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ScienceWeek
SCIENCE-WEEK
A Weekly Email Digest of the News of Science
A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.
September 15, 2000 -- Vol. 4 Number 37
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Do not undertake a scientific career in quest of
fame or money. There are easier and better ways to
reach them. Undertake it only if nothing else will
satisfy you; for nothing else is probably what you
will receive. Your reward will be the widening of
the horizon as you climb. And if you achieve that
reward you will ask no other.
-- Cecilia Payne-Gaposchkin (1900-1979)
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Section 1
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Contents of this Issue (Full reports in Section 2):
1. SCIENCE POLICY: ON THE PATENTING OF KNOWLEDGE
The essential issue is as follows: A research group, academic or
commercial, identifies the DNA sequence for a particular gene.
The research group applies for a patent on this sequence, is
issued such a patent by the US Patent Office, and once the patent
is issued, the research group requires that anyone who applies
_knowledge_ of that sequence for any use -- medical, commercial,
or whatever -- must pay royalties to the patent-holder.
(Technology Review Sep/Oct 2000)
2. MOLECULAR BIOLOGY: ON THE NEED FOR A CHIMPANZEE GENOME
The human genome will soon be completely sequenced, a milestone
in the history of biology and medical science. Intensive research
effort is now focused on the next logical biomedically relevant
target -- the mouse. After the mouse, then what? From a
biomedical standpoint, a strong argument can be made that the
complete sequencing of the genome of our closest evolutionary
relative, the chimpanzee (Pan troglodytes), will be a biomedical
imperative. (Genome Research August 2000 10:1065)
3. MEDICAL BIOLOGY: CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease is a serious condition
afflicting an estimated 14 million people in the US alone. In the
US, airflow obstruction has been found in approximately 14
percent of white male smokers, as compared with approximately 3
percent of white male nonsmokers. This disease is now the 4th
leading cause of death in the US, and it is the only common cause
of death that is increasing in incidence.
(New England J. Med. 27 Jul 00 343:269)
4. EARTH SCIENCES: NEW EVIDENCE ON SEAFLOOR SPREADING
The first 3-dimensional reflection experiment on a mid-ocean
ridge suggests the geometry of melt distribution is inconsistent
with large-scale crustal redistribution of melt away from centers
of upswelling. In the future, 3-dimensional imaging of the
structure of the crust, as well as of the underlying mantle, will
be increasingly seen as essential for understanding the volcanic,
tectonic, and hydrothermal processes that accompany the formation
of ocean crust. (Nature 10 Aug 00 406:614)
5. CONDENSED-MATTER PHYSICS: ON THE ISING MODEL
The Ising model, named after Ernst Ising (1900-1998), was first
formulated in 1920 by Wilhelm Lenz, who proposed it as a
simplified version of a ferromagnet. Various versions of the
model have been of great utility in studies of cooperative
phenomena in condensed-matter systems, and the model itself has
an interesting human story attached to it.
(American Scientist Sep/Oct 2000 88:384)
6. CONDENSED-MATTER PHYSICS: QUASI-CRYSTALS
New experiments provide direct information concerning whether
conduction electrons (Fermi electrons) in quasicrystals are more
localized than in a normal metal. A mapping of the energies and
momenta of electrons in the quasicrystal Al-Ni-Co demonstrates
that some of the electron states must be delocalized and
therefore contribute to the pool of conduction electrons.
(Nature 10 Aug 00 406:602)
7. IN FOCUS: ON THE ELECTROMAGNETIC FIELD
8. FROM THE SCIENCEWEEK ARCHIVE:
WETTERHAHN LABORATORY POISONING CASE: FINAL MEDICAL REPORT
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Section 2
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1. SCIENCE POLICY: ON THE PATENTING OF KNOWLEDGE
Although currently muted and confined to the molecular
biology and biotechnology communities, the debate concerning gene
patenting will probably boil up into a major public discussion
within the next few years. The essential issue is as follows: A
research group, academic or commercial, identifies the DNA
sequence for a particular gene. The research group applies for a
patent on this sequence, is issued such a patent by the US Patent
Office, and once the patent is issued, the research group
requires that anyone who applies _knowledge_ of that sequence for
any use -- medical, commercial, or whatever -- must pay royalties
to the patent-holder.
From the viewpoint of the physical sciences, this is
certainly a strange situation: In the physical sciences, if a
research group identifies the molecular constituents and
molecular formula for, let us say, a found mineral, it is
certainly not possible to obtain a patent on the _knowledge_ of
the constituents of the mineral and require payment of royalties
for use of that knowledge in any application, commercial or
noncommercial. So something is brewing here, and lest anyone
think there is only a _potential_ for problems, it should be
realized that in the US alone more than 15,000 patents on human
genes are now pending in the Patent Office.
... ... Antonio Regalado (Technology Review, US) presents a
commentary on the developing debate concerning gene patenting,
the author making the following points:
1) The top 10 human gene patent-holders (patents already
awarded) are as follows:
... ... Incyte Genomics 397 patents
... ... University of California 253
... ... Glaxo SmithKline 248
... ... US Dept. Health & Human Services 205
... ... Novo Nordisk 196
... ... Genentech 165
... ... Isis Pharmaceuticals 146
... ... Chiron 135
... ... American Home Products 130
... ... Novartis 128
Human Genome Sciences holds patents on 103 human genes,
including those believed to be involved in osteoporosis and
arthritis, and the company has pending patents on another 7500
genes. Celera, which only began decoding DNA in 1999, has already
filed patent claims on at least 6500 human gene sequences.
2) The author points out that no US Congressional vote or
Supreme Court decision has ever directly addressed the question
of whether human genes should be patentable at all. Many
scientists and lay people believe the knowledge of human genes
and how they work ought to be public property. Physicians and
scientists are complaining that the thicket of patent rights is
already stifling biomedical research, and even interfering with
the care of patients. Even those in the pharmaceutical and
biotechnology industries who readily embrace intellectual
property protections are confronting the question: Is today's
deluge of patents on human genes really good for innovation?
3) As an example of the current situation: In April 2000,
the University of Rochester (US) was granted a patent on the
human gene Cox-2. University officials immediately filed a
lawsuit against G.D. Searle, a subsidiary of Pharmacia. The basis
of the lawsuit: Searle markets a highly lucrative pain-killer
(analgesic) called "Celebrex" which acts by blocking the enzyme
encoded by the Cox-2 gene. The University of Rochester claims
that Searle's drug infringes its patent, which describes not just
the DNA letters of the gene, but also the "general idea" of using
a drug that blocks Cox-2 as a way to alleviate pain. In 1999, the
first year on the market, Celebrex sales amounted to US$1.5
billion. A recent University of Rochester press release states
the university's patent is "likely to be the most lucrative in US
history."
4) Another example: A research group at the Miami Children's
Hospital (Florida, US) helped discover (and then patented) the
mutations that cause Canvan disease, an inherited neurological
disorder. Knowledge of the mutation allows physicians to test
patients who fear they might be carriers of the defect by taking
blood samples and checking for specific DNA mutations on
chromosome 17, where the Canvan gene is located. Miami Children's
Hospital requires a royalty payment of US$12.50 for every test
performed, even though the test procedure itself is not covered
by the patent. A similar situation exists with companies that
have patents on genes that can predict the onset of breast cancer
or Alzheimer's disease. Royalties are demanded for use of
_knowledge_ of the genes.
5) The author concludes: "Although gene patenting has been
going on for years, as far as the man and woman on the street are
concerned, the debate has just begun. And if it follows the
course of other recent biomedical controversies over cloning and
stem cell research, it may be one argument that politicians and
ordinary citizens will not be content to leave in the hands of
scientists, pharmaceutical companies, or patent lawyers."
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Antonio Regalado: The great gene grab.
(Technology Review Sep/Oct 2000)
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Summary by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON THE PATENTING OF GENE FRAGMENTS
In this context, a "clone" is a nucleic acid sequence that is
inserted by some means into the genome of a host so that the new
host genome can then replicate the original sequence in high
quantity. The term "gene library" refers to a collection of DNA
fragments resulting from laboratory digestion of a genome by a
suitable enzyme. Each DNA fragment can then be cloned in
quantity. Libraries of *complimentary DNA (cDNA) are libraries of
those genes currently operational (active) in a living system or
living cell or tissue. An "expressed sequence tag" is a partial
sequence of a clone picked at random from a cDNA library and used
in the identification of genes being expressed in a particular
tissue. The expressed sequence tag technique exploits automated
DNA sequencing and sequence data handling, and a high number of
expressed sequence tags have been found to be associated with
previously unknown genes, which are identified by the predicted
primary protein structure apparently encoded by the gene and the
relation of these proteins to proteins of known structure.
Expressed sequence tags have proved valuable in mapping the human
genome, and there is controversy about attempts to patent such
fragments. ... ... Tony Reichhardt (*Nature*, UK) reports on the
current debate concerning the patenting of gene fragments, the
author making the following points: 1) The recent award of the
first US patent for expressed sequence tags has led to
speculation that similar rights might soon be granted for gene
fragments whose patents have been pending for years. The recent
patent award occurred in October to Incyte Pharmaceuticals (Palo
Alto, CA US), the patent granted for one full-length gene and
polynucleotides that encode more than 40 *protein kinases. 2)
There is apparent disagreement between the US National Institutes
of Health (NIH) and the US Patent Office concerning the patenting
of gene fragments. Although NIH has expressed concern about the
granting of proprietary rights to gene fragments, the US Patent
Office appears poised to grant such rights, and the office
evidently now has applications covering millions of expressed
sequence tags. 3) Last week, at a meeting on intellectual
property rights at the US National Academy of Sciences, Francis
Collins, head of the NIH National Human Genome Research
Institute, called the Incyte patent award a "disturbing turn of
events" and expressed the fear that it signalled the willingness
of the US Patent Office to grant overly broad proprietary rights.
4) Meanwhile, the European Union has published a directive to be
implemented by the year 2000, the directive allowing patents on
isolated human genes and gene fragments with known functions, as
well as on *transgenic life.
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Tony Reichhardt: Patent on gene fragment sends researchers a
mixed message...
(Nature 10 Dec 98 396:499)
QY: Tony Reichhardt nature@nature.com
-----------
Text Notes:
... ... *complimentary DNA (cDNA): Complementary DNA, denoted as
cDNA, is DNA that is synthesized in vitro from an RNA template
using the enzyme reverse transcriptase, 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.
Essentially, the idea is that if the RNA template is active RNA
in a particular cell type, then the cDNA derived from that RNA
can demarcate the active (operational) genes in that cell type --
the original genes that produced the active RNA.
... ... *protein kinases: In biochemistry, a kinase is an enzyme
that catalyzes a reaction involving the transfer of phosphate
groups, the transfer usually activating another enzyme involved
in a specific function.
... ... *transgenic life: A transgenic organism is an organism
into which genetic material from another organism has been
transferred, the transferred and incorporated new genes then
being expressed with the resultant production of specific
proteins.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Jan99
-------------------
Related Background:
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
description, 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 dissemination 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)
-------------------
Related Background:
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
(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
transcriptase, 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
(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) (Science-Week 21 Nov 97)
-------------------
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
ostensible 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) (Science-Week 10 Oct 97)
-------------------
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) (Science-Week 29 Aug 97)
-------------------
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) (Science-Week 3 Jul 97)
-------------------
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) (Science-Week 8 May 97)
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
2. MOLECULAR BIOLOGY: ON THE NEED FOR A CHIMPANZEE GENOME
The human genome will soon be completely sequenced, a milestone
in the history of biology and medical science. Intensive research
effort is now focused on the next logical biomedically relevant
target -- the mouse. As a mammalian species of importance in
biomedical research, primarily due to economies of research on
this small easily bred animal, the mouse has no equal. And after
the mouse, what next? There have been calls to sequence the
genomes of the rat (Rattus rattus), the African clawed toad
(Xenopus laevis), and the zebra fish (Danio rerio), all
laboratory animals for which there is an enormous literature of
published laboratory experiments. These are certainly species of
great importance to biology. From a biomedical standpoint,
however, a strong argument can be made that the complete
sequencing of the genomes of none of these animals would be as
important as the complete sequencing of the genome of our closest
evolutionary relative, the chimpanzee (Pan troglodytes).
... ... Ajit Varki (University of California San Diego, US)
presents a commentary calling for the sequencing of the
chimpanzee genome, the author making the following points:
1) Chimpanzees and humans share nearly 99 percent of their
genomes. Knowing the complete chimpanzee genome will give us a
window into genes that contribute to "humanness". The emergence
of humans can be regarded as one of the major transitions in
evolution, and the complete explanation of this phenomenon ranks
as one of the greatest unsolved mysteries of science.
2) Extrapolating findings in physiology and pathology from
mice, rats, toads, or fish to humans can be difficult, because of
the physiological and genetic differences between humans and
these species. In contrast, the greater than 99 percent identity
of amino acid sequences of most chimpanzee and human proteins
predict a stronger likelihood of finding genetic explanations for
any disease differences. Studies of the chimpanzee genome could
be considered a logical extension of the current emphasis on
exploiting sequence differences between various human groups to
identify important disease susceptibility genes.
3) Some pathological states in humans seem to represent the
normal situation in chimpanzees, including closure of the skull
sutures around the time of birth (perinatal period)
(craniosynostosis), a high white blood cell count (general
leukocytosis), and hairiness (extensive hypertrichosis). Several
other diseases or physiological states of humans appear to be
rare or markedly attenuated in the chimpanzee. Some of these
diseases can be attributed to anatomic differences between the
species, including protracted, painful, and dangerous childbirth
(resulting from the larger head of the human fetus and the
altered pelvis of the bipedal human female), wisdom tooth
impaction (resulting from reduced jaw size in humans and the lack
of a post-molar gap), and various diseases attributed to gravity
effects on bipedal humans (vertebral osteoarthritis,
intervertebral disc protrusion, varicose veins, and hemorrhoids).
There are also a few anatomically unique diseases of great apes
that do not occur in humans, such as infection of the pharyngeal
air sacs (an organ that is absent in humans). The higher
frequency in humans of anatomical disorders of the central
nervous system (e.g., hydrocephalus) is also intriguing, but
could be explained on the basis of increased perinatal trauma.
4) But many other differences between humans and chimpanzees
cannot be explained on any obvious behavioral, dietary, anatomic,
cellular, or biochemical basis. The author suggests it is these
differences that justify the biomedical imperative of the
sequencing of the chimpanzee genome. The author summarizes these
significant differences as follows:
... ... a) The failure of HIV infection to progress to AIDS in
the chimpanzee. Despite many studies attempting to find the
answer, the mystery remains: the HIV retrovirus seems to live in
a symbiotic state within the chimpanzee immune system, whereas it
almost routinely destroys the helper T cells of humans.
... ... b) Alzheimer's disease is a common and devastating
disease causing dementia in elderly humans, the human brain
pathology characterized by the accumulation of amyloid plaques
together with neurofibrillary tangles. The pathological lesion,
including the neurofibrillary tangles, has never been observed in
the brains of elderly chimpanzees. In contrast, age-matched
samples from human brain specimens show a significant rate of
these classic lesions, often well before symptoms of dementia
have become evident. Neurofibrillary tangles can even exist in
human brains independent of plaques, beginning virtually at birth
and reaching a 50 percent prevalence by age 48. The fact that the
full-blown lesion of Alzheimer's disease has also not been
observed in other long-lived animals (e.g., elderly elephants),
increases the significance of this finding, and makes a
comparison between humans and the corresponding chimpanzee genes
of great potential benefit.
... ... c) Of all the different forms of malaria, that caused by
the pathogen Plasmodium falciparum is the most aggressive and
acutely life-threatening; it is a major cause of mortality
worldwide. Chimpanzees are apparently immune to infection by this
parasite, and instead get infected by its close relative
Plasmodium reichnowii, which evidently does not make the
chimpanzee very ill. The knowledge gleaned from comparative
studies of the relevant parasite genomes as well as the human and
chimpanzee genomes could be of great importance.
... ... d) The most common human cancers, epithelial neoplasms
such as carcinomas of the breast, ovary, lung, stomach, colon,
pancreas, and prostate, cause more than 20 percent of deaths in
modern human populations. In contrast, the cancer incidence rates
for non-human primates is only approximately 2 to 4 percent and
seems to be even lower in the great apes. It is of interest that
a cell-surface sugar modification that is lost in the human
lineage due to genomic mutation is reported to reappear in human
cancers.
... ... e) Several aspects of female reproductive biology appear
to be different between great apes and humans. For example,
menopause has not been observed in long-lived captive female
chimpanzees. Compared to chimpanzees, human females are unusual
in having a high frequency of breast diseases such as fibrocystic
disease and cancer. Also, the absence of external signs of
ovulation in human females may result in fertilization taking
place at suboptimal times with regard to the condition of the
ovum. Thus, the question arises whether fertilization of
deteriorating eggs may explain -- at least partly -- the
relatively high rate of gross chromosomal and other genetic
abnormalities in human fetuses.
... ... f) In addition to the above examples, anecdotal evidence
suggests that some other common human conditions are rare in
great apes in captivity: i) Despite a high frequency of atopic
rhinitis and polyps, bronchial asthma is rarely diagnosed in
chimpanzees. ii) Acne vulgaris, the common skin affliction of
human teenagers, also appears to be uncommon in the adolescent
chimpanzee. iii) Rheumatoid arthritis has not been detected in
chimpanzees.
-----------
Ajit Varki: A chimpanzee genome project is a biomedical
imperative.
(Genome Research August 2000 10:1065)
QY: Ajit Varki avarki@ucsd.edu
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MOLECULAR BIOLOGY:
ON THE RAT AS A MODEL SYSTEM IN FUNCTIONAL GENOMICS
In a few years, the complete sequence of nucleotide bases in the
human genome will be determined. But that is only the first phase
of the new human biology of the 21st century: after specification
of the complete sequence will come years of arduous work
identifying specific new genes and relating the proteins encoded
by these genes to specific sets of events in health and disease.
This second phase of genome research, the "functional genomics
era", will be carried out, for the most part, on animals, using
animal models to formulate hypotheses concerning the role played
by various parts of the human genome in human biology. The basis
for the use of animal models in this undertaking is the strong
apparent similarity of the genomes and physiology of certain
mammalian species to the human genome and human physiology. The
mouse, a small mammal easily maintained and easily bred, is
currently the favorite animal model used in mammalian genetics
research, but there are a number of candidates for future
functional genomics, and researchers, as always, will need to
make important strategic decisions concerning the focus of their
laboratory work. Intrinsic to the use of an animal model in
functional genomics is the complete sequencing of the genome of
that animal.
... ... Howard J. Jacob (Medical College of Wisconsin, US)
presents a review of the role the rat will play in annotating the
human genome in the functional genomics era. The author makes the
following points:
1) The author points out that the laboratory rat, _Rattus
norvegicus_, was the first mammalian species domesticated for
scientific research, with work dating back to before 1850. From
this beginning, the rat has become the most widely studied
experimental animal model for biomedical research. Since 1966,
nearly 500,000 research articles reporting the use of rats have
been published, with most of these articles focused on evaluating
the biology and/or pathobiology of the rat. In contrast to its
central role in the study of behavior, biochemistry,
neurobiology, physiology, and pharmacology, the rat has lagged
far behind the mouse as a genetic model organism.
2) The author points out that although research on rat
genetics and mouse genetics historically had a parallel
beginning, the mouse soon became the model of choice for
mammalian geneticists, whereas the rat became the model of choice
for physiologists, nutritionists, and other biomedical
researchers. Geneticists preferred the mouse because of its
smaller size, which simplified housing requirements, and the
availability of many coat-color and other mutants exhibiting
Mendelian patterns of inheritance. In contrast, physiologists and
other biomedical researchers favored the rat because its larger
size facilitated experimental interventions, and over time a
large number of rat models were used to develop disease models by
selective breeding that fixed natural disease *alleles in
particular strains or colonies.
3) The author concludes: "The rat offers many advantages for
identification of gene functions that relate to common human
diseases, because of the existing body of knowledge of
physiological mechanisms, the availability of models that mimic
these diseases, the ease of breeding, and the ability to generate
new and better models that match subsets of patients at both the
*phenotypic and genomic levels... Once genes and their functions
are identified in rats, pathophysiologic mechanisms can be
elucidated, and human genetic counterparts can be more easily
identified."
-----------
Howard J. Jacob: Functional genomics and rat models.
(Genome Research November 1999 9:1013)
QY: Howard J. Jacob, Laboratory for Genetic Research, The Medical
College of Wisconsin, Milwaukee, WI 53226 US)
-----------
Text Notes:
... ... *alleles: An allele is one of two or more forms of a
given gene that control a particular characteristic, with the
alternative forms occupying corresponding loci on homologous
chromosomes.
... ... *phenotypic and genomic levels: 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.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 24Mar00
For more information: http://scienceweek.com/swfr.htm
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=
3. MEDICAL BIOLOGY: CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease (COPD) is more a
constellation of symptoms than a single disease entity with a
specific etiology, associated specific symptoms, and specific
anatomic changes. In general, the disorder is characterized by
the progressive development of lung airflow limitation that is
not fully reversible. The term "chronic obstructive pulmonary
disease", according to one scheme, encompasses chronic
obstructive bronchitis, with obstruction of small airways in the
lung, and emphysema, with enlargement of air spaces and
destruction of lung cells (lung parenchyma), loss of lung
elasticity, and closure of small airways. In another approach,
chronic obstructive pulmonary disease can be considered a chronic
lung airway obstruction syndrome associated with any or all of
the following: chronic bronchitis, emphysema, asthma.
This is a serious condition afflicting an estimated 14
million people in the US alone. In the US, airflow obstruction
has been found in approximately 14 percent of white male smokers,
as compared with approximately 3 percent of white male
nonsmokers. Chronic obstructive pulmonary disease is now the 4th
leading cause of death in the US, and it is the only common cause
of death that is increasing in incidence.
The increase in incidence is also occurring worldwide: the
World Health Organization predicts that by 2020 chronic
obstructive pulmonary disease will rise from its current ranking
as the 12th most prevalent disease worldwide to the 5th, and from
the 6th most common cause of death to the 3rd. Reasons for the
dramatic increase in worldwide incidence evidently include
reduced mortality from other causes, such as cardiovascular
disease in industrialized countries and infectious diseases in
developing countries. But a marked increase in cigarette smoking
and environmental pollution in developing countries is apparently
also contributing to the increased incidence.
... ... Peter J. Barnes (Imperial College London, UK) presents a
review of current research in and treatment for chronic
obstructive pulmonary disease, the author making the following
points concerning the medical biology of this disorder:
1) In general, the mechanisms of airflow limitation in
chronic obstructive pulmonary disease are as follows: In the
peripheral airways of patients with this disease, as compared
with normal peripheral airways, there is airflow limitation due
to a variable mixture of a) loss of *alveolar mechanisms; b)
*inflammatory obstruction of the airway; and c) luminal
obstruction with mucus.
2) Molecular genetics: Long-term monitoring of lung function
reveals that progressive and substantial airflow obstruction
occurs in only a minority of cigarette smokers (15 percent of
whites and 5 percent of Asians), and this strongly suggests that
genetic factors may determine in which smokers airway limitation
will develop. Further evidence that genetic factors are important
comes from the familial clustering of patients with early-onset
chronic obstructive pulmonary disease and from the differences in
the prevalence of the disease among racial groups. There are
certain genetic anomalies: The reported risk of chronic
obstructive pulmonary disease is 10 times the normal level in a
Taiwanese population with a certain specific *polymorphism (a
polymorphism in the promotor region of the gene for *tumor
necrosis factor alpha). However, members of a British population
with the same polymorphism do not have an increased risk of the
disease.
3) Risk factors: In industrialized countries, cigarette
smoking accounts for most cases of chronic obstructive pulmonary
disease, but in developing countries other environmental
pollutants, such as particulates associated with cooking in
confined spaces, are important causes. It is likely that there
are important interactions between environmental factors and a
genetic predisposition to the disease. Air pollution
(particularly with sulfur dioxide and particulates), exposure to
certain occupational chemicals (e.g., cadmium), and passive
smoking may all be risk factors.
4) Inflammation: It is now apparent that there is a chronic
inflammatory process in chronic obstructive pulmonary disease,
but it differs markedly from that seen in asthma, with different
inflammatory cells, mediators, inflammatory effects, and
responses to treatment. Histopathological studies indicate that
most inflammation in chronic obstructive pulmonary disease occurs
in the peripheral airways (bronchioles) and lung parenchyma. The
bronchioles are obstructed by *fibrosis and infiltration with
*macrophages and *T lymphocytes: lung parenchyma is destroyed and
the number of macrophages and T lymphocytes is increased.
5) The author concludes: "In view of the high and increasing
global prevalence of chronic obstructive pulmonary disease, its
continuing high *morbidity and mortality, and the consequent high
health care costs, more attention should be focused on the
prevention and treatment of the disease... [This disease] remains
insufficiently recognized in family practice and is often still
treated as poorly responsive asthma. Smoking cessation is of the
utmost importance, but chronic obstructive pulmonary disease may
also be due to other causes. Why only some people are susceptible
to [the disease] is not yet understood, but it is likely that
advances in molecular genetics will provide the means to identify
those at risk in the future. At present, smoking cessation is the
only strategy that prevents the relentless progression of airflow
obstruction..."
-----------
Peter J. Barnes: Chronic obstructive pulmonary disease.
(New England J. Med. 27 Jul 00 343:269)
QY: Peter J. Barnes p.j.barnes@ic.ac.uk
-----------
Text Notes:
... ... *alveolar mechanisms: A "bronchus" is one of the two
subdivisions of the trachea that serve as airways to and from the
lungs, and a "bronchiole" is one of the approximately 6
generations of linear branches of the bronchi. In general, an
"alveolus" is a small cavity or socket, and in this context, a
[pulmonary] alveolus is one of the thin-walled sac-like terminal
dilations of the respiratory bronchioles and alveolar ducts
across which gas exchange occurs between alveolar air and the
pulmonary capillaries.
... ... *inflammatory obstruction: In general, an "inflammatory
change" is a response of tissues to irritation or injury. The
response involves a dynamic complex of cellular and chemical
reactions that occur in the affected blood vessels and adjacent
tissues.
... ... *polymorphism: A genetic 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
percent.
... ... *tumor necrosis factor alpha: A *cytokine produced by
various types of cells, mediating the expression of a variety of
genes, and capable of causing *cytolysis of certain tumor cell
lines.
... ... *cytokine: A cytokine is any substance that promotes cell
growth and cell division. Certain cytokines are endogenous, and
need to be controlled by cell regulatory mechanisms. When these
mechanisms fail, endogenous cytokines may be implicated in
serious human diseases such as rheumatoid arthritis, where
apparently deregulated cytokines cause the inflammatory response
that produces the symptoms. As a promoter of cell growth and
division, a cytokine acts as a messenger to cells, and the
transmission of the message requires a binding of the cytokine
molecule to a cytokine-specific receptor on the cell surface.
This receptor is either a protein or a protein complex or a part
of a protein.
... ... *cytolysis: In general, the breakdown of cells,
especially by destruction of their outer membranes.
... ... *fibrosis: In general, the formation of fibrous tissue as
a reparative or reactive process (e.g., scarring).
... ... *macrophages: Amoeba-like white blood cells (leukocytes)
that are able to surround and digest foreign entities such as
bacteria and protozoa.
... ... *T lymphocytes: (T-cells) Lymphocytes (lymph cells,
lympho-leukocytes) are a type of leukocyte (white blood cell)
involved in the immune response. There are two classes of such
lymphocytes: 1) the B-cells, which after a cascade of immune
system events involving a specific antigen change into
proliferating specific antibody producing plasma cells; 2) the
T-cells, one subclass of which (cytotoxic T-cells) interacts
directly with foreign invaders such as bacteria and viruses,
while the other subclass of T-cells (helper T-cells) is involved
in the proliferation of antibody-specific B-cells.
... ... *morbidity: In general, in medicine, this refers to a
diseased state; in particular, the term refers to the ratio of
the diseased to the well in a community.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
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4. EARTH SCIENCES: NEW EVIDENCE ON SEAFLOOR SPREADING
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).
Plate tectonics is the modern theory that unifies many of
the features and characteristics of continental drift and sea
floor spreading into a coherent model. Continental drift is the
slow movement of the Earth's land masses, a shifting across the
underlying molten material. Sea-floor spreading is the process
whereby sea floor is continuously created as the crustal plates
move apart and continuously destroyed where the plates push
against each other. The term "mid-ocean(ic) ridge" refers to a
topographic feature of a tectonic spreading center between
diverging oceanic plates. New crustal material is formed by
upswelling magma (molten material from which rock forms) as the
plates diverge.
Approximately 20 cubic kilometers of new ocean crust is
formed each year along the spreading centers of the global mid-
ocean ridge system. These spreading centers are usually not
simple linear structures, but are broken into offset and
sometimes overlapping segments. Most of molten rock (melt or
magma) that solidifies into ocean crust resides within shallow
magma chambers beneath the axes of the ridges before erupting at
the sea floor or "freezing" onto the edges of the separating
tectonic plates. The relationship between the crustal magma
chambers, the segmentation of spreading centers, and the supply
of melt from the underlying mantle is still poorly understood.
... ... G.M. Kent et al (11 authors at 2 installations, US UK)
present 3-dimensional images of seismic reflectivity beneath a
mid-ocean ridge to investigate the nature of melt distribution
across a ridge-axis discontinuity. Reflectivity slices through
the 9 deg 03' N overlapping spreading center on the East Pacific
Rise suggest that it has a robust magma supply, with melt bodies
underlying both limbs, and ponding of melt beneath large areas of
the overlap basin. The authors suggest the geometry of melt
distribution beneath this offset is inconsistent with large-scale
crustal redistribution of melt away from centers of upswelling.
The complex distribution of melt seems instead to be caused by a
combination of vertical melt transport from the underlying mantle
and subsequent focusing of melt beneath a magma freezing boundary
in the mid-crust.
... ... In a commentary on this work, Robert S. Detrick (Woods
Hole Oceanographic Institution, US) states: "As the first 3-
dimensional reflection experiment on a mid-ocean ridge, this
study is a milestone. In the future, 3-dimensional imaging of the
structure of the crust, as well as of the underlying mantle, will
be increasingly seen as essential for understanding the volcanic,
tectonic, and hydrothermal processes that accompany the formation
of ocean crust."
-----------
G.M. Kent et al: Evidence from three-dimensional seismic
reflectivity images for enhanced melt supply beneath mid-ocean-
ridge discontinuities.
(Nature 10 Aug 00 406:614)
QY: G.M. Kent gkent@ucsd.edu
-----------
Robert S. Detrick: Portrait of a Magma Chamber
(Nature 10 Aug 00 406:578)
QY: Robert S. Detrick rdetrick@whoi.edu
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
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5. CONDENSED-MATTER PHYSICS: ON THE ISING MODEL
In theoretical physics, one approach that has proved to be
of great general utility is to begin with an attempt to identify
and understand the simplest model exhibiting the same essential
features as the physical problem in question. In condensed-matter
physics, such a model is the so-called "Ising model", an approach
that has been applied to ferromagnetism, and also to a number of
other systems. In general, the Ising model consists of an array
of entities in one, two, or three dimensions, with each entity
capable of being in one of two possible states, with each entity
interacting only with its nearest neighbors, with a condition
that when two neighboring entities are in the same state the
total energy of the pair is reduced compared to when the same two
neighboring entities are in opposite states. These are the
elements of the model, with other conditions imposed depending on
how the model is used. Various versions of the model have been of
great utility in studies of cooperative phenomena in condensed-
matter systems, and the model itself has an interesting human
story attached to it.
A "ferromagnet" is a material (e.g., iron) in which there
may be a permanent magnetic moment (magnetic dipole moment), and
in which the *spins of the atoms are aligned parallel to each
other. Concerning permanent magnetic moments: In general,
according to theory, the intrinsic spins of the electrons in an
atom, together with the motion of the electrons around the
nucleus, give rise to a magnetic field around the atom, and the
magnitude of this field is related to the magnetic dipole moment
of the atom or ion. The term "Curie point" refers to the
temperature above which ferromagnetic materials lose their
ferromagnetism. The Curie point is thus the critical point for a
phase transition.
... ... Brian Hayes (American Scientist, US) presents an essay on
the Ising model and its application to ferromagnetism, the author
making the following points:
1) The Ising model was invented in 1920 by Wilhelm Lenz, who
proposed it as a simplified version of a ferromagnet (Physik. Z.
1920 21:613). In 1925, a student of Lenz, Ernst Ising, chose the
model as the subject of his doctoral dissertation at the
University of Hamburg (DE), and the model has subsequently borne
Ising's name.
2) Lenz and Ising formulated the original model in terms of
"spins", although the concept of rotation is never used. In the
original model, a spin is merely one of two states, characterized
by an arrow pointing either up or down but in no other direction.
The spins are arranged in a grid or lattice pattern. Spins at
neighboring sites prefer to point the same way: the energy is
lower when adjacent spins are parallel, and the energy is higher
when adjacent spins are antiparallel. Except for these nearest
neighbor preferences, the spins do not interact at all. Thermal
fluctuations tend to randomize the spins. Finally, an external
magnetic field may impose a bias on the spin directions.
3) Hayes points out that the Ising model is indeed a crude
picture of a ferromagnet: a) the Ising spins correspond to
spinning electrons in iron atoms; b) the lattice represents the
crystal structure; c) the nearest neighbor interaction mimics the
overlap of quantum mechanical wave functions in adjacent iron
atoms. The one element in the model that has no obvious
counterpart in real systems is the requirement that spins take on
only two possible orientations.
4) Ising's doctoral dissertation examined whether the
1-dimensional version of the model exhibited a Curie point. The
results were negative: the 1-dimensional Ising model exhibits no
phase transition at any temperature above absolute zero. Ising
apparently believed this negative result would hold in higher
dimensions as well, but in this conjecture he was wrong.
5) Ising's published results (Z. fur Physik 1925 31:253)
were essentially ignored until 1936, when Rudolf Peierls (1907-
1995) showed that a 2-dimensional Ising model might exhibit a
temperature-dependent phase transition . An exact calculation of
such a system, a mathematical tour de force, was made by Lars
Onsager (1903-1976) in 1944. Exact calculations for 3-dimensional
Ising models have remained intractable, but approximations and
computer simulations involving the model have proved extremely
useful, and the value of the model has grown rather than
diminished through the years. An important approximation method
is known as "the renormalization group": the simplest version of
this algorithm gathers sets of spins into blocks, replaces each
block with a single new spin, and finally adjusts the couplings
between spins to compensate for the coarsening of the lattice.
6) Concerning Ernst Ising, there is no record of Ising ever
publishing anything else in physics. After receiving his
doctorate, Ising taught physics in German public high schools,
but as a Jew he was dismissed from his teaching post when Hitler
came to power in 1933. Ising then taught at a Jewish boarding
school in Potsdam (DE), until that school was destroyed in the
Kristallnacht pogrom of 1938. Ising and his wife fled Germany,
but they escaped only as far as Luxembourg before the war
overtook them. They managed to survive the occupation, and they
finally reached the US in 1947. Ising taught physics and
mathematics in Minot, North Dakota (US), and then taught for
almost 30 years more at Bradley University in Peoria, Illinois
(US). In 1998, Ernst Ising died at the age of 98.
-----------
Brian Hayes: The world in a spin.
(American Scientist Sep/Oct 2000 88:384)
QY: Brian Hayes bhayes@amsci.org
-----------
Text Notes:
... ... *spins: In quantum mechanics, electrons, protons, and
neutrons have an intrinsic angular momentum known as "spin", and
a magnetic moment parallel or antiparallel to that angular
momentum. When electrons are combined together to form an atom or
ion, there is a resultant angular momentum which is a combination
of the intrinsic spin of the electrons and the angular momentum
due to their motion about the nucleus, and this is the "spin" of
the atom or ion. Atoms or ions with non-zero spin are magnetic
atoms or ions.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
PHYSICS: ON STATISTICAL PHYSICS AND ITS APPLICATIONS
Statistical physics (statistical mechanics) is the branch of
physics that attempts to explain the macroscopic properties of a
system on the basis of the properties of its microscopic
constituents. Usually the number of constituents is extremely
large, and all the characteristics of the constituents and their
interactions are presumed to be known. Although as a distinct
research area, statistical physics dates back to James Clerk
Maxwell (1831-1879) and Ludwig Boltzmann (1844-1906) and their
work on probability distributions in the kinetic theory of gases,
the field was substantially transformed in the 20th century, and
it has now been fruitfully applied to nearly all states of matter
including biological systems.
... ... Philip Ball (_Nature_, UK) presents a commentary on the
history and applications of statistical physics, the author
making the following points:
1) Statistical physics, and more specifically the theory of
transitions between states of matter, more or less defines what
we know about everyday matter and its transformations. In
addition, statistical physics provides a conceptual apparatus for
dealing with complex collective quantum phenomena of current
intense interest, particularly: a) Bose-Einstein condensation (in
which a collection of particles all occupy the same quantum
ground state); and b) high-temperature superconductivity (i.e.,
superconductivity above 35 degrees kelvin). Many of the states of
condensed matter that promise new technological applications,
ranging from *block copolymers to magnetic multilayers, can be
understood as the consequence of the kind of collective behavior
that statistical physics describes.
2) From the 1960s to the 1980s, statistical physicists were
primarily concerned with "critical points", the points in
thermodynamic phase diagrams at which two or more phases become
identical. The reasons for this interest are twofold: a) the
behavior of a system at its critical point also determines its
behavior in the broad vicinity of the critical point (within a
so-called "critical region"; b) the behavior of a system at a
critical point reveals kinships between different systems. For
example, liquid-gas criticality and the behavior of some magnets
at their Curie point (the temperature above which they lose their
*ferromagnetism) have numerically equal *critical exponents, and
both can be modeled by the so-called "*Ising model", a model
based on a lattice of two-state *spins. Commonality of critical
exponents gives rise to the idea of universality, the idea that
there are generic models in statistical physics that describe a
variety of apparently different many-body systems. This means
that solving one problem in statistical physics generally
delivers solutions for several other problems at the same time.
In addition, there is an implication that many-body behavior is
fundamentally determined only by global aspects such as the range
of interparticle forces, the dimensionality of the system, and
the nature of the "*order parameter" (whose abrupt change from a
zero to a non-zero value defines the transition from one state to
another).
3) A fruitful present area of research is the intersection
of statistical physics with quantum mechanics, in particular, the
many-body behavior of electrons in condensed matter. Correlated
behavior of electrons, in which electrons display a degree of
collective or coherent dynamics, produces superconductivity, the
*integer and fractional quantum Hall effect, so-called "*heavy-
fermion" behavior, *spin density waves, and *colossal
magnetoresistance. All of these collective phenomena have in
recent years been shown to underlie unexpected and potentially
useful properties of novel materials. Colossal magnetoresistance,
for example, may lead to the development of highly-sensitive
read-out heads for magnetic memories.
4) The author suggests that despite the proven value to cell
biology of some concepts from the study of phase transitions (for
example, the entropic effect of fluctuations on interactions of
lipid membranes), there remains much skepticism as to whether
biological phenomena can be approached as arising from collective
emergent behavior of statistical interacting ensembles rather
than from the closely controlled protein relays to which cell
biologists are accustomed. Yet statistical physics must
inevitably provide the baseline even in the cell: proteins may
phase-separate and membranes may adopt equilibrium conformations
unless actively opposed by cell processes.
-----------
Philip Ball: Transitions still to be made.
(Nature 2 Dec 99 402supp:C73)
QY: Philip Ball [p.ball@nature.com]
-----------
Text Notes:
... ... *block copolymers: A copolymer in which a number of units
of the same monomer are located adjacent to one another (in
"blocks" of monomers).
... ... *ferromagnetism: A "ferromagnet" is a material (such as
iron) in which there may be a permanent *magnetic moment, and in
which the *spins of the atoms are aligned parallel to each other.
... ... *magnetic moments: (magnetic dipole moment) The intrinsic
spins of the electrons in an atom, together with the motion of
the electrons around the nucleus, give rise to a magnetic field
around the atom, and the magnitude of this field is related to
the magnetic dipole moment of the atom or ion.
... ... *critical exponents: In this context, a "critical
exponent" is a parameter that characterizes the temperature
dependence of a thermodynamic property of a substance near its
critical point. The temperature dependence has the form
|T-T(subc)|^(n), where T is the temperature, T(subc) is the
critical temperature, and (n) is the critical exponent.
... ... *Ising model: In general, a simplified model in which the
atomic *spins are assumed to be aligned parallel or antiparallel
in a given direction.
... ... *spins: In quantum mechanics, electrons, protons, and
neutrons have an intrinsic angular momentum known as "spin", and
a magnetic moment parallel or antiparallel to that angular
momentum. When electrons are combined together to form an atom or
ion, there is a resultant angular momentum which is a combination
of the intrinsic spin of the electrons and the angular momentum
due to their motion about the nucleus, and this is the "spin" of
the atom or ion. Atoms or ions with non-zero spin are magnetic
atoms or ions. The idea of electron spin was first proposed by
Goudsmit and Uhlenbeck in 1925 to explain the splitting of atomic
spectroscopic emission lines in the presence of a magnetic field.
Elementary particle spin involves a virtual rotation about the
axis of the particle, which means only two spin states are
possible, one clockwise and one counterclockwise.
... ... *order parameter: In general, a quantity that
characterizes the phase of a system below its transition
temperature, the parameter having a nonzero value below the
transition temperature and a zero value above the transition
temperature. If the phase transition is continuous, the order
parameter falls to zero continuously as the transition
temperature is approached.
... ... *integer and fractional quantum Hall effect: In classical
physics, the Hall effect is the development of a transverse
voltage across a current-carrying conductor in a magnetic field,
the voltage being perpendicular to both the direction of the
current and the direction of the magnetic field. In quantum
physics, there are two other Hall effects, an integer charge
quantum Hall effect, and a fractional charge quantum Hall effect,
these quantum Hall effects being observed at extremely low
temperatures (a few degrees Kelvin) and extremely intense
magnetic fields (at least several tesla). Both quantum Hall
effects were first noted in the 1980s, and the fractional quantum
Hall effect, although experimentally observed, has not been
theoretically resolved.
... ... *heavy-fermion: "Heavy-fermion systems" are solids in
which electrons behave as if they have masses several hundred
times their normal masses. Substances containing such electrons
have unusual thermodynamic, magnetic, and superconducting
properties that are not completely understood.
... ... *spin density waves: In general, propagating collective
spin-variation excitations associated with certain magnetic
systems.
... ... *colossal magnetoresistance: (giant magnetoresistance)
The term "magnetoresistance" refers to a change in the electrical
resistance of a conductor or semiconductor upon the application
of a magnetic field, a property of certain systems. Giant
magnetoresistance is a quantum mechanical effect observed in
magnetic thin-film structures composed of alternating
ferromagnetic and nonmagnetic layers.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 3Mar00
For more information: http://scienceweek.com/swfr.htm
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6. CONDENSED-MATTER PHYSICS: QUASI-CRYSTALS
In general, the high conduction properties of metals depends
on the availability of a "sea" of delocalized electrons, the
delocalized electron sea resulting from the crystalline atomic
periodicity of the metal substance.
The term "quasicrystal" refers to a solid with conventional
crystalline properties but exhibiting symmetry characteristics
inconsistent with translational periodicity. Like crystals,
quasicrystals display discrete (although anomalous) diffraction
patterns, crystallize into polyhedral forms, and have long-range
orientational order, all of which indicates that their structure
is not random. But the unusual symmetry, and the discrete but
anomalous diffraction patterns, suggest a solid that is
quasiperiodic. The existence of quasicrystals contradicts a long-
held belief that all crystals should be periodic arrangements of
atoms or molecules. Icosahedral quasicrystals were discovered in
1982 during a study of rapid solidification of molten alloys of
aluminum with one or more transition elements such as manganese,
iron, and chromium. Since 1982, many different alloys of two or
more metallic elements have led to quasicrystals with a variety
of symmetries and structures.
In this context, a "band" is a closely spaced group of
energy levels in atoms, in particular a range of energies that
electrons can have in a solid. Each band represents a large
number of allowed quantum states. The outermost electrons of the
atoms form the "valence band" of the solid. In order for
electrons to move through a solid, there must exist empty quantum
states with the same energy, and this can occur only in an
unfilled band, the "conduction band". In general, so-called
"metals" are good conductors because the partly filled conduction
band overlaps with a filled valence band, and vacant energy
states in the conduction band are thus readily available to
electrons.
In general, the term "photoemission" (photoelectric effect)
refers to the process in which electrons are emitted by a
substance as a result of exposure of the substance to
electromagnetic radiation. The number of the electrons emitted
depends on the intensity of the radiation, and the kinetic energy
of the electrons emitted depends on the frequency of the
radiation. The technique of "angle-resolved photoemission"
(angle-resolved photoelectron spectroscopy) is a type of
photoelectron spectroscopy which measures the kinetic energies of
electrons emitted by the photoelectric effect from a solid
surface and the angles at which they are emitted relative to the
surface. Application of theory to the data permits an analysis of
electron energy distributions in the solid.
... ... E. Rotenberg et al (4 authors at 4 installations, US DE)
present new data on electron distributions in a quasicrystal, the
authors making the following points:
1) The authors point out that quasicrystals are metallic
alloys that possess perfect long-range structural order, in spite
of the fact that their rotational symmetries are incompatible
with long-range periodicity. The exotic structural properties of
this class of materials are accompanied by physical properties
which are unexpected for metallic alloys. Considerable progress
in resolving the geometric structures of quasicrystals has been
made using x-ray and neutron diffraction, and concepts such as
the quasi-unit-cell model have provided theoretical insights. But
the basic properties of the valence electronic states -- whether
they are extended as in periodic crystals or localized as in
amorphous materials -- are still largely unresolved.
2) The authors report an investigation of the electronic
bandstructure of quasicrystals via angle-resolved photoemission
experiments on decagonal Al(sub71.8)Ni(sub14.8)Co(sub13.4). The
authors report the observation of bands similar to free-electron
bands, the free-electron-like bands distributed in momentum space
according to the surface diffraction pattern, suggesting that the
electronic states are not dominated by localization.
... ... In a commentary on the this work, P.A. Thiel and J.M.
Dubois (2 installations, US FR) point out that Rotenberg et al
provide direct information about whether conduction electrons
(Fermi electrons) in quasicrystals are more localized than in a
normal metal. "By mapping out the energies and momenta of
electrons in the quasiperiodic plane of decagonal Al-Ni-Co, they
show convincingly that some of the electron states must be
delocalized and therefore contribute to the electron sea."
-----------
E. Rotenberg et al: Quasicrystalline valence bands in decagonal
Al-Ni-Co.
(Nature 10 Aug 00 406:602)
QY: Eli Rotenberg erotenberg@lbl.gov
-----------
P.A. Thiel and J.M. Dubois: Electrons in a strange sea.
(Nature 10 Aug 00 406:570)
QY: Patrica A. Thiel thiel@ameslab.gov
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 15Sep00
For more information: http://scienceweek.com/swfr.htm
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7. IN FOCUS: ON THE ELECTROMAGNETIC FIELD
"Science is not just a collection of laws, a catalogue of
unrelated facts. It is a creation of the human mind, with its
freely invented ideas and concepts. Physical theories try to form
a picture of reality and to establish its connection with the
wide world of sense impressions. Thus the only justification for
our mental structures is whether and in what way our theories
form such a link... The psychological subjective feeling of time
enables us to order our impressions, to state that one event
precedes another. But to connect every instant of time with a
number, by the use of a clock, to regard time as a one-
dimensional continuum, is already an invention. So also are the
concepts of Euclidean and non-Euclidean geometry, and our space
understood as a three-dimensional continuum. Physics really began
with the invention of mass, force, and an inertial system. These
concepts are all free inventions. They led to the formulation of
the mechanical point of view. For the physicist of the early 19th
century, the reality of our outer world consisted of particles
with simple forces acting between them and depending only on the
distance. He tried to retain as long as possible his belief that
he would succeed in explaining all events in nature by these
fundamental concepts of reality. The difficulties connected with
the deflection of the magnetic needle, the difficulties connected
with the structure of the ether, induced us to create a more
subtle reality. The important invention of the electromagnetic
field appears. A courageous scientific imagination was needed to
realize fully that not the behavior of bodies, but the behavior
of something between them, that is, the field, may be essential
for ordering and understanding events."
-----------
A. Einstein and L. Infeld: _The Evolution of Physics_
(Simon & Schusterm, New York 1938)
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8. FROM THE SCIENCEWEEK ARCHIVE:
WETTERHAHN LABORATORY POISONING CASE: FINAL MEDICAL REPORT
In the spring of 1997, the science community, and in particular
the chemistry community, was saddened to learn of the tragic
death of Karen E. Wetterhahn, age 48, a professor of chemistry
(Dartmouth College, US) and a noted researcher on the effects of
heavy metals in biological systems. Wetterhahn died of
dimethylmercury poisoning as the result of the accidental
spillage of a few drops of the chemical on her latex glove-
covered hand. The accident occurred on August 14, 1996, and the
poisoning produced progressive destruction of Wetterhahn's
nervous system, until she finally died 10 months later. Before
she lapsed into a vegetative state, Karen Wetterhahn requested
that her case be presented to the general medical community, to
scientists working with mercury, and to toxicologists, in the
hope of improving the recognition, treatment, and prevention of
future cases of mercury poisoning. The full medical case report
of the illness, death, and autopsy of Karen E. Wetterhahn has now
been published. Nierenberg et al (9 authors at 2 installations,
US), the authors of the report, make the following points: 1)
Dimethylmercury is lethal at a dose of approximately 400 mg of
mercury (equivalent to a few drops, or approximately 5 mg per
kilogram of body weight. It is classified as a "supertoxic"
chemical. 2) Records suggest that Wetterhahn handled dimethyl-
mercury on only one day, while wearing latex gloves and working
under a ventilated hood designed to prevent exposure to chemical
fumes. She had delayed but ultimately fatal neurotoxic effects
similar to those caused by methylmercury compounds, and this case
illustrates the potent toxicity of dimethylmercury and the need
for additional safety precautions if it is to be used in any
scientific research. 2) Five months after the accident, on
January 20, 1997, Wetterhahn was admitted to the university
medical center with a 5 day history of progressive deterioration
in balance, gait, and speech. She had lost 15 lb over a period of
2 months, and had experienced several brief episodes of nausea,
diarrhea, and abdominal discomfort. 3) Wetterhahn recalled that
in August 1996, while transferring liquid dimethylmercury from a
container to a capillary tube, she spilled several drops from the
tip of the pipette onto the back of her gloved hand. She reported
that she had cleaned up the spill and then removed the protective
gloves. (The date of the accident was established from her
notebooks and other laboratory data to be August 14, 1996.) 4) On
February 6th, 22 days after the first neurologic symptoms
developed (and 176 days after exposure), Wetterhahn became
unresponsive to all visual, verbal, and light-touch stimuli. 5)
The authors report they could find only 3 previously reported
cases of poisoning with dimethylmercury, all of which were fatal,
and that equally bleak outcomes had been reported in patients
with severe methylmercury poisoning. In view of the dismal
prognosis, and after more than 3 months of aggressive treatment
and support, Wetterhahn's advance directives were followed, and
she died peacefully on June 8, 1998, 298 days after exposure. 6)
Some anatomical findings from the autopsy report: "The cortex of
the cerebral hemispheres was diffusely thinned, to 3 mm. The
visual cortex around the calcarine fissure was grossly gliotic,
as was the superior surface of the superior temporal gyri. The
cerebellum showed diffuse atrophy of both vermal and hemispheric
folia. Microscopical study showed extensive neuronal loss and
gliosis bilaterally within the primary visual and auditory
cortices, with milder loss of neurons and gliosis in the motor
and sensory cortices. There was widespread loss of cerebellar
granular-cell neurons, Purkinje cells, and basket-cell neurons,
with evidence of loss of parallel fibers in the molecular
layer... An extensive high mercury content was found in the
frontal lobe and visual cortex, liver, and kidney cortex. The
mercury content of the brain was approximately 6 times that of
whole blood at the time of death... 7) The authors conclude:
"Dimethylmercury appears to be so dangerous that scientists
should use less toxic mercury compounds whenever possible. Since
dimethylmercury is a "supertoxic" chemical that can quickly
permeate common latex gloves and form a toxic vapor after a
spill, its synthesis, transportation, and use by scientists
should be kept to a minimum, and it should be handled only with
extreme caution and with the use of rigorous protective
measures."
QY: David W. Nierenberg, Dartmouth-Hitchcock Medical Center,
Hinman Box 7506, Lebanon, NH 03756 US.
(New England J. Med. 4 Jun 98 338:1672)
(Science-Week 26 Jun 98)
-------------------
Related Background:
DEATH OF PROMINENT CHEMIST PROMPTS CALL FOR CHANGE IN NMR METHODS
The international chemistry community was shocked recently by the
death of Karen E. Wetterhahn, age 48, Professor of Chemistry at
Dartmouth College (NH US). Wetterhahn was a well-known authority
on the effects of heavy metals on biological systems. Ten months
ago, in the course of calibrating a nuclear magnetic resonance
(NMR) apparatus with the standard dimethylmercury, Wetterhahn
accidentally spilled a few drops of the substance on her latex-
covered hand. Unexpectedly, the substance penetrated the glove,
and within a few months the first neurological symptoms of
mercury poisoning appeared. She died on June 8th. John Winn, head
of the Dartmouth Chemistry Department, and others, have now
called for the chemical community to establish an NMR standard
safer than dimethylmercury.
(Chemical & Engineering News 16 Jun 97)
(Science-Week 26 Jun 97)
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