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.

September 3, 1999 -- Vol. 3 Number 36

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

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Contents of This Issue:

1. On Non-Profit Scientific Journals as Ventures for Profit
2. Dilute Electron Systems in Two Dimensions
3. On Explanations of Protein Folding
4. On the Neanderthals in Human Evolution
5. Genetic Control of Branching Morphogenesis
6. Brain Sex Differences and Adult Brain Plasticity

In Focus: On Developmental Pathways

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1. ON NON-PROFIT SCIENTIFIC JOURNALS AS VENTURES FOR PROFIT
     What is often overlooked in considering scientific societies
and their ownership of journals is that the major difference
between a "for-profit" organization (e.g., a corporation such as
DuPont) and a "non-profit" organization (e.g., a scientific
society such as the American Chemical Society) is a question of
shareholders and not of profits. Corporations have shareholders;
non-profit scientific societies do not. Ignoring capital
accumulation and investment, in a corporation all profits after
expenses and operating salaries may be distributed to
shareholders; in a non-profit scientific society all profits
after expenses and operating salaries are distributed as more
salaries and fringe benefits, or held for future use in non-
profit endeavors. In both cases, the term "expenses" includes
political, educational, legal, and charitable expenses. Thus, the
people salaried by non-profit organizations are in essence its
shareholders -- they receive personal capital distributed from
profits. In both cases, for-profit and non-profit, there is
considerable motivation to maximize profits. In the case of a
for-profit corporation, the _publicly_ acknowledged motivation
for maximizing profits is to maximize return of investment to
shareholders; in the case of a non-profit scientific society, the
_publicly_ acknowledged motivation for maximizing profits is to
provide funds for political, educational, legal, and charitable
expenses of the society. But in addition to public motivations,
there are also private motivations: the managers of a for-profit
corporation expect and receive increased salaries when profits
are increased, and the same is generally true for the managers of
non-profit scientific societies and their journals. If the
publishing manager of a profit-making journal owned by a non-
profit society substantially increases the profits of that
journal, the manager expects, and usually receives, a significant
salary increase.
     As an illustration of for-profit and non-profit differences,
the journal _Nature_ is owned by Macmillan Ltd., which is a for-
profit corporation; the journal _Science_ is owned by the
American Association for the Advancement of Science, which is a
non-profit organization. In the category of general science
journals, they are the two leading science journals in the world.
Both journals are extremely profitable, with advertising and
subscription revenues in the many millions of dollars, with
offices or representatives in every major city in the world, and
with hundreds of employees in their executive, editorial, and
clerical divisions. In the case of _Nature_, profits after
salaries and expenses are distributed to the shareholders of
Macmillan Ltd.; in the case of _Science_, profits from the
journal are retained and distributed internally to the journal
and to the American Association for the Advancement of Science as
increased salaries, investment in plant, investment in other
"non-profit" enterprises, etc.
     Recently, two other non-profit scientific societies have
been in the news, the American Medical Association (and its
_Journal of the American Medical Association_ [JAMA]), and the
Massachusetts Medical Society (and its _New England Journal of
Medicine_ [NEJM]). Each journal recently fired its highly
respected editor, events that brought the journals and their
societies to the attention of the public, and it is quite
extraordinary that at the present time the two leading medical
journals in the US are without chief editors. In the case of
JAMA, the editor was apparently removed for publishing a paper
whose results were relevant to a contemporaneous political
scandal; in the case of NEJM, the editor was apparently removed
for objecting to the use of his journal's name to increase the
profits of the Massachusetts Medical Society through other
publishing ventures not under NEJM authority.
     Writing of these events in particular and of the publishing
of medical journals in general, in a recent major article in the
_New York Times_ (24 Aug 99), physician and science writer
Lawrence K. Altman noted: "The journals have increasingly become
cash cows for the medical societies and companies that own them,
with annual profits in the tens of millions of dollars, largely
from drug company advertisements. And the imperative to sustain
and build those profits is changing how the journals do business
-- and how the public learns about medicine -- in ways their
founders could scarcely have envisioned."
... ... Drummond Rennie, Deputy Editor (West) of JAMA, now
presents an editorial in that journal concerning the recent
events at the New England Journal of Medicine. Rennie makes the
following points:
     1) The author points out that of the issues dividing the
owner and editor of the _New England Journal of Medicine_, the
most important involve the application of the impressive brand
name of the journal to spin-off journals and to various consumer
letters and magazines. These latter publications are advertised
as being from "the publishers of the _New England Journal of
Medicine_." Rennie notes: "A true enough statement, but
misleading in that these publications would not have gone through
the rigorous competitive selection process of peer review and
revision necessary to satisfy the high standards of that
journal's editors."
     2) The author notes that in 1998 the Massachusetts Medical
Society apparently derived approximately 95 percent of its US$73
million annual budget from publishing, so the success of the _New
England Journal of Medicine_ as a medical journal is reflected in
massive revenues to its owners. "Medical societies always have
important and pressing agendas, political, educational, legal,
and charitable. They always need more money, so there is
increasing pressure on journals to produce even more profits from
their owners. But the owners of the _New England Journal of
Medicine_, in their natural desire to increase profits by milking
the reputation of their journal, are in danger of losing the
respect and confidence of those who make their journal what it
is. And without reputation the owners will find they have nothing
to sell."
     3) The author concludes: "As a reader of, contributor to,
and one-time deputy editor of the _New England Journal of
Medicine_, I am saddened by the blow to the reputation of our
sister journal and hope that the owners will listen carefully to
what their authors, reviewers, and editors are telling them."
-----------
Drummond Rennie: Editors and owners -- Stretching reputation too
far.
(J. Amer. Med. Assoc. 25 Aug 99 282:783)
QY: D. Rennie, JAMA, 515 N. State St., Chicago, IL 60610. US.
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 3Sep99


2. DILUTE ELECTRON SYSTEMS IN TWO DIMENSIONS
In general, in the context of the electrical properties of
condensed matter, a "hole" is a vacant electron position in the
lattice structure of a solid, the hole behaving like a mobile
positive charge carrier. A 2-dimensional system of electrons or
holes is one in which the positions of the electrons and their
motion are restricted to a plane. Physical realization of such
systems can be found in very thin films, sometimes at the
surfaces of bulk materials, in layered "*quantum well" systems
specifically engineered for this purpose, and in silicon metal
oxide-semiconductor *field effect transistors (silicon MOSFETs).
Two-dimensional electron systems have been studied for nearly 40
years, and have yielded a number of important discoveries of
physical phenomena that directly reflect the quantum mechanical
nature of our world. Such discoveries include the "*integer
quantum Hall effect", which reflects the quantization of electron
states by a magnetic field, and the "*fractional quantum Hall
effect", which is a manifestation of the quantum mechanics of
many electrons acting together in a magnetic field to yield
curious effects such as fractional (rather than whole) electron
charges. ... ... M.P. Sarachik and S.V. Kravchenko (2
installations, US) present a review of current work on novel
phenomena in 2-dimensional dilute electron systems, the authors
making the following points:
     1) For nearly two decades it was believed that in the
absence of a magnetic field all 2-dimensional systems of
electrons are insulators in the limit of zero temperature, and
these expectations were supported by theory. Confirmation that 2-
dimensional systems of electrons are insulators in zero field was
provided by experiments in thin metallic films and silicon
MOSFETs, where the conductivity behavior suggested extrapolation
to infinite resistivity in the limit of zero temperature.
     2) But recent experiments in silicon MOSFETs suggest that a
transition from insulating to conducting behavior occurs with
increasing electron density at a very low critical density of
approximately 10^(11)/square centimeter. These experiments
involved unusually high quality samples, allowing measurements at
considerably lower electron densities than had been possible in
the past. The results were first viewed with considerable
skepticism, but the findings were soon confirmed in other
laboratories, and then for other materials.
     3) It was soon realized that the low electron (and hole)
densities at which these experimental observations were made
correspond to a regime where the energy of the repulsive *Coulomb
interactions between the electrons exceeds the *Fermi energy
(approximately, their kinetic energy of motion) by an order of
magnitude. Rather than being a small perturbation, as previously
assumed, Coulomb interactions instead provide the dominant energy
in these very dilute systems.
     4) For a very high-mobility (low-disorder) silicon MOSFET,
there is a well-defined crossing at a "critical" electron
density, below which the resistivity increases as the temperature
is decreased, and above which the reverse is true. A resistivity
that increases with decreasing temperature generally signals an
approach to infinite resistance at zero temperature (i.e.,
insulating behavior), while a resistivity that decreases as the
temperature is lowered is characteristic of a metal if the
resistivity tends to a finite value, or of a *superconductor if
the resistivity tends to zero.
     5) Strongly interacting systems of electrons in 2-dimensions
are currently the focus of intense interest, with numerous
theoretical attempts to account for the presence and nature of
the conducting phase. Most theories postulate esoteric new states
of matter. Some theories attribute the unusual behavior to
effects that are essentially classical in nature. Although some
researchers may strongly advocate a particular view, all would
agree that no consensus has been reached.
-----------
M.P. Sarachik and S.V. Kravchenko: Novel phenomena in dilute
electron systems in two dimensions.
(Proc. Natl. Acad. Sci. US 25 May 99 96:5900)
QY: M.P. Sarachik, City College of the City of New York, US.
-----------
Text Notes:
... ... *quantum well: In general, the term "quantum well" refers
to a thin layer of material (e.g., between 1 and 10 nanometers in
thickness) within which the potential energy of an electron is
less than outside the layer, with the result that the motion of
the electron perpendicular to the layer is quantized.
... ... *field effect transistors: A transistor is essentially a
semiconductor device in which it is possible to control voltage
or current in such a way as to achieve gain or switching action.
A "field effect transistor" is a transistor in which current flow
depends on the movement of "majority carriers" only, with
unipolar current flowing through a narrow conducting channel
between two regions to which electrodes are attached. The current
is modulated by an electric field applied to a third electrode
attached to the "gate" region surrounding the conducting channel.
(In semiconductors, "majority carriers" are carriers constituting
more than half of the total charge carrier concentration. In "n-
type" semiconductors, the majority carriers are electrons; in "p-
type" semiconductors, the majority carriers are holes.) A "metal
oxide field effect transistor" (MOSFET; also, insulated-gate
field effect transistor, or IGFET) is a field effect transistor
in which the input electrode is capacitatively coupled to the
conducting channel, with the capacitative insulating layer a thin
layer of a metal oxide, usually silicon dioxide. 
... ... *integer quantum Hall effect: In classical physics, the
Hall effect is the development of a transverse voltage across a
current-carrying conductor in a magnetic field, the voltage being
perpendicular to both the direction of the current and the
direction of the magnetic field. In quantum physics, there are
two other Hall effects, an integer charge quantum Hall effect,
and a fractional charge quantum Hall effect, these quantum Hall
effects being observed at extremely low temperatures (a few
degrees Kelvin) and extremely intense magnetic fields (at least
several tesla). Both quantum Hall effects were first noted in the
1980s. The integer quantum Hall effect is accounted for in terms
of noninteracting electrons, whereas the fractional quantum Hall
effect is believed to result from many-electron interactions in
2-dimensional systems.
... ... *fractional quantum Hall effect: See previous note.
... ... *Coulomb interactions: In general, a "Coulombic force" is
a force of attraction or repulsion resulting from the interaction
of the electric fields surrounding two charged particles, with
the magnitude of the force inversely proportional to the square
of the distance between the particles.
... ... *Fermi energy: (Fermi level) In general, the "Fermi
level" is the energy in a solid at which one-half of the quantum
states are occupied.
... ... *superconductor: Superconductivity is a property of many
metals, alloys, and chemical compounds at temperatures near
absolute zero, at which temperatures their electrical resistivity
vanishes and they become strongly diamagnetic. Diamagnetic
substances such as the alkalis and alkaline earth metals, the
halogens, and the noble gases are repelled by magnets and tend to
position themselves at right angles to the magnetic lines of
force.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99


3. ON EXPLANATIONS OF PROTEIN FOLDING
Since the 3-dimensional configuration of a protein is an
essential determinant of what the protein does in a biological
system, protein "folding", the process that leads to this
configuration, is a central focus in biophysical chemistry.
... ... William A. Eaton (National Institutes of Health, US)
presents a review of current research in this field, the author
making the following points:
     1) There are two aspects to the problem of protein folding.
The first is predicting the 3-dimensional structure of a protein
from its amino acid sequence; the second is to understand _how_
proteins fold. The problem of protein folding has recently
assumed additional importance as more and more human diseases
(e.g., Alzheimer's and Parkinson's diseases) are believed to be
caused by aggregation of misfolded proteins.
     2) The question of _how_ a protein folds can be phrased more
precisely as follows: What are the sequences of structural
changes that occur in a polypeptide as it finds its way from the
myriad of possible structures in the *denatured state to the
final unique *native structure? How many different folding routes
exist, and what are their relative probabilities?
     3) Until approximately a decade ago, the problem of
understanding how proteins fold was addressed by identifying and
characterizing one or two metastable structures believed to be
obligatory intermediates in a sequential process along a well-
defined protein-folding pathway. The prevailing view was that
structural characterization of such intermediates would give the
clue to the basic underlying mechanism, as in the study of
organic chemical reactions. However, unlike small-molecule
chemical reactions, in which covalent bonds are broken and new
bonds formed in a structurally well-defined transition state, the
many degrees of freedom of a polypeptide chain demand a different
approach. A polypeptide of 100 amino acids has a huge number of
conformations, even if only a tiny fraction of the more than
2^(100) (= 10^(30)) possible conformations are thermally
occupied. Understanding the complexities of protein folding at
the microscopic level, and developing models that make
quantitative predictions, therefore requires a statistical
approach, i.e., the theoretical and computational tools of modern
statistical mechanics.
     4) Nonexponential kinetics have played an important role in
understanding conformational changes in native proteins. They are
particularly interesting for protein folding because they could
arise from a process that is "downhill" in free energy, i.e, one
in which the overall free energy barrier separating the native
from the denatured state is very small or nonexistent. For large
barriers, only the structures of the initial and final states are
observable, because structures along the folding route are too
sparsely populated. If, however, the barrier becomes very small
or disappears altogether, all of the structures can in principle
be detected and characterized by spectroscopy.
     5) At the present time, there exists the exciting prospect
of performing single molecule experiments for direct exploration
of the energy landscape and folding routes. Finding proteins that
fold with a "downhill scenario" is an essential first step in
this quest. That some proteins will exhibit downhill folding,
moreover, is one of the novel theoretical predictions of an
energy landscape analysis of protein folding.
-----------
Editor's note: In addition to the background material below, see
the 8 Aug 99 issue of SW (#32), report #3)
-----------
William A. Eaton: Searching for "downhill scenarios" in protein
folding.
(Proc. Natl. Acad. Sci. US 25 May 99 96:5897)
QY: William A. Eaton [eaton@helix.nih.gov]
-----------
Text Notes:
... ... *denatured state: In biochemistry, the term
"denaturation" refers to the complete unfolding
and loss of catalytic activity of a protein.
... ... *native structure: The "native" structure or
configuration of a biological macromolecule is the functional
state or configuration ordinarily assumed by the molecule in the
biological system in which the molecule occurs.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99
-------------------
Related Background:
ON THE CHEMICAL PHYSICS OF PROTEIN FOLDING
... ... C.L. Brooks et al present a short review of protein
folding from the perspective of chemical physics, and with a
focus on the work of their own group, the authors make the
following points: 1) The question of the mechanism of protein
folding was once thought to be entirely analogous to the question
of mechanism in intermediary metabolism or classical organic
chemistry: the essential classical idea was that a protein
folding pathway involves a series of discrete intermediates. Such
discrete intermediates do occur in the late stages of protein
folding, but to answer the practical questions of structure
prediction and design, a new viewpoint on folding is required. 2)
The authors suggest this new viewpoint is that of chemical
physics rather than that of classical chemistry, and that the
chemical physics view requires a new set of theoretical ideas,
computational techniques, and major advances in experimental
methodology. 3) The authors suggest the theoretical framework for
the new chemical physics approach to protein folding should be
that of "*energy landscape theory", which asserts that "a full
understanding of the folding process requires a global overview
of the energy landscape." 4) The authors propose that the protein
folding energy landscape resembles a partially rough funnel
riddled with energy traps where the protein can transiently
reside. There is no unique pathway but a multiplicity of
convergent folding routes toward the native state... The authors
state that the essence of the funnel energy landscape idea is
competition between the tendency toward the folded state and
trapping because of "ruggedness" of the funnel. 5) Concerning
theoretical modeling, the authors point out that simulations with
detailed atomic models are extremely intensive numerically, so
that the number and size of systems that can be studied is
limited. Simulation models of intermediate complexity have
therefore been used. 6) Concerning experimental approaches to
exploring the energy landscape of protein folding, there are
various new methods involving the physical monitoring of folding
from an unfolded state, for example, monitoring in the
microsecond range following initiation of folding by a
nanosecond-scale step-change in ambient temperature. The authors
conclude: "Experiments are beginning to build up a *phase diagram
of folding kinetics that can be used to test and refine
theoretical models."
-----------
C.L. Brooks et al (4 authors at 3 installations, US)
Chemical physics of protein folding.
(Proc. Natl. Acad. Sci. US 15 Sep 98 95:11037)
QY: Charles L. Brooks, Scripps Research Institute 619-784-1000.
-----------
Text Notes:
... ... *energy landscape: The "energy landscape" here refers to
the contours of what is essentially a classical energy/entropy
diagram, with the native configuration state positioned at the
bottom of a deep potential well, in this case a funnel with sides
containing miniature energy wells or "traps".
... ... *phase diagram: A classical graphical representation of
the equilibrium relationships between phases of a chemical
system.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 23Oct98


4. ON THE NEANDERTHALS IN HUMAN EVOLUTION
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-three 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?
... ... I. Tattersall and J.H. Schwartz present a review of
recent research in this area, the authors making the following
points:
     1) Although many paleoanthropologists have lately begun to
look favorably on the view that Neanderthals merit species
recognition in their own right as Homo neanderthalensis, at least
as many paleoanthropologists still regard the Neanderthals as no
more than a strange variant of our own species, Homo sapiens.
This difference in viewpoint represents far more than a simple
matter of taxonomic hair-splitting, since if the Neanderthals are
considered as a single species they must be analyzed and
understood on their own terms. In contrast, if the Neanderthals
are merely subspecies variants of ourselves, they can be
dismissed as little more than an evolutionary epiphenomenon, a
minor and ephemeral appendage to the history of Homo sapiens.
     2) Recently, Duarte et al (1999) proposed that the skeleton
of a 4-year-old child, unearthed in late 1998 at the 24,500-year-
old site of Lagar Velho in Portugal, represents not merely a
casual result of a Neanderthal/modern human mating, but rather is
the product of several millennia of hybridization among members
of the resident Neanderthal population and the invading Homo
sapiens.
     3) In general, "Neanderthals" is the informal designation of
a morphologically distinctive group of large-brained *hominids
who inhabited Europe and western Asia between approximately
200,000 and less than 30,000 years ago. They are sharply
distinguished from modern humans by a wide range of cranial and
*postcranial characteristics, although they do share a number of
derived bony features with other members of the European/western
Asian hominid *clade that diversified in this part of the world
after approximately 500,000 years ago. Subsequent to
approximately 150,000 years ago, the Neanderthals appear to have
been the sole surviving species of this clade.
     4) The Neanderthals were apparently highly successful over a
large region for a substantial period of time, but this situation
changed dramatically with the arrival in Europe of the first
modern humans, Homo sapiens. The evidence is that these "Cro-
Magnons" had begun to arrive both in eastern Europe and in the
far northeast of the Iberian Peninsula by approximately 40,000
years ago, and within little more than 10,000 years, the
Neanderthals were gone. The mechanism of their eviction has long
been debated, but there are four main possibilities. The first
and second of these possibilities, that the Neanderthals were
eliminated by the moderns in direct conflict or by indirect
economic competition, both imply the separate species status of
the Neanderthals, as does any combination of these two
possibilities. The alternative possibilities, that the
Neanderthals had simply evolved rapidly into moderns, or that the
genes of the invading moderns simply "swamped" those of the
Neanderthals, both imply some form of species continuity.
     5) The authors suggest that the analysis by Duarte et al of
the Lagar Velho child's skeleton is "a brave and imaginative
interpretation" which the majority of paleoanthropologists will
consider unproven. The archeological context of Lagar Velho is
that of a typical *Gravettian burial, with no sign of *Mousterian
cultural influence, and the specimen itself lacks not only
derived Neanderthal characteristics, but also lacks any
suggestion of Neanderthal morphology.
     6) the authors conclude: "The probability must thus remain
that this is simply a chunky Gravettian child, a descendant of
the modern invaders who had evicted the Neanderthals from Iberia
several millennia earlier. However, in this contentious and
poorly documented field, any new data are eagerly sought, and
Duarte et al's courageous speculations will doubtless spur much-
needed new research."
-----------
I. Tattersall and J.H. Schwartz: Hominids and hybrids: The place
of Neanderthals in human evolution.
(Proc. Natl. Acad. Sci. US 22 Jun 99 96:7117)
QY: Ian Tattersall [iant@amnh.org]
-----------
Text Notes:
... ... *hominids: In general, any primate in the human family.
... ... *postcranial: In general, this refers to the skeleton
behind the cranium in a quadruped and below the cranium in a
biped.
... ... *clade: A "clade" is a cluster of taxa derived from a
single common ancestor.
... ... *Gravettian: A paleolithic culture in Europe extending
from approximately 30,000 to approximately 22,000 years ago.
... ... *Mousterian: Neanderthals lived by hunting and gathering,
probably in small, nomadic groups, an existence that evidently
required extraordinary strength. Their tool technology involved
the so-called "*Levallois technique" to produce flakes that were
then further worked to yield as many as 60 different implements.
For the Neanderthals, this Middle Paleolithic technology is
termed "Mousterian" after a cave at Le Moustier, France.
Mousterian flakes could be used for many purposes, including
cutting flesh, scraping hides, and working wood.
... ... *Levallois technique: Named after the site in France
where the first examples of such tools were found. This tool-
making technique involves the preparation of a large stone "core"
with a flat upper surface and a convex lower surface. Broad
flakes are detached from the core by striking the core sharply at
an angle on an anvil. The resulting flakes are broad and thin.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99
-------------------
Related Background:
ON MODERN HUMAN ORIGINS
The study of human origins, the field called paleoanthropology,
has intrinsic difficulties because of the relative scarcity of
data, but these difficulties are magnified enormously by the
simple fact that paleoanthropology, in essence, represents a
species attempting to reconstruct its own early history. As might
be expected, an objective reconstruction, one without biases and
preconceptions, is far from easy. The human group we call the
"Neanderthals" lived in much of Europe, part of Asia, and the
Middle East between 150,000 to probably less than 30,000 years
ago. Neanderthals were the first fossil humans to be discovered,
and they have long been the focus of anthropological
investigation. More bones of Neanderthals are known than for any
other human-related (hominine) fossil group, including 30 nearly
complete skeletons, so the preoccupation of the anthropology
community with the Neanderthals is perhaps understandable. One of
the important questions concerning the Neanderthals is what
happened to them? Hypotheses have shifted back and forth since
the first discovery in 1856 of Neanderthal bones, with two major
views. One view is that the Neanderthals were the direct
ancestors of modern Europeans. The other view regards the
Neanderthals as a side branch of human evolution, with extinction
as their fate. This latter view is apparently the majority view
in the paleoanthropology community.
... ... G.A. Clark (Arizona State University, US) presents a
review of current research controversies and methods concerning
the transition from early humans to modern humans that apparently
occurred during the period from 50,000 to 10,000 years ago
(Middle-Upper Paleolithic transition). A central question is
whether the transition occurred abruptly or gradually. The author
makes the following points:
     1) Insufficient data is only part of the reason the question
of human origins remains unresolved. Researchers in this area
come from various research traditions, and in each of these
traditions different assumptions about the remote human past
determine what is considered relevant data, which questions are
asked of the data, and how the data are interpreted. More data do
not remove the paradigmatic bias implicit within each research
tradition, and in consequence people from the different relevant
fields fail to communicate effectively.
     2) The disciplines that contribute to the field (archeology,
human paleontology, and molecular biology) tend to be discovery-
driven and focused on methodology. The result is a common absence
of concern for the logic of inference underlying claims of
knowledge. European archeological studies of modern human origins
are a particularly good example of such epistemological naivete.
These studies are based on a century-old typological systematics
that emphasizes retouched stone tools, coupled with a set of
biases and preconceptions concerning the relationships between
developments in tool-making and developments of cultures.
     3) On the surface, the voluminous literature produced by the
debate concerning modern human origins suggests an informed and
sophisticated interdisciplinary research in which data are
absorbed and digested, arguments assimilated, and methodologies
understood, compared, and evaluated. The author suggests "this is
a gross simplification of a much more complex reality."
     4) The author concludes: "We are, in effect, consumers of
one another's research conclusions, but we select among
alternative sets of research conclusions in accordance with our
biases and preconceptions. These biases and preconceptions must
be subjected to critical scrutiny. As long as there is no
explicit concern with the logic of inference -- how we know what
we think we know about the past -- there can be no consensus."
-----------
G.A. Clark: Highly visible, curiously intangible.
(Science 26 Mar 99 283:2029)
QY: G.A. Clark [gaclark@asu.edu]
-------------------
Summary by SCIENCE-WEEK [http://scienceweek.com] 28May99
-------------------
Related Background:
HUMAN EVOLUTION: THE FATE OF THE NEANDERTHALS
The current consensus in paleoanthropology is that the
Neanderthals were an extinct side-line of human evolution.
European Neanderthals are thought to have diverged from the
lineage that gave rise to modern humans at least 500,000 years
ago. The current view is that approximately 30,000 to 40,000
years ago the Neanderthals were replaced by modern populations,
probably from an ultimately African source. A present debate
concerns how this population replacement occurred.
... ... Paul Mellars, in a short review of a recent conference
(28-30 Aug 1998, Gibraltar, UK) on the Neanderthals, makes the
following points: 1) The current consensus is that in the
southern part of the Spanish peninsula, roughly to the south of
the Ebro valley, the local Neanderthals survived for at least
5000 to 10,000 years after the arrival of modern populations in
the adjacent parts of northern Spain and the Mediterranean coast.
2) The most likely explanation for the prolonged coexistence of
these two populations lies in the ecological differences between
the northern and southern parts of the Iberian peninsula. 3)
Studies of Neanderthal skeletal remains reinforce the conclusion
that the Neanderthals were a divergent lineage that probably made
no contribution to the evolution of anatomically modern humans.
This is consistent with the DNA evidence that the two lineages
separated at least 500,000 years ago, and even longer divergence
times are favored by some researchers. 4) The impression at the
end of the conference was that the Neanderthals were really quite
different from humans -- well adapted to survive in the harsh
glacial environments of Europe, but with distinct anatomical and
behavioral patterns different from their modern human successors.
The author concludes: "The eagerness of some scientists to claim
close kinship with the Neanderthals could come close to denying
that human evolution actually took place."
-----------
Paul Mellars (University of Cambridge, UK)
The fate of the Neanderthals.
(Nature 8 Oct 98 395:539)
-------------------
Summary by SCIENCE-WEEK  6Nov98
-------------------
Related Background:
FIRST ANALYSIS OF DNA FROM A NEANDERTHAL BONE
... For more than a century, one of the central questions in
paleoanthropology has been whether modern man evolved from this
race [the Neanderthals] -- 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 July)
(Science-Week 18 Jul 97)
-------------------
Related Background:
A POSSIBLE COMMON ANCESTOR OF NEANDERTHAL AND HOMO SAPIENS
The reconstruction of human evolutionary history is a slow and
halting process, the evidence scattered and fragmentary. But
paleoanthropologists persist. They gather the evidence, when they
can find it, and at intervals they conclude it necessary to
redraw the theoretical lines of evolution leading to modern man.
This week, from Spain, there is a suggestion that once again the
lines need to be redrawn. Antonio Rosas et al [National Museum of
Natural Sciences, Madrid ES; Complutense University of Madrid
(ES); Rovira i Virgili University, Tarragona (ES)] have presented
evidence from a find of 80 human fossil remains recovered between
1994 and 1996 in the Pleistocene cave site of Gran Dolina, Sierra
de Atapuerca, Burgos (ES). Included among the fossils is that of
an adolescent male, the bones approximately 800,000 years old,
with facial features a mix of both Neanderthal and modern
aspects. The Spanish team has named this a new species, Homo
antecessor, and they suggest the simplest explanation for the
various skeletal attributes is that H. antecessor is the common
ancestor of both H. neanderthalensis and H. sapiens, and that the
evolutionary lines need to be redrawn to show these two as
separate branches from the H. antecessor stem. Not all
paleoanthropologists agree, primarily because the basis for the
introduction of a new species into the evolutionary gallery is
the partial fossil of a single immature individual, in this case
a boy 10 or 11 years old. Despite the disagreement, what is
certain is that the evidence will be the focus of attention among
paleoanthropologists for some time.
(Science 30 May) (Science-Week 5 Jun 97)


5. GENETIC CONTROL OF BRANCHING MORPHOGENESIS
Many essential organs -- such as the lung, vascular system,
kidneys, and most glands -- are composed of ramifying networks of
*epithelial tubes that transport fluids. The exquisite branching
patterns of these organs have fascinated biologists and
mathematicians since Aristotle, but the mechanisms that generate
these complex 3-dimensional structures during embryonic
development have remained a mystery. Despite remarkable progress
during the past two decades in developmental biology, the
molecules and mechanisms that dictate complex organ structures
have been elusive. ... ... R.J. Metzger and M.A. Krasnov
(Stanford University, US) present a review of current work in
this field, the authors making the following points:
     1) Essentially all branched tubular networks in organisms
are constructed of an epithelial sheet-like monolayer of cells
wrapped into a tubular structure. Most of these structures begin
development as a simple epithelial sac or tube from which new
branches successively bud, giving rise to a tree-like structure
of interconnected tubes. In some organs, such as the lung,
additional supporting cell layers develop around the epithelial
tubes, but in other organs, such as the fruit fly (Drosophila
melanagaster) *tracheal system, the tubes remain unadorned.
     2) There are hundreds to millions of branches in most
organs, and the patterns of branching, although exceedingly
complex, are seldom random [*Note #1]. At least for the early
branch generations, the patterns are highly stereotyped, implying
that they are under fixed developmental control. Furthermore,
there are certain regularities in the structures of the branches.
For example, in the lung there is a consistent relationship
between branch generation and branch diameter, which facilitates
flow through the network.
     3) The genetic programs that direct formation of the tree-
like structures of two animal organs have begun to be elucidated.
In both the developing Drosophila tracheal (respiratory) system
and the mammalian (mouse) lung, a *fibroblast growth factor (FGF)
signaling pathway is apparently reiteratively used to pattern
successive rounds of branching. The initial pattern of signaling
appears to be established by early and more global embryonic
patterning systems. The fibroblast growth factor pathway is then
modified at each stage of branching by genetic feedback controls
and other signals to give distinct branching outcomes. The
reiterative use of a fibroblast growth factor signaling pathway
by both insects and mammals suggests a general scheme for
patterning branch morphogenesis.
-----------
R.J. Metzger and M.A. Krasnow: Genetic control of branching
morphogenesis.
(Science 4 Jun 99 284:1635)
QY: Mark A. Krasnow [krasnow@cmgm.stanford.edu]
-----------
Text Notes:
... ... *epithelial tubes: 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.
... ... *tracheal system: In general, a "trachea" is a tube
through which oxygen enters the body. The human trachea, for
example, is a single tube that runs through the throat, then
divides to form the bronchi, which in turn divide to form the
airway passages of the lung. In terrestrial arthropods (which
include insects), multiple tracheae lead from pores (spiracles)
on the body, dividing into finer and finer branches (tracheoles)
which penetrate muscles and organs to finally distribute oxygen
by diffusion.
... ... *Note #1: In the human lung, for example, 20 or more
generations of branches can be anatomically identified.
... ... *fibroblast growth factor: A fibroblast is a type of
connective tissue cell, secreting structural proteins (e.g.,
collagen) that form certain tissue components. Growth factors are
peptide hormones that regulate the growth of cells and tissues. 
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99


6. BRAIN SEX DIFFERENCES AND ADULT BRAIN PLASTICITY
Sex differences in brain structure have been recognized since the
work of Raisman and Field in 1971. In general, brain sex
differences have been considered to arise in late fetal and
neonatal development (perinatal development) through the actions
of the *hormone testosterone secreted by the developing testes,
and these sex differences have been believed to persist even when
gonadal hormones in adult life are absent. This scenario is very
much like that of the male and female reproductive tracts, which
are also developmentally determined, and whose general structures
remain fixed. Recent evidence, however, has forced a change in
this view. The fundamental scheme of sex differences now appears
to be the result of a cascade of events beginning with the role
of the sex-determining genes in sexual differentiation and
continuing with the actions of hormones in embryonic, neonatal,
pubertal, and adult life. In other words, the current view is
that significant changes in the adult brain (in both animals and
humans) can occur as a result of adult hormonal changes.
... ... Bruce S. McEwen (The Rockefeller University, US) presents
a review of current research in this field, the author making the
following points:
     1) The emphasis on early developmental programming of brain
structural sex differences was reinforced during the past two
decades by the long-standing view that the brain is not capable
of significant structural changes in adulthood. This view,
however, is changing. There is recent evidence, for example, of a
particular brain sex difference in rats controlled entirely by
circulating androgens. Cooke et al (1999) [*Note #1] have
reported that a particular cluster of neurons (posterodorsal
*nucleus) in the medial *amygdala of the rat is larger in male
rats than in females, but castration of adult males causes the
volume of the nucleus to decrease to female levels within 4
weeks. As a corollary, testosterone treatment of adult females
for 4 weeks enlarges the volume of this nucleus to male levels.
Not only is the volume of the anatomical nucleus affected, but
the individual neuron cell bodies are also increased in size by
the hormone androgen, irrespective of genetic sex of the animal.
Thus, hormone actions in the adult brain apparently affect not
only neurochemistry, but also the structure of nerve cells, and
this realization constitutes a paradigm shift in our thinking
about the plasticity of the adult brain.
     2) In humans, certain nuclei in the *hypothalamus are known
to differ between male and females. There are also some
indications that such nuclei may differ in size between
homosexual and heterosexual males, and between transsexual and
heterosexual males. Notable among these are hypothalamic nuclei
for which sex differences are absent at birth, develop around 4
years of age, and persist until approximately 50 to 60 years of
age, at which time there is a decrease in volume at different
rates in both sexes.
     3) The author suggests the following scenario for the
cascade of effects leading to *phenotypic sex differences:
Sex-determining genes promote the differentiation of the testes,
and testosterone secretion during embryonic, neonatal, pubertal,
and adult life masculinizes and defeminizes the brain. Estrogen
hormone actions in the female brain activate functions that have
been allowed to develop in the absence of testosterone, and
testosterone given to a genetic female early in development
produces an individual with many phenotypic characteristics of a
genetic male, particularly regarding brain function and secondary
sex characteristics. Experiences during the lifespan interact
with the hormone actions to produce the final phenotype of the
individual.
     4) The author concludes: "The study by Cooke et al (1999)
highlights the dynamic nature of the mature nervous system in its
ability to change reversibly in response to circulating hormones.
Thus, when a sex difference in the structure of the brain is
reported, the role of adult hormone secretion must be considered
along with the developmental actions of gonadal hormones."
-----------
Bruce S. McEwen: Permanence of brain sex differences and
structural plasticity of the adult brain.
(Proc. Natl. Acad. Sci. US 22 Jun 99 96:7128)
QY: Bruce S. McEwen [mcewen@rockvax.rockefeller.edu]
-----------
Text Notes:
... ... *hormone: In general, a "hormone" is a chemical
messenger, a molecular entity secreted by one part of an
organism, and which affects the growth, development, behavior,
etc. of other parts.
... ... *Note #1: B.M. Cooke et al (Proc. Natl. Acad. Sci. US
99/96:7538)
... ... *nucleus: In this context, a "nucleus" is an anatomically
recognizable cluster of a large number of nerve cells.
... ... *amygdala: A nucleus in the temporal lobe with major
involvements in autonomic, emotional, and sexual behavior.
... ... *hypothalamus: A deep brain structure with various
clusters of nerve cells controlling several important homeostatic
functions such as temperature regulation and food intake, and in
addition the sex drive, aggressive emotions, psychosomatic
effects, etc. The hypothalamus essentially integrates the
activity of the autonomic nervous system, and it acts as an
intermediary between the endocrine (hormone) system and the
nervous system, with various hypothalamic neuron types secreting
hormones themselves.
... ... *phenotypic: The term "phenotype" is used in various
ways, but in general refers to the total appearance of an
organism as determined by the interaction between its genetic
constitution (genotype) and the environment. In this context,
"appearance" refers to the appearance (anatomy) of the brain, and
"environment" includes all factors other than direct genetic
factors.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99
-------------------
Related Background:
EFFECT OF ESTROGEN ON HUMAN BRAIN ACTIVATION PATTERNS
Estrogen is a collective term for the female hormones, the most
powerful of which is estradiol. They control female secondary
sexual characteristics, and prepare and maintain the uterine
lining. Perhaps the single most important biological event for
most middle-aged women is menopause, which results in decreased
levels of circulating estrogen. The declining estrogen levels
characteristic of menopause affect a range of systems, including,
in addition to the reproductive system, the cardiovascular and
skeletal systems. There is also evidence that estrogen affects
basic neural processes in mature animals, and estrogen has been
shown to affect cognitive function in animals. There have been
studies of the effect of estrogen on cognitive function in
postmenopausal women, but the results have been inconsistent.
Recent advances in technology now permit the noninvasive
measurement of brain function as individuals perform memory and
other cognitive tasks. This technique, called "*functional
magnetic resonance imaging", exploits the differences in the
magnetic properties of oxygenated compared with deoxygenated
blood. In performing a cognitive task, such as *working memory,
blood flow and oxygen  concentration are altered in those brain
regions engaged in the task. ... ... S.E. Shaywitz et al (16
authors at 2 installations, US) report a study to investigate the
effects of estrogen on brain activation patterns in
postmenopausal women as they performed verbal and nonverbal
working memory tasks. The study involved 46 right-handed
postmenopausal women age 33 to 61 years in a randomized, *double-
blind, placebo-controlled, *crossover trial from 1996 through
1998. The intervention consisted of a 21 day treatment with
*conjugated equine estrogens (1.25 milligrams/day), randomly
crossed over with identical placebo, and a 14-day washout between
treatments. The authors measured brain activation patterns using
functional magnetic resonance imaging, and the authors report
that treatment with estrogen increased activation in the
*inferior parietal lobe during storage of verbal material, and
decreased activation in the inferior parietal lobe during storage
of nonverbal material. Estrogen also increased activation in the
*right superior frontal gyrus during retrieval tasks, accompanied
by greater left-hemisphere activation during *encoding. The
authors conclude that estrogen in a therapeutic dosage alters
brain activation patterns in postmenopausal women in specific
brain regions during the performance of the sorts of memory
function that are called upon frequently during any given day.
The authors suggest these results indicate that estrogen affects
brain organization for memory in postmenopausal women.
-----------
S.E. Shaywitz: Effect of estrogen on brain activation patterns in
postmenopausal women during working memory tasks.
(J. Amer. Med. Assoc. 7 Apr 99 281:1197)
QY: Sally E. Shaywitz [Sally.Shaywitz@yale.edu]
-----------
Text Notes:
... ... *functional magnetic resonance imaging: First, we
distinguish between magnetic resonance imaging (MRI) and
"functional" magnetic resonance imaging (fMRI) as applied to the
brain. The former is essentially a technique for examining
morphology, while the latter is a technique for examining
activity of brain tissue. Both techniques involve computerized
analysis of data. In general, MRI involves magnetic coils
producing a static magnetic field parallel to the long axis of
the patient or subject, combined with inner concentric magnetic
coils producing a static magnetic field perpendicular to the long
axis. A radio-frequency coil specifically designed for the head
perturbs the static fields to generate a magnetic resonance
image. The interaction physics in this technique is that between
the magnetic fields and atomic nuclei in brain tissue. "Sliced"
views can be obtained from any angle, and the resolution is quite
high and on the order of millimeters for current magnetic field
strengths of 1.5 tesla. Functional magnetic resonance imaging
(fMRI), the variant of MRI discussed here, is based on the fact
that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a
different magnetic resonance signal than deoxyhemoglobin, the
oxygen-depleted form of hemoglobin. Activated brain areas utilize
more oxygen, which transiently decreases the levels of
oxyhemoglobin and increases the levels of deoxyhemoglobin, and
within seconds the brain microvasculature responds to the local
change by increasing the flow of oxygen-rich blood into the
active area. This local response thus leads to an increase in the
oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for
the fMRI signal in this technique. Because of its high spatial
resolution (millimeters) and high temporal resolution (seconds)
compared to other imaging techniques, fMRI is now the technology
of choice for studies of the functional architecture of the human
brain.
... ... *working memory: In this context, the term "working
memory" refers to a particular type of short-term memory
involving the ability to hold things in mind long enough to carry
out sequential actions.
... ... *double-blind: In general, a "double-blind" experimental
procedure is one in which neither the subjects nor the
experimenters know the makeup of the test and control group
during the actual course of the experiments.
... ... *crossover trial: In general, a "crossover trial" is an
experimental or clinical procedure in which subjects are divided
randomly into at least as many groups as there are kinds of
treatment to be given, and then the groups are interchanged until
every subject has received each treatment.
... ... *conjugated equine estrogens: This is an amorphous
preparation of naturally occurring water-soluble conjugated forms
of mixed estrogens obtained from the urine of pregnant mares. The
principal estrogen present is sodium estrone sulfate.
... ... *inferior parietal lobe: the parietal lobe is
approximately the middle portion of each cerebral hemisphere seen
from the side. In this context, the term "inferior" refers to the
lower part.
... ... *right superior frontal gyrus: The term "gyrus" refers to
any of the visible convoluted ridges of the cerebral hemispheres.
Seen from the side, the superior frontal gyrus is the foremost
ridge of the frontal lobe.
... ... *encoding: In this context, the term "encoding" refers to
the first stage of the memory process, prior to storage and
retrieval, and associated with receiving stimuli through one or
more of the senses.
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 30Jul99


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

IN FOCUS: ON DEVELOPMENTAL PATHWAYS
"We think of development as a process of inexorable progressive
change by which a single cell is transformed into a complex
multicellular organism, made up of many tissues and organs, each
with a distinctive structure and function. In any given species,
the progression from the simple to the complex occurs in an
orderly fashion that is repeated with little or no variation in
millions of individuals, generation after generation. Barring
severe genetic mutations or environmental trauma, all individuals
of a species develop in identical fashion and the final products,
the adult animals, resemble each other to a remarkable degree. As
a rule, developmental pathways are highly resistant to genetic
and environmental variation, a phenomenon that goes variously by
the names of canalization, robustness, or developmental
homeostasis. Superimposed on this constancy, some animals have
evolved the ability to develop into drastically different adult
forms by switching to one of several alternative developmental
pathways, depending on certain signals from their environment.
Although the general phenomenology has long been known, it is
only recently that methods have been developed to study the
genetic and molecular mechanisms that underlie such developmental
switches, [e.g., the mechanism that controls whether a honey bee
larva will develop into a queen or into a worker]... It has long
been known that queen and worker bees differ in many
characteristics. A queen bee is larger than a worker and has a
functional reproductive system (the worker is sterile), but she
has a substantially smaller brain, and her appendages, mouth
parts, and stinger have a simpler anatomy than those of a worker.
The developmental switch is controlled by the nutrition a larva
receives. Larvae that are fed royal jelly, a secretion from the
mandibular (salivary) glands of worker bees, during the latter
portion of their larval life will develop into queens, whereas
larvae that are fed only pollen and nectar during this period
develop into workers. The difference in food quality alters the
pattern of hormone secretion, so that the queen larvae have a
higher titer of *juvenile hormone than worker larvae during a
juvenile hormone-sensitive period that occurs during the fourth
and fifth larval *instars. A presumptive worker larvae can, in
fact, be induced to develop queen characters by a simple topical
application of juvenile hormone during this sensitive period."
-----------
H. Frederik Nijhout: When developmental pathways diverge.
(Proc. Natl. Acad. Sci. US 11 May 99 96:5348)
-----------
Text Notes:
... ... *juvenile hormone: In general, "juvenile hormone" is a
hormone found in insects that prevents *metamorphosis into the
adult form and maintains larval characteristics. This hormone
functions antagonistically to the hormone "ecdysone", which
promotes *molting and differentiation into the adult. Juvenile
hormone is produced in specialized secretory cells in the corpus
allatum, a structure near the insect brain. At least 3 varieties
of juvenile hormones have been chemically identified: all are
derivatives of farnesoic acid.
... ... *metamorphosis: In general, the process during which an
animal undergoes a comparatively rapid change from larval to
adult form.
... ... *molting: (ecdysis) In general, periodic shedding of an
outer layer. In insects, the process is controlled by the hormone
ecdysone ("molting hormone").
... ... *instars: The stages between molts.
-------------------
Notes by SCIENCE-WEEK [http://scienceweek.com] 3Sep99


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