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.

March 26, 1999 -- Vol. 3 Number 13

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We measure things. We spend countless dull hours
measuring the swing of a pendulum, the heat of an acid,
the twitch of a muscle. But only with these measurements
in hand can we begin our dialogue with the Cosmos.
-- Anonymous

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A Note from the Editors: Three search engines have now been added
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[http://scienceweek.com/swfr.htm] and
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Contents of This Issue:

1. Impact of Biotechnology on Future Health Care Economics
2. Observation of Relativistic Nonlinear Thomson Scattering
3. Origin of a Chloroplast Protein Importer
4. On Genetics and Human Cancers
5. Cell Microenvironment and Cell Neoplasticity
6. Gene Therapy for Aging-Related Loss of Muscle Function

-- In Focus: On the Laws of Physics

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

1. IMPACT OF BIOTECHNOLOGY ON FUTURE HEALTH CARE ECONOMICS
Many economists and policy-makers believe that one of the most
serious problems to face the US health care system and the US
economy in the 21st century will be the demographic shift caused
by the aging of persons born between 1946 and 1963 (the "baby
boom" population). ... ...  H. Pardes et al (6 authors at 6
installations, US) present a proposal that progress in
biotechnology may seriously reduce the magnitude of the problem
of health care in the next century by rapidly altering medical
knowledge and practice, health delivery and outcomes, and total
health costs. The authors identify the following factors:
... 1) Declining disability among people over 65 years of age:
The age-adjusted chronic disability prevalence rate has been
declining 1.3 percent annually over the past 13 years, and this
is consistent with the introduction of new biotechnologies, e.g.,
better drug treatments of osteoporosis, stroke, Parkinson's
disease, and congestive heart failure.
... 2) Changing paradigms of medicine: Technological advances are
defining new paradigms for medicine to which traditional economic
theory may not apply. Improved understanding of human biology at
the molecular level may make invasive surgery, intensive care
units, and long-term nursing home care far less necessary.
... 3) Reduced health care cost at later ages: Health costs in
the last 2 years of life in fact decline in persons dying at
later ages (e.g., persons dying at age 90 as opposed to persons
dying at age 67. The cost ratio is 1:3)
... 4) The developing revolution in pharmaceutical methods:
Savings resulting from new medical knowledge will be multiplied
by the ability to screen promising compounds at rates
unimaginable a few years ago. Miniaturization and robotic
chemistry, allied with genetics and high-throughput screening and
bioinformatics, both provide a clearer picture of drug efficacy
before clinical trials and may reduce certain pretrial
development costs by a factor of 100.
... 5) An increase in public expectations about health at later
ages: A better-educated older population will be driven by rising
health expectations, resulting in behavioral changes identified
by biomedical research as improving health.
... 6) Labor productivity as a function of improved health:
Decreased morbidity will increase the productivity of the labor
force and extend such productivity to older populations. This
will make feasible the raising of the age of Medicare and Social
Security eligibility.
... 7) Growing importance of biotechnology to the economy: Beyond
its impact on individual health, biotechnology is an important
engine of US economic growth, and biotech industries could
experience growth similar to that experienced by the computer
industry during the past 20 years, with a resulting significant
increase in the gross domestic product.
... The authors conclude: "Looking at health care as a
multicomponent dynamic subsystem of the US economy allows us to
appreciate the multiplier effects biotechnological innovations
may produce to control future costs. However, there may by a 15-
to 20-year lag between a scientific observation and its clinical
implementation. We must increase investment heavily in biomedical
research to realize benefits in time to control the impact of
Medicare costs."
-----------
H. Pardes et al: Effects of medical research on health care and
the economy.
(Science 1 Jan 99 283:36)
QY: H. Pardes [hp2@columbia.edu]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 26Mar99


2. OBSERVATION OF RELATIVISTIC NONLINEAR THOMSON SCATTERING
In general, the "scattering" of electromagnetic radiation is a
process in which the radiation is deflected by particles in the
matter through which the radiation passes. What is called
"Thomson scattering" (after J.J. Thomson [1856-1940]) refers to
the scattering of electromagnetic radiation by free charged
particles, particularly by electrons. Classical Thomson
scattering is a linear process, i.e., the frequency of the
radiation does not change. Also, in classical Thomson scattering,
the magnetic-field component of light is not involved. But if the
light intensity is extremely high (greater than approximately
10^(18) watts per square centimeter), electrons are theoretically
expected to oscillate during the scattering process with
velocities approaching the speed of light. In such a relativistic
regime, the effective electron mass will increase, and the
effects of magnetic and electric fields on the electron motion
are expected to become comparable. As a result, electrons in such
high fields are predicted by theory to "quiver" nonlinearly,
moving in figure-eight patterns rather than in straight lines,
with scattered photons radiated at harmonics of the frequency of
the incident light, and each harmonic having its own unique
*angular distribution. Ultra-peak-power lasers offer a means of
creating the extremely high photon densities required to study
relativistic (i.e., nonlinear) Thomson scattering.
... ... S. Chen et al (University of Michigan, US) now report the
use of such an approach to obtain direct experimental
confirmation of the theoretical predictions of relativistic
Thomson scattering. The experiment involved the use of a laser
beam 50 millimeters in diameter focused with a parabolic mirror
onto the front edge of a supersonic helium gas jet, the helium
gas fully ionized by the foot of the laser pulse. The authors
suggest that in the future it may be possible to achieve
*coherent generation of the harmonics produced by such
scattering, and that this could be utilized in the construction
of "table-top" x-ray sources.
-----------
S. Chen et al: Experimental observation of relativistic nonlinear
Thomson scattering.
(Nature 17 Dec 98)
QY: Donald Ulmstadter [dpu@umich.edu]
-----------
Text Notes:
... ... *angular distribution: In this context, the distribution
of angle, relative to an experimentally specified direction, of
each radiation frequency resulting from Thomson scattering. In
this context, the experimentally specified direction might be
that of the incident laser beam.
... ... *coherent generation of the harmonics: In general,
coherent scattering is scattering for which there is a well-
defined relationship between the phase of the incoming wave and
the phase of the outgoing wave. In this context, the essential
idea is that a system exhibiting coherent generation of harmonics
would make it possible to design devices whose distribution of
output harmonics is quantitatively controlled.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Mar99
-------------------
Related Background:
ON ULTRAHIGH-INTENSITY LASERS
In general, resonance is a marked increase in the oscillation
amplitude of a system when the system is subjected to an
oscillating force whose frequency is the same or close to the
natural frequency of the system as determined by the system
parameters. The phenomenon occurs in all systems, including
optical systems. Coherent light waves are light waves of similar
phase, direction, and amplitude, and a laser (light amplification
by stimulated emission of radiation) is a device that converts
input power into a very narrow intense beam of coherent visible
or infrared light, the conversion mechanism essentially involving
excitation of atoms to a higher energy state producing resonator-
forced in-phase radiation. During the past decade, achieved laser
intensities have increased by more than four orders of magnitude
to the order of 10^(20) watts/centimeter^(2). Such intense
energies can be used to produce extreme fields: electric,
magnetic, pressure, temperature, and acceleration -- field
intensities found only in stellar interiors or close to the
horizon of a black hole. The technological advances that have
made such laser intensities possible began in 1987 with the
development of the "chirped-pulse" laser, a device whose essent-
ial basis is the use of ultra-short pulses [10^(-15) seconds]
whose parameters are manipulated before amplification. Mourou et
al (3 authors at 3 installations, US), in a review of chirped
pulse amplification in laser physics, suggest this new technology
has opened a path to research in areas of physical extremes
previously inaccessible in university laboratories, and that
phenomena that could previously only be studied at large install-
ations or not at all will soon be accessible on student labor-
atory desktops.
QY: Gerard A. Mourou, Univ. of Michigan 313-764-7433
(Physics Today January 1998) (Science-Week 16 Jan 98)


3. ORIGIN OF A CHLOROPLAST PROTEIN IMPORTER
In general, photosynthesis is the utilization of light energy to
power biosynthesis, and chloroplasts are the plant cell
organelles in which photosynthesis occurs, the chloroplasts
containing several photosynthetic pigments (chlorophylls).
Chloroplasts are found in all photosynthetic plant cells, but not
in photosynthetic prokaryotes (i.e., not in cells without
membrane-bound organelles). The typical higher plant chloroplast
is lens-shaped, approximately 5 microns across the larger
dimension, and the number of chloroplasts per cell can vary from
1 to 100 depending on the type of cell. A mature chloroplast is
typically bounded by two membranes, an inner membrane and an
outer membrane, the membranes possessing significantly different
chemical constituents. In addition to a number of enzymes
involved in photosynthesis, chloroplasts also contain in their
interior a circular DNA molecule and protein synthetic machinery
typical of prokaryotes. The current consensus is that
chloroplasts may have originated from *cyanobacteria that became
*endosymbionts, an origin similar to that of mitochondria, which
are believed to have originated from so-called "*purple
bacteria". During evolution, chloroplasts (like mitochondria)
have apparently relinquished the majority of their genes to the
host nucleus, since chloroplast DNA codes only for some of the
proteins required by chloroplasts. The protein products of such
transferred genes are evidently imported into chloroplasts with
the help of biochemical import machinery distributed across the
inner and outer chloroplast membranes. The evolutionary origin of
this machinery is considered a puzzle, since the two bounding
membranes of the cyanobacteria have exhibited no functionally
similar protein import system. Recently, however, in the genome
of a species of cyanobacteria (Synechocystis), an apparent gene
(an "*open reading frame") has been identified that codes for an
amino acid sequence that shares an approximate 22 percent amino
acid identity with a protein-transporting channel in the outer
envelope of pea chloroplasts. ... ... B. Bolter et al (5 authors
at 2 installations, DE) now report that the protein coded by the
open reading frame of the Synechocystis cyanobacterium is located
in the outer membrane of that organism (the lipopolysaccharide
layer), and apparently transports polyamines and peptides. The
authors suggest their results indicate that a component of the
chloroplast protein import system may have been recruited from a
preexisting channel-forming protein of the cyanobacterial outer
membrane, and that in addition the presence of a protein in the
chloroplast outer envelope which is *homologous to a
cyanobacterial protein provides support for the general
prokaryotic nature of the outer membrane of chloroplasts.
-----------
B. Bolter et al: Origin of a chloroplast protein importer.
(Proc. Natl. Acad. Sci. US 22 Dec 98 95:15831)
QY: Jurgen Soll [jsoll@bot.uni-kiel.de]
-----------
Text Notes:
... ... *cyanobacteria: A phylum of bacteria characterized by
blue-green (cyan) photosynthetic pigments, abundant in a variety
of habitats, particularly in fresh water and soil. Cyanobacteria
are responsible for generating a large portion of the free oxygen
in the Earth's atmosphere. They apparently produced stromatolite
limestone deposits, as well as the bulk of modern petroleum
deposits. (Stromatolites are laminated calcareous microbial
fossil deposits formed principally by cyanobacteria and algae.)
... ... *endosymbionts: Endosymbiosis is an arrangement in which
one organism lives inside another organism, but the term is
usually restricted to arrangements of mutual benefit, thus not
including parasite-host relationships. A number of eukaryotic
cell organelles (including mitochondria) are believed to have
originated from endosymbiotic relationships between eukaryotic
cells and simpler cells.
... ... *purple bacteria: Specifically, any of the various
photosynthetic bacteria that contain bacteriochlorophyll, and are
thus distinguished by purplish or reddish-brown pigments. But the
term "purple bacteria" is sometimes used as a synonym for the
phylum Proteobacteria, a general category comprising a large
number of diverse forms.
... ... *open reading frame: The term "reading frame" refers to a
specific permutation of nucleotide triplets in DNA as "framed" by
a preceding start triplet (start codon), and an open reading
frame is any DNA sequence of triplets that potentially encodes a
protein.
... ... *homologous: In this context, the term refers to similar
sequences of amino acids in two proteins.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Mar99
-------------------
Related Background:
GENOME OF THE TYPHUS PARASITE AND THE ORIGIN OF MITOCHONDRIA
The Rickettsia are small bacteria (600 x 300 nanometers, or
spherical as "cocci"), classified as a type of proteobacteria
(i.e., "purple" bacteria, a huge phylum including many common
bacteria). The Rickettsia are obligate intracellular parasites
(i.e., they can replicate only inside living cells), and one of
the most notorious of these parasites is R. prowazekii, the agent
of epidemic louse-born typhus in humans. R. prowazekii is
estimated to have infected 20 to 30 million humans in the wake of
the First World War and killed another few million humans
following the Second World War. Because it is apparently the
descendent of free-living organisms, the genome of R. prowazekii
may provide insight into the adaptations producing an obligate
intracellular lifestyle. Also, phylogenetic analyses based on
sequences of *ribosomal RNA and *heat-shock proteins indicate
that *mitochondria may be derived from the proteobacteria, and
indeed the closest extant relatives of the ancestor to
mitochondria seem to be the Rickettsia. Finally, the genome of R.
prowazekii is a small one, making it amenable to genome analysis.
... ... S.G.E. Andersson et al now report the complete genome
sequence (1,111,523 *base pairs) of R. prowazekii. The authors
report this genome contains 834 protein-coding genes, the
functional profiles of which show similarities to those of
mitochondrial genes: no genes required for anaerobic glycolysis
are found in either R. prowazekii or mitochondrial genomes, but a
complete set of genes encoding components of the *tricarboxylic
acid cycle and the *respiratory-chain complex is found in R.
prowazekii (and in mitochondria). In effect, *ATP production in
Rickettsia is the same as that in mitochondria. Many genes
involved in the biosynthesis and regulation of biosynthesis of
amino acids and *nucleosides in free-living bacteria are absent
from R. prowazekii and mitochondria, and such genes have
apparently been replaced by homologues in the host genome. The R.
prowazekii genome contains the highest proportion of non-coding
DNA (24 percent) detected so far in a microbial genome, and the
authors suggest such non-coding sequences may be *degraded
remnants of "neutralized" genes that await elimination from the
genome. The authors finally suggest that phylogenetic analyses
indicate that R. prowazekii is more closely related to
mitochondria than is any other microbe studied thus far.
-----------
S.G.E. Andersson et al (10 authors at 2 installations, SE US)
The genome sequence of Rickettsia prowazekii and the origin of
mitochondria.
(Nature 12 Nov 98 396:133)
QY: Charles G. Kurland 
-----------
Text Notes:
... ... *ribosomal RNA: A class of RNA molecules that have an
important role in the structure of ribosomes, the large molecular
entities that carry out protein synthesis in all cells.
... ... *heat-shock proteins: A group of specific proteins
apparently synthesized by both prokaryotes (cells without
membrane-bound organelles) and eukaryotes (cells with membrane-
bound organelles) in response to a sudden elevation of ambient
temperature.
... ... *mitochondria: Mitochondria are double-membrane enclosed
organelles of cells that are involved with several important
biochemical pathways, including electron transport and oxidative
metabolism. Various types of eukaryotic cells may contain from a
few to several thousand mitochondria in each cell type. The
mitochondria are relatively large cylindrical structures up to 10
microns long and up to 2 microns in diameter, and most biologists
believe mitochondria are cell organelles that may have originated
as separate organisms that became resident in eukaryotic cells.
Mitochondrial DNA is independent of nuclear DNA. It consists of a
circular molecule, 16,569 base pairs long in humans, with a known
nucleotide sequence.
... ... *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).
... ... *tricarboxylic acid cycle: (Krebs cycle, citric acid
cycle) In aerobic respiration, the set of oxidative reactions
occurring after *glycolysis.
... ... *glycolysis: One of the 2 main energy-producing pathways
of the cell, this involves the anaerobic breakdown of glucose
with the generation of 2 molecules of adenosine triphosphate
(*ATP).
... ... *respiratory-chain complex: (electron transport chain)
Refers to a sequence of steps in the final stage of the aerobic
respiration biochemical pathway in which high energy electrons
are effectively passed through a series of membrane-bound carrier
molecules to support a proton gradient involved in energy
storage. The term "transport" here refers essentially to a
chemical flow diagram and not necessarily to an actual spatial
translocation of electrons.
... ... *ATP: (adenosine triphosphate) ATP 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.
... ... *nucleosides: The base-sugar moieties of nucleotides.
... ... *degraded remnants: In this context, the idea is that the
Rickettsia are descendents of bacteria with substantially larger
genomes, and that both Rickettsia and mitochondria are the
products of several types of reductive evolution.
-------------------
Summary & Notes by SCIENCE-WEEK  18Dec98


4. ON GENETICS AND HUMAN CANCERS
The current consensus is that cancer results from the
accumulation of mutations in the genes that directly control the
birth and death of biological cells. But the mechanisms through
which these mutations are generated are the subject of continuing
debate and much research. It has been argued that an underlying
genetic instability is absolutely essential for the generation of
the multiple mutations that underlie cancer. On the other hand,
it has also been suggested that normal rates of mutation, coupled
with waves of *clonal expansion, are sufficient for the cancer
process to occur in humans. ... ... C. Lengauer et al (Johns
Hopkins University, US) present a review of observations
concerning the stability of the genome of human cancer cells, the
authors making the following points:
... 1) Numerous genetic alterations that affect growth-
controlling genes have been identified in neoplastic cells over
the past 15 years, and these observations provide persuasive
evidence for the genetic basis of human cancer. The alterations
can be divided into 4 major categories:
... ... a) Subtle sequence changes: These changes involve
nucleotide base substitutions or deletions or insertions of a few
nucleotides in the genome, and unlike the alterations described
below, they cannot be detected via cytogenetic analysis. Such
mutations, for example, occur in over 80 percent of pancreatic
cancers.
... ... b) Alterations in chromosome number: Such alterations
involve losses or gains of whole chromosomes. Such changes are
found in nearly all major human tumor types.
... ... c) Chromosome translocations: These alterations can be
detected cytogenetically as fusions of different chromosomes or
of normally non-contiguous segments of a single chromosome. At
the molecular level, such translocations produce fusions between
two different genes, endowing the fused genetic entity with
tumorigenic properties. Such translocations are known to occur in
the *chronic myelogenous leukemias.
... ... d) Gene amplifications: These are seen at the cytogenetic
level as homogeneously stained regions, and at the molecular
level they involve multiple copies of a gene. An example of gene
amplification occurs in advanced *neuroblastomas.
... 2) All 4 of the alterations described above occur commonly in
specific tumor types but are rarely or never observed in normal
cells. However, the existence of genetic alterations in a tumor,
even when frequent, does not mean that the tumor is genetically
unstable. By definition, instability is a matter of rate, and the
existence of a mutation provides no information about the rate of
its occurrence. The higher prevalence of mutations in tumor cells
compared with normal cells still requires explanation.
... The authors conclude: "One can argue persuasively that all
chemotherapeutic compounds used at present are more toxic to
cancer cells than to normal cells only and specifically because
of the defective *checkpoints that occur in cancer cells. This
line of reasoning suggests that, although instability may be
essential for neoplasia to develop, it may also prove to be its
Achilles' heel when the tumor is attacked by the right agents.
Further research to define the molecular and physiological bases
of instability may, therefore, yield entirely new approaches to
treating common forms of cancer."
-----------
Editor's note: In addition to the background material appended to
this report, see report #5 in this issue.
-----------
C. Lengauer et al: Genetic instabilities in human cancers.
(Nature 17 Dec 98 396:643)
QY: Christoph Lengauer [lengauer@jhmi.edu]
-----------
Text Notes:
... ... *clonal expansion: In this context, this refers to the
expansion of a population of cells all deriving from a single
mutated cell.
... ... *chronic myelogenous leukemias: (granulocytic leukemias)
These leukemias are characterized by an uncontrolled
proliferation of myelopoietic cells (blood cells derived from
bone marrow).
... ... *neuroblastomas: Neuroblastomas are malignant neoplasms
characterized by only slightly differentiated immature nerve
cells of embryonic type.
... ... *checkpoints: In this context, the term "checkpoint"
refers to a point in the eukaryotic cell division cycle where the
cycle can be halted until conditions are suitable for the cell to
proceed to the next stage. (eukaryotic = containing membrane-
bound organelles such as a nucleus.)
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Mar99
-------------------
Related Background:
ANEUPLOIDY AND GENETIC INSTABILITY OF CANCER CELLS
In general, germ cells (egg cells and sperm cells) and somatic
cells (non-germ cells) carry different numbers of chromosomes,
with germ cells carrying exactly half the number (haploid number)
of somatic cell chromosomes (diploid number). The term
"aneuploidy" (heteroploidy) refers to a condition in which the
number of chromosomes in a cell is not an integer multiple of the
haploid number typical for that cell or organism. For example,
the haploid human chromosome number is 23; the normal somatic
cell contains 46 chromosomes; a somatic cell with 47 or 44
chromosomes is aneuploid. Some authors, however, use the term
"aneuploidy" to indicate merely an abnormal number of
chromosomes. In cell biology, the term "karyotype" refers to the
characteristics profile (number, size, and shape) of a set of
chromosomes of a cell or organism. In this context, the term
"phenotype" refers to the total appearance of a cell as
determined by the interaction during development between its
genetic constitution (genotype) and the cell's environment.
Genetic and phenotypic instability are hallmarks of cancer cells,
but the cause of the instability is not clear. The leading
hypothesis suggests that a poorly defined gene mutation generates
genetic instability and that one or more of the many subsequent
mutations then cause cancer [*Note #1]. ... ... P. Duesberg et al
(2 installations, DE US) report an investigation of the
hypothesis that genetic instability of cancer cells is caused by
aneuploidy, which they define as "an abnormal balance of
chromosomes". The authors point out that because symmetrical
segregation of chromosomes during mitosis depends on exactly two
copies of the genes involved in mitosis ("mitosis genes"),
aneuploidy involving chromosomes bearing mitosis genes will
destabilize the karyotype. The authors propose that the
aneuploidy hypothesis predicts that the degree of genetic
instability should be proportional to the degree of aneuploidy,
and it should thus be difficult to maintain the particular
karyotype of a highly aneuploid cancer cell on *clonal
propagation. The authors report this prediction is confirmed with
clonal cultures of chemically transformed aneuploid Chinese
hamster embryo cells. Defining the "ploidy factor" as the
quotient of the modal chromosome number divided by the normal
number of the species, it was found that the higher the ploidy
factor of a clone, the more unstable was its karyotype. The
authors point out that work by others has established an exact
correspondence between the karyotype instability of human colon
cancer cell lines and the degree of aneuploidy. The present
authors suggest that, independent of gene mutation, aneuploidy is
sufficient to explain genetic instability and the resulting
karyotypic and phenotypic heterogeneity of cancer cells. The
authors further suggest that because aneuploidy has also been
proposed to cause cancer, their hypothesis "offers a common,
unique mechanism of altering and simultaneously destabilizing
normal cellular phenotypes."
-----------
P. Duesberg et al: Genetic instability of cancer cells is
proportional to their degree of aneuploidy.
(Proc. Natl. Acad. Sci. US 10 Nov 98 95:13692)
QY: Peter Duesberg 
-----------
Text Notes:
... ... *Note #1: In 1976, Peter Nowell postulated that a
precancerous mutation generates exceptional "genetic instability"
or "mutability", and that the highly mutable "premalignant" cell
then suffers many further gene mutations, including those that
cause cancer (P.C. Nowell, Science 194:21 1976).
... ... *clonal propagation: In general, in this context, a
"clone" is a line of identical cells produced from one or a few
originating cells.
-------------------
Summary & Notes by SCIENCE-WEEK  22Jan99
-------------------
Related Background:
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)


5. CELL MICROENVIRONMENT AND CELL NEOPLASTICITY
The genesis of a tumor (tumorigenesis) is apparently a complex
molecular and cellular process that culminates in the growth of
aberrant cells in the context of a specific tissue
microenvironment in which the growth of normal cells is tightly
controlled. Potential cancer cells undergoing *neoplastic
transformation evidently incur multiple genetic aberrations that
enable them to grow autonomously (i.e., independent of local
regulatory mechanisms) in a regulative tissue environment. It has
been hypothesized that age is a major risk factor in the
development of cancer, with age of the tissue related to the time
available for a potential cancer cell to accumulate a sufficient
number and variety of the genetic abnormalities that enable the
cell to grow autonomously. Although genetic malfunction is
apparently an essential feature of neoplastic cells, age-
dependent changes in the elements of the tissue microenvironment
involved in regulation of the growth of cells may also have an
important role in the increasing frequency of cancer with
advancing age. ... ... K.D. McCullough et al (6 authors at
University of North Carolina, US) report the development of an
experimental system with which to analyze the interacting roles
of cellular *genotype and tissue microenvironment in the
development of tumors, including age-dependency of tumor
development. The experimental system involves intrahepatic (i.e.,
liver-to-liver) transplantation of *aneuploid liver epithelial
cells. The authors have previously demonstrated (1997) that in
young rats such transplants rapidly produce small localized
tumors at the site of inoculation, these tumors regressing in
young rats within 1 month of their formation. In contrast,
similar transplants into old rats quickly produce expanding liver
tumors that kill the host rat. The authors suggest that their
previous studies support the hypothesis that a) elements of the
liver microenvironment can regulate the proliferation and
differentiation of genetically aberrant liver cells, b) aneuploid
tumorigenic cells may be normalized by *epigenetic influences, c)
the regulatory potency of the liver microenvironment declines
with advancing age. In the present study, the authors examined
the epigenetic influences of microenvironments in young and old
animals when tumorigenic liver cells are widely disseminated
throughout the liver by inoculation of cells into the spleen
(which distributes the tumorigenic cells to the liver via the
blood). The authors report that under these experimental
conditions, as in their previous studies, the microenvironment of
the liver in young rats apparently induces transplanted aneuploid
liver epithelial cells to adopt morphological and functional
features of liver-cell differentiation with inhibition of
tumorigenesis, but that in old rats this inhibition of
tumorigenesis does not occur and abnormal proliferation of the
transplanted tumorigenic cells results. In conclusion, the
authors suggest that changes in tissue milieu, such as those that
accompany normal aging, may determine the ability of a
genetically aberrant cell to produce a tumor. [Editor's note: The
essence of this report is as follows: While it is apparently true
that in general the aging of tissue provides time for the
accumulation of tumorigenic mutations, the aging of tissue
(specifically, liver tissue) also apparently results in a
weakening of microenvironmental control systems that effectively
regulate the growth of tumorigenic cells.]
-----------
K.D. McCullough et al: Plasticity of the neoplastic *phenotype in
vivo is regulated by epigenetic factors.
(Proc. Natl. Acad. Sci. US 22 Dec 98 95:15333)
QY: Gary J. Smith [cellsort@med.unc.edu].
-----------
Text Notes:
... ... *neoplastic transformation: In general, a "neoplasm" is
any new growth. But the term is usually used to refer to abnormal
growth, particularly tumors, referring to abnormal tissue that
grows by cellular proliferation more rapidly than normal tissue
and which continues to grow after the stimulus that initiated the
new growth ceases. Neoplasms show partial or complete lack of
structural organization and functional coordination with the
normal tissue, and the neoplasm usually forms a distinct mass of
tissue which may be either benign (benign tumor) or malignant
(cancer).
... ... *genotype: The genetic constitution of an individual
organism or individual cell.
... ... *aneuploid liver epithelial cells: In animals, epithelial
cells compose the cell layers that form the interface between a
tissue and the external environment, for example, the cells of
the skin, the lining of the intestinal tract, and the lung airway
passages. The epithelial cells of the liver (hepatocytes) are the
primary functional cells of the liver. "Aneuploid" cells are
cells with an abnormal of chromosomes.
... ... *epigenetic influences: In general, this refers to
influences on gene expression other than those produced by direct
changes in the genome.
... ... *phenotype: In general, the phenotype is the individual
organism or cell as determined by the interaction of the genetic
constitution (genotype) and the environment. (The term is
sometimes also used to describe discrete expressions of the
genome, rather than the entire individual organism or cell.)
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Mar99


6. GENE THERAPY FOR AGING-RELATED LOSS OF MUSCLE FUNCTION
One of the primary consequences of aging, a consequence which
leads to significantly impaired function in the elderly
population, is the loss of *skeletal muscle strength and mass.
Both of these decrease up to one-third in humans between the ages
of 30 and 80 years. In addition, loss of the fastest and most
powerful muscle fiber types has been documented. Similar aging-
related muscle alterations have been observed in rats and mice,
indicating that the trend is maintained in other mammalian
species. The mechanisms underlying this aging-related muscle loss
have remained unclear, but there is some evidence that so-called
"insulin-like growth factor-I" may be involved. The term
"insulin-like growth factor" refers to a group of polypeptides
structurally homologous to *insulin, and which share many of the
biological activities of insulin, but which are apparently
biochemically distinct from it. These substances are "mitogens",
i.e., they enhance or induce cell division (mitosis). Insulin-
like growth factor-I (insulin-like growth factor type I) is a
monomer of 70 amino acids. ... ... E.R. Barton-Davis et al (5
authors at 2 installations, US) now report an attempt to moderate
the aging-related loss of muscle in mice by increasing the
regenerative capacity of muscle. The study involved the injection
of a genetically engineered virus to direct overexpression (i.e.,
genome-based protein overproduction) of insulin-like growth
factor-I in adult muscle. The authors report that insulin-like
growth factor-I expression promotes an average increase of 15
percent in muscle mass and a 14 percent increase in strength in
young adult mice, and prevents aging-related muscle changes in
old adult mice. In old adult mice, muscle mass and fiber type
distributions were maintained at levels similar to those in young
adults. The authors propose that these effects are primarily due
to stimulation of muscle regeneration via the activation of
*satellite cells by insulin-like growth factor-I. The authors
suggest this supports the hypothesis that the primary cause of
aging-related impairment of muscle function is a cumulative
failure to repair damage sustained during muscle utilization. The
authors further suggest that gene transfer of insulin-like growth
factor-I into muscle could form the basis of a human gene therapy
for preventing the loss of muscle function associated with aging,
and may be of benefit in diseases where the rate of damage to
skeletal muscle is pathologically accelerated.
-----------
Editor's note: In addition to the background material below, see
the SW Focus Report "Biology of Aging" at URL 
[http://scienceweek.com/swfr041.htm].
-----------
E.R. Barton-Davis et al: Viral mediated expression of insulin-
like growth factor I blocks the aging-related loss of skeletal
muscle function.
(Proc. Natl. Acad. Sci. US 22 Dec 98 95:15603)
QY: H. Lee Sweeney [Lsweeney@mail.med.upenn.edu]
-----------
Text Notes:
... ... *skeletal muscle: (striated muscle, voluntary muscle)
Muscle in which cross striations occur in the fibers as a result
of regular overlapping of thick and thin filament structures.
Although cardiac muscle is not "voluntary" muscle, it is also
striated in appearance.
... ... *insulin: A protein hormone that promotes uptake by body
cells of free glucose and/or amino acids, depending on target
cell type.
... ... *satellite cells: The satellite cells of skeletal muscle
are cells associated with muscle fibers that are believed to play
a role in muscle repair and regeneration.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 26Mar99
-------------------
Related Background:
ON HUMAN GENE THERAPY
The first approved clinical protocol for somatic gene therapy
began trials in 1990. Since then, more than 300 clinical
protocols have been approved worldwide, and over 3000 patients
have carried genetically engineered cells in their body. The
conclusions from these trials are that gene therapy has the
potential for treating a broad array of human diseases, and that
the procedure appears to carry a very low risk of adverse
reactions. However, the efficiency of gene transfer and express-
ion in human patients is still disappointingly low. Except for
anecdotal reports of individual patients being helped, there is
still no conclusive evidence that a gene-therapy protocol has
been successful in the treatment of a human disease.
... ... W. Anderson (University of Southern California, US)
reviews the status of the field and the difficulties that have
delayed advances, the author making the following points: 1) Gene
therapy is a powerful new technology that will require several
years before it will make a noticeable impact on the treatment of
disease. 2) Several major problems still exist, including poor
delivery systems, both viral and non-viral, and poor gene
expression after genes are delivered. 3) The reason for the low
efficiency of gene transfer and expression in human patients is
that we still lack a basic understanding of how vectors should be
constructed, what regulatory sequences are appropriate for which
cell types, how in vivo immune defenses can be overcome, and how
to manufacture efficiently the vectors that we do make. 4)
Although it not surprising that we have not yet had notable
clinical successes, the lessons we are learning in the clinic are
invaluable in illuminating the problems that future research must
solve. 5) Despite our present lack of knowledge, gene therapy
will almost certainly revolutionize the practice of medicine over
the next 25 years. In every field of medicine, the ability to
give the patient therapeutic genes offers extraordinary
opportunities to treat, cure, and ultimately prevent a vast range
of diseases that now plague mankind.
QY: W. French Anderson, Univ. of Southern California 213-740-2311
(Nature 30 Apr 98 392/supp:25) (Science-Week 29 May 98)
-------------------
Related Background:
THE PROSPECTS FOR GENE THERAPY
At the present time, more than 200 clinical trials of gene
therapy are apparently in place worldwide, with hundreds of
patients enrolled, but there is still not a single case of gene
therapy that can be called an unequivocal success. The major
problem is evidently gene delivery, getting the therapeutic gene
or genes or bits of DNA into cells in a way such that the new
genetic materials will be allowed to express their proteins in an
enduring cellular environment. There are basically two methods
for gene delivery, viral and non-viral, and neither method has
yet proved satisfactory. Success with either method, absent some
serendipitous laboratory or clinical discovery, will most likely
depend on further basic research. This has not been a good year
for the gene therapy community, considering the publicized lack
of clinical success, and considering that in Germany one of the
foremost gene therapy researchers has been accused of long-term
fraud and suspended from his professorship. But there are still
optimists, and this is still a field of vital importance to
medicine. In a recent review, Inder M. Verma and Nikunj Somia
propose that "in the not too distant future, gene therapy will
become as routine a practice as heart transplants are today."
QY: I. M. Verma, The Salk Institute, La Jolla CA 92037 US
(Nature 18 Sep 97) (Science-Week 3 Oct 97)
-------------------
Related Background:
A RECOMBINANT GENE THERAPY FOR HUMAN RHEUMATOID ARTHRITIS
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 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, and
one would expect that if we could synthesize the receptor and
introduce the synthesized product into the extracellular fluid,
the cytokine for which this receptor is specific would bind to
the receptor and be prevented from delivering its chemical signal
to the cells. Test-tube synthesis of most complex proteins
produced by biological cells is not yet possible, but what one
can do, after calculating the DNA code for the active part of the
receptor protein, is incorporate the necessary DNA sequence into
the genome of some mammalian cell line, and have these cells act
as chemical factories to produce the cytokine receptor that we
are unable to synthesize otherwise. We then gather the factory
product, administer it to the patient, and expect the cytokine
receptor to bind its specific cytokine in extracellular fluid and
thus reverse the course of the disease. This is essentially what
"recombinant gene therapy" is all about. It is a field less than
a decade old, and like all fields involving clinical medicine, it
moves slowly because procedures that involve human patients must
be carefully developed. This week, Larry W. Moreland et al (12
authors at various installations, US) report the successful
treatment of rheumatoid arthritis with a recombinant human
cytokine receptor complex produced by the method outlined above.
It is a beginning. Like all treatments involving recombinant gene
therapy, much work needs to be done. But the path ahead is clear,
and there is an expectation of important results from this area
of clinical medicine.
(New England Journal of Medicine 17 Jul 97)
(Science-Week 18 July 97)
-------------------
Related Background:
GENE-BASED IMMUNOTHERAPY FOR CERTAIN CANCERS EXPECTED SOON
Theodore Friedmann, director of the gene therapy program at the
University of California San Diego (US), points out that at
present no gene therapy approach has definitely improved the
health of a single one of the more than 2,000 patients who have
enrolled in gene therapy trials worldwide. Nevertheless,
Friedmann predicts that in the future gene therapy will be a
standard form of treatment for many diseases. In particular, he
says it seems likely that gene-base immunotherapies will succeed
with some malignancies such as neuroblastoma and melanoma in the
next few years, and will become helpful additions to existing
therapies for these diseases.
(Scientific American June 1997) (Science-Week 5 Jun 97)


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
IN FOCUS: ON THE LAWS OF PHYSICS

"What is a physical law? The word _law_ is a good illustration of
the difficulty associated with the use of everyday language in
the statement of scientific propositions. It has too many
meanings, and this fact has led to great confusion in much of
popular writing about science... We must recognize strict
limitations in the applicability of a physical law. It is only a
symbolic description of a limited range of phenomena, and we must
always be wary about extrapolation. Because a particular law
furnishes an accurate short-hand description of a given group of
operations, we must not immediately assume that similar
operations under different initial conditions will be equally
well subsumed by the same law. This emphasizes the extreme
importance in every experimental operation of noting carefully
all apparently subsidiary conditions, such as temperature, state
of atmosphere, proximity of neighboring bodies, time of day or
night, etc. Naturally, it is necessary to grant the practical
impossibility of reproducing again and again the same conditions
in the performance of a given experiment. The best we can hope
for is close approximation, and we may well expect that the law
chosen as the best description of a routine of experience will
have its form determined to a certain extent by the degree of
approximation of the routine. The more exactly the experiment is
done and the more carefully controlled the various factors that
enter into it, the more precise will be the resulting law...
[But] the more thoroughly a given experimental operation is
carried out, the more difficult it is in general to fit the
results with a law of simple form. We appear to have traveled
considerably beyond the view at one time held that the very
simplicity of a physical law was a guarantee of its truth."

-- R.B. Lindsay and H. Margenau: _Foundations of Physics_
   (Dover Publications, New York 1957, p.14,17,18)


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