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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy makers.
November 27, 1998 -- Vol. 2 Number 48
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For the real amazement, if you wish to be amazed, is this
process: You start out as a single cell derived from the coupling
of a sperm and an egg; this divides in two, then four, then
eight, and so on, and at a certain stage there emerges a single
cell which has as all its progeny the human brain. The mere
existence of such a cell should be one of the great astonishments
of the Earth. People ought to be walking around all day, all
through their waking hours calling to each other in endless
wonderment, talking of nothing except that cell.
-- Lewis Thomas (1913-1993)
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Contents of This Issue:
1. A Critique of the Nobel Prize
2. A Circumstellar Dust Disk in a Star-Planet System
3. Microwave Spectroscopy of a Quantum Dot Molecule
4. Isotopic Evidence for the Cretaceous-Tertiary Impactor
5. Embryonic Stem Cells Derived from Human Blastocysts
6. Cell Cytoskeleton: Plectin Regulation of Actin Dynamics
7. On the Biology and Treatment of Breast Cancer
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1. A CRITIQUE OF THE NOBEL PRIZE
There are supreme awards in nearly all the branches of science,
but none of them have acquired the popular interest of the Nobel
prizes, and certainly no science prizes except the Nobel prizes
have had even a remotely comparable portrayal in melodrama.
... ... E. Crawford, a sociologist and historian of science,
presents a critique of the Nobel prizes and the Nobel prize
system, the author making the following points: 1) Nobel intended
his prizes to encourage promising young scientists, so it would
no doubt be a surprise for him to see the prizes become the
standards for the highest achievements of modern science. 2) The
notion that the Nobel prizes parallel the history of modern
science ignores the fact that the awards cover only a small part
of modern science, neglecting a number of important fields such
as technology, astronomy, meteorology, and psychiatry. Thomas
Edison, the Wright brothers, the astrophysicists G.E. Hale and
Arthur Eddington, the meteorologist Vilhelm Bjerknes, Sigmund
Freud -- all did not receive a Nobel prize. Before the 1920s,
even theoretical physics and theoretical chemistry were
neglected, and Arnold Sommerfeld, G.N. Lewis, Ludwig Boltzmann,
Josiah Willard Gibbs, Oliver Heaviside, and Henri Poincare also
did not receive a Nobel prize. 3) The manner in which attention
has focused on the prize winners -- never on the candidates -- is
one reason for the extraordinary success of the prizes. Another
reason is the wholesale acceptance of the justification provided
by the prize awarders for the choices. Major eligible discoveries
have indeed received prizes, but for the most part, the awarders
of the prize "have been engaged in the rather humdrum business of
choosing among works produced by what Kuhn called 'normal'
science." 4) From the beginning, secrecy has been at the heart of
the Nobel system, the statutes of the Nobel Foundation adopted in
1901 stipulating that no part of the prize deliberations could be
made public, nor could a prize decision be appealed. But in 1974
the statutes of the Nobel Foundation were changed to authorize
the four institutions that award Nobel prizes to permit access to
archival documents at least 50 years old for purposes of
historical research. 5) Myths are necessary for the cohesion of
institutions and groups, and the myth of the Nobel laureate as
the lone discoverer may appear to be one that preserves some of
the innocence of science in an age of multimillion dollar
research projects and research teams involving hundreds of
collaborators. But the winner-take-all mentality masks the
realities of doing science in the 20th century. 6) It is
important to bear in mind that prize winners are chosen from a
large pool of worthy candidates, and that the choices are
conditioned not only by the predilections of the Swedish prize
awarders but also by their ties to international networks that so
far have centered almost exclusively in Europe and North America,
allowing for few prize winners residing in Russia, India, and
Japan, and none in China.
-----------
E. Crawford (Universite Louis Pasteur, FR)
Nobel: Always the winners, never the losers.
(Science 13 Nov 98 282:1256)
QY: Elisabeth Crawford, Institut d'Histoire des Sciences,
Universite Louis Pasteur, 7 rue de l'Universite, 67070
Strasbourg, FR.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 27Nov98
2. A CIRCUMSTELLAR DUST DISK IN A STAR-PLANET SYSTEM
In 1997, a planet with a minimum mass of 0.84 Jupiter-mass was
indirectly detected in a close orbit (radius 0.11 *AU, period
14.65 days) around the star 55 Cancri, a star of *spectral type
G8 and approximately 3 billion years old. The detection of excess
infrared emission from this system also suggested the presence of
circumstellar dust. Our Solar System has a disk of dust (and
larger bodies) that is roughly coplanar with the planets -- the
so-called *Kuiper Belt. ... ... D.E. Trilling and R.H. Brown now
report infrared *coronagraphic observations of 55 Cancri in which
light from the primary star is blocked, allowing the authors to
image a circumstellar dust disk. The authors report that the 55
Cancri dust lies in a disk that extends to at least 40 AU,
comparable to the expected extent of our Solar System Kuiper
Belt, but the inferred mass of the 55 Cancri dust disk is
approximately 10 times the estimated Kuiper Belt mass. The
authors report that the disk around 55 Cancri is relatively dark
at a wavelength of 2.3 microns, which is consistent with the
absorption of light by methane ice on the dust particles.
Assuming that the disk is coplanar with the planet, the authors
determine the mass of the planet to be 1.9 (+1.1, -0.4) Jupiter-
mass. The authors suggest that all the available evidence
indicates a mature planetary system around 55 Cancri, and that
further study of this and other circumstellar disks will allow
the characterization of global properties, and will in turn lead
to an increased understanding of our own Kuiper Belt. [Editor's
note: A collection of related previous SCIENCE-WEEK briefs can be
found at URLhttp://scienceweek.com under the title "Astrophysics:
Extrasolar Planets".]
-----------
D.E. Trilling and R.H. Brown (University of Arizona, US)
A circumstellar dust disk around a star with a known planetary
companion.
(Nature 22 Oct 98 395:775)
QY: David E. Trilling
-----------
Text Notes:
... ... *AU: Astronomical Unit. 1 AU = the mean distance from the
Sun to the Earth = approximately 93 million miles, and exactly
149,597,870 kilometers.
... ... *spectral type G8: Stars are categorized according to the
properties of their spectra. The current classification system
classifies stars as type O, B, A, F, G, K, or M in order of
decreasing surface temperature, and each type is further
subdivided into subclasses from 0 (hottest) to 9 (coolest). Our
own Sun is a G2 star.
... ... *Kuiper Belt: In 1951 the astronomer Gerard P. Kuiper
(1905-1973) postulated the existence of a belt of objects beyond
the orbit of Pluto. Both the existence and nature of the objects
were matters of speculation for decades, and finally in 1992
Jewitt and Luu identified the first Kuiper object. The current
estimate is that as many as 10^(8) objects larger than 10
kilometers in diameter may exist in what is called the "Kuiper
Belt", a disc that hugs the plane of the planetary system and
lies between 35 and 1000 AU from the Sun. Observations to date
have yielded some 55 trans-Neptune bodies with radii on the order
of 100 km or larger, and Pluto is considered by some astronomers
to be a member of this population.
... ... *coronagraphic observations: A coronagraph is an
instrument that makes it possible to observe a star's corona (the
extremely hot ionized gas immediately surrounding the star). The
basis of the instrument is the placement of a blocking disk at
prime focus (the focal point of the primary mirror) to form an
artificial eclipse.
3. MICROWAVE SPECTROSCOPY OF A QUANTUM DOT MOLECULE
Quantum dots are small conductive regions in a semiconductor, the
regions containing a variable number of electrons (from 1 to
1000) that occupy well-defined, discrete quantum states -- for
which reason they are often referred to as "artificial atoms".
Connecting quantum dots to current and voltage contacts allows
the discrete energy spectra of the system to be probed by charge-
transport measurements. Two quantum dots can be connected to form
an "artificial molecule", and depending on the strength of the
inter-dot coupling (which supports *quantum-mechanical tunnelling
of electrons between the dots), the two dots can form "ionic" or
"covalent" bonds. In the ionic bond case, the electrons are
localized on individual dots, and in the covalent bond case, the
electrons are delocalized over both dots. ... ... T.H. Oosterkamp
et al now report a transition from ionic bonding to covalent
bonding in a quantum-dot "artificial molecule" probed by
microwave excitations. The authors suggest their results
demonstrate controllable *quantum coherence in single-electron
devices, an essential requirement for practical applications of
quantum-dot circuitry in the construction of quantum computers.
-----------
T.H. Oosterkamp et al (7 authors at 3 installations, NL JP)
Microwave spectroscopy of a quantum-dot molecule.
(Nature 29 Oct 98 395:873)
QY: T.H. Oosterkamp
-----------
Text Notes:
... ... *quantum-mechanical tunnelling: "Tunnelling" is a quantum
mechanical phenomenon involving an effective penetration of an
energy barrier resulting from the width of the barrier being less
than the wavelength of the particle.
... ... *quantum coherence: 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.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
-------------------
Related Background:
A TUNABLE KONDO EFFECT IN QUANTUM DOTS
Quantum dots are small electrically conducting regions, typically
less than 1 micron in diameter, that contain from one to a few
thousand electrons. Because of the small volume, the electron
energies within the dot are quantized, and the behavior of the
quantum dot is intermediate between that of an atom and that of a
classical macroscopic object. Such intermediate systems are
called "mesoscopic" systems, and in the past several years great
attention has been devoted to the physics of such systems, since
they apparently can provide insights into quantum systems in
general. The electronic states in quantum dots can be probed by
transport when a small *tunnel coupling is allowed between the
dot and nearby source and drain leads. ... ... Cronenwett et al
(3 authors at 2 installations, NL US) report the realization of a
tunable *Kondo effect in small quantum dots, with the capability
of switching a dot from a Kondo system to non-Kondo system as the
number of electrons on the dot is changed from odd to even. The
*Kondo temperature can be tuned by means of a gate voltage as a
single-particle energy state nears the *Fermi energy.
Measurements of the temperature and magnetic field dependence of
a *Coulomb-blockaded dot show good agreement with prediction of
both equilibrium and nonequilibrium Kondo effects.
QY: Sara M. Cronenwatt, Stanford University 415-723-0830.
(Science 24 Jul 98 281:540) (Science-Week 14 Aug 98)
-------------------
Related Background:
... ... *tunnel coupling: This refers to tunneling, a quantum
mechanical phenomenon involving an effective penetration of an
energy barrier resulting from the width of the barrier being less
than the wavelength of the particle.
... ... *Kondo effect: The Kondo effect is a large anomalous
increase in the resistance of certain dilute alloys of magnetic
materials in nonmagnetic hosts as the temperature is lowered. In
general, the Kondo effect occurs when an impurity atom with an
unpaired electron is placed in a metal, producing an interaction
of localized electrons with delocalized electrons.
... ... *Kondo temperature: The temperature at which the Kondo
effect predominates.
... ... *Fermi energy: The average energy of electrons in a
metal.
... ... *Coulomb-blockaded: This refers to an effective blockade
of quantum mechanical tunneling produced by specific energy
barrier constraints.
-------------------
Related Background:
KONDO EFFECT IN A SINGLE ELECTRON TRANSISTOR
A transistor is essentially a semiconductor device in which it is
possible to control voltage or current in such a way as to
achieve gain or switching action, and a single-electron
transistor is a transistor of extremely small dimensions isolated
from its leads by potential barriers narrow enough to permit
electron tunneling, with a minute electron source that is
essentially a droplet of electrons. A single-electron transistor
switches on and off with the addition of each electron, in
contrast with the ordinary transistor which sustains a switched-
on state given a flow of added electrons. This quantized behavior
of the single-electron transistor is due to its dimensions, the
electron droplet essentially behaving as an artificial atom.
... ... Goldhaber-Gordon et al (6 authors at 2 installations, US
IL) report measurements on single-electron transistors smaller
than those previously made, and which exhibit all of the
predicted aspects of the Kondo effect in such systems. The
authors suggest the increased functionality of single electron
transistors may eventually be technologically important.
QY: M.A. Kastner
(Nature 8 Jan 98) (Science-Week 23 Jan 98)
-------------------
Related Background:
ON QUANTUM COMPUTING WITH MOLECULES
In general, in quantum mechanics, the "superposition principle"
holds that any two quantum mechanical states can be combined in
infinitely many ways to form states that have characteristics
intermediate between those of the two that are combined.
Entanglement is unique to quantum mechanics, and involves a
relationship (a "superposition of states") between the possible
quantum states of two entities such that when the possible states
of one entity collapse to a single state as a result of suddenly
imposed boundary conditions, a similar and related collapse
occurs in the possible states of the entangled entity no matter
where or how far away the entangled entity is located. The idea
of quantum computing received a significant impetus in 1994 when
Peter W. Shor of ATT (US) proposed that quantum entanglement and
superposition could in principle be used to accomplish many
numerical tasks, in particular the factoring of large numbers,
much faster than the best classical calculator. Since the
security of many important encryption systems depends on the
difficulty of factoring large numbers, quantum computing suddenly
became of great practical importance, and Shor's algorithm
provoked computer scientists to learn about quantum mechanics,
and physicists to begin serious considerations of the require-
ments of a quantum computer science. ... ... Gershenfeld and
Chuang (2 installations, US), review the theoretical bases and
current status of quantum computing, in particular their own work
applying nuclear magnetic resonance techniques. The authors point
out the following: 1) In classical computation, the state of a
bit (the fundamental unit of information) is specified by one
number, 0 or 1. An n-bit binary word in a typical computer is
thus described by string of n zeroes and ones. In contrast, in a
quantum computer, the qubit (the fundamental unit of information)
might be represented by an atom in one of two different states, 0
or 1, but unlike classical bits, qubits can exist simultaneously
as 0 or 1, with the probability for each state given by a
numerical coefficient. 2) A quantum computer promises to be
immensely powerful because it can be in multiple states at once
(superposition), and because it can act on all its possible
states simultaneously. Thus, a quantum computer could naturally
perform myriad operations in parallel, using only a single
processing unit. This is the essence of the idea of quantum
computing, although one must understand the expression here is
quite general. 3) The authors have investigated the construction
of a quantum computer based on the nuclear magnetic resonance
behavior of a simple molecular liquid [chloroform, CHCl(sub3)],
with the 2 possible quantum mechanical "spin" states of atoms as
the basic qubit states. Since chloroform is a simple molecule,
the fundamental limitation in this particular system is the small
number of qubits. The authors and other researchers are actively
working to increase the size of the basic molecule in
experimental quantum computing systems, and thus increase the
number of available qubits. 4) The authors conclude: "All along,
ordinary molecules have known how to do a remarkable kind of
computation. People were just not asking them the right
questions."
QY: Neil Gershenfeld, Massachusetts Institute of Technology 617-
253-1000.
(Scientific American June 1998) (Science-Week 12 Jun 98)
[Editor's note: Experimental details of the method and algorithm
used in the above mentioned NMR quantum computing technique were
recently presented by Chuang et al (5 authors 4 installations,
US) in Nature 14 May 1998 393:143]
4. ISOTOPIC EVIDENCE FOR THE CRETACEOUS-TERTIARY IMPACTOR
The Cretaceous period is the geological period ranging approxi-
mately from 146 million years ago to 65 million years ago, and
was apparently characterized towards its end by the rapid
extinction of a number of species, including the dinosaurs. There
have been five major extinctions according to the fossil record,
the Cretaceous extinction one of them, and the consensus is that
these extinctions were related to violent geophysical events,
perhaps asteroid impacts. The Chicxulub impact crater in the
Yucatan peninsula of Mexico is a large impact crater apparently
caused by a 10 kilometer-diameter asteroid, the impact area
extending at least 100 kilometers from the impact center. Using
Argon(40)/Argon(39) isotope dating methods, this impact crater
has been dated with high precision at 64.98 million years ago,
which places the impact at the end of the Cretaceous, and the
most popular current hypothesis to explain the Cretaceous
extinction is the global effect of the Chicxulub impact on the
extant life forms. This hypothesis was first proposed by Luis and
Walter Alvarez in the 1970s on the basis of non-terrestrial dust
of presumed cosmic origin in deposits at the K/T boundary, but
the Yucatan crater was unknown at that time and was not
discovered until the 1990s. But direct isotope evidence of an
impactor is still missing, and some researchers have argued that
high concentrations of iridium and other noble metals in K/T
boundary sediments, the basis for the K/T impactor hypothesis,
can be explained by enhanced volcanic activity that occurred near
the end of the Cretaceous, bringing up noble metals from Earth's
mantle, which similar to meteorites has high concentrations of
noble metals. ... ... A. Shukolyukov and G.W. Lugmair now report
a high-precision *mass spectrometric analysis of chromium in
sediment samples from the K/T boundary confirms the cosmic
origins of the K/T phenomenon. The authors report that the
isotopic composition of chromium in K/T boundary samples from
Stevns Klint, Denmark, and Caravaca, Spain, is different from
that of Earth and indicates its extraterrestrial source. The
authors suggest the chromium isotope signature is consistent with
a *carbonaceous chondrite-type impactor, and that the observed
differences in the chromium isotopic composition among the
various meteorite classes can serve as a diagnostic tool for
deciphering the nature of impactors that have collided with Earth
during its history.
-----------
A. Shukolyukov and G.W. Lugmair (Univ. of Calif. San Diego, US)
Isotopic evidence for the Cretaceous-Tertiary Impactor and its
Type.
(Science 30 Oct 98 282:927)
QY: A. Shukolyukov, Univ. of Calif. San Diego 619-534-2230.
-----------
Text Notes:
... ... *mass spectrometric analysis: The mass spectrometer is a
device in which molecules are ionized and the accelerated ions
are separated according to their mass to charge ratio. The
relative abundance of isotopes or other ionized species can thus
be determined by measuring positive or negative ion currents.
... ... *carbonaceous chondrite: "Stony" meteorites (aerolites)
are meteorites formed solely of rock-forming silicates, and
chondrites are a type of stony meteorite consisting of an
agglomeration of millimeter-sized globules (chondrules) that are
thought to be unchanged since the original condensation out of
the nebula from which the sun and solar system formed. A
carbonaceous chondrite is a chondritic meteorite that contains a
relatively large amount of carbon, with a resultant dark
appearance.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
-------------------
Related Background:
ON METEORITE IMPACT AND THE K/T MASS EXTINCTION
... In a short review of the meteorite impact hypothesis and the
K/T extinction, K.O Pope et al make the following points: 1)
Confirmation of the impact portion of the Alvarez hypothesis
marks a turning point in the study of the K/T mass extinction, a
turning point away from speculations about possible causes and
toward linking the extinctions to a single catastrophic event. 2)
Advances in computer modeling of the impact, coupled with
knowledge of the target rocks and their behavior under the
high-pressure shock, have shed light on what happened during the
first few seconds after impact. A key aspect of the Yucatan site
is that the upper 3 kilometers of rock were rich in water,
carbonate, and sulfate, which upon impact produced about 200
gigatons each of SO(sub2) and H(sub2)O vapor and other gases that
greatly altered the properties of the stratosphere. 3) Early work
predicted that smoke and dust from the impact plunged the Earth
into a freezing blackout. Recent computer simulations and
atmospheric models indicate that within a few weeks to months
temperatures and light levels would have begun to rebound due to
the release of heat stored in the oceans and the coagulation and
fall of the dust and soot. The major effects of the dust and soot
would last about 1 year or less, but SO(sub2) and water vapors
would remain in the stratosphere and ultimately produce sulfuric
acid aerosols. Models indicate that a global aerosol cloud would
be continuously produced for approximately 12 years, blocking out
over 50 percent of the sunlight during the first 10 years. The
authors conclude: "Now that we have a better understanding of the
dynamics of the impact, gleaned from the discovery of the crater
and the studies that followed, we can begin to address a wide
range of complex global effects. There is much work ahead, but
the course is clear."
-----------
K.O. Pope et al (3 authors at 3 installations, US)
Meteorite impact and the mass extinction of species at the
Cretaceous/Tertiary boundary.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11028)
QY: Kevin O. Pope, Geo Eco Arc Research, 2222 Foothill Blvd., La
Canada, CA 91011 US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 23Oct98
-------------------
Related Background:
ANALYSIS OF THE CHICXULUB IMPACT CRATER
... An important parameter of the [Chicxlulub] impact is the
total area of the impact crater, since that area would be related
to the amount of debris thrown into the atmosphere. Until now,
the usual figure for the largest dimension of the impact crater
has been approximately 300 kilometers. Morgan et al (20 authors
at 8 installations, UK US MX CA) now report an analysis of
seismic data of the Chicxulub impact, determining the diameter of
the transient cavity at about 100 kilometers. The authors suggest
this parameter is critical for constraining any proposed impact-
related effects on the Cretaceous environment, and that the
seismic data indicate the morphology of the crater is similar to
large impact structures observed on other planets such as Venus.
QY: Mike Warner
(Nature 4 Dec 97) (Science-Week 26 Dec 97)
5. EMBRYONIC STEM CELLS DERIVED FROM HUMAN BLASTOCYSTS
*Embryonic stem cells are derived from *totipotent cells of the
early mammalian embryo and are capable of *unlimited and
undifferentiated proliferation in vitro. In *chimeras with intact
embryos, mouse embryonic stem cells contribute to a wide range of
adult tissues, including *germ cells, providing a powerful
approach for introducing specific genetic changes into the mouse
*germ line. ... ... J.A. Thompson et al now report the production
of human *blastocyst-derived *pluripotent cell lines that have
normal chromosome characteristics, express high levels of
*telomerase activity, and express *cell surface markers that
uniquely characterize primate embryonic stem cells. The authors
report that after undifferentiated proliferation in vitro for 4
to 5 months, these cells still maintained the developmental
potential to form *trophoblast, and to form derivatives of *all 3
embryonic germ layers, including gut *epithelium (mesoderm) and
neural epithelium, embryonic *ganglia, and *stratified squamous
epithelium (ectoderm). The authors suggest these cell lines
should be useful in human developmental biology, drug discovery,
and transplantation medicine. ... ... In a related commentary in
the same journal, J. Gearhart makes the following points: 1) A
renewable tissue-culture source of human cells capable of
differentiating into a wide variety of cell types would have
broad applications in basic research and transplantation
therapies. A major step in realizing this goal has now been taken
with the demonstration that human embryonic stem cells can be
grown in culture. 2) In the work of J.A. Thompson et al, four
cell lines tested produced *teratomas when grown in
*immunosuppressed mice. Histology of the tumors revealed
differentiated cells derived from all 3 embryonic germ layers
(ectoderm, mesoderm, and definitive endoderm) -- a result
consistent with pluripotency. 3) The derivation of human
embryonic stem cells now raises a whole new set of expectations.
On the basis of the already completed use and study of mouse
embryonic stem cells, the research and clinical potential for
human embryonic stem cells is enormous. They will be important
for in vitro studies of normal human embryogenesis, abnormal
development (through the generation of cell lines with targeted
gene alterations and engineered chromosomes), human gene
discovery, drug and *teratogen testing, and as a renewable source
of cells for tissue transplantation, cell replacement, and gene
therapies. These latter applications could eventually make
unnecessary the direct use of fetal tissue in transplantation
therapies [*Note #1].
-----------
J.A. Thompson et al (7 authors at 2 installations, US IL)
Embryonic stem cell lines derived from human blastocysts.
(Science 6 Nov 98 282:1145)
QY: James A. Thompson, University of Wisconsin 608-262-3961.
-----------
J. Gearhart (Johns Hopkins University, US)
New potential for human embryonic stem cells.
(Science 6 Nov 98 282:1061)
QY: John Gearhart
-----------
Text Notes:
... ... *Embryonic stem cells: In general, the term "stem" cells
refers to undifferentiated cells that upon differentiation can
give rise to various specialized cell lines such as blood cells,
skin cells, nerve cells, etc. Adult bone marrow, for example,
contains stem cells that are the precursors of the various
specialized types of blood cells. "Embryonic" stem cells are
specifically stem cells derived from the embryo only.
... ... *totipotent cells: Cells that have the ability to
differentiate into any type of cell and thus form a new organism
or regenerate any part of an organism.
... ... *unlimited and undifferentiated proliferation in vitro:
In general, differentiated "normal" cells in tissue culture
produce a limited number of replications. In contrast, embryonic
stem cells and many types of cancer cells in tissue culture show
unlimited replications, and are thus called "immortal" cell
lines. In this context, "undifferentiated" proliferation is
simply proliferation without cell differentiation
(specialization).
... ... *chimeras: In this context, an animal that has received a
transplant of genetically and immunologically different tissue.
In this report, the transplant involves the injection of human
cultured stem cells into mice.
... ... *germ cells: In general, reproductive cells. All other
cells are "somatic" cells.
... ... *germ line: In general, this refers to the line of
differentiated germ cells.
... ... *blastocyst: A mammalian egg in the later stages of
*cleavage but before implantation in the uterus. The blastocyst
consists of a hollow fluid-filled ball of cells and an inner cell
mass (embryonic stem cells) from which the embryo develops.
... ... *cleavage: The early and rapid division stage that
divides the fertilized egg into smaller and smaller cells
(blastomeres) while retaining the same overall size of the
embryo.
... ... *pluripotent cell: A cell that has the potential,
depending on conditions, to give rise to many differentiated cell
lines but which lacks complete totipotency.
... ... *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.
... ... *cell surface markers: Cell surface proteins or protein
components that can be chemically identified.
... ... *trophoblast: In the early vertebrate embryo, the outer
ectodermal cell layer of the blastocyst. In mammals, it is the
trophoblast that attaches to the uterus and forms the placenta.
... ... *all 3 embryonic germ layers: In the embryos of higher
animals, there occurs the transformation of a single-layer
blastula into a 3-layered gastrula consisting of ectoderm,
mesoderm, and endoderm surrounding a cavity with one opening. The
3 layers are called the "germ layer", and these layers, via
further cell differentiation and proliferation, determine the
development of all the major body systems and organs.
... ... *epithelium: In animals, epithelial cells (epithelium)
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.
... ... *ganglia: (singular: ganglion) In the context of cells,
the original meaning of "ganglion" was any cluster of nerve cell
bodies in the central or peripheral nervous system. Currently,
the term "ganglion" refers to a aggregation of nerve cell bodies
located in the peripheral nervous system. Unfortunately, many
neuroanatomy texts still label certain neuron clusters in the
central nervous system in the old way (e.g., basal ganglia).
... ... *stratified squamous epithelium: The cells of the
epithelium are for the most part closely packed cells with little
extracellular material between adjacent cells, the cells arranged
in continuous sheets in either single or multiple layers. The
cells may be flat, cubelike, columnar, or a combination of
shapes, and "squamous" cells are flattened and scalelike. In this
context, "stratified squamous epithelium" refers to a structure
consisting of distinctly layered epithelial cells (layers varying
in size and shape of cells), the top layer of which are squamous
cells.
... ... *teratomas: A teratoma is a neoplasm (tumor) composed of
multiple tissues, including tissues not normally found in the
organ in which it arises. A teratoma in the adult human ovary,
for example, can contain hair, teeth, skin, heart muscle, nerve
cells, and so on -- all a result of "wild" cellular
differentiation of neoplastic cells, but with enough regulation
so that distinct tissues are formed. In the context of this
report, the teratomas occurred in mice after injection of
cultured human stem cells, thus demonstrating the ability of
those stem cells to differentiate into organized specific tissue-
producing cells.
... ... *immunosuppressed mice: In general, this refers to mice
whose immune system response has been suppressed by chemical,
biological, or physical means. In this report, the purpose of the
immunosuppression was to allow the development of a mouse
teratoma provoked by injection of human stem cells. Without
immunosuppression, the human stem cells would be immediately
attacked and possibly destroyed by the mouse immune system before
the stems cells could differentiate.
... ... *teratogen: Any drug or other agent that causes abnormal
fetal development.
... ... *Note #1: We repeat here a quotation that appeared at the
head of a recent issue of SW: "Between the fifth and tenth days
the lump of stem cells differentiates into the overall building
plan of the mouse embryo and its organs. It is a bit like a lump
of iron turning into the space shuttle. In fact it is the
profoundest wonder we can still imagine and accept, and at the
same time so usual that we have to force ourselves to wonder
about the wondrousness of this wonder." -- Miroslav Holub
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
6. CELL CYTOSKELETON: PLECTIN REGULATION OF ACTIN DYNAMICS
Plectin is a multidomain protein of large size and apparently
versatile binding properties. It has been shown to interact in
vitro with *intermediate filament proteins of various types and
to physically link intermediate filament proteins with
*microfilaments and *microtubules. In various cell types and
tissues, plectin has been localized at specific *cytoskeleton-
*plasma membrane junctional complexes (e.g., *epidermal
hemidesmosomes, *dense plaques of smooth muscle, and *focal
adhesions). Other prominent locations of plectin are *Z-lines,
intracellular junctional structures of *striated muscle, and
*intercalated disks of cardiac muscle. Consistent with its
versatile binding properties and strategic cellular localization,
various studies have shown that plectin is essential for the
mechanical integrity of skin and muscle cells.
... ... K. Andra et al now report a study of *fibroblast and
*astroglial cell cultures derived from genetically engineered
plectin-deficient mice, and the authors report the following
results: 1) Only minor changes in microtubule and intermediate
filament network organization were detectable in plectin-
deficient cells. 2) Plectin deficiency leads to an increased
number of *actin stress fibers and focal adhesion contacts. 3)
The capability of plectin-deficient cells to rearrange their
actin cytoskeleton upon short-term stimulation with soluble
ligands was compromised. 4) Plectin-deficient fibroblasts exhibit
reduced motility and increased adherence. The authors suggest
their results reveal a novel role of plectin as a regulator of
cellular processes involving actin filament dynamics that goes
beyond its proposed role in scaffolding and mechanical
stabilization of cells.
-----------
K. Andra et al (5 authors at 2 installations, AT DE)
Not just scaffolding: plectin regulates actin dynamics in
cultured cells.
(Genes & Development 1 Nov 1998 12:3442)
QY: Gerhard Wiche
-----------
Text Notes:
... ... *intermediate filament proteins, *microfilaments,
*microtubules, *cytoskeleton: The structural framework of
eukaryotic cells (cells with nuclei and other membrane-bound
internal structures), called the "cytoskeleton", consists of an
arrangement of macromolecular structures: microtubules,
intermediate filaments, and microfilaments. The microtubules are
hollow cylinders about 24 nanometers in diameter, many microns in
length, and consist of heterodimers of alpha- and beta-tubulin
proteins plus a variable set of other proteins. They form the
scaffolding of the mitotic spindle (an important structure in
cell division), organize other cytoplasmic structures, and are
the structural core of various organelles involved in cell
movement (cilia and flagella). The intermediate filaments are
about 10 nanometers in diameter, many microns in length, are
specific for various cell types, and are not found in all cell
types. Microfilaments are 4 to 6 nanometers in diameter, highly
variable in length, and are found in all eukaryotic cells. They
are composed of a protein called "actin" and several other
accessory proteins, and they are important in cell locomotion and
in the molecular dynamics of muscle cells.
... ... *plasma membrane: In general, this refers to the surface
membrane of cells, 5 to 10 nanometers in thickness, comprising a
lipid bilayer and embedded or attached proteins.
... ... *epidermal hemidesmosomes: A desmosome is a site of
adhesion between 2 *epithelial cells, the site consisting of a
dense attachment plaque separated from a similar structure in the
other cell by a thin layer of extracellular material. A
hemidesmosome is a half desmosome occurring in certain types of
epithelial cells. The term "epidermal" refers to the superficial
epithelial portion of the skin.
... ... *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.
... ... *dense plaques of smooth muscle: (dense bodies of smooth
muscle) Smooth muscle fibers are found in the viscera, blood
vessels, and the eye. The fibers are non-striated (smooth) and
contract more slowly than the striated fibers of the skeletal
muscle system. In general, smooth muscle is involved in
"involuntary" action, while striated muscle is involved in
"voluntary" action. The dense bodies of smooth muscle fibers are
anchoring structures to which intermediate filaments are
attached.
... ... *focal adhesions: (adhesion plaques) In general, a focal
adhesion is an intracellular attachment structure under the cell
surface where the cell attaches to the extracellular matrix in
vivo or to the substrate in cultured cells. Internal actin
filaments connect to the focal adhesion.
... ... *Z-lines: (Z-disks, intermediate disks) A cross-striation
bisecting the I band of striated muscle myofibrils (muscle
filaments) and serving as the anchoring point of actin filaments
at either end of the *sarcomere.
... ... *sarcomere: Region extending from one Z disk to the next
in skeletal (striated) muscle fibers.
... ... *striated muscle: skeletal or voluntary muscle in which
cross striations occur in the fibers as a result of regular
overlapping of thick and thin filaments. Although cardiac muscle
is not "voluntary" muscle, it is also striated in appearance.
... ... *intercalated disks: Specialized intercellular attachment
structures found in cardiac muscle.
... ... *fibroblast: A type of connective tissue cell, secreting
structural proteins (e.g., collagen) that form certain tissue
components, including the extracellular matrix.
... ... *astroglial cell: (astrocyte) Neuroglia are non-neuronal
cellular elements of the central and peripheral nervous systems,
and astroglia are a type of neuroglia. In general, neuroglia are
thought to have important metabolic functions.
... ... *actin stress fibers: In general, stress fibers are
bundles of contractile filaments resembling tiny myofibrils
(muscle fibrils). They occur in the cytoplasm of cultured
fibroblasts and are composed of actin, myosin, or other
cytoskeletal proteins.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
-------------------
Related Background:
RHO ENZYMES AND THE ACTIN CYTOSKELETON
... Guanosine triphosphate is a high-energy compound that
provides energy to drive other chemical reactions in biological
cells, and the G-proteins are a class of guanosine triphosphate
binding proteins that are membrane-bound and that serve as signal
transducers between the cell surface and the cell interior. The
ras-proteins are a group of G-protein enzymes that among other
things catalyze the hydrolysis of guanosine triphosphate (they
are thus guanosine triphosphatases), and the rho-proteins are a
subgroup of ras-proteins. All of these proteins have been
implicated in trans-membrane cell signaling and in the effects of
such signals on the intracellular cytoskeleton. ... ... A. Hall
(University College London, UK) reviews the mediation by the
actin cytoskeleton of a variety of essential biological functions
in eukaryotic cells: cell shape, cell polarity, cell movement,
and cell division. The author suggests that understanding the
biochemical mechanisms that control the organization of actin is
a major goal of contemporary cell biology with implications for
health and disease, and that members of the rho family of small
guanosine triphosphatases have emerged as key regulators of the
actin cytoskeleton. In addition, the interaction of these rho
enzymes with multiple target proteins apparently ensures
coordinated control of many other important cellular activities,
including gene transcription and chemotaxis.
QY: Alan Hall
(Science 23 Jan 98) (Science-Week 6 Feb 98)
7. ON THE BIOLOGY AND TREATMENT OF BREAST CANCER
Breast cancer is a major public health problem worldwide, and the
incidence of breast cancer in the US has been increasing
gradually for the past 3 decades. The estimate is that 181,600
new cases of breast cancer were diagnosed in the US in 1997 and
that 44,190 people would die of breast cancer in that same year.
Recent decreases in mortality have been reported in the US, UK,
and Sweden. ... ... G.N. Hortobagyi presents a review of the
treatment of breast cancer, and the author makes the following
points about our current knowledge of the biology of this
disease: 1) The recent identification and *cloning of the genes
BRCA1 and BRCA2 has expanded knowledge of familial breast
cancer. *Germ-line mutations in these 2 genes are associated with
a 50 to 85 percent lifetime risk of breast cancer, ovarian
cancer, or both. Tests for these mutations exist, and research
efforts to develop comprehensive genetic screening and counseling
programs are continuing. 2) All breast cancers have *somatic
genetic abnormalities. In non-familial ("sporadic") breast
cancer, abnormalities have been identified in several genes
(e.g., p53), and in some cases normal genes or gene products
are *overexpressed. However, the number and types of mutations
necessary for the development of non-familial breast cancer are
not known. 3) Many factors that stimulate or inhibit growth
influence the growth and proliferation of breast cancer cells.
*Gonadal steroid hormones, *growth factors, and various
*cytokines and *lymphokines influence the behavior and
*phenotypic expression of breast cells. The recognition that
these factors influence the growth and dissemination of breast
cancer has provided new targets for therapeutic and preventive
intervention. 4) Breast cancer also induces *neovascularization
(angiogenesis), which in turn facilitates the *metastatic
process. Metastatic spread is not a random mechanical phenomenon,
but requires systemic interaction among breast cells, *stroma,
and surrounding normal tissue at both primary and metastatic
sites. *Adhesion molecules, local mediators, hormones, and growth
factors must all act for metastases to develop. On the basis of
this new information, diagnosis and treatment have changed, and
many new *cytotoxic and hormonal agents have emerged from new
biological concepts and are being developed for clinical use.
-----------
G.N. Hortobagyi (University of Texas, US)
Treatment of breast cancer.
(New England J. Med. 1 Oct 98 339:974)
QY: Gabriel N. Hortobagyi, University of Texas M.D. Anderson
Cancer Center, 1515 Holcombe Blvd., Box 56, Houston, TX 77030 US.
-----------
Text Notes:
... ... *cloning: In general, the term "cloning" has two
meanings. 1) With reference to cells, cloning is any process by
which a line of identical cells is produced from one or a few
originating cells. 2) With reference to DNA, cloning is any
process by which a gene or fragment of DNA is spliced into a
*vector so that the DNA can be amplified many times by
transferring the recombinant (i.e., foreign) DNA molecule into a
host organism (usually a bacterium or yeast) that can be grown in
large quantities.
... ... *vector: In this context, a vector is any DNA that can
propagate itself rapidly in a host cell and maintain this
capability after insertion of foreign DNA into the vector. For
example, one can introduce a human DNA fragment (e.g., a gene)
into the DNA of a virus, have this virus infect its usual host
cells (e.g., bacteria or animal cells), and if the virus is
rapidly replicating, the fragment of human DNA will also be
rapidly replicated. The procedure, in other words, uses viral DNA
as a means (a vector) to introduce the foreign DNA (here a human
DNA fragment incorporated into the viral DNA) into a host cell to
use the host cell-virus system as a chemical factory to produce
relatively large quantities of the foreign DNA fragment.
... ... *Germ-line mutations: In general, "germ-line" cells are
reproductive cells, or any cell giving rise to a reproductive
cell such as an oocyte (egg cell) or spermatocyte (sperm cell).
All other cells are called somatic cells. Mutations in germ-line
cells, because they involve reproductive cells, are carried from
the parent generation to the offspring generation, while
mutations in somatic cells are not transferred to the next
generation.
... ... *somatic genetic abnormalities: In this context, the term
refers to abnormalities of the genome of somatic cells that do
not derive from germ-line mutations. An example are the
alterations (abnormalities) of the genome of somatic cells that
can be produced by ultraviolet light or specific chemical
substances.
... ... *overexpressed: In general, the term "expression" refers
to any gene activity, but particularly to activity that results
in the production of the specific protein encoded by the gene.
The expression of genes is closely regulated in the cell, so that
underexpression and overexpression are potential pathological
abnormalities of cell function.
... ... *Gonadal steroid hormones: This refers to estrogens,
progestins, and androgens -- all hormones involved in the
physiology of sex cells.
... ... *growth factors: A group of small secreted polypeptides
that bind to receptors on certain specific target cells and
stimulate cell division in those target cells. Many growth
factors have an apparently close relationship to *oncogenes.
... ... *oncogenes: An oncogene is the activated form of a proto-
oncogene. A proto-oncogene is a normal cellular gene that upon
specific alteration (activation), acts to induce a cancerous
state. Transformation from proto-oncogene to oncogene may involve
a virus, a mutation, chromosomal translocation, etc.
... ... *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
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.
... ... *lymphokines: (interleukins) Hormones secreted by certain
antigen-processing cells of the immune system, the hormones
causing immune cells specific for the antigen to proliferate.
... ... *phenotypic expression: In general, this refers to an
individual specific profile of expressed genes as distinguished
from the profile of expressed genes common to all members of the
species.
... ... *neovascularization: (angiogenesis) 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.
... ... *metastatic process: In general, the term "metastasis"
refers to the spread of any disease from one part of the body to
another, but in the context of this report the term refers
specifically to the spread of cancer cells from a primary tumor
to other parts of the body via the lymphatic system or blood
vessels or any of the fluid-filled body spaces. The essential
aspect of metastasis is the break-out of cancer cells from the
tissue or organ of origin and into tissues that may be near or
quite distant if the cancer cells are carried by the blood, for
example. Apart from any deleterious complications caused by a
tumor in place, the metastasis of tumor cells to vital organs is
the most dangerous aspect of the cancer diseases.
... ... *stroma: The framework, usually of connective tissue, of
an organ, gland, or other structure.
... ... *Adhesion molecules: Molecules expressed on the surface
of a cell that mediate the adhesion of the cell to other cells or
to the extracellular matrix. Adhesion molecules bind to receptors
that are classed collectively as "integrins". Abnormalities in
cellular adhesion properties are characteristic of many types of
cancer cells.
... ... *cytotoxic: In general, anything detrimental or
destructive to cells.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 27Nov98
-------------------
Related Background:
MECHANISMS OF TUMOR SUPPRESSOR GENES
Cancer is fundamentally a genetic disease in which damage to
cellular DNA leads to disruption of the normal mechanisms that
control cellular proliferation. ... ... Ellisen and Haber (2
installations, US) review current knowledge concerning the genes
targeted in human cancer, and they make the following points: 1)
In general, cancer genes have been divided into 2 classes, proto-
oncogenes and tumor suppressor genes. 2) Proto-oncogenes are
genes that sustain activating changes in human cancer. These
changes may take the form of point mutations or gene
rearrangements that lead to increased or uncontrolled activity of
the encoded protein, or they make take the form of gene
amplification, which results in increased levels of protein
expression. 3) Tumor suppressor genes are characterized by
inactivating changes in human cancer, typically point mutations
that result in truncation or functional inactivation of the
encoded protein, or gross deletions of chromosomal fragments
carrying these genes. 4) Tumor suppressor genes are of particular
interest in cancer genetics because they are the genes most
commonly associated with hereditary predisposition to cancer. In
cases where familial cancer is linked to inheritance of a mutant
allele of a tumor suppressor gene, inactivation of the remaining
wild-type allele of that gene constitutes the critical genetic
event that initiates the development of cancer. 5) Although much
attention has focused on the initial tumor suppressor gene
mutation that initiates malignant transformation, cancer actually
results from the accumulation of a large number of genetic
events, both in tumor suppressor genes and in proto-oncogenes.
The authors tabulate 14 selected different tumor suppressor
genes, indicating the related familial syndrome, the types of
sporadic tumors containing mutations of these genes, and the
presumed normal function (mechanism of action) of these genes.
Mutations of the tumor suppressor gene have been found in
approximately 50 percent of all cancers. The authors conclude:
"As the understanding of genetic heterogeneity evolves,
population studies are likely to uncover the contribution of
common subtle genetic variations to the risk of developing
different types of cancer. Together with societal and ethical
guidelines on the use of such genetic information, the study of
mutations in tumor suppressor genes and of their role in cancer
predisposition may provide important clues to the clinical
management of human cancer."
QY: Leif W. Ellisen, Dana-Farber Cancer Institute, Boston, MA US.
(Science & Medicine Jul/Aug 1998) (Science-Week 17 Jul 98)
-------------------
Related Background:
EVIDENCE THAT BREAST CANCER GENE IS APOPTOSIS COACTIVATOR
In molecular biology, the term "transcription" refers to the
sequence of biochemical events producing the conversion of DNA
code to RNA code. Apoptosis is programmed cell death produced by
control mechanisms designed to destroy defective cells or cells
that must be discarded in the process of tissue differentiation.
Mutations of the gene {BRCA1} have been linked to 45% of the
cases of familial breast cancer, and to 80% to 90% of families
with both breast and ovarian cancer. ... ... Now Ouchi et al (5
authors at 4 installations, US) report that {BRCA1} stimulates
artificial and genomic entities that contain elements responsive
to the tumor suppressor protein p53, which is known to be
involved in apoptosis. The authors suggest their findings
indicate the gene {BRCA1} is involved in transcriptional
regulation and has a function as a p53 coactivator.
QY: Hidesaburo Hanafusa (saburo@rockvax.rockefeller.edu)
(Proc. Natl. Acad. Sci. US 3 Mar 98)
(Science-Week 2 Apr 98)
-------------------
Related Background:
NO LARGE US COMMERCIAL MARKET FOR CANCER GENE TESTING
Contrary to the expectations of financial analysts, commercial
genetic tests for breast cancer and colon cancer in the US are
not only not making money for the companies that offer them, but
they are proving to be overwhelmingly rejected by the public. The
tests are based on identification of inherited mutations in
specific genes, and have high predictive value for certain types
of family-related breast and colon cancers. Oncormed Inc.
(Gaithersburg, Md US), which offers breast and colon cancer
tests, is reports to be doing approximately 100 tests a month,
one-tenth of what was expected. Myriad Genetics Inc. (Salt Lake
City, Ut US), which offers the breast cancer gene test, has
reported only 262 tests in the entire last quarter of 1997. A
third company, Genetics IVF Institute (Fairfax, Va US) declines
to give numbers, but admits a similar low total of tests
administered. One problem is apparently that genetic testing may
result in individuals being refused health insurance coverage by
US insurers. At the present time, cancer gene tests cost
approximately $2000 each, and are often paid for by insurance
companies. Wall Street analysts had predicted a US$100 million a
year market in the US, but the market has not materialized.
Timothy Triche, CEO at Oncormed, says, "Everyone misunderstood
this field." (New York Times 27 Mar 98)
-------------------
Related Background:
THE BEGINNINGS OF THE BATTLE OVER BREAST CANCER GENES
Legal papers filed in two different court jurisdictions in the
past 6 weeks indicate that a significant battle is looming
concerning exploitation rights for discoveries of two breast
cancer genes, BRCA1 and BRCA2. The major litigants are
Oncormed Inc. of Gaithersburg, MD US, and Myriad Genetics of Salt
Lake City, UT US. Each company holds patent rights from
independent research teams, and each company sells genetic tests
used to estimate a woman's risk of breast or ovarian cancer.
These legal entanglements highlight the questions that are being
raised about the value of gene patents in general. In this
particular case, there has been criticism of the US Patent
Office, which has apparently awarded patents to two different
groups for the same use of the gene BRCA1, albeit with vari-
ations of the gene involved in the methodology. One geneticist
calls the Patent Office decision "just crazy". The US Patent
Office is headed by Bruce Lehman, who has also come under fire
from scientists and librarians for his support of restrictive
electronic database copyright protection legislation promulgated
by commercial interests.
(Science 12 Dec 97) (Science-Week 2 Jan 98)
-------------------
Related Background:
CONSTRAINTS IMPOSED IN USE OF BREAST CANCER GENE PATENTS
BRCA1 and BRCA2 are known breast cancer susceptibility genes,
discovered in 1994 and 1995, and it has been reported that a
protein made by BRCA2 plays a critical role in cell repair of DNA
damage. Both cancer genes are apparently somehow involved in
tumor suppression or in the production of proteins vital for DNA
repair and the suppression of mutations. Patents for both genes
have been awarded to university-industry consortiums. From the
commercial standpoint, the value of such a patent is the
potential for making profit from diagnostic tests, since if one
has a patent on an important gene, one also has exclusive rights
to market diagnostic tests for disease-producing mutations of
that gene. Since breast cancer kills many millions of women
worldwide each year, there are many millions of women who are a
potential market for a diagnostic test that will tell them if
they are at risk. A similar paradigm applies to many other
patents that have been awarded or will soon be awarded for genes
in the human genome. That is the commercialization aspect of the
story. The scientific aspect is that identifying genes in the
human genome, their expressed proteins and the function of their
expressed proteins, and coupling such genes to specific disease
entities -- all of it is enormously expensive. So for the past
decade such research projects have been deliberately opened to
venture capital from private interests with the idea that
exclusive patents would be used to recoup the initial investments
with a profit. The basic science of the human genome has thus
been commercialized. A reasonable analogue would be the use of
private venture capital in particle physics to identify a new
elementary particle with the arrangement such that the private
commercial interest would have an exclusive patent on that
elementary particle. In any case, this is the current situation
in molecular biology. Now a British patent for the BRCA2 gene
has been awarded to a consortium of the Cancer Research Campaign
Technology (UK) and Duke University (US), and this consortium has
in turn granted an exclusive worldwide license to the patent for
diagnostic services and products to the company Oncormed of
Gaithersburg, MD US. What is apparently a new wrinkle in this
game is that Oncormed must apparently meet certain strict
conditions in exercising its license: broad sub-licensing of
diagnostic tests to other concerns, a requirement for pre- and
post-test counseling for women tested, a ban on direct advertis-
ing to the public for screening tests, and no charge for use of
the techniques by the UK National Health Service. Everyone agrees
that genetic testing ought to be conducted ethically and
responsibly, but apparently not everyone agrees that agreements
with private companies can effectively replace government
regulation. The story of the commercialization of molecular
biology has yet to unfold its denouement. (Nature 27 Nov 97)
-------------------
Related Background:
LACK OF CORRELATION OF DDT LEVELS WITH BREAST CANCER RISK
There are a number of environmental contaminants that have week
estrogenic properties, the most noted being the polychlorinated
biphenyls (PCBs), the insecticide DDT, and its breakdown product
DDE. Both PCBs and DDE exist in the global ecosystem in fish,
wildlife, human tissue, blood, and milk, and it has been
suggested (and promoted by the media) that these organochlorine
"xenoestrogens" and related compounds contribute to the increased
incidence of breast cancer in women, decreases in sperm counts in
men, and neurodevelopmental deficits in children. David J. Hunter
et al (8 authors at 6 installations, US) now report a controlled
study of 240 women who gave blood samples in 1989 or 1990 and who
were subsequently diagnosed with breast cancer before mid-year
1992. They measured plasma levels of 1,1-dichloro-2,2-bis(p-
chlorophenyl)ethylene (DDE) and polychlorinated biphenyls in the
blood samples and in matched controls, and they found no support
for the hypothesis that exposure to DDT and PCBs increases the
risk of breast cancer. They found, in fact, that the median
levels of DDE and PCBs was actually non-significantly lower in
the blood samples of the women who later developed breast cancer.
These results are consistent with results from other recent
studies in other countries. In a separate editorial in the same
journal, Stephen H. Safe (University of Texas A & M, US) cautions
the research, legislative, and media communities to avoid the
"paparazzi science" that often produces chemophobia in the public
at large. On the other hand, apathy concerning chemical
contamination of the environment is also not the ideal, as a
number of well-publicized tragedies involving chemical pollutants
demonstrate. One can only hope for a future public educated
enough to distinguish between scientific evidence and mere
forceful rhetoric. QY: D. J. Hunter, Channing Laboratory, 181
Longwood Avenue, Boston, MA 02115 US (New England J. Med. 30 Oct
1997)
-------------------
Related Background:
ENVIRONMENTAL FACTORS AND BREAST CANCER RISK
Fewer than 10 per cent of breast cancers are due to inherited
genetic defects, and sporadic cases cannot be explained by known
risk factors. Devra Lee Davis, et al, (Yeshiva University, New
York) summarize present research on the incidence of breast
cancer in various ethnic groups and geographic regions. Aside
from radiation, most established breast cancer risk factors are
related to total lifetime exposure to estrogen. The key
component is the estrogen receptor, which is linked to the
transcription of a variety of important genes, some of which
control tumor induction and tumor growth. Davis and her group
emphasize the importance of xenoestrogens, environmental agents
that function as estrogens and can affect the rate of estradiol
metabolism and the type of metabolites produced, alter binding
with the estrogen receptor, change breast cell proliferation,
and thereby influence the development of breast cancer and other
hormonally related diseases. Some xenoestrogens (e.g., in
certain soy products) are protective, while others (e.g., in
certain insecticides) greatly increase breast cancer risk.
(Science and Medicine May/Jun 1997 )
(Science-Week 15 May 97)
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