ScienceWeek

SCIENCE-WEEK

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

May 15, 1998 - Issue #54

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I am somehow less interested in the weight and convolutions of
Einstein's brain than in the near certainty that people of equal
talent have lived and died in cotton fields and sweatshops.
-- Stephen Jay Gould
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Contents of This Issue:

1. The Impending Genetics Research Referendum in Switzerland
2. Accidental Nuclear War: A Contemporary Assessment
3. A Medical View of the Dangers of Private Arsenals in the US
4. A Proposal for a Common-Sense Climate Index
5. A New Method for Computing Solutions of Intractable Problems
6. Simulations of Liquid Iron Viscosity at Earth's Core
7. Brownian Dynamics Simulations of Protein Folding
8. On the Pathway Structure of Biochemical Reaction Networks
9. On Asymmetric Cell Division
10. On the Evolution of Genome Protein-Coding Capacity
11. On Antibodies to DNA
12. Cisplatin and Telomere Loss in Cells
13. Complexities in Alcohol Consumption Mortality Risk
14. On the Problem of Multi-Drug Microbial Resistance
15. Risk of Cancer Among Offspring of Childhood-Cancer Survivors

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1. THE IMPENDING GENETICS RESEARCH REFERENDUM IN SWITZERLAND
The next 2 months will mark an extremely important short period
in the history of the already initiated Genomics Revolution. On
June 7th, the people of Switzerland will vote yes or no to a ban
on the production and distribution of transgenic animals, field
trials with genetically modified organisms of any sort, and the
patenting of genetically modified animals and plants. Postal
voting on the ban will actually begin on May 10th. If the ban is
approved, modern biological research in Switzerland, and the
extremely successful pharmaceutical industry in Switzerland, will
for all practical purposes come to an end. At the moment, the
scientific community in Switzerland is worried enough so that
they have taken to marching in the streets, and many scientists
have made contingency plans to leave the country. The Swiss
government is against the ban, but the public mood, greatly
influenced by various political activist groups, seems in favor
of more or less ending modern biology in their country. In an
unsigned editorial, the journal *Nature* says, "It is not often
that a country's population deliberately commits a thriving
research and industrial activity to the grave... To do so as a
result of ignorance or political accident would be a tragic
folly." Switzerland is one of the most scientifically advanced
countries in the world, particularly in biological and medical
research, and the existence of this sort of huge chasm between
the public and the scientific research community does not bode
well for either developed or underdeveloped countries with
intentions of participating in the Genomics Revolution. That
revolution will no doubt be of ultimate immense benefit to
humanity, but it appears the immediate road ahead will have
places of considerable turmoil. The editorialist in *Nature*
concludes: "If Switzerland does vote in June to cut itself off
from one of the most potentially valuable channels of modern
biomedical research, the blame should be apportioned more widely
than to a group of highly organized activists."
(Nature 23 Apr 98) (Science-Week 8 May 98)

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Related Background:

SWISS GOVERNMENT TO PREEMPT GENE TECHNOLOGY REFERENDUM
The Swiss government is attempting to preempt the June 1998
referendum on a constitutional provision that would impose major
restrictions on genetic engineering and the use of transgenic
animals. The proposed constitutional provision, put into process
in 1992, is supported by environmental and animal rights groups
but opposed by the majority of Swiss scientists and apparently
also by the majority of the public. The government, however, is
evidently taking no chances, viewing passage of the referendum as
a potential catastrophe that may ruin Swiss biomedical research
and the huge Swiss pharmaceutical industry. The government plans
to initiate legislative measures that would provide for strict
controls without banning what is deemed to be ethical and
necessary research. (Nature 22 Jan 98)

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Related Background:

ANOTHER VIEW OF THE SWISS GENE TECHNOLOGY REFERENDUM
F. Cavalli (Ospidale San Giovanni Bellinzona, CH), a member of
the Swiss Parliament, in a letter to the journal Science,
responds to the recent editorial by Nobel Laureate Rolf M.
Zinkernagel concerning the coming Swiss referendum on a
constitutional prohibition of gene manipulation. Cavalli suggests
that Zinkernagel and others have made an erroneous assessment of
the current situation in Switzerland, and that there is distrust
throughout Europe "of giant companies whose solicitude for their
shareholders appears to outweigh their concern for their
thousands of workers."QY: Franco Cavalli, Ospidale San Giovanni,
6500 Bellinzona, CH. (Science 9 Jan 98)

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Related Background:

ON THE SWISS CONSTITUTIONAL PROHIBITION OF GENE MANIPULATION
There is an interesting science policy development brewing in
Switzerland. A policy formulation called the Gene Protection
Initiative has come into existence, and it will be voted on in a
national referendum in 1998. This initiative, if approved by the
public referendum, will result in a constitutional prohibition of
gene manipulation, prohibition of the use and patenting of gene-
modified animals (including worms and flies), and prohibition of
the cultivation of gene-modified plants. The Swiss scientific
community says that if the referendum is passed it will cause the
end of Swiss biotechnology and molecular biology. Both houses of
the Swiss parliament have voted against the Initiative, agreeing
with the scientists and the Swiss industrial biotechnology
community that passing the referendum will produce a disaster. At
the present time it is not clear how the public will vote. Those
supporting the initiative claim that gene-modified plants cause
allergies, that science is one step away from the creation of
super-monsters, that scientists lack ethics, morals, and a sense
of responsibility, and that scientists have let the public down
on too many occasions. So they say gene technology must be banned
from Switzerland, and they hope the rest of the world will follow
suit. In an editorial in the journal Science, Rolf M. Zinkernagel
(Institute for Experimental Immunology, Univ. of Zurich, CH) is
optimistic that the good sense of the Swiss public will prevail
and that the Gene Protection Initiative will be defeated in the
referendum, but he points out that scientists must play their
part in dispelling the negative image of science and scientists,
and they must educate the public concerning the beneficial
applications of modern science. (Science 14 Nov 97)

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Related Background:

MOVEMENTS IN UK AND EU TO BAN TRANSGENIC ANIMAL RESEARCH
There are movements underway in Britain and Europe to ban or
rigidly control the use of transgenic animals in biological
research. In the UK there are calls for a commission of inquiry
to investigate the welfare of transgenic animals. A recent survey
supported by the European Commission into public attitudes to
biotechnology evidently showed most respondents in EU countries
consider the creation of transgenic animals for research and for
organ transplantation to be morally unacceptable. In Switzerland,
Swiss scientists have issued a warning that biomedical research
in universities will be seriously harmed if a referendum to be
held next year to restrict genetic engineering (including a ban
on the use of transgenic animals) wins approval. An irony is that
surveys in Switzerland have shown that although three-quarters of
the population is against field trials of genetically modified
organisms, novel food, and cloning, a majority are in favor of
medical applications of technology. The apparent view of most
biologists about this matter is not complicated. The feeling
among biologists is that after centuries of arduous struggle by
thousands of biological researchers to understand fundamental
principles and apply them in medicine to alleviate suffering and
extend life, we are now, at the end of the 20th century, at the
threshold of the most important applications of basic biological
science to human health and the control of human disease. Genetic
engineering and the use of transgenic animals are absolutely
essential to extend molecular biology and apply it expeditiously
to human clinical medicine. It is indeed ironic that the same
people who call for a halt to transgenic animal research expect
the ultimate in scientific expertise when they or their children
are victims of disease or other biological misfortunes. It is sad
to have a public uneducated about these matters; it is even
sadder that many politicians deem it wisdom to follow the public
mood rather than lead it. (Nature 24 Jul 97)


2. ACCIDENTAL NUCLEAR WAR: A CONTEMPORARY ASSESSMENT
Forrow et al (9 authors at 8 installations, US), in a special
report in a prestigious medical journal, review the current
probability for nuclear war. In the 1980s, many medical
organizations identified the prevention of nuclear war as one of
the medical professions's most important goals. For this report,
the authors reviewed the recent literature on the status of
nuclear arsenals and the risk of nuclear war, then estimated the
likely medical effects of a scenario identified by leading
experts as posing a serious danger: an accidental launch of
nuclear weapons. The authors found that US and Russian nuclear
weapons systems remain on high alert. This fact, combined with
the aging of Russian technical systems, has recently increased
the risk of an accidental nuclear attack. As a conservative
estimate, an accidental intermediate-size launch of weapons from
a single Russian submarine would result in the deaths of
6,838,000 persons from firestorms in 8 US cities. Millions of
other people would probably be exposed to potentially lethal
radiation from fallout. The authors propose that the risk of an
accidental nuclear attack has increased in recent years,
threatening a public health disaster of unprecedented scale, and
they suggest that physicians and medical organizations should
work actively to help build support for the policy changes that
would prevent such a disaster. "The prevention of nuclear war
should be one of the medical profession's most important goals."
QY: Lachlan Forrow, Harvard Univ. Medical School 617-432-1550.
(New England J. Med. 30 Apr 98) (The Monday Review 11 May 98)


3. A MEDICAL VIEW OF THE DANGERS OF PRIVATE ARSENALS IN THE US
In an editorial, J. Kassirer, Editor-in-Chief of the New England
Journal of Medicine, writes of the killing of 5 people and the
wounding of 15 others by two boys, ages 11 and 13, in Jonesboro,
Arkansas. Kassirer points out that although we many never know
precisely *why* the boys did what they did, we certainly know
*how*. The vast array of powerful firearms available to the boys
is remarkable. Would the carnage have been so great if the boys
had been unable to gain access to two gun arsenals? Would so many
people be dead if such lethal weapons had not been in either
arsenal? Kassirer proposes that the US must ratchet down its
firepower, that it is time to eliminate semi-automatic firearms
from private homes. The 1994 federal ban on new assault weapons
with high-capacity ammunition clips must be tightened to stop the
manufacture and sale of military weapons modified to have a
sporting appearance. A ban on these large ammunition clips should
also include those produced before 1994. Kits to convert semi-
automatic weapons into fully automatic machine guns should be
outlawed. A federal code for storing firearms in the home should
be developed, and all firearms should be registered with local
authorities. The author suggests it is time to end the firearm
industry's status as America's last unregulated industry, and a
federal agency should be given standard-setting authority over
the industry and its products.
QY: Jerome P. Kassirer, New England J. Med. 617-734-9800.
(New England J. Med. 7 May 98 338:1376) (Science-Week 15 May 98)


4. A PROPOSAL FOR A COMMON-SENSE CLIMATE INDEX
Hansen et al (National Aeronautics and Space Administration, US)
propose an index of climate change based on practical climate
indicators such as heating degree days and the frequency of
intense precipitation. The authors report they find that in most
regions the index is positive, the sense predicted to accompany
global warming. In a few regions, especially in Asia and western
North America, the index indicates that climate change should be
apparent already, but in most places climate trends are too small
to stand out above year-to-year variability. The climate index is
strongly correlated with global surface temperature, which has
increased as rapidly as projected by climate models in the 1980s.
The authors suggest that the global area with obvious climate
change will increase notably in the next few years, but the
growth of greenhouse gas climate forcing has declined in recent
years, providing an opportunity to keep climate change in the
21st century at levels less than "business-as-usual" scenarios.
QY: James Hansen (jhansen@giss.nasa.gov)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4113)
(Science-Week 15 May 98)

(continued in Part 2)

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SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

May 15, 1998

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5. A NEW METHOD FOR COMPUTING SOLUTIONS OF INTRACTABLE PROBLEMS
There are many problems in science whose solution is described by
a set of differential equations, but where the solution of these
equations is so complicated that it cannot be found in practice,
even numerically, because it cannot be resolved properly. An
accurate numerical solution requires that the problem be well-
resolved, i.e., that enough variables (degrees of freedom) be
retained in the calculation to represent all relevant features of
the solution. Well-known examples where good resolution cannot be
achieved in practice include turbulence and various problems in
statistical physics and economics. ... ... Chorin et al (Lawrence
Berkeley National Laboratory, US) present a method for computing
the average solution of problems that are too complicated for
adequate resolution, but where information about the statistics
of the solution is available. The method involves computing
average derivatives by interpolation based on linear regression,
and an updating of a measure constrained by the available crude
information. Examples are given in connection with Gaussian
distributions, a linear Schroedinger equation, and a nonlinear
Hamiltonian system.
QY: Alexandre J. Chorin, Dept. of Mathematics, Lawrence Berkeley
National Laboratory, Mailstop 50A-2152, 1 Cyclotron Road,
Berkeley, CA 94720 US.
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4094)
(Science-Week 15 May 98)


6. SIMULATIONS OF LIQUID IRON VISCOSITY AT EARTH'S CORE
The current idea is that the Earth's outer core consists mainly
of liquid iron, and that the convection of this metallic liquid
is responsible for the Earth's magnetic field. However, a full
understanding of the dynamics is hampered by uncertainty
regarding the viscosity of the outer core, with viscosity
estimates by various researchers ranging over 12 orders of
magnitude. ... ... Wijs et al (7 authors at 3 installations, UK
AT) present dynamical first principles simulations of liquid iron
which indicate that the viscosity of iron at Earth core
temperatures and pressures is at the low range of previous
estimates -- roughly 10 times that of typical liquid metals at
ambient pressure. The authors suggest this estimate supports the
approximation commonly made in magnetohydrodynamic models that
the outer core is an inviscid fluid undergoing small-scale
circulation and turbulent convection, rather than large-scale
global circulation.
QY: Michael J. Gillan (pha71@keele.ac.uk)
EMAIL
(Nature 23 Apr 98) (Science-Week 15 May 98)

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

Related Background:

EXPERIMENTAL APPROACHES TO THE ANALYSIS OF EARTH'S CORE
Computer models of the Earth's core, combined with seismic
information, have suggested that the iron crystals in the inner
core are aligned, that the inner core has an intrinsic rotation,
and that the rotation velocity is slightly faster than that of
the rest of the planet. Seismologists have also suggested, on the
basis of seismic studies, that the core is not isotropic. Gallium
is a metallic element similar to mercury, with a low melting
point (29.78 degrees Centigrade) and a high boiling point (2403
degrees Centigrade). In a review of experimental work in
geophysics, A. Frank (Univ. of Rochester, US) emphasizes the
advantages of experimental methods over computer simulations.
Recent experiments involve using molten gallium as a model for
the Earth's core, with measurements of the effects of local
conditions such as the flow of heat, magnetic fields, and
rotation on the grain of the liquid metal. Among other observat-
ions, the Olson group (Johns Hopkins Univ., US) has apparently
already provided evidence that temperature changes in Earth's
core did not create the crystalline arrangements, and that it is
rotation that may be the cause of the apparent core asymmetries.
QY: Adam Frank, Univ. of Rochester, Dept. of Physics 716-275-4356
(Earth February 1988) (Science-Week 2 Jan 98)

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

Related Background:

ROTATION DIFFERENCES OF EARTH'S INNER CORE AND MANTLE
Seismic wave propagations are the propagated shock waves produced
by earthquakes, and quantitative analysis of these waves can tell
us much about the structure of the Earth. Seismic studies
indicate the interior of the Earth consists of three parts: a
metallic core, a dense rocky mantle, and a thin low-density
crust. The central part of the core is solid, but the outer part
of the core is evidently liquid. The mantle, the layer of dense
rock and metal oxides between the molten part of the core and the
surface, has plastic properties (i.e., it is a solid capable of
flow under pressure). Apparently, the Earth's magnetic field is a
direct result of its rapid rotation and its molten core, and the
theoretical account of this is called the "dynamo effect". The
essential idea is that the liquid metallic core is stirred by
convection, the rotation of the Earth couples this motion into a
circulation that generates electric currents, and the electric
currents in turn generate a magnetic field according to classical
electromagnetic theory. K. Creager (Univ. Washington Seattle, US)
reports a model that uses observations of particular seismic wave
propagations and proposes that the inner core of the Earth is
rotating 0.2 degrees to 0.3 degrees per year faster than the
mantle. The author suggests this low difference raises the upper
limit for inner core viscosity and thus constrains parameters for
future dynamo models.
QY: Kenneth C. Creager 
(Science 14 Nov 97) (Science-Week 5 Dec 97)


7. BROWNIAN DYNAMICS SIMULATIONS OF PROTEIN FOLDING
Protein folding occurs on a time scale ranging from milliseconds
to minutes for a majority of proteins. Computer simulation of
protein folding, from a random configuration to the native
structure, is nontrivial due to the large disparity between the
simulation and folding time scales. In order to overcome this
limitation, simple models with idealized protein subdomains,
e.g., the diffusion-collision model, have gained some popularity.
The diffusion-collision protein-folding mechanism postulates the
early-stage formation of fluctuating quasiparticles (micro-
domains), which may be incipient secondary structures (alpha-
helices and beta-sheets) or hydrophobic clusters. These micro-
domains move via diffusion, and their coalescence leads to the
formation of folded proteins. Thus, the diffusion-collision model
reduces the complexity of the folding process from a consider-
ation of individual amino acids to that of the properties of a
few microdomains and their interactions. ... ... Rojnuckarin et
al (3 authors at 2 installations, US) present an analysis of the
folding of a 4-helix protein bundle within the framework of a
diffusion-collision model. Even with the simplifying assumptions
of a diffusion-collision model, a direct application of standard
Brownian dynamics methods would consume 10,000 processor-years on
current supercomputers. The authors circumvented this difficulty
by invoking a special Brownian dynamics simulation. They report
that a coarse-grained (i.e., crude) model of the 4-helix bundle
can be simulated in several days on current supercomputers, and
that such simulations yield folding times that are in the range
of time scales observed in experiments.
QY: Sangtae Kim (kim01@aa.WL.com) EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4288)
(Science-Week 15 May 98)

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Related Background:

A MODEL FOR BETA-HAIRPIN FOLDING IN PROTEINS
To be biologically active, proteins must adopt specific tertiary
configurations, a specific "folding". Although many natural
proteins spontaneously refold once they have been forced to
unfold, synthetic proteins are often produced in an insoluble
unfolded state and are thus inactive and useless until correctly
folded. One important aspect of protein folding is the kinetic
process, the rate at which folding occurs. Were a single
conformation to be found by random searching of all the possible
conformations, the number of years required would range from
10^(7) to 10^(66). In actuality, protein folding occurs on the
scale of microseconds, so there is clearly much yet to be learned
about these macromolecules. Probabilistic analysis of the
kinetics and energetics of a system of entities can be made
within the framework of the theory of statistical mechanics, and
the application of this theory is an important part of current
research into protein folding. In general, protein chains fold
into alpha-helices or beta-sheet structures, and the minimal
beta-structural element is the "beta-hairpin", a turning of the
polypeptide chain that has the shape of a hairpin. As far as
experimental methods are concerned, analysis of folding kinetics
in response to temperature variation is one of the key experi-
mental procedures, and there are now sophisticated methods for
temperature control provided by the coupling of computers and
laser physics. One such method is laser "temperature jump"
spectroscopy, which involves jump-heating (jump-discontinuity
heating) of a small volume of aqueous solution in a short time
domain coupled with spectroscopy in some part of the electro-
magnetic spectrum. Munoz et al (4 authors: National Institutes of
Health, US) used a nanosecond laser temperature jump apparatus
coupled with laser fluorescence excitation to study the kinetics
of folding of a protein beta-hairpin consisting of 16 amino acid
residues, and they report that folding of the beta-hairpin occurs
at 6 microseconds at room temperature, which is 30 times slower
than alpha-helix formation. The authors offer a statistical
mechanical model that provides a structural explanation for their
observations.
QY: Victor Munoz 
(Nature 13 Nov 97) (Science-Week 5 Dec 97)

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Related Background:

A SYNTHETIC OLIGOMER THAT MIMICS PROTEIN FOLDING
The existence of helical folding in polymers such as proteins and
nucleic acids is of extreme importance in biological systems, but
biological polymers are not the only polymers to assume such
special folding arrangements. Beta-peptides, for example, non-
biological polymers synthesized from beta amino acids, form
helices stabilized by hydrogen bonds. Now Jeffrey S. Moore et al
(University of Illinois Urbana-Champaign, US) report that syn-
thetic oligomers with an all-carbon backbone, linear phenyl-
acetylenes with ester-substituted benzene rings linked to one
another by acetylene groups, spontaneously fold into a stable
helical configuration in acetonitrile, and that this apparently
involves a "solvophobic" mechanism similar to the hydrophobic
collapse model of protein folding in water. In both systems, the
phenylacetylene oligomers and biological proteins, hydrophobic
groups associate to form a compact structure that excludes the
solvent. The phenylacetylene oligomers have longitudinal cavities
that might be used for binding metals and other reactive species.
The authors also suggest such systems could be used in the design
and construction of synthetic enzymes.
QY: J. S. Moore, Univ. Illinois Urbana-Champaign, Chemistry (217)
333-0722 (Science 19 Sep 97) (Science-Week 3 Oct 97)

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

Related Background:

PROTEIN-FOLDING MECHANISMS IN PROKARYOTES VS. EUKARYOTES
In biological systems, proteins are the molecules that do most of
the biological work, and the various proteins are the ultimate
expression of the genome of any organism. As polymers, proteins
are similar to the polymers known to polymer chemists, but the
chemical activities of proteins (and their biological functions)
depend mostly on higher-order folding into specific configur-
ations rather than on quasi-crystalline backbone arrays, as is
often the case in non-biological polymer chemistry. It is these
specific configurations that are responsible for the important
specificity and high catalytic power of the proteins that are
enzymes. The configurations, in turn, are an ultimate result of
amino acid sequences which form the backbone of proteins,
sequences which are not simple, as are the backbone sequences of
most non-biological polymers, but are specific, cryptic (coded),
and heterogenous. It is now recognized that complex proteins
usually have more than one folding domain, each involving a
sequence of 100 to 300 amino acids. The entire folding
architecture of a complex protein must be precisely constructed
in order for protein functionality to exist. Which provokes the
question of how the specific folding of particular proteins is
ensured by the biological system. The answer is evident for
simple proteins in vitro: the final configuration is
predetermined by the amino acid sequence, there being a single
energetically favored configuration that will always be attained
at equilibrium. This is Anfinsen's Rule, first proposed by the
protein biochemist C. B. Anfinsen more than 30 years ago. In
vivo, however, and particularly for complicated proteins, the
situation is more involved. This week W. J. Netzer and F. U.
Hartl (Sloan Kettering Cancer Center, NY US; Max Planck Inst.
Biochemistry, Martinsried DE) report an analysis of the
differences between protein folding in prokaryotes (organisms,
such as bacteria, without membrane-bound organelles such as the
nucleus) and eukaryotes (organisms with membrane-bound
organelles). Perhaps the most interesting difference is that in
prokaryotes protein folding is delayed until translation (final
synthesis by the ribosome) is completed (post-translational
folding), while in eukaryotes folding of each protein domain
occurs as each domain is translated (co-translational folding).
One result is that new prokaryote proteins can often be
misfolded. There are helper proteins at work in both prokaryotes
and eukaryotes to chaperon the proteins to their final
configurations, but there is still more possibility for errors in
the prokaryotes. One important consequence of this analysis is
that when bacteria are genetically engineered to synthesize human
protein for clinical use, the susceptibility of prokaryote
protein synthesis to folding errors must be considered.
(Nature 24 Jul 97) (Science-Week 8 Aug 97)


8. ON THE PATHWAY STRUCTURE OF BIOCHEMICAL REACTION NETWORKS
Schilling and Palsson (University of California San Diego, US),
in a study of the problem of the functional definition of
biochemical pathways and their role in the context of the whole
cell, propose that the mass balance constraints that govern the
function of biochemical reaction networks lead to the translation
of the problem into the realm of linear algebra. The functional
capabilities of biochemical reaction networks, and thus the
choices that cells can make, are reflected in the null space of
their stoichiometric matrix, with the null space spanned by a
finite number of basis vectors. The authors present an algorithm
for the synthesis of a set of basis vectors that represent the
underlying biochemical pathways fundamental to the corresponding
biochemical reaction network. The authors suggest their
development yields a holistic definition of biochemical pathways
in contrast to definitions that have arisen from the history of
knowledge of these pathways.
QY: Bernhard O. Palsson (palsson@ucsd.edu)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4193)
(Science-Week 15 May 98)

(continued in Part 3)

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SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

May 15, 1998

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9. ON ASYMMETRIC CELL DIVISION
Asymmetric cell division, in which a cell divides into two cells
of different developmental potentials, is a fundamental means of
generating cell diversity. In principle, asymmetric cell divis-
ions may involve extrinsic or intrinsic factors. With extrinsic
factors, daughter cells are initially equivalent but adopt
different fates as the result of the interactions of the daughter
cells with each other or with their environment. With intrinsic
factors, unequal amounts of cell-fate determinants are partit-
ioned into the two daughter cells. The mechanisms underlying
asymmetric cell division have been studied in organisms ranging
from bacteria, yeast, worms, and flies, to mammals. Intrinsic
determinants have been identified in several systems, and at
present the key molecular questions are 1) What controls the
asymmetric localization of the determinants during mitosis? and,
2) How do the determinants control daughter cell fate?
... ... Jan and Jan (University of California San Francisco, US)
review this field, focusing primarily on the Drosophila nervous
system, using other systems for comparison. The authors propose
that with the recent identification of intrinsic cell-fate
determinants for asymmetric cell division in several systems,
biologists have begun to gain insight into the cellular mechan-
isms by which these determinants are preferentially segregated
into one of the two daughter cells during mitosis. The authors
suggest that the intensive efforts directed at several
experimental systems will soon identify common and varied
mechanisms involved in asymmetric cell divisions.
QY: Yuh Nung Jan, Dept. of Physiol., Univ. of Calif. San
Francisco 415-476-4044.
(Nature 23 Apr 98 392:775) (Science-Week 15 May 98)


10. ON THE EVOLUTION OF GENOME PROTEIN-CODING CAPACITY
Gene number can be considered a pragmatic measure of biological
complexity, but reliable data is scarce. Estimates for
vertebrates are 50,000 to 100,000 genes per haploid genome,
whereas invertebrate estimates fall below 25,000.
... ... Simmen et al (5 authors at 2 installations, UK) report an
examination of the hypothesis that the origin of vertebrates
coincided with extensive gene creation. A prediction is that gene
number will differ sharply between invertebrate and vertebrate
members of the chordate phylum. The authors developed a gene
number estimation method, and validated the method with
Caenorhabditis elegans (a worm whose entire genome has been
sequenced). Using the method, the authors then estimated that the
invertebrate chordate Ciona intestinalis has 15,500 protein-
coding genes (+- 3,700), a number significantly lower than gene
numbers of vertebrate chordates, but similar to those of
invertebrates in distantly related phyla. The authors suggest the
data indicate that evolution of vertebrates was accompanied by a
dramatic increase in protein-coding capacity of the genome, but
that a more stringent test of the hypothesis awaits data from
cephalochordates and primitive vertebrates.
QY: Martin W. Simmen (m.simmen@ed.ac.uk)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4437)
(Science-Week 15 May 98)


11. ON ANTIBODIES TO DNA
B. Hahn (University of California Los Angeles, US) reviews
current ideas concerning antibodies to DNA and the involvement of
such antibodies in the human disease systemic lupus erythem-
atosus. Antibodies to DNA were first described in 1957, and they
constitute a subgroup of antinuclear antibodies that bind single-
stranded DNA, double-stranded DNA, or both. Antibodies that bind
exclusively to single-stranded DNA can bind its component bases,
nucleosides, nucleotides, oligonucleotides, and ribose-phosphate
backbone, all of which are exposed in single strands of DNA. In
contrast, antibodies that bind double-stranded DNA bind to the
ribose-phosphate backbone, base pairs, or particular conformat-
ions of the double helix. Antibodies to double-stranded DNA are
characteristic of human and mouse systemic lupus erythematosus,
and they are good markers of the disease. Current research is
targeted to specific suppression of the production of antibodies
to DNA as a means to suppress the clinical activity of the
disease, and the author suggests that such therapy should have
fewer adverse effects than the broad immunosuppressive therapies
now in use.
QY: Bevra Hannahs Hahn, Univ. of Calif. Los Angeles, Dept. of
Medicine 310-825-6081.
(New England J. Med. 7 May 98 338:1359) (Science-Week 15 May 98)


12. CISPLATIN AND TELOMERE LOSS IN CELLS
Cisplatin is one of the most effective and broadly used anti-
cancer drugs, the apoptosis (programmed cell death) induced by
this drug generally believed to be mediated by the formation of
covalent DNA adducts that block replication and transcription.
But the detailed mechanism by which the DNA damage triggers cell
death remains unknown. Telomeres are regions at the ends of
chromosomes consisting of repeats of particular nucleotide
sequences, and with each somatic cell division a small part of
the telomere is ordinarily lost. What has been observed is that
in germline cells the lengths of telomeres are maintained
constant by repair, while in somatic cells this repair does not
occur, and this difference has led to the idea that the finite
proliferative capacity of somatic cells is related to the
ultimate depletion of telomere lengths. HeLa cells are a contin-
uously cultured line of human cancer cells (cervical carcinoma)
widely used in research and first derived from the patient
Henrietta Lacks (d. 1951), whose cervical carcinoma was the
source of the cell line. ... ... Ishibashi and Lippard (Massa-
chusetts Institute of Technology, US), using tissue-culture
monolayers of HeLa cells, report that telomeres in cisplatin
treated HeLa cells are markedly shortened and degraded. The
authors suggest that this result and the dependence of cell
proliferation on telomeric repeats indicates the shortening and 
degradation of telomeres may contribute to cisplatin
cytotoxicity.
QY: Stephen J. Lippard, Dept. of Chemistry, Mass. Inst. of
Technology 617-253-1845.
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4219)
(Science-Week 15 May 98)


13. COMPLEXITIES IN ALCOHOL CONSUMPTION MORTALITY RISK
The question of the beneficial vs. harmful effects of moderate
alcohol consumption in adults is not at all settled, despite
media trumpeting that moderate alcohol consumption reduces
mortality of middle-aged and older people. The provocation for
the media attention was the appearance of an article in the New
England Journal of Medicine of 11 Dec 97. Now 4 letters appear in
the same journal (one a response from the authors of the original
article), and it appears that conclusions from this study that
forms the basis of current popular views concerning alcohol may
not be firm. One letter writer, John D. Potter, who wrote an
editorial on the subject in the NEJM issue of 11 Dec 97, now says
"perhaps it is time to reexamine our conclusions about any
benefits that accrue from alcohol; it is certainly time to renew
attention to its deleterious health consequences."
(New England J. Med. 7 May 98 338:1385) (Science-Week 15 May 98)

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

Related Background:

ALCOHOL CONSUMPTION AND MORTALITY: A NEW MASSIVE STUDY
Ethyl alcohol is widely used as a psychoactive drug and has been
for thousands of years. That ethyl alcohol has a deleterious
effect on individual biological cells is known to any biologist
who has ever mixed ethyl alcohol into a drop containing living
cells under a microscope. In the body, however, the deleterious
cellular effects of ethyl alcohol are complicated by the systemic
detoxification mechanisms that result in the breakdown or trans-
formation of ethyl alcohol into innocuous substances, and the
result of this is that the systemic toxicity (and psychoactive
effects) of ethyl alcohol is a question of how much intact ethyl
alcohol is actually circulating in the blood, rather than how
much has been imbibed. As a further complication, there is
evidence that low levels of ethyl alcohol are protective against
heart disease and stroke, perhaps due to the ethyl alcohol
affecting the complexing of cholesterol with lipoproteins. Now
Thun et al (7 authors at 2 installations, US UK) report an
analysis of mortality data of 490,000 men and women (mean age 56
years, range 30 to 104) who reported their alcohol and tobacco
use in 1982. The authors followed this group from 1982 to 1991,
and they report the evidence indicates that moderate alcohol
consumption slightly reduced overall mortality, the benefit
increasing with age. The background cardiovascular risk with
increased alcohol consumption was far smaller than the large
increase in risk produced by tobacco. The authors suggest the
implications of their findings for social policy are beyond the
scope of their report. QY: Michael J. Thun, American Cancer
Society, 1599 Clifton Road NE, Atlanta, GA 30329-4251 US
(New England J. Med. 11 Dec 97) (Science-Week 19 Dec 97)


14. ON THE PROBLEM OF MULTI-DRUG MICROBIAL RESISTANCE
S. Levy (Tufts University, US) reviews the problem of multi-drug
resistant microbes. Antibiotic resistance, initially a problem in
hospitals and developing countries, today affects the world at
large. Some strains of disease-causing bacteria in the US may now
be untreatable: the vancomycin-resistant enterococcus,
Mycobacterium tuberculosis, Pseudomonas aeruginosa, and
Acinetobacter baumanii. The author proposes 5 principles
underlying the problem: 1) Given sufficient time and drug use,
antibiotic resistance will emerge. 2) Resistance is progressive,
evolving from low levels through intermediate to high levels. 3)
Organisms that are resistant to one drug are likely to become
resistant to others. 4) Once resistance appears, it is likely to
decline slowly, if at all. 5) The use of antibiotics by one
person affects others in the extended as well as immediate
environment.
QY: Stuart B. Levy, Tufts Univ. School of Medicine 617-636-6639
(New England J. Med. 7 May 98 338:1377) (Science-Week 15 May 98)
Note: A collection of reports on this subject appears in the
issue of SCIENCE-WEEK 8 May 1998 available at the following URL:
WWW


15. RISK OF CANCER AMONG OFFSPRING OF CHILDHOOD-CANCER SURVIVORS
Increasing numbers of children with cancer survive and reach
reproductive age, but the risk of cancer (other than
retinoblastoma) in the offspring of childhood and adolescent
cancer is uncertain. ... ... Sankila et al (10 authors at 9
installations, FI DK SE NO IS), using data from national cancer
and birth registries, report a study assessing the risk of cancer
among 5847 offspring of 14,652 survivors of cancer in childhood
or adolescence diagnosed since the 1940s and 1950s in Denmark,
Finland, Iceland, Norway, and Sweden. The data represent all the
cases of cancer diagnosed in a population of about 20 million
people during a 25-to-35-year period. The data provide no
evidence of a significantly increased risk of nonhereditary
cancer among the offspring of survivors of cancer in childhood. 
The authors suggest their results imply that fear of cancer in
their offspring is no reason to discourage the survivors of
sporadic childhood cancer from having children, and efforts to
screen for cancer in offspring of the survivors of sporadic
cancer in childhood or adolescence are not warranted.
QY: Risto Sankila, Finnish Cancer Registry, Liisankatu 21B, FIN-
00170, Helsinki, FI.
(New England J. Med. 7 May 98) (Science-Week 15 May 98)

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