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.

December 22, 2000 -- Vol. 4 Number 51

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There is no doubt that great revolutions of human
scientific thought will occur in the next century,
and in the century after that, and in thousands of
centuries afterward. So which of our current pet
scientific dogmas will be among the first washed
away by new facts and sudden clarities?
-- Anonymous

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

1. EXPERIMENTAL PHYSICS: ON BOSE-EINSTEIN CONDENSATES
In an atomic Bose-Einstein condensate, several thousand atoms
essentially become a single atom, a "superatom", and this effect
has been observed experimentally with atoms of rubidium and
lithium, the atoms trapped and cooled by special methods. The
excitement in contemporary physics concerning Bose-Einstein
condensates derives from the expectation that these manipulable
real systems can illuminate the fundamentals of quantum
mechanics, superfluidity, superconductivity, the properties and
interactions of atoms, laser physics, and nonlinear optics, i.e.,
some of the most important research areas in modern physics.
(Scientific American December 2000)

2. THEORETICAL PHYSICS:
JOHN ARCHIBALD WHEELER ON QUANTUM PHYSICS
John Archibald Wheeler is one of the grand old people of physics.
It was Wheeler who introduced the term "black hole" to describe
the cosmic singularities that result from the gravitational
collapse of supermassive stars. Now, in a new essay, Wheeler says
the greatest mystery in physics is still the question, How come
the quantum? 100 years after its birth, the underpinning of
quantum physics is still murky. Nevertheless, despite all the
uncertainty surrounding it, quantum physics is both a practical
tool and the basis of our understanding of much of the physical
world. It has explained the structure of atoms and molecules, the
thermonuclear burning that lights the stars, the behavior of
semiconductors and superconductors, the radioactivity that heats
the Earth, and the comings and goings of particles from neutrinos
to quarks. (New York Times 12 Dec 00)

3. PLANETARY SCIENCE: ON THE SEDIMENTARY ROCKS OF EARLY MARS
An analysis of Mars Global Surveyor Mars Orbiter Camera
photographs indicates that in the Martian Noachian period (the
period prior to 3.5 billion years ago) Mars may have been warm
enough to be wet enough to sustain bodies of liquid water on its
surface. The evidence suggests that the materials in craters and
chasms considered for 20 years to be younger than 3.5-billion-
years-ago in age (i.e., in the Amazonian period) were instead
formed in the Noachian period, that there are many more outcrops
of these materials than previously known, that they could indeed
represent sediment deposited in lakes, and that they are a small
part of a substantially more complex and previously unanticipated
Martian history. (Science 8 Dec 00 290:1927)

4. DEVELOPMENTAL BIOLOGY:
ORIGINS OF ENDOTHELIAL CELLS AND MUSCLE CELLS IN BLOOD VESSELS
Compared to our knowledge of the development of other tissues,
very little is known about the development of blood vessels. The
conventional notion has been that in blood vessels the
endothelial cells and smooth muscle cells arise from separate
precursor cells through a series of cell divisions and
specialization (differentiation). But this idea has now been
overturned by discovery of a type of blood vessel precursor cell
from which both endothelial and smooth muscle cells can derive in
both tissue culture and mice. Which type of specialized cell is
produced depends on exposure of the precursor cell to a specific
growth factor. (Nature 2 Nov 00 408:43)

5. MEDICAL BIOLOGY:
USE OF NEURAL STEM CELLS IN COMBATING BRAIN TUMORS
Neural stem cells have been recently recognized for their
remarkable ability to migrate throughout the central nervous
system, become normal constituents of the host neural tissue
architecture (cytoarchitecture), and disseminate bioactive
molecules expressed a result of neural stem cell genetic
engineering. New evidence indicates a powerful tropic interaction
between neural stem cells and intracranial pathology, and
suggests that exogenous neural stem cells, genetically engineered
_ex vivo_ and strategically implanted, may provide a platform for
the dissemination of therapeutic genes and/or gene products to
previously inaccessible infiltrating tumor cells.
(Proc. Natl. Acad. Sci. US 7 Nov 00 97:12393)

6. MEDICAL BIOLOGY: ON THE P-53 TUMOR SUPPRESSOR GENE
The p53 gene, first described in 1979, was the first tumor-
suppressor gene to be identified. It was originally believed to
be an oncogene, but genetic and functional data obtained 10 years
after its discovery demonstrated that p53 is a tumor-suppressor
gene. It is now known that the p53 protein does not function
correctly in most human cancers: in approximately half of these
tumors, the p53 protein is inactivated directly as a result of
mutations in the p53 gene; in many other cancers, the p53 protein
is inactived indirectly through binding to viral proteins, or as 
a result of alterations of genes whose products interact with p53
or transmit information to or from p53.
(Nature 16 Nov 00 408:307)

7. IN FOCUS: CONCEPTUAL CHANGES IN PHYSICAL THEORIES

8. FROM THE SCIENCEWEEK ARCHIVE:
ON TWO CULTURES FORTY YEARS LATER


=-=-=-=-=-=-=-=-=
Section 2
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1. EXPERIMENTAL PHYSICS: ON BOSE-EINSTEIN CONDENSATES
     Because the particles of systems whose behavior can be
described only by the rules of quantum mechanics occupy a
discontinuous spectrum of energy states, only special (i.e., non-
Boltzmann) statistics can be applied to energy distributions in
such systems. From the standpoint of the mathematics of
statistical physics, the essential general constraint of quantum
statistics is that in partition functions of quantum systems it
is sums over energy levels that must be used rather than
integrals over phase space.
     In general, quantum statistics is concerned with the
equilibrium distribution of elementary particles of a particular
type among the various possible quantized energy states, with an
assumption that these particles are indistinguishable. Quantum
statistics, in turn, takes one of two forms, depending on
distribution constraints: Fermi-Dirac statistics or Bose-Einstein
statistics.
     In "Fermi-Dirac statistics", the Pauli exclusion principle
is obeyed, so that no identical particles (called "fermions" if
they obey this condition) can be in the same quantum state (as
specified by the set of quantum numbers that define such a
state). In a Fermi-Dirac system, the exchange of two identical
fermions (e.g., two electrons) does not affect the probability of
distribution, but it does involve a change in the sign of the
wave function (the exchange is "antisymmetric") [*Note #1].
     In Bose-Einstein statistics, the Pauli exclusion principle
is not obeyed, so that any number of identical particles (called
"bosons" if they obey this condition) can be in the same quantum
state. In a Bose-Einstein system, the exchange of two bosons of
the same type affects neither the probability of distribution nor
the sign of the wave function (the exchange is "symmetric")
[Note#2].
     At high temperatures and low concentrations, both forms of
quantum statistics reduce to classical Boltzmann statistics.
     In quantum mechanics, electrons, protons, and neutrons have
an intrinsic angular momentum known as "spin", and a magnetic
moment parallel or antiparallel to that angular momentum. When
electrons are combined together to form an atom or ion, there is
a resultant angular momentum which is a combination of the
intrinsic spin of the electrons and the angular momentum due to
their motion about the nucleus, and this is the "spin" of the
atom or ion. Atoms or ions with non-zero spin are magnetic atoms
or ions. The idea of electron spin was first proposed by Goudsmit
and Uhlenbeck in 1925 to explain the splitting of atomic
spectroscopic emission lines in the presence of a magnetic field.
Elementary particle spin involves a virtual rotation about the
axis of the particle, which means only two spin states are
possible, one clockwise and one counterclockwise.
     All particles in nature are either fermions or bosons, with
fermions (always elementary particles) having half-integer spin
(spin-states characterized by half-integer multiples of Planck's
constant divided by 2ã), and bosons (all other particles) having
integer spin (spin-states characterized by integer multiples of
Planck's constant divided by 2ã).
     What is important in this context is that particular real
systems can be manipulated in the laboratory into a condition in
which quantum behavior becomes both apparent and controlling. An
example is the Bose-Einstein condensate, a system long ago
predicted but first experimentally realized in 1995, a system in
which a gas of atoms at extremely low temperature becomes a gas
of bosons obeying Bose-Einstein statistics [*Note #3].
     In general, "Bose-Einstein condensation" is a phenomenon
occurring in a macroscopic system consisting of a relatively
large number of bosons at a sufficiently low temperature
(microkelvins down to nanokelvins) in which a significant
fraction of the particles occupy a single quantum state of lowest
energy (the ground state). In an atomic Bose-Einstein condensate,
several thousand atoms essentially become a single atom, a
"superatom", and this effect has been observed experimentally
with atoms of rubidium and lithium, the atoms trapped and cooled
by special methods. The excitement in contemporary physics
concerning Bose-Einstein condensates derives from the expectation
that these manipulable real systems can illuminate the
fundamentals of quantum mechanics, superfluidity,
superconductivity, the properties and interactions of atoms,
laser physics, and nonlinear optics, i.e., some of the most
important research areas in modern physics.
... ... Graham P. Collins presents a survey of current research
on Bose-Einstein condensates, the author making the following
points concerning experimental methods for trapping and cooling
atoms:
     1) The experimental problem in creating a gaseous Bose-
Einstein condensate is to cool a dilute gas of atoms in a vacuum
chamber to an extremely low temperature. Almost all methods
involve laser cooling, in which laser beams reduce the motion of
atoms, cooling them to approximately 50 microkelvins.
     2) The most common precooling device used in such
experiments is the magneto-optical trap, which combines laser
cooling with trapping of the atoms by magnetic fields. The
magnetic fields help to compress the gas to a higher density.
Many laboratories use a sequence of to magneto-optical traps
optimized, respectively, for collecting atoms, and then for
cooling them.
     3) The final cooling stage in Bose-Einstein condensate
experiments involves evaporation: While a magnetic trap holds the
atoms, the hottest fraction of atoms is continuously removed, so
that increasingly lower-temperature gas remains. Unlike laser
cooling, evaporative cooling works best at higher particle
densities.
-----------
Graham P. Collins: The coolest gas in the Universe.
(Scientific American December 2000)
QY: Graham P. Collins: editors@sciam.com
-----------
Text Notes:
... ... *Note #1: Fermi-Dirac statistics is named after Enrico
Fermi (1901-1954) and Paul A. Dirac (1902-1984). While a lecturer
in mathematical physics at the University of Florence (IT) in
1924, Fermi worked out the theoretical properties of a gas
consisting of particles that obey the Pauli exclusion principle.
Dirac made the same calculation independently.
... ... *Note #2: Bose-Einstein statistics is named after
Satyendra Nath Bose (1894-1974) and Albert Einstein (1879-1955).
In 1924, while at the University of Dacca (IN), Bose developed a
method to derive Planck's equation for black body radiation using
a statistical approach to a photon gas, the approach involving
quantum statistical rules. Bose wrote a paper about this
discovery and sent it to Einstein, who immediately saw the
importance of what Bose had accomplished and arranged for the
publication of the paper in the Zeitschrift f�r Physik, after
which Einstein developed the idea and applied it to particles
other than photons. Bose made no other major contribution to
science, and later in life Bose said: "I was like a comet, a
comet which came once and never returned again." Although never
returned, the Bose "comet" influenced and still influences nearly
all of physics.
... ... *Note #3: In 1995, a group led by E.A. Cornell and C.E.
Wieman at the Joint Institute of Laboratory Astrophysics (US)
succeeded in cooling approximately 2000 atoms of rubidium gas to
170 nanokelvin, at which temperature the atoms formed a Bose-
Einstein condensate less than 100 microns in diameter. The
condensate endured for approximately 15 seconds.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm
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Related Background:
PHYSICS: FIRST MOLECULES IN A BOSE-EINSTEIN CONDENSATE
In 1997, Steven Chu, Claude Cohen-Tannoudji, and William D.
Philips shared the Nobel Prize in Physics for their work in the
1980s involving laser-cooled atoms, work that ultimately led to
the cooling of atoms to extremes close to absolute zero degrees
kelvin, and finally to the creation by Anderson et al (Science
269:198 1995) of a Bose-Einstein condensation in a dilute gas of
rubidium atoms. The essential idea behind these techniques
involves a reduction in the momentum of an atom when it absorbs a
photon. Bose-Einstein statistics is the statistical mechanics of
a system of indistinguishable particles for which there is no
restriction on the number of particles that may simultaneously
exist in the same quantum energy state. Bosons are particles that
obey Bose-Einstein statistics, and they include photons, pi
mesons, all nuclei having an even number of particles, and all
particles with integer spin. In low temperature physics, the
Bose-Einstein condensation is a phenomenon that occurs in the
study of systems of bosons: below a critical temperature, the
quantum ground state becomes highly populated, individual wave
equations merging into a single wave equation, the particles
indistinguishable, and the condensate of particles behaving as a
singe entity.
... ... R. Wynar et al (5 authors at University of Texas Austin,
US) now report the production of rubidium-87 dimers that are
essentially at rest by assembling them from ultracold rubidium
atoms in an atomic Bose-Einstein condensate. In a commentary in
the same journal, C.J. Williams and P.S. Julienne (National
Institute of Standards and Technology, US) point out that this
work is the first observation of molecule formation in a Bose-
Einstein condensate, that a method for the ultraprecise
measurement of molecular binding energies has now been
introduced, and that the work is the first measurement of the
interaction energy between a condensate and a molecule.
-----------
R. Wynar et al: Molecules in a Bose-Einstein Condensate.
(Science 11 Feb 00 287:1016)
QY: D.J. Heinzen: heinzen@physics.utexas.edu
-----------
C.J. Williams and P.S. Julienne: Molecules at rest.
(Science 11 Feb 00 287:986)
QY: paul.julienne@nist.gov
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Summary by SCIENCE-WEEK http://scienceweek.com 3Mar00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
FESHBACH RESONANCES IN A BOSE-EINSTEIN CONDENSATE
... The term "Feshbach resonance" refers to a transient
"sticking" of two colliding atoms, the sticking involving a
resonance coupling that occurs when the molecular state has
nearly zero energy. The term "optical trapping" refers to the
confinement of entities in a restricted geometry by the
controlled action of light. In this report, the term "inelastic"
refers to a collision process in which the total kinetic energy
of the colliding particles is not the same after the collision as
before it, and the term "coherent beams of atoms" refers to beams
composed of atoms moving in unison. ... ... Inouye et al (6
authors at Massachusetts Institute of Technology, US) report new
observations in a Bose-Einstein condensate. It has long been
predicted that the scattering of ultra-cold atoms can be altered
significantly through a so-called "Feshbach resonance". Two such
resonances have now been observed in optically trapped Bose-
Einstein condensates of sodium atoms by varying an external
magnetic field. The resonances gave rise to enhanced inelastic
processes and a dispersion variation of the scattering length by
a factor of over two. The authors suggest these results open new
possibilities for the study and manipulation of Bose-Einstein
condensates, may also be important in atom optics, for modifying
the atomic interactions in an atom laser, or more generally, for
controlling nonlinear coefficients in atom optics with coherent
beams of atoms.
QY: W. Ketterle, Mass. Inst. of Technology 617- 253-1000
(Nature 12 Mar 98) (Science-Week 27 Mar 98)
For more information: http://scienceweek.com/swfr.htm

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2. THEORETICAL PHYSICS:
JOHN ARCHIBALD WHEELER ON QUANTUM PHYSICS
John Archibald Wheeler is one of the grand old people of physics.
Now 89 years of age, Wheeler studied with Niels Bohr (1885-1962)
from 1933 to 1935, taught physics at Princeton University (US)
from 1938 to 1976, and at the University of Texas (US) from 1976
to his retirement in 1986. Wheeler's field is theoretical
physics, particularly the development of a unified field theory.
He introduced the concept of the "geon", a gravitational-
electromagnetic entity. He collaborated with Richard Feynman
(1918-1988) on a formulation of an approach to the concept of
action-at-a-distance in physics. It was Wheeler who introduced
the term "black hole" to describe the cosmic singularities that
result from the gravitational collapse of supermassive stars.
... ... In an essay on quantum physics, Wheeler makes the
following points:
     1) What is the greatest mystery in physics today? Different
physicists have different answers. Wheeler states his candidate
for the greatest mystery in physics is a question now a century
old: "How come the quantum?"
     2) Wheeler points out that despite all the uncertainty
surrounding it, quantum physics is both a practical tool and the
basis of our understanding of much of the physical world. It has
explained the structure of atoms and molecules, the thermonuclear
burning that lights the stars, the behavior of semiconductors and
superconductors, the radioactivity that heats the Earth, and the
comings and goings of particles from neutrinos to quarks.
     3) Wheeler points out that 100 years, after all, is not so
long a time for the underpinning of a wonderfully successful
theory to remain murky. Consider gravity: Isaac Newton, when he
published his monumental work on gravitation in the 17th century,
knew he could not answer the question, "How come gravity?" Newton
was wise enough not to try. "I frame no hypotheses," Newton said.
     4) Wheeler concludes: "Here, a hundred years after Planck,
is quantum physics, the intellectual foundation for all of
chemistry, for biology, for computer technology, for astronomy
and cosmology. Yet, proud foundation for so much, it does not yet
know the foundation for its own teachings. One can believe, and I
do believe, that the answer to the question, 'How come the
quantum?' will prove to be also the answer to another question,
'How come existence?'"
-----------
John Archibald Wheeler: A practical tool, but puzzling too.
(New York Times 12 Dec 00)
QY: John Archibald Wheeler: Univ. of Texas Austin 512-471-3434
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Summary by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON THE MEANING OF QUANTUM THEORY
"To some extent, I myself am not deeply troubled by the prospect
of a reality which is not independent of the observer or the
measuring device. However, I do not share the uncompromising
views characteristic of the positivist. I am convinced that the
desire to relate their theories to elements of an independent
reality is part of the psychological make-up of many scientists.
They feel it is necessary to try continually to go beyond the
symbols in a mathematical equation and attach a deeper meaning to
them. Without this continual attempt to penetrate to an
underlying reality, science would be a sterile, passive, and
rather unemotional activity. This it certainly is not. Like all
acts of faith, the search for an independent reality involves
striving for a goal that can never be reached. This does not mean
that the effort is any less worthwhile. On the contrary, it is
through this process of striving for the unachievable that
progress in science is made. With regard to quantum theory, my
personal view is that we still do not yet know enough about the
physical world to make a sound judgment about its meaning. The
positivist says that the theory is all there is, but the realist
says: Look again, we do not yet have the whole story. As to where
we might look, my recommendation is to watch _time_ closely: we
do not yet seem to have a good explanation of it. This is not to
say that a better understanding of time will automatically solve
all the conceptual problems of quantum theory. Time, I suppose,
will tell. I am reasonably certain of one thing. The
unquestioning acceptance of the Copenhagen interpretation of
quantum theory has, in the last 40 years or so, held back
progress on the development of alternative theories. It has been
very difficult for the voices raised against the orthodox
interpretation to be heard. Remember that it was John Bell -- an
opponent of the dogmatic Copenhagen view -- whose curiosity and
determination led to Bell's theorem and ultimately to new
experimental tests. Blind acceptance of the orthodox position
cannot produce the challenges needed to push the theory
eventually to its breaking point. And break it will, probably in
a way no one can predict to produce a theory no one can imagine.
The arguments about reality will undoubtedly persist, but at
least we will have a better theory."
-----------
Jim Baggott: _The Meaning of Quantum Theory_
(Oxford University Press, Oxford UK, p.210)
-------------------
SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
QUANTUM PHYSICS: ON ONE HUNDRED YEARS OF QUANTUM PHYSICS
After 100 years of development, quantum physics is no longer just
a field, it is the bedrock of all of modern physics, and it will
be the origin, during the next 100 years, of new knowledge and
new applications not yet imaginable.
... ... D. Kleppner and R. Jackiw (Massachusetts Institute of
Technology, US) present a review of the first century of quantum
physics, the authors making the following points:
     1) Although quantum mechanics was created to describe an
abstract atomic world far removed from daily experience, its
impact on our daily lives could hardly be greater. The
spectacular advances in chemistry, biology, and medicine -- and
in essentially every other science -- could not have occurred
without the tools that quantum mechanics made possible. Without
quantum mechanics there would be no global economy to speak of,
because the electronics revolution that brought us the computer
age is a child of quantum mechanics. So is the photonics
revolution that brought us the Information Age. The creation of
quantum physics has transformed the world, bringing with it all
the benefits -- and the risks -- of a scientific revolution.
     2) The principal players in the creation of quantum theory
were young. In 1925, Wolfgang Pauli was 25 years old, Werner
Heisenberg and Enrico Fermi were 24 years old, Paul Dirac and
Pascual Jordan were 23 years old. Erwin Schroedinger, at age 36,
was a late bloomer. Max Born and Niels Bohr were older still, and
it is significant that their contributions were largely
interpretive. The profoundly radical nature of the intellectual
achievement is revealed by Einstein's reaction. Having invented
some of the key concepts that led to quantum theory, Einstein
rejected it. His paper on Bose-Einstein statistics was his last
contribution to quantum physics and his last significant
contribution to physics. That a new generation of physicists was
needed to create quantum mechanics is hardly surprising. Lord
Kelvin described why in a letter to Niels Bohr congratulating
Bohr on his 1913 paper proposing the planetary model of the atom.
Kelvin said there was much truth in Bohr's paper, but he would
never understand it himself. Kelvin recognized that radically new
physics would need to come from unfettered minds.
     3) The unique situation of quantum theory, this crucial yet
elusive theory, is perhaps best summarized by the following
observation: Quantum theory is the most precisely tested and most
successful theory in the history of science. Nevertheless, not
only was quantum mechanics deeply disturbing to its founders,
today -- 75 years after the theory was essentially cast in its
current form --  some of the luminaries of science remain
dissatisfied with its foundations and its interpretations, even
as they acknowledge its stunning power.
-----------
D. Kleppner and R. Jackiw: One hundred years of quantum physics.
(Science 11 Aug 00 289:893)
QY: Daniel Kleppner, Mass. Inst. of Technology 617-253-1000.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 1Sep00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON CHANGES IN THE DOING AND LEARNING OF QUANTUM PHYSICS
"Our understanding of atomic physics, of what we call the quantum
theory of atomic systems, had its origins at the turn of the
century and its great synthesis and resolutions in the 1920s. It
was a heroic time. It was not the doing of any one man; it
involved the collaboration of scores of scientists from many
different lands, though from first to last the deeply creative
and subtle and critical spirit of Niels Bohr guided, restrained,
deepened, and finally transmuted the enterprise. It was a period
of patient work in the laboratory, or crucial experiments and
daring action, of many false starts and many untenable
conjectures. It was a time of earnest correspondence and hurried
conferences, of debate, criticism, and brilliant mathematical
improvisations... When quantum theory was first taught in the
universities and institutes, it was taught by those who had
participated, or had been engaged spectators, in its discovery.
Some of the excitement and wonder of the discoverer was in their
teaching; now, after two or three decades, it is taught not by
the creators but by those who have learned from others who have
learned from those creators. It is taught not as history, not as
a great adventure in human understanding, but as a piece of
knowledge, as a set of techniques, as a scientific discipline to
be used by the student in understanding and exploring new
phenomena in the vast work of the advance of science, or its
application to invention and to practical ends. It has become not
a subject of curiosity and an object of study but an instrument
of the scientist to be taken for granted by him, to be used by
him, to be taught to him as a mode of action, as we teach our
children to spell and to add."
-----------
J. Robert Oppenheimer: _Science and the Common Understanding_
(Simon & Schuster, New York 1953)
(Science-Week 14 Jul 00)
-------------------
Related Background:
IN FOCUS: ON THE FOUNDATIONS OF QUANTUM MECHANICS
"The foundational aspects of physics during the first half of the
20th century have been principally concerned with the
characterization of the "elementary" constituents of matter and
the elucidation of the nature of the space-time framework in
which their interactions take place. The discovery of the
electron by Thomson, the precise characterization of its charge
by Millikan, the demonstration of the nuclear atom by Rutherford,
the photon hypothesis of Planck and Einstein, and Bohr's
explanation of the spectrum of hydrogen were some of the
landmarks of that history. These early efforts culminated in the
mid-twenties with the formulation of quantum mechanics by
Heisenberg, Dirac, and Schroedinger. The revolutionary
achievements in the period 1925 to 1927 stemmed from the
confluence of a theoretical understanding (the description of the
dynamics of microscopic particles by quantum mechanics) and the
apperception of an approximately stable ontology (electron and
nuclei). Approximately stable meant that these particles
(electrons, nuclei), the building blocks of the entities (atoms,
molecules, simple solids) that populated the domain that was
being carved out, could be treated as ahistoric objects (whose
physical characteristics were seemingly independent of their mode
of production and whose lifetimes could be considered as
essentially infinite). These entities could be assumed to be
"elementary" point-like objects that were specified by their
mass, spin, and statistics (whether bosons or fermions), and by
electromagnetic properties such as their charge and magnetic
moment. Quantum mechanics came to be seen as correctly
describing that domain of nature delineated by Planck's constant
(h): any system whose characteristic length (l), mass (m), and
time (t) were such that the product ml^(2)/t was of the order h,
and such that l/t was much smaller than c, the velocity of
light, was quantum mechanical and was to be described by the new
nonrelativistic quantum mechanics. Quantum mechanics reasserted
that the physical world presented itself hierarchically. The
world was not carved up into terrestrial, planetary, and
celestial spheres, but was layered by virtue of certain
constants of nature... Planck's constant allows the world to be
parsed into microscopic and macroscopic realms."
-----------
Silvan S. Schweber: _QED and the Men Who Made it: Dyson, Feynman,
Schwinger, and Tomonaga_
(Princeton University Press, Princeton 1994, p.xxi)
(Science-Week 24 Dec 99)
-------------------
Related Background:
IN FOCUS: ON THE IMPACT OF QUANTUM THEORY
"By the late 1920s, the interpretation of the new quantum theory
was intact. A generation of young physicists grew up with it, but
they were less interested in the problems of interpretation than
in applications. The new theory emphasized, as never before, the
paramount role of mathematics in theoretical physics. Individuals
with great technical power in abstract mathematics, and the
ability to apply it to physical problems, came to the fore. The
new quantum theory became the most powerful mathematical tool for
the explication of natural phenomena that ever fell into human
hands, an incomparable achievement in the history of science. The
theory released the intellectual energy of thousands of young
scientists in the industrial nations of the world. No single set
of ideas has ever had a greater impact on technology, and its
practical implications will continue to shape the social and
political destiny of our civilization. We have made contact with
new components of the cosmic code -- the immutable laws of the
Universe -- which are now programming our development. Practical
devices, such as the transistor, the microchip, lasers, and
cryogenic technology, have given rise to entire industries at the
vanguard of technical civilization. When the history of this
century is written, we shall see that political events -- in
spite of their immense cost in human lives and money -- will not
be the most influential events. Instead the main event will be
the first human contact with the invisible quantum world and the
subsequent biological and computer revolutions."
-----------
Heinz R. Pagels: _The Cosmic Code_
(Simon & Schuster, New York 1982)
(ScienceWeek 23 Apr 99)
For more information: http://scienceweek.com/swfr.htm

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3. PLANETARY SCIENCE: ON THE SEDIMENTARY ROCKS OF EARLY MARS
     The term "early Mars" refers to the first 600 to 1000
million years after the planet first formed, and corresponds to
the time of intense impact cratering in the Solar System and the
emergence of life on Earth. Martian geochronology is divided into
3 periods: the Noachian period, the earliest, is defined as the
period dominated by heavy impact cratering and widespread
degradation of the cratered terrains; the Hesperian period,
generally thought to be a short transitional time as the impact
rate and other geomorphic processes tapered off and major ridged
plains formed to cover considerable tracts of cratered terrain;
and the Amazonian period, the recent period that includes Mars as
it is seen today. The absolute ages of these periods are not
known, but attempts have been made to estimate the ages by
assuming that the Martian cratering rate is some function of the
lunar cratering rate. In the present context, the Noachian period
is taken as the period prior to 3.5 billion years ago, and the
Amazonian period is taken to be the period up to the present from
the time-frame of approximately 3.5 to 1.8 billion years ago.
     The Mars Global Surveyor spacecraft was launched in November
1996 and achieved orbit about Mars in September 1997. The
spacecraft carries the Mars Orbiter Camera, which consists of
three cameras: a narrow-angle system that obtains high spatial
resolution images (1.5 to 12 meters per pixel), and red and blue
wide-angle cameras to acquire regional and global views (0.24 to
7.5 kilometers per pixel).
     The term "subaerial processes" refers to processes "under
the atmosphere"; the term "eolian (aeolian) processes" refers to
processes involving wind; the term "lacustrine" refers to lakes.
... ... M.C. Malin and K.S. Edgett (Malin Space Science Systems,
US) present an analysis of apparent sedimentary rocks of early
Mars, the analysis based on photographs obtained by the Mars
Orbiter Camera. The authors make the following points:
     1) The authors point out that one of the primary questions
concerning the Noachian period is whether it was warmer and
wetter than the cold and arid Mars we see today, such that liquid
water could persist on the surface of Mars for thousands to
millions of years. Similarly, a key question regarding the
Amazonian period is whether there were climate excursions after
the present cold and dry conditions were established, climate
excursions that again allowed liquid water to persist on the
surface long enough for lakes or seas to have occupied certain
geological chasms and many impact craters around the surface of
the planet. Speculative affirmative answers to both of these
questions are widely cited to support the idea that Mars may have
had conditions favorable to the development and persistence of
life.
     2) The authors present geologic evidence that the above two
hypotheses are linked, that the materials in craters in chasms
considered for 20 years to be Amazonian in age were instead
formed in the Noachian period, that there are many more outcrops
of these materials than previously known, that they could indeed
represent sediment deposited in lakes, and that they are a small
part of a substantially more complex and previously unanticipated
Martian history.
     3) Specifically, the authors present evidence that layered
and massive outcrops on Mars, some as thick as 4 kilometers,
display the geomorphic attibutes and stratigraphic relations of
sedimentary rock. Repeated beds in some locations imply a dynamic
depositional environment during early Martian history. Subaerial
(e.g.,  eolian, impact, and volcaniclastic) and subaqueous
processes may have contributed to the formation of the layers.
The apparent affinity of these layers for impact craters suggests
dominance of lacustrine deposition; alternatively, the materials
may have been deposited in a dry subaerial setting in which
atmospheric density and variations of atmospheric density
mimicked a subaqueous depositional environment. The source
regions and transport paths for the material have apparently not
been preserved.
     4) The authors conclude: "When applied to the two questions
posed at the outset of this research article, our results show no
evidence for climate excursions in the Amazonian but do provide
evidence that can be used to support the contention that Mars in
the Noachian was warm enough to be wet enough to sustain bodies
of liquid water on its surface. But [our results] can also be
used to argue that Mars was very different from any of our
previous views."
-----------
M.C. Malin and K.S. Edgett: Sedimentary rocks of early Mars.
(Science 8 Dec 00 290:1927)
QY: Michael C. Malin: Malin Space Science Systems, PO Box 910148,
San Diego, CA 92191-0148 US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
PLANETARY SCIENCE:
NEW EVIDENCE FOR RECENT UNDERGROUND WATER ON MARS
Life as we know it requires water, so the presence or absence of
water on a planet or other astronomical body is an important
issue. As our nearest neighbor, Mars is of most interest, and
sooner or later Mars will be explored, will be visited by
astronauts and researchers who will be able to examine the
surface of Mars as the surface of the Earth has been examined.
Meanwhile, our major geological studies of Mars are photographic,
and as the photographic technology improves, new information
concerning Mars continues to become available.
... ... M.C. Malin and K.S. Edgett (Malin Space Science Systems,
US) report a high-resolution (2 to 8 meters/pixel) analysis of
more than 20,000 images relayed by the Mars Orbiter Camera since
1997. The authors make the following points:
     1) Mars is now a desert world on which liquid water, because
of ambient conditions, is not likely to be found at the surface:
average temperatures are below 273 degrees kelvin and atmospheric
pressures are at or below water's triple-point vapor pressure of
6.1 millibars. However, in 1972 the Mariner 9 orbiter mission
photographed evidence -- in the form of apparent giant flood
channels and arborized networks of small valleys -- that liquid
water might have been stable in the surface environment at some
time in the past. Analysis of Mars 4 and Mars 5 data, Viking
orbiter images (1976-1980), and observations of flood terrain by
Mars Pathfinder in 1997 supported this conclusion.
     2) The Mars Global Surveyor orbiter reached the planet in
1997, and one of the most important early results of the Mars
Orbiter Camera investigation was the absence of evidence for
precipitation-fed overland flow of water. For example, there are
no contributory rills, gullies, and/or small channels associated
with the Martian valley networks. Whatever the explanation for
the absence of these features, the possibility that liquid water
flowed across the Martian surface in a sizable volume for an
extended period of time, and especially in the recent past, now
seems quite remote.
     3) The authors, however, report that relatively young
landforms on Mars, seen in high-resolution images acquired by the
Mars Global Surveyor Mars Orbiter Camera since March 1999,
suggest the presence of sources of liquid water at shallow depths
beneath the Martian surface. Found at middle and high Martian
latitudes (particularly in the southern hemisphere), gullies
within the walls of a very small number of impact craters, south
polar pits, and two of the larger Martian valleys display
geomorphic features that can be explained by processes associated
with ground-water seepage and surface runoff. The relative youth
of the landforms is indicated by the superposition of the gullies
on otherwise geologically young surfaces, and by the absence of
superimposed landforms or cross-cutting features, including
impact craters, small polygons, and wind-formed (eolian) dunes.
The limited size and geographic distribution of the features
argue for constrained source reservoirs.
     3) The authors conclude: "Although the available evidence
suggests that the processes that created these landforms acted in
the relatively recent past and could even be contemporary, the
absence of old, degraded, or cratered examples remains a
mystery."
-----------
M.C. Malin and K.S. Edgett: Evidence for recent groundwater
seepage and surface runoff on Mars.
(Science 30 Jun 00 288:2330)
QY: Michael C. Malin, Malin Space Science Systems, PO Box 910148,
San Diego, CA 92191-0148 US.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 18Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON THE SEARCH FOR LIFE ON MARS
"There will be people on Mars long before the end of the twenty-
first century. It's inevitable, and irresistible. It might happen
before 2020. It could happen by 2011. Mars is our next frontier.
The plans are being laid now, the missions designed. The
technology exists. The latter-day equivalents of Magellan,
Columbus and Cook, and the other explorers of the age of European
expansion, are preparing themselves. The motives are many, as
always, but central for scientists is the search for life, or
former life. At stake is the issue, are we alone in the
Universe?... The first people on Mars will find the sky pink from
suspended bright red dust. The sunrises and sunsets may be even
more beautiful than ours, though they might resemble those that
follow wildfires in the Australian bush. Just before dawn on some
nights there will be water-ice clouds, high in the sky; these
will dissipate shortly after sunrise. The ground will be dry and
barren, and strewn with grey rocks. Instead of soil there will be
red dust. On many days, light winds will ripple the ground, and
during the northern winter, great storms may develop, enveloping
the planet in dust. In summer, temperatures near the equator will
rise as high as 17 degrees centigrade during the day, but at
night will plummet to minus 80 degrees, or less. Perhaps
somewhere, on the flank of a volcano, or deep in Valles
Marineris. our explorers will find a place where the ground is
damp, maybe in a fresh landslip, in the heat of summer. On that
summer's day, in that Martian spring, they might just find the
microbes that will show that Earth is not the only inhabited
planet. And you and I could still be alive to contemplate that
moment."
-----------
Malcolm Walter: _The Search for Life on Mars_
(Perseus Books, Cambridge MA 1999, p. 1 and 154)
-----------
[Malcolm Walter is at the University of Sydney (AU), and is
associated with the US National Aeronautics and Space Agency
(NASA) program directed to searching for life on Mars.]
-------------------
SCIENCE-WEEK http://scienceweek.com 26Nov99

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4. DEVELOPMENTAL BIOLOGY:
ORIGINS OF ENDOTHELIAL CELLS AND MUSCLE CELLS IN BLOOD VESSELS
     All higher animals consist of an arrangement of function-
related tissues: nervous system, muscles, glands, vascular
system, etc. These tissues consist of specialized cells,
biological units that have differentiated from less specialized
precursor cells, which in turn have differentiated from totally
unspecialized "stem cells". Indeed, programmed cell
differentiation, the specialization of biological cells for
specific functions in the multicellular colony of cells we call
the "animal", is not only the most important phenomenon in
development from embryo to adult, but in the adult animal it is
absolutely essential for the maintenance of certain tissues whose
cells need to be constantly replaced.
     What controls the paths of cell differentiation? Among the
most important controlling entities are certain "growth factors",
specific proteins that apparently result in specific gene
activations and/or inactivations, with a consequent
differentiation of cell progeny. The genome, the same in all
cells of the same animal, holds the information for every cell
type; how a cell differentiates depends on which parts of the
genome are active or inactive. Numerous growth factors have been
identified, some well-characterized and purified, and some yet to
be isolated, all of them chemical messengers in the intricate
orchestration that constitutes tissue development.
     The blood vascular system of animals is a tissue, a vast
tubular network that serves as a conduit for blood, which in
turn, among other things, serves as a transporter of oxygen to
other tissues, and a transporter of waste products from these
tissues to elimination centers. Blood is in two businesses at
once, fuel delivery and waste management, and the blood vascular
system can be thought of a vast arrangement of pipes leading to
and from every corner of the body. But this enormous and
intricate hydraulic assembly has no counterpart in human
engineering, for an important property of this biological
hydraulic system is that the diameters of all the pipes in the
system, from the smallest to the largest, are under both local
and centralized computerized control, the diameters of various
pipes changing almost immediately as function demands. These
changes in blood vessel diameter are brought about by muscle
cells enfolding the outside of each vessel, these muscle cells
controlled by both local chemical messengers and nerve impulses
from the autonomic division of the nervous system. Blood vessels
do experience passive elastic changes in diameter in response to
hydraulic pressure changes, but it is the programmed muscle-
induced changes in diameter that are of most importance in the
functioning of medium and small diameter blood vessels throughout
the body.
     The muscle cells whose contractions and relaxations control
the diameters of blood vessels are called "smooth muscle". Smooth
muscle was originally differentiated from striped ("striated")
muscle on the basis of microscopic appearance, but there are
important other differences both functional and molecular. In
general, smooth muscle is specialized for slow sustained
contractions such as those involved in the control of the
diameters of blood vessels. Striated muscle is 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.
     In blood vessels, smooth muscle cells are found in an outer
layer wrapped around the blood vessel. In general, each blood
vessel comprises a lumen (through which blood flows) and a wall
constructed of layers. The innermost layer of a blood vessel is
an arrangement of specialized cells called "endothelial cells".
In general, in animals, endothelial cells are flat cells forming
a layer lining blood vessels, lymphatic vessels, the heart, etc.)
... ... Peter Carmeliet (Katholieke Universiteit Leuven-
Gasthuisberg, BE) presents a commentary on recent research
concerning the development of blood vessels, the author making
the following points:
     1) The author points out that compared to our knowledge of
the development of other tissues, very little is known about the
development of blood vessels. The conventional notion has been
that in blood vessels the endothelial cells and smooth muscle
cells arise from separate precursor cells through a series of
cell divisions and specialization (differentiation). But this
idea has now been overturned by the work of J. Yamashita et al
(Nature 408:92 2000) (10 authors at 2 installations, JP), who
report a type of blood vessel precursor cell from which both
endothelial and smooth muscle cells can derive in both tissue
culture and mice.
     2) Yamashita et al have discovered that one type of
embryonic precursor in the mouse can give rise to either
endothelial cells or smooth muscle cells depending on the growth
factor to which the precursor cell is exposed. In response to one
growth factor (PDGF-BB), the blood vessel precursor cell
differentiates to form smooth muscle cells, with these smooth
muscle cells surrounding endothelial channels in tissue culture
and _in vivo_. In contrast, when blood vessel precursor cells are
exposed to another growth factor (VEGE), the precursor cells are
sent along a different developmental pathway to become
endothelial cells.
     3) The author (Carmeliet) points out that it is rather
surprising that a common progenitor for endothelial and smooth
muscle cells has only now been discovered, since precursors that
give rise to several distinct types of neural cell, or to the
different types of blood cell, have already been reported. In
fact, it is known that the endothelial cells that line the inner
surface of the heart share a common origin with their surrounding
cardiac muscle fibers, and it is also known that endothelial
cells can differentiate into skeletal muscle cells.
     4) Concerning the medical implications of the discovery of
Yamashita et al, the author (Carmeliet) poses the following
questions: Do the newly discovered growth-factor-directed
precursor cells contribute to the growth of smooth muscle cells
that occurs in atherosclerosis (the accumulation of lipids in,
and thickening of, arterial walls)? Are these precursor cells
involved in the formation of new blood vessels (angiogenesis)
that accompanies tumor development? Blindness results when a
certain type of cell (pericytes) are lost from blood vessels in
the retina: might it become possible to selectively shift these
newly discovered precursor cells to become pericytes?
-----------
Peter Carmeliet: One cell, two fates.
(Nature 2 Nov 00 408:43)
QY: Peter Carmeliet: peter.carmeliet@med.kuleuven.ac.be
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm

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5. MEDICAL BIOLOGY:
USE OF NEURAL STEM CELLS IN COMBATING BRAIN TUMORS
     Malignant brain tumors (malignant intracranial tumors) have
high fatality rates. In adults, 20 to 40 percent of such tumors
are spread from cancers in the breast, lung, stomach, intestines,
kidney, or any site of a cancerous skin tumor, i.e., they are
"secondary tumors". Primary brain tumors are tumors that
originate in the brain, and of these 40 percent are gliomas,
which are tumors of brain interstitial cells (glial cells), cells
which are not nerve cells but which play an important role in
maintaining nerve cell viability.
     Gliomas are virtually untreatable and inevitably lethal
despite extensive surgical excision, chemotherapy, or radiation
treatment. This treatment resistance is apparently related to the
exceptional migratory nature of such tumors and their ability to
insinuate themselves seamlessly and extensively into normal
neural tissue, often migrating great distances from the main
tumor mass.
     In this context, the term "differentiation" refers to
developmental cell specialization (morphology and biochemistry)
resulting from activation of specific parts of the cell genome,
and 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.
Recently, it has become apparent that the adult brain contains
similar stem cells (neural stem cells) that are capable of
differentiating into both new nerve cells and new glial cells.
... ... K.S. Aboody et al (12 authors at 4 installations, US) now
report the use of neural stem cells as a possible treatment
method for intracranial giiomas, the authors making the following
points:
     1) The authors point out that neural stem cells have been
recently recognized for their remarkable ability to migrate
throughout the central nervous system, become normal constituents
of the host neural tissue architecture (cytoarchitecture), and
disseminate bioactive molecules expressed a result of neural stem
cell genetic engineering.
     2) The authors report that neural stem cells, when implanted
into experimental intracranial gliomas _in vivo_ in adult
rodents, distribute themselves quickly and extensively throughout
the tumor bed and migrate uniquely in juxtaposition to widely
expanding and aggressively advancing tumor cells, while
continuing to stably express a foreign gene. The neural stem
cells "surround" the invading tumor border while "chasing down"
infiltrating tumor cells. When implanted intracranially at
distant sites from the tumor (e.g., into normal tissue, into the
contralateral hemisphere, or into the cerebral fluid spaces
(cerebral ventricles), the neural stem cells migrate through
normal tissue targeting the tumor cells (including human
*glioblastomas implanted in the rodent brain). When implanted
outside the central nervous system via the vascular system,
neural stem cells will target an intracranial tumor.
     3) The authors report that neural stem cells can deliver a
therapeutically relevant molecule (e.g., cytosine deaminase) such
that quantifiable reduction in tumor mass results. The authors
propose these data suggest the use of inherently migratory neural
stem cells as a delivery vehicle for targeting therapeutic genes
and vectors to refractory, migratory, invasive brain tumors. More
broadly, the authors suggest that neural stem cell migration can
be extensive, even in the adult brain and along nonstereotypical
routes, if tumor pathology (as modeled in their work) is present.
     4) The authors state: "Having documented this powerful
*tropic interaction between neural stem cells and intracranial
pathology, we believe that exogenous neural stem cells,
genetically engineered _ex vivo_ and strategically implanted, may
provide a "platform" for the dissemination of therapeutic genes
and/or gene products to previously inaccessible infiltrating
tumor cells."
... ... In a commentary on this work, Mark Noble (University of
Rochester, US) states: "The problems that remain to be resolved
in obtaining benefit from this novel therapeutic approach are
formidable ones. Nonetheless, the consistent failure, year after
year, to significantly increase the survival of patients with
malignant brain tumors makes it clear that obtaining dramatic
improvements in outcome in this devastating disease requires the
development of fundamentally new treatment strategies."
-----------
K.S. Aboody et al: Neural stem cells display extensive tropism
for pathology in adult brain: Evidence from intracranial gliomas.
(Proc. Natl. Acad. Sci. US 7 Nov 00 97:12846)
QY: Evan Y. Snyder: snyder@a1.tch.harvard.edu
-----------
Mark Noble: Can neural stem cells be used to track down and
destroy migratory brain tumor cells while also providing a means
of repairing tumor-associated damage?
(Proc. Natl. Acad. Sci. US 7 Nov 00 97:12393)
QY: Mark Noble: mark_noble@urmc.rochester.edu
-----------
Text Notes:
... ... *glioblastomas: A glioblastoma is a particularly
aggressive type of glioma.
... ... *tropic: From tropism. In this context, a tropism is an
affinity for specific locations, a tendency to move towards a
specific target.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY: USE OF POLIOVIRUS TO TREAT A CANCER
     In general, "glial cells" are cells of the central and
peripheral nervous system that metabolically support neurons,
with certain of such cells also producing the multiple membrane
layers called myelin and enfolding nerve cell axons with it. The
glial cells are found everywhere in the brain and spinal cord,
and they are usually categorized according to morphology.
"Astrocytes" (astroglia) are the largest glial cells, with many
extensions radiating outward like a starburst, and at least one
of their functions is apparently to maintain the so-called
"blood-brain barrier" effectively separating neural tissue from
blood.
     A malignant glioma, in general, is a cancer of any type of
glial cell, and in humans, malignant gliomas are the most common
primary tumors of the central nervous system. Such tumors are
usually diffuse and spread rapidly throughout the brain;
treatment is usually limited in effectiveness, and death usually
occurs within 1 or 2 years after first symptoms. The resistance
of malignant gliomas to conventional therapies has produced a
search for novel strategies, and recently these strategies have
involved animal viruses, either as delivery vehicles for foreign
genetic material intended to result in the self-destruction of
tumor cells, or as attenuated variants of pathogenic viral
species that can directly and specifically invade and destroy
tumor cells during the viral replication process.
     Poliovirus is an RNA virus that is the causative agent of
the human disease paralytic poliomyelitis. The majority of
poliovirus infections remain asymptomatic, but 1 to 2 percent of
such infections result in neurological complications within the
spinal cord and brainstem, the complications producing a
characteristic clinical syndrome dominated by flaccid paralysis.
Selective targeting of neurons that innervate muscle
(motorneurons) in the spinal cord by poliovirus apparently
involves a specific motorneuron cell-surface receptor (CD155),
with a contribution of certain favorable intracellular
conditions.
... ... M. Gromeier et al (5 authors at 3 installations, US) now
report that genetically engineered poliovirus (PV1RIPO) can
specifically infect and propagate in cell lines derived from
malignant gliomas. The authors make the following points:
     1) The study involved a genetically engineered (recombinant)
polio virus containing genome components of a human common cold
virus (rhinovirus type 2), the resultant genome hybrid (chimera)
characterized by exceedingly poor growth in normal neuron tissue
cultures, and the chimera virus nonpathogenic in both mice and
monkeys.
     2) The authors report that treatment of mice bearing
subcutaneous or intracerebral human glioma *xenografts with the
indicated genetically engineered polio virus halted tumor
progression and resulted in tumor elimination.
     3) The authors conclude: "This study provides evidence that
highly attenuated poliovirus/human rhinovirus type 2 chimeras
possess strong *oncolytic activity against malignant gliomas. The
neuropathogenic properties inherent to poliovirus are greatly
reduced in the recombinant poliovirus described. This *phenotype,
combined with a natural *tropism for malignant cells that express
CD155, suggests that polio/human rhinovirus type 2 chimeras may
be suitable for the treatment of malignant disease of the central
nervous system."
... ... In a commentary on the above work, Eric C. Holland (M.D.
Anderson Cancer Center Houston, US) states: "The paper by
Gromeier et al... [describes] a hybrid virus that infects and
kills clonal human glioma cell lines, in culture and *athymic
mice, without affecting nonneoplastic cells within the brain. For
those viewing this battle from a distance, the continued
unsuccessful attempts at novel therapies for this disease
[specifically, glioblastoma multiforme, the most aggressive of
the malignant gliomas] may be difficult to understand. However,
for those treating these patients, and certainly for the patients
themselves, the importance and urgency of each attempt is clear."
-----------
M. Gromeier et al: Intergeneric poliovirus recombinants for the
treatment of malignant glioma.
(Proc. Natl. Acad. Sci. US 6 Jun 00 97:6803)
QY: Eckard Wimmer [ewimmer@ms.cc.sunysb.edu]
-----------
Eric C. Holland: Glioblastoma multiforme: The terminator
(Proc. Natl. Acad. Sci. US 6 Jun 00 97:6242)
QY: Eric C. Holland [eholland@mdanderson.org]
-----------
Text Notes:
... ... *xenografts: In general, a graft of tissue from one
species into the body of another species.
... ... *oncolytic activity: In general, activity that destroys
tumor cells. 
... ... *phenotype: In this context, the term "phenotype" refers
to the specific individuality of a cell line as determined by the
interaction between its genetic constitution (genotype) and the
environment.
... ... *tropism: In this context, an affinity for specific
locations in the body.
... ... *athymic mice: An "athymic mouse" is a mouse with an
absent thymus gland. This study involved so-called "nude mice", a
mutant strain of mice lacking the thymus gland. The reported
experiments involved xenografts, in this case the grafting of
human glioma cell lines into mice, and such grafts ordinarily do
not endure long enough for experimental study because of
rejection by the host immune system. Use of mice without a thymus
gland, the maturation site of a major component of immune system
cells (immune system T lymphocytes), is one way to achieve
relatively long-lasting xenografts.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Aug00
For more information: http://scienceweek.com/swfr.htm

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6. MEDICAL BIOLOGY: ON THE P-53 TUMOR SUPPRESSOR GENE
     Nowhere is the direct link between molecular biology and
medicine more evident than in our current understanding that
cancer is essentially a disease of genes. All forms of cancer
involve uncontrolled proliferation of cells, population growth
run wild, and in each case it is apparent that one or more of the
genes that control cell proliferation have become damaged
(mutated) with a consequent appearance of cancer.
     It should be emphasized that the idea that cancer is
essentially a disease of genes does not imply that cancer is an
"inherited" disease, but simply that any factor, genetically
transmitted or resulting from specific environmental insults or
produced by internal metabolic dysfunctions -- any factor that
affects certain genes controlling cell growth may produce cancer.
A good example is ultraviolet radiation, which may cause skin
cancer if certain genes controlling cell growth are affected by
the radiation.
     The term "cell cycle" refers to the complete cycle of cell
replication: cell growth, DNA replication, division into two
daughter cells, cell growth (of daughter cells). Many genes
control cell proliferation, these genes producing proteins that
act in various ways to halt the cell cycle. Three types of genes
are now recognized to be important in limiting or promoting cell
proliferation -- with the corollary that damage to one or more of
these genes can produce cancer:
     a) Oncogenes: These genes stimulate appropriate cell growth
under normal conditions, as required, for example, by the
continued turnover and replenishment of the skin,
gastrointestinal tract, and blood cells. Cells with mutant
oncogenes continue to grow (or refuse to die) even when such
cells are receiving no growth signals. Examples are the genes
_Ras_, activated in pancreatic and colon cancers, and _Bcl-2_,
activated in lymphoid tumors.
     b) Tumor-suppressor genes: These genes keep cell numbers
down, either by inhibiting progress through the cell cycle and
thereby preventing the formation of new cells, or by promoting
programmed cell death (apoptosis). When several of these genes
are rendered non-functional through mutation, the cell becomes
malignant. Examples are the gene encoding the retinoblastoma
protein (this gene inactived in retinoblastomas), and the p53
gene, which is dysfunctional in most human cancers.
     c) Repair genes: Unlike oncogenes and tumor-suppressor
genes, repair genes do not control cell birth or cell death
directly, but they control the rate of mutation of all genes.
When repair genes are mutated, cells acquire mutations in
oncogenes and tumor-suppressor genes at an accelerated rate,
driving the initiation and progression of tumors. Examples are
*nucleotide-excision-repair genes and *mismatch-repair genes,
whose inactivation leads to susceptibility to skin and colon
tumors, respectively. 
     The p53 gene, first described in 1979, was the first tumor-
suppressor gene to be identified. It was originally believed to
be an oncogene, but genetic and functional data obtained 10 years
after its discovery demonstrated that p53 is a tumor-suppressor
gene. It is now known that the p53 protein does not function
correctly in most human cancers: in approximately half of these
tumors, the p53 protein is inactivated directly as a result of
mutations in the p53 gene; in many other cancers, the p53 protein
is inactived indirectly through binding to viral proteins, or as
a result of alterations of genes whose products interact with p53
or transmit information to or from p53.
     The p53 protein is a 53 kilodalton phosphoprotein found in
the cell nucleus, and among other things it apparently acts
negatively to regulate cell division by controlling a set of
genes required for this process. Three functional domains of the
p53 protein have been defined. The DNA-binding domain recognizes
a DNA motif in genes that are activated by p53, and mutations in
p53 that are associated with human cancers generally cluster in
the DNA-binding domain.
... ... B. Vogelstein et al (3 authors at 3 installations, US UK)
present a review of current research on the p53 gene, the authors
making the following points:
     1) The authors point out that the realization that p53 is a
common denominator in human cancer has stimulated an avalanche of
research since 1989. From 1989 until the present there have been
more than 17,000 publications focused on p53 -- 3300 in the past
year alone -- and over 10,000 tumor-associated mutations in the
p53 gene have been discovered in organisms ranging from humans to
clams. As might be expected, this work has led not only to
considerable insights into tumor development, but also to
considerable confusion and controversy. The authors suggest that
signaling pathways involving p53 -- like cellular signaling
pathways in general -- cannot be understood by looking at
isolated components. "Instead, it is essential to consider the
entangled networks into which these signaling components are
integrated."
     2) The authors point out that recent data suggest that even
a complete characterization of the "genome" (all the genes in an
organism [and in its cells]), the "transcriptome" (the genes that
are actually expressed in *messenger RNA (mRNA) at a given time),
and the "proteome" (the proteins that are produced from the
expressed genes), would not provide a very accurate portrait of
the state of the p53 protein in any cell. The condition of this
protein cannot be accurately predicted from just its sequence,
since the protein is extensively "decorated" by different
chemical groups.
     3) In addition to covalent modifications of the p53 protein,
numerous proteins bind to p53 and may modify its stability as
well as its ability to activate production of proteins involved
in regulating cell growth. Moreover, in a damaged or stressed
cell there is not a single monolithic p53 species, but rather a
variety, each species of p53 protein modified in a specific
fashion. And any detailed characterization of p53 must also
include time. The state of p53 can change rapidly as cells adapt
to the regulatory-network-initiating stimulus and respond to the
numerous feedback and feedforward systems that are thereby in
motion.
     4) The authors conclude: "The most important question in p53
research is how do we attack a cellular network that is already
compromised by inactivation of one of its most highly connected
nodes [p53]? New work suggests possible tactics for such an
attack -- and ways to dramatically affect the management of a
diverse array of cancers."
-----------
B. Vogelstein et al: Surfing the p53 network.
(Nature 16 Nov 00 408:307)
QY: Arnold J. Levine: alevine@rockvax.rockefeller.edu
-----------
Text Notes:
... ... *nucleotide-excision-repair genes: The term "excision
repair" refers to one of the intracellular mechanisms for the
repair of DNA lesions, e.g., single-strand breaks, damaged
nucleotide bases, etc. Removal of a damaged nucleotide region is
effected by two enzymes, and then the nucleotide region is
replaced (by DNA polymerase) and the polymer spliced (by DNA
ligase).
... ... *mismatch-repair genes: The term "mismatch repair" refers
to a system for the correction of errors introduced during DNA
replication when an incorrect nucleotide base, which cannot form
hydrogen bonds with the corresponding base in the parent strand,
is incorporated into the daughter strand. Specific enzymes
(excinuculeases) recognize a pair of non-hydrogen-bonded bases
and cause a segment of the polynucleotide chain to be excised,
thereby removing the mismatched bases. The resulting gap is then
filled with correct bases (by DNA polymerase 1) and the polymer
spliced (by DNA ligase).
... ... *messenger RNA (mRNA): The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MECHANISMS OF TUMOR SUPPRESSOR GENES
Cancer is fundamentally a disease of genes 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 _p53_ 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) (ScienceWeek 17 Jul 98)
For more information: http://scienceweek.com/swfr.htm

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7. IN FOCUS: CONCEPTUAL CHANGES IN PHYSICAL THEORIES
"Modern physics owes a large part of its difficulty to the
apparent inappropriateness of many of our former concepts; and to
enlarge and modify these concepts much of the labor of modern
theoretical physicists is directed. The necessity for enlarging
our ideas in natural philosophy is not surprising. To take a
simple illustration, we have but to imagine a man who, after
having lived for years in his home town out of contact with the
world at large, decided to travel. He would discover strange
people, climates, trees, and animals, of which he had never
dreamed, and he would return with a less dogmatic viewpoint. His
views would conflict with those of his fellow citizens who had
remained at home, believing the entire world to be like the
little world of their limited experience -- a belief they would
doubtless back up with arguments they would call 'logical'. It is
the same in natural philosophy. Cooped as we are in the world of
common experience, we must endeavor to break away and explore the
remoter levels, and construct theories befitting not solely the
commonplace levels, but also all those we have explored. Only
thus can knowledge (limaited at that) be acquired. Those who have
failed to explore will naturally construct theories compatible
with their restricted experience but entirely out of touch with
the wider fields which they ignore. The Greeks have given an
illustration of the stagnation of knowledge that results from a
restricted viewpoint, and it will always be to the immortal glory
of Galileo and Newton that they founded the methods of
investigation which initiated intellectual emancipation. At the
same time, the restricted viewpoint accounts for the feeling of
diffidence which the layman experiences when informed of many of
the conclusions of the modern theories, e.g., the paradoxes of
the theory of relativity. He feels that these conclusions
conflict too strongly with the notions he has formed from his
long association with the commonplace level, and, like the man
who has never left his home town, he believes that the whole
unexplored Universe should conform to the ideas he happens to
cherish. His arguments are vain, for we have seen that there is
no real conflict between the disclosures of the more advanced
theories and those drawn from our daily activities: the former
tend to merge into the latter when we pass from the remoter
levels to the level of common experience. An apparent conflict
arises only when we pursue the unjustifiable course of assuming
that all the levels are mere repetitions of the one we know
best. The greatest revolutions in modern thought have issued from
a study of the remoter levels, and they would never have arisen
had these levels been ignored."
-----------
A. d'Abro: _The Rise of the New Physics_
(Dover Publications, New York 1951, vol. 1, p.43)
-------------------
SCIENCE-WEEK http://scienceweek.com 22Dec00

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8. FROM THE SCIENCEWEEK ARCHIVE:
ON TWO CULTURES FORTY YEARS LATER
The novelist C.P. Snow (1905-1980) was a scientist before
becoming a novelist, having studied science at Leicester
University and Cambridge University. He held a position as a
tutor at Cambridge from 1935 to 1945, and during World War II, he
was chief of scientific personnel for the Ministry of Labor.
After the war, Snow became widely known for his novels about
power and prestige in the university and scientific communities,
and in 1959 he delivered what was to become a famous lecture
entitled "Two Cultures". In that lecture, Snow discussed the
dichotomy between science and literature and his belief in closer
contact between them. During the subsequent decades, the concept
was generally elaborated by the educated public to denote the
apparent deep cultural divide between the humanities and the
sciences, including that between professionals educated in these
two general areas. The phrase "Two Cultures" has often been used
to denote the divide between the scientific community and the
non-professional public in general, but that divide was not the
central focus of Snow's 1959 lecture. No matter these
distinctions, during the past 40 years the conceptual and
cultural divide between scientists and non-scientists has been a
subject of analysis, discussion, and concern. In a recent
unsigned editorial, however, the journal _Nature_ proposes that
for the most part Snow's concerns have become "gratifyingly
irrelevant". The editorial in _Nature_ makes the following
points:
     1) No one can complain, as C.P. Snow did 40 years ago, of a
lack of assimilation of science by novels, poetry, and paintings
that have been infused with science, and have wide appeal, for
that basic concern to be sustained.
     2) Few Western administrations and governments now suffer
fundamentally from a lack of scientific and technological
perspective.
     3) Although the public continues to have a low level of
scientific knowledge, the divide between the public and the
scientific community has narrowed, suggesting that scientists
willing to communicate, and science writers and publishers,
"should take their bow".
     4) Snow's prediction that the poor nations of the world will
take up technology in the 20th century has proved wrong and this
sounds a warning against optimistic technocratic naivety.
     5) However, Snow's concerns about scientific incomprehension
are as relevant as ever, as displayed in debates about the use of
genetically modified organisms, especially in Europe and parts of
the developing world.
     6) In summary: Although time has eroded many of the cultural
fissures that Snow addressed in 1959, current debates about
biotechnology highlight continuing problems of mutual
incomprehension.
-----------
[The Editors of ScienceWeek do not agree with most of the above
points made in the _Nature_ editorial. In particular, we do not
believe that the existence of more plays, novels, poetry, and
paintings apparently "infused" with science indicates any
narrowing of the divide between the Two Cultures. The enormous
increase in media density during the past four decades has
naturally produced more of everything in the media, but we
believe the divide noted by Snow is still wide in both the
university and other communities, and still a matter of concern.
We believe that in some aspects the divide is a wide and deep 
chasm, and a potential serious problem for the 21st century.]
-----------
(Nature 11 Mar 99 398:91)
QY: Editor [nature@nature.com]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 18Jun99


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