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.

January 5, 2001 -- Vol. 5 Number 1

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

Science keeps moving us away from the Apes.
Of course, if one wants to be an ape, one
objects to the movement.
-- Anonymous

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

Please note: You can help support ScienceWeek by
buying your books via the ScienceWeek connection to
Amazon.Com at http://www.scienceweek.com/books.htm

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

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

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

1. EARTH SCIENCES: TRANSPACIFIC AIR POLLUTION
The once-pristine air above the North Pacific Ocean is now
polluted, with pollutants transported on mid-latitude westerly
winds from Eurasia to the Pacific Ocean basin and across to North
America. It is expected that the economic expansion around the
Pacific Rim and in the rest of the world will deliver even more
pollution unless preventive measures are taken. The risk of
adverse effects on wildlife, ecosystems, climate, and human
health throughout the Pacific region will increase. Even remote
areas such as Arctic and alpine environments are threatened, and
ocean productivity and the atmospheric energy budget over the
North Pacific Ocean could be altered.
(Science 6 Oct 00 290:65)

2. MATERIALS SCIENCE: NANOELECTROMECHANICAL SYSTEMS
Nanoelectromechanical systems are characterized by small 
dimensions, with the dimensions relevant to the function of the
devices. Critical feature sizes may range from hundreds down to a
few nanometers. New physical properties, resulting from the small
dimensions, may dominate the operation of the devices, and new
fabrication approaches may be required to construct such devices.
The new class of nanoelectromechanical devices may provide a
revolution in applications such as sensors, noninvasive medical
diagnostics, displays, high-density data storage, and
nanoelectromechanical devices will enable experiments on the
structure and function of individual biomolecules.
(Science 24 Nov 00 290:1532)

3. QUANTUM PHYSICS: ON MAX PLANCK
After a decade of work on the problem, Max Planck eventually
found a full explanation of blackbody radiation only after
forcing himself "to an act of despair" by assuming that energy
can only be exchanged between the light field inside the
blackbody box and the walls of the container in discrete quanta,
multiples of the energy E = hv, where (v) is the frequency of the
light and (h) is a constant (now called "Planck's constant"). For
many years, Planck tried unsuccessfully to find an alternative
derivation of this experimentally successful radiation law from
other known laws of physics, but he gradually came to accept the
realization that he had found something fundamentally new. Thus,
the quantum idea, in the work of Planck, actually predated 1900,
but Planck disbelieved it and refused to publish it.
(Nature 7 Dec 00 408:639)

4. EVOLUTIONARY BIOLOGY: HOW DO NEW SPECIES ARISE?
One of the most persistent questions in evolutionary biology is,
How do new species arise? As with many simple questions, there is
no simple answer, only complex answers to a number of
interrelated questions. New evidence demonstrates significant
premating reproductive divergence between Drosophila melanogaster
populations adapted to distinct, but closely adjacent, habitats,
and the work suggests that reproductive isolation has evolved _in
situ_ as a result of adaptive divergence in response to
contrasting environments -- despite the fact that the populations
in the study are within easy "cruising range" of each other.
(Proc. Natl. Acad. Sci. US 7 Nov 00 97:12398)

5. CELL BIOLOGY: ON PROTEASOMES
Proteasomes are large multi-subunit multicatalytic enzyme
complexes that selectively degrade intracellular proteins,
literally chop the proteins into constituent amino acids so that
the amino acids can be recycled to the synthesis of other
proteins, the synthesis carried out elsewhere in the cell by
ribosomes. A typical cell in the human body contains
approximately 30,000 proteasomes, each of which is a relatively
enormous structure. Whereas the average protein has a molecular
weight of the order of 40,000 to 80,000 daltons, most proteasomes
of higher organisms have a molecular weight in excess of 2
million daltons. (Scientific American January 2001)

6. MEDICAL BIOLOGY: ORIGINS OF CANCER
Cancer results from the accumulation of mutations in genes that
regulate cellular proliferation. These mutations can occur early
in the process of malignant transformation or later, during
progression to an invasive carcinoma. The earliest mutations
occur in the germ line, as in the case of cancer-prone families.
In these instances, the inheritance of a mutated allele is
commonly followed by the loss of the second allele from a somatic
cell, leading to the inactivation of a tumor-suppressor gene and
triggering malignant transformation. Genes important to the
development of cancer regulate diverse cellular pathways,
including the progression of cells through the cell cycle,
resistance to programmed cell death (apoptosis), and the response
to signals that direct cellular differentiation.
(New England J. Med. 23 Nov 00 343:1566)

7. IN FOCUS: ON THE HISTORY OF SCIENCE

8. FROM THE SCIENCEWEEK ARCHIVE: COMPUTER SCIENCE: ALAN TURING


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

1. EARTH SCIENCES: TRANSPACIFIC AIR POLLUTION
     In general, the term "air pollution" refers to the release
into the atmosphere of gases, finely divided solids, or finely
dispersed liquid aerosols at rates that exceed the capacity of
the atmosphere to dissipate them or to dispose of them through
incorporation into solid or liquid layers of the biosphere. Not
all air pollution is anthropogenic: dust storms in desert areas
and smoke from forest and grass fires contribute to chemical and
particulate pollution of the atmosphere. For example, dust blown
from the Sahara Desert in Africa has been detected in West Indian
islands. Pesticides have been discovered in Antarctica, where
they have never been used, suggesting the extent to which aerial
transport can carry pollutants from one geographic region to
another. Another example: fallout of tetraethyl lead from urban
automobile exhausts has been observed in the oceans and on the
Greenland ice sheet. Perhaps the most important natural source of
air pollution is volcanic activity, which can pour great amounts
of ash and toxic fumes into the atmosphere.
     In this context, the term "aerosol" refers to a dispersion
in which a finely divided solid is suspended in air and the
particles are of colloidal dimensions. The term "colloidal
dimensions" usually refers to the range approximately 1 nanometer
to 100 nanometers in diameter, although some authors include
larger diameters.
... ... K.E. Wilkening et al (3 authors at 3 installations, CA
US) present a commentary on recent evidence of trans-Pacific air
pollution, the authors making the following points:
     1) The authors point out that the once-pristine air above
the North Pacific Ocean is now polluted, with pollutants
transported on mid-latitude westerly winds from Eurasia to the
Pacific Ocean basin and across to North America. The authors
suggest the expected economic expansion around the Pacific Rim
and in the rest of the world will deliver even more pollution
unless preventive measures are taken. The risk of adverse effects
on wildlife, ecosystems, climate, and human health throughout the
Pacific region will increase. Even remote areas such as Arctic
and alpine environments are threatened, and ocean productivity
and the atmospheric energy budget over the North Pacific Ocean
could be altered.
     2) The authors point out that two recent events have been
particularly important in focusing attention on trans-Pacific
pollutant transfer: a) in 1997, rapid transport of pollutants
from Asia to the Olympic peninsula of Washington State was
observed; and b) in April 1998, satellite remote sensing showed
aerosols being transported across the Pacific to North America
from a massive dust storm in Western China. Observational data,
computer simulations, and research on pollutant concentrations in
various media such as snow, fish, or eagles have since provided
additional evidence of a potential pan-Pacific air quality
problem.
     3) The authors conclude: "Research into the dynamics of
long-range transport, deposition, and impacts of atmospheric
pollutants in the Pacific region is only beginning. The nature,
magnitude, and spatial distribution of the pollutants and their
effects are largely unknown. Greatly expanded interdisciplinary
and international research effort is required before trans-
Pacific air pollution and other environmental issues in the
Pacific region can be addressed effectively."
-----------
K.E. Wilkening et al: Trans-Pacific air pollution.
(Science 6 Oct 00 290:65)
QY: K.E. Wilkening: kew@unbc.ca
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm

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

2. MATERIALS SCIENCE: NANOELECTROMECHANICAL SYSTEMS
Every working scientist is aware of how present knowledge is
constrained by present technologies. Science and technology are
often considered as separate enterprises, but they are actually
intertwined and inseparable, for science provokes new technology,
which in turn provokes new science via new instruments, a
continuing upward spiral of interaction that changes the world
and the way we live in it. These days, there is great excitement
in technology quarters about micron-scale and nanoscale devices.
The first impacts of such devices in basic science research are
already apparent, and there is a portent for the appearance
during the next several decades of new tools that will push
various sciences forward into new ground.
... ... H.G. Craighead (Cornell University, US) presents a review
of current research on nanoelectromechanical systems design, the
author making the following points:
     1) The author points out that micron-scale electromechanical
systems (microelectromechanical systems) have been studied for
decades, with interest recently increasing because of growing
commercial applications. The importance of microelectromechanical
systems is not so much the size, but rather the use of planar
processing technologies, related to those used in the fabrication
of electronic integrated circuits, to simultaneously "machine"
large numbers of relatively simple mechanical devices in an
integrated fashion.
     2) Nanoelectromechanical systems are characterized by even
smaller dimensions, with the dimensions relevant to the function
of the devices. Critical feature sizes may range from hundreds
down to a few nanometers. New physical properties, resulting from
the small dimensions, may dominate the operation of the devices,
and new fabrication approaches may be required to construct such
devices. Microelectronics fabrication technologies are pushing
forward to manufacture smaller transistors packed with increasing
density on integrated circuit chips. The economic driving forces
for this miniaturization are strong and have driven transistor
minimum feature sizes down to the 100-nanometer regime. The
miniaturization of commercial electronics has occurred with an
allied physics-motivated study of electron transport and magnetic
properties of mesoscopic and nanoscale devices. The nanoscale
studies often involve a wider range of materials and higher
spatial resolution fabrication processes than the silicon
microelectronics processes. Similar advanced fabrication
processes can be exploited to further miniaturize
electromechanical systems to bring us into the regime of
nanoelectromechanical systems. The new class of
nanoelectromechanical devices may provide a revolution in
applications such as sensors, noninvasive medical diagnostics,
displays, and high-density data storage. Nanoelectromechanical
devices will enable experiments on the structure and function of
individual biomolecules. The initial research in science and
technology related to nanoelectromechanical systems is taking
place now in a growing number of laboratories throughout the
world.
     3) Of importance in this context is "nanofluidics". Many
chemical, biological, and biophysical processes and experiments
take place in liquid environments. Therefore, a class of
nanoelectromechanical devices of considerable importance is
nanofluidic systems, with critical dimensions comparable to
relevant length scales in fluid environments. These length scales
include diffusion lengths of nanoparticles and molecules,
molecular size, and the *electrostatic screening lengths of ionic
conducting fluids. Microfluidics is now accepted as
technologically important for miniaturized chemical processing
systems, and micro total analytical systems or "lab-on-a-chip"
systems use microfabricated fluid systems primarily to transport
liquids in channels on the order of tens to hundreds of microns.
-----------
H.G. Craighead: Nanoelectromechanical systems.
(Science 24 Nov 00 290:1532)
QY: H.G. Craighead: Cornell University 607-254-4636
-----------
Text Notes:
... ... *electrostatic screening: In general, in this context,
"screening" is a reduction of the effective electric field at a
point, the reduction due to the space charge of ambient charged
particles of sign opposite to the source of the field. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm

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

3. QUANTUM PHYSICS: ON MAX PLANCK
     Since last year was the 100th anniversary of the official
birth of quantum physics, the subject has received much attention
in the scientific and popular media. Max Planck (1858-1947), the
father of quantum physics, received the Nobel Prize in Physics in
1918 for his work on energy quanta. Planck's initial professional
interest was thermodynamics, and he studied under Hermann
Helmholtz (1821-1894), Rudolf Clausius (1822-1888), and Gustav
Kirchhoff (1824-1887) at the University of Berlin, where he
received his doctorate _summa cum laude_ in 1879. Of his
doctorate and his illustrious mentors, Planck said Helmholtz did
not read his dissertation, Kirchhoff read it but did not approve
of it, and Clausius was not at all interested in it. In fact,
Planck's doctoral dissertation was of only minor importance and
certainly not a harbinger of things to come. Helmholtz did,
however, recognize Planck's talent, and Helmholtz was later
instrumental in getting Planck a professorship at the University
of Berlin in 1885, where Planck remained until he retired in
1926.
     In physics, an ideal radiator or absorber absorbs and thus
emits radiation of all frequencies equally and fully. A
radiator/absorber of this kind is called a "blackbody", and its
radiation spectrum is referred to as "blackbody radiation", which
depends on only one parameter, its temperature. The classical
idealized experiment involves the spectral distribution of
blackbody heat radiation emerging from a hole in a black box kept
at a certain temperature. At the end of the 19th century, there
were no satisfactory theoretical explanations of the experimental
observations of blackbody radiation. Planck's theoretical
explanation, which was eminently successful, was based on the
totally new idea of discrete energy quanta -- and thus quantum
physics was born.
... ... Anton Zellinger (University of Vienna, AT) presents a
commentary on the quantum centennial, the author making the
following points concerning Max Planck:
     1) Planck began working on the problem of black body
radiation during the early years of his professorship at the
University of Berlin. In 1894, the general problem was how to
explain the colors emitted by glowing bodies. The classical
explanation of that time worked well for the short parts of the
light spectrum, but did not agree with experiments for all
wavelengths. Planck had the advantage of close access to the most
recent experimental results on the spectral distribution of
blackbody heat radiation, results obtained by Otto Lummer (1860-
1925), Ernst Pringsheim (1859-1917), and Ferdinand Kurlbaum (?-?)
and Heinrich Rubens (?-?) at the University of Berlin.
     2) The author (Zellinger) points out that after a decade of
work on the problem, Planck eventually found a full explanation
of blackbody radiation only after forcing himself "to an act of
despair" by assuming that energy can only be exchanged between
the light field inside the blackbody box and the walls of the
container in discrete quanta, multiples of the energy E = hv,
where (v) is the frequency of the light and (h) is a constant
(now called "Planck's constant"). For many years, Planck tried
unsuccessfully to find an alternative derivation of this
experimentally successful radiation law from other known laws of
physics, but he gradually came to accept the realization that he
had found something fundamentally new. Thus, the quantum idea, in
the work of Planck, actually predated 1900, but Planck
disbelieved it and refused to publish it.
     3) Zellinger points out that the next important step in the
early days of quantum physics occurred in 1905, when Albert
Einstein (1879-1955) introduced the radical hypothesis of quanta
of light to explain the photoelectric effect. For some time, this
remained the only significant instance of the idea of the quantum
being taken seriously. Einstein's hypothesis met with strong
objections from his contemporaries, including from Planck
himself. As late as 1913, Planck, together with his colleagues
Heinrich Rubens, Walther Nernst (1864-1941), and Emil Warburg (?-
?), wrote in a recommendation letter for Einstein's election to
the Prussian Academy of Sciences: "One should not hold against
him too much that in his speculations he might have occasionally
overshot the goal, as for example in his hypothesis of the quanta
of light." It is an irony that it was this hypothesis that gained
Einstein the Nobel Prize in Physics in 1921.
     The history of quantum physics is a classic instance of how
ultimately successful revolutionary ideas in science are
sometimes hardly ever accepted in the beginning, even by their
originators. It is not easy to shake the mind out of a deep
groove.
-----------
Anton Zellinger: The quantum centennial.
(Nature 7 Dec 00 408:639)
QY: Anton Zellinger: University of Vienna, Boltzmanngasse 5, 1090
Wien, AT.
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
IN FOCUS: ON MAX PLANCK
"Many kinds of men devote themselves to science, and not all for
the sake of science herself. There are some who come into her
temple because it offers them the opportunity to display their
particular talents. To this class of men science is a kind of
sport in the practice of which they exult, just as an athlete
exults in the exercise of his muscular prowess. There is another
class of men who come into the temple to make an offering of
their brain pulp in the hope of securing a profitable return.
These men are scientists only by the chance of some circumstance
which offered itself when making a choice of career. If the
attending circumstances had been different, they might have
become politicians or captains of business. Should an angel of
God descend and drive from the temple of science all those who
belong to the categories I have mentioned, I fear the temple
would be nearly emptied. But a few worshippers would still remain
-- some from former times and some from ours. To these latter
belongs our Planck. And that is why we love him."
-----------
Albert Einstein: from the preface to _Where is Science Going?_ by
Max Planck.
(Original German text 1933, English text Ox Bow Press 1981)
-------------------
SCIENCE-WEEK http://scienceweek.com 7May99

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

4. EVOLUTIONARY BIOLOGY: HOW DO NEW SPECIES ARISE?
     In biology, the term "species" has had a history filled with
controversy, since the term essentially involves categorizations
of living systems, and such categorizations can range from the
subjective to the objective, but with objective categorizations
heavily dependent on extant knowledge of biological systems. Both
present and past biological systems show an extreme diversity of
form and function, and thus far no single definition of the term
"species" has been accepted as universally useful. The current
general view among biologists is to consider a species to be a
group of organisms that resemble each other and that are
generally able to interbreed and produce fertile offspring. This
is the so-called "biological species concept", derived from
Georges Buffon (1707-1788) and others, the concept defining a
species as a sexually interbreeding or potentially interbreeding
group of individuals normally separated from other species by the
absence of genetic exchange, i.e., by "reproductive isolation".
In contrast to this is the "evolutionary species concept",
championed by George Gaylord Simpson (1902-1984), an influential
paleontologist who proposed the idea that species be defined in
terms of differences that are not dependent on sexual isolation
but rather on their evolutionary isolation, of which sexual
isolation is only one aspect. In Simpson's words: "An
evolutionary species is a lineage (an ancestor-dependent sequence
of populations) evolving separately from others and with its own
unitary evolutionary role and tendencies." Neither concept of
species can be universally applied to all biological systems.
Some organisms, for example, exhibit asexual reproduction, which
makes irrelevant the idea of reproductive isolation as defining
speciation. Similarly, the application of the evolutionary
species concept depends on extensive knowledge of lineages, and
detailed lineages are not always apparent.
     Concerning both concepts, a natural and important question
is, How do species arise? What is the mechanism of "speciation"?
In the context of this report, this question is posed within the
framework of the biological species concept.
     In this context, an important idea is that of "natural
selection" (selection by natural circumstances, as opposed to
selection ["artificial selection"] by human intervention). The
theory of natural selection asserts that the genetic composition
of an evolutionary lineage will change through time by non-random
transmission of genes from one parental generation to the next, a
non-randomness ("selection") due solely to the fact that not all
gene combinations are equally suited to a given environment, and
that consequently individuals differ in their biological fitness.
     In contrast to natural selection is "genetic drift", which
refers to a statistically significant change in population gene
frequencies resulting not from selection, emigration or
immigration, but from causes operating randomly with respect to
the fitnesses of the genes concerned. For example, external
events suddenly impacting a population can result in an abrupt
shift in gene frequencies in that population.
     In this context, the term "genetic revolution" refers to the
emergence of new species by a process involving drastic changes
-- changes in many genes, as opposed to the emergence of new
species by a process involving changes in only a few genes.
     The term "founder event" refers to the "founder effect", the
principle that when a small sample of a large population
establishes itself as a newly isolated entity, its gene pool
carries only a fraction of the genetic diversity represented in
the parental population, and the evolutionary fates of the
parental and derived populations are thus likely to diverge.
     The term "gene flow" refers to the exchange of genes between
different populations of the same species produced by population
migrants, the process usually resulting in simultaneous changes
in gene frequencies at many loci in the recipient gene pool.
     A "premating (prezygotic) isolation mechanism" is any factor
that tends to reduce or prevent interbreeding between members of
genetically divergent populations or species, with the factor
functioning before fertilization occurs: e.g., ecological,
temporal, ethological, and other isolating factors. A "postmating
(postzygotic) isolation mechanism is any factor that similarly
reduces or prevents interbreeding, but with the factor
functioning after fertilization has occurred: e.g., hybrid
inviability, hybrid sterility, hybrid breakdown.
     In this context, the term "ecological selection" refers to
natural selection dependent on the relationships between
organisms plus the relationships between organisms and their
surroundings (ecological factors), and the term "ecological
speciation" refers to an ecologically forced emergence of new
species.
     At Lower Nahal Oren, Mount Carmel, Israel is a geologic
formation that has come to be known in the evolutionary biology
community as "Evolution Canyon". The opposite slopes of this
canyon, separated by only 100 meters at the bottom and 400 meters
at the top, manifest dramatic biotic contrasts because of the
higher (as much as 600 percent more) solar radiation on the
south-facing slope than on the north-facing slope. The south-
facing slope is warmer, drier, microclimatically more
fluctuating, and less predictable than the north-facing slope.
Previous studies have demonstrated a strong Evolution Canyon
interslope differentiation of the fruit fly Drosophila for a
complex of adaptive traits. These traits include changes in
viability and longevity caused by short-term and lifetime
temperature treatments, changes in fly weight because of
desiccation/starvation treatments at different temperatures,
different levels in the variation of fluctuating asymmetry,
different rates of mutation and *recombination, and changes in
habitat choice (preferred locus temperature for deposition of
eggs [oviposition temperature]). This remarkable differentiation
has evolved despite the small interslope distance (a few hundred
meters), a distance well within the dispersal capability of
Drosophila species. So far, there have been approximately 80
publications resulting from studies in Evolution Canyon, nearly
all studies showing adaptive divergence to the microscale climate
differences in the canyon.
... ... Christopher J. Schneider (Boston University, US) presents
a commentary on some recent work on Drosophila in Evolution
Canyon (A. Korol et al: Proc. Nat. Acad. Sci. US 97:12637 2000),
the author (Schneider) making the following points:
     1) The author points out that one of the most persistent
questions in evolutionary biology is, How do new species arise?
As with many simple questions, there is no simple answer, only
complex answers to a number of interrelated questions: How do
sexually reproducing organisms become reproductively isolated?
How do environment and ecological interactions influence the
formation of new species? Are the processes of local adaptation
and the evolution of reproductive isolation the same (i.e., both
resulting from the accumulation of small adaptive genetic
changes), or are the genetic changes leading to reproductive
isolation fundamentally different (i.e., large and rapid genetic
changes such as chromosomal rearrangements, genetic revolutions,
or founder events)? Is the disruption of gene flow necessary?
What are the relative roles of chance events (e.g., genetic
drift) and natural selection in speciation?
     2) The author (Schneider) suggests the short answer to all
of the above questions is that reproductive divergence can evolve
in a number of ways: Both drift and selection can be important,
depending on the number, degree of interaction, and magnitude of
effect of genes involved in reproductive isolation; depending on
the relationship between genes controlling reproductive
compatibility and *phenotypic characters that may be under
ecological selection; and depending on the historical effective
population size of the diverging populations.
     3) Korol et al report highly significant mate choice by
Drosophila flies from different slopes of Evolution Canyon, with
preference for sexual partners originating from the same slope.
No preferences were found when the sexual partners belonged to
different *isofemale lines from the same slope.
     4) Schneider suggests that the report by Korol et al
demonstrates significant premating reproductive divergence
between Drosophila melanogaster populations adapted to distinct,
but closely adjacent, habitats in Evolution Canyon. Korol et al
suggest that reproductive isolation has evolved _in situ_ as a
result of adaptive divergence in response to the contrasting
environments of north- and south-facing slopes in Evolution
Canyon, despite the fact that the populations are within easy
"cruising range" of each other. Korol et al suggest that the
divergence of Drosophila occupying distinct habitats in Evolution
Canyon represents an early stage in ecological speciation in
which divergent natural selection drives the accumulation of
genetic differences among populations, resulting in reproductive
isolation.
-----------
Christopher J. Schneider: Natural selection and speciation.
(Proc. Natl. Acad. Sci. US 7 Nov 00 97:12398)
QY: Christopher J. Schneider: cschneid@bio.bu.edu
-----------
Text Notes:
... ... *recombination: In general, integration of DNA fragments
into a particular site in a genome.
... ... *phenotypic characters: In general, the term "phenotype"
refers to the total appearance of an organism as determined by
the interaction during development between its genetic
constitution (genotype) and the environment.
... ... *isofemale lines: In general, a genetic lineage derived
from a single inseminated female.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm

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

5. CELL BIOLOGY: ON PROTEASOMES
     During the past three or four decades, many biologists who
study the molecular aspects of the structure and function of the
various parts of biological cells have felt a growing sense of
"complexity-shock", a deep astonishment at the complexity of the
molecular-scale machines, literally thousands of them in a single
cell, that operate in an integrated fashion to keep the cell
alive, make the cell perform various functions, and choreograph
the replication of the cell and its genome when the cell divides
to become two daughter cells. With each decade, new complexities
come into view, and researchers have not yet arrived at schemes
or perspectives that shake all the complexities down to a set of
useful basic principles. The molecular physiology of the
biological cell, how it does what it does molecule by molecule,
is still a baffling puzzle.
     Proteasomes are large multi-subunit multicatalytic enzyme
complexes that selectively degrade intracellular proteins,
literally chop the proteins into constituent amino acids so that
the amino acids can be recycled to the synthesis of other
proteins, the synthesis carried out elsewhere in the cell by
*ribosomes. Enzymes that degrade (hydrolyze) proteins are called
"proteases", and a proteasome is not merely a molecule but a
large protease machine consisting of a number of enzymes working
together. The proteasome subunits are arranged in 4 heptameric
rings which are stacked together to form a hollow cylinder with
the protease activity on the inside of the cylinder. The size of
the channel in the cylinder is such that the protein to be
chopped into amino acids must be unfolded at the entry and any
disulfide bonds reduced. The protein is then fed into the
channel, where hydrolysis of its peptide bonds occurs, the
proteasome machine releasing amino acids to rejoin the amino acid
pool of the cell. In some cases, proteins are degraded by
proteasomes into small polypeptides plus individual amino acids,
the polypeptides then processed to be antigenic cell-surface
markers.
     Ubiquitin is a small protein (76 amino-acid residues),
present in all *eukaryotic cells, and which by a sequence of
enzymatic processes is used by the cell system to tag proteins
destined for destruction by proteasomes. Ubiquitin is synthesized
in the cell as a poly-ubiquitin precursor with exact head-to-tail
amino-acid repeats, the number of repeats differing between
species.
     Proteasomes play a role in controlling cellular processes
(e.g., metabolism and the *cell cycle) through signal-mediated
hydrolysis of key enzymes and regulatory proteins. Proteasomes
also operate in the so-called "*stress response" by removing
abnormal proteins, and in the immune response by generating
antigenic peptides. Ribosomes are the intracellular machines that
create proteins; proteasomes are the intracellular machines that
destroy proteins.
... ... A.L. Goldberg et al (3 authors 2 installations, US)
present a review of our current understanding of proteasomes, the
authors making the following points:
     1) A typical cell in the human body contains approximately
30,000 proteasomes, each of which is a relatively enormous
structure. Whereas the average protein has a molecular weight of
the order of 40,000 to 80,000 daltons, most proteasomes of higher
organisms have a molecular weight in excess of 2 million daltons.
     2) Most proteins in a biological cell are replaced every few
days, even in cells that divide rarely, such as cells in the
liver or nervous system. Different proteins are degraded at
markedly different rates: some proteins have half-lives as short
as 20 minutes, while other proteins in the same cell may last for
days or weeks. These rates of protein breakdown can change
drastically according to changing conditions of the organism.
     3) Although the continuous destruction of cell constituents
such as proteins may appear wasteful, it serves a number of
essential functions. Degrading a crucial enzyme or regulatory
protein, for example, is a common mechanism used by cells to slow
or stop a biochemical reaction. In contrast, many cellular
processes are activated by the degradation of a critical
inhibitory protein. This rapid elimination of regulatory proteins
is particularly important in timing the transitions between the
stages of the cell cycle. Protein degradation also plays special
roles in the overall regulation of body metabolism. In times of
need (e.g., malnourishment or disease), the proteasome pathway
becomes more active in muscles, providing amino acids that can be
converted into glucose and burned for energy. This excessive
protein breakdown accounts for the muscle-wasting and weakness
seen in starving individuals and in those with advanced cancer,
AIDS, and untreated diabetes. Protein breakdown by proteasomes
also serves as a cellular quality-control system that prevents
the accumulation of aberrant and potentially toxic proteins.
Bacterial and mammalian cells selectively destroy proteins with
highly abnormal conformations that can arise from mutation,
errors in synthesis, or damage.
     4) The vast majority of proteins destined to be destroyed by
proteasomes are first tagged with ubiquitin, which is small
enough to be attached to larger proteins in long chains. These
poly-ubiquitin tails act as markers that target proteins destined
for destruction by proteasomes. The process for targeting and
directing a protein to a proteasome for degradation requires 3
enzymes working in concert to tag the protein with a chain of
ubiquitin molecules. The first enzyme (E1) binds to and activates
a ubiquitin molecule, and then passes it on to the second enzyme
(E2), which in turn joins to a third enzyme (E3). When an E3
enzyme binds to a protein, the ubiquitin molecule carried by E2
is broken off and transferred to the protein. The cycle repeats
until the protein is tagged with a chain of ubiquitins
(ubiquitination). This chain binds to the proteasome, which
allows enzymes near the channel entry of the proteasome to
catalyze the unfolding of the protein and push the protein strand
into the proteasome channel, where other enzymes begin chopping
the protein into pieces. The authors conclude: "The more we learn
about proteasomes and the ubiquitination selection machinery, the
more we appreciate how much of life is linked to protein death."
-----------
A.L. Goldberg et al: The cellular chamber of horrors.
(Scientific American January 2001)
QY: Alfred L. Goldberg: Harvard Univ. Med. School 617-432-1550.
-----------
Text Notes:
... ... *ribosomes: A ribosome (not to be confused with riboZYME)
is a small particle, a complex of various ribonucleic acid
component subunits and proteins that functions as the site of
protein synthesis.
... ... antigenic: In general, an antigen is any substance or
moiety that produces an immune response. In the present context,
foreign protein, e.g., viral protein, is degraded by proteasomes
and polypeptide fragments eventually locate on the surface of the
cell where they act as antigens that stimulate attack of the cell
by the immune system.
... ... *eukaryotic cells: In general, biological cells that
contain internal membrane-bound organelles such as a cell
nucleus.
... ... *cell cycle: In this context, the term "cell cycle"
refers to the entire life history of a single cell from mitosis
to mitosis, including the sequence of intervening phases
(stages).
... ... *stress response: Biological cells have various stress
responses, each triggered by one or more types of environmental
insult or stress, the main consequence being increased stress
tolerance levels. The "heat shock response" is one of the best
characterized of the cellular stress responses: exposure to high
but nonlethal temperatures ("heat shock") and to certain
chemicals causes increased activity of certain heat-shock
inducible genes and ultimate production of certain "heat-shock
proteins". A wide range of organisms, from bacteria to the higher
vertebrates, have been shown to display dramatic changes in gene
expression with heat shock.                                       
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm

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

6. MEDICAL BIOLOGY: ORIGINS OF CANCER
     In general, cancer involves a loss of normal cellular growth
control, the loss of control producing a growing tissue mass
called a "tumor" or "neoplasm". Uncontrolled growth occurs not
because the replication rate of cancer cells is always greater
than the replication rate of normal cells, but because of the
difference between the replication rate of cancer cells and the
rate of loss of cancer cells. In normal tissue, a precise balance
between replication rate and rate of loss is maintained; in a
growing neoplasm, this balance is absent and the replication rate
exceeds the rate of loss.
... ... Daniel Haber (Massachusetts General Hospital, US)
presents a review of the etiology of breast cancer, the author
making the following points concerning the origins of cancer in
general:
     1) The author points out that cancer results from the
accumulation of mutations in genes that regulate cellular
proliferation. These mutations can occur early in the process of
malignant transformation or later, during progression to an
invasive carcinoma. The earliest mutations occur in the *germ
line, as in the case of cancer-prone families. In these
instances, the inheritance of a mutated *allele is commonly
followed by the loss of the second allele from a somatic cell,
leading to the inactivation of a tumor-suppressor gene and
triggering malignant transformation. A classic example is
hereditary retinoblastoma, in which there is inheritance of a
mutant germ-line _RBI_ allele (a *tumor-suppressor gene) followed
by somatic mutation of the normal _RBI_ allele.
     2) Genes important to the development of cancer regulate
diverse cellular pathways, including the progression of cells
through the *cell cycle, resistance to programmed cell death
(apoptosis), and the response to signals that direct *cellular
differentiation. Moreover, the inactivation of genes that
contribute to the stability of the genome itself can favor the
acquisition of errors in other genes that regulate proliferation.
     3) Errors in DNA that arise during normal replication of the
molecule (nucleotide mismatches), or that are induced by ionizing
radiation or genotoxic drugs, can cause mutations in coding
sequences or breaks in double-stranded chromosomal DNA. If the
nucleotide mismatch is not repaired before a round of DNA
replication occurs, that mutation is transmitted to daughter
cells. An unrepaired break in double-stranded DNA can cause a
mitotic catastrophe when the cell attempts to segregate broken
chromosomes. Studies of yeast have identified genes that sense
damaged DNA and cause the arrest of the cell cycle, which allows
time for the molecular defect to be repaired. These genes operate
at several specific "checkpoints" in the cell cycle as a means of
ensuring genomic integrity before DNA is synthesized.
     4) The most critical checkpoint gene yet identified that is
related to cancer in humans is the tumor suppressor gene _p53_.
This gene is not essential for cell viability, but it is critical
for monitoring damage to DNA. Inactivation of _p53_ is an early
step in the development of many kinds of tumors. In cases of
cancer without _p53_ mutations, there are frequently alterations
in two other genes (_MDM2_ and _p14_) that regulate the
expression of _p53_.
-----------
Daniel Haber: Roads leading to breast cancer.
(New England J. Med. 23 Nov 00 343:1566)
QY: Daniel Haber: Massachusetts General Hospital, Boston, MA
02114 US.
-----------
Text Notes:
... ... *germ line: A germ cell is any cell from which gametes
(sperm cells and egg cells) are derived. All other cells are
called "somatic" cells. In general, the term "germ line" refers
to the line of differentiated germ cells.
... ... *allele: 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.
... ... *tumor-suppressor gene: In general, cancer genes have
been divided into 2 classes, proto-oncogenes and tumor suppressor
genes. Proto-oncogenes are genes that sustain activating changes
in human cancer. These changes may take the form of point
mutations or gene rearrangements that lead to increased or
uncontrolled activity of the encoded protein, or they make take
the form of gene amplification, which results in increased levels
of protein expression. In contrast, tumor suppressor genes are
characterized by inactivating changes in human cancer, typically
point mutations that result in truncation or functional
inactivation of the encoded protein, or gross deletions of
chromosomal fragments carrying these genes. 
... ... *cell cycle: In this context, the term "cell cycle"
refers to the entire life history of a single cell from mitosis
to mitosis, including the sequence of intervening phases.
... ... *cellular differentiation: In general, in this context,
the term "differentiation" refers to the structural and
functional specialization of cells, developmental cell
specialization (morphology and biochemistry) resulting from
activation of specific parts of the cell genome.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 5Jan01
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY: ON MUTATIONS AND CANCER
The term "cancer", which means "crab" in Latin, was introduced by
Hippocrates (460-370 B.C.) to describe diseases in which tissues
grow and spread unrestrained throughout the body, eventually
causing death. Cancers can originate in almost any tissue of the
body, including nerve, muscle, blood, connective tissue, etc.
Depending on the cell type involved, cancers are grouped into 3
main categories: a) carcinomas, the most common types of cancer,
arise from the *epithelial cells that cover external and internal
body surfaces, with lung, breast, and colon cancers the most
frequent cancers of this type; b) sarcomas originate in
supporting tissues of *mesodermal origin, such as bone,
cartilage, fat, connective tissue, and muscle; c) lymphomas and
leukemias arise from cells of blood and *lymphatic origin, the
term "leukemia" used when such cancer cells circulate in large
numbers in the bloodstream rather than growing mainly as solid
masses of tissue. Cancer is a disease of the genomic apparatus of
the cell, in particular of the growth-regulation apparatus, and
considering the vast number of activities that must be
coordinated and regulated by the genomic apparatus during the
lifetime of each cell, it is not surprising that malfunctions
arise. In general, cancer is the most prominent of the many
diseases arising from aberrations in cell function, with more
than 25 percent of people in the US now expected to develop
cancer in their lifetime.
... ... C.R. Boland and L. Ricciardiello (2 installations, US)
present a review of current research on the genomic basis of
cancer, the authors making the following points:
     1) It has been known during most of this century that cancer
is often associated with visible derangements in the nucleus of
the cell. The cells of solid tumors commonly exhibit chromosome
duplications, deletions, and rearrangements, but before the
organization of the human cell nucleus was understood, these
chromosome aberrations were difficult to categorize and were of
little help in understanding the biological basis of cancer.
     2) Within a few decades after the discovery of the structure
of DNA, cancer-related genes (oncogenes) were isolated, and these
were frequently found to be mutant versions of normal cellular
genes in which an activating *point mutation or an aberrant
*genetic amplification process resulted in a gain of function for
that gene product, and a growth advantage for that aberrant cell.
But as more and more oncogenes were identified, researchers
realized that tumor growth was also associated with loss of
function of certain "tumor suppressor genes". These tumor
suppressor genes were often inactivated by their deletion from
the nucleus, and the phrase "loss of heterozygosity" (LOH) was
applied to genetic loci in which both *alleles were present in
normal tissues, but one copy was lost in tumor tissue. In many
instances, tumor suppressor genes were first identified by virtue
of germ-line mutations that were present at a high frequency in a
rare tumor, e.g., retinoblastoma, but it soon became apparent to
researchers that many tumor suppressor genes were associated with
a variety of different tumors, many of which were not rare at
all.
     3) There are no oncogenes or tumor suppressor genes that are
activated or deleted in and from all cancers. Even tumors of a
single organ rarely have uniform genetic alterations, although
tumor types from one specific organ do have a tendency to share
mutations in certain genes or in different genes within a single
growth-regulatory pathway.
     4) At the present time, it is not known how many critical
mutations are required to convert a single normal cell into a
malignant cell. Human cells have been difficult to transform in
vitro, and the basis for this difficulty is not yet understood.
The simplest model of tumorigenesis is as follows:
... ... a) Human cells experience a certain number of mutations
each day as a result of exposure to carcinogens or as a result of
ordinary biological degradation, both of which can alter
nucleotide sequences. Errors will also occur during new DNA
synthesis and in the process of disentangling the chromosomes
during *mitosis. Most of these errors would be either irrelevant
to the life of the cell or deleterious because of the loss of a
gene critical for cellular viability.
... ... b) By chance, an occasional genomic mutation might create
a growth advantage for a cell, permitting increased net cellular
growth, because of increased proliferation or a reduction in
programmed cell death (reduction in apoptosis), with a resulting
*clonal expansion of that lineage. A second genomic alteration
might then occur within this expanding clone, again by chance,
providing an additional growth advantage for that cell and its
progeny. By virtue of these two advantages, the cells of this
clone would eventually overgrow neighboring cells, creating yet
another expanding clone. This scenario would repeat as a
consequence of each new mutation that provided an additional
growth advantage. The accumulation of these growth promoting
mutations is the basis of the current view of "multistep
carcinogenesis".
-----------
C.R. Boland and L. Ricciardiello: How many mutations does it take
to make a tumor?
(Proc. Natl. Acad. Sci. US 21 Dec 99 96:14675)
QY: C. Richard Boland [crboland@ucsd.edu]
-----------
Text Notes:
... ... *epithelial cells: In animals, "epithelial cells"
compose the cell layers that form the interface between a tissue
and the external environment, for example, the cells of the skin,
the lining of the intestinal tract, and the lung airway passages.
... ... *mesodermal: In the embryos of higher animals, there
occurs the transformation of a single-layer "blastula" into a
3-layered "gastrula" consisting of ectoderm (outermost layer),
mesoderm (middle layer), and endoderm (innermost layer)
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.
... ... *lymphatic: The lymphatic system is a complex network
for the distribution of lymph fluid (which is similar to blood
plasma -- blood without red cells). Lymph is collected by
drainage from the tissues throughout the body, flows in the
lymphatic vessels through the lymph nodes, and is eventually
added to the venous blood circulation.
... ... *point mutation: A minor changes in the genome; a single
base-pair substitution.
... ... *genetic amplification process: The production, by
various means, of additional copies of a stretch of genomic DNA.
... ... *alleles: 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. 
... ... *mitosis: Programmed division of the nucleus during cell
replication.
... ... *clonal expansion: This refers to the expansion of a
population of cells all derived from repeated replications of
progeny of a single cell.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 14Jan00
For more information: http://scienceweek.com/swfr.htm]
-------------------
Related Background:
ON GENETICS AND HUMAN CANCERS
The current consensus is that cancer results from the
accumulation of mutations in the genes that directly control the
birth and death of biological cells. But the mechanisms through
which these mutations are generated are the subject of continuing
debate and much research. It has been argued that an underlying
genetic instability is absolutely essential for the generation of
the multiple mutations that underlie cancer. On the other hand,
it has also been suggested that normal rates of mutation, coupled
with waves of *clonal expansion, are sufficient for the cancer
process to occur in humans. ... ... C. Lengauer et al (Johns
Hopkins University, US) present a review of observations
concerning the stability of the genome of human cancer cells, the
authors making the following points:
... 1) Numerous genetic alterations that affect growth-
controlling genes have been identified in neoplastic cells over
the past 15 years, and these observations provide persuasive
evidence for the genetic basis of human cancer. The alterations
can be divided into 4 major categories:
... ... a) Subtle sequence changes: These changes involve
nucleotide base substitutions or deletions or insertions of a few
nucleotides in the genome, and unlike the alterations described
below, they cannot be detected via cytogenetic analysis. Such
mutations, for example, occur in over 80 percent of pancreatic
cancers.
... ... b) Alterations in chromosome number: Such alterations
involve losses or gains of whole chromosomes. Such changes are
found in nearly all major human tumor types.
... ... c) Chromosome translocations: These alterations can be
detected cytogenetically as fusions of different chromosomes or
of normally non-contiguous segments of a single chromosome. At
the molecular level, such translocations produce fusions between
two different genes, endowing the fused genetic entity with
tumorigenic properties. Such translocations are known to occur in
the *chronic myelogenous leukemias.
... ... d) Gene amplifications: These are seen at the cytogenetic
level as homogeneously stained regions, and at the molecular
level they involve multiple copies of a gene. An example of gene
amplification occurs in advanced *neuroblastomas.
... 2) All 4 of the alterations described above occur commonly in
specific tumor types but are rarely or never observed in normal
cells. However, the existence of genetic alterations in a tumor,
even when frequent, does not mean that the tumor is genetically
unstable. By definition, instability is a matter of rate, and the
existence of a mutation provides no information about the rate of
its occurrence. The higher prevalence of mutations in tumor cells
compared with normal cells still requires explanation.
... The authors conclude: "One can argue persuasively that all
chemotherapeutic compounds used at present are more toxic to
cancer cells than to normal cells only and specifically because
of the defective *checkpoints that occur in cancer cells. This
line of reasoning suggests that, although instability may be
essential for neoplasia to develop, it may also prove to be its
Achilles' heel when the tumor is attacked by the right agents.
Further research to define the molecular and physiological bases
of instability may, therefore, yield entirely new approaches to
treating common forms of cancer."
-----------
C. Lengauer et al: Genetic instabilities in human cancers.
(Nature 17 Dec 98 396:643)
QY: Christoph Lengauer: lengauer@jhmi.edu
-----------
Text Notes:
... ... *clonal expansion: In this context, this refers to the
expansion of a population of cells all deriving from a single
mutated cell.
... ... *chronic myelogenous leukemias: (granulocytic leukemias)
These leukemias are characterized by an uncontrolled
proliferation of myelopoietic cells (blood cells derived from
bone marrow).
... ... *neuroblastomas: Neuroblastomas are malignant neoplasms
characterized by only slightly differentiated immature nerve
cells of embryonic type.
... ... *checkpoints: In this context, the term "checkpoint"
refers to a point in the eukaryotic cell division cycle where the
cycle can be halted until conditions are suitable for the cell to
proceed to the next stage. (eukaryotic = containing membrane-
bound organelles such as a nucleus.)
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 26Mar99
-------------------
Related Background:
ANEUPLOIDY AND GENETIC INSTABILITY OF CANCER CELLS
In general, germ cells (egg cells and sperm cells) and somatic
cells (non-germ cells) carry different numbers of chromosomes,
with germ cells carrying exactly half the number (haploid number)
of somatic cell chromosomes (diploid number). The term
"aneuploidy" (heteroploidy) refers to a condition in which the
number of chromosomes in a cell is not an integer multiple of the
haploid number typical for that cell or organism. For example,
the haploid human chromosome number is 23; the normal somatic
cell contains 46 chromosomes; a somatic cell with 47 or 44
chromosomes is aneuploid. Some authors, however, use the term
"aneuploidy" to indicate merely an abnormal number of
chromosomes. In cell biology, the term "karyotype" refers to the
characteristics profile (number, size, and shape) of a set of
chromosomes of a cell or organism. In this context, the term
"phenotype" refers to the total appearance of a cell as
determined by the interaction during development between its
genetic constitution (genotype) and the cell's environment.
Genetic and phenotypic instability are hallmarks of cancer cells,
but the cause of the instability is not clear. The leading
hypothesis suggests that a poorly defined gene mutation generates
genetic instability and that one or more of the many subsequent
mutations then cause cancer [*Note #1]. ... ... P. Duesberg et al
(2 installations, DE US) report an investigation of the
hypothesis that genetic instability of cancer cells is caused by
aneuploidy, which they define as "an abnormal balance of
chromosomes". The authors point out that because symmetrical
segregation of chromosomes during mitosis depends on exactly two
copies of the genes involved in mitosis ("mitosis genes"),
aneuploidy involving chromosomes bearing mitosis genes will
destabilize the karyotype. The authors propose that the
aneuploidy hypothesis predicts that the degree of genetic
instability should be proportional to the degree of aneuploidy,
and it should thus be difficult to maintain the particular
karyotype of a highly aneuploid cancer cell on *clonal
propagation. The authors report this prediction is confirmed with
clonal cultures of chemically transformed aneuploid Chinese
hamster embryo cells. Defining the "ploidy factor" as the
quotient of the modal chromosome number divided by the normal
number of the species, it was found that the higher the ploidy
factor of a clone, the more unstable was its karyotype. The
authors point out that work by others has established an exact
correspondence between the karyotype instability of human colon
cancer cell lines and the degree of aneuploidy. The present
authors suggest that, independent of gene mutation, aneuploidy is
sufficient to explain genetic instability and the resulting
karyotypic and phenotypic heterogeneity of cancer cells. The
authors further suggest that because aneuploidy has also been
proposed to cause cancer, their hypothesis "offers a common,
unique mechanism of altering and simultaneously destabilizing
normal cellular phenotypes."
-----------
P. Duesberg et al: Genetic instability of cancer cells is
proportional to their degree of aneuploidy.
(Proc. Natl. Acad. Sci. US 10 Nov 98 95:13692)
QY: Peter Duesberg: duesberg@uclink4.berkeley.edu
-----------
Text Notes:
... ... *Note #1: In 1976, Peter Nowell postulated that a
precancerous mutation generates exceptional "genetic instability"
or "mutability", and that the highly mutable "premalignant" cell
then suffers many further gene mutations, including those that
cause cancer (P.C. Nowell, Science 194:21 1976).
... ... *clonal propagation: In general, in this context, a
"clone" is a line of identical cells produced from one or a few
originating cells.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Jan99
For more information: http://scienceweek.com/swfr.htm

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

7. IN FOCUS: ON THE HISTORY OF SCIENCE
"Scientific history, like much of history, is often told in terms
of personalities. We learn who made the key discoveries and
inventions, and when; the implication, though rarely stated, is
that the course of scientific history might have been very
different if great individuals like Isaac Newton, Charles Darwin,
Marie Curie, or Niels Bohr had never lived. But this is a false
impression... The progress of science is inextricably linked with
the progress of technology, and in addition scientific advances
build on what has gone before. It is inconceivable, for example,
that Isaac Newton could have come up with Albert Einstein's
theory of relativity, because he had neither the knowledge about
the nature of light on which Einstein built nor the mathematical
techniques that were developed in the 19th century and that
provided just the tools Einstein needed for his description of
the interrelationships between space and time. Scientific
advances tend to be products of their time, and if one scientist
hadn't made a particular discovery, then almost certainly another
scientist would have done so at about the same time. The classic
example of this is the theory of evolution by natural selection.
Charles Darwin's great achievement is widely regarded as the most
important scientific idea of all time -- but it was discovered in
exactly the same form, building on exactly the same body of
earlier work, by another naturalist, Alfred Russel Wallace, soon
after Darwin made his breakthrough. Darwin had kept his ideas
secret, not least because he worried about their effect on his
wife, a traditionally devout Christian; he published them only
when Wallace sent a resume of his own identical theory to Darwin
asking for his opinion of it. If Darwin had never lived, we would
probably now regard Wallace's theory of evolution by natural
selection as arguably the most important scientific idea of all
time."
-----------
John Gribbin (with Mary Gribbin):_Stardust: Supernovae and Life
-- The Cosmic Connection.
(Yale University Press, New Haven 2000, p.68)
-------------------
SCIENCE-WEEK http://scienceweek.com 5Jan01

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

8. FROM THE SCIENCEWEEK ARCHIVE:
COMPUTER SCIENCE: ALAN TURING
In 1936, the mathematician Alan M. Turing (1912-1954) proposed
consideration of an abstract computer that subsequently came to
be known as a "Turing machine". Essentially, the simplest Turing
machine system consists of a movable input tape, a black box (the
Turing machine) that reads the tape according to an internal
algorithm, and an output tape that records the output of the
black box. The machine originally considered by Turing was a bit
more complex, with a single input/output tape demarcated into
discrete small sections, and the machine capable of being in any
one of a set of states (determined by the algorithm or "Rule
Set") according to which section of the tape the machine happened
to be reading, and the output capable of moving the tape backward
or forward. As a mathematician, Turing's interest was to
determine the universe of problems capable of being solved by
such a machine, and his ideas have been of considerable influence
in both mathematical and engineering theories of computing
machines. Turing was also interested in several biological
problems, and to a number of mathematically inclined
biologists the Turing machine in its simplest form has been for
many decades an intriguing model for certain computational
processes in the nervous system. More recently, in molecular
biology, the Turing machine has been recognized as an analog of
the behavior of nucleic acid polymerases such as DNA polymerase
and RNA polymerase (enzymes which catalyze the formation of
nucleic acid polymers), which sequentially synthesize an output
polymer (output tape) according to the sequential reading of the
individual units of an input polymer (input tape). Also of
interest to neural systems researchers has been a little-known
paper by Turing on learning behavior of artificial neural
networks not published until 14 years after his death.
... ... B.J. Copeland and D. Proudfoot (University of Canterbury,
NZ) present a biographical essay on Alan Turing, the authors
making the following points:
     1) All current digital computers are essentially Turing
machines. Turing also pioneered the field of artificial
intelligence, proposing the widely debated "*Turing test" as a
method of determining whether a suitably programmed computer
exhibits "intelligence" (i.e., can "think"). During World War II,
as part of a British intelligence unit, Turing was instrumental
in breaking the German "Enigma" code, a feat that has been said
to have shortened the war by two years. At the end of his short
life, Turing was engaged in the earliest work on what would now
be called "artificial life", his research involving simulation of
the chemistry of biological growth.
     2) Throughout his career, Turing had no great interest in
publicizing his ideas, and as a consequence important aspects of
his work have been neglected or forgotten over the years. In
particular, few people are familiar with Turing's anticipation of
"connectionism" or neuron-like computing. Also neglected are his
groundbreaking theoretical concepts in the area of
"hypercomputation", a field devoted to the computational solution
of apparently intractable problems.
-----------
B.J. Copeland and D. Proudfoot: Alan Turing's forgotten ideas in
computer science.
(Scientific American April 1999)
B.J. Copeland, Dept. of Philosophy, University of Canterbury, NZ.
-----------
Text Notes:
... ... *Turing test: The Turing test is essentially a protocol
for distinguishing between real (human) thought and simulated
(computer) thought. A classic statement of the Turing test is as
follows: One room contains a person and another room contains a
machine. An interrogator in a third room asks questions of both
in an attempt to identify them. When the interrogator cannot
distinguish between them by questioning, the machine can be said
to possess human-like intelligence. [Editor's note: There are
aspects of the test as thus stated which are ill-defined. For
example, there is no operational definition of "intelligence".
Secondly, in terms of procedure, the test is perhaps more useful
when amended as follows: If a determined questioner can find no
question that can enable absolute identification of the machine,
then it can be concluded that, in the frame of reference of the
questioner, the analytical processes of the machine are at least
qualitatively equivalent to the analytical processes of the
human.]
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 9Jul99
-------------------
Related Background:
ON COMPUTING WITH DNA
... ... Leonard M. Adleman (University of Southern California,
US) presents an essay on a computing ensemble involving DNA, the
ensemble based on the author's recognition of the Turing machine
as an analog of DNA polymerase, and the ensemble applied to the
solution of a mathematical problem known as the "Hamiltonian Path
Problem". As a mathematician and computer scientist, Adleman's
objective is the demonstration that his DNA ensemble can perform
as a powerful computer and solve a posed mathematical problem.
The author considers the following as the tools of a potential
DNA computing system: *Watson-Crick pairing, *polymerases,
*ligases, *nucleases, *gel electrophoresis, DNA synthesis, and
the *polymerase chain reaction. The author presents the
Hamiltonian Path Problem as follows: Given a graph with directed
edges and a specified start vertex and end vertex, one says there
is a Hamiltonian path if and only if there is a path that starts
at the start vertex, ends at the end vertex, and passes through
each remaining vertex exactly once. The Hamiltonian Path Problem
is to decide for any given graph with specified start and end
vertices whether a Hamiltonian path exists or not. The specific
problem chosen by the author involves a 7-vertex graph. Each
vertex is identified by a specific assigned sequence of nucleic
acid bases, and using the repertoire of biochemical tools
indicated above (and an added auxiliary separation technique),
the author demonstrates that this particular problem is easily
solved. Considering molecular computers, the author points out
their advantages: 1) The possibility of extremely dense
information storage. "For example, one gram of DNA, which when
dry would occupy a volume of approximately one cubic centimeter,
can store as much information as approximately 10^(9) CDs." 2)
The possibility for enormous parallelism. In the author's
problem, approximately 10^(14) connection paths were
simultaneously concatenated in about 1 second. 3) Extraordinary
energy efficiency. In principle, 1 joule is sufficient for
approximately 2 x 10^(19) DNA ligation operations. The author
suggests that his experiment "can be viewed as a manifestation of
an emerging new area of science made possible by our rapidly
developing ability to control the molecular world."
QY: Leonard M. Adleman, Univ. of Southern California 213-740-2311
(Scientific American August 1998) (Science-Week 31 Jul 98)
-------------------
Related Background:
... ... *Watson-Crick pairing: Also known as complementary base
pairing. This refers to the specific chemical affinities between
specific base pairs in a nucleic acid: adenine always pairs with
thymine, and guanine always pairs with cytosine. In pairing
between DNA and RNA, the uracil of RNA always pairs with adenine.
Complementary base pairing is not only responsible for the DNA
double helix, but it is also essential for various in vitro
techniques such as PCR (*polymerase chain reaction).
... ... *polymerases: Refers to any enzyme that directs the
synthesis of a polymer by linking individual monomers. Examples
in biological systems are DNA polymerase and RNA polymerase.
... ... *ligases: Ligases are enzymes that catalyze the stitching
together of polymer fragments. DNA ligase, for example, catalyzes
phosphodiester bond formation between two DNA fragments, and this
enzyme is involved in normal DNA replication, repair of damaged
chromosomes, and various in vitro techniques in genetic
engineering that involve linking DNA fragments.
... ... *nucleases: Refers to any enzyme that acts on nucleic
acids, e.g., DNase, RNase, endonuclease, etc.
... ... *gel electrophoresis: In general, electrophoresis is a
laboratory technique used to separate macromolecules on the basis
of electric charge and size, the technique involving application
of an electric field to a population of macromolecules dispersing
according to their electric mobilities. In gel electrophoresis,
the porous medium through which the macromolecules move is a gel.
... ... *polymerase chain reaction (PCR): A technique for
isolating and amplifying any specifically desired DNA sequence.
The reaction is facilitated by a heat-stable DNA polymerase
(e.g., Taq, which is obtained from a thermophilic bacterium) that
can withstand the many cycles of heating and cooling involved in
the technique. PCR is considered by many molecular biologists to
be the most important technical advance in molecular biology in
the second half of the 20th century. The inventor of the
technique, Kary Mullis, received the Nobel Prize in Chemistry in
1993 for his discovery. 
-------------------
Summary & Notes by SCIENCE-WEEK [http://scienceweek.com] 31Jul98


=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
 
NOTICES  
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-= 

CHANGE OF EMAIL ADDRESS:
If at any time you need to change the Email address at which you
receive SW, please send the information to:
request@scienceweek.com

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

SCIENCE-WEEK SUBSCRIPTIONS:
Subscriptions to ScienceWeek cost as little as US$15 a year.
Complete subscription information is available at:
http://scienceweek.com/subinfo.htm

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

The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
been published regularly each week since that date. SW is
designed to cross existing conceptual and linguistic barriers
between the scientific disciplines. In general, the biology is
written for physicists and chemists, and the physics and
chemistry are written for biologists, with an attempt to retain
some exactitude in the particular science involved in the news.
These are the aims. Undoubtedly, we are not always successful,
and for that we apologize. In any case, what we hope is that our
readers are reading out of their fields more than in their
fields, since that is the essence of this publication.

We welcome comments, suggestions, and criticisms from our
subscribers. Public letters relevant to any report are also
welcome. Editorial contact: editors@scienceweek.com

Editor/Publisher: Dan Agin
Managing Editor: Claire Haller
Associate Editor: Joan Oliner

Copyright (c) 1997-2000 SCIENCE-WEEK/Spectrum Press Inc.
All Rights Reserved
US Library of Congress ISSN 1529-1472

---------------------------------------------
ScienceWeek has a liberal copying policy.
For information about copying, see the following:
http://www.scienceweek.com/copying.htm
ScienceWeek is published by Spectrum Press Inc.,
3023 N. Clark Street #109, Chicago, 60657-5205 IL, USA.
---------------------------------------------
-----end file