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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.
December 11, 1998 -- Vol. 2 Number 50
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Theories come and theories go. The frog remains.
-- Jean Rostand
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Contents of This Issue:
1. On the Impact of Society on Science
2. On the Origin of the Solar System
3. Sequencing of a Chromosome of the Human Malaria Parasite
4. Cell Surface Ectodomains and Protein Shedding
5. Plasticity of Cerebral Cortex after Peripheral Injury
6. On the Medical Applications of Cloning
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1. ON THE IMPACT OF SOCIETY ON SCIENCE
*Sydney Brenner presents an essay on current interactions between
science and society at large, the author making the following
points: 1) Evidence for the impact of science on society is
ubiquitous, and little more remains to be said about it. Science
and the technologies it has spawned form the basis of all human
activity, including housing, food, transportation, and the
electronic gadgetry used for information and entertainment. 2)
But when we speak of the impact of science on society, we are
speaking about the more advanced countries, and when we speculate
on the future, it usually concerns those areas of the world. The
underdeveloped world remains outside the arena of progress, with
famines and pointless wars still exacting a terrible toll of
human lives. 3) Like the evidence for the impact of science on
society, the impact of society on science is also ubiquitous,
mainly in the form of the large (but never sufficient) funding
that science enjoys in the more advanced countries. But in
stimulating and supporting science, society, as the paymaster,
has taken a much shorter term view of research than most
scientists would like. 4) The answer to the question of which
type of science to fund is actually quite simple: Since all
science is problem driven, it should be judged by the quality of
the problems posed, and the quality of the solutions provided.
5) The increased funding for scientific research in recent years,
especially in the health fields, has resulted in a great
expansion of the number of scientists, and thus an increased
competition for academic and research funds. We have established
an elaborate system of peer review for funding and a similar
process for publication of scientific results, and all of this
has subtle consequences for the scientific enterprise. If you
know what sort of research is wanted by a committee, you write
your grant to satisfy these expectations, and if you know what
the oligarchy believes is the correct view of a subject, you give
your paper that slant. Further, it is only through the use of
subterfuge such as applying for money for work already done that
innovative research can be freely pursued. 6) These matters must
be taken seriously, otherwise science will lose the independence
of thought required for innovation that it has cherished for
centuries.
-----------
Sydney Brenner (Molecular Sciences Institute Berkeley, US)
The impact of society on science.
(Science 20 Nov 98 282:1411)
QY: Sydney Brenner, Molecular Sciences Institute Inc., 2168
Shattuck Avenue, Berekeley, CA 94704 US.
-----------
Text Notes:
... ... *Sydney Brenner: The author is one of the pioneers of
genetic engineering, and the discover of *messenger RNA. He is
also responsible for instigating and promoting much of the modern
work on the molecular genetics of the *nematode worm C. elegans.
... ... *messenger RNA: (mRNA) The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
... ... *nematode worm C. elegans: Caenorhabditis elegans is a
small (1 mm) nematode worm. It is transparent, hermaphroditic,
free-living, and found in soil. It has a relatively small genome
(approximately 19,000 genes), and only a few types of cells in
its body. It has a 16-hr embryogenesis that can be achieved in a
petri dish, and is thus highly suitable for the study of
developmental and behavioral genetics.
... ... *nematode: An abundant and ubiquitous phylum of
unsegmented roundworms.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
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Related Background:
ON FASHIONS IN SCIENCE AND TECHNOLOGY
Rolf Landauer (IBM Corp., US), in a review of fashions in science
and technology, points out both the negative and positive aspects
of such fashions in general, and in particular in his own field,
condensed matter physics. Among other problems, Landauer notes:
1) Fashions in science and technology draw attention away from
other deserving areas. 2) Funding agencies make an apparently
sensible initial decision to support a particular exploratory
scientific path, but they too easily become emotionally tied to
their choice. 3) The competition for grants and employment causes
public relations activities to have an increasing greater role in
the practice of science. 4) Whereas in the past judgments in an
institution about the quality of a colleague's work were based on
an assumed understanding of that work, at present promotions
depend on the ability to get funding, citation index scores,
etc., and in-house evaluations often are less important than
external evaluations. 5) These days a single publication is lost
in the deluge of papers, and the only way to be heard in the
scientific community is to repeatedly publish essentially the
same information over and over again. This produces a large
publication volume per researcher, which in turn forces other
researchers to do the same if they want to advance in status in
their installations and in their field. As any working scientist
is aware, these are only some of the problems inherent in the
present structure of professional science. Landauer suggests that
fashions in science have a mostly negative impact, and that more
serious debate is needed about how fashions affect professional
science and the training of new scientists.
QY: Rolf Landauer,
Thomas J. Watson Research Center, IBM Corp., Yorktown Hts, NY US
(Physics Today December 1997) (Science-Week 12 Dec 97)
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 11Dec98
2. ON THE ORIGIN OF THE SOLAR SYSTEM
During the past two centuries, astronomers have considered two
types of theories for the origin of our Solar System planets.
Catastrophic theories proposed that these planets formed from
some improbable cataclysm such as the collision of the sun and
another star, while gradualist theories proposed that the planets
formed naturally with the Sun. At the present time, as a result
of evidence accumulated during the past five decades, the
gradualist idea is the consensus idea, and nearly all astronomers
now believe that planets form naturally as a by-product of star
formation. ... ... John A. Wood presents an extensive review of
current ideas concerning the origin of the Solar System, and the
author makes the following points: 1) The current theory is that
the Sun and the planets were born from a rotating disk of cosmic
gas and dust (the "solar nebula"), and the flattened form of the
disk constrained the planets that formed from it to have orbits
lying in the same plane, or nearly so, the planets all moving in
the same direction in which the disk had turned. 2) The idea of a
solar nebula was first formulated in 1755 by *Immanuel Kant.
Although his treatment of the problem was only qualitative, its
precepts were remarkably similar to those considered fundamental
today, and at the present time, Kant's original idea is
considered to be correct: stars and their disks form in much the
same way he pictured, the formation resulting from the
gravitational collapse of huge volumes of thinly dispersed
interstellar gas and dust onto appropriate nuclei. 3) The present
view is that the solar nebula was hot near its center, tapering
off to a cold region, then a very cold region at its outermost
margins. Thus, the falloff of nebula temperature with
heliocentric distance defined 3 radial zones. The innermost zone
was too warm for water to condense as ice; objects forming in the
innermost zone consisted entirely of *silicate minerals and other
*refractory materials, and ultimately became the terrestrial
planets (Mercury, Venus, Earth, and Mars). The next zone of the
solar nebula was colder, water ice was stable, and a vast
blizzard of snowflakes gave rise to the much larger Jovian
planets (Jupiter, Saturn, Uranus, and Neptune). In the outermost
and thus coldest zone of the solar nebula, condensed matter was
also icy, but matter was too sparsely distributed to accrete into
sizable planets; instead matter remained dispersed in small icy
planetesimals -- comet nuclei -- in what is now called the
*Kuiper belt. Evidence suggests the planets assembled themselves
quickly: Although the process differed in detail from zone to
zone, virtually everything was in place within 10 million years,
by which time the solar nebula had largely dissipated. 4) Nearly
four centuries of telescopic observation, combined with four
decades of space exploration, have taught us this essential truth
about the Solar System: While the Sun and its planetary system
surely arose from one grand spiral of gas and dust in a flurry of
collective activity, the results are hardly a homogeneous set of
characterless orbiting entities. Instead this grand scheme of
formation has yielded amazing diversity in the properties of the
various objects in the Solar System.
-----------
John A. Wood (Smithsonian Astrophysical Observatory, US)
Forging the planets.
(Sky and Telescope January 99)
QY: John A. Wood, Smithsonian Astrophysical Observatory,
Cambridge, MA US.
-----------
Text Notes:
... ... *Immanuel Kant (1724-1804): Kant is best known as a
philosopher, but he first studied mathematics and physics, and
the year he obtained his doctorate degree (1755) he published his
physical view of the Universe in *General History of Nature and
Theory of the Heavens). In this treatise, Kant described the
solar nebula hypothesis of planet formation, suggested that our
own galaxy is a lens-shaped collection of stars and that other
such "island universes" exist, and suggested that *tidal friction
slows the rotation of the Earth. All three propositions are the
current view in astrophysics.
... ... *tidal friction: A force between the oceans of the Earth
and the ocean floors caused by the gravitational attraction of
the Moon.
... ... *silicate minerals: (silicates) The most important and
abundant group of rock-forming minerals.
... ... *refractory materials: (refractory minerals) Minerals
resistant to decomposition by heat, pressure, or chemical attack.
The term is most commonly applied to heat resistance.
... ... *Kuiper belt: In 1951 the astronomer Gerard P. Kuiper
(1905-1973) postulated the existence of a belt of objects beyond
the orbit of Pluto. Both the existence and nature of the objects
were matters of speculation for decades, and finally in 1992
Jewitt and Luu identified the first Kuiper object. The current
estimate is that as many as 10^(8) objects larger than 10
kilometers in diameter may exist in what is called the "Kuiper
belt", a disc that hugs the plane of the planetary system and
lies between 35 and 1000 *AU from the Sun. Observations to date
have yielded some 55 trans-Neptune bodies with radii on the order
of 100 km or larger, and Pluto is considered by some astronomers
to be a member of this population.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
-------------------
Related Background:
A MODEL FOR THE MIGRATION OF MASSIVE PLANETS
Planetesimals are bodies with dimensions of 10^(-3) to 10^(3)
meters that are believed to form planets by a process of
accretion. The term "accretion" refers to an aggregation, an
increase in the mass of a body by the addition of smaller bodies
that collide and adhere to it, provided the relative velocities
are low enough for coalescence. As the mass of the agglomerate
increases, so does the rate of accretion, and this accretion
process is believed to generally occur in the form of a disk. A
stellar accretion disk is a swarm of dust grains that evolve into
planetesimals and then planets. There is now evidence of apparent
massive planets in close orbits around stars, but the formation
of such massive planets in close orbits is unexplained. One
possibility is that these massive planets were formed in a more
distant orbit and then migrated inward. ... ... Murray et al (4
authors at 2 installations, CA) now report a theoretical analysis
of the behavior of planets and planetesimals in a stellar disk.
The calculations predict that gravitational interactions and
collisions between planet and planetesimals, if total
planetesimal surface density exceeds a certain value, may drive
the planet inward a great distance. The authors suggest this
mechanism may explain the presence of Jupiter-mass objects in
small orbits around nearby stars.
QY: N. Murray, Univ. of Toronto, Dept. of Theoretical Astro-
physics, Toronto, ON M5S 3H8 CA.
(Science 2 Jan 98) (Science-Week 16 Jan 98)
-------------------
Related Background:
EVIDENCE OF A PROTOPLANETARY DISK AROUND A YOUNG STAR
The current nebula theory of planet formation proposes that
star-planet systems begin as a contracting cloud of gas and dust
that flattens into a rotating disk. The center of this cloud
becomes the star, and the planets eventually form in the disk of
the nebula. In the inner part of the nebula, the hottest part,
only high density minerals can form solid grains. The outer
regions are cooler, and in those regions icy materials of lower
density are formed. Planets grow from these solid materials,
beginning as dust grains, which grow by condensation and
accretion into planetesimals that range from a few centimeters to
a few kilometers in diameter. These planetesimals settle into a
thin plane around the star and accumulate into larger bodies, the
largest of which grow the fastest and eventually become
protoplanets. Once the star becomes a luminous object, the
remaining nebula is cleared as the star's radiation and the
stellar-wind (powerful streams of charged particles from the
star's surface) push the remnants out of the system. Thus ends
the phase of planet-building. As might be expected, the above
theory is also the current view of the history of our own solar
system. Since the details of disk formation, and the physical
properties of protoplanetary disks, can be modelled by
quantitative theory, the general idea is to investigate such
disks that are apparent around stars to test the theoretical
models. There is no way to do that with our own solar system,
because the protoplanetary disk is long gone. One needs young
stars. ... ... This week Vincent Mannings et al (California
Institute of Technology, CA US) report observations and analysis
of the apparent protoplanetary disk of a star only 6 million
years old, with a mass of 2.3 solar masses. The mass of the disk
is evidently greater than the minimum required to form a
planetary system like our own.
QY: V. Mannings
(Nature 7 Aug 97) (Science-Week 15 Aug 97)
-------------------
Related Background:
A GRAVITATIONAL INSTABILITY MODEL FOR GIANT PLANET FORMATION
Until recently, the consensus theory for the formation of large
planets such as Jupiter was the core accretion model involving
the formation of cores of approximately 10 times Earth mass,
followed by rapid accretion of gas from the primitive solar
nebula. The problem with this model is that the time needed for
accretion (about 1 million years) is of the order of magnitude of
the time during which a young solar-type star's gas dissipates.
The other possible model is one involving a gravitational
instability mechanism in which the solar nebula breaks up into
giant gaseous protoplanets which then contract and collapse to
form giant planets. This model was in the past abandoned because
the extant data concerning the masses of Jupiter and the outer
planets seemed incompatible with the model. But there is now new
data concerning the masses of Jupiter and the outer planets, and
this week Alan P. Boss (Carnegie Institution of Washington, DC
US) reported a revisit to the gravitational instability model,
with computer solutions of the relevant equations of
hydrodynamics coupled with the Poisson equation in a spherical
coordinate system, such solutions providing evidence that the
formation of giant protoplanets in a gaseous nebula disk can
indeed occur. The old gravitational instability model has
therefore apparently been revived.
QY: Alan P. Boss
(Science 20 Jun 97) (Science-Week 26 Jun 97)
-------------------
Related Background:
GIANT PLANET EVIDENCE CONFOUNDS SOLAR SYSTEM THEORISTS
Until recently, speculations and theories about planets orbiting
other stars than our sun have depended on our own solar system as
the guiding model. But during the past two years, astronomers
have been able to gather information about nine such planets, and
the evidence is apparently not in harmony with expectations. The
three variables that are evidently making trouble for theorists
are planet size, proximity to the parent star, and orbital
eccentricity. For example, the planet orbiting the star 51 Pegasi
is large enough to have about half the mass of Jupiter, but seems
to be orbiting the star at a radius of one-sixth the radius of
Mercury's to our sun. This is a puzzle, although there appears to
be still controversy about whether this planet is actually a
planet. Others of the discovered planets are apparently in highly
eccentric and unexplained orbits. So the theorists are busy
revising models for planet formation, establishment of orbits,
planetary orbital drift, and so on. The major difficulty is that
there are no direct observations of these discovered planets --
their existence is proposed to explain perturbations in the
behavior of their parent stars. Stephen Lubow of the Space
Telescope Science Institute (Baltimore MD US) says of the recent
observations: "It's been a revolution."
(Science 30 May 97) (Science-Week 5 Jun 97)
3. SEQUENCING OF A CHROMOSOME OF THE HUMAN MALARIA PARASITE
The disease malaria is caused by a protozoan parasite of the
genus Plasmodium, and it is one of the most dangerous diseases
infecting human populations. Approximately 300 million to 500
million people are infected annually, and 1.5 million to 2.7
million lives are lost to malaria each year, with most deaths
occurring among children in sub-Saharan Africa. Of the 4 species
that cause malaria in humans, P. falciparum is the greatest cause
of *morbidity and mortality. The resistance of the malaria
parasite to drugs and the resistance of mosquitoes to
insecticides have resulted in a resurgence of malaria in many
parts of the world and a pressing need for vaccines and new
drugs. The identification of new targets for vaccine and drug
development is dependent on the expansion of our understanding of
parasite biology, an understanding that is hampered by the
*complexity of the parasite life cycle. The sequencing of the
Plasmodium genome may circumvent many of these difficulties and
rapidly increase our knowledge concerning these parasites. The P.
falciparum genome contains 30 million *base pairs and 14
*chromosomes. ... ... M.J. Gardner et al now report the
sequencing of chromosome 2 of P. falciparum. This sequence
contains 947,103 base pairs and encodes 210 predicted genes. The
authors report that in comparison with the yeast genome,
chromosome 2 of P. falciparum has a lower gene density, *introns
are more frequent, and proteins are markedly enriched in
nonglobular domains. A family of cell surface proteins (rifins)
that may play a role in *antigenic variation was identified. The
authors suggest that the complete sequencing of chromosome 2 of
the organism indicates that the complete sequencing of the entire
genome of P. falciparum is technically feasible.
-----------
M.J. Gardner et al (27 authors at 5 installations, US)
Chromosome 2 sequence of the human malaria parasite Plasmodium
falciparum.
(Science 6 Nov 98 282:1126)
QY: Stephen L. Hoffman
-----------
Text Notes:
... ... *morbidity: In general, this refers to a diseased state;
in particular, the term refers to the ratio of the diseased to
the well in a community.
... ... *complexity of the parasite life cycle: See Related
Background below.
... ... *base pairs: The term "base pair" refers to the bases
(nucleotides) always found chemically bonded together in the DNA
double helix (adenine, for example, always bonds with thymine,
and guanine with cytosine).
... ... *chromosomes: In organisms with chromosomes, the
chromosomes are the physical structure into which DNA is
organized and on which genes are carried.
... ... *introns: A portion of DNA that lies between two exons
(regions of DNA expressed into proteins via *messenger RNA).
Introns are intervening sequences that are not expressed; they
are eliminated during the process that forms messenger RNA.
... ... *messenger RNA: (MRNA) The ribonucleic acid molecule
transcribed from DNA that carries the coded information
specifying the sequence of amino acids in a protein.
... ... *antigenic variation: In general, an antigen is any
chemical entity that activates an immune response, especially an
entity originating outside the body. The human immune response to
microbial parasites, for example, depends on the recognition by
the human immune system of specific chemical components of the
microbes, and such chemical components are termed "antigens".
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
-------------------
Related Background:
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
(Proc. Natl. Acad. Sci. US 14 Apr 98 95:4425)
(Science-Week 22 May 98)
-------------------
Related Background:
IDENTIFICATION OF THE INDUCER OF MOSQUITO MALARIA DEVELOPMENT
The disease malaria is caused by a type of protozoan with the
general name Plasmodium, an organism characterized by a sequence
of life cycles involving different organismic forms. The asexual
cycle occurs in the liver and red blood cells of vertebrates
(including humans), and the sexual cycle occurs in mosquitoes.
Essentially, the asexual form is ingested by blood-sucking
mosquitoes, and in the mosquito the asexual form is induced to
produce the sexual form necessary to complete the total life
cycle. The details of the process are as follows: Plasmodium
cells called "gametocytes" (precursors of gametes) in human blood
are ingested by the mosquito, and in the mosquito, apparently
within seconds, gametocytes are induced into "gametogenesis",
producing gametes. These gametes produce a cell-type called
"sporozoites", which accumulate in the salivary gland of the
mosquito, from where they are injected into the vertebrate blood
stream when the mosquito feeds on vertebrate blood. The sporo-
zoites accumulate in the vertebrate liver, where they multiply
and produce a form (merozoites) that invades red blood cells,
replicates, destroys red blood cells, and so on, with an eventual
decline in this asexual replication. However, after invasion of
red blood cells, some merozoites produce gametocytes, which have
the genomic potential for restarting the total life cycle. These
gametocytes cannot self-replicate, and they die unless ingested
by a mosquito, but once in the mosquito, the total life cycle
begins again. There are apparently 2 inducers of gametogenesis in
vivo (i.e., in the mosquito): one inducer is a pH of 7.5 to 7.6,
and the other inducer has been thought to be an unknown mosquito-
derived gametocyte-activating factor. ... ... Now Billker et al
(9 authors at 2 installations, UK US) report that the second
inducer in vivo of gametocyte induction in the mosquito is
apparently xanthurenic acid, and that low concentrations of
xanthurenic acid can act together with pH to induce gametogenesis
in vitro. The authors suggest these data could form the basis of
the rational development of new drugs to interrupt the
transmission of malaria, or for the development of methods
producing the selection of new mosquito genotypes (species
variants) resistant to infection.
QY: R.E. Sinden, Dept. of Biology, Imperial College London, SW7
2BB UK.
(Nature 19 Mar 98) (Science-Week 4 Apr 98)
-------------------
Related Background:
MALARIA: GENETICS OF HOST-PARASITE COEVOLUTION
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.
An antigen is any chemical moiety that provokes an immune
response in vertebrates, in particular by binding to an antibody,
and the term "epitope" refers to the region of an antigen
molecule responsible for its specificity in an antigen-antibody
interaction: the epitope is recognized by the antigen-binding
site of a specific antibody molecule. Cytotoxic T-cells are cells
of the vertebrate immune system that kill foreign cells by
production of certain proteins. In cell biology, the term "down-
regulation" refers to a gradual desensitization of cell surface
receptors that occurs upon repeated exposure to their specific
ligands. The term "host-parasite coevolution" refers to an
interdependent simultaneous evolution of a parasite species and
its host species. ... ... Hill et al (10 authors at 3 install-
ations, UK GM) report a study of the variants of an antigenic
epitope of Plasmodium falciparum that induces a cytotoxic T-cell
response. It was found that in African children with malaria, the
extant epitope variants are influenced by the presence of a human
leukocyte antigen type that restricts the immune response to this
epitope. The authors suggest that the distribution of parasite
variants may be further influenced by the ability of cohabiting
parasite strains to facilitate each other's survival by down-
regulating cellular immune responses using altered peptide ligand
antagonism, and that combined genetic, immunological, and
mathematical analyses of further such examples from natural
populations should provide a molecular understanding of the
mechanisms driving host-parasite coevolution.
QY: Adrian V.S. Hill
(Science 20 Feb 98) (Science-Week 6 Mar 98)
-------------------
Related Background:
EVIDENCE FOR LINKAGE BETWEEN AIDS AND MALARIA
Africa south of the Sahara is the focus of two of the most
serious diseases: AIDS and malaria. At a recent meeting in
Hyderabad (IN), evidence was presented that AIDS and malaria may
be linked. Altaf Lal (Centers for Disease Control and Prevention,
Atlanta US) reported in vitro studies showing that malaria
infection, by stimulating the white blood cells that are the
target of HIV, can increase the replication rate of the virus by
30 to 100-fold. Added to this is the fact that recent epidemio-
logical studies in Africa suggest that malaria may be a deadly
cofactor for HIV, hastening the death of those who carry both
infections. Sub-Sahara Africa now has 13.3 million cases of AIDS
and 450 million cases of malaria each year. There seems little
reason to be optimistic about the future of public health in the
region.
(Science 5 September) (Science-Week 19 Sep 97)
4. CELL SURFACE ECTODOMAINS AND PROTEIN SHEDDING
During the past several decades, research in molecular biology
has revealed the interface between the biological cell and its
environment -- the cell membrane -- to be complex in both its
structure and dynamics. In particular, the outer surface of the
cell membrane (the cell membrane "ectodomain") has come into
special focus, since this is the region of release by the cell of
intercellular regulator molecules, and also the region of first
interaction with messenger hormones, pathogenic entities,
nutrient molecules, etc. For the most part, release of regulators
and interactions involve specific sites in proteins embedded in
the outer surface, or attached to the outer surface, or extending
into the outer surface from the interior, and certain classes of
protease enzymes (i.e., enzymes that hydrolyze proteins) have
been suggested to be of critical importance in the ongoing
reconfigurations of the ectodomain that apparently occur. ... ...
Z. Werb and Y. Yan present a short review of cell membrane
ectodomain dynamics (and a commentary on the J.J. Peschon et al
paper discussed below), the authors making the following points:
1) During its life history, the cell alters the repertoire of
proteins displayed on its surface many times. Membrane-anchored
*adhesion molecules, *receptors, ligands, and enzymes are removed
and replaced as the cell proceeds through development and as its
activation state changes. How is this wholesale refurnishing of
the cell membrane orchestrated? 2) One key mechanism is
proteolytic processing of the ectodomain of *transmembrane
proteins. Cleavage or shedding of the ectodomains of plasma
membrane proteins -- widely observed in cells in culture -- is
blocked by inhibitors of *metalloproteases. 3) This result
suggests that transmembrane and soluble metalloproteases are
rate-limiting for shedding. The authors conclude: "Cells use a
limited number of strategies to remodel their micro-environments.
It is clear that the shedding process is an ancient, conserved,
and fundamental pathway present from worms to humans. Thus,
proteolysis by cell-surface-shedding enzymes provides a mechanism
by which the wardrobe of externally displayed molecules can be
changed or discarded. Spatial restriction of the enzymes and
their substrates allows for either instant action or sustained
activity." ... ... In a contiguous paper, J.J. Peschon et al
report experimental evidence concerning a new ectodomain shedding
protease. The tumor-necrosis-factor-alpha-converting enzyme *TACE
is a known surface-shedding enzyme previously believed to be
involved only with processing of *tumor necrosis factor-alpha,
but the authors now report that analysis of cultured mouse cells
lacking this enzyme reveals an expanded role of the enzyme in the
processing and shedding of other important cell surface
proteins,
and the authors suggest this enzyme may play an essential role
during mouse embryonic development.
-----------
Z. Werb and Y. Yan (University of California San Francisco, US)
A cellular striptease act.
(Science 13 Nov 98 282:1279)
QY: Zena Werb
-----------
J.J. Peschon et al (19 authors at 4 installations, US)
An essential role for ectodomain shedding in mammalian
development.
(Science 13 Nov 98 282:1281)
QY: Jacques J. Peschon
-----------
Text Notes:
... ... *adhesion molecules: Molecules expressed on the surface
of a cell that mediate the adhesion of the cell to other cells or
to the extracellular matrix. Adhesion molecules bind to
receptors
that are classed collectively as "integrins". Abnormalities in
cellular adhesion properties are characteristic of many types of
cancer cells.
... ... *receptors: In general, in this context, cell surface
macromolecules that bind ligands.
... ... *transmembrane proteins: A transmembrane or membrane-
spanning protein essentially has 3 domains: extracellular,
membrane, and cytoplasmic (intracellular). In other words, the
protein extends completely through the plasma membrane,
protruding from the outer surface and inner surface of the
membrane. The outer portion of the protein may be a receptor for
one or more ligands, the protein acting to transduce a signal to
the interior of the cell.
... ... *metalloproteases: A metalloprotease is a proteolytic
enzyme that requires the presence of a metal ion as a cofactor
for its catalytic activity. A "metalloprotein" is a more general
term, and refers to any protein whose structure and/or function
depends upon a specific metal ion or group of metal ions.
... ... *TACE: A metalloprotease that requires the presence of
the zinc ion.
... ... *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.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
5. PLASTICITY OF CEREBRAL CORTEX AFTER PERIPHERAL INJURY
The term "plasticity" in the context of brain research refers in
general to the ability of the brain to alter its connections or
dynamics as a result of experience or changes in conditions. So,
for example, the ability of certain parts of the brain,
particularly the cerebral cortex, to assume new functions
following destruction by disease or trauma of other parts is an
example of brain plasticity. The various parts of the brain do
not show the same degree of plasticity, and in general the degree
of plasticity of any part may change with the life history of the
individual. The brains of infants and young children, for
example, are extremely plastic. The mammalian brain region called
"somatosensory cortex" is the part of the cerebral cortex
functionally involved in the analysis of sensory input from
various body parts. The reorganization of somatosensory cortex
has been observed in monkeys with forelimb amputation or forelimb
sensory deafferentation (loss of neural input from the forelimb),
and in human amputees, and this reorganization is presumed to be
the basis for the sensation of *phantom limbs and perhaps for
*phantom pain. An important question is how such large-scale
changes are mediated in the adult brain. ... ... S.L. Florence et
al now report a study of the distributions of *thalamic and
cortical connections in 4 *macaque monkeys with long-standing
accidental trauma to a forelimb, the purpose of the study to
determine whether the growth of new connections plays a role in
the reorganization of somatosensory cortex known to occur after
major alterations in peripheral somatosensory inputs. The authors
report that microelectrode recordings demonstrated massive
reorganizations of the cortex related to the affected limb.
Tracer injections revealed normal patterns of thalamo-cortical
connections, but markedly expanded lateral connections ("cortico-
cortical" connections; also, "intracortical" connections) in
somatosensory cortex. The authors suggest their results indicate
that the growth of intracortical connections but not thalamo-
cortical connections could account for much of the reorganization
of the *sensory maps in cerebral cortex.
-----------
S.L. Florence et al (3 authors at Vanderbilt University, US)
Large-scale sprouting of cortical connections after peripheral
injury in adult macaque monkeys.
(Science 6 Nov 98 282:1117)
-----------
Text Notes:
... ... *phantom limbs: In general, the term "phantom limb"
refers to the sensation that an amputated limb is still present.
Also called "stump hallucination".
... ... *phantom pain: Phantom limb is often associated with
painful sensations of burning, prickling, tickling, or tingling
in the missing part of the limb.
... ... *thalamic and cortical connections: The thalamus is a
deep brain structure that consists of groups of nerve cells that
project to various other regions of the brain. In general, these
groups of nerve cells are specific relay stations for sensory
information (e.g., visual, auditory, pain, temperature, etc.) The
"connections" referred to here are those from the thalamus to the
cortex and those inside the cortex from cortical neurons to other
cortical neurons.
... ... *macaque monkeys: Macaca is a large genus of Old World
monkeys that includes macaques, rhesus monkeys, and the Barbary
apes.
... ... *sensory maps: The mammalian cerebral cortex is
essentially a multilayered surface, highly convoluted in the
higher forms, and it is into the layers of this surface that
sensory information input from the various sensory systems is
projected for analysis. Depending on the sensory system involved,
these projections are more or less isomorphic with the
distribution of the sensory receptors of the system. Thus, for
example, there is in effect a "map" of the hand in the
somatosensory cortex, and there is a "map" of each retina of the
eye in the visual cortex, and so on. The mapping in somatosensory
cortex is of the entire body.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
-------------------
Related Background:
THE ROLE OF VISUAL EXPERIENCE IN DEVELOPMENT OF VISUAL CORTEX
The visual system of vertebrates, especially that of the higher
vertebrates, is highly organized. The retina of the eye, for
example, which is essentially a surface upon which photons
impinge to be absorbed by chemical photosensors, is "mapped" by
exiting nerve fibers, and light-induced activation of the retinal
map are relayed with some transformations to various levels of
the central nervous system and finally to what is called the
"primary visual projection area" of the cerebral cortex (also
called "primary visual cortex"). The processing of this mapping
information is, in fact, the key to how we perceive the world
around us. ... ... Crair et al (3 authors at 2 installations, US)
report a study of the development of cortical maps for orient-
ation and eye preference in the primary visual cortex of normal
and binocularly deprived cats. These cortical maps were present
by 2 weeks after birth, and developed until nearly 3 weeks of age
whether or not the eyes were open. With continued visual depriv-
ation, responses to both eyes deteriorated. The authors suggest
that the basic structure of visual cortical maps is innate, but
experience is essential for specific features as well as for
maintaining the responsiveness and selectivity of cortical
neurons.
QY: Michael P. Stryker
(Science 23 Jan 98)
-------------------
Related Background:
EVIDENCE OF CROSS-MODAL PLASTICITY IN BLIND HUMANS
In neurobiology, the term "plasticity" is the name given to the
capacity of neural tissue to adjust to change. One variant of
this concerns the dependence of the "wiring" of the nervous
system on its input. Another variant concerns the degree to which
one region can under certain conditions assume the function of
another region. Plasticity does not occur everywhere in the
nervous system, but it is often evident in the cerebral cortex of
the brain, the cortex being the thin layer of cells apparently
responsible for higher analysis of sensory input, language,
ideation, and other so-called higher functions lumped together in
the category "cognitive processes". Last week Leonardo G. Cohen
et al (11 authors at 4 installations in US, AR, JP) reported the
results of studies of cross-modal plasticity in blind humans.
These studies involved non-invasive interference with cortical
activity by applying transient magnetic stimulation from outside
the skull. It has been demonstrated that such stimulation can
affect brain activity, and in this study the apparatus threshold
for stimulation of the motor cortex was first determined, and
then transient magnetic stimulation 10% above that threshold
applied to the occipital lobes of the brain through the overlying
skull to interfere with electrical activity in the visual cortex.
The experiments involved various location and procedural
controls, and also a group of sighted individuals. Essentially,
what was found is that in people blind from an early age, the
visual cortex is apparently involved in somato-sensory function
(fingertip reading of individual Braille characters), while the
same is not true for sighted subjects.
QY: L.G. Cohen (Nature 11 Sep 97)
-------------------
Notes by ScienceWeek:
One striking example of plasticity concerns the so-called
"critical period" for histological development of the visual
system in mammals. This is a period between birth and a later
time during which the neuron circuits in the visual areas of the
cerebral cortex are being developed. Once the system is comp-
letely developed, keeping one or both eyes closed has no effect
on vision. For example, an adult human can develop a cataract in
one eye, not have it removed for years, but once it is removed
and a lens substitute in place, the vision in that eye is normal.
The critical period for vision in humans lasts from birth to
about 6 years, and there is much histological evidence that the
visual cortex is changing during that time. A similar critical
period exists in other mammals. If both eyes are kept covered
from birth throughout the critical period in cats and monkeys,
and the eyes are then uncovered, the animals remain functionally
blind. It can be shown there is a gradation of the effect of the
absence of input from the eyes: the effect is greater during the
early part of the critical period than later on. And damage can
also be demonstrated by keeping only one eye covered. In all of
this, the eyes themselves are optically normal after they are
uncovered, the cells in the retina and in the lower visual
centers appear to function normally in their response to visual
input. But the deprived eye or deprived eyes are "blind", and the
changes or lack of development responsible for this loss of
visual function are in the visual cortex and are due to its
plasticity, its dependence on appropriate input for the formation
of working connections.
-------------------
Related Background:
PHANTOM SENSATIONS EVOKED BY HUMAN THALAMIC MICROSTIMULATION
One of the most fascinating phenomena in human neurobiology is
the so-called "phantom limb", the essentials of which are as
follows: Our sensations are based on sensory information arriving
at the higher centers of the central nervous system, the
connections being for the most part "hard-wired" through
embryology and early development. The sensory cerebral cortex, in
fact, quickly develops a hard map of all the peripheral sensory
receiving elements in the body, and the map is thus fixed. Now
consider the amputation of a leg. The relevant peripheral sensory
neurons have cell bodies close to the spinal cord and long axons
that extend to the lower leg. If the lower part of the leg is
removed, the sensory axons are cut at the stump, but the sensory
neuron cell bodies are still intact and most of these cells
survive the amputation. But input from these particular neurons
is hard-wired in the brain to represent input from the lower leg.
So although the lower leg is now absent, anything that excites
the axons of these particular neurons will be interpreted by the
central nervous system as an input from the lower leg as if the
lower leg had not been removed at all. Hence, the term "phantom
limb". In particular, amputees can often feel pain in part or all
of a limb that no longer exists. A stereotaxic device is a rigid
metal coordinate frame into which the head of an animal or human
is fixed so that microscale positioning of electrodes at any
particular coordinate position can be effected without displace-
ment caused by movement of the subject and with some fidelity as
far as the locus of placement at a point is concerned. "Function-
al stereotactic mapping" refers to using a stereotactic device to
map a particular region of the brain under conditions in which
that particular region is functional. The thalamus is an
important part of the sub-cortical brain relaying sensory inform-
ation to the cerebral cortex, and the ventrocaudal thalamus is a
subregion of the thalamus. ... ... Davis et al (6 authors at
University of Toronto, CA), in experiments designed to assist the
treatment of severe phantom or stump pain, report that micro-
electrode recordings and microstimulation during functional
stereotactic mapping of the ventrocaudal thalamus in human
amputees reveals an unusually large thalamic stump representation
consistent with the findings from animal experiments. The authors
suggest their results support the hypothesis that the thalamic
representation of the amputated limb remains functional in
amputees with phantoms.
QY: Karen D. Davis
(Nature 22 Jan 98)
6. ON THE MEDICAL APPLICATIONS OF CLONING
Ian Wilmut, who led the research team that cloned the sheep
Dolly, presents an essay describing the general techniques of
cloning and the possible medical applications. The author makes
the following points: 1) The author says the announcement of the
sheep Dolly's birth in February 1997 attracted enormous press
interest, perhaps because Dolly drew attention to the theoretical
possibility of cloning humans. The author says this is an outcome
he hopes never comes to pass. But the ability to make clones from
cultured cells derived from easily obtained tissue should bring
numerous practical benefits in animal husbandry and medical
science, as well as answer critical biological questions. (*Note
#1) 2) The ability to produce offspring from cultured cells opens
up relatively easy ways to make genetically modified (transgenic)
animals. Such animals are important for research and can produce
medically valuable human proteins. 3) Cloning offers many other
possibilities. One is the generation of genetically modified
animal organs that are suitable for transplantation into humans.
4) Another promising area is the rapid production of large
animals carrying genetic defects that mimic human diseases such
as *cystic fibrosis. 5) The power to make animals with precisely
engineered genetic constitution could also be employed more
directly in cell-based therapies for important diseases,
including *Parkinson's disease, *diabetes, and *muscular
dystrophy. 6) Cloning could also be a means of producing herds of
cattle that lack the *prion protein gene, which makes cattle
susceptible to infection with prions, the agents that cause "*mad
cow disease". 7) The cloning technique might curtail the
transmission of genetic disease by treating an embryo with
advanced forms of gene therapy to modify the nuclei of embryonic
cells so that the subsequent fetus and child was free of a
specific genetic disease and unable to pass the disease to the
next generation. 8) The author states that none of the suggested
uses of cloning for making copies of existing people is ethically
acceptable to his way of thinking, "because they are not in the
interests of the resulting child. It should go without saying
that I strongly oppose allowing cloned human embryos to develop
so that they can be tissue donors." The author concludes: "It
nonetheless seams clear that cloning from cultured cells will
offer important medical opportunities. Predictions about new
technologies are often wrong; societal attitudes change;
unexpected developments occur. Time will tell. But biomedical
researchers probing the potential of cloning now have a full
agenda." [Editor's note: In addition to the related background
material below, further background from past issues of SW is
gathered in a report entitled "Cloning and Genetic Engineering:
Policy Aspects", the report available at
]
-----------
Ian Wilmut (Roslin Institute Edinburgh, UK)
Cloning for medicine.
(Scientific American December 1998)
-----------
Text Notes:
... ... *Note #1: The cloning procedure here is based on nuclear
transfer and involves the use of two cells. The recipient cell is
usually an unfertilized egg cell taken from an animal soon after
ovulation. The DNA-containing chromosomes are removed from the
recipient cell, and then the donor cell (containing the genome to
be copied) is fused with the recipient egg cell, and the new
fused cell is stimulated to begin the normal process of embryonic
development. Essentially, the key event is the apparent
reprogramming of the adult somatic donor cell genome by the egg
cell cytoplasm so that the donor genome now behaves like the
genome of a fertilized embryonic cell and normal development
results.
... ... *cystic fibrosis: An inherited disease of the exocrine
glands, primarily affecting the gastrointestinal tract and
respiratory systems. The "exocrine" glands are glands that secret
material via excretory ducts (e.g., mucous secreting glands).
... ... *Parkinson's disease: A neurological disorder first
described by James Parkinson (1817) and associated with
degeneration of a specific small region of the brain and a
resultant loss of projection to several important brain centers.
... ... *diabetes: When used without a qualifier, this refers to
diabetes mellitus, a metabolic disease in which carbohydrate
utilization is reduced and that of lipid and protein enhanced,
the disease caused by an absolute or relative deficiency of the
hormone insulin.
... ... *muscular dystrophy: This is a general term for a number
of hereditary, progressive degenerative disorders affecting
skeletal muscles, and often other organ systems as well.
... ... *prion protein: Prions are a class of poorly understood
proteins implicated in a number of exotic human neurological
diseases and in some common animal diseases such as sheep scrapie
and bovine spongiform encephalopathy in cattle ("mad cow
disease").
... ... *mad cow disease: (bovine spongiform encephalopathy)
Although the precise structure of the infectious agent that
causes prion diseases is still unknown, important features of its
molecular genetics have been revealed, and the evidence suggests
possible transmissibility of bovine spongiform encephalopathy to
humans.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 11Dec98
-------------------
Related Background:
CONFIRMATIONS OF WILMUT CLONING RESEARCH
The adult *somatic cell clone experiments of the Ian Wilmut group
in the UK have apparently now been unequivocally confirmed. Most
biologists expected this, but a few prominent doubters expressed
their doubts to the popular media and made newspaper headlines
(see related background below). Three reports have now appeared,
two reports establishing by DNA analysis that the probability of
fetal cell contamination or mistaken mixed cell cultures in the
Wilmut research is "vanishingly small", and the third report
presenting evidence of 22 healthy female mice from successfully
cloned cultured differentiated cells. ... ... Ashworth et al (11
authors at 3 installations, UK) report a more detailed *DNA
microsatellite analysis than was originally presented when the
cloned sheep Dolly was first announced. On the basis of their new
data, the authors estimate the probability that another sheep
from the same population would have the same genotype as the 6-
year old ewe (the proposed source of Dolly) as between 1.9 x
10^(-12) and 2.7 x 10^(-10), and they conclude that it is
"extraordinarily unlikely that Dolly was derived from a different
Finn Dorset animal," and therefore they reject the hypothesis of
Sgaramella and Zinder that "imagined and unimagined experimental
error" occurred. The authors then state that if Dolly were
derived from a fetal cell, she would have derived half of her
*alleles from the sire of the fetus and half from the 6-year old
ewe, and the authors calculate the chance of a fetal cell having
the same genotype as the 6-year old ewe to be between 1.1 x
10^(-6) to 9.2 x 10^(-6). They conclude that, as originally
proposed, "Dolly was derived from a mammary cell of the 6-year
old donor ewe." ... ... Signer et al (7 authors at 2
installations, UK) report a *DNA fingerprint analysis to
determine the origin of the donor cell used in the *nuclear
transfer that produced Dolly, and the authors state that on the
basis of their results they have "confirmed the authenticity of
Dolly." They state: "The probability that a second unrelated
sheep has by chance the same profile as the donor tissue can be
conservatively estimated at 6 x 10^(-10). We therefore reject the
possibility that Dolly was derived from a contaminating cell
culture." Concerning whether Dolly could have been derived from a
fetal cell, the authors calculated the probability as between 8.6
x 10^(-5) and 3.5 x 10^(-7), and they state: "We therefore
conclude that Dolly is derived from the nucleus of a cell from
the mammary gland of the adult donor." ... ... Wakayama et al (5
authors at 4 installations, US JP IT) report an investigation of
the factors governing embryonic development, the experiments
involving the introduction of nuclei from somatic cells (*Sertoli
cells, neuronal cells, and *cumulus cells) taken from adult mice
into enucleated mouse oocytes (egg cells). The authors report
they found that some enucleated oocytes receiving Sertoli or
neuronal nuclei developed in vitro and implanted following
transfer, but none developed beyond 8.5 days after implantation.
However, a high percentage of oocytes receiving cumulus nuclei
developed in vitro, and once transferred, many of these embryos
implanted, and 2 to 2.8 percent developed to term. The authors
conclude: "Our results suggest that, contrary to previous
opinion, mammals can be reproducibly cloned from adult somatic
cells. Furthermore, we believe that the success of these
experiments in the mouse provides an amenable model with which to
evaluate the molecular mechanisms that regulate the
reprogramming
of somatic cell genomes, *genomic imprinting, embryonic *genome
activation, and cell *differentiation."
QY: Ian Wilmut
QY: Esther N. Signer
QY: R. Yanagimachi, University of Hawaii 808-956-8975.
(Nature 23 Jul 98 394:329,369) (Science-Week 14 Aug 98)
-------------------
Related Background:
... ... *somatic cell: Somatic cells are cells other than
germline cells (egg cells and sperm cells).
... ... *DNA microsatellite analysis: Satellite DNA consists of
highly repeated DNA sequences that are present in the genome, are
not coded for proteins, and have utility as genetic markers and
elements in DNA profile analysis. Microsatellite DNA consists of
tandem repeats of short DNA sequences up to 6 nucleotides long.
Minisatellite DNA refers to similar larger repeat groups up to 30
nucleotides long.
... ... *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.
... ... *DNA fingerprint analysis: This refers to DNA profile
analysis of *polymorphic loci. A profile compiled from a
sufficient number of rare alleles can be considered unique.
... ... *polymorphic: 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.
... ... *nuclear transfer: The nuclear transfer technique
indicated involves the transfer of the nucleus of a somatic cell
(which contains the genome for the individual) to an enucleated
egg cell. The egg cell now has a new nucleus, and it is the
genome in the new nucleus that determines the development of the
egg cell.
... ... *Sertoli cells: Large cells in the vertebrate testis that
support and nourish developing sperm cells.
... ... *cumulus cells: Cells surrounding the ovulated mammalian
egg cell, and which quickly disperse in the presence of sperm.
... ... *genomic imprinting: Parental genetic imprinting. An
important genetic mechanism whereby some genes in an organism are
predominantly expressed from either the paternally or the
maternally inherited chromosome.
... ... *genome activation: Refers to regulated activation of
specific target genes during development, etc.
... ... *differentiation: Refers to developmental cell
specialization (morphology and biochemistry) resulting from
activation of specific parts of the cell genome.
-------------------
Related Background:
CLONED TRANSGENIC CALVES FROM FETAL FIBROBLASTS
Research has been in progress for more than a decade to develop a
system for genetic modification and large-scale cloning in
cattle, an important species in agriculture, biotechnology, and
human medicine. During the past 18 months, there has been much
publicity concerning the cloning of sheep using somatic cell
donor cells, the research conducted by the Wilmut group in the
UK. ... ... Now Cibelli et al (8 authors at 3 installations, US)
report similar results (but with a different method) in cattle.
Actively dividing fetal fibroblasts were genetically modified
with a marker gene, a clonal line was selected, and the cells
were fused to enucleated mature oocytes. Out of 28 embryos
transferred to 11 recipient cows, three healthy, identical,
transgenic calves were generated. Furthermore, the life span of
near senescent donor fibroblasts could be significantly extended
by nuclear transfer. With the ability to extend the life-span of
these primary cultured cells, this system would be useful for
inducing complex genetic modification in cattle. The authors
suggest their somatic cell nuclear transfer procedure could
improve the efficiency of producing transgenic cattle and broaden
the scope of applications for transgenic cattle.
QY: James M. Robl (robl@vasci.umass.edu)
EMAIL
(Science 22 May 98 280:1256) (Science-Week 12 Jun 98)
------------------
Related Background:
SHEEP CLONING RESEARCH RESULTS: QUESTIONS AND ANSWERS
In a rare public exposure of what is usually a private or at
least specialist-restricted dispute between researchers,
Sgaramella and Zinder (2 installations, IT US), in a letter to
the journal Science and in interviews with various news media,
have extensively criticized the Roslin (Scotland, UK) sheep
cloning group headed by Ian Wilmut. Sgaramella and Zinder focus
on the cloning of the sheep Dolly from an adult ovine cell, and
state there has been a lack of any confirmation of this experi-
ment, that the original experiment was poorly controlled, the
interpretations untested, corollary mitochondrial data not
provided, and so on. Sgaramella and Zinder suggest that endless
debates about cloning are less than correct in the face of both
"the scientific weaknesses of the experiment and the possible
impact on the societal credibility of science itself" by debates
based on "facts" only presumed. In a contiguous reply, Campbell
et al (including Ian Wilmut) provide details explaining the
protocols used in the original Dolly cloning, say the Dolly
cloning was an unexpected and unplanned tangent from other
research, say the fact that Dolly is a Finn Dorset ewe restricts
the origin of Dolly to a single laboratory culture existing at
the time, that corollary data have indeed been provided to third
parties, that only 11 months have passed since publication of the
results, and since the gestation period in sheep is 5 months,
there has not yet been enough time to complete similar experi-
ments and publish data. Despite this public conflict, the
apparent consensus among embryologists is that the work of the
Wilmut group will be confirmed. QY: Norton D. Zinder, Rockefeller
University, 1230 York Avenue, New York, NY 10021 US; Ian Wilmut,
Roslin Institute, Roslin, Midlothian E-125 9PS, Scotland, UK.
(Science 30 Jan 98) (Science-Week 13 Feb 98)
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