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.

January 15, 1999 -- Vol. 3 Number 3

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It took a million years to move from counting
pebbles to the elaborations of quantum mechanics.
Certainly this was an arduous migration of the
multitude -- not a private party of physicists,
but the Long March of the entire human race.
-- Anonymous

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Contents of This Issue:

1. A Dangerous New Source of Environmental Lead
2. On Magnetoelectronics
3. Theoretical Biology: Controlling Cell Cycle Dynamics
4. Transgenic Cattle: Reverse-Transcription Gene Transfer
5. Genetic Control of Social Organization in Ants
6. Biology of Cancer: On the Enigmas of Kaposi's Sarcoma
7. Infant Autism: Use of Movement Analysis in Diagnosis
 
Following the main text: Notices, subscription information,
editorial contacts, etc.

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1. A DANGEROUS NEW SOURCE OF ENVIRONMENTAL LEAD
There is ample evidence that the developing nervous system of a
child is highly sensitive to a number of toxic substances, the
effects of which are various encephalopathies (brain disorders)
[*Note #1]. One environmental toxic substance of considerable
importance in this context is lead, an urban environmental
contaminant that in the past few decades has become a focus of
public awareness. The classical sources of urban environmental
lead contamination are the gasoline exhaust fumes of motor
vehicles and lead-based paints, but recently another important
source of such contamination has become apparent. ... ... Howard
W. Mielke (Xavier University New Orleans, US) presents a review
of the problem of lead in inner cities with emphasis on the newly
recognized danger of lead contamination of inner city soil and
dust. The author makes the following points: 1) Since the 1920s,
millions of US children have been quietly poisoned by lead, and
thousands of deaths are attributed to this over the long term. 2)
Although childhood lead exposure in the US has diminished during
the past 2 decades, the problem has not been solved. Instead, the
demographics has shifted. 3) Over 50 percent (and perhaps even 70
percent) of children living in the inner city of New Orleans and
Philadelphia have blood lead levels above the current guideline
of 10 micrograms per deciliter [*Note #2]. In contrast, in the
concrete "jungle" of Manhattan, where very little of the soil is
exposed and almost all apartments and housing contain lead-based
paints, only between 5 and 7 percent of children under the age of
6 have been reported to have blood-lead levels of 10 micrograms
per deciliter or higher. It is of significance that in Brooklyn,
across the river from Manhattan, where yards containing soil are
common, the percentage of affected children is several times
higher than in Manhattan. 4) The serious of the problem has been
recognized by the US Centers for Disease Control and Prevention
since the early 1990s, which has called pediatric lead poisoning
"entirely preventable". 5) The author suggests that effective
prevention assumes an accurate identification of the
environmental reservoirs of lead, and that current policies to
reduce lead exposure are based on the assumption that the
greatest lead hazard comes from lead-based paints [*Note #3].
Most lead-based have now been removed from the market, and
parents have been instructed to guard their children from eating
paint flakes. However, for children, paint is now neither the
most abundant nor the most accessible source of lead. The common
problem is lead dust in the environment, with the soil a giant
reservoir of tiny particles of lead. The greatest risk for
exposure of inner city children is in the yards around houses and
to a lesser extent in public playgrounds. 6) The author suggests
that an accurate and complete appreciation of the distribution of
lead in the environment can help shape policies that more
effectively protect the health of children. The author concludes:
"It took nearly 10 decades for lead to accumulate to its current
levels in urban areas. With judicious planning, the problem can
be resolved in much less time."
-----------
Howard W. Mielke: Lead in inner cities.
(American Scientist Jan/Feb 1999 87:62)
QY: Howard W. Mielke 
-----------
Text Notes:
... ... *Note #1: There is much data concerning certain
syndromes, e.g., fetal alcohol syndrome, lead poisoning, etc. One
research problem is that effects of low levels of environmental
toxins on the developing nervous system can be subtle and not
detected unless specific rather than general behavioral measures
are applied.
... ... *Note #2: There is hardly a consensus concerning
acceptable levels of lead in the whole blood of children. Some
clinicians consider the danger point to be in the region of 50
micrograms per deciliter whole blood; other clinicians consider
anything above 10 micrograms per deciliter as a cause for alarm.
In terms of low-level effects on the developing central nervous
system, general concentration cut-off points are perhaps
arbitrary, since there is considerable individual variation in
toxic susceptibility.

... ... *Note #3: In the US, lead was used in residential paint
between 1884 and 1978, and leaded paint remains on the walls of
many old buildings.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
PRENATAL LEAD EXPOSURE AND POSTNATAL LEAD TOXICITY
Lead is a highly toxic metal, especially in children, but
unfortunately the incidence of lead poisoning in metropolitan
slums remains high due to past widespread use of lead based
paints and lead water pipes. There are also other sources that
contribute to dangerous concentrations in the environment. In
children, concentrations of lead in the range 40 micrograms per
deciliter, and probably as low as 10 micrograms per deciliter,
will produce definite serious cognitive deficits. Higher blood
concentrations produce encephalopathies that are both malignant
and difficult to treat. In the past, the focus has been on the
exposure of young children to environmental lead, since children
are the most vulnerable and environmental lead the apparent
primary source. Now William H. Bowen et al (University of Roch-
ester, US) present evidence that in rats toxic concentrations of
lead can pass from mother to offspring when mother rats are
drinking water that produces blood lead levels of only 40 micro-
grams per deciliter, with transmission evidently occurring via
blood to the fetus and via milk to the postnatal rat pup. Evid-
ently one consequence in these lead-exposed rat pups is a high
incidence of dental caries. Bowen's group is a dental research
group, and they apparently became interested in the problem after
considering that although dental caries in children has shown a
marked drop in prevalence in the U.S., about 80 per cent of the
cases that still occur are occurring in only about 20% of the
children -- those that live in inner cities, where lead exposures
can still be relatively high. Metropolitan children are thus
faced with another source of lead poisoning -- lead of maternal
origin.
QY: W. Bowen, University of Rochester (716) 275-3221
(Nature Medicine September 1997) (Science-Week 12 Sep 97)


2. ON MAGNETOELECTRONICS
There is an emerging apparently important approach to electronics
based on the up or down "*spin" of the carriers rather than on
electrons or holes as in traditional semiconductor electronics.
The physical basis for the observed effects is called "giant
magnetoresistance" (GMR). ... ... Gary A. Prinz presents a review
of GMR and its applications, the author making the following
points: 1) GMR is a quantum mechanical effect observed in
magnetic thin-film structures composed of alternating
*ferromagnetic and nonmagnetic layers. When the *magnetic moments
of the ferromagnetic layers are parallel, the *spin-dependent
scattering of the carriers is minimized, and the material has its
lowest resistance. When the ferromagnetic layers are anti-
aligned, the spin-dependent scattering of the carriers is
maximized, and the material has its highest resistance. The
directions of the magnetic moments are manipulated by external
magnetic fields applied to the materials. These materials can now
be fabricated to produce significant changes in resistance in
response to relatively small magnetic fields, and to operate at
room temperature. 2) The first report of the discovery of GMR
appeared in 1988 [M. Baibich et al, Phys. Rev. Lett. 61:2472].
The first commercial product using GMR (a magnetic field sensor)
became available in 1994. The first products involving GMR to
have major economic impact are "read" heads for magnetic hard
disk drives, these devices announced by IBM in November 1997. The
next major economic impact from the discovery of GMR is expected
to come from nonvolatile magnetic computer memory. The Honeywell
Corporation announced the demonstration of GMR random access
memory (RAM) in January 1997. 3) The exploitation of *spin
polarization of carriers represents not only a departure for the
field of magnetism and magnetic materials, but also a new
direction for the field of electronics. Technological advances in
the ability to make increasingly smaller electronic devices, and
in the ability to combine dissimilar materials within a device,
both serve to increase the potential importance of spin-polarized
effects.
-----------
Gary A. Prinz: Magnetoelectronics.
(Science 27 Nov 98 282:1660)
QY: Gary A. Prinz, Naval Res. Lab., Washington, DC 20375 US.
-----------
Text Notes:
... ... *spin: In quantum mechanics, electrons, protons, and
neutrons have an intrinsic angular momentum known as "spin", and
a *magnetic moment parallel or antiparallel to that angular
momentum. When electrons are combined together to form an atom or
ion, there is a resultant angular momentum which is a combination
of the intrinsic spin of the electrons and the angular momentum
due to their motion about the nucleus, and this is the "spin" of
the atom or ion. Atoms or ions with non-zero spin are magnetic
atoms or ions. The idea of electron spin was first proposed by
Goudsmit and Uhlenbeck in 1925 to explain the splitting of atomic
spectroscopic emission lines in the presence of a magnetic field.
Elementary particle spin involves a virtual rotation about the
axis of the particle, which means only two spin states are
possible, one clockwise and one counterclockwise.
... ... *ferromagnetic: A ferromagnet is a material (such as
iron) in which there may be a permanent *magnetic moment, and in
which the spins of the atoms are aligned parallel to each other.
... ... *magnetic moments: (magnetic dipole moment) The intrinsic
spins of the electrons in an atom, together with the motion of
the electrons around the nucleus, give rise to a magnetic field
around the atom, and the magnitude of this field is related to
the magnetic dipole moment of the atom or ion.
... ... *spin-dependent scattering: In this context, the term
"scattering" refers to the change in direction of a particle
because of a collision with another particle or system.
... ... *spin polarization: In a spin-polarized system, the
majority of spin-particles have spin-components pointing in one 
direction rather than at random.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
ON COHERENT SPIN STATES OF OPTICALLY EXCITED ELECTRONS
... Any system [such as a particle spin-state system] with two
possible states is an intrinsic binary logic system, and so the
question naturally arises whether the system could be used in
information processing in a way that would mean improvements over
current technologies. But in order for a system to be used to
process and transfer information, the system must be "coherent"
in its parts. In quantum physics, coherence is matter of locking
of phase differences between wave functions. The wave functions
of two or more particles are said to be coherent if the phase
difference between their wave functions remains constant. So if
new quantum electrodynamic information processing devices are to
be developed, methods must be found to keep the quantum states of
the parts of the system coherent long enough for information to
be processed and transferred from one place to another. J. M.
Kikkawa et al (University of California Santa Barbara, US;
Pennsylvania State University, US) now report the production of
coherent spin states in the nanosecond range in optically excited
electrons, a time frame far longer than electron-hole
recombination time frames, and the coherent condition evidently
endures at room temperatures. The authors suggest applications to
the technology of ultra-fast optical techniques involving quantum
semiconductor devices.
QY: D. D. Awschalom, Univ. Calif. Santa Barbara (805) 893-2881
(Science 29 Aug 97)  (Science-Week 19 Sep 97)


3. THEORETICAL BIOLOGY: CONTROLLING CELL CYCLE DYNAMICS
During the past few decades, studies of the *cell division cycle
have revealed many of the genes and proteins that drive and
regulate cell division, and methods for the artificial control of
the cell cycle have become apparent. Such manipulations are
typically achieved by introducing mutations into the genes that
regulate the cycle. These mutations, however, usually result in
uncontrolled cell division, or complete suppression of cell
division, or cause the cell to commit fatal errors during the
cell cycle. ... ... T.S. Gardner et al (3 authors at Boston
University, US), using mathematical modeling of cell division
cycle dynamics, report a potential mechanism for the precise
control of the frequency of cell division and regulation of the
size of the dividing cell. The work of the authors involves the
application of a specific biochemical constraint to two already
existing mathematical models of cell cycle dynamics (models by A.
Goldbeter; B. Novak and J.J. Tyson). The authors report that
control of the cell cycle in their application is achieved by
artificially expressing a protein that reversibly binds and
inactivates any one of the cell division cycle proteins. In the
simplest case (the Goldbeter model), the frequency of cell
division cycle oscillations can be increased or decreased by
regulating the rate of synthesis, the binding rate, or the
equilibrium constant of the binding protein. In a more complex
model of cell division (the Novak-Tyson model), the authors
report that the same reversible binding reaction can alter the
mean cell mass in a continuously dividing cell. The authors
suggest that because their control scheme is general and requires
only the expression of a single protein, it provides a practical
means for tuning the characteristics of the cell cycle in vivo.
-----------
T.S. Gardner et al: A theory for controlling cell cycle dynamics
using a reversible binding inhibitor.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14190)
QY: James J. Collins 
-----------
Text Notes:
... ... *cell division cycle: (cell cycle) Prior to each cell
division, a cell passes through a series of preparatory stages
that are collectively known as the "cell cycle". The cycle is
considered to begin when two new cells are formed by the division
of a single parent cell, and it ends when one of these new cells
in turn divides to form two more cells. The paramount process is
the transfer of a complete set of genetic instructions to each
new cell. The periodicity of the cycle varies from one type of
cell to another, and within a single type, the periodicity can
also vary in response to ambient conditions. Laboratory methods
are now available to not only control the periodicity of the cell
cycle, but also to synchronize the periodicities of a population
of cultured cells. The obvious oscillatory behavior of biological
cells has for many decades been the focus of much research
involving mathematical modeling.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99


4. TRANSGENIC CATTLE: REVERSE-TRANSCRIPTION GENE TRANSFER
*Pronuclear injection has been widely used in attempts to produce
*transgenic cattle and other livestock, but after a decade of use
this technique has apparently not succeeded in achieving
transgenesis in more than 1 percent of injected embryos. Another
technique is the use of *retroviral transgenesis, in which
genetic information is transferred as an RNA molecule. This was
actually the earliest method used for gene transfer into embryos.
Here, also, there has been little success, with repeated attempts
over the years demonstrating that the lack of control of gene
dose and timing in this process results in nearly all of the
animals being born as *genetic mosaics. In general, *replication-
defective retroviral vectors have seen only limited use in
*transduction of embryos, and no transgenic farm animals have
been produced. A critical requirement for integration of
retroviruses (other than HIV and possibly related *lentiviruses)
is the breakdown of the *nuclear envelope during *mitosis.
Nuclear envelope breakdown occurs during the mitotic phase of the
cell cycle (M-phase), the envelope reforming immediately after
cell division. It is nuclear envelope breakdown that evidently
permits the translocation of the retroviral preintegration
complex into the nucleus and thus enables integration to proceed.
In the oocyte, during *metaphase II of the second meiosis, the
nuclear envelope is also absent, the oocyte remaining in an
arrested state without a nuclear envelope for a much longer
period of time compared with the M-phase in a *somatic cell.
... ... A.W.S. Chan et al (5 authors at 3 installations, US) now
report the use of a retroviral vector injected into the
*perivitelline space of bovine oocytes during metaphase II, and
the authors report that reverse-transcription gene transfer can
occur in an oocyte which is in metaphase II meiosis arrest, and
that this gene transfer leads to the production of viable
offspring, the majority of which are transgenic. The authors
suggest this mechanism has implications as both a means of
production of transgenic livestock and as a model for naturally
occurring recursive transgenesis.
-----------
A.W.S. Chan et al: Transgenic cattle produced by reverse-
transcribed gene transfer in oocytes.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14028)
QY: Robert D. Bremel 
-----------
Text Notes:
... ... *pronuclear: The term "pronucleus" refers to the nucleus
of either the ovum or the sperm cell following fertilization.
Once the ovum is fertilized, there are two pronuclei, one
originating from the ovum, the other from the sperm cell that
produced fertilization. The two nuclei do not fuse until
immediately before the first cleavage, when each pronucleus loses
its membrane to release its contents.
... ... *transgenic cattle: A transgenic cow is a cow into which
genetic material from another organism has been transferred, the
transferred and incorporated new genes then being expressed with
the resultant production of specific proteins. Concerning
pronuclear microinjection transgenic research, the first reported
production of transgenic mice from microinjected eggs occurred in
1980.
... ... *retroviral transgenesis: 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 into the host cell's genome, where it codes for
the synthesis of viral components. Certain retroviruses have been
modified to become vehicles for the delivery, stable integration,
and expression of genes in a wide variety of cells.
... ... *genetic mosaics: In generating a transgenic animal, it
is desirable that all the cells in the organism receive the
translocating gene (the "transgene"), since the presence of the
transgene in the germ cells of the organism enables the gene to
be passed on to succeeding generations, a requirement for long-
term usefulness of the organism. A "mosaic" embryo is an embryo
in which only some of the cells carry the transgene.
... ... *replication-defective retroviral vectors: The essential
meaning here is that the retrovirus which is used as a vector for
gene transfer is engineered so that following the gene transfer
the replication of the virus (and any viral disease process) is
prevented.
... ... *transduction of embryos: In general, in this context,
the term "transduction" refers to the translocation of genetic
material from one organism to another via an intermediary vector.
... ... *lentiviruses: A subclass of retroviruses, the subclass
including the human immune deficiency virus (HIV).
... ... *nuclear envelope: The nuclear envelope (nuclear
membrane) is a double membrane approximately 40 nanometers in
total thickness, including a 20 nanometer gap between two
bilayers, the envelope perforated with pores 30 to 100 nanometers
in diameter. The pores are of apparently complex structure and
control the selective exchange of materials with the cytoplasm of
the cell.
... ... *mitosis: In this context, the division phase of the cell
cycle.
... ... *metaphase II of the second meiosis: In general, meiosis
is the process of reductive cell division leading to progeny
cells containing half the genetic complement of the parent cell.
In general, meiosis produces "haploid" gametes (egg cells and
sperm cells with half the chromosome number), and fusion of the
gametes (egg cell and sperm cell) in the process of
"fertilization" restores the chromosome number. In animals,
meiosis occurs twice (a first meiosis and a second meiosis), and
metaphase II is one of the early stages of the second meiosis.
... ... *somatic cell: In general, a "somatic" cell is any cell
other than a germ cell (egg cell or sperm cell).
... ... *perivitelline space: Referring to the mammalian egg
cell, this is the space formed between the egg cell itself and
the thick clear membrane (zona pellucida) surrounding the egg
cell.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
CLONED TRANSGENIC CALVES FROM FETAL FIBROBLASTS
Research has been in progress for more than a decade to develop a
system for genetic modification and large-scale cloning in
cattle, an important species in agriculture, biotechnology, and
human medicine. During the past 18 months, there has been much
publicity concerning the cloning of sheep using somatic cell
donor cells, the research conducted by the Wilmut group in the
UK. ... ... Now Cibelli et al (8 authors at 3 installations, US)
report similar results (but with a different method) in cattle.
Actively dividing fetal fibroblasts were genetically modified
with a marker gene, a clonal line was selected, and the cells
were fused to enucleated mature oocytes. Out of 28 embryos
transferred to 11 recipient cows, three healthy, identical,
transgenic calves were generated. Furthermore, the life span of
near senescent donor fibroblasts could be significantly extended
by nuclear transfer. With the ability to extend the life-span of
these primary cultured cells, this system would be useful for
inducing complex genetic modification in cattle. The authors
suggest their somatic cell nuclear transfer procedure could
improve the efficiency of producing transgenic cattle and broaden
the scope of applications for transgenic cattle.
QY: James M. Robl 
(Science 22 May 98 280:1256) (Science-Week 12 Jun 98)
-------------------
Related Background:
TRANSGENIC SHEEP EXPRESSING HUMAN CLOTTING FACTOR PROTEIN
A transgenic animal is an animal into which genetic material from
another organism has been transferred, the transferred and
incorporated new animal genes then being expressed with the
resultant production of specific proteins. Human clotting factor
IX, which is vitamin K dependent, is one of the blood plasma
factors involved in the series of events involved in blood
coagulation, and deficiency of factor IX is the genesis of human
hemophilia type B. The term "somatic cells" is a generic term for
all cell other then egg cells and sperm cells, and transfection
is the uptake of exogenous (foreign) DNA fragments in solution
directly into animals cells in laboratory culture, and is one
method of introducing foreign genes into cells. Nuclear transfer
is a technique involving the transfer of the nucleus of one cell
into another cell, and in the context of this report involves the
transfer of the nucleus of a transfected cell into egg cells that
have had their nuclei removed. Schnieke et al (9 authors at 2
installations, UK) report the production by means of nuclear
transfer of transgenic sheep expressing human clotting factor IX
in sheep milk. The authors suggest their results demonstrate that
somatic cells can be subjected to genetic manipulation in vitro
and produce viable animals by nuclear transfer, with the product-
ion of transgenic sheep by nuclear transfer requiring fewer than
half the animals needed by previous methods (reported by this
group) involving microinjection of DNA into the nuclei of fertil-
ized egg cells. They further point out that their procedures for
transfection and growth from single-cell clones are essentially
the same as those required for gene targeting, and that the
realistic prospect of targeted genetic manipulation in a live-
stock species should open a vast range of new applications and
research possibilities.
QY: Angelika E. Schnieke, PPL Therapeutics, Roslin, Midlothian,
EH25 9PP, Scotland, UK.
(Science 19 Dec 97) (Science-Week 9 Jan 98)
-------------------
Related Background:
A TRANSGENIC MOUSE MODEL FOR SICKLE CELL DISEASE
A transgenic mouse is a mouse into which genetic material from
another organism has been transferred, the transferred and
incorporated new mouse genes then being expressed with the
resultant production of specific proteins. Sickle cell disease is
a chronic hemolytic anemia occurring almost exclusively in the
black population and is characterized by sickle-shaped red blood
cells due to homozygous inheritance of a variant of hemoglobin
called Hb-S. There is a milder heterozygous form which produces
some sickling of red blood cells, but without the debilitating
anemia. At present there are approximately 75,000 individuals in
the U.S. with the homozygous form of the disease. There is no
cure, and individuals usually die at about the age of 40 due to
the effects of the disease. Ryan et al (Univ. of Alabama, US)
have produced a transgenic mouse that synthesizes only human
sickle hemoglobin in its adult red blood cells. Similar to many
human patients with sickle cell disease, the mice developed
severe hemolytic anemia and extensive organ pathology, with
numerous sickled erythrocytes observed in peripheral blood.
Although chronically anemic, most animals survived 2 to 9 months
and were fertile. The authors suggest this mouse model can now be
used to test drug and genetic therapies for human sickle cell
disease. (Note: a following paper by Paszty et al reports
essentially the same results.)
QY: T. M. Townes 
(Science 31 Oct 97) (Science-Week 21 Nov 97)


5. GENETIC CONTROL OF SOCIAL ORGANIZATION IN ANTS
Biological evolution is marked by a number of major transitions,
one of which is the evolution of complex social behavior. Animal
social life can take a variety of forms, each distinguished by
features such as group size and the reproductive roles of group
members. One focus in evolutionary biology is to identify the
causes of social behavior and its conspicuous variation, and to
determine the extent to which social organization is under
genetic control. Such information is useful for reconstructing
pathways of animal social evolution. Current views on insect
social evolution stress the importance of ecological and
behavioral environments in molding what are largely plastic
social behaviors. ... ... K.G. Ross and L. Keller (2 installat-
ions, US CH) report evidence that major variation in the social
organization of fire ant colonies is under simple genetic
control, providing a demonstration of an apparent strong genetic
component to complex social behavior. The authors report that a
single genomic element (the gene ) is responsible for the
existence of two distinct forms of social organization in the
fire ant *Solenopsis invicta. This genetic factor apparently
influences the reproductive *phenotypes and behavioral strategies
of ant queens and determines whether workers tolerate a single
fertile queen or multiple queens per colony. The authors suggest
"these findings reveal how a single genetic factor can have major
effects on complex social behavior and influence the nature of
social organization."
-----------
K.G. Ross and L. Keller: Genetic control of social organization
in an ant.
(Proc. Natl. Acad. Sci. US 24 Nov 98 95:14232)
QY: Kenneth G. Ross 
-----------
Text Notes:
... ... *Solenopsis invicta: The fire ant S. invicta is an
introduced pest species in the southern US, the species existing
in two distinct social forms. The "monogyne" form features
colonies with a single fertile (egg-laying) queen, whereas the
"polygyne" form features colonies with multiple fertile queens.
The two social forms differ in other major aspects of their
reproductive biology.
... ... *phenotypes: The term "phenotype" refers to the total
appearance of an organism as determined by the interaction during
development between its genetic constitution (genotype) and the
environment.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
ON HONEYBEE SOCIAL BEHAVIOR, GENES, AND THE ENVIRONMENT
The so-called social insects live in societies that rival human
societies in complexity and internal cohesion. Honey bees, for
example, apparently always follow 3 rules: a) they live in
colonies with overlapping generations; b) they care cooperatively
for offspring other than their own; and, c) they maintain a
reproductive division of labor. ... ... In a review of research
(much of it from the author's own laboratory) concerning the
genetic and environmental factors responsible for honey bee
behavior, Gene E. Robinson (University of Illinois Urbana-
Champaign, US) makes the following points: 1) Genes do not play
an exclusive role in regulating behavior: biologists have long
realized that behavior is influenced by genes, the environment,
and interactions between the two. 2) Genes never act alone. They
must operate in an environment where they code for proteins that
participate in many systems in an organism, with these systems in
turn influencing the expression of genes. Consequently,
biologists must take a broad approach in assessing the impact of
any gene. 3) The research group of the author uses the Western
honey bee, Apis mellifera. Honey bees pass through different life
stages as they age, and their behavioral responses to
environmental and social stimuli change in predictable ways.
Although worker bees go through a consistent path of behavioral
development, this path is not rigidly determined. Bees can
accelerate, retard, or even reverse their behavioral development
in response to changing environmental and colony conditions. 4)
Experimental evidence indicates that juvenile hormone, one of
the most important hormones influencing insect development, helps
time the pace of behavioral maturation in honey bees. The rate of
endocrine-mediated behavioral development is influenced by
inhibitory social interactions. Older bees inhibit the behavioral
development of younger bees: the rate of behavioral development
is negatively correlated with the proportion of older bees in a
colony. Inhibitory social interactions that influence the rate of
behavioral development involve chemical communication between
colony members. 5) Evidence from the laboratory of the author in
1993 indicated the so-called mushroom bodies in the bee brain are
involved in the behavioral changes occurring during maturation,
the volume of the bodies increasing, and the volume increase
associated with an increase in synapses with neurons from brain
regions devoted to sensory input. The author suggests this was
the first report of brain plasticity in an invertebrate. 6) The
author suggests that, in general, two-way interactions between
the nervous system and the genome contribute fundamentally to the
control of social behavior. Information about social conditions
that is acquired by the nervous system is likely to induce
changes in genomic function that in turn produce adaptive
modifications of the structure and function of the nervous
system. 7) The author proposes a new research initiative called
"sociogenomics", defined as a "wide-ranging approach to identify
genes that influence social behavior, determining the influence
of these genes on underlying neural and endocrine mechanisms, and
exploring the effects of the environment -- particularly the
social environment --  on gene action."
QY: Gene E. Robinson, Dept. of Entomology, Univ. of Illinois
Urbana-Champaign 217-333-3090.
(American Scientist Sep/Oct 1998 86:456)
(Science-Week 11 Sep 98)


6. BIOLOGY OF CANCER: ON THE ENIGMAS OF KAPOSI'S SARCOMA
Kaposi's *sarcoma (multiple idiopathic hemorrhagic sarcoma) is an
ordinarily rare cancer that can be common in humans with
compromised immune systems (e.g., in AIDS). The neoplasm is
characterized by vascular skin tumors that appear in several
distinctive forms. In the past, Kaposi's sarcoma occurred mainly
in men of Italian or Jewish ancestry over 60 years of age. But
now the disease is endemic in equatorial Africa, where it occurs
commonly in children and young men, and it accounts for nearly 10
percent of all malignancies in Zaire and Uganda. Since 1981, the
aggressive form of Kaposi's sarcoma has occurred in at least 30
percent of patients with AIDS, and the disease has assumed
epidemic proportions in the US and many other countries.
... ... Robert C. Gallo (University of Maryland, US) presents a
review of current research concerning Kaposi's sarcoma, the
author making the following points: 1) There are many
difficulties in understanding the tumor biology of Kaposi's
sarcoma: a) The etiology of the tumor is not easy to define; b) a
metastatic malignancy cannot easily be distinguished from a
nonmalignant growth that occurs in multiple sites; c) many
distinct factors apparently contribute to the pathogenesis of
Kaposi's sarcoma. 2) There are 4 epidemiological forms of the
disease, and it is not certain whether these are actually the
same disease or whether they are similar only because the same
kinds of cells are involved. The classical form of Kaposi's
sarcoma occurs in older males of mainly Mediterranean or Eastern
European Jewish backgrounds and has no known contributing
environmental factor. A second form, found in parts of equatorial
Africa, occurs in all age groups and also has no known
precipitating environmental factor. Neither of these two forms is
typically associated with immune system deficiency. In contrast,
the remaining 2 types of Kaposi's sarcoma -- those associated
with organ transplants and with human immunodeficiency virus type
I (*HIV-1) -- are accompanied by immune system impairment. Males
are predominantly afflicted in all forms. 3) Another problem is
the elusive nature of the tumor cell in the disease. Many cells
in the lesion are clearly normal cells that have infiltrated the
tumor (e.g., *leukocytes). The predominant cell in the tumor is a
spindle-shaped cell, which is accompanied by abnormal blood
vessel development and leakage of blood. There is no direct
evidence that this spindle cell is an autonomously growing
neoplastic cell rather than a hyperproliferating but otherwise
normal cell (i.e., hyperplasia). Thus the question: Are any of
the cells in the Kaposi's sarcoma lesion neoplastic, or are they
all the result of a chronic *inflammatory response? In other
words, is Kaposi's sarcoma a malignancy or is it a proliferative
inflammatory response, or both? Several lines of evidence
indicate that most or all Kaposi's sarcoma proliferative cells
are not in fact neoplastic. 4) One factor that ties together the
4 epidemiological forms of Kaposi's sarcoma is that the herpes
virus KSHV (also known as HHV-8) is invariably found in Kaposi's
sarcoma tissues. If, as evidence suggests, HHV-8 is not merely
present in all tissues, its consistent presence in Kaposi's
sarcoma must indicate a key etiological role, which in turn would
imply that the 4 forms of Kaposi's sarcoma are indeed one, but
with different (but unknown) augmenting cofactors. The author
concludes: The Kaposi's sarcoma tumor is complex in its cellular
composition, origin, epidemiology, and pathogenesis. It begins as
a result of different stimuli that promote microvascular
inflammation. One major stimulus is HIV-1 infection. Development
as a clinical tumor may depend on activation by herpes virus HHV-
8 and by *cytokines in the inflammatory lesion. Herpes virus HHV-
8, in turn, may promote cell growth by augmentation of cytokines.
"It is likely, then, that Kaposi's sarcoma begins as a
hyperplasia and may evolve into malignant clones in some
patients, but the neoplastic cells may be a small minority."
-----------
Robert C. Gallo: The enigmas of Kaposi's sarcoma.
(Science 4 Dec 98 282:1837)
QY: Robert C. Gallo 
-----------
Text Notes:
... ... *sarcoma: A connective tissue neoplasm, usually highly
malignant.
... ... *HIV-1: 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.
... ... *leukocytes: White blood cells of the immune system, of
which there are several types with different specific functions.
... ... *inflammatory response: In general, the response of
tissues to irritation or injury. The response involves a dynamic
complex of cellular and chemical reactions that occur in the
affected blood vessels and adjacent tissues.
... ... *cytokines: A cytokine is any substance that promotes
cell growth and cell division. Certain cytokines are endogenous,
and need to be controlled by cell regulatory mechanisms. When
these mechanisms fail, endogenous cytokines may be implicated in
serious human diseases such as rheumatoid arthritis, where
apparently deregulated cytokines cause the inflammatory response
that produces the symptoms. As a promoter of cell growth and cell
division, a cytokine acts as a messenger to cells.
-------------------
Summary & Notes by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
KAPOSI'S SARCOMA: FURTHER EVIDENCE FOR ROLE OF HERPES VIRUS
Kaposi's sarcoma is an ordinarily rare cancer that can be common
in humans with compromised immune systems (for example, in AIDS).
Kaposi's sarcoma-associated herpes virus (KSHV) (also called
"human herpes virus 8") is invariably present in Kaposi's sarcoma
lesions. KSHV contains several viral *oncogenes, and there is
evidence that KSHV infection is necessary for the development of
Kaposi's sarcoma. However, cellular transformations by this virus
have not so far been demonstrated. In Kaposi's sarcoma lesions,
the virus has been found in *endothelial cells and cells of
endothelial origin. ... ... Flore et al (6 authors at 3
installations, US IT IE) report an investigation of the
biological consequences of infecting cultured human primary
endothelial cells with purified KSHV particles. The authors
report that infection causes long-term proliferation and survival
of these cells, the effects associated with the acquisition of
*telomerase activity and *anchorage-independent growth. KSHV was
present in only a subset of cells, with *paracrine mechanisms
responsible for the survival of uninfected cells, perhaps by
*upregulation of a receptor for vascular endothelial growth
factor. The authors suggest their results indicate that
transformation of endothelial cells by KSHV, as well as paracrine
mechanisms that are induced by this virus, may be critical in the
pathogenesis of Kaposi's sarcoma.
QY: Ethel Cesarman 
(Nature 6 Aug 98 394:588) (Science-Week 28 Aug 98)
-------------------
Related Background:
... ... *oncogenes: There are two general meanings of this term
in current use. The first meaning refers to any of a family of
cellular genes that normally code for proteins involved in cell
growth or regulation, but which may produce malignant processes
when mutated or activated by viruses. The second meaning of the
term "oncogene" refers to viral genes found in certain DNA tumor
viruses, genes that are required for viral replication, but whose
activation produces malignant transformations.
... ... *endothelial cells: Flat cells forming a layer lining
blood vessels, lymphatic vessels, the heart, etc.
... ... *telomerase: Telomeres are defined ends of chromosomes
that contain specific repeated DNA sequences. They are essential
for normal chromosome replication, and since their length
shortens a bit with each replication, they are believed to be
involved in the aging of the cell. Telomerase is an enzyme that
repairs damage to telomeres, and it is thought by some that
cancerous cells may have mutant telomerase, the mutant enzyme
conferring immortality on the cancer cell.
... ... *anchorage-independent growth: In multicellular
organisms, cells are specialized to be either free-floating
(e.g., blood cells) or anchored to the extracellular matrix
(e.g., cells forming the tissues of organs). Anchored cells are
known to require their anchorage: if the anchorage is lost, the
cells normally undergo apoptosis (programmed cell death).
Malignant cells, however, have lost both anchorage dependence and
the consequent apoptosis.
... ... *paracrine mechanisms: These are localized chemical
regulatory mechanisms  -- as opposed to hormonal mechanisms,
which are systemic rather than localized.
... ... *upregulation: An increase in the number of receptor
molecules present within the plasma membrane.
-------------------
Related Background:
FURTHER EVIDENCE OF HERPES VIRUS ROLE IN KAPOSI'S SARCOMA
Kaposi's sarcoma is a human cancer of skin cells (and sometimes
cells of certain internal tissues), appearing for the most part
in elderly men or in younger men with compromised immune systems.
The disease was first described by the Hungarian dermatologist
Moritz Kaposi (1837-1902). ... ... Martin et al (6 authors at 3
installations, US) report a study of human herpes virus type 8
(HHV-8). The prevalence of HHV-8 infection is high among
homosexual men, correlates with the number of homosexual
partners, and is temporally and independently associated with
Kaposi's sarcoma. The authors suggest their observations are
further evidence that HHV-8 has an etiological role in Kaposi's
sarcoma and is sexually transmitted among men, and that
understanding the epidemiology of HHV-8 is a critical first step
in designing interventions to decrease the transmission of this
pathogen.
QY: Dean H. Kedes, Univ. of Calif. San Francisco 415-476-4044.
(New England J. Med. 2 Apr 98) (Science-Week 10 Apr 98)
-------------------
Related Background:
HERPES VIRUS AS A VIRAL ONCOGENE AND ANGIOGENESIS ACTIVATOR
Kaposi's sarcoma is an ordinarily rare cancer that can be common
in humans with compromised immune systems (for example, in AIDS),
and the herpes viruses are a class of viruses producing the
complex of herpes diseases, some of which are sexually transmit-
ted diseases clinically associated with AIDS. In cell biology,
the term "receptor" denotes a cell surface chemical entity,
usually a protein, that interacts with messenger molecules (e.g.,
hormones) in the extracellular solution. G-proteins are a family
of signal-coupling proteins that act as intermediaries between
activated cell receptors and effectors, for example, the trans-
duction of hormonal signals from the cell surface to the cell
interior. 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 (which
begins a cascade of signals in the interior of the cell), the G-
protein thus acting as a trans-membrane signal transducer. In the
context of this report, the term "transformation" refers to the
conversion of normal cells into malignant cells exhibiting
uncontrolled growth and loss of functional specialization
(dedifferentiation). Angiogenesis, the origin and development of
blood vessels, is an important consideration in the growth of
cancerous tumors, since the tumor provokes directed angiogenesis
into itself with the end result that the tumor is supplied with
oxygen and nutrients. Without angiogenesis, tumors can attain
only a small size before becoming self-inhibiting. A cytokine is
any substance that promotes cell growth and cell division, and an
inflammatory cytokine is a cytokine involved in the inflammatory
response to tissue injury and infection. As a promoter of cell
growth and division, a cytokine acts as a messenger to cells, and
the transmission of the message requires a binding of the
cytokine molecule to a cytokine-specific receptor on the cell
surface. This receptor is either a protein or a protein complex
or a part of a protein. The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells), and lymphoma is a general
term for a tumor (benign or malignant) of tissue of the lymphatic
system. Bais et al (10 authors at 2 installations, US) report
that signaling by the Kaposi's sarcoma-associated herpes virus G-
protein-coupled receptor leads to cell transformation and tumor
growth, and activates angiogenesis by mechanisms similar to those
produced by inflammatory cytokines. The authors suggest this is
the first demonstration that a Kaposi's sarcoma-associated
herpes virus gene is capable of inducing both transformation and
angiogenesis, and that this evidence strongly supports the idea
that Kaposi's sarcoma-associated herpes virus infection plays a
direct role in Kaposi's sarcoma pathogenesis and lymphoma-
genesis. QY: Enrique A. Mesri 
(Nature 1 Jan 98) (Science-Week 16 Jan 98)
-------------------
Related Background:
VIRUSES IN NORMAL CELLS MAY DRIVE GROWTH OF TUMOR CELLS
The idea that viruses are implicated in cancer has existed for
decades, and indeed in a few types of malignancy a related virus
has been identified. But the thinking has always been that if a
virus is implicated in cancer, it is because it invades a cell
type, corrupts the cell's genetic machinery, and the result is a
wild cell that rapidly proliferates. Now a new scheme has
appeared, reported by M. B. Rettig et al (various installations
in Los Angeles, including the University of California Los
Angeles; US). What they have found is that in cases of the human
cancer multiple myeloma, healthy neighboring dendritic cells in
human bone marrow are infected with Kaposi sarcoma-associated
herpes virus, and that this virus is orchestrating the production
by these healthy cells of interleukin-6, a protein which is known
to stimulate myeloma growth. What is striking, is that the virus
does not infect the malignant cells. If these results are
independently confirmed, there will be an intense new interest in
the possibility of viral promotion of various human malignancies.
(Science 20 Jun 97) (Science-Week 26 Jun 97)


7. INFANT AUTISM: USE OF MOVEMENT ANALYSIS IN DIAGNOSIS
Autism is a behaviorally defined syndrome of unknown etiology
associated with poor social interaction, disordered language, and
atypical responses to people, objects, and events. The syndrome
is classically manifested by severe disturbances in cognition,
language, and behavior that appear before the age of 30 months.
In some cases, there is an apparent hyperarousal state. Autistic
children often exhibit ritualized body movements, repeated
touching and sniffing of objects, ritualistic ordering, checking,
and collecting, and insistence on precisely following routines.
The ratio of male to female cases ranges from 2:1 to 4:1, and
studies of monozygotic and dizygotic twins indicate an important
role for genetic factors. There is presently a controversy over
whether movement disorders play a central role in the phenomenon
of autism and even whether such movement disorders exist in
autism at all. ... ... P. Teitelelbaum et al (5 authors at
University of Florida Gainesville, US) now report that a study of
17 autistic children showed disturbances of movement that could
be detected at the age of 4 to 6 months and sometimes even at
birth. The authors used a standard movement analysis system (the
Eshkol-Wachman system) in combination with still-frame videodisc
analysis to study videos obtained from parents of children who
had been diagnosed as autistic by conventional methods, the
diagnosis usually occurring at about age 3 years. The videos
showed the behaviors of the children when they were infants, long
before they had been diagnosed as autistic. The authors report
that movement disorders varied from child to child, with
disturbances revealed in the shape of the mouth and in some or
all of the milestones of development, including lying, righting,
sitting, crawling, and walking. The authors suggest their
findings support the view that movement disturbances play an
intrinsic part in the phenomenon of autism, that movement
disturbances in autistic children are present at birth, and that
such movement disturbances can be used to diagnose the presence
of autism in the first few months of life. The authors further
suggest these results indicate the need for the development of
methods of therapy to be applied from the first few months of
life in autistic children. [Editor's note: See the related
background report below for an indication of the existing
practical clinical problems associated with investigation of the
genetic basis of a syndrome such as autism.]
-----------
P. Teitelbaum et al: Movement analysis in infancy may be useful
for early diagnosis of autism.
(Proc. Natl. Acad. Sci. US 10 Nov 98 95:13982)
QY: Philip Teitelbaum 
-------------------
Summary by SCIENCE-WEEK  15Jan99
-------------------
Related Background:
MOLECULAR BIOLOGISTS VS. CLINICIANS IN ACCESS CONFLICT
We have had a number of reports in recent issues of this
publication concerning the resistance of corporate and university
entities to releasing scientific data, such resistance apparently
based on the desire for financial gain. Lest anyone think the
corporate and university institutional entities are alone in this
sort of behavior, there is growing evidence of a similar attitude
among individual investigators. The current situation is appar-
ently as follows: For many decades now, a large number of
clinical studies (in the US these are usually funded by the
National Institutes of Health) have involved the routine
collection of blood samples from families both nuclear and
extended in connection with research on the familial bases of a
number of common diseases. These blood samples of course contain
DNA, and molecular biologists now have the techniques that
usually allow them to rapidly identify genes and markers
associated with various diseases. So they would like samples of
these blood materials in order to do the molecular genetic
investigations. But the clinical investigators who spent so much
time and effort tracking down families and gathering the material
over years and even decades are loath to release it to the
molecular biologists, calling the molecular biologists scientific
"gunslingers" who will take the fruit of their labors and win
Nobel Prizes with it. The various funding agencies are in an
apparent quandary, undecided about the duration of time they
should allow clinical researchers to maintain exclusive control
of blood samples. Should it be one year or 10 years? For those
whose instinctive answer is that exclusive control should last
about 10 minutes, the funding agencies argue that without the
incentive of exclusive control of materials, individual invest-
igators will have no incentive to do the research in the first
place. Which of course is also the argument that is made to
justify proprietary rights over scientific data (including the
patenting of genes) already granted to corporate and university
entities. So now we have a problem whereby molecular biologists
can probably rapidly identify the genetic etiology of a number of
complex multi-gene familial based diseases (for example, autism
and schizophrenia), but they cannot get the material because the
people who gathered the DNA from the familial populations, who
are clinicians and not molecular biologists, are reluctant to
sacrifice their prospects for important discoveries that will
bring them fame and fortune.
(Science 24 Oct 97) (Science-Week 14 Nov 97)


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