ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.

October 30, 1998 -- Vol. 2 Number 44

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

Humanity is far from perfect in its understanding,
abilities, or intentions. We must not imagine, however,
that we and our civilization are less than precious.
We have the gift of intelligence, and that is the
finest thing this planet has ever produced.
-- Michael A. Seeds

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

Contents of This Issue:

1. Controversy in US: Genetic Testing for Alzheimer's Disease
2. Astrophysics: Electron-Positron Jets from a Quasar
3. Astrophysics: Supernovae and Gamma Ray Bursts
4. Quantum Physics: A 2-Dimensional Quantized Hall Insulator
5. Evolution: 1 Billion Yr Old Fossils of Triploblastic Animals
6. The Evolution of Agriculture in Ants
7. Neurobiology: On Melatonin
8. On New Developments in the Biology and Treatment of HIV

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

1. CONTROVERSY IN US: GENETIC TESTING FOR ALZHEIMER'S DISEASE
     During the past 2 decades in the US, one relatively new
feature of the scientific enterprise has been a mushrooming of
the number of prominent academic researchers in molecular biology
who have become high-level corporate research managers. Often
these high-level research managers maintain ties to the
universities that originally hosted their research, ties, for
example, that may involve patent partnerships. Where patents are
involved, in many cases, the research underlying the patents was
financed by US federal funds, while the patents are now the basis
for extensive private commercial ventures. This situation was
made possible by explicit US Congressional legislation in the
1980s.
     Last May, in a long article, the journal *Science* presented
a detailed profile of Allen Roses, a neurologist at Duke
University (US), who in 1997 became head of genetics research at
Glaxo Wellcome, Roses overseeing a US$50 million genetics
research budget that is part of the Glaxo Wellcome US$2 billion
annual research and development effort.
     Prior to his move to Glaxo Wellcome, Roses achieved
prominence as the head of a research group at Duke University
that discovered a gene variant that apparently increases a
carrier's risk of developing the common late-onset form of
Alzheimer's disease (the most common form) -- a discovery that
was initially ignored by many researchers in the field but is now
considered to be of some importance.
     After assuming his new position at Glaxo Wellcome, Roses
apparently set about creating an international "network of
clinicians" to provide data and clinical material to Glaxo in its
"hunt for disease-related genes", with the evident interest of
Glaxo Wellcome that of patenting key discoveries (including
genes) and manufacturing drugs based on the new discoveries. The
focus is on pathologies such as asthma, cardiovascular disease,
mental depression, schizophrenia, inflammatory bowel disease,
dermatitis, and susceptibility to infectious agents -- in other
words, a wide array of human diseases with possible genetic
involvements. The essential idea is apparently to build up
detailed indexes of variations in human genes and use these
indexes to scan the genomes of patients or volunteers.
     Concerning Alzheimer's disease, the approach of Roses and
his group has been criticized because their marker for
Alzheimer's disease, a gene variant (called APOE4) of an
*apolipoprotein gene called APOE, does not appear to cause the
disease directly but appears to only increase the risk. Many
researchers believe that other genes and other proteins,
particularly so-called *beta-amyloid proteins, are involved in
Alzheimer's disease.
     The Allen Roses profile in *Science* appeared 15 May 1998.
     On 28 August 1998, J.F. Merz et al, in a letter to the
journal *Science*, pointed out that the article about Roses and
his advocacy of wide genetic testing for Alzheimer's disease did
not mention that Roses is named as an inventor on a patent
claiming exclusive rights to the detection of the APOE *allele,
a patent now held in exclusive license from Duke University and
Roses by a company called AthenaDiagnostics, and that
AthenaDiagnostics has attempted to stop anyone anywhere from
performing APOE genotyping for the purpose of diagnosing
Alzheimer's disease. In other words, AthenaDiagnostics
effectively owns the gene that may be one of the causes of
Alzheimer's disease, and no one can use that gene (which when
present appears as part of human chromosome 19) for diagnostic
purposes without paying a royalty fee. Considering the advocacy
by Roses of genetic testing for Alzheimer's disease, J.F Merz et
al stated: "This situation raises ethical concerns, not the least
of which is that those who benefit financially from the
performance of genetic testing and screening could be said to
have a conflict of interest that might lead to aggressive
promotion of those tests."
     On 18 September 1998, Allen Roses responded to the J.F. Merz
et al letter in *Science*, and also to other related commentary
by J.F. Merz et al in *Nature Medicine*. In summary, Roses
criticized his critics for "incorrect notions and opinions",
stated that it is not true that he receives 50% of the licensing
fees for the APOE gene, stated that he was being attacked
personally without relevant facts, and that he had not been able
to respond to the criticisms in *Nature Medicine* because that
journal does not entertain responses.
     On 9 October 1998, A.J. Ivinson, the editor of *Nature
Medicine*, published a letter in *Science* in response to the
Roses letter, Ivinson stating that *Nature Medicine* does
sometimes invite responses, and that during a face-to-face
discussion Roses was specifically invited to respond to the
*Nature Medicine* text and he failed to do so, "making his
comments regarding our policy on responses all the more
surprising."
     Finally, we return to 19 February 1998, to a paper published
in the *New England Journal of Medicine* by a large research
group that included the Roses research team, in which study the
authors reviewed clinical and autopsy APOE data on 2188
patients at various installations referred for evaluation of
dementia, and in which paper the authors (Allen Roses among them)
conclude: "APOE genotyping does not provide sufficient
sensitivity or specificity to be used alone as a diagnostic test
for Alzheimer's disease, but when used in combination with
clinical criteria, it improves the specificity of the diagnosis."
     All the backbiting and considerations of conflict of
interest aside, the last paragraph is the essence of this
brouhaha: Given that the direct and unique involvement of the
APOE gene in Alzheimer's disease has not been demonstrated,
should APOE genotyping (and consequent labeling of people as
"Alzheimer's prone") be widely used? The bioethicists say no,
that given the uncertainties in diagnosis, the social dangers are
too great; while Allen Roses, Glaxo Wellcome, and others say
yes,
that genotyping can substantially improve clinical diagnostics.
     As is seen in the attached background material below, the
problem is now not unique to the US. In fact, it is a safe guess
that in the next few decades, for many human genes, this sort of
problem will be commonplace.
     [Editor's note: A collection of relevant past SCIENCE-WEEK
briefs can be found at URL http://scienceweek.com in a Focus
Report under the title "Science and Commerce in Conflict".]
-----------
A.J. Ivinson (*Nature Medicine*)
Nature Medicine's reply policy.
(Science 9 Oct 98 282:239)
QY: Adrian J. Ivinson 
-----------
A.D. Roses (Genetics Glaxo Wellcome Research and Development, US)
Patent income.
(Science 18 Sep 98 281:1805)
QY: Allen D. Roses 
-----------
J.F. Merz et al (3 authors at University of Pennsylvania, US)
Testing for Alzheimer's.
(Science 28 Aug 98 281:1288)
QY: Jon F. Merz 
-----------
E. Marshall (*Science)
Allen Roses: From "street fighter" to corporate insider.
(Science 15 May 98 280:1001)
QY: Eliot Marshall 
-----------
R. Mayeux et al (10 authors at 8 installations, US)
Utility of the apolipoprotein E genotype in the diagnosis of
Alzheimer's disease.
(New England J. Med. 19 Feb 98 338:505)
QY: Richard Mayeux, Columbia Univ. 212-854-1754.
-----------

Text Notes:
... ... *apolipoprotein gene: An apolipoprotein is the protein
component of a lipoprotein (lipid + protein) complex. In its non-
pathological form, the apolipoprotein gene is involved in the
metabolism of fats. Concerning the pathological form of the gene,
apparently confirmed data indicate that white persons 60 to 80
years old with two copies of the variant allele are 9 times more
likely to get Alzheimer's disease than those who do not carry the
variant. But almost everything else about the gene is in
controversy.
... ... *beta-amyloid proteins: Post-mortem tissue analysis of
Alzheimer's disease patients and Down syndrome patients reveals
anomalous protein deposits (beta-amyloid protein) in brain nerve
cells. Many researchers believe these deposits are in some way
related to the etiology of both of these disease entities.
... ... *allele: An allele is one of two or more forms of a given
gene that control a particular characteristic, with the altern-
ative forms occupying corresponding loci on homologous chromo-
somes. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98

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

Related Background:

REPORT URGES CAUTION ON GENETIC TESTING FOR MENTAL DISORDERS
The continuing identification of specific gene mutations involved
in the pathogenesis of certain diseases will have as one
consequence an improvement in diagnostic and therapeutic
techniques that will considerably benefit patients with these
diseases. There is another consequence, however, a consequence
that is less certain to be uniformly beneficial: there are no
doubt many diseases whose pathogenesis involves one or more gene
mutations, but with the process such that the pathological
outcome is only more or less probable but not certain. The
identification of people with such probabilistic genetically
based pathologies is of great interest to commercial health
insurance and other interests, and there is thus a danger of a
type of branding of potential commercial insurance clients,
employees, children in various social contexts, and others on the
basis of genetic testing for "susceptibility genes". Britain's
main bioethics advisory panel has now issued a strong warning
against attempts to use genetic screening to predict an
individual's susceptibility to common mental health disorders
such as schizophrenia and Alzheimer's disease. There is concern
that commercial over-the-counter genetic tests for such diseases
will soon be available, and that the voluntary industry and
government constraints now in place will not be sufficient to
prevent the widespread use of such tests. The Nuffield Council on
Bioethics, Britain's national forum in this domain, has therefore
suggested in its recent report that regulations could be needed.
The report is titled: *Mental disorders and genetics: the ethical
context*. In a letter to the journal *Nature*, a group from the
Nuffield Council writes: "Even if a number of susceptibility
genes were identified for a particular disorder, the Nuffield
Council takes the view that, without an understanding of their
interaction, they would not be adequate for predicting individual
risk in a clinical setting. It has therefore recommended that
genetic testing for susceptibility genes which offer relatively
low predictive or diagnostic certainty be discouraged unless and
until there is clear medical benefit to the patient."
-----------
D. Dickson (*Nature*)
Panel urges caution on genetic testing for mental disorders.
(Nature 24 Sep 98 395:309)
QY: David Dickson 
----------
S. Thomas (Nuffield Council on Bioethics)
Restrict genetic susceptibility tests.
(Nature 24 Sep 98 395:317)
QY: Sandy Thomas, Nuffield Council on Bioethics, 28 Bedford
Square, London WC1B 3EG, UK
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 23Oct98


2. ASTROPHYSICS: ELECTRON-POSITRON JETS FROM A QUASAR
The most luminous objects in the Universe are distant *quasars
and *active galactic nuclei. Some of these objects emit strongly
at radio wavelengths, the emission evidently powered by twin jets
of *plasma streaming at close to the speed of light from the
nucleus of the underlying galaxy. The core of such a nucleus is
believed to be a supermassive *black hole of 10^(8) to 10^(9)
solar-masses. The composition of the jet plasma has been an
unresolved issue ever since the discovery of the jets, but the
two main candidates for the composition are an ordinary plasma
consisting of protons and *relativistic electrons, and a "pair"
plasma consisting only of relativistic electrons and *positrons.
... ... J.F.C. Wardle et al now report the detection of
*circularly polarized radio emission from the jets of quasar
3C279. This quasar, at an apparent *redshift of z = 0.538, is one
of the most luminous objects in the sky from radio to gamma-ray
wavelengths, and is violently variable across the electromagnetic
spectrum. The authors propose that the observed circular
polarization is produced by *Faraday conversion, and following
certain assumptions concerning energy flux and energy
distribution, the authors demonstrate the implication of this is
that electron-positron pairs must be an important component of
the jet plasma of quasar 3C279. The authors further suggest that
similar detections in 3 other radio sources indicate that, in
general, *extragalactic radio jets are composed mainly of
electron-positron pairs.
-----------
J.F.C. Wardle et al (3 authors at Brandeis University, US)
Electron-positron jets associated with the quasar 3C279.
(Nature 1 Oct 98 395:457)
QY: J.F.C. Wardle 
-----------

Text Notes:
... ... *quasars: (quasi-stellar objects) Extremely luminous
sources radiating energy over the entire spectrum from x-rays to
radio waves, and which are apparently the oldest and most distant
astronomical objects known. Their cores are thought to be
massive
*black holes.
... ... *active galactic nuclei: Central regions of galaxies in
which considerable energy is generated by processes other than
those operating in ordinary stars. The energy may result from the
accretion of material into a massive black hole situated at the
core of the galaxy.
... ... *plasma: A state of matter consisting of ions and
electrons moving freely. Stars, for example, consist of plasma.
Because a plasma is highly ionized, it can be affected by
external electrical and magnetic fields, and the charged
particles of the plasma interact electrically and magnetically.
... ... *black hole: If the terminal stages of star death leave a
remnant star mass greater than 3 solar masses, the ultimate
gravitational collapse will produce a "black hole", a
relativistic singularity. A black hole is a localized region of
space from which neither matter nor radiation can escape. The
"trapping" occurs because the requisite escape velocity, which
can be calculated from the relevant equations, exceeds the
velocity of light and is therefore unattainable. Another view of
a black hole is that it is a mass that has collapsed to such a
small volume that its gravity prevents the escape of all
radiation.
... ... *relativistic electrons: This refers to electrons
traveling close to the speed of light.
... ... *positrons: The positron is the antiparticle of the
electron. It has a charge identical but opposite to that of the
electron, and a rest mass identical to that of the electron.
In general, antiparticles are homologs of elementary particles
but with opposite charge. Matter composed entirely of
antiparticles is called antimatter.
... ... *circularly polarized: Electromagnetic radiation involves
the propagation of both electric and magnetic forces, and at each
point in a light beam, there is a component electric field and a
component magnetic field, both of which oscillate in all
directions perpendicular to each other and to the direction in
which the beam is propagated. In plane-polarized light, the
component electric field oscillates as in ordinary light except
that the direction of oscillation is contained within a plane.
Likewise, in plane-polarized light, the component magnetic field
oscillates within a plane, the planes in question being
perpendicular. Circularly polarized light has a component
electric field that varies in direction but not in magnitude, so
that the field traverses a spiral path in either a clockwise or
counterclockwise direction.
... ... *redshift: 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 = 5.
... ... *Faraday conversion: This is a conversion of linear
polarization to circular polarization which can occur with
radiative transfer in an anisotropic plasma.
... ... *extragalactic radio jets: The term "extragalactic" here
means outside our own Galaxy. Inside our own galaxy, radio jets
are associated with protostars (embryonic stars) or microquasars
(small versions of ordinary quasars [see below]).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98

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

Related Background:

ON QUASARS
... Michael Disney (University of Wales, UK) provides an
excellent review of the history and current status of quasar
research. Recent observations have led astronomers to the idea
that quasars are associated with massive galactic-center black
holes generating huge amounts of energy under special
circumstances. The author suggests that in terms of theory, we
need to understand how and when massive black holes form in the
first place. Did they precede or follow the formation of their
host galaxies? Secondly, we need a convincing physical model to
explain exactly how such black holes convert in-falling matter
into all the varieties of quasar radiation, from gamma rays to
superluminal radio jets, and the formulation of such a model may
not be easy. The author concludes with a quote by Carole Mundell
of the Jodrell Bank Observatory (UK): "Observing quasars is like
observing the exhaust fumes of a car from a great distance and
then trying to figure out what is going on under the hood."
QY: Michael Disney, University of Wales, Cardiff, UK.
(Scientific American June 1998) (Science-Week 5 Jun 98)

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

Related Background:

ON MICROQUASARS IN OUR GALAXY
... Space and time essentially have no meaning in a black hole.
The boundary of the black hole is called the "event horizon",
because any event within the boundary is invisible outside, the
invisibility resulting from the fact that no radiation can escape
to be detected. The radius of the black hole depends upon how
much matter has fallen into the region; it is called the
"Schwarzchild radius", and it is usually a few kilometers.
However, massive black holes are possible and are thought to be
the source of quasars... If quasars indeed involve black holes,
the radiation is from material just outside the black hole, and
not from anything within it. Nothing inside a black hole can get
out of it. Quasar black holes are believed to be black holes of
several million solar masses. In contrast to quasar black holes,
there have been identified black holes of only stellar mass
associated with "microquasars". ... ... Mirabel and Rodriguez (2
installations, FR MX) review the accumulated evidence concerning
microquasars in our Galaxy. Microquasars mimic on a smaller scale
many of the phenomena seen in quasars, and their discovery opens
the way for a new understanding of the connection between the
accretion of matter onto black holes and the origin of the
relativistic jets observed in remote quasars. The repeated
observation of two-sided moving jets in microquasars has led to a
much greater acceptance of the idea that the emission from quasar
jets is associated with material moving at speeds close to that
of light.
QY: I.F. Mirabel 
(Nature 16 Apr 98 392:673) (Science-Week 8 May 98) 


3. ASTROPHYSICS: SUPERNOVAE AND GAMMA RAY BURSTS
Supernovae are violent explosions marking the terminal stage of
certain stars. They are classified into two broad types, Type I
and Type II. A Type II supernova shows hydrogen in its spectrum,
while a Type I supernova shows no hydrogen in its spectrum. Type
I supernovae are further classified as Type 1a, Type 1b, and Type
Ic. A Type 1a supernova is believed to be due to the explosion of
a *white dwarf star in a binary star system, the result of matter
falling onto it from the companion star. When the mass of the
white dwarf exceeds the *Chandrasekhar limit, the white dwarf
undergoes runaway carbon burning and explodes. Type Ib and Ic
supernovae are thought to result from the collapse of the cores
of massive stars which have lost their hydrogen envelopes. Type
II supernovae arise from the explosion of stars of more than 8
solar masses. In this case, the explosion involves a violent
blow-off of outer-layer material after the massive star has
collapsed into a *neutron star or a black hole. Despite the
existing classification scheme, Type Ib and Type Ic supernovae
are more closely related to Type II supernovae than to Type Ia
supernovae. Gamma ray bursts are intense flashes of *gamma rays
detected at energies up to 10^(6) *electronvolts. They were
discovered by US Air Force satellites in 1967 but not
declassified until 1973. The detection of these bursts averages
about 1 per day, and measurements indicate the distribution of
bursts is isotropic, i.e., they are uniformly distributed across
the sky. The current consensus is that gamma ray bursts are
produced by the merger of two neutron stars, and up to this
point, the bursts that have been noted apparently originate
outside our own galaxy. ... ... In 3 contiguous reports in the
same journal, 3 research teams now report an association of the
gamma ray burst of 25 April 1998 (GRB980425) with the supernova
SN1998bw, which exploded at approximately the same time as the
gamma ray burst. Although in general the properties of supernovae
are very different from those of gamma ray bursts, the apparent
new consensus is that supernova SN1998bw establishes a second
class of gamma ray burst which is distinctly different from the
cosmological kind. It is suggested that in some supernovae the
outer layer of the exploding star is given sufficient energy to
cause it to expand at speeds approaching the speed of light, and
that this initially produces a burst of gamma rays and a
subsequent radio emission. If this suggestion is correct, gamma
ray bursts may be produced by two substantially different
mechanisms.
-----------
S.R. Kulkarni et al (9 authors at 5 installations, US AU)
Radio emission from the unusual supernova 1998bw and its
association with the gamma-ray burst of 25 April 1998.
(Nature 15 Oct 98 395:663)
QY: S.R. Kulkarni 
-----------
T.J. Galama et al (50 authors at 21 installations, NL US CL IT JP
UK DE AU)
An unusual supernova in the error box of the gamma-ray burst of
25 April 1998.
(Nature 15 Oct 98 395:670)
QY: T.J. Galama 
-----------
K. Iwamoto et al (27 authors at 9 installations, JP IT CL DE NL
US)
A hypernova model for the supernova associated with the gamma-ray
burst of 25 April 1998.
(Nature 15 Oct 98 395:672)
QY: K. Nomoto 
-----------

Text Notes:
... ... *white dwarf star: White dwarf stars are extremely dense
and compact stars that have undergone gravitational collapse.
They are the final stage in the evolution of low-mass stars after
they have lost their outer layers. White dwarf stars are about
the size of Earth, but with a mass about that of the Sun.
... ... *Chandrasekhar limit: The remnant mass after the blow-off
during the terminal stage of the life of a star determines the
ultimate fate of the star. If the remnant mass is less than 1.44
solar masses (the Chandrasekhar limit for a star with no hydrogen
content), the star collapses into a white dwarf. If the remnant
mass is greater than 1.44 solar masses, depending on the remnant
mass, the star collapses into either a neutron star or a black
hole. Named after Subrahmanyan Chandrasekhar (1910-1995), who
first proposed the modern theory of stellar gravitational
collapse, and who received the Nobel Prize in Physics 1983.
... ... *neutron star: If, following its terminal stages, the
remnant mass of a star is between 1.4 and 2 to 3 solar masses,
the star will collapse into a neutron star, a body with a radius
of 10 to 15 kilometers, with a core so dense that its component
protons and electrons have merged into neutrons. The average
density of a neutron star is 10^(15) grams per cubic centimeter,
and the weight of an object on the surface of a neutron star
would be 10^(11) its weight on the surface of the Earth. Neutron
stars apparently have an outer shell of iron, but it is iron like
no Earth iron, an iron of 4 orders of magnitude greater density.
... ... *gamma rays: Gamma rays are radiation of high energy,
from about 10^(5) electronvolts to more than 10^(14)
electronvolts -- radiation with the shortest wavelengths and
highest frequencies, the gamma ray region of the electromagnetic
spectrum merging into the adjacent lower energy x-ray region.
... ... *electronvolts: (eV) A unit of energy defined as the
energy acquired by an electron in falling through a potential
difference of 1 volt. 1 electronvolt = 1.602 x 10^(-19) joule.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98


4. QUANTUM PHYSICS: A 2-DIMENSIONAL QUANTIZED HALL INSULATOR
In classical physics, the *Hall effect is the development of a
transverse voltage across a current-carrying conductor in a
magnetic field, the voltage being perpendicular to both the 
direction of the current and the direction of the magnetic field.
In quantum physics, there are two other Hall effects, an integer
charge quantum Hall effect, and a fractional charge quantum Hall
effect, these quantum Hall effects being observed at extremely
low temperatures (a few degrees Kelvin) and extremely high
magnetic fields (at least several tesla). Both quantum Hall
effects were first noted in the 1980s. In the quantum Hall
effect, the Hall resistance, the ratio of the voltage to the
current, is precisely related to Planck's constant, the
electronic charge, and an integer or rational fraction.
Concerning the electrical properties of matter, the general
theoretical definition of an insulator is a material in which the
conductivity vanishes at the absolute zero of temperature. In
classical insulators, vanishing conductivities lead to infinite
resistivities. But other insulators can show more complex
behavior, particularly in the presence of a high magnetic field,
where different components of the resistivity can display
different behaviors. For example, in magnetoresistive systems the
*magnetoresistance becomes infinite as the temperature approaches
zero, but the transverse (Hall) resistance remains finite. Such
systems are known as "Hall insulators". ... ... M. Hilke et al
now report experimental evidence for a *quantized Hall insulator
in a 2-dimensional electron system confined in a *semiconductor
quantum well. The authors report the Hall resistance is quantized
in the quantum unit of resistance of given by the ratio of
Planck's constant to the square of the electronic charge. At low
fields, the sample reverts to a normal Hall insulator. The
authors suggest the existence of these insulators can serve as
guidelines for a complete understanding of 2-dimensional systems
in strong magnetic fields.
-----------
M. Hilke et al (6 authors at 2 installations, US)
Experimental evidence for a two-dimensional quantized Hall
insulator.
(Nature 15 Oct 98 395:675)
QY: M. Hilke 
-----------

Text Notes:
... ... *Hall effect: The importance of the classical Hall
effect, discovered by E. H. Hall in 1879, is that it indicates
the sign of the charge carriers in a conductor. Hall placed a
metal strip carrying a current in a magnetic field, and observed
a voltage difference produced across the strip. The side of the
strip at the higher voltage depends on the sign of the charge
carrier, and Hall's observations demonstrated that in metals the
charge carriers are negative. It was only later that the metal
charge carriers were identified as electrons. The Hall effect
again became an active area of research with the discovery of the
quantized Hall effect by Klaus von Klitzing, who received the
Nobel Prize in Physics for his discovery in 1985. Before von
Klitzing's discovery, it was believed that the amount of voltage
difference across the conducting strip varied in direct
proportion to the strength of the magnetic field. Von Klitzing
demonstrated that under the special conditions of low
temperature, high magnetic field, and two-dimensional electron
systems in which electrons are confined to move in a plane, the
voltage difference is quantized, increasing in a series of steps
with increasing magnetic field. 
... ... *magnetoresistance: A change in the electrical resistance
of a conductor or semiconductor upon the application of a
magnetic field, a property of magnetoresistive systems.
... ... *quantized: In experimental physics, a quantized variable
is a variable taking only discrete multiple values of a quantum
mechanical constant. In theoretical physics, "quantizing" means
the consistent application of certain rules that lead from
classical to quantum mechanics. In general, "quantization" is a
transition from a classical theory or a classical quantity to a
quantum theory or the corresponding quantity in quantum
mechanics.
... ... *semiconductor: This experiment involved a silicon-
germanium system doped with boron.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98


5. EVOLUTION: 1 BILLION YR OLD FOSSILS OF TRIPLOBLASTIC ANIMALS
There are two contradictory views concerning the early history of
*metazoans. The "*Cambrian explosion" hypothesis is based on
Cambrian shell fossils and *Burgess-type exceptionally well-
preserved fossil deposits ("lagerstatten"). This hypothesis
suggests that animal phyla originated rather suddenly
approximately 580 million years ago during the *Proterozoic-
Phanerozoic transition. The alternative hypothesis (called "slow
burn") suggests that animals developed more slowly, first
appearing, according to some molecular analyses, more than 1
billion years ago. ... ... A. Seilacher et al now report data
from the Mesoproterozoic Chorhat Sandstone site in central India.
The authors report that certain *bedding plane features are
biological and can be interpreted as the burrows of wormlike
undermat miners (i.e., *infaunal animals that excavated tunnels
underneath *microbial mats). The authors suggest these burrows
indicate that *triploblastic animals existed more than a billion
years ago. The authors further suggest their evidence indicates
that the diversification of animal designs proceeded very slowly
before the appearance of organisms with hard skeletons during the
Cambrian evolutionary explosion, and that the diversification
occurred before the ecological changes that accompanied that
explosion.
-----------
A. Seilacher et al (3 installations, DE IN US)
Triploblastic animals more than 1 billion years ago: Trace fossil
evidence from India.
(Science 2 Oct 98 282:80)
QY: Friedrich Pfluger, Yale University, 203-432-4771.
-----------

Text Notes:
... ... *metazoans: In general, the term "metazoa" refers to all
multicellular animals. Among important distinguishing
characteristics of metazoa are cell differentiation and
intercellular communication. For certain multicellular colonial
entities such as sponges, some biologists prefer the term
"parazoa".
... ... *Cambrian: Refers to the time-frame 500 to 600
million years ago.
... ... *Burgess-type: The Burgess Shale fossil deposit site in
British Columbia (CA) is apparently a geological accident of
superb preservation, and one that has revealed to paleontologists
the limitations of their views of the varieties of life in the
*Cambrian period. All the fossils expected for the Cambrian are
found in the Burgess Shale, but studies have demonstrated in
addition a remarkable array of perfectly preserved soft-bodied
animals, including a variety of worms, *arthropods, sponges,
*brachiopods, and some bizarre forms seemingly unrelated to any
known groups. The consequence was a new appreciation among
paleontologists of the tremendous increase in metazoan diversity
that apparently occurred during the Cambrian period, and indeed
this increase is now considered one of the most important events
in the history of life on Earth. 
... ... *arthropods: The largest phylum in the Animal Kingdom in
terms of both number of taxa and biomass, but the taxonomy has
undergone revision, and it is now essentially an informal
classification. In general, the arthropods are characterized by a
tough chitinous protective covering (exoskeleton) flexible only
at the joints (e.g., insects).
... ... *brachiopods: A phylum of bivalve coelomate invertebrates
resembling bivalve molluscs. The term "bivalve" refers to the
presence of a hinged shell; the term "coelomate" refers to the
presence of a true body cavity.
... ... *Proterozoic-Phanerozoic transition: The Proterozoic eon
is the time-frame 2600 million years ago to 600 million years
ago. The Phanerozoic eon is the time-frame 600 million years ago
to the present. During the Phanerozoic, atmospheric oxygen
apparently increased by a factor of 10 to its present value.
... ... *bedding plane: A distinct surface separating two
strata, the bedding plane marking a break in the continuity of
sedimentation, a break that can be caused by a period of erosion
or a cessation of sediment supply.
... ... *infaunal: Refers to an organism that burrows into the
substrate.
... ... *microbial mats: A dense microbial layer. The authors
propose this served as a food source for wormlike animals
exploiting its decaying base.
... ... *triploblastic animals: These are animals with a body
organization derived from 3 germ layers (ectoderm, endoderm,
mesoderm). The category includes all metazoans except
*coelenterates, which are diploblastic.
... ... *coelenterates: A phylum of mostly marine multicellular
animals. (e.g., jellyfish).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98


6. THE EVOLUTION OF AGRICULTURE IN ANTS
Fungus farming by ants of the tribe Attini apparently originated
in the early *Tertiary period and thus predates human agriculture
by approximately 50 million years. During its extensive
evolutionary history, this *symbiosis between "attine" ant
farmers and their fungal *cultivars has acquired an astonishing
complexity involving, among other things, secretion of antibiotic
"herbicides" to control weed molds and elaborate manuring regimes
that maximize fungal harvests. Of the over 200 known extant
attine ant species, all are *obligate fungus farmers. Cultivars
are propagated vegetatively as *clones within nests, and between
parent and offspring nests. In the few studied cases, the
foundress ant queen carries in her mouth a pellet of fungus from
the origin nest that she uses to start her own garden. This mode
of propagation has suggested the long-standing hypothesis that
the fungi of attine ants are ancient clones that have strictly
coevolved with their hosts. ... ... U.G. Mueller et al now report
an analysis of the evolutionary history of this ant-fungi
symbiosis as revealed in phylogenetic and population-genetic
patterns of 553 cultivars isolated from the gardens of relatively
primitive fungus-growing ants. The authors report these patterns
suggest that fungus-growing ants succeeded at domesticating
multiple cultivars, that the ants are capable of switching to
novel cultivars, that single ant species farm a diversity of
cultivars, and that cultivars are shared occasionally between
distantly related ant species, probably by lateral transfer
between ant colonies.
-----------
U.G. Mueller et al (3 authors at 3 installations, PA US)
The evolution of agriculture in ants.
(Science 25 Sep 98 281:2034)
QY: Ted R. Schultz 
-----------

Text Notes:
... ... *Tertiary period: A geological period comprising the
time-frame 70 million to 3 million years ago.
... ... *symbiosis: In biology, symbiosis is an intimate and
protracted association of individuals of different species.
Mutualism is a type of symbiosis in which both participants
receive benefits from the association.
... ... *cultivars: In general, a variety of plant produced by
selective breeding, i.e., a distinct subspecies that does not
occur naturally in the wild.
... ... *obligate: In this context, refers to an essentiality for
survival. Thus, "obligate fungus farmers" here denotes ants for
which fungus farming is essential for ant survival.
... ... *clones: In general, cloning is a reproduction of
individual organisms asexually, as in propagating a plant through
stem or leaf cuttings, or the production of a population of
organisms by successive replications from a single organism. A
"clone" is an organism or group of organisms so produced.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98


7. 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

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

Related Background:

CIRCADIAN OSCILLATORS: RESETTING BY TEMPERATURE CHANGES
Many organisms exhibit daily (circadian) rhythms, cyclical
variations in various bodily functions, metabolisms, etc., the
variations having considerable endurance even in constant light
or constant darkness. Such biological clocks are most easily
studied in simple organisms. Recent research has resulted in the
identification of common elements in the molecular mechanisms of
circadian rhythms and in the ways that these mechanisms respond
to environmental cues such as light and temperature. Phase
resetting by light is understood in terms of rapid light-induced
responses of central clock biochemical components. However, a
description of how small, naturally occurring temperature cycles
can reset a clock is lacking. ... ... Liu et al (4 authors at
Dartmouth Medical School, US) now report a study of the clock
protein FRQ in *Neurospora. Levels of FRQ were measured at
various temperatures. At higher temperatures, the amount of FRQ
oscillated around higher levels. Absolute FRQ amounts thus
identified different times at different temperatures, so
temperature shifts corresponded to shifts in clock time without
immediate synthesis or turnover of components. Moderate
temperature changes could dominate light-to-dark shifts in the
influence of circadian timing. The authors suggest their results
provide insight into how physiologically and ecologically
relevant temperature steps and pulses act to reset a day-phase
circadian oscillator. They further suggest their results provide
another example in which highly conserved and plainly adaptive
behaviors of a circadian system can be understood in terms of the
straightforward responses of clock components to factors in the
environment of the organism.
QY: Jay C. Dunlap 
(Science 7 Aug 98 281:825) (Science-Week 4 Sep 98)

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

Related Background:

... ... *Neurospora: (pink bread mold) A genus of fungi grown in
culture and widely used in research in genetics and biochemistry.

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

Related Background:

CIRCADIAN RHYTHMS IN HUMANS: EXTRA-VISUAL PHOTOTRANSDUCTION
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, for example, the endogenous rhythm will continue,
but will tend to drift out of synch. Restoring the external
light-dark cue will reset the clock to its normal intrinsic
rhythm. ... ... 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) (Science-Week 30 Jan 98)

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

Related Background:

DISSEMINATED INDEPENDENT CIRCADIAN CLOCKS IN THE FRUIT FLY
Drosophila melanogaster is a fruit fly that has been extensively
used in research in genetics, development, and molecular biology.
A transgenic Drosophila is a fruit fly into which genetic
material from another organism has been transferred, the trans-
ferred and incorporated new genes then being expressed with the
resultant production of specific proteins. Bioluminescence is the
production of light in biological organisms, the process usually
involving the protein luciferin and the enzyme luciferase. In
molecular biology, a "promoter" is a DNA sequence essential for
the initiation of the transcription of RNA from a particular gene
sequence. Many organisms exhibit daily (circadian) rhythms,
cyclical variations in various bodily functions, metabolisms,
etc., even in constant light or constant darkness. Such
biological clocks are most easily studied in simple organisms,
but several clock genes have been identified that have apparently
been conserved in evolution and are present in both simple
organisms and higher forms such as mammals. Now Plautz et al (4
authors at 2 installations, US) report that using transgenic
Drosophila expressing either luciferase or a green fluorescent
protein derived from the promotor of the clock gene period to
monitor the circadian clock in various explanted body parts
reveals that such tissues show rhythmic bioluminescence that can
be reset by light. The authors suggest their results show that
autonomous circadian oscillators are present throughout the body
of Droso-phila, that individual cells in Drosophila are capable
of supporting their own independent clocks, and that the idea of
a master oscillator controlling all other oscillators may need to
be revised.
QY: Steve A. Kay, Scripps Research Inst. 619-784-1000
(Science 28 Nov 97) (Science-Week 19 Dec 97)

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

Related Background:

IDENTIFICATION OF A MAMMALIAN CIRCADIAN RHYTHM GENE
Circadian rhythms are *biological rhythms based on a 24-hour
cycle apparently controlled by an endogenous biochemical clock.
The essential aspect is that if the environmental cues are
removed, the rhythm will continue for some time before the
periodicity degenerates. These rhythms are observed in both
primitive organisms and in mammals including humans, and in
primitive organisms as well as in insects, several genes have
been isolated that apparently are involved in the endogenous
clock process. Cheng-Chi Li et al (Baylor College of Medicine,
Houston TX US) have now isolated a gene in mice and humans that
is apparently similar to the "period" per gene of the fruit fly
Drosophila melanogaster. Previous evidence shows the fruit fly
gene is switched on and off in a daily cycle, and with several
other genes produces the oscillating mechanism responsible for
the organism's diurnal clock. This is apparently the first
evidence that clock genes have been conserved through the course
of evolution.
QY: C-C. Li, Baylor College of Medicine (713) 798-4841
(Cell 19 Sep) (Science-Week 10 Oct 97)

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

Related Background:

... ... *biological rhythms: Cyclic behaviors of various kinds
have been observed in organisms ranging from single-celled
protozoans and primitive plants to the most recently evolved
primates. In animals, an endogenous clock apparently exists in
the brain, and the light-sensitive production of the hormone
melatonin is evidently involved in this brain clock. Many
biologists believe primeval 13-hour tidal rhythms and monthly
lunar cycles influenced the clocks of primitive seashore
creatures, beginning the evolution of related biological clocks.
But of course the most significant periodicity to which the Earth
biosphere has always been exposed is the day-night light cycle,
and the term "circadian" technically applies only to this 24-hour
cycle.

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

Related Background:

ANALYSIS OF MELATONIN ROLE IN HUMAN CIRCADIAN RHYTHMS
... 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 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 some insects, the biological clock
may be located in the optic lobes of the brain, and biological
clocks of one sort or another have been found at nearly all
levels of organism complexity. In humans, there is some evidence
that our biological clocks can be implicated in psychiatric
entities known as mood disorders, which is not surprising, since
the hypothalamus and nearby structures are known to play a key
role in emotions. But more generally, the biological clock is
apparent to anyone who has experienced jet-lag upon travelling
long distances east or west, the jet-lag effects resulting from
the body's biological clock being out of synch with the
light-dark cycle. The key question, of course, is that if
melatonin is involved in the workings of the human biological
clock, exactly how does it function? A number of laboratories
have been concerned with this problem, and this week Steven
Reppert et al (installations in MA, CT US) report that melatonin
apparently has two receptors, a major and a minor, and that the
result of binding to the minor receptor is a lowering of activity
in the suprachiasmatic nucleus, which seems to indicate a
chemical negative feedback loop. Identification of such feed-
back loops are the key to understanding brain function. The
studies were carried out on genetically altered mice lacking the
major melatonin receptor.
QY: S. Reppert, Harvard Med. School, Boston MA US (617) 432-1000
(Neuron 25 Jul 97) (Science-Report 1 Aug 97)

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

Related Background:

IDENTIFICATION OF A CLOCK GENE IN THE MOUSE
The unraveling of the molecular mechanisms of biorhythmicity
received new impetus recently. Two weeks ago Loros and Dunlap
reported the identification of two new clock genes in the bread
mold Neurospora, the genes chemically related to those already
known in Neurospora and also in the fruit fly, and now Joseph
Takahashi and his colleagues (Northwestern Univ., Evanston IL
US) report the identification of the first mammalian clock gene
in the mouse. Circadian rhythms in mice are precise, animals
kept in darkness beginning exercise on a treadmill each night
with a 23.7 hour cycle. The method used by Takahashi and his
group was to produce random chemical mutations of the entire
mouse genome until one mouse was found that had its clock
altered. Proceeding from there, the damaged gene was identified.
The gene's function was proved by repairing the clock in mutant
mice by substituting a correct piece of DNA. Of great interest
is the news that one domain of the mouse clock protein is the
same as a domain in the clock proteins of the fruit fly and
Neurospora, which supports the idea that circadian rhythms in
mammals have evolved from biochemical feedback loops in
primitive organisms.
(Cell 16 May) (Science-Week 22 May 97)

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

Related Background:

CLOCK GENES: RESPONSES TO LIGHT AND CIRCADIAN RHYTHMS
... Now Susan K. Crosthwaite et al (Dartmouth Medical School, US)
have shown that certain clock genes in the fungus Neurospora are
also involved in the production of proteins necessary for the
organism's response to light, suggesting that circadian
oscillators in more complex organisms evolved from light-
regulated pathways in simpler organisms.
(Science 2 May) (Science-Week 8 May 97) 


8. ON NEW DEVELOPMENTS IN THE BIOLOGY AND TREATMENT OF HIV
HIV-1 is the subtype of HIV (human immune-deficiency virus) that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV is a retrovirus (subclass
lentivirus), and retroviruses are single-stranded RNA viruses
that have an enzyme called reverse transcriptase. With this
enzyme the viral RNA is used as a template to produce viral DNA
from cellular material. This DNA is then incorporated into the
host cell's genome, where it codes for the synthesis of viral
components. After initial transmission of HIV, viral particles
accumulate in blood to high levels within a few weeks, but levels
then fall as a result of the onset of the host immune response.
Thereafter, the disease usually remains quiescent for a prolonged
period, often for years or even decades, a phase termed "clinical
latency." ... ... F. Bushman et al present a short review of new
developments in HIV-1 biology and make the following points: 1)
Recent studies have revealed that the development of HIV viral
variants resistant to antiviral agents is a consequence of the
highly dynamic nature of the virus replication process. After
initial HIV infection, during the period of clinical latency, new
*virions are synthesized at a very high rate, with as many as
10^(10) virions produced and destroyed per day. The small HIV
genome of 10^(4) *base pairs is copied by two error-prone
enzymes: host-cellular *RNA polymerase and viral reverse
transcriptase. The enzyme reverse transcriptase makes
approximately 1 error per 10^(4) bases copied, so that each viral
genome bears on average one mutation. Because of this relatively
high mutation rate and the very large population of viruses in
vivo, many drug-insensitive mutant viruses are already present in
patients before treatment even begins. 2) The recent introduction
of effective anti-HIV drugs depends on the idea that if treatment
can suppress viral replication to a low enough level, then drug-
insensitive mutants have a greatly reduced probability of
arising. The development of anti-HIV *protease inhibitors has
brought this goal within reach for many patients. Most effective
of all therapies have been mixtures of antiviral drugs,
particularly "cocktails" of two reverse transcriptase inhibitors
and a protease inhibitor (triple combination therapy). 3)
Unfortunately, combination therapy is not a cure. Recent studies
report that patients who have maintained very low viral loads for
up to 30 months nevertheless harbor replication-competent virus
in a small number of *CD4(+) T-cells. This discovery of long-
lived reservoirs of virus-infected cells has caused hopes for a
cure to recede. 4) The emergence of drug-resistant variants of
HIV represents a long-term threat to the success of triple
combination therapy. It is estimated, for example, that 30 to 40
percent of HIV-infected people in the US may already have viruses
resistant to protease inhibitors. 6) Although many HIV-infected
people in the developed world can now be treated with therapy
likely to improve the length and quality of life, in the
developing world AIDS continues to spread and is unchecked. The
authors conclude: "The AIDS pandemic will likely remain
devastating for a long time to come."
-----------
F. Bushman et al (3 installations, US)
New developments in the biology and treatment of HIV.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11041)
QY: Frederic Bushman, Salk Institute, 10010 N. Torrey Pines Road,
La Jolla, CA 92037 US.
-----------

Text Notes:
... ... *virions: The complete virus particle that is
structurally intact and infectious.
... ... *base pairs: The term "base pair" refers to the bases
(nucleotides) always found chemically bonded together in the DNA
double helix (adenine, for example, always bonds with thymine,
and guanine with cytosine).
... ... *RNA polymerase: RNA polymerase is an enzyme that
polymerizes ribonucleoside triphosphates into RNA in the order
dictated by a DNA or RNA template. RNA polymerases are found in
all living cells, with one type found in prokaryotes (cells
without a cell nucleus and other membrane-bound organelles), and
3 types found in eukaryotes (cells with a cell nucleus).
... ... *protease: In general, any enzyme that cleaves proteins,
usually by hydrolysis. Late during HIV replication, the HIV virus
proteins must undergo precise cleavage at several sites to
complete formation of infectious virus particles. The HIV encodes
an enzyme that performs this function, and this enzyme is known
as the HIV protease.
... ... *CD4(+) T-cells: (CD4[+] lymphocytes) Lymphocytes (lymph
cells, lympholeukocytes) are a type of leukocyte (white blood
cell) responsible for the immune response. There are two classes
of lymphocytes: 1) the B-cells, when presented with a foreign
chemical entity (antigen), change into antibody producing plasma
cells; and, 2) the T-cells interact directly with foreign
invaders such as bacteria and viruses (cytotoxic T-cells), or
assist in the activation and cloning of antibody-producing B-
cells (helper T-cells). The T-cells express various surface
marker macromolecules, and CD4+ is the notation for a specific
expressed helper T-cell surface marker that can be identified by
assay. HIV exhibits great specificity for the helper T-cells of
the human immune system.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 30Oct98