as a result of circadian disturbances. Similar
pathophysiologic mechanisms have been proposed for advanced and
delayed sleep-phase syndromes as well as for winter depression."
     6) The authors conclude: "Free-running circadian rhythms in
blind people can be entrained to a 24-hour cycle with a daily
dose of melatonin, thereby preventing a burdensome sleep
disorder."
-----------
R.L. Sack et al: Entrainment of free-running circadian rhythms by
melatonin in blind people.
(New England J. Med. 12 Oct 00 343:1070)
QY: Robert L. Sack: sackr@ohsu.edu
-----------
Text Notes:
... ... *polysomnography: This technique involves synchronized
recordings of electrical activity in the brain, muscles, and
eyes, as well as other physiological measures (e.g.,
electrocardiogram) during sleep.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY: ON MELATONIN
Melatonin is a hormone secreted by the human pineal gland during
night-time darkness, and it is now being marketed in the US as a
nutritional supplement. The hormone is an indoleamine compound
derived from the amino acid *tryptophan, with *serotonin as an
intermediate precursor. ... ... R.L. Sack reviews the
neurobiology and medical aspects of melatonin, and makes the
following points: 1) The most important role of melatonin in all
species is to provide a hormonal signal of night-time darkness.
The secretion of the hormone is tightly controlled by the
*circadian pacemaker. 2) Melatonin is a phylogenetically ancient
hormone, found even in some single-cell organisms and in some
plants. In lower vertebrates (e.g., reptiles), the pineal body
lies close to the skin and is directly photosensitive: sunlight
falling on the overlying skin inhibits melatonin production. In
these species, the pineal body has been called a "third eye". In
mammals, the pineal gland is deep within the skull and is not
photosensitive. The timing of melatonin secretion in mammals is
controlled by neural pathways: tracts from the retina of the eye
to the *hypothalamus (retino-hypothalamic tract) and from the
hypothalamus (suprachiasmatic *nucleus) to the pineal gland. The
suprachiasmatic nucleus of the hypothalamus is the master
circadian pacemaker in mammals, controlling the timing of most
circadian rhythms, including core body temperature, *cortisol
secretion, sleepiness, and melatonin secretion. 3) At the
cellular level, melatonin receptors are members of the
superfamily of *G protein-coupled receptors, which
characteristically have 7 *transmembrane domains. Activation of
these receptors inhibits *cyclic AMP production by the enzyme
adenylyl cyclase. 4) The author suggests that as a therapeutic
agent, melatonin can be useful in the treatment of certain sleep
and mood disorders. The author suggests the basis for this is
circadian phase-shifting and the release of accumulated sleep
drive. 5) Concerning its use as a nutritional supplement, the
author says, "Melatonin appears to be remarkably safe, at least
for short-term use... The effects of long-term administration are
not defined." Concerns have been raised about possible
reproductive effects, but most studies have shown little or no
effect on reproductive hormone levels. There are reports that
melatonin modifies the *vasoconstriction response in rat
arteries.
-----------
R.L Sack (Oregon Health Sciences University, US)
Melatonin
(Science & Medicine Sep/Oct 1998)
QY: Robert L. Sack, Oregon Health Sciences Univ. 503-494-2998.
-----------
Text Notes:
... ... *tryptophan: A nutritionally essential amino acid that
serves as a precursor for many molecular entities of importance
in the nervous system.
... ... *serotonin: (5-hydroxytryptamine, 5-HT) Synthesized from
tryptophan. Acts as both a peripheral neurotransmitter in the gut
and a central neurotransmitter in the brain.
... ... *circadian pacemaker: Many organisms exhibit daily
(circadian) rhythms, cyclical variations in various bodily
functions, metabolisms, etc., even in constant light or constant
darkness. In simple organisms, the pacemakers are biochemical
reaction loops; in higher organisms, complex signaling structures
are involved in the rhythms.
... ... *hypothalamus: 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.
... ... *nucleus: In this context, the term "nucleus" refers to a
cluster of nerve cells involved in a particular neurological
function.
... ... *cortisol: A corticosteroid hormone secreted by the
adrenal gland.
... ... *G protein: G-proteins are a family of signal-coupling
proteins that act as intermediaries between activated cell
receptors and effectors, for example, the transduction of
hormonal signals from the cell surface to the cell interior, and
certain G-proteins are known to interact with adenylyl cyclase.
The G-protein is apparently embedded in the cell membrane with
parts exposed on the outside surface and inside surface. The
outside moiety is activated by the first messenger, and the
inside moiety activates the second messenger, the G-protein thus
acting as a trans-membrane signal transducer.
... ... *transmembrane domains: A transmembrane domain is a
segment of protein anchored in the plasma membrane bilayer. If
one visualizes the protein as a long linear polymer, the polymer
can be looped back and forth across the plasma membrane with
different segments of the protein anchored in the membrane
according to lipid solubility characteristics of the segments of
the polymer chain.
... ... *cyclic AMP: ATP (adenosine triphosphate) is the most
important chemical energy source in all living cells, intimately
involved in various cell functions and cell metabolism, and an
entity in numerous cyclic chemical pathways involved in the
synthesis of components. One of the reaction products of ATP is
cAMP (cyclic AMP, or adenosine 3,5-monophosphate), which acts as
an intracellular hormone (i.e., a chemical messenger). Cyclic AMP
is derived from ATP in a reaction catalyzed by the enzyme
adenylyl cyclase (also called adenyl cyclase and adenylate
cyclase). Cyclic AMP is called the second messenger; the first
messenger is the hormone that interacts with its receptor on the
cell surface.
... ... *vasoconstriction response: In general, the term
vasoconstriction refers to a narrowing of blood vessels, which in
higher organisms is under physiological control via various
signaling systems. Vasoconstriction produces an increase in blood
pressure, systemic or local, depending on the distribution of
signals.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
CIRCADIAN RHYTHMS IN HUMANS: EXTRA-VISUAL PHOTOTRANSDUCTION
... ... Campbell and Murphy (Cornell Univ., US) report
measurements of the response of the human circadian clock to
extraocular light exposure involving light pulses presented to
the popliteal region (the area behind the knee). They report a
systematic relation between the timing of the light pulse and the
magnitude and direction of clock phase shifts. The authors
suggest their findings challenge the belief that mammals are
incapable of extraretinal circadian phototransduction, and that
the findings also have implications for the development of more
effective treatments of sleep and circadian rhythm disorders.
QY: Scott S. Campbell, Cornell Univ. Medical College 212-746-1067
(Science 16 Jan 98) (ScienceWeek 30 Jan 98)
For more information: http://scienceweek.com/swfr.htm

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3. BIOPHYSICS:
MEASUREMENTS OF BIOLOGICAL CELLS VIA CAPACITANCE CYTOMETRY
From the perspective of physics and physical chemistry, one view
of a biological cell is that it consists of a dilute solution of
various kinds of molecules, many of which are electrically
charged, the solution separated from an exterior dilute solution
by a semipermeable membrane. With appropriate physical
techniques, various global parameters of biological cells should
be amenable to measurement: volume, mass, internal pressure,
electrical conductance, electrical capacitance, spectral
absorption, and so on. All of these parameters have indeed been
measured, either directly or indirectly, and the measurements
have often yielded both useful basic information and interesting
applications.
... ... L.L. Sohn et al (6 authors at Princeton University, US)
present a new technique for single-cell electrical capacitance
measurements, the authors making the following points:
     1) Previous electrical studies of biological cells have
focused on external macroscopic properties, such as cell membrane
response or volume, and have reflected primarily the properties
of large ensembles of cells. The authors report a new technique
that allows investigation of some of the internal properties of
individual cells, the technique called by the authors
"capacitance cytometry". The authors report this technique can
quantify the DNA content of single *eukaryotic cells from a
diverse set of organisms ranging from yeast to mammals. In
addition, capacitance cytometry can be used as an assay for
abnormal changes in DNA content, such as are frequently
encountered in neoplastic cells.
     2) Although also able to measure certain parameters of
individual cells, the extant standard technique of laser flow
cytometry requires sample preparation such as sample staining or
manipulation of cells. In contrast, capacitance cytometry
requires no special preparation, and the technique thus has the
potential to be simpler, faster, and less expensive than laser
flow cytometry.
     3) The fundamental basis of capacitance cytometry is an AC
capacitance measurement. This extremely sensitive yet robust
electronic technique allows one to probe the polarization
response of a wide range of materials, both organic and
inorganic, to an external electric field. In the past,
capacitance measurements have been used to identify and
investigate a number of different materials in bulk. More
recently it has been used to investigate ensembles of biological
cells, determining cell size and cellular membrane capacitance,
to assay *cell-cycle progression and to differentiate normal and
malignant white blood cells. In contrast, the authors use
capacitance measurements as a means of detecting and quantifying
the polarization response of DNA within the nucleus of single
eukaryotic cells. Because DNA is a highly charged molecule, in an
applied low-frequency AC electric field its polarization
response, in combination with the motion of the surrounding
counterions, can be substantial. The authors measure this
response as a change in total capacitance across a pair of
microelectrodes as individual cells suspended in *buffer solution
flow one by one through a channel 30 microns in diameter.
     4) The authors report they have observed a linear
relationship between the DNA content of eukaryotic cells and the
change in capacitance that is evoked by the passage of individual
cells across a 1-kHz electric field. This relationship is species
independent, and the authors consequently suggest they have
developed a new technique to quantify the DNA content of single
eukaryotic cells and to analyze the cell-cycle kinetics of
populations of cells. The authors report that comparisons with
standard flow cytometry demonstrate the sensitivity of this new
technique.
-----------
L.L. Sohn et al: Capacitance cytometry: Measuring biological
cells one by one.
(Proc. Natl. Acad. Sci. US 26 Sep 00 97:10687)
QY: L.L. Sohn: sohn@princeton.edu
-----------
Text Notes:
... ... *eukaryotic cells: In general, biological cells that
contain internal membrane-bound organelles such as a cell
nucleus.
... ... *cell-cycle: In this context, the term "cell cycle"
refers to the entire life history of a single cell from mitosis
to mitosis, including the sequence of intervening phases.
... ... *buffer solution: In general, any solution containing
substances designed to keep the pH of the solution constant.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm

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4. ASTROPHYSICS:
A NEW CALIBRATION OF CEPHEID-BASED DISTANCES
     One of the primary challenges of astronomy is to determine
with some exactitude the distances to various astronomical
objects outside our Galaxy. Given the enormous distances
involved, the difficulties are formidable. But such data are of
tremendous importance in constraining various models of the
Universe, and are thus at the heart of the quest to understand
where we are.
     Variable stars are stars whose apparent physical parameters
vary, usually periodically, with the cause of the variation
either intrinsic (produced by the internal physics of the star)
or extrinsic (produced by the proximity of another star).
     The Hubble constant is a measure of the rate of expansion of
the Universe, the average value of velocity of recession divided
by distance. Since the constant is time-dependent, it is more
correctly termed a parameter. It's present value is believed to
be between 50 and 100 km/sec/megaparsec.
     "Cepheids" are supergiant stars that regularly change in
size and brightness, their intrinsic variation having periods
between 1 and 60 days. The period of variation for each star has
been found to be related to its luminosity, and this relation
makes it possible to use Cepheids as "standard candles" to
estimate the distance of astronomical objects (*Note #1).
... ... B.F. Lane et al (5 authors at California Institute of
Technology, US) present a new and independent calibration of the
period-luminosity relation of a Galactic Cepheid star (zeta-
Geminorum), the authors making the following points:
     1) The authors point out that Cepheids are a class of
variable (pulsating) stars whose absolute luminosities are
related in a simple manner to their pulsational periods. By
measuring the period and using the "period-luminosity"
relationship, astronomers can use the observed visual brightness
to determine the distance to the star. Because these stars are
very luminous, they can be observed in other galaxies, and
therefore can be used to help determine the expansion rate of the
Universe (the Hubble constant). Calibration of the period-
luminosity relation is a necessary first step, but the small
number of sufficiently nearby Cepheids has forced the use of
indirect techniques, with associated systematic uncertainties.
     2) The authors report a determination of the distance to the
Cepheid star zeta-Geminorum, the determination made using a
direct measurement (by an *optical interferometer: the Palomar
Testbed Interferometer) of its changes in diameter as it pulses.
The authors report that within their uncertainty of 15 percent,
their distance is in agreement with previous indirect
determinations. The authors suggest that planned improvements in
the instrument will allow them to calibrate directly the period-
luminosity relation to better than a few percent.
... ... In a commentary on the above work, Tyler Nordgren (US
Naval Observatory Flagstaff, US) states: "Lane et al report the
first unambiguous detection of the pulsating diameter of a
Cepheid variable star... In their observations of zeta-
Gem[inorum], [these researchers] have done an excellent job of
comparing their observations to a wide range of previous Cepheid
observations. With new-found confidence in these difficult
observations, optical interferometry is now ready to move beyond
merely confirming previous discoveries to making new ones of its
own."
-----------
B.F. Lane et al: Direct detection of pulsations of the Cepheid
star zeta-Gem and an independent calibration of the period-
luminosity relation.
(Nature 28 Sep 00 407:485)
QY: B.F. Lane: bfl@astro.caltech.edu
-----------
Tyler Nordgren: The resolution revolution
(Nature 28 Sep 00 407:462)
QY: Tyler Nordgren: nordgren@nofs.navy.mil
-----------
Text Notes:
... ... *Note #1: In general, the periodic pulsations of Cepheid
variable stars involve expansion and contraction with as much as
a 30% change in size in each cycle, and a typical average
luminosity approximately 10,000 times that of our Sun. In 1912,
Henrietta Swan Leavitt discovered a simple relationship between
the period of light variation and the absolute magnitude of a
Cepheid variable. This relationship, called the "period-
luminosity law", enabled the calculation of distances to the
stars in our own Galaxy and to the stars in other galaxies. In
1952 it was discovered that there are two types of Cepheid
variables, which meant an error had been introduced in the
earlier calculations of distances, and when the correction was
made, the apparent size of the universe abruptly doubled. During
1908-1912, Leavitt (1868-1928), a graduate of Radcliffe College
on the staff of the Harvard Observatory, discovered 2400 variable
stars, doubling the number known in her time. In the early years
of stellar spectroscopy, particularly at the Harvard Astronomical
Observatory, nearly all the data was catalogued and analyzed by
female astronomers, called "computers", who were trained
professional astronomers but forbidden because of their sex to
use the telescopes. It is an irony of the social history of
science that the work of such female astronomers as Henrietta
Swan Leavitt and Annie Jump Cannon (1863-1941) came to be of
greater significance than the work of many of the male
astronomers who considered these female astronomers to be no more
than menial assistants.  
... ... *optical interferometer: An interferometer combines the
light from two or more widely spaced mirrors, resulting in an
array with the same resolution as a single large telescope of the
same diameter as the separation between the mirrors. Radio
astronomers using the Very Long Baseline Array are thus able
simulate a single radio telescope the size of North America.
Unfortunately, most stars emit radiation at optical rather than
radio wavelengths, and technical obstacles have prevented optical
telescopes being built on this scale. The Palomar Testbed
Interferometer (PTI), located on Palomar Mountain in California
(US), has the resolving capability of a single 110-meter infrared
telescope, much larger than any single telescope built so far,
and good enough to resolve stars as small as a few
milliarcseconds in diameter. Such interferometers are now
operating or under construction in Britain, continental Europe,
Australia, Hawaii, and North and South America.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ASTROPHYSICS: ON THE DETERMINATION OF THE HUBBLE CONSTANT
     Far down the road, it will be written that five centuries
after the astronomer Copernicus placed the Earth as a small
object in orbit around the Sun, the astronomers of the 20th
century placed the Sun as an ordinary star in our Milky Way
Galaxy, and then placed that galaxy as an ordinary galaxy in the
local cluster of galaxies, and then placed that local cluster as
an ordinary cluster in an even vaster supercluster, and that
supercluster as an apparent ordinary supercluster in an apparent
limitless population of superclusters in a Cosmos without
apparent boundaries. Whenever in the far future there will be
talk of the human species and where it is, our time will be noted
as the time of the Second Displacement after the First
Displacement by Copernicus.
     Since we are still in the Second Displacement, it is often
difficult to comprehend its nature and significance, but one
advantage of our presence in this time is that the important
events are clear, the remarkable achievements of the astronomers
and astrophysicists of this century still fresh and vibrant.
     In this context, three signal events occurred early in this
century. The first, in 1918, was the demonstration by Harlow
Shapley (1885-1972) that the Sun was not, as many believed, at
the center of our Galaxy, but was in fact 50,000 light-years
distant from the center (the figure was later reduced to 30,000
light-years by the work of J.H. Oort [1900-1992]).
     The second signal event, in 1924, was the demonstration by
Edwin Hubble (1889-1953) that the Andromeda Nebula was not in
fact, as nearly everyone then believed, a mass of gas and dust in
our Galaxy, but a galaxy like our own and 800,000 light-years
away (a figure later determined to be an underestimate), the
nearest of many galaxies outside the Milky Way Galaxy, each
galaxy containing millions or billions of suns.
     The third signal event occurred in 1929, but this requires
some elaboration since it was the culmination of years of work by
many people. The essential story is that following the
realization that the so-called "nebulae" were in fact galaxies,
astronomers began studying the spectra of these galaxies, and it
was soon apparent that almost all the spectra had spectral lines
shifted toward longer wavelengths (shifted to the red =
"redshift"). At that time, this was interpreted as a consequence
of the Doppler effect, these redshifts implying that the galaxies
were receding [*Note #1]. In 1929, Edwin Hubble announced a
general law of redshifts now known as the "Hubble law", the law
stating that the velocity of recession of a galaxy equals a
constant times its distance. Thus, the more distant a galaxy, the
faster its apparent recession from us. The constant, now denoted
as H(sub0), is called the "Hubble constant" (or Hubble parameter,
since in some models it is time dependent), is a critical
quantity in all current cosmological models, and enormous efforts
have been made to determine its exact value.
     One important aspect of the Hubble constant is that with
certain simplifying assumptions this constant allows one to
estimate the age of the universe. There are a number of methods
to do this, some more direct than others, and at present no one
in cosmology is apparently satisfied with the results [*Note #2].
... ... W.L. Freedman and L.L. Feng (2 installations, US CN)
present a review of current efforts to determine the Hubble
constant, the authors making the following points:
     1) What is required to measure an accurate value of the
Hubble constant? According to the Hubble law, what is needed are
measurements of both redshifts of galaxies (via spectral lines),
and distances to galaxies (at sufficiently large distances where
peculiar motions relative to the smooth *Hubble flow are slow).
The Hubble constant then follows immediately from the slope of
correlation between the redshift and distance. However, the
precise determination of galaxy distances remains a longstanding
fundamental problem in astronomy. In principle, measuring the
distance of a distant galaxy relies on a particular property of
the propagation of light in space: the apparent brightness of a
light source varies inversely with the square of distance.
Accordingly, the distance to an object may be determined by
knowing the intrinsic luminosity and then comparing that with its
apparent brightness.
     2) Establishing accurate extragalactic distances has
provided an immense challenge to astronomers since the 1920s. The
situation has improved dramatically as better detectors have
become available, and as several new and promising techniques
have been developed. For the first time in the history of this
difficult field, relative distances to galaxies are being
compared on a case-by-case basis, and their quantitative
agreement is being established. New instrumentation, the
development of new techniques for measuring distances, and
recent measurements with the *Hubble Space Telescope all have
resulted in new distances to galaxies with precision at the +- 5
to 20 percent level. The current statistical uncertainty in some
methods for measuring the Hubble constant is now only a few
percent, and with systematic errors, the total uncertainty is
approaching +- 10 percent. Thus, the authors state, "the
historical factor-of-two uncertainty in the value of the Hubble
constant is behind us."
-----------
W.L. Freedman and L.L. Feng: Determination of the Hubble
constant.
(Proc. Natl. Acad. Sci. US 28 Sep 99 96:11063)
QY: Wendy L. Freedman, Carnegie Observatories Pasadena US.
-----------
Text Notes:
... ... *Note #1: Redshift (symbol: z) is a lengthening of the
wavelengths of electromagnetic radiation from a source caused
either by the movement of the source (Doppler effect) or by the
expansion of the universe (cosmological redshift). Redshift is
defined as the change in wavelength of a particular spectral line
divided by the unshifted wavelength of that line. Large redshifts
imply large radial velocities (which imply large distances,
according to current cosmological theory), but at redshifts
greater than about 0.2 there is a relativistic divergence from a
linear relation. A redshift of 4.0 corresponds to an object
receding with a radial velocity 92% that of the velocity of
light. The largest astrophysical redshifts so far observed are of
the order of z = 4.9.
... ... *Note #2: Concerning the age of the Universe in this
context, the relevant term is the "Hubble time", i.e., the time
required for the Universe to expand to its present size, assuming
that the Hubble constant has remained unchanged since the
Universe came into existence. The Hubble time is defined as the
reciprocal of the Hubble constant, and according to current
estimates is between 9 and 18 billion years, depending on both
the value of the Hubble constant and on the cosmological model in
which it is applied.
... ... *Hubble flow: The general outward motion of galaxies
resulting from the uniform expansion of the Universe. All motions
lie in a radial direction from the observer, and the apparent
velocities are proportional to the distances of the galaxies. The
actual pattern of galaxy motions is perturbed by gravitational
interactions, but these gravitational interactions are
significant only locally and are small compared with the overall
Hubble flow.
... ... *Hubble Space Telescope: The Hubble Space Telescope was
launched from a space shuttle in 1990 into a 600-kilometer
low-Earth orbit and has been providing extensive imaging and
spectroscopic observations critical for the development of
astronomy and astrophysics. The new information has concerned hot
stars, stellar chromospheres and coronas, the interstellar
medium, galaxies and galactic clusters, quasars, etc. -- all of
it information uncorrupted by the Earth's atmosphere, which is
the problem for ground based telescopes.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 19Nov99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON EDWIN HUBBLE
At the time of his death, Edwin Hubble (1889-1953) was the most
eminent and celebrated observational astronomer in the world, a
man as well-known to the public as to the scientific community.
Essentially, Hubble made 3 major contributions during his
scientific career: 1) He provided the first evidence (1923) of
the existence of galaxies other than our own; 2) he proposed (in
the 1920s) a classification of galaxies as ellipticals, spirals,
and *barred spirals, a classification scheme still in use; 3) he
provided observational evidence (1928) for the recession of
galaxies (the expansion of the Universe), and he proposed (1929)
what is known as "Hubble's Law" relating the observed recession
rate of galaxies to their distance. The first and last of these
contributions have certainly been a most important part of the
foundation of 20th century cosmology. In much of his telescope
observational work, Hubble was assisted by Milton Humason (1891-
1972), an accomplished astronomer who was something of a Michael
Faraday in American astronomy: Humason had little formal
education and he first worked for Hubble as a janitor at the
Mount Wilson Observatory [*Note #1]. ... ... Gale E. Christianson
(Indiana State University) presents a biographical essay on
Hubble, the author making the following points: 1) Hubble was 6
feet 2 inches tall, weighed 190 pounds, constantly smoked a pipe,
favored a tightly-belted military trenchcoat, sported an English
accent acquired during his days as a Rhodes scholar at Oxford
University (where he studied law, not astronomy), and had a
special observatory wardrobe consisting of knickers, jodhpurs,
high-topped military boots, and a *Norfolk jacket. The author, in
fact, states that Hubble was disappointed when he arrived in
France during World War I only days before the November
armistice, "ending his dreams of leading men into battle." 2)
Hubble settled at the Mount Wilson Observatory in 1919, and
immediately began working with the 100-inch Hooker telescope. In
1923, working with the Hooker telescope, Hubble discovered
*Cepheid variable stars in the Andromeda *nebula M31 (later to be
called the Andromeda galaxy). Using the well-known period-
luminosity relationship established for Cepheid variables, Hubble
estimated the distance of the Andromeda galaxy as 300,000
*parsecs from Earth, a distance which apparently astounded
everyone. 3) Following the Andromeda galaxy work, in search of an
understanding of the formation and evolution of galaxies, Hubble
proposed what is now known as the "tuning fork diagram", a galaxy
classification scheme: the handle of the tuning fork consists of
an evolving sequence of elliptical galaxies (from spherical to
true elliptical), with one arm of the tuning fork diagramming the
evolution of spiral galaxies, and the other arm of the tuning
fork diagramming the evolution of the "barred" spiral galaxies.
4) In 1928, Hubble and Humason began a systematic study of the
*redshifts of galaxies, and in 1929 this resulted in the proposal
that the distances and recessional speeds of the nebulae
(galaxies) are in direct proportion to each other ("Hubble's
Law"): double the distance to a galaxy and the speed of recession
doubles; triple the distance and the speed triples [*Note #2]. 5)
In 1931, Einstein visited Hubble in Pasadena, and apparently when
Hubble was working at the observatory, Grace Hubble, Edwin
Hubble's wife, drove Einstein to his meetings and appointments.
The author concludes: "He [Einstein] was silent sometimes, and
sometimes he would talk in French or English, for Grace knew no
German. One afternoon he broke his silence to say, 'Your
husband's work is beautiful.'" [Editor's note: It was Hubble's
demonstration of the apparent expansion of the Universe that
caused Einstein to call his rather ad hoc introduction of the so-
called "cosmological constant" into his relativity equations "the
greatest aesthetic blunder of my life." Einstein's relativity
model proposed a non-expanding Universe essentially held static
by the cosmological constant term. In addition to the background
material below, considerably more background material can be
found in various SW Focus Reports located at the SW website:
[http://scienceweek.com/swfr.htm]].
-----------
Gale E. Christianson: Mastering the Universe.
(Astronomy February 1999)
QY: Gale E. Christianson, Indiana State University 812-237-2121.
-----------
Text Notes:
... ... *barred spirals: In general, a barred spiral galaxy is a
type of galaxy with spiral arms extending from an almost
rectangular or cigar-shaped bar of stars across its central
region.
... ... *Norfolk jacket: From Norfolk UK (c. 1866). A loose-
fitting belted single-breasted jacket with box pleats.
... ... *Cepheid variable stars: See main report.  
... ... *nebula: Before Hubble, all of the fuzzy astronomical
objects that appeared in telescopes, many of which are now known
to be galaxies, were thought to be clumps of gas and dust. There
are indeed clumps of gas and dust everywhere in the Universe, and
they are correctly termed "nebulae". But since the work of
Hubble, which means since the 1920s, the use of the term "nebula"
for a galaxy is obsolete and incorrect.
... ... *parsecs: 1 parsec equals 3.262 light-years, or 30.86 x
10^(12) kilometers.
... ... *Note #1: In general, the Hubble tuning fork diagram
contains 10 galaxy categories. An 11th category, "irregular
galaxies", is usually diagrammed as an extending tine between the
two tuning fork arms. The result is a 3-prong "pitchfork"
diagram, rather than a "tuning fork" diagram.
... ... *redshifts: See previous report.
... ... *Note #2: Humason measured the speed of recession of
approximately 800 galaxies. In 1956, three years after the death
of Hubble, Humason and others refined Hubble's Law, making the
proportionality constant (Hubble constant) in the relationship
between recession velocity and distance essentially time-
dependent. The "Hubble constant" is thus more properly called the
"Hubble parameter".
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 26Feb99
For more information: http://scienceweek.com/swfr.htm

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5. PLANETARY SCIENCE:
DETECTION OF DAILY CLOUDS ON SATURN'S MOON TITAN
The moon Titan is the largest satellite of Saturn and the second
largest moon in the Solar System. Titan was discovered by
Christiaan Huygens (1629-1695) in 1655, and with a diameter of
5150 kilometers it is larger than the planet Mercury. Titan is
believed to be composed of rock and ice in equal parts, and it is
apparently the only moon in the Solar System to have a
substantial atmosphere. This atmosphere consists mainly of
nitrogen, with 2 to 10 percent methane, and trace quantities of
hydrogen, ethane, propane, carbon monoxide, and several other
gases. The surface atmospheric pressure is 1.5 bars; the surface
temperature of the moon is -180 degrees centigrade. It has been
speculated that methane snow and rain may exist on the surface.
... ... C.A. Griffith et al (3 authors at 2 installations, US)
now report the detection of daily clouds on Titan, the authors
making the following points:
     1) The authors point out that the atmosphere of Titan has
often been compared to that of Earth, and that Titan may support
a methane cycle (resembling Earth's hydrologic cycle), with
clouds, rain, and seas. In the past decade, dozens of images and
spectra have been recorded through narrow spectral regions
("windows") where Titan's otherwise optically thick atmosphere is
largely transparent. No evidence, however, has been found for the
presence of rain and oceans, which are difficult to ascertain by
remote measurements. Observations have also shown no evidence of
clouds (relatively easy to detect), with one exception.
     2) The authors report they have discovered frequent
variations in the near-infrared spectrum of Titan, variations
which are indicative of the daily presence of sparse clouds
covering less than 1 percent of the area of the moon. The
thermodynamics of Titan's atmosphere and the apparent altitude of
the clouds suggest that convection governs the evolution of these
clouds. The authors suggest the short lives of these clouds point
to the presence of rain. The authors propose that Titan's
atmosphere resembles Earth's, with clouds, rain, and an active
weather cycle.
-----------
C.A. Griffith et al: Detection of daily clouds on Titan.
(Science 20 Oct 00 290:509)
QY: Caitlin A. Griffith, Dept. of Physics and Astronomy, Northern
Arizona University, Flagstaf, AZ 86011-6010 US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm

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6. CHEMISTRY: A FIRST NOBLE GAS-NOBLE METAL COMPOUND
     The so-called 'noble gases" ("rare gases"; "inert gases")
were discovered, beginning in 1894, by William Ramsay (1852-
1916), and Ramsay received the Nobel Prize for Chemistry in 1904
for his work. According to the valence shell model of atoms, the
atoms of the noble gases all have valence shells that are closed
octets (except helium, where there is a duet). These closed
shells are quite stable, consistent with their high ionization
potentials. The noble gas elements are all low-boiling gases
whose physical properties vary systematically with atomic number,
and the boiling point of helium is the lowest of any known
substance. The boiling points increase monotonically with
increasing atomic number, which is a consequence of the monotonic
increase of the heats of vaporization. The heats of vaporization
are essentially measures of the work that must be done to
overcome interatomic forces. Since there are no ordinary
electron-pair interactions between noble gas atoms, these weak
forces must be of the van der Waals or London type. Such forces
are proportional to the polarizability and inversely proportional
to the ionization potentials of the atoms, and they therefore
increase as the size and diffuseness of the electron clouds
increase.
     In 1962, Neil Bartlett, then 30 years old, discovered that
the noble gases can engage in genuine chemical reactions.
Bartlett observed that O(sub2) reacts with PtF(sub6) to give the
compound [O(sub2)(sup+)][PtF(sub6)(sup-)], and he recognized that
since the ionization potential of xenon is almost identical with
that of the oxygen molecule, an analogous reaction should occur
with xenon. This was confirmed, and Bartlett's discovery led to
extremely rapid and extensive developments in xenon chemistry,
and to the discoveries of chemical reactions involving several
other noble gases.
... ... S. Seidel and K. Seppelt (Free University Berlin, DE) now
report the first metal-xenon compound, the authors making the
following points:
     1) The authors point out that since the creation of the
first noble gas compound, XePtF(sub6), in 1962, xenon compounds
with direct bonds to fluorine, oxygen, nitrogen, carbon, xenon
itself, and most recently, chlorine, have been established, with
the list for krypton-bonded elements much shorter. All these
bonded atoms are electronegative main-group elements, and noble
gas chemistry would be greatly enhanced if xenon (or other noble
gases) could be bonded directly to metal atoms or ions.
     2) The authors report the first metal-xenon compound with
direct metal-xenon (in this case, gold-xenon) bonds was achieved
by reduction of AuF(sub3) with elemental xenon. The square planar
AuXe(sub4)(sup2+) was established by a single-crystal structure
determination, with a gold-xenon bond length of approximately
2.74 angstroms. The bonding between gold and xenon is of the
sigma-donor type, resulting in a charge of approximately 0.4 per
xenon atom.
     3) The authors conclude: "The isolation of the
AuXe(sub4)(sup2+) cation raises many questions that at present
cannot be answered satisfactorily. The main question is, of
course, whether this compound remains unique or if this is the
first of a series of new complexes. Predictions are difficult
because... stoichiometry and structure for [Au(sup2+) complexes]
are rare if not entirely new."
... ... In a commentary on this work, Pekka Pyykkoe (University
of Helsinki, FI) states: "Since [the discovery of a xenon
compound by Bartlett in 1962] numerous noble gas compounds have
been synthesized. Generally, gas-phase cations are easier to make
than neutral species, and neutral species dispersed in noble gas
matrices (cold environments containing excess noble gas) are
easier to make than bulk compounds. Neutral species containing
covalent bonds to light noble gases, such as argon, have until
recently remained elusive. [But] L. Kriachtchev et al (2000) have
[recently] synthesized the first neutral covalently bonded argon
compound, proving that such a bond is possible. And [now] Seidel
and Seppelt report the first bulk compound containing a noble-
gas-noble-metal bond, thus overcoming a double challenge, as both
noble gases and noble metals are considered unreactive."
-----------
S. Seidel and K. Seppelt: Xenon as a complex ligand: The tetra
xenono gold(II) cation in AuXe(sub4)(sup2+)(Sb(sub2)F(sub11)(sup-
))(sub2).
(Science 6 Oct 00 290:117)
QY: Konrad Seppelt: seppelt@chemie.fu-berlin.de
-----------
Pekka Pyykkoe: Noblesse oblige.
(Science 6 Oct 00 290:64)
QY: Pekka Pyykkoe: Pekka.Pyykko@helsiki.fi
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 3Nov00
For more information: http://scienceweek.com/swfr.htm

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7. IN FOCUS: ON SIZE AND EVOLUTION
----------
Editor's note: In biology, an interesting group of plain
questions concerns the sizes of organisms: Why is there such
tremendous diversity in the sizes of the various species of
living things. Is an increase in size always an adaptive change?
Are organisms with specialized cells necessarily more successful
than organisms without such specialization? There are as many
answers to these questions as there are fields in biology, and
within any one field one can find still more diverse opinions.
Here is an opinion on the matter presented by a biologist nearly
50 years ago, an opinion that is arguable but still pertinent:
-----------
"There is no living form or structure that does not impinge on
the problem of magnitude, but it must always be remembered that
when we consider the size of an object we always compare it with
something greater or smaller and that size has no meaning to us
except by comparison. The natural impulse of a man is to use
himself as a yardstick, and we call an elephant large and a mouse
small. In experimental science there are rulers and balances, but
even when one individual plant or animal is measured, it is
compared to the ruler or the balance, and furthermore we cannot
escape thinking of other plants or animals which are of a similar
or of a different size. Such being the case, if we wish to speak
of magnitude, we must compare organisms of different sizes; or if
we speak of one organism, it must be of different stages in its
development where again there are different sizes to compare...
It is customary to think that in the course of evolution there
arose a progressive division of labor [among cells] because the
organisms thereby became more efficient and better adapted to the
perilous process of natural selection. There is no question but
that these specialized forms have been successful, and we
ourselves are such a form, but we must not forget that the lowly,
minute, and often highly undifferentiated organisms have also
been successful, existing everywhere in the world in great
abundance, apparently since the very beginning of life on Earth.
The difference is that the larger forms with divided labor do not
compete directly with the smaller ones; they occupy different
niches in the environment. They differ in that some are large and
the others are small (albeit there are many grades of largeness
and smallness) and they have virtually separate micro and macro
environments. Thus size alone... is an aspect of adaptation, a
vital cog in the wheel of evolution. And with increase in size
and magnitude come progressive division of labor, progressive
differentiation."
-----------
John Tyler Bonner: _Morphogenesis: An Essay on Development_
(Princeton University Press, Princeton NJ 1952)
-------------------
SCIENCE-WEEK http://scienceweek.com 3Nov00

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8. FROM THE SCIENCEWEEK ARCHIVE:
A CRITIQUE OF THE NOBEL PRIZE
There are supreme awards in nearly all the branches of science,
but none of them have acquired the popular interest of the Nobel
prizes, and certainly no science prizes except the Nobel prizes
have had even a remotely comparable portrayal in melodrama.
... ... E. Crawford, a sociologist and historian of science,
presents a critique of the Nobel prizes and the Nobel prize
system, the author making the following points: 1) Nobel intended
his prizes to encourage promising young scientists, so it would
no doubt be a surprise for him to see the prizes become the
standards for the highest achievements of modern science. 2) The
notion that the Nobel prizes parallel the history of modern
science ignores the fact that the awards cover only a small part
of modern science, neglecting a number of important fields such
as technology, astronomy, meteorology, and psychiatry. Thomas
Edison, the Wright brothers, the astrophysicists G.E. Hale and
Arthur Eddington, the meteorologist Vilhelm Bjerknes, Sigmund
Freud -- all did not receive a Nobel prize. Before the 1920s,
even theoretical physics and theoretical chemistry were
neglected, and Arnold Sommerfeld, G.N. Lewis, Ludwig Boltzmann,
Josiah Willard Gibbs, Oliver Heaviside, and Henri Poincare also
did not receive a Nobel prize. 3) The manner in which attention
has focused on the prize winners -- never on the candidates -- is
one reason for the extraordinary success of the prizes. Another
reason is the wholesale acceptance of the justification provided
by the prize awarders for the choices. Major eligible discoveries
have indeed received prizes, but for the most part, the awarders
of the prize "have been engaged in the rather humdrum business of
choosing among works produced by what Kuhn called 'normal'
science." 4) From the beginning, secrecy has been at the heart of
the Nobel system, the statutes of the Nobel Foundation adopted in
1901 stipulating that no part of the prize deliberations could be
made public, nor could a prize decision be appealed. But in 1974
the statutes of the Nobel Foundation were changed to authorize
the four institutions that award Nobel prizes to permit access to
archival documents at least 50 years old for purposes of
historical research. 5) Myths are necessary for the cohesion of
institutions and groups, and the myth of the Nobel laureate as
the lone discoverer may appear to be one that preserves some of
the innocence of science in an age of multimillion dollar
research projects and research teams involving hundreds of
collaborators. But the winner-take-all mentality masks the
realities of doing science in the 20th century. 6) It is
important to bear in mind that prize winners are chosen from a
large pool of worthy candidates, and that the choices are
conditioned not only by the predilections of the Swedish prize
awarders but also by their ties to international networks that
so far have centered almost exclusively in Europe and North
America, allowing for few prize winners residing in Russia,
India, and Japan, and none in China.
-----------
E. Crawford (Universite Louis Pasteur, FR)
Nobel: Always the winners, never the losers.
(Science 13 Nov 98 282:1256)
QY: Elisabeth Crawford, Institut d'Histoire des Sciences,
Universite Louis Pasteur, 7 rue de l'Universite, 67070
Strasbourg, FR.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 27Nov98
For more information: http://scienceweek.com/swfr.htm


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