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.

February 16, 2001 -- Vol. 5 Number 7

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I can live with doubt and uncertainty and not knowing.
I think it's much more interesting to live not knowing
than to have answers which might be wrong. I have
approximate answers and possible beliefs and different
degrees of certainty about different things, but I'm not
absolutely sure of anything and there are many things
I don't know anything about...
-- Richard Feynman (1918-1988)

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=-=-=-=-=-=-=-=-=
Section 1
=-=-=-=-=-=-=-=-=

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

1. ASTROPHYSICS: ON PULSARS AND MAGNETARS
Most neutron stars are detected as "ordinary" radio pulsars with
magnetic fields of 10^(12) gauss -- 10^(12) times as strong as
the magnetic field of Earth -- and spin periods between 16
milliseconds and 8.5 seconds. The rapid rotation combines with
the strong magnetic field to produce electric forces that
generate particles moving near the speed of light. During the
past 5 years, considerable interest has focused on objects that
appear to be even more highly magnetized than typical radio
pulsars. These are the so-called "magnetars", objects with
magnetic fields that range from approximately 10^(13) to 10^(15)
gauss. (Nature 18 Jan 01 409:296)

2. EXPERIMENTAL PHYSICS: FIRST EFFECTIVE ZERO-VELOCITY LIGHT
Electromagnetically induced transparency is a quantum
interference effect that permits the propagation of light through
an otherwise opaque atomic medium. A coupling laser is used to
create the interference necessary to allow the transmission of
resonant pulses from a probe laser. This technique has previously
been used to slow and spatially compress light pulses by 7 orders
of magnitude, resulting in their complete localization and
containment within an atomic cloud. Now the same laboratory
reports the use of electromagnetically induced transparency to
bring laser pulses to a complete stop in a magnetically trapped
cold cloud of sodium atoms (approximately 11 million sodium atoms
at 0.9 microkelvins). (Nature 25 Jan 01 409:490)

3. QUANTUM PHYSICS: ON ATOMIC TUNNELING
Researchers report they have tracked and visualized the quantum
tunneling of individual atoms for the first time. By using a
scanning tunneling microscope, they were able to monitor the
motion of individual hydrogen atoms on a metal surface, and they
found that the atoms remain mobile down to temperatures as low as
9 degrees kelvin. Classically, thermal diffusion or motion is
expected to fade away as the temperature is lowered. But the
constant movement of hydrogen in these experiments implies that
there is a quantum effect that allows the atoms to tunnel along
the surface of the metal. (Nature 25 Jan 01 409:471)

4. NEUROBIOLOGY: CONTROL OF SYNAPSE NUMBER BY NEUROGLIA
New evidence demonstrates that in preparations of cultured nerve
cells few synapses form in the absence of glial cells, and that
the few synapses that do form are functionally immature. The
presence of astrocytes increases the number of mature functional
synapses on central nervous system neurons by 7-fold, and
astrocytes are required for maintenance of synapses in vitro. The
new observations are taken to demonstrate a previously unknown
function for glial cells in inducing and stabilizing central
nervous system synapses, with evidence that the number of
synapses on central nervous system neurons can be profoundly
regulated by non-neuronal signals. (Science 26 Jan 01 291:657)

5. ANTHROPOLOGY: ANCIENT DNA AND THE ORIGIN OF MODERN HUMANS
The "recent out of Africa" model of human origins, proposes that
over the period since humans began to leave Africa, there have
been several species of Homo. In this model, H. sapiens emerged
in Africa approximately 100,000 years ago and then spread
globally, replacing other species of Homo that it encountered
during the expansion. This model proposes that all current
regional morphologies, especially those outside Africa, developed
within the last 100,000 years. New data now present a serious
challenge to interpretation of contemporary human mitochondrial
DNA variation as supporting the "recent out of Africa" model.
(Proc. Natl. Acad. Sci. US 16 Jan 01 98:537)

6. MEDICAL BIOLOGY: THE PROSPECT FOR STEM CELL THERAPIES
Clinicians have exploited stem cells for therapeutic purposes for
more than 40 years. Bone marrow transplantation (hematopoietic
stem cell transplantation), for example, is life-saving for
patients with certain types of bone marrow diseases and
malignancies. But the usefulness of stem cell transplantation has
been limited by the fact that many organs (e.g., brain, spinal
cord, heart, kidney) were believed to lack detectable stem cells.
It was also believed that cells from these organs could not be
reprogrammed to differentiate into different cell types during
adulthood. Three recent discoveries have revolutionized stem cell
biology and have demonstrated the clinical potential of stem
cells in a wide range of human diseases.
(J. Amer. Med. Assoc. 7 Feb 01 285:545)

7. IN FOCUS: ON HUMAN FOSSILS AND HUMAN BRAINS

8. FROM THE SCIENCEWEEK ARCHIVE:
ON THE INVENTOR OF MODERN SCIENCE

=-=-=-=-=-=-=-=-=
Section 2
=-=-=-=-=-=-=-=-=

1. ASTROPHYSICS: ON PULSARS AND MAGNETARS
     In astrophysics, the term "nova" refers to a class of
exploding stars whose luminosity temporarily increases from
several thousand to as much as 10^(5) times its normal level.
Most novas are thought to involve special double-star systems
("close binaries"), one star a red giant and the other star a
white dwarf. If an expansion of the red giant encroaches the
gravitational domain of the white dwarf, the intense
gravitational field of the white dwarf pulls material from the
red giant, and this material accumulates on the surface of the
white dwarf until a nuclear explosion occurs.
     The term "supernova" refers to a completely different
phenomenon: a supernova is any of a class of violently exploding
stars whose luminosity after eruption suddenly increases millions
or billions of times its normal level, the supernova explosion,
unlike a nova explosion, a cataclysmic event associated with the
essential end of the active (energy-generating) life of the star.
In general, the cause of the explosion is believed to be as
follows:
     a) When a star exhausts its nuclear fuel, the star undergoes
gravitational collapse, this collapse resulting in one of 3
possible objects, depending on the mass of the collapsing star:
black hole, neutron star, white dwarf. If the mass is greater
than approximately 3 solar-masses, a black hole will result; if
the mass if less than 3 but more than approximately 1.4 solar-
masses, a neutron star will result; is the mass is less than
approximately 1.4 solar-masses, a white dwarf star will result.
     b) The core of a collapsing star of intermediate mass (1.4
to 3 solar-masses) soon consists almost entirely of neutrons, the
core with a diameter of only approximately 20 kilometers, and
with a mass equal to at least several solar-masses -- the result
a core of enormous density.
     c) It is believed that a supernova explosion occurs when
material falling in from the outer layers of the star rebounds
off the dense core, which has stopped collapsing and now presents
a hard surface (iron of enormous density) to the infalling gases.
The shock wave generated by this collision propagates outward and
blows off the outer layers of the star. When a star "goes
supernova", material equaling the material of several Suns may be
blasted into space with enough energy so that the supernova
outshines its entire home galaxy.
     The existence of neutron stars was first proposed by Lev
Landau (1908-1968) in 1932, and their relationship to supernovas
was first suggested by W. Baade (1893-1960) and F. Zwicky (1898-
1974) in 1934, who wrote the following famous sentence in a short
paper: "With all reserve we advance the view that a supernova
represents the transition of an ordinary star into a neutron star
consisting mainly of neutrons." It took 33 years for the first
apparent evidence of neutron stars to be obtained -- the objects
called "pulsars" -- a discovery made by A. Hewish and J. Bell in
1967 [see *Note #1 on (Susan) Jocelyn Bell]. Meanwhile, in 1939,
J. Robert Oppenheimer (1904-1967) and others developed the idea
of neutron star production in the cores of supernovas into an
important theory of stellar evolution.
     A "pulsar" (pulsating radio star) is any of a class of
cosmic objects that emit extremely regular pulses of radio waves,
with several such objects known to emit pulses of visible light,
x-rays, and gamma-rays as well. In general, pulsars are believed
to be rapidly rotating neutron stars. It is believed that
neutrons at the surface of the neutron star decay into protons
and electrons, and as these charged particles are released from
the surface, they enter an intense magnetic field surrounding the
star and rotate with the star. The particles accelerate to speeds
approaching the velocity of light, and the particles give off
electromagnetic radiation by "synchrotron emission" -- the
electromagnetic radiation emitted by charged particles moving in
a magnetic field at a velocity close to that of light. This
radiation is released as intense beams from the magnetic poles of
the pulsar, and since the magnetic poles do not coincide with the
rotational poles, the emitted radiation beam is rotated and
sweeps regularly past the Earth with each complete rotation (like
the rotating beam of a light-house), the result an evenly-spaced
series of pulses detected by ground-based telescopes. At present,
approximately 600 pulsars have been identified.
     On August 27, 1998, a tremendous burst of gamma-rays and x-
rays, the burst lasting approximately 5 minutes, impacted the
Earth, the burst powerful enough to produce noticeable ionization
of the Earth's atmosphere. The x-rays were found to vary with a
5.16 second period, precisely the same as that of a known active
x-ray source in a galaxy 20,000 light-years from Earth in the
constellation Aquila. Such x-ray sources are believed to be
highly magnetic rotating neutron stars, and it was suggested that
the burst was caused by a "starquake" on a neutron star with an
intense magnetic field possibly 10^(15) times larger than that of
Earth. Such stellar objects were named "magnetars", and one
proposal is that a magnetar's enormous magnetic field
occasionally cracks open the crust of the star, and this leads in
some way to the production of energetic charged particles and
gamma-rays.
... ... Jim Cordes (Cornell University, US) presents a commentary
on some recent research on pulsars, the author making the
following points concerning pulsars and magnetars:
     1) The author points out that most neutron stars are
detected as "ordinary" radio pulsars with magnetic fields of
10^(12) gauss -- 10^(12) times as strong as the magnetic field of
Earth -- and spin periods between 16 milliseconds and 8.5
seconds. The rapid rotation combines with the strong magnetic
field to produce electric forces that generate particles moving
near the speed of light. These relativistic particles radiate
intense electromagnetic waves directed along the magnetic poles
of the neutron star, which appear to an observer as pulses of
radiation as the star rotates. The magnetic field also slows the
rotation of the pulsar down through "magnetic braking", an effect
caused by the radiation carrying away the angular momentum of the
star. Ordinary pulsars remain radio "loud" for approximately 10
million years, the time it takes for the pulsar to slow down to a
spin rate at which particle creation stops.
     2) During the past 5 years, considerable interest has
focused on objects that appear to be even more highly magnetized
than typical radio pulsars. These are the so-called "magnetars",
objects with magnetic fields that range from approximately
10^(13) to 10^(15) gauss. A few magnetars have been identified in
x-ray and gamma-ray observations. Magnetars spin down much more
rapidly than radio pulsars, on timescales of 10,000 years.
     3) A combination of data from two x-ray satellites recently
led to the discovery of a very young pulsar with an unusually
high magnetic field (E. Gotthelf et al: Astrophys. J. Lett.
542:37 2000). This x-ray pulsar is associated with the supernova
remnant Kesteven 75. Although neutron stars are thought to be
created in supernova explosions, there are surprisingly few clear
examples of this. Gotthelf et al suggest that the unusual x-ray
pulsar observed by them may be a missing link between different
classes of pulsars, and that this new pulsar could provide
important clues to understanding how particles are created and
radiate in the magnetospheres surrounding neutron stars. Cordes
states: "It may turn out that many of the neutron stars in our
Galaxy are born with properties similar to this pulsar rather
than to the bulk of previously known neutron stars."
-----------
Jim Cordes: Pulsars crash the magnetar party.
(Nature 18 Jan 01 409:296)
QY: Jim Cordes: cordes@spacenet.tn.cornell.edu
-----------
Text Notes:
... ... *Note #1: It is generally agreed that [Susan] Jocelyn
Bell, who was 24 years old and Hewish's graduate student at the
time (1967), made the actual discovery of the first pulsar by
noticing unexplained pulses in radio telescope data contained in
100-foot lengths per day of paper charts, and that her discovery
was instrumental in Hewish winning his Nobel Prize in Physics in
1974, which he shared with Martin Ryle (1918-1984), a prime
figure in the development of radio-telescope astronomy. The Bell
discovery was made while Bell, Hewish, and Ryle were at Cambridge
University (UK), and the astronomer Martin Rees, who was of the
faculty at Cambridge at that time, writes of Jocelyn Bell as
follows: "Jocelyn Bell received less than her fair share of
credit for the discovery of pulsars. This happened, I think,
because of the social pressures which (then even more than now)
impeded women's careers, and lowered their scientific
aspirations. After getting her PhD, Jocelyn Bell left active
research for several years -- giving priority to her husband's
career seemed at that time the 'natural' thing to do. Had she
instead continued, and acquired 'visibility' by joining the small
cohort of radio astronomers who, over the next few years [after
1967] consolidated our knowledge of pulsars and discovered many
more -- as, almost certainly, a _man_ with her extraordinary
initial record would have done -- it is hard to believe her
achievements would have been slighted to the same extent."
[Martin Rees: _Before the Beginning_, (1997) p.263]. It has been
suggested that in an earlier age CP-1919, the first observed
pulsar, would have been called "Bell's Star". No matter the name
of the first observed pulsar, it was discovered by Susan Jocelyn
Bell (now Susan Jocelyn Bell Burnell), and there are many who
believe that the Nobel Prize in Physics of 1974 should read Ryle,
Hewish, and Bell. Bell Burnell, however, disagrees, and she has
stated: "Nobel prizes are based on long-standing research, not on
flash-in-the-pan observation by a research student. The award to
me would have debased the prize."
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ASTROPHYSICS: ON THE AGES OF PULSARS
     Neutron stars are believed to form when a massive star
exhausts its fuel and the mass of the stellar core remaining
after a consequent supernova explosion is between 1.4 solar-
masses (the Chandrasekhar limit) and 2 to 3 solar-masses. With
diameters of only 10 to 15 kilometers, intense magnetic fields
[e.g., 10^(8) tesla], and extremely rapid spin (e.g., as much as
500-700 rotations per second), young neutron stars are evidently
responsible for various intrinsic pulsation phenomena, and thus
are called "pulsars".
     Current views concerning the life and death of a star are
based primarily on quantitative models which are designed to
predict astrophysical observations, and each new set of
observations becomes a test of any extant related model. In
theory, the total energy emitted by a pulsar is a combination of
emitted radiation and outflow of particles. These particles
transfer part of their energy to the cloud of atoms surrounding
the pulsar, which forces the cloud to glow as a bright region of
ionized gas. As pulsars lose energy through emitted radiation,
their period of rotation becomes longer, so that the present
observed period of rotation depends on both the initial period
and the rate of its increase. Theoretically, if one assumes a
very fast initial period and energy loss from pure radiation
(i.e., without consideration of emitted particles), a
"characteristic age" can be calculated for a pulsar based on its
present period of pulsation. In general, it is believed the
characteristic age should be close to the true age of the pulsar,
and any set of observations which would contradict this would
have important theoretical ramifications.
... ... B.M. Gaensler and D.A. Frail (2 installations, US)
present data concerning the age of a particular pulsar (B1757-24)
determined by analysis of its motions. The authors make the
following points:
     1) The assumption that the characteristic age of a pulsar is
approximately its true age has led to some puzzling results,
including many pulsars with small characteristic ages having no
associated supernova remnants. The properties of the pulsar
B1757-24, which is located just outside the edge of a supernova
remnant, indicate that the pulsar was born at the center of the
remnant with a substantial velocity, and that it has subsequently
overtaken the expanding blast wave. With a characteristic age of
16,000 years, this pulsar is expected to have a proper motion of
63 to 80 milliarcseconds (mas) per year.
     2) The authors report observations of the nebula surrounding
pulsar B1757-24, and the observations limit the proper motion of
this pulsar to 25 milliarcseconds per year. This implies a
minimum age of 39,000 years. A more detailed analysis suggests
the true age of this pulsar may be 170,000 years, which is
significantly larger than the characteristic age. The authors
suggest from this result and from other discrepancies associated
with pulsars, that characteristic ages greatly underestimate the
true ages of pulsars.
     3) The authors conclude: "If other pulsars are indeed older
than they seem, our understanding of pulsar velocities,
asymmetries in supernova explosions, the fraction of supernovae
that produce pulsars, and the physics of neutron star structure
and cooling must be reconsidered."
     4) In a commentary on the above work, John H. Seiradakis
(University of Thessaloniki, GR) states: "This discrepancy
between the characteristic age of the pulsar [B-1757-24] and the
age of the supernova remnant poses a serious problem to either
the association between the pulsar and the supernova remnant or
[to] the common belief that the characteristic age of pulsars
represents their true age."
-----------
B.M. Gaensler and D.A. Frail: A large age for the pulsar B1757-24
from an upper limit on its proper motion.
(Nature 13 Jul 00 406:158)
QY: B.M. Gaensler [bmg@space.mit.edu]
-----------
John H. Seiradakis: Older than they look.
(Nature 13 Jul 00 406:139)
QY: John H. Seiradakis [jhs@astro.auth.gr]
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
A RADIO PULSAR THAT CHALLENGES EMISSION MODELS
*Black holes, neutron stars, and *white dwarf stars are perhaps
the three most exotic objects in the known Universe, the object
in each case the result of a gravitational collapse following
exhaustion of the fuel of a star ("star death"). According to
theory, which particular object results depends on the remnant
mass of a star following its final blow-off of gas and matter
[*Note #1]. If the remnant mass of a star is between 1.4 and 2 to
3 solar-masses, the star will collapse into a neutron star, a
body with a radius of 10 to 15 kilometers, with a core so dense
that its component protons and electrons have merged into
neutrons. The average density of a neutron star is 10^(15) grams
per cubic centimeter, and the weight of an object on the surface
of a neutron star would be 10^(11) its weight on the surface of
the Earth. Neutron stars apparently have an outer shell of iron,
but it is iron like no Earth iron, an iron of 4 orders of
magnitude greater density. Theory predicts that a neutron star
should rotate very rapidly, be extremely hot, and have an intense
magnetic field. "Radio pulsars" are apparently rotating neutron
stars that emit beams of radio waves from regions above their
magnetic poles, with the radio emission arising from the
acceleration of charged particles above the magnetic poles. As
the neutron star rotates, a beam of radio waves sweeps across the
Earth and a radio pulse is observed, much like the beam from a
lighthouse. The pulse periods of neutron stars can be measured to
an accuracy of approximately 1 part in 10^(10). Current theories
of the emission mechanism require continuous electron-*positron
pair production, with the potential responsible for accelerating
the particles inversely related to the spin period. According to
theory, production of electron-positron pairs will cease when the
potential drops below a threshold, and thus the models predict
that radio emission will cease when the pulsation period exceeds
a value that depends on the strength and configuration of the
magnetic field. For a number of years, this general scheme has
been the consensus view concerning pulsars, but new evidence has
now arrived which is in apparent serious conflict with current
ideas concerning pulsar dynamics.
... ... M.D. Young et al (3 authors at 3 installations, AU) now
report that the pulsar PSR J2144-3933, previously thought to have
a period of 2.84 seconds, actually has a period of 8.51 seconds,
which is by far the longest period of any known radio pulsar. The
authors point out that under the usual model assumptions this
slowly rotating pulsar should not be emitting a radio beam. The
authors suggest that either the model assumptions are wrong, or
current theories of radio emission must be revised. The authors
further point out that consideration of the luminosity parameters
of PSR J2144-3933 imply that we can observe only a very small
proportion of the total population of such objects in the Galaxy.
The authors conclude: "While extrapolation from the detection of
a single object is always uncertain (some would say foolhardy),
there is no reason to suppose that PSR J2144-3933 is unique. With
this caveat, this detection implies a Galactic population of
similar pulsars of the order of 10^(5), comparable to previous
estimates of the size of the total pulsar population [in our
Galaxy]."
-----------
M.D. Young et al: A radio pulsar with an 8.5-second period that
challenges emission models.
(Nature 26 Aug 99 400:848)
QY: M.D. Young [matthew@physics.uwa.edu.au]
-----------
Text Notes:
... ... *Black holes: See Note #1 below.
... ... *white dwarf stars: See Note #1 below.
... ... *Note #1: If the terminal stages of star death leave
a remnant star mass greater than 3 solar masses, the ultimate
gravitational collapse will produce a black hole, a relativistic
singularity. A black hole is a localized region of space from
which neither matter nor radiation can escape. The "trapping"
occurs because the requisite escape velocity, which can be
calculated from the relevant equations, exceeds the velocity of
light and is therefore unattainable. Another view of a black hole
is that it is a mass that has collapsed to such a small volume
that its gravity prevents the escape of all radiation. White
dwarf stars are approximately the size of Earth, but with a mass 
approximately that of the Sun. If the remnant mass after star-
death blow-off is less than 1.44 solar masses (the Chandrasekhar
limit for a star with no hydrogen content), the star collapses
into a white dwarf.
... ... *positron: The positron is the antiparticle of the
electron. It has a charge identical but opposite to that of the
electron, and a rest mass identical to that of the electron.
In general, antiparticles are homologs of elementary particles
but with opposite charge. Matter composed entirely of
antiparticles is called antimatter.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 1Oct99
For more information: http://scienceweek.com/swfr.htm

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

2. EXPERIMENTAL PHYSICS: FIRST EFFECTIVE ZERO-VELOCITY LIGHT
Experiments involving the control of light pulses in a quantum
mechanical regime hold great promise for a future technology of
quantum computing involving optical information storage and
transmission. In 1999, L.V. Hau et al succeeded in slowing light
to a velocity of 30 meters per second in an ultracold sodium gas.
Now the same laboratory reports effectively stopping light
completely for an interval of 1 millisecond before releasing the
pulse to resume normal velocity. Essentially, the phenomenon
involves "storing" the light pulse in the quantum states of the
atoms, with the light pulse reconstituted for propagation at a
later time.
... ... C. Liu et al (4 authors at 2 installations, US) report
observations of halted light pulses, the authors making the
following points:
     1) The authors point out that "*electromagnetically induced
transparency" is a quantum interference effect that permits the
propagation of light through an otherwise opaque atomic medium. A
"coupling laser" is used to create the interference necessary to
allow the transmission of resonant pulses from a "probe laser".
This technique has previously been used to slow and spatially
compress light pulses by 7 orders of magnitude, resulting in
their complete localization and containment within an atomic
cloud.
     2) The authors report the use of electromagnetically induced
transparency to bring laser pulses to a complete stop in a
magnetically trapped cold cloud of sodium atoms (approximately 11
million sodium atoms at 0.9 microkelvins). Within the spatially
localized pulse region, the atoms are in a *superposition state
determined by the amplitude and phases of the coupling and probe
laser fields. Upon sudden turn-off of the coupling laser, the
compressed probe pulse is effectively stopped, and *coherence
information initially contained in the laser fields is "frozen"
in the atomic medium for up to 1 millisecond. When the coupling
laser is turned back on, the probe pulse is regenerated: the
stored coherence is read out and transferred back into the
radiation field. The authors present a theoretical model from
which it is concluded that the system is self-adjusting to
minimize dissipative loss during the "read" and "write"
operations. The authors state: "We anticipate applications of
this phenomenon for quantum information processing."
... ... In a commentary on this work, Eric A. Cornell (University
of Colorado, US) states: "The key fact here is that as the pulse
of light penetrates into the dense region of the ultracold atomic
cloud, it turns into a "quantum coherence pattern" printed on the
sodium atoms -- the information in the light beam becomes stored
in the quantum phase relationships within the internal atom
states. In the final limit, when the pulse comes to a dead stop,
all the photons have been "imprinted" (absorbed in a fully
reversible way) into the coherence pattern. Later, when the
coupling light is turned back on, the information contained in
the pattern is read out and converted back into propagating
photons that accelerate to the conventional speed of light as
they come to the edge of the atom sample."
-----------
C. Liu et al: Observation of coherent optical information storage
in an atomic medium using halted light pulses.
(Nature 25 Jan 01 409:490)
QY: Chien Liu: chien@deas.harvard.edu
-----------
Eric A. Cornell: Stopping light in its tracks.
(Nature 25 Jan 01 409:461)
QY: Eric A. Cornell: cornell@jila.colorado.edu
-----------
Text Notes:
... ... *electromagnetically induced transparency: In his
commentary, Cornell states: "The key to slowing light is the
presence of a second laser beam, the so-called 'coupling' pulse.
Distinguishable from the propagating (or 'probe') pulse by its
polarization, the coupling light delicately adjusts the internal
energy levels of the atoms, suppressing their ability to absorb
the probe light -- in effect, a single absorption level is split
into two levels that cancel each other out. This phenomenon is
known as 'electromagnetically induced transparency'.
... ... *superposition state:  In this context, the general idea
is that the cloud of sodium atoms (335 microns by 55 microns in
this experiment), under these laser conditions, behaves almost as
a single quantum mechanical entity: the quantum states of the
atoms are superposed into a single wave function for the entire
system.
... ... *coherence information: In quantum physics, coherence
involves the 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. In general, a perfectly coherent system of
particles can be described by a single macroscopic wave function.
In general, in optics, the term "coherence" refers to the
existence of a correlation between the phases of two or more
waves. In this context, the term "coherence information" refers
to information contained in and dependent upon the coherence of
the laser pulse.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm

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3. QUANTUM PHYSICS: ON ATOMIC TUNNELING
     In 1924, Louis de Broglie (1892-1987) suggested that all
particles have wave properties in addition to particle
properties, with the wave properties given by what is now called
the "de Broglie equation": l = h/(mv), where (l) is the
wavelength of the particle, (h) is Planck's constant, (m) is the
mass of the particle, and (v) is the velocity of the particle.
This relationship provided the basis for quantum mechanics as
formulated by Erwin Schroedinger (1897-1961) in 1925-1926. In
1927, the wave nature of electrons was detected experimentally.
Macroscopic objects have a computed wavelength much smaller than
that of electrons, so the wave properties of macroscopic objects
are never detected: macroscopic objects exhibit only particle
behavior.
     In general, the term "quantum mechanical tunneling" refers
to a quantum mechanical phenomenon involving an effective
penetration of an energy barrier by a particle resulting from the
width of the barrier being less than the de Broglie wavelength of
the particle. Essentially, the idea is that the square of the
amplitude of the wavefunction of the particle determines the
probability distribution of the particle, and if the dimensions
of that probability distribution exceed the dimensions of the
barrier, there is a finite probability the particle will "tunnel"
through the energy barrier to the other side. In general, for
particles of known mass and velocity, if the height and thickness
of the energy barrier are known, this tunneling probability can
be calculated via quantum mechanics. The phenomenon of quantum
tunneling has many important applications, including explanations
of *alpha particle emission in radioactive decay, and in the
theory and engineering of the *Esaki diode (tunnel diode).
     The new technology of scanning probe microscopy has created
a revolution in microscopy, with applications ranging from
condensed matter physics to biology. The first scanning probe
microscope, the scanning tunneling microscope, was invented by G.
Binnig and H. Rohrer in the 1980s (they received the Nobel Prize
in Physics in 1986), and the invention has been the catalyst of a
technological revolution. Scanning probe microscopes have no
lenses. Instead, a "probe" tip is brought very close to the
specimen surface, and the interaction of the tip with the region
of the specimen immediately below it is measured. The type of
interaction measured essentially defines the type of scanning
probe microscopy. When the interaction measured is the force
between atoms at the end of the tip and atoms in the specimen,
the technique is called "atomic force microscopy". When the
quantum mechanical tunneling current is measured, the technique
is called "scanning tunneling microscopy". These two techniques,
atomic force microscopy (AFM) and scanning tunneling microscopy
(STM) have been the parents of a variety of scanning probe
microscopy techniques investigating a number of physical
properties. In general, in scanning tunneling microscopy,
electrons quantum mechanically tunnel between the tip and the
surface of the sample. This tunneling process is sensitive to any
overlap between the electronic wave functions of the tip and
sample, and depends exponentially on their separation. The
scanning tunneling microscope makes use of this extreme
sensitivity to distance. In practice, the tip is scanned across
the surface, while a feedback circuit continuously adjusts the
height of the tip above the sample to maintain a constant
tunneling current. The recorded trajectory of the tip creates an
image that maps the electronic wave functions at the surface,
revealing the atomic landscape in fine detail.
     In this context, the term "phonon" refers to a quantum of
vibrational energy, the quantum considered a discrete particle,
and used in mathematical models to calculate thermal and
vibrational properties of solids. This idea is essentially a
reversal of the application of the de Broglie equation to
particles: In general, any propagated wave (or field
perturbation) can be considered as a particle whose momentum (mv)
is given by the de Broglie equation as mv = h/l, where (mv) is
the momentum of the particle, h is Planck's constant, and (l) is
the wavelength of the propagated perturbation.
... ... Ali Yazdani (University of Illinois Urbana-Champaign, US)
presents a commentary on recent work (L.J. Lauhon and W. Ho:
Phys. Rev. Lett. 85:4566 2000) on tunneling of individual
hydrogen atoms on a metal surface. The author (Yazdani) makes the
following points:
     1) The author points out that in condensed matter physics,
quantum tunneling of atoms is believed to play an important role
in phenomena such as the diffusion of impurities in solids and
the properties of *glasses at low temperatures. An atom can be
described as "resting" in an energy well, and it can tunnel to
another energy well if the mass of the atom is low enough and if
the energy barrier between the wells is sufficiently small.
Because the hydrogen atom is so low in mass, it is particularly
open to the possibility of quantum tunneling. On the surface of
metals, the constant movement of hydrogen has been reported down
to low temperatures, but whether this diffusion arises from
classical thermal motion or from quantum tunneling is unclear.
Some of the uncertainty can be attributed to the fact that
previous experiments measured the average behavior of a group of
atoms, and so could not resolve the role of surface defects in
the tunneling process. A localized probe, such as the tip of a
scanning tunneling microscope, sidesteps these complications.
     2) Lauhon and Ho (2000) now report that they have tracked
and visualized the quantum tunneling of individual atoms for the
first time. By using a scanning tunneling microscope, they were
able to monitor the motion of individual hydrogen atoms on a
metal surface, and they found that the atoms remain mobile down
to temperatures as low as 9 degrees kelvin. Classically, thermal
diffusion or motion is expected to fade away as the temperature
is lowered. But the constant movement of hydrogen in these
experiments implies that there is a quantum effect that allows
the atoms to tunnel along the surface of the metal. Quantum
tunneling of atoms at low temperatures has been inferred from
experiments on relatively large groups of atoms, but never before
has quantum motion been observed so directly -- one atom at a
time.
     3) By detailed analysis of the scanning-tunneling-microscope
-measured diffusion rate for hydrogen, Lauhon and Ho identify
different temperature regimes in which phonon- or electron-
*scattering predominates. Most intriguing is their observation
that at the lower temperatures in the experiment, the tunneling
rate increases as the surface is cooled. This classically
impossible behavior suggests that hydrogen tunneling improves
over longer periods of time as the surface gets colder. The
author (Yazdani) suggests that perhaps reducing the temperature
by a further factor of 10 or 100 will reveal a new regime in
which hydrogen atoms can eventually tunnel over greater
distances.
-----------
Ali Yazdani: Watching an atom tunnel.
(Nature 25 Jan 01 409:471)
QY: Ali Yazdani: ayazdani@uiuc.edu
-----------
Text Notes:
... ... *alpha particle emission in radioactive decay: In
radioactive decay alpha particle emission, a nucleus emits an
alpha particle (a helium nucleus). The alpha particle has
insufficient energy as a particle to overcome the force barrier
surrounding the nucleus, but as a wave the particle can tunnel
through the barrier, i.e., the particle has a finite probability
of being found outside the nucleus. The quantum explanation of
alpha particle emission in radioactive decay was provided
independently by George Gamow (1904-1968) and by Ronald W. Gurney
(?-?) and Edward Condon (1902-1974) in 1928.
... ... *Esaki diode: A semiconductor electron-hole (p-n)
junction diode based on the tunnel effect. The device has a
current-voltage curve described by a cubic equation, with one
limited region of the curve showing a "negative resistance",
i.e., the current falling as the bias voltage is increased.
... ... *glasses: In this context, the term "glass" refers to an
amorphous solid whose atoms form a random network.
... ... *scattering: In this context, the term "scattering"
refers to the change in direction of a particle resulting from
collision with another particle.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

4. NEUROBIOLOGY: CONTROL OF SYNAPSE NUMBER BY NEUROGLIA
     In general, nerve cells in the central and peripheral
nervous systems of mammals (including humans) are surrounded by
satellite cells that play various roles in neural function. In
the central nervous system, these satellite cells are called
"neuroglial cells" (glial cells), and they constitute
approximately one-half of the volume of the human brain and
greatly outnumber neurons in the brain. Neurons and glial cells
in the brain are densely packed together, their surface membranes
separated from each other by fluid-filled extracellular spaces
approximately 20 nanometers wide. Glial cell membranes, like
those of neurons, contain channels for ions, receptors for
transmitter substances, ion transport pumps, and amino-acid
transporters. In addition, many glial cells are linked to each
other by low-resistance junctions that permit direct passage of
ions and small molecules. Glial cells usually have more negative
resting potentials than neurons, but glial cells do not generate
action potentials.
     So-called "protoplasmic astrocytes" are a type of glial cell
with many protoplasmic extensions, and they are abundant in brain
cortex around nerve cell bodies, dendrites, and synapses [*Note
#1].
     Although neuroglial cells in the brain have been known and
categorized since the 19th century, until recently their various
involvements in the functioning of neurons in the brain have been
unclear and enigmatic. The earliest idea, first proposed in the
19th century, was that glial cells in the brain existed simply to
"hold up" the neurons of the brain ("stutzfunktion"). By the
middle of the 20th century, neuroglia were believed to have
important but still unspecified metabolic roles. During the last
decade, the work of many laboratories has provided a more
detailed accounting of the involvements of neuroglia in the
activity of neurons, and there have been a number of surprises.
     In this context, the term "plasticity" refers to that
ability of neurons (or synapses) to modify behavior as the result
of past inputs. Currently, most neurobiologists believe that the
plasticity of synapses is an important component of learning and
memory in the mammalian brain.
... ... E.M. Ullian et al (4 authors at Stanford University, US)
now report analyses by histological, electrophysiological, and
optical techniques that indicate that in preparations of cultured
nerve cells (retinal ganglion cells) few synapses form in the
absence of glial cells, and that the few synapses that do form
are functionally immature. The presence of astrocytes increases
the number of mature functional synapses on central nervous
system neurons by 7-fold, and astrocytes are required for
maintenance of synapses in vitro. The authors also demonstrate
that in vivo most synapses are generated concurrently with the
development of glial cells. The authors suggest these data a)
demonstrate a previously unknown function for glial cells in
inducing and stabilizing central nervous system synapses; b)
demonstrate that the number of synapses on central nervous system
neurons can be profoundly regulated by non-neuronal signals; and
c) raise the possibility that glial cells may actively
participate in synaptic plasticity.
-----------
E.M. Ullian et al: Control of synapse number by glia.
(Science 26 Jan 01 291:657)
QY: Erik M. Ullian: emu@stanford.edu
-----------
Text Notes:
... ... *Note #1: In general, nerve cells have a single long
extension (the "axon") that propagates the electrical output (the
*action potential) of the cell. The general input extensions of
nerve cells are called "dendrites", and they may be extensively
branched. Dendrites generally receive input and axons generally
propagate output, but the electrical architecture of most neurons
is complicated, and in many types of nerve cells activation of
the axon produces electrical activity that not only propagates
down the axon but also propagates backward through the cell body
and dendrites. The term "synapse" refers to the junction between
the terminal of a neuron's axon and another neuron (or muscle
cell, if the synapse is a neuromuscular junction), and the number
of synapses on any neuron may range from a few to thousands, the
junctions scattered over the dendrites and cell body of the post-
synaptic nerve cell. The general scheme of neural network
activity is that output propagated along an axon ultimately
causes secretion of a "transmitter substance" at the termination
of that axon, the transmitter substance diffusing into the
synaptic junction to interact with the surface membrane of the
post-synaptic neuron, the result a production of excitation or
inhibition of the post-synaptic neuron, depending on the type of
transmitter substance.
... ... *action potential: (nerve impulses) In general,
transient pulses (e.g., 1 millisecond) of reversed membrane
potential propagated over the long extensions of neurons (axons).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY:
ON DIRECT INVOLVEMENT OF BRAIN GLIA IN INFORMATION NETWORKS
     In the middle of the 19th century, the anatomist Rudolf
Virchow (1821-1902) recognized that cells in the brain could be
categorized into two distinct groups: a) neurons (nerve cells),
and b) a far more numerous group of cells that appear to surround
the neurons and fill the spaces between them. Virchow called this
second category of cell the "neuroglia", or "nerve glue", the
idea being that one of the functions of these cells is to hold
the neurons in place ("stutzfunktion"). Although this gluing
function of neuroglia (glia; glial cells) was long ago abandoned
for lack of evidence, the name of these cells has survived.
     Glial cells are in turn subdivided into several classes
based on their appearance in the microscope. In the central
nervous system, the two main types of glial cells are the
"astrocytes" and the "oligodendrocytes". Astrocytes have a star-
like appearance, with numerous long processes radiating out from
a central cell body; the oligodendrocytes also have a central
cell body, but with radial arms that tend to be shorter and more
branched than those of the astrocytes.
     Because glia do not generate *action potentials and do not
have *axons, they were initially thought incapable of propagating
neural impulses. In recent years, however, calcium-imaging
studies have demonstrated that astrocytes are capable of
propagating cellular signals as waves of intracellular calcium
changes that spread from astrocyte to astrocyte. Furthermore,
calcium waves through astrocyte networks have been shown to
influence the activity of adjacent neurons and modulate *synaptic
transmission.
     Glutamate, the anion of glutamic acid (one of the amino acid
components of proteins), is an *excitatory neurotransmitter
substance of considerable importance in the brain, and there is
increasing evidence that glutamate released by astrocytes may
affect the behavior of nerve cells and thus provide a link
between propagated astrocyte events and propagated neuronal
events.
     The term "flash photolysis" refers to a technique for
producing intracellular changes in calcium ion concentration, the
technique based on the use of "calcium cage" molecules which are
taken up by biological cells, the caged calcium subsequently
released by exposure of the cells to a short-duration (e.g.
several nanoseconds) laser pulse.
... ... V. Parpura and P.G. Haydon (Iowa State University, US)
present a study of glutamate release by astrocytes, the authors
making the following points:
     1) The authors point out that astrocytes can release
glutamate in a calcium-dependent manner and consequently signal
to adjacent neurons. Whether this glutamate release pathway is
used during physiological signaling or is involved only under
pathophysiological conditions is not clear. One reason for this
lack of understanding is the limited knowledge concerning the
levels of calcium necessary to stimulate release from astrocytes,
and how these levels compare with the range of physiological
calcium levels in these cells.
     2) The authors report they used flash photolysis to raise
internal calcium in astrocytes, while monitoring astrocytic
calcium levels and glutamate. The changes in astrocytes caused
slow inward electrical currents in single neurons grown on micro-
islands of astrocytes in a tissue culture preparation.
     3) The authors suggest that with their approach they have
demonstrated that modest changes of astrocyte calcium (from 84 to
140 nanomoles) result in substantial glutamate-dependent
("glutamatergic") currents in neighboring neurons. Since various
neurotransmitters (e.g., glutamate, norepinephrine, dopamine) all
raise calcium in astrocytes to levels exceeding 1.8 micromolar,
the authors suggest their quantitative studies also demonstrate
that the astrocytic glutamate release pathway is engaged at
physiological levels of internal calcium. "Consequently, the
calcium-dependent release of glutamate from astrocytes functions
within an appropriate range of astrocytic calcium levels to be
used as a signaling pathway within the functional nervous
system."
... ... In a commentary on the above work, Joseph J. LoTurco
(University of Connecticut Storrs, US) states: "The most
challenging and important questions to be addressed in the future
relate to specifying exactly what aspects of neural processing
are determined and shaped by glia. For example, do they
participate in *synaptic plasticity, or do they shape *receptive
fields? Ultimately, experiments will have to be designed in which
glia are selectively removed from or silenced in central nervous
system circuits. Answers to these and other questions will likely
reshape our view of neural circuits in the next century from
exclusively neuronal to glial/neuronal circuits."
-----------
V. Parpura and P.G. Haydon: Physiological astrocytic calcium
levels stimulate glutamate release to modulate adjacent neurons.
(Proc. Natl. Acad. Sci. US 18 Jul 00 97:8629)
QY: Vladimir Parpura: vlad@iastate.edu
-----------
Joseph J. LoTurco: Neural circuits in the 21 century: Synaptic
networks of neurons and glia.
(Proc. Natl. Acad. Sci. US 18 Jul 00 97:8196)
QY: Joseph J. LoTurco: LoTurco@oracle.prib.uconn.edu
-----------
Text Notes:
... ... *action potentials: See main report.
... ... *axons: See main report.
... ... *synaptic transmission: See main report.
... ... *excitatory neurotransmitter substance: See main report.
... ... *synaptic plasticity: See main report.
... ... *receptive fields: In all higher animals, each array of
sensory receptors constituting a sensory organ projects activity
to a corresponding array of neurons in the central nervous
system. In many cases, both the sensory receptor array and the
central nervous system neuron array are more or less two
dimensional. The term "receptive fields", in this context, refers
to groups of neurons in the central nervous system receiving
direct or indirect isomorphic input from corresponding sensory
receptors in the periphery. (The term "receptive field" is also
used to describe an array of receptors in a sense organ.)
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 25Aug00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
A SPECIFIC GLIAL-NEURONAL SIGNALING PATHWAY
... ... L-L. Yuan and B. Ganetzky (University of Wisconsin
Madison, US) now report that in the fruit fly Drosophila a
specific gene (axotactin) encodes a member of the *neurexin
protein superfamily, the protein secreted by glia and
subsequently localized to *axonal tracts. Null mutation (i.e.,
elimination of the gene by mutation) caused temperature sensitive
paralysis and a corresponding blockade of axonal conduction. The
authors suggest that the protein expressed by this gene (the
protein denoted as AXO) appears to be a component of a glial-
neuronal signaling mechanism that helps to determine the membrane
electrical properties of target axons. 
-----------
L-L. Yuan and B. Ganetzky: A glial-neuronal signaling pathway
revealed by mutations in a neurexin-related protein.
(Science 26 Feb 99 283:1343)
QY: Barry Ganetzky: ganetzky@facstaff.wisc.edu
-----------
Text Notes:
... ... *neurexin protein superfamily: Neurexins are a family of
neuronal cell surface proteins with apparent roles in cell
adhesion and intercellular signaling. Three distinct genes
encoding neurexins have been identified in vertebrates. The
neurexins have been grouped with several other proteins into a
"superfamily". In general, in this context, a "superfamily" is
any group of genes and their cognate proteins that can be related
by sequence homology.
... ... *axonal tracts: Axons transmitting information to distal
regions are usually grouped, and in the central nervous system
the groupings are called "tracts".
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 14May99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
SECRETION OF GLUTAMATE BY BRAIN ASTROCYTES
Glial cells are more numerous than neurons in the brain, but
their function has been generally characterized as "metabolic" or
"supportive", without much discussion of details, and more is
known about peripheral glial cells than glial cells in the
central nervous system. Astrocytes 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. ... Kainic acid, an algal neurotoxin, is a structural
analogue of glutamate, and it has been extensively used in
research, since at high concentrations it selectively destroys
glutamate receptor neurons (glutaminergic neurons). Glutamate is
known to act on 3 classes of receptors, one of them called the
kainate receptor because at low concentrations of kainic acid the
action of glutamate on this receptor is enhanced. The chemistry
of this kainate receptor is not yet well-characterized, mainly
because selective ligands for it are not known. Another class of
glutamate receptor is the AMPA receptor [AMPA = (RS)-alpha-amino-
3-hydroxy-5-methyl-4-isoxazoleproprionic acid], and the third is
NMDA (N-methyl-D-aspartate). These 3 receptors are ionotropic,
i.e., their activation produces changes in membrane ion
permeability. According to another and more recent scheme of
glutamate receptor classification, one receptor type is
AMPA/kainate (ionotropic), another receptor type is NMDA
(ionotropic), and a third receptor type is a slow-acting receptor
type coupled to G-proteins and called metabotropic receptors.
(The G-proteins are membrane-bound proteins that act as
transducers between messenger molecules interacting with the cell
surface and the intracellular messenger system). Prostaglandins
are fatty acids secreted by cells that have hormone-like actions
in the immediate vicinity, and one circumstance that produces
their release is tissue injury.
... ... Bezzi et al (8 authors at 2 installations, IT) report
that coactivation of the AMPA/kainate and metabotropic glutamate
receptors on astrocytes stimulates these cells to release
glutamate through a calcium-dependent process mediated by
prostaglandins. The authors suggest their results reveal a new
pathway of regulated transmitter release from astrocytes, and
that interactions between neurons and astrocytes may play a
critical role in synaptic plasticity and neurotoxicity. They also
suggest that the prostaglandin-mediated glutamate release from
astrocytes may be involved in the pathophysiology of various
brain diseases and injuries.
-----------
QY: Andrea Volterra: andrea.volterra@unimi.it
(Nature 15 Jan 98) (Science-Week 30 Jan 98)
For more information: http://scienceweek.com/swfr.htm

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

5. ANTHROPOLOGY: ANCIENT DNA AND THE ORIGIN OF MODERN HUMANS
     Mitochondria are double-membrane enclosed organelles of
cells, the mitochondria involved with several important
biochemical pathways, including electron transport and oxidative
metabolism. Various types of cells containing internal membrane-
bound organelles (eukaryotic cells) may contain from a few to
several thousand mitochondria in each cell type. The mitochondria
are relatively large cylindrical structures up to 10 microns long
and up to 2 microns in diameter, and most biologists believe
mitochondria are cell organelles that may have originated as
separate organisms that became resident in eukaryotic cells.
Mitochondrial DNA is independent of nuclear DNA, consisting of a
circular molecule, 16,569 base pairs long in humans, with a known
nucleotide sequence.
     Investigations of human mitochondrial DNA have revealed two
facts relevant to questions of human origins: a) the variation
among modern human populations is small compared, for example, to
that between apes and monkeys, which has been interpreted to
indicate the recency of human origins; b) there is a distinction
between African and other human mitochondrial types, which has
been interpreted to indicate the relative antiquity of the
African peoples and the relative recency of other human
populations.
     Interpretations of mitochondrial DNA evidence have been much
debated in anthropology. Such evidence is a crucial part of the
"single origin" model of human origins, which proposes that one
early population of modern humans spread out of Africa
approximately 60,000 to 100,000 years ago and eventually replaced
all less modern populations of the genus Homo worldwide. Thus,
the difference between "African" and "non-African" mitochondrial
DNA is explained by the idea that small "founder" populations
left Africa, carrying with them only a small sample of the
genetic variation found in Africa as a whole, and that such
founder populations then expanded as they occupied Eurasia,
growing into a large population with a distinctly non-African
mitochondrial DNA structure. This idea became popular in the late
1980s, when it was called the "Mitochondrial Eve" or "Out of
Africa" hypothesis. Although since then this hypothesis has lost
some support, it is still one of the major ideas concerning human
origins.
     Support for the opposing "regional-continuity" model is
based primarily on evidence of gradual morphological change,
mainly of the skull, from ancient to modern inhabitants in
different parts of the world. In this scenario, modern humans
developed almost simultaneously in various geographical regions
around the world, replacing less evolved Homo species beginning
approximately 1.5 million years ago.
     These are only the general outlines of a hotly debated
complex area of research in human evolution.
... ... G.J. Adcock et al (7 authors at 3 installations, AU)
present a report of a study of mitochondrial DNA sequences in
ancient Australians of modern morphology, the authors making the
following points:
     1) The authors point out that since its beginning more than
25 years ago, the debate over recent human origins has focused on
two models. The regional-continuity hypothesis postulates that
ever since humans began to migrate out of Africa more than 1.5
million years ago, there has been a single evolving species, Homo
sapiens, distributed throughout the Old World, with all regional
populations connected, as they are today, by gene flow. Some
skeletal features developed and persisted for varying periods in
the different regions, so that recognizable regional morphologies
have developed in Africa, Europe, and Asia.
     2) The other view, the "recent out of Africa" model, argues
that over the period since humans began to leave Africa, there
have been several species of Homo. In this model, H. sapiens
emerged in Africa approximately 100,000 years ago and then spread
globally, replacing other species of Homo that it encountered
during the expansion. This model proposes that all current
regional morphologies, especially those outside Africa, developed
within the last 100,000 years.
     3) These alternative models arose from interpretations of
morphological evidence. During the last 15 years, molecular data,
particularly nucleotide sequences drawn from populations of
living humans, have made an increasing contribution to the
debate. Analysis has demonstrated that humans have remarkably
little mitochondrial DNA sequence variation, and that the
earliest branching lineages are found in East Africa. These
findings were interpreted as strongly supporting the "recent out
of Africa" model. The authors suggest, however, that this
interpretation fails to recognize that the demographic history of
a species cannot be inferred from the pattern of variation of a
single nucleotide segment. Patterns of variation in different
regions of the genome must be considered and interpreted in the
context of paleontological and archeological evidence.
     4) The authors report mitochondrial DNA sequence evidence
from 10 fossils, all agreed to be anatomically modern, rather
than archaic, Homo sapiens (4 "*gracile" and 6 "*robust"
specimens). The 10 fossils range in age from less than 10,000
years ago to approximately 60,000 years ago. The authors report
that in one fossil (Lake Mungo 3, dated at 60,000 years ago), the
mitochondrial DNA sequence is the most divergent of all of the
Australian fossils analyzed, and this is evidently an example of
a mitochondrial DNA lineage that existed in an ancient modern
human but is absent in living human mitochondria. The authors
state: "Our data present a serious challenge to interpretation of
contemporary human mitochondrial DNA variation as supporting the
'recent out of Africa' model. A separate mitochondrial DNA
lineage in an individual whose morphology is within the
contemporary range and who lived in Australia would imply [from
the out of Africa model and its usage of mitochondrial DNA data]
both that anatomically modern humans were among those that were
replaced and that part of the replacement occurred in Australia."
... ...  In a commentary on this work, John H. Relethford (State
University of New York College of Oneonta, US) states: "If the
mitochondrial DNA present in a modern human (Lake Mungo 3) can
become extinct, then perhaps something similar happened to the
mitochondrial DNA of *Neanderthals. If so, then the absence of
Neanderthal mitochondrial DNA in living humans does not reject
the possibility of _some_ genetic continuity with modern
humans... The modern human origins debate can be informed by
genetic data, both living and ancient, but can only be resolved
by also considering the fossil and archeological evidence. The
picture presented by Adcock et al suggests that modern human
origins were more complicated than once envisioned."
-----------
G.J. Adcock et al: Mitochondrial DNA sequences in ancient
Australians: Implications for modern human origins.
(Proc. Natl. Acad. Sci. US 16 Jan 01 98:537)
QY: W. James Peacock: jim.peacock@pi.csiro.au
-----------
John H. Relethford: Ancient DNA and the origin of modern humans.
(Proc. Natl. Acad. Sci. US 16 Jan 01 98:390)
QY: John H. Relethford: relethjh@oneonta.edu
-----------
Text Notes:
... ... *gracile: In general, a Homo fossil with a lightly built
skull. The Lake Mungo 3 fossil is a gracile specimen.
... ... *robust: In general, a Homo fossil with a heavily built
skull.
... ... *Neanderthals: See background material below.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ANTHROPOLOGY: RECOMBINATION IN HOMINID MITOCHONDRIAL DNA
     The origin of modern humans is an ongoing major focus of
research in anthropology and paleontology, and also a research
area that has seen its share of contentious disputes. There are
two conflicting views concerning the geographic aspects of human
origins: 1) in one view, the geographic origins of modern man are
multiple, with modern man (Homo sapiens) appearing more or less
at the same time on various continents; while in the second view
b) modern man originated in Africa approximately 200,000 years
ago, with modern humans migrating from Africa to the rest of the
globe.
     The major evidence for the "Out of Africa" hypothesis was
published in the late 1980s by R.L. Cann et al (1987), the
evidence based primarily on analysis of mitochondrial DNA in
diverse existing human groups...
     In the late 1980s, most anthropologists and paleontologists
believed that the mitochondria of sperm cells do not enter the
egg cell (or if they do, are quickly destroyed upon entry), so
that male sperm mitochondrial DNA does not mix (*recombine) with
female egg mitochondrial DNA. The idea, therefore, was that
mitochondrial DNA is of pure maternal lineage, and since analysis
of human mitochondrial DNA suggested a single origin of Homo
sapiens in Africa, the notion of an "African Eve" was quickly
publicized by the popular media [*Note #1]
     In recent years, however, the notion that mitochondria are
of pure maternal lineage has been challenged, and the dispute
among anthropologists and paleontologists concerning multiple-
origins vs. a single-origin for Homo sapiens has flared up again.
... ... P. Awadalla et al (3 authors at 2 installations, UK) now
present an analysis of possible DNA recombination in human and
chimpanzee mitochondrial genomes, the authors making the
following points:
     1) The authors point out that for many years it has been
accepted that mitochondria are inherited exclusively from the
mother in mammals, and that the inheritance of mitochondrial DNA
is therefore "clonal". This assumption has been used extensively
to date events in human prehistory, including the age of our last
common female ancestor, called "Eve", and to date the spread of
Homo sapiens in Asia and Europe. However, mitochondria do contain
the enzymes necessary for *homologous recombination, and there
are at least two routes by which the rule of strict maternal
inheritance of mitochondrial DNA could be broken: a) the entrance
of paternal mitochondria into the egg cell at fertilization
[*Note #2]; and b) the transfer of nuclear genome copies of
mitochondrial DNA sequences back to mitochondrial DNA.
     2) The authors suggest that the assumption that human
mitochondrial DNA is inherited from one parent only and therefore
does not recombine is questionable. The work of the authors
indicates that *linkage disequilibrium in human and chimpanzee
mitochondrial DNA declines as a function of the distance between
genome sites, and this pattern can be attributed to one mechanism
only: recombination.
     3) The authors conclude: "Many inferences about the pattern
and tempo of human evolution and mtDNA evolution have been based
on the assumption of clonal inheritance. These inferences will
now have to be reconsidered."
-----------
P. Awadalla et al: Linkage disequilibrium and recombination in
hominid mitochondrial DNA.
(Science 24 Dec 99 286:2524)
QY: Adam Eyre-Walker: a.c.eyre-walker@sussex.ac.uk
-----------
Text Notes:
... ... *recombine: In this context, the term "recombination"
refers to a genome with a combination of genes other than those
that occurred in the precursor genome(s), the recombination, in
this context, produced naturally. Thus, if mitochondrial DNA has
naturally spliced into it one or more sequences of nuclear DNA or
DNA from another line of mitochondria, the mix is called
"recombination". (See note below on "homologous recombination".)
... ... *Note #1: Apart from its proposed exclusive maternal
lineage (which has now been challenged), mitochondrial DNA has a
number of research advantages: a) The complete nucleotide
sequence of human mitochondrial DNA is known, the genome
identified as a circular DNA molecule of 16,569 base pairs. b)
Since there are as much as thousands of copies of mitochondrial
DNA per cell, mitochondrial DNA can be more easily isolated from
human tissues than nuclear DNA, which has only two copies per
cell. c) It is believed that mutations occur in mitochondria 10
times more frequently than in nuclear DNA, and the consequent
rapid evolution of the mitochondrial genome enables comparisons
between groups that would be more difficult to differentiate
using slower and more complex nuclear DNA sequences.
... ... *homologous recombination: In general, the term
"homologous recombination" refers to genetic recombination that
occurs between DNAs with long stretches of homology, and which is
mediated by certain enzymes involved in DNA repair and
replication. In this context, the terms "homologous" and
"homology" refer to sequences having fundamental similarities due
to the same evolutionary origin, even if the functions of the two
sequences are quite different.
... ... *Note #2: See relevant background material below.
... ... *linkage disequilibrium: In this context, the term
"linkage" refers to gene sequences (genetic loci) that tend to be
inherited together more often than would be expected by chance.
Genetic linkage is a reflection of the physical location of the
loci on the same chromosome segment or DNA molecule. Loci which
are close together are less likely to be separated by
recombination and are therefore more likely to be inherited
together. The distance between linked loci is measured in terms
of the frequency of recombination events occurring between them.
The term "linkage disequilibrium" refers to a situation in which
a particular combination of gene variants (alleles) at two
closely linked loci appears more frequently than would be
expected by chance. The essential idea of the authors in this
report is that recombination can be detected by considering the
relation between linkage disequilibrium and gene loci distance
(genetic distance). As the distance between loci increases, the
effect of recombination should increase, and recombination should
therefore manifest itself as a significant decline in linkage
disequilibrium with distance. The study of the authors consisted
of analysis of previously published data concerning mtDNA
sequences in humans and chimpanzees (Pan troglodytes).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 4Feb00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON MITOCHONDRIA, DNA, AND SPERM CELLS
... During the maturation of sperm cells in the human testes
(spermiogenesis), the mitochondria of sperm cells are relocated:
the mature sperm cell consists of 3 parts, the head, midpiece,
and tail (flagellum), and all the mitochondria are densely packed
into the midpiece of the mature sperm cell.
     One of the major techniques used to investigate ancient
human lineages involves the genetic analysis of mitochondrial
DNA, with such DNA considered to be primarily of maternal origin.
However, there is apparently some confusion about the reasons for
the primarily maternal origin of mitochondrial DNA. For example,
the 1998 textbook _Principles of Human Evolution_ by Roger Lewin
(Harvard University, US) [*Note #1] contains on page 414 an
illustrative drawing depicting the fate of sperm mitochondria,
the drawing showing the midpiece and tail of the sperm cell
"discarded" upon fertilization of the egg cell. The drawing has
the following caption: "Unlike nuclear DNA, for which we inherit
half from our mother and half from our father, mitochondrial DNA
is passed on only by females. When the sperm fertilizes the egg,
it leaves behind all of its mitochondria: the developing fetus
therefore inherits mitochondria only from the mother's egg."
     The above presentation by Lewin contradicts current
information in cell biology. The idea that sperm lose their
mitochondria at fertilization as a result of extracellular
"discard" of the midpiece and tail is not correct. The current
view in cell biology is that the entire human sperm cell (head,
midpiece, and tail) penetrates the egg cell during the
fertilization process. Sperm mitochondria are apparently lost
(destroyed) shortly after penetration of the egg by specific
enzymatic reactions, but the destruction of sperm mitochondria
inside the egg cell is believed to be not always complete. The
current view in cell biology is that since the sperm mitochondria
and the sperm flagellum disintegrate inside the egg, very few, if
any, sperm-derived mitochondria are found in developing or adult
organisms. In mice it is estimated that only 1 out of every
10,000 mitochondria are sperm-derived. Nevertheless, the
significance of contaminating paternal mitochondria in the use of
mitochondrial DNA to establish genetic lineages is in controversy
in the literature, and the issue is not yet resolved [*Note #2].
[The Editors wish to thank James M. Cummins, Murdoch University
(AU) for calling our attention to the question of the fate of
sperm cell mitochondria.]
-----------
By the Editors of SCIENCE-WEEK [http://scienceweek.com] 14Jan00
-----------
Text Notes:
... ... *Note #1: Roger Lewin: Principles of Human Evolution,
Blackwell Science, 1998, p.414.
... ... *Note #2: For additional material, cf. F. Ankel-Simons
and J.M. Cummins (Proc. Natl. Acad. Sci. US 1996 93:13859) and
Jim Cummins (Rev. of Reproduction 1998 3:172).
-------------------
Related Background:
PALEOLITHIC HUMAN POPULATION EXPANSION IN AFRICA
Human populations have undergone dramatic expansions in size, but
other than the growth associated with agriculture, the dates and
magnitudes of those expansions have never been resolved. Genetic
approaches to the study of human population expansions have
focused on variation at a single genetic locus, the "control
region" of *mitochondrial DNA. But in the study of demographic
history, single-locus investigations suffer from pronounced
statistical and biological limitations. The statistical problem
is that the conclusions rely on only one particular realization
of a gene genealogy, the "tree" determining the ancestral
relationships among a set of *alleles. The biological problem is
that there are a large number of functional genes in the
mitochondrion, and due to a complete linkage, a selective sweep
for any one of the genes may lead to a spurious signal of
expansion. ... ... Reich and Goldstein (University of Oxford, UK)
present two new statistical tests for population expansion, using
variation at a number of unlinked genetic markers to study the
demographic histories of natural populations. The authors report
that analysis of genetic variation in various aboriginal
populations throughout the world reveals highly significant
evidence for a major human population expansion in Africa, but no
evidence of expansion outside of Africa. The inferred African
expansion is estimated to have occurred between 49,000 and
640,000 years ago, certainly before the Neolithic expansions, and
probably before the splitting of African and non-African
populations. The authors suggest that in showing a significant
difference between African and non-African populations, their
analysis supports the unique role of Africa in human evolutionary
history. The authors also suggest that the missing signal in non-
African populations may be the result of a population bottleneck
associated with the emergence of these populations from Africa,
as postulated in the "Out of Africa" model of modern human
origins.
QY: David B. Goldstein: david.goldstein@zoo.ox.ac.uk
(Proc. Natl. Acad. Sci. US 7 Jul 98 95:8119)
(Science-Week 7 Aug 98)
-------------------
Related Background:
... ... *mitochondrial DNA: See main report.
... ... *alleles: An allele is one of two or more forms of a
given gene that control a particular characteristic, with the
alternative forms occupying corresponding loci on homologous
chromosomes.
-------------------
Related Background:
Y CHROMOSOME EVIDENCE INDICATES AFRICAN ORIGINS OF MAN
The Y chromosome is one of the two chromosomes that determine sex
in many animals, including humans, and it carries mostly male-
specific genes. Genetic polymorphisms are individual functional
variations of specific genes or genetic markers that occur in a
population with a significant frequency, e.g., more than 1%.
Mitochondrial DNA (sometimes denoted as mtDNA), found in the
mitochondria of all eukaryotes, is believed to evolve in parallel
with nuclear DNA and to be inherited only in the maternal lineage
in animals. Until now, it has been mitochondrial DNA that has
been greatly exploited in studies of the evolution of humans. At
a recent symposium on human evolution (Cold Spring Harbor
Laboratory, NY US), a consensus was apparently reached that
current studies of human Y chromosome polymorphisms indicate that
the major human migrations that occurred had their source in
Africa, and that a small number of present African populations,
the Ethiopians, Sudanese, and south African Khoisans, possess
markers that have been conserved since that time. The data are
considered to confirm the recent mitochondrial DNA studies which
also indicate Africa as the source of human migrations. Some
paleoanthropologists are calling the Y chromosome results an
"unquestionable major breakthrough". (Science 31 Oct 97)
(Science-Week 21 Nov 97)
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
FIRST ANALYSIS OF DNA FROM A NEANDERTHAL BONE
About 10 kilometers east of Dusseldorf in Germany, in the valley
of the Dussel, there is a little town called Neander. One hundred
and forty-one years ago, in the summer of 1856, some workmen
broke into a cave to get at the limestone inside and discovered a
set of ancient bones. Most of the bones were smashed to bits by
the workmen, but some of the bones, including part of the skull,
survived, and the skeleton was soon recognized by anthropologists
as belonging to an ancient race of men who came to be known as
the Neanderthals. A Neanderthal fossil had actually been
discovered some years earlier in Gibraltar, but not recognized as
such. Neanderthal-like fossils have also been found in France,
Spain, Italy, Yugoslavia, Iraq, China, Java, and Israel. For more
than a century, one of the central questions in paleoanthropology
has been whether modern man evolved from this race -- or was the
Neanderthal a separate branch that became extinct? Until
recently, the primary laboratory method of investigation of such
a question was analysis of the morphology of bone fragments. This
week, the field of paleoanthropology has apparently crossed an
important watershed, as M. Krings et al (University of Munich,
DE; Pennsylvania State University, US) report the first analysis
of DNA from an extinct human, in this case DNA extracted from the
actual Neanderthal skeleton found near Dusseldorf in 1856. The
key to the investigation was the analysis of mitochondrial rather
than nuclear DNA. Mitochondrial DNA is usually present in
concentrations two or three orders of magnitude greater than
nuclear DNA, and they were able to find enough of it still intact
to amplify with the PCR technique and piece together a total DNA
sequence of 379 base pairs. Comparison of this sequence with
contemporary human sequences leads to the conclusion that
Neanderthal and modern man are separate evolutionary lines, and
that the latter did not evolve from the former. The work will
have to be replicated with other Neanderthal fossils, but most
paleoanthropologists are excited by the results and expect them
to be confirmed. The technology of evolutionary paleoanthropology
has evidently now progressed from caliper measurements of bones
to measurements of bone DNA fragments.
(Cell 11 Jul 97) (Science-Week 18 Jul 97)
For more information: http://scienceweek.com/swfr.htm

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

6. MEDICAL BIOLOGY: THE PROSPECT FOR STEM CELL THERAPIES
     Adult multicellular animals (metazoans) are composed of a
number of distinct types of cells: in humans, there are
approximately 200 different types of cells organized into
tissues, with each tissue typically consisting of an organization
of a small number of cell types. The ultimate production of
various cell types from the primordial fertilized egg cell is
called "differentiation", and the biochemical basis of cell
differentiation is the synthesis by cells of particular sets of
proteins, carbohydrates, and lipids. These syntheses are
catalyzed by special proteins (enzymes), and each enzyme is in
turn synthesized in accordance with a particular gene, a sequence
of nucleotides in the DNA of the cell nucleus. In general, any
particular state of cell differentiation corresponds to
particular sets of genes expressed and repressed, and to the
levels of that expression and repression. No matter what the cell
type, all of the genes of an organism are present in the cell
nucleus: the variations between tissues are due not to the
presence or absence of certain genes, but to the expression of
some genes and the repression of other genes. For example, one of
the best understood cases of cell differentiation is that of the
red blood cell, the major protein of which is hemoglobin. The
hemoglobin gene is present in the cells of all other tissues, but
in these tissues the gene is barely or never expressed. In
contrast, in the DNA of the developing red blood cell, "enhancer"
nucleotide sequences have been identified in and around the
regions encoding hemoglobin, and these enhancers apparently
interact with regulatory proteins specific to red blood cells,
the result the full-scale *transcription of hemoglobin genes only
in those cells.
     The term "stem cells" refers to cells capable of
differentiation after one or more replications into various types
of specialized cells, with "totipotent stem cells" those stem
cells that can differentiate into any type of cell, and
"pluripotent stem cells" those stem cells whose differentiation
range is narrowed. The ultimate totipotent stem cell is the
original fertilized egg cell, which progressively differentiates
and replication into an entire adult organism. In embryos, there
are many types of stem cells, totipotent and pluripotent, that
during embryological development are triggered ("induced") to
differentiate into various types of tissue cells. In adult
organisms, certain tissues (e.g., skin) contain stem cells that
are involved primarily in cell-replacement functions.
     In general, cell differentiation, dependent on the
expression and repression of particular sets of genes in the
genome, is the key to the development of a complete adult
individual from a single fertilized egg cell. Given that many
diseases involve defective cell types and/or injured tissues,
possible therapeutic uses of stem cells are a natural and
important focus of attention.
... ... E.H. Kaji and J.M. Leiden (Harvard University, US)
present a review of current research on gene and stem cell
therapies, the authors making the following points concerning
stem cell therapy:
     1) The authors point out that clinicians have exploited stem
cells for therapeutic purposes for more than 40 years. Bone
marrow transplantation (hematopoietic stem cell transplantation),
for example, is life-saving for patients with certain types of
bone marrow diseases and malignancies. But the usefulness of stem
cell transplantation has been limited by the fact that many
organs (e.g., brain, spinal cord, heart, kidney) were believed to
lack detectable stem cells. It was also believed that cells from
these organs could not be reprogrammed to differentiate into
different cell types during adulthood.
     2) Three recent discoveries have revolutionized stem cell
biology and have demonstrated the clinical potential of stem
cells in a wide range of human diseases:
... ... a) Stem cells have been detected in organs (e.g., brain
and muscle) previously thought to lack stem cells and
regenerative potential. For example, several areas of the brain
are now known to contain stem cells that maintain the ability to
proliferate and to mature into differentiated neural cell types
in vitro and in vivo. Similarly, skeletal muscle stem cells
(myoblasts) have been cultured in vitro and transplanted into
recipient muscle, where they differentiate into developing muscle
fibers (myotubes) that fuse with endogenous muscle fibers to
repopulate damaged muscle.
... ... b) Organ-specific adult stem cells appear to display much
more plasticity than previously thought, and stem cells isolated
from one tissue can differentiate into a variety of unrelated
cell types and tissues. For example, recent animal experiments
have demonstrated that neural stem cells can differentiate into
hematopoietic cell types. Similarly, bone-marrow-derived stem
cells can differentiate into several non-hematopoietic cell
types, including skeletal muscle, certain types of *glial cells
in the brain, and liver cells (hepatocytes). These findings
suggest the possibility of using bone marrow transplantation to
treat a wide variety of disorders, such as muscular dystrophies,
Parkinson's disease, stroke, and liver failure. In addition,
animal cloning experiments with sheep, mice, cows, and monkeys
have now demonstrated that nuclei from terminally differentiated
cells can be reprogrammed to totipotency. Thus, it might be
possible to generate specific types of therapeutic stem cells in
vitro beginning with a small number of differentiated cells from
the patient to be treated (e.g., a skin or muscle biopsy
specimen), thereby avoiding immune responses to the transplanted
cells.
... ... c) Human embryonic stem cells can be isolated from early
fetuses and made to differentiate in vitro into a wide variety of
cell types. Embryonic stem cells are totipotent cells derived
from the inner cell mass of an early-stage fertilized embryo.
Under appropriate tissue culture conditions, embryonic stem cells
have the capacity for unlimited replication while maintaining
totipotency, and when reimplanted into a *blastocyst, such
cultured embryonic stem cells can contribute to all of the organs
of the resulting adult animal.
     3) The authors conclude: "The discovery of stem cells in
adult tissues, the unexpected plasticity of both adult stem cells
and differentiated cells, and the isolation of human embryonic
stem cells have expanded the potential therapeutic utility of
[stem-] cell-based therapies... [Stem-] cell based therapies
using autologous donor cells [i.e., cells from the same
individual] hold tremendous promise for the treatment of both
acquired and inherited diseases involving tissue degeneration and
cellular dysfunction."
-----------
E.H. Kaji and J.M. Leiden: Gene and stem cell therapies.
(J. Amer. Med. Assoc. 7 Feb 01 285:545)
QY: Jeffrey M. Leiden: jeff.leiden@abbott.com
-----------
Text Notes:
... ... *transcription: "Transcription" is the process
by which genetic information in DNA is converted into RNA, with
the RNA ultimately "translated" into protein.
... ... *glial cells: Glial cells are cells of the central and
peripheral nervous system that metabolically support neurons.
Such cells also produce the multiple membrane layers called
myelin and enfold nerve cell axons with it. Glial cells are found
everywhere in the brain and spinal cord.
... ... *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.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 16Feb01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON HUMAN EMBRYONIC STEM CELL RESEARCH
In a multicellular living organism such as a human or a mouse,
what differentiates one cell type from another is apparently not
the genome, since the genome is the same in every cell, but which
parts of the genome are operational. In other words, each cell
type, skin cell, muscle cell, etc., has a particular gene profile
characteristic of that cell type. Cells of a particular cell type
are said to be "differentiated". Stem cells, present in all early
embryos and in some tissues, are undifferentiated cells that in
response to appropriate signals differentiate and give rise to a
variety of cell types. Embryonic stem cells are "totipotent",
i.e., they have the potential to differentiate into any type of
tissue cell. These cells form at a very early stage in human
development and remain in an undifferentiated state for only a
short period of time. They are first clearly recognizable
approximately 5 to 7 days after fertilization, when a human
embryo forms a structure called a "blastocyst", a hollow fluid-
filled sphere consisting of only 140 cells. There are two types
of cells in the blastocyst at this stage: a) "trophoblast cells",
which form the wall of the sphere, and which will become
supporting tissues of the fetus (e.g., the placenta); b) "inner-
cell-mass cells", a clump of cells located at one end within the
blastocyst interior, and which are the undifferentiated cells
(stem cells) that will divide and develop into the individual.
The expected future medical applications of stem cells,
particularly embryonic stem cells, are extremely promising, but
because of the involvement of embryos and certain other
considerations, basic stem cell research has provoked intense
controversy. ... ... Shirley J. Wright (University of Dayton, US)
presents a review of those aspects of human embryonic stem cell
research that have been the focus of science policy controversy,
the author making the following points:
     1) Human blastocysts -- each capable of developing into a
complete human being -- are a potential source of embryonic stem
cells, undifferentiated cells with the potential to develop into
any cell type in the body. These cells have enormous therapeutic
potential for the replacement of damaged or diseased tissues, but
current legal and ethical concerns limit the nature of the
research that can be performed with these cells because of their
source.
     2) At the 5 day stage, the human blastocyst is approximately
200 microns in diameter. Cells of the inner cell mass can give
rise to all 3 germ layers -- the ectoderm, mesoderm, and endoderm
-- which in turn give rise to all the tissues in the body. The
ectoderm cells develop into skin, nerves and eyes; the mesoderm
cells develop into bone, blood, and muscles; the endoderm cells
develop into the lungs, liver, and the lining of the intestines.
At the 5 to 7 day stage, the inner cell mass can be removed from
the blastocyst and cultured in a dish as embryonic stem cells.
     3) Early human embryos can also provide undifferentiated
pluripotent cells (i.e., cells capable of differentiating into
certain cell types but not all cell types) in the form of
primordial germ cells, the precursors of eggs and sperm cells.
The primordial germ cells do not differentiate early, remaining
in the yolk sac until approximately the 6th to 8th week of
development, when they migrate to the developing gonads in the
embryo. These primordial germ cells may be extracted as
pluripotent embryonic germ cells beginning approximately 24 days
after fertilization.
     4) Embryonic stem cells obtained from the inner cell mass of
a blastocyst can be grown in a culture dish on a layer of
"feeder" cells derived from irradiated mouse *fibroblasts. The
layer of feeder cells arrests the differentiation of the stem
cells by releasing various inhibitory factors. Cell lines derived
in this manner are immortal -- they can divide indefinitely to
form more undifferentiated cells, thus providing a ready source
for future research.
     5) Fusing a human somatic cell (i.e., any human non-germ
cell) with an enucleated egg cell allows the creation of person-
specific embryonic stem cells, thus avoiding the complications of
tissue incompatibility. In this technique, a patient's somatic
cell is placed next to an enucleated egg cell, and the two cells
are fused by application of an electric current, the somatic cell
nucleus entering the egg cytoplasm. The egg is then activated and
develops into a blastocyst embryo, and the blastocyst can now
provide embryonic stem cells compatible with the patient. This is
the technique that was used Ian Wilmut and his group to produce
the cloned sheep Dolly.
     6) Transfer of a human somatic-cell nucleus (such as a cheek
*epithelial-cell nucleus) to an enucleated bovine egg cell
produces a "*chimera" that could be the source of embryonic stem
cells. Such an experiment was successfully performed by Robl and
Cibelli in 1996. The embryo developed to the 32-cell stage, but
was not allowed to develop further.
     7) Production of human replacement tissue (e.g., neural
cells, pancreatic cells, or heart-muscle cells) in a culture dish
is one of the important potential clinical applications of
embryonic stem-cell technology. Once cultured, the differentiated
cells would be injected into the damaged organ, where they would
replace the damaged tissue. But this has not yet been achieved,
and the clinical technology will require years of development.
     8) The author concludes: "As a society we must identify the
ethical, social, legal, medical, theological, and moral issues
that surround this research. People from all walks of life --
scientists, lawyers, ethicists, clergy, and the general public --
should be involved in making the decision. We are also at the
crossroads where further scientific evidence is needed to explore
the full potential of these cells, and yet many of the necessary
experiments raise further ethical issues. The question of how we
should use these powerful cells remains a challenging problem for
the next century."
-----------
Shirley J. Wright: Human embryonic stem-cell research: Science
and ethics.
(Amer. Scientist Jul/Aug 99 87:352)
QY: Shirley J. Wright [wrights@neelix.udayton.edu]
-----------
Text Notes:
... ... *fibroblasts: A type of connective tissue cell, secreting
structural proteins (e.g., collagen) that form certain tissue
components, including the extracellular matrix.
... ... *epithelial-cell: 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.
... ... *chimera: In general, a "chimera" is any cell or organism
with genetic material from two or more genotypes (e.g., two or
more species). 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 20Aug99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
CONVERSION OF NEURAL STEM CELLS INTO BLOOD CELLS
... Stem cells are common in embryos, but they have also been
identified in adult tissues that undergo extensive cell
replacement due to physiological turnover or injury, e.g., the
*hematopoietic, intestinal, and *epidermal systems. Stem cells
have also been found in the central nervous system, a tissue
believed to be capable of only extremely limited self-repair.
Central nervous system stem cells can generate the 3 major cell
types found in the adult brain: *astrocytes, *oligodendrocytes,
and neurons. This is consistent with the view that the
developmental potential of stem cells is restricted to the
differentiated elements of the tissue in which they reside. But
some developmental peculiarities suggest certain cells may be
able to differentiate into cell types that are not of the same
origin. ... ... C.R.R. Bjornson et al (5 authors at 4
installations, CA IT) now report an investigation to determine
whether stem cells are restricted to produce specific cell types,
namely, those from the tissue in which they reside. The authors
report that after transplantation into *irradiated host mice,
genetically labelled mouse neural stem cells were found to
produce a variety of blood cell types, including *myeloid and
*lymphoid cells, as well as early hematopoietic cells. The
authors suggest that neural stem cells appear to have a wider
differentiation potential than previously thought, and that if
they behave similarly to their mouse counterparts, human neuronal
stem cells may provide a renewable and characterized source of
cells that could be used in approaches aimed at hematopoietic
reconstitution in various blood diseases and disorders.
-----------
C.R.R. Bjornson et al: Turning brain into blood: A hematopoietic
fate adopted by adult neural stem cells in vivo.
(Science 22 Jan 99 283:534)
QY: Christopher R.R. Bjornson [adanac@u.washington.edu]
-----------
Text Notes:
... ... *hematopoietic: From hematopoiesis (hemopoiesis,
hematogenesis) Refers to the formation and development of the
various types of blood cells. 
... ... *epidermal: The term "epidermal" refers to the
superficial epithelial portion of the skin. 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.
... ... *astrocytes: (astroglia, macroglia) Glial cells are more
numerous than neurons in the brain, but their function has been
generally characterized as "metabolic" or "supportive", without
much discussion of details. Astrocytes 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.
... ... *oligodendrocytes: (oligodendroglia) Glial cells
characterized by sheet-like processes that are wrapped around
individual neuron axons to form the myelin sheath of nerve fibers
in the central nervous system. (The myelin sheath of a nerve
fiber is effectively a periodically interrupted insulation which
increases the propagation velocity of nerve impulses.)
... ... *irradiated host mice: In this investigation, host
animals were radiated before transplantation in order to reduce
the population of immune system blood cells, this reduction
apparently intensifying the signals resulting in donor stem cell
differentiation.
... ... *myeloid: Refers to bone marrow cells or cells derived
from bone marrow cells.
... ... *lymphoid cells: Refers to cells of the lymphatic system.
The lymphatic system is a complex network for the distribution of
lymph fluid (which is similar to blood plasma -- blood without
red cells).
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 2Apr99
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
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 [gearhart@jhmi.edu]
-----------
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
For more information: http://scienceweek.com/swfr.htm

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7. IN FOCUS: ON HUMAN FOSSILS AND HUMAN BRAINS
[Editor's note: Prehistoric peoples ranging back to the dawn of
the human species have left us their bones, and from these bones
(when we can find them) we attempt to construct an image of our
ancestors. It is an enormously difficult and murky undertaking,
and the results perhaps most ambiguous when we try to establish
an idea of the perished brains of human fossils. Skulls are
measured to determine the volume of the brain, endocasts are made
to establish the inner surfaces of the skull and perhaps the
convolutions of the brain once protected by that skull, and there
is much controversy in anthropology concerning interpretations of
data. Here is a commentary by a brain neuroanatomist on the
difficulties of knowing the brains of ancient peoples, his words
nearly 40 years old but still relevant.]
-----------
"The results of our inquiries into the brains of fossil men are
somewhat meager: we cannot deduce any details about their mental
life, whether they believed in God, whether they could speak or
not, or how they felt about the world around them... That the
brain increases in size as we go from the Australopithecinae to
modern man -- or to the Upper Paleolithics, for that matter -- 
is quite obvious and, of course, gratifying. But the meaning of
the increase is again not quite clear because, as we all know,
brain size as such is a very poor indicator of mental ability.
This has been shown best perhaps by [Karl] Pearson [1857-1936]
(1925) some years ago. In his series, very gifted persons, such
as Leon Gambetta [1838-1832], Anatole France [1844-1924], or
Franz Joseph Gall [1758-1828], had very small brains, of about
1100 grams. Other equally gifted persons had very large brains;
thus [George Gordon] Byron [1788-1824] and Dr. [Samuel] Johnson
[1709-1784] had brains of about 2000 grams. And, of course, some
very ordinary persons had equally large brains. So brain size was
certainly not very important, and the correlation between brain
size and mental capacity was insignificant. But whether this
argument can be extended to an evolutionary series is again
another matter. For one thing, we know far too little about the
bodily proportions of fossil forms. Obviously, the brain stands
in a certain relation to the rest of the body, and this rest is
still largely hidden from us. Brain size as such is none too
meaningful. Moreover, mere size completely leaves out of account
the inner structure of the brain, which may be different in
different forms and which may determine to a great extent what
the brain can do."
-----------
Gerhardt von Bonin: _The Evolution of the Human Brain_
(University of Chicago Press, 1963, p.76)
-------------------
SCIENCE-WEEK http://scienceweek.com 16Feb01

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8. FROM THE SCIENCEWEEK ARCHIVE:
ON THE INVENTOR OF MODERN SCIENCE
There are two broad approaches to the writing of intellectual
history. One can focus on movements, on changing and evolving
concepts and attitudes; or one can focus on individuals, on a
series of key players whose personal discoveries and influences
on each other form a chain that connects the past to the present.
The second method, which considers the histories and
contributions of real people, their fortunes and misfortunes, is
usually more amenable to dramatic presentation and concrete
images. The first method, which primarily considers the complex
flow of ideas in time, is more abstract, of more interest to
scholars, and more frightening to the editors of weeklies who
fear losing their readers. But, in truth, no one is holding a gun
to our heads and telling us we must use one approach or the other
exclusively; each approach has its merits, and each approach can
be instructive and interesting in its own way. ... ... In a short
essay entitled, "The Inventor of Modern Science", physicist
Freeman J. Dyson (Institute for Advanced Study Princeton, US)
considers the life and contributions of the 18th century
astronomer James Bradley (1693-1762), with Dyson making the
following points:
     1) Modern science began in 1729, when it became based on
measurements of high precision, and since James Bradley was the
first to make high-precision measurements, James Bradley can be
called the inventor of modern science. Bradley was the first to
understand that accurate measurement requires meticulous
monitoring and control of possible sources of error. In addition
to a number of important discoveries, Bradley was the first to
record temperature and barometric pressure whenever he made an
observation.
     2) Using a plumb-line and micrometer screw, Bradley measured
the angle between a star and the local vertical with 6-figure
accuracy. He was the first person to measure anything with 6-
figure accuracy. He measured angles a hundred times more
accurately than the astronomers of Newton's time, and this
accuracy was responsible for his discovery of "aberration", the
displacement of the image of a star in the sky due to the speed
of the Earth in its orbit and the finite velocity of light. Over
the course of a year, Bradley found the displacements of each
star to form a closed ellipse. At that time, both astronomers and
the educated public in Europe considered these elliptical
displacements the first direct demonstration that the Copernican
view of the Universe was correct, the elliptical motions visual
proof that the Earth is moving around the Sun [*Note #1].
     3) By considering the aberration displacements
quantitatively, Bradley was able to provide the first accurate
determination of the velocity of light, calculating a value
within 1 percent of the modern value [*Note #2].
     4) The influence of Bradley extended far beyond astronomy,
his insistence on 6-figure accuracy spreading to other countries
and to other sciences. One hundred and fifty years after Bradley,
Michelson and Morley attempted to measure the 2nd-order
aberration of light caused by the Earth's motion through the
ether, and by their negative result led the way to the theory of
relativity.
-----------
Freeman J. Dyson: The inventor of modern science.
(Nature 1 Jul 99 400:27)
QY: Freeman J. Dyson, Institute for Advanced Study, Princeton NJ
08540 US.
... ... *Note #1: In his essay, the author states: "Bradley found
that all stars moved in elliptical paths in the sky, coming back
to their original positions after a year." This should perhaps be
qualified, since the ellipse becomes a circle for a star at the
pole of the ecliptic (the mean plane of the Earth's orbit around
the Sun), and the ellipse becomes a straight line for a star on
the ecliptic.
... ... *Note #2: The angular displacement (a) of an observed
star is given by the relation tan(a) = v/c, where v is the
Earth's orbital velocity and c is the speed of light.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 16Jul99


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