ScienceWeek

SCIENCE-WEEK

SCIENCE-WEEK - Part 1/3

A Free Weekly Digest of the News of Science

May 22, 1998

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There is no national science just as there is no national
multiplication table; what is national is no longer science.
-- Anton Chekhov
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Contents of This Issue:

Part 1:
1. On the Advantages of DNA Patenting
2. A Caution Against DNA Patenting

Part 2:
3. Problems in British Forensic Science
4. Vigorous Star Formation in a Galaxy at Redshift 1.44
5. Discovery of Two New Distant Irregular Moons of Uranus
6. Accretion of Cosmic Spherules Measured at the South Pole
7. Peptoids: Alpha-Helix Formation Without Hydrogen Bonds

Part 3:
8. A Molecular Timescale for Vertebrate Evolution
9. Apoptosis of Neurons Produced by HIV-1 Virus
10. A New Method for Detection of Carcinoma Cells in Blood
11. Malaria Pathogen Genome: Evidence for Recent Divergence
12. Cardiac Arrest and Recovery of Neuronal Activity

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1. ON THE ADVANTAGES OF DNA PATENTING
In the international community of molecular biologists, a debate
has been underway for some time concerning the patenting of DNA.
Now John J. Doll (US Government), Director of Biotechnology
Examination at the US Patent and Trademark Office presents the
following points concerning this issue: 1) Just as the issuing of
broad product claims at the early stages of polymer technology
did not deter development of other new vulcanizable copolymers,
the issuing of relatively broad claims in genomic technology
should not deter inventions in genomics. 2) The same patent-
ability analysis is conducted for every patent application,
regardless of whether the application is for a computer chip, a
mechanical apparatus, a pharmaceutical, or a piece of DNA. In
every field of technology -- whether emerging, complex, or
competitive -- all the conditions for patentability (such as
statutory subject matter utility, enablement, written descript-
ion, novelty, and non-obviousness) must be met before a claim is
allowed. 3) In order for DNA sequences to be distinguished from
their naturally occurring counterparts, which cannot be patented,
the patent application must state that the invention has been
purified or isolated or is part of a recombinant molecule or is
now part of a vector. 4) Once a product is patented, that patent
extends to any use, even those that have not been disclosed in
the patent. A future non-obvious method of using that product may
be patentable, but the first patent will be dominant and a
license for the use of the product may be required. 5) Without
the incentive of patents, there would be less investment in DNA
research, and scientists might not disclose their new DNA
products to the public. It is only with the patenting of DNA
technology that some companies, particularly small ones, can
raise sufficient venture capital to bring beneficial products to
the marketplace or fund further research. 6) A strong US patent
system is critical for the continued development and dissem-
ination to the public of information on DNA sequence elements.
QY: John J. Doll, Technology Center 1600, USPTO, Washington, DC
20231 US. (Science 1 May 98 280:689) (Science-Week 22 May 98)


2. A CAUTION AGAINST DNA PATENTING
In a lengthy and detailed essay, Heller and Eisenberg (University
of Michigan Law School, US) consider the question of whether
patents, particularly biotechnology patents, can deter
innovation. The authors refer to the "tragedy of the commons"
idea first proposed by Garrett Hardin 30 years ago: people often
overuse resources they own in common because they have no
incentive to conserve. Heller and Eisenberg propose that the
recent proliferation of intellectual property rights in
biomedical research suggests a different tragedy, an
"anticommons" tragedy in which people underuse scarce resources
because too many owners can block each other. The authors suggest
that privatization of biomedical research must be more carefully
deployed to sustain both upstream research and downstream product
development, otherwise more intellectual property rights may lead
paradoxically to fewer useful products for improving human
health. In particular, the authors point out that "upstream
patent rights, initially offered to help attract further private
investment, are increasingly regarded as entitlements by those
who do research with public funds. A researcher who may have felt
entitled to coauthorship or a citation in an earlier era may now
feel entitled to be a coinventor on a patent or to receive a
royalty under a material transfer agreement. The result has been
a spiral of overlapping patent claims in the hands of different
owners, reaching ever further upstream in the course of
biomedical research."
QY: Michael A. Heller (mheller@umich.edu)
EMAIL
(Science 1 May 98 280:698) (Science-Week 22 May 98)

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Related Background:

RESEARCHERS SAY DNA PATENTING WILL IMPEDE MEDICAL PROGRESS
Complementary DNA, denoted as cDNA, is DNA that is synthesized in
vitro from an RNA template using the enzyme reverse transcript-
ase, and it can be used in cloning to investigate the presence of
various genes, or as a probe for homologous sequences in various
tissues or species. ... ... Glasner and Rothman (University of
West England Bristol, UK), in a letter to the journal Nature,
tabulate results of a survey of the Human Genome Mapping Project
resource center as an indication of the views of laboratory bench
scientists concerning the legal protection of biotechnological
inventions. This was a UK survey, with 525 respondents, nearly
90% of them located in the UK. Of those surveyed, 86.8% of 508
respondents believe that patenting of partial and uncharacterized
complementary DNA sequences without a knowledge of their
biological function will impede future development of medical
diagnostics and therapeutics.
QY: Harry Rothman (h-rothman@wpg.uwe.ac.uk)
EMAIL
(Nature 26 Mar 98) (Science-Week 10 Apr 98)

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Related Background:

GENOME PATENTING: THE MERCK EXCEPTION
In the arena of science, a discovery presupposes the preexistence
of something and implies a finding rather than a making, whereas
an invention implies fabricating something useful as the result
of original thought or experiment. In the arena of law, however,
the differences between discovery and invention are often not so
clear. A rather heated and significant debate, for example, has
arisen in recent years concerning the awarding of patents by the
US Patent Office for bits and pieces of the human genome --
certainly found (discovered) material rather than "invented"
material -- the policy ostensibly in place to provide incentive
for commercial biotechnology research, but also providing as a
consequence various proprietary blockades to access of research
material and research data, the blockades being found onerous and
antithetical to the spirit of science by many researchers.
Biotechnology is an infant discipline, and the legal structure
surrounding it is in process of evolution. That much said, it
should also be said that no one is in apparent agreement on
either side about exactly how that evolution should develop.
Recently, a representative of Merck & Co., one of the major
commercial interests in biotechnology research, outlined
Merck's position in a letter in response to a previous published
report on the human genome patenting problem. Merck's position is
apparently that human genome patenting and researcher access to
materials and data are not mutually exclusive, an attitude
supported by many people in biotechnology. But also in the letter
is the following: "Merck does not believe that patents should be
awarded to either genes or expressed sequence tags for which the
function or utility is purely speculative." Which is consistent
with classical US patent law, but which is not entirely
consistent with the attitudes of many commercial and university
research laboratories that hurry to file patents on bits and
pieces of the human genome whose function is indeed not yet
clarified. QY: Alan R. Williamson, Merck Research Labs., Merck &
Co. Inc., Rahway, NJ 07065-0900 US (Science 31 Oct 97)

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Related Background:

CONTINUING PROBLEMS OF GENOME PATENTING
The U.S. decision in the 1980s to allow anyone to obtain patent
rights to parts of the human genome is producing fruits these
days that many biologists are calling rotten. Of concern now are
genetic markers called "single nucleotide polymorphisms". A DNA
polymorphism is a DNA sequence that occurs in the population in
two or more variants, each with a significant frequency of more
than abut 1%. A single nucleotide polymorphism is an alteration
occurring in a single nucleotide base, and the alteration may or
may not be involved in a disease process. What is significant in
this context is that these alterations can be used as markers by
researchers scanning an entire genome for significant mutations.
Many researchers consider single nucleotide polymorphisms so
obvious scientifically that they should not be patentable. But
that is not the current situation, and there is concern that the
U.S. Patent Office is handing out patents in molecular biology
without much understanding of the science involved, the ostens-
ible purpose that of promoting commercial funding of potentially
useful health applications. Most biotechnology companies are
exceedingly happy about this attitude. Abbot Laboratories, for
example, has now announced it will invest up to US$20 million of
equity in a company called Genset (Paris, FR), and support up to
US$22.5 million in research for the purpose of acquiring
proprietary rights to as many single nucleotide markers as
possible. Researchers are concerned that commercial entities will
tie up so many parts of the human genome with patents (there are
about 100,000 genes in the human genome) that no one will be
able
to do any substantive research on the human genome without paying
royalties to someone. (Science 19 Sep 97)

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Related Background:

STATISTICS ON U.S. PUBLIC SECTOR PATENTS ON HUMAN DNA
In a correspondence, S. M. Thomas et al (two installations in the
UK) present results of an analysis of patents published in 1995
that include claims for human DNA sequences. 40% of the patents
are from public-sector institutions such as universities, and
most of them from the U.S. This is double the estimate for the
previous decade. The authors call the increase "remarkable".
(Nature 21 Aug 97)

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Related Background:

SCIENTISTS URGE CAUTION IN AWARDING OF HUMAN GENE PATENTS
Continuing the expression of concern about the manner in which
current U.S. intellectual property laws may interfere with
scientific research, the U.S. National Academy of Sciences has
joined the National Institutes of Health and the Human Genome
Organization in protesting an interpretation of current patent
law that would permit the issuing of patents on what are called
"expressed gene sequence tags". Bruce Alberts, president of the
National Academy of Sciences, warns against "patents that allow
an early group of inventors who have disclosed little new
knowledge to constrain the actions of subsequent investigators."
(Nature 26 Jun 97)

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Related Background:

COMPANY OBTAINS PATENT FOR SKIN CANCER MELANOMA GENE
Under present U.S. and European patent law it is possible to
obtain a patent on a human gene in the same manner as one
obtains a patent on a chemical compound. Myriad Genetics, the
Salt Lake City company that has two patents pending for breast
cancer genes (BRCA-1 and BRCA-2), has now received a patent for
the gene it claims causes melanoma (Multiple Tumor Suppressor 1
or MTS1), and for the method of testing for the presence of that
gene in humans. Lisa Cannon-Albright, a University of Utah
geneticist, Mark Skolnik, a Myriad geneticist, and Alexander
Kamb, a Myriad molecular biologist are listed as the inventors.
(New York Times 5 May 97)


(continued in Part 2)

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SCIENCE-WEEK - Part 2/3

A Free Weekly Digest of the News of Science

May 22, 1998

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3. PROBLEMS IN BRITISH FORENSIC SCIENCE
There are two extant meanings of the term "forensic". In the
first sense, the adjective is used to describe something suitable
for use in the courts, litigations, prosecutions, etc. In the
second sense, the adjective is used to describe "an argumentative
exercise". When one speaks of "forensic science", one is usually
invoking the first sense,  considering the use of scientific
evidence in legal proceedings. But unhappily it is not uncommon
for forensic science in the courtroom to involve the second usage
as well as the first. In a recent issue, the UK journal *Nature*
publishes a letter from a British forensic scientist calling
attention to faulty or incompetent forensic science practices in
that country, and one suspects that similar comments could be
made about forensic science in any country where such a thing
exists. Forensic science, after all, is the use of science for
advocacy, and it is the advocates and not the scientists who
control that use and the presentation or non-presentation of
scientific evidence. In the *Nature* letter, Z. Erzinclioglu
points out that in the UK miscarriages of justice resulting from
faulty or incompetent forensic science practices began to attract
public notice in the 1980s. Two investigating commissions,
including one team to investigate the discovery that contaminated
centrifuges had been used to secure convictions in 12 terrorist
cases, concluded the problems were isolated cases. The author of
the letter does not agree with that assessment, and suggests that
forensic science in the UK is in "a very poor and disordered
state." In the first place, standards, both scientific and
ethical, have fallen and will continue to do so unless the
present structure and organization of the profession are
reformed. And in the second place, the way forensic evidence is
handled after leaving the laboratory often results in its
perversion, through handling not only by the police but also by
lawyers in court. The author concludes that "the main difficulty
lies in convincing those who need to be convinced that a serious
problem exists at all."
QY: Zakaria Erzinclioglu, 28 Harlton Rd., Cambridge CB3 7HB, UK.
(Nature 30 Apr 98 392:859) (Science-Week 22 May 98)


4. VIGOROUS STAR FORMATION IN A GALAXY AT REDSHIFT 1.44
Redshift (symbol: z) is a lengthening of the wavelengths of
electromagnetic radiation from a source caused either by the
movement of the source (Doppler effect) or by the expansion of
the universe (cosmological redshift). Redshift is defined as the
change in wavelength of a particular spectral line divided by the
unshifted wavelength of that line. Large redshifts imply large
radial velocities (which imply large distances, according to
current cosmological theory), but at redshifts greater than about
0.2 there is a relativistic divergence from a linear relation. A
redshift of 4.0 corresponds to an object receding with a radial
velocity 92% that of the velocity of light. Near-infrared surveys
have revealed a substantial population of faint galaxies that are
extremely red in their optical to near-infrared colors, and it is
believed these numerous galaxies are red either because of an
absence of recently formed stars, or because the galaxies contain
large amounts of dust, which reddens the light emitted by the
stars by preferentially absorbing the shorter-wavelength
radiation. ... ... Cimatti et al (4 authors at 4 installations,
IT NL US) report the detection of continuum emission from HR10,
considered an archetype of extremely red galaxies, and which
shows a redshift z value of 1.44. The authors propose the
evidence demonstrates that HR10 is a dusty galaxy undergoing a
burst of massive star formation, and that their results provide a
clear example of a high-redshift galaxy where the star-formation
rate inferred from the ultraviolet luminosity (the usual method
at such redshifts) would be underestimated by a factor of more
than 500. The authors further propose that star formation in
distant objects (galaxies) occurs in different modes, and that
the most vigorous episodes of star formation probably arise in
dusty environments as predicted by several models. The authors
therefore suggest that great caution must be used to infer the
global star-formation history of the Universe from optical and
ultraviolet observations.
QY: Andrea Cimatti (cimatti@arcetri.astro.it)
EMAIL
(Nature 30 Apr 98 392:895) (Science-Week 22 May 98)


5. DISCOVERY OF TWO NEW DISTANT IRREGULAR MOONS OF URANUS
The systems of satellites and rings surrounding the giant planets
in the Solar System have remarkably similar architectures.
Closest to each planet are rings with associated moonlets, then
large "regular" satellites on nearly circular orbits close to the
planet's equatorial plane, and finally one or more distant
"irregular" satellites on highly elliptical or inclined orbits.
Until now, the only departure from this broad classification
scheme was the satellite system around Uranus, in which no
irregular satellites had been found. ... ... Gladman et al (7
authors at 4 installations, CA US) now report the discovery of
two satellites orbiting Uranus at distances of several hundred
planetary radii. The satellites have inclined retrograde orbits
of moderate eccentricity that clearly identify them as irregular.
Both moons are unusually red in color, suggesting a link between
these objects -- which were presumably captured by Uranus early
in the history of the Solar System -- and other recently
discovered bodies orbiting in the outer Solar System. The authors
suggest the physical properties of these new moons may provide
valuable clues to conditions in the early Solar System.
QY: Brett J. Gladman (gladman@cita.utoronto.ca)
EMAIL
(Nature 30 Apr 98 392:897) (Science-Week 22 May 98)


6. ACCRETION OF COSMIC SPHERULES MEASURED AT THE SOUTH POLE
Micrometeorites are terrestrially collected extraterrestrial
particles smaller than about 1 mm, and which account for most of
the mass being accreted to the Earth. Compared with meteorites,
micrometeorites more completely represent the Earth-crossing
meteoroid complex, and include fragments of asteroids, comets,
Mars and our Moon, as well as pre-Solar and interstellar grains.
Previous measurements of the flux of micrometeoroids that survive
to the Earth's surface have large uncertainties owing to the
destruction of particles by weathering, inefficiencies in
magnetic collection or separation techniques, low particle
counts, poor age constraint, or highly variable concentrating
processes. ... ... Taylor et al (3 authors at 2 installations,
US) report an attempt to circumvent these problems through the
collection of thousands of well-preserved and dated micrometeor-
ites from the bottom of the South Pole water well that supplies
drinking water for the Scott-Amundsen station. This well is a
5000 m^(3) subsurface water pool. Micrometeorites originally on
the snow surface became incorporated into essentially horizontal
ice layers whose depth-age relationship has been determined from
the stratigraphy of an ice core. As the well melts downward,
micrometeorites released from the ice remain on the bottom of the
water-filled cavity. Using this collection of micrometeorites,
the authors have determined precise estimates of flux and mass
distribution for 50 to 700 micron cosmic spherules (melted
micrometeorites). The authors suggest their results indicate that
about 90% of the incoming mass of submillimeter particles
evaporates during atmospheric entry, and that their results
provide constraints for models describing the survival
probability of micrometeoroids.
QY: James H. Lever (jlever@crrel.usace.army.mil)
EMAIL
(Nature 30 Apr 98 392:899) (Science-Week 22 May 98)


7. PEPTOIDS: ALPHA-HELIX FORMATION WITHOUT HYDROGEN BONDS
Peptoids are a family of oligomers originally developed for use
in combinatorial drug discovery programs. These non-natural
oligomers are based on a polyglycine backbone whose side chains
are appended to the amide nitrogen (rather than to the alpha-
carbon as in peptides). An extremely diverse series of function-
alized oligomers can be easily obtained from starting materials.
One interesting aspect is that many of the mechanisms that direct
the self-assembly of biopolymer structures are lacking in
peptoids. Specifically, peptoids lack amide protons, and thus no
hydrogen bond network along the polymer backbone is possible.
Likewise, because the main chain contains no chiral centers,
peptoids have no intrinsic handedness. ... ... Kirshenbaum et al
(9 authors at 2 installations, US) report the synthesis and
characterization of a family of structured oligo-N-substituted-
glycines (peptoids) up to 36 residues in length. They report that
some of these sequences have stable secondary structure (helix
conformations) in both aqueous and organic solvents despite the
achirality of the polymer backbone and the absence of hydrogen
bond donors. Their evidence indicates that polypeptoid secondary
structure is highly stable, and that unfolding is reversible and
cooperative. Thermodynamic parameters obtained for unfolding are
similar to those obtained for the alpha-helix-to-coil transitions
of peptides. The authors suggest this class of biomimetic
polymers may enable the design of self-assemblying macromolecules
with novel structures and functions, and may have potential use
as reagents for DNA and drug delivery.
QY: Ronald N. Zuckermann (Ron_Zuckermann@cc.chiron.com)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4403,4409)
(Science-Week 22 May 98)

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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) (Science-Week 3 Oct 97)

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Related Background:

STUDIES WITH BETA-PEPTIDES PROMISE NEW ERA IN DRUG DESIGN
There is apparently an intense interest these days among chemists
and biochemists in the synthesis of oligomers that produce stable
complex structures. The specific catalytic power of a natural
enzyme is based primarily on how it is folded, since the folding
creates a special reactive site for the catalytic process. A
number of chemical laboratories are now synthesizing what are
called "beta-peptides", which are oligomers consisting of beta
amino acids rather than the naturally occurring alpha amino
acids. These beta-peptides have been found to fold into the same
general kinds of defined structures as ordinary peptides do,
suggesting that biological activity may be possible. All of this
work is the beginning of a chemistry of synthetic biologically
active enzymes, which will ultimately have a profound effect on
drug design and basic research into cellular biochemical
processes. (Chemical & Engineering News 16 June)
(Science-Week 26 Jun 97)

(continued in Part 3)

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SCIENCE-WEEK - Part 3/3

A Free Weekly Digest of the News of Science

May 22, 1998

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8. A MOLECULAR TIMESCALE FOR VERTEBRATE EVOLUTION
A timescale is necessary for estimating rates of molecular and
morphological change in organisms, and for interpreting patterns
of macroevolution and biogeography. Timescales have usually been
obtained from the fossil record, where the earliest represent-
atives of two lineages establish a minimum time of divergence of
these lineages. An alternative method involves the clock-like
accumulation of sequence differences in certain genes. Estimates
from single genes may have large statistical errors, but studies
of multiple genes provide a more reliable estimate of divergence
time. ... ... Kumar and Hedges (Pennsylvania State University,
US) report an analysis of 658 nuclear genes to provide divergence
time estimates for mammalian orders and major lineages of
vertebrates. The molecular times agree with most early
(Paleozoic) and late (Cenozoic) fossil-based times, but indicate
major gaps in the Mesozoic fossil record. The authors propose
that at least 5 lineages of placental mammals arose more than 100
million years ago, and most of the modern orders seem to have
diversified before the Cretaceous/Tertiary extinction of the
dinosaurs. The authors suggest their molecular timescale for
vertebrate evolution will be useful in calibrating local
molecular clocks and in estimating intra-ordinal divergence times
more reliably, especially in groups with poor fossil records.
QY: S. Blair Hedges (sbh1@psu.edu)
EMAIL
(Nature 30 Apr 98 392:917) (Science-Week 22 May 98)


9. APOPTOSIS OF NEURONS PRODUCED BY HIV-1 VIRUS
HIV-1 is the subtype of HIV (human immune-deficiency virus) that
causes most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa. HIV-1 has a complex genome that
encodes at least 6 accessory gene products that play a crucial
role in regulating viral replication. One of these products is
the 96-amino acid virus protein R (Vpr). This small accessory
protein is a multifunctional protein that is present in the serum
and cerebrospinal fluid of AIDS patients, and that apparently can
form cation-selective ion channels across in vitro planar lipid
bilayers. ... ... Pillar et al (4 authors at Australian National
University, AU) now report that the small HIV-1 accessory protein
(Vpr) associates with the plasma membrane of hippocampal neurons,
and causes a large inward cation current and depolarization of
the plasma membrane, and eventual cell death (apoptosis). The
authors suggest they have demonstrated a physiological action of
the virus protein and its mechanistic basis, and that these
findings may have important implications for neuropathologies in
AIDS patients who possess significant amounts of the virus
protein Vpr in cerebrospinal fluid.
QY: David A. Jans (David.Jans@anu.edu.au)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4595)
(Science-Week 22 May 98)


10. A NEW METHOD FOR DETECTION OF CARCINOMA CELLS IN BLOOD
There is evidence that primary cancers begin shedding neoplastic
cells into the blood circulation at an early stage, and an
important clinical goal is the detection of such cells as early
as possible. One method that has been used is the polymerase
chain reaction (usually denoted as PCR), which is a synthetic
method allowing bulk replication of minute quantities of a chosen
segment of a nucleic acid to take place accurately and effic-
iently in vitro. ... ... Racila et al (7 authors at 4 install-
ations, US) now report the development of a cellular assay more
sensitive than PCR, and which allows precise enumeration and
characterization of circulating carcinoma cells. The basis of the
method is that carcinoma cells (which are of ectoderm origin)
differ from leukocytes (which are of mesoderm origin) in their
gene expression, and thus each of these two cell populations has
tissue-specific molecules on its surface or intracellularly. The
assay involves the use of a combination of cytological techniques
(flow cytometry and immunocytochemistry) to recognize these
tissue-specific molecules. The authors report the assay can
detect 1 epithelial cell or less in 1 milliliter of blood. The
method was used to assay peripheral blood from human patients
with carcinoma of the breast, prostate cancer, and 13 controls,
and highly significant differences in the number of circulating
epithelial cells were found between normal controls and patients
with cancer, even supposed organ-confined cancer. The authors
suggest their assay is measuring circulating tumor cells and may
be helpful in early detection of cancer, in monitoring disease,
and in prognostication.
QY: Jonathan W. Uhr (juhr@mednet.swmed.edu)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4589)
(Science-Week 22 May 98)


11. MALARIA PATHOGEN GENOME: EVIDENCE FOR RECENT DIVERGENCE
Malaria, an infectious disease caused by a parasitic protozoan
transmitted by a mosquito bite, blood transfusion, or the use of
a common syringe by drug addicts, kills one or two million people
each year. There are actually 4 types of protozoan parasites that
cause the disease, with Plasmodium falciparum the most dangerous.
A DNA polymorphism is a naturally occurring variation in the
normal nucleotide sequence of the genome within individuals in a
population. Variations are denoted as polymorphisms only if they
cannot be accounted for by recurrent mutation and occur with a
frequency of at least about 1%. The term "synonymous DNA poly-
morphism" refers to a polymorphism which does not involve changes
in the amino acid sequences of the encoded proteins.... ... Rich
et al (4 authors at University of California Irvine, US) report
an analysis of DNA sequences from world-wide geographic strains
of Plasmodium falciparum, the data showing a complete absence of
synonymous DNA polymorphism at 10 gene loci. The authors suggest
that all extant world populations of the parasite have recently
derived (within several thousand years) from a single ancestral
strain, and that the recent origin of the world-wide P.
falciparum populations may account for its virulence as the most
malignant of human malarial parasites.
QY: Francisco J. Ayala (fjayala@uci.edu)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4425)
(Science-Week 22 May 98)


12. CARDIAC ARREST AND RECOVERY OF NEURONAL ACTIVITY
Cardiac arrest lasting a few seconds to a few minutes can be
reversed (by cardiopulmonary resuscitation) without brain damage.
However, after cardiac arrest that lasts longer, reperfusion of
the brain is accompanied by delayed irreversible brain damage
that occurs several days after the reperfusion of brain tissue.
The post-ischemic period during which neuronal activity recovers,
but which precedes the appearance of delayed irreversible damage,
constitutes a therapeutic window in which to prevent delayed cell
death. In animal models of global ischemia at normal temperatures
it has been shown that this post-ischemic period occurs even
after a complete interruption of cerebral blood flow lasting up
to 1 hour. ... ... Charpak and Audinat (Centre National de la
Recherche Scientifique, FR) report a study to evaluate the
maximal duration of cardiac arrest compatible with the occurrence
of the postischemic recovery period, the study involving analysis
of the early phase of the period in acute preparations of brain
tissue (rat and guinea pig) prepared after a cardiac arrest of
several hours and maintained in vitro. The authors report that
during a permanent cardiac arrest, rodent brain tissue is
physiologically preserved in situ in a particular quiescent state
characterized by the absence of electrical activity and by a
critical period of 5 to 6 hours during which brain tissue can be
reactivated (both neurophysiologically and biochemically) upon
restoration of a simple energy supply (glucose/oxygen). The
authors suggest that in rodents the duration of cardiac arrest
compatible with a short-term recovery of neuronal activity is
much longer than previously expected, and that analysis of the
parameters that regulate this duration may bring new insights
into the prevention of post-ischemic damage.
QY: S. Charpak (serge.charpak@espci.fr)
EMAIL
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4748)
(Science-Week 22 May 98)

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BOOK NOTES:

Michael Gross: LIFE ON THE EDGE
Amazing Creatures Thriving in Extreme Environments
Plenum, 1998, 200p, US25.95 CA35.95 (July)
This is a well-written little book on extremophile biological
forms, with an index, extensive bibliography, and a helpful
glossary for non-biologists. The explications are precise, and
usually include an excellent summary of the relevant molecular
biology. Life and its limits, extreme environments and their
inhabitants, the cell's survival kit, relevance of extremes for
biotechnology and medicine, extremists and the tree of life, life
beyond Earth. The author is a Research Fellow at Oxford
University, UK.

Clifford A. Pickover: STRANGE BRAINS AND GENIUS
The Secret Lives of Eccentric Scientists and Madmen
Plenum, 1998, 340p, US28.95 CA40.50 (June)
Despite the sensationalist title and subtitle, this is an
interesting potpourri of fact and rumor concerning the link
between apparent psychological aberrations and apparent "genius".
Among individuals considered at length are Nikola Tesla, Oliver
Heaviside, Samuel Johnson, Richard Kirwan, Jeremy Bentham, Henry
Cavendish, Francis Galton, Geoffrey Pike, and the Unabomber
Theodore Kaczinski. The author is a science journalist.

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