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ScienceWeek
SCIENCE-WEEK
SCIENCE-WEEK - Part 1/3
A Free Weekly Digest of the News of Science
May 29, 1998
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Imagine a survivor of a failed civilization with only a tattered
book on aromatherapy for guidance in arresting a cholera
epidemic. Yet, such a book would more likely be found amid the
debris than a comprehensible medical text.
-- James Lovelock
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Contents of This Issue:
Part 1:
1. A Proposal for a Permanent Record of Our Civilization
2. Analysis of a Gamma Ray Burst from a High Redshift Galaxy
3. A Single-Wall Carbon Nanotube Room-Temperature Transistor
Part 2:
4. On Modular Cognitive Systems in the Human Brain
5. Cell Receptor Clustering as a Mechanism to Control Sensitivity
6. On Drug Delivery and Targeting
7. New Directions for Organ Transplantation
Part 3:
8. On Cell Therapy
9. On Human Gene Therapy
10. Adolescent Behavior: A New Survey Technology
11. An Analysis of Demographic Trajectories of Human Longevity
12. A Suggested Revision of Creutzfeld-Jakob Disease Nomenclature
---------------------------------------------
1. A PROPOSAL FOR A PERMANENT RECORD OF OUR CIVILIZATION
J. Lovelock (Oxford University, UK) presents an essay on
catastrophe, civilization, and information storage. The author
makes the following points: 1) We try to guard against local
hazards, but we tend to ignore threats global in scale. 2) We
fail to distinguish between the life-span of civilizations and
that of the species. Civilizations are ephemeral compared with
the species: humans have lasted a million years, but there have
been 30 civilizations in the past 5000 years. 3) As individuals,
we are amazingly ignorant and incapable. The important difference
that separates us from the social insects is that they carry the
instructions for nest building in their genes. We have no
permanent ubiquitous record of our civilization from which to
restore it should it fail. We would have to start again at the
beginning. 4) What we need is a primer on science, clearly
written and unambiguous in its meaning -- a primer for anyone
interested in the state of the Earth and how to survive and live
well on it. One that would serve also as a primary school science
text. It would be the scientific equivalent of the Bible. 5)
Modern media are more fallible instruments for long-term storage
than was the spoken word. They require the support of a
sophisticated technology that we cannot take for granted. 6) What
we need is a book written on durable paper with long-lasting
print, a book written with authority and readable enough to
ensure a place in every home, school, library, and place of
worship -- on hand whatever happened.
QY: James Lovelock, Coombe Mill, St. Giles on the Heath,
Launceton PL15 9RY, UK.
(Science 8 May 98 280:832) (Science-Week 29 May 98)
2. ANALYSIS OF A GAMMA RAY BURST FROM A HIGH REDSHIFT GALAXY
Gamma rays are radiation of high energy, from about 10^(5)
electronvolts to more than 10^(14) electronvolts -- radiation
with the shortest wavelengths and highest frequencies, the gamma
ray region of the electromagnetic spectrum merging into the
adjacent lower energy x-ray region. Gamma ray bursts are intense
flashes of gamma rays detected at energies up to 10^(6) electron
volts. Knowledge of the properties of gamma-ray bursts has
increased substantially following recent detections of
counterparts at x-ray, optical, and radio wavelengths. But the
nature of the underlying physical mechanism that powers these
sources remains unclear. An important question is the total
energy in the burst, for which an satisfactory estimate of the
distance is required, and until now the best estimate is that the
bursts lie at cosmological distances. ... ... Kulkarni et al (16
authors at 9 installations, US IN IT) now report identification
of the host galaxy of a previously optically detected burst
(GRB971214), with a determination of the galaxy redshift at z =
3.42. When combined with the measured flux of gamma-rays from the
burst, this large redshift implies an energy of 3 x 10^(53) ergs
in the gamma-rays alone, assuming the emission is isotropic. This
is much larger than the energies previously considered, and the
authors suggest it poses a challenge for theoretical models of
the bursts.
QY: S.R. Kulkarni (srk@surya.caltech.edu)
EMAIL
(Nature 7 May 98 393:35) (Science-Week 29 May 98)
-------------------
Related Background:
GAMMA RAY BURST FIREBALL MODEL MAY NEED REVISION
... The current consensus is that gamma ray bursts are produced
by the merger of two neutron stars, and up to this point, the
bursts that have been noted apparently originate outside our own
galaxy. ... ... Castro- Tirado et al (27 authors at 15
installations, ES DE SE DK IT UK US) report an optical transient
from a gamma ray burst (GRB 970508) imaged 4 hours after the
event, displaying a strong ultraviolet excess and reaching
maximum brightness 2 days later. The optical spectra did not show
any emission lines, and no variations on time scales of minutes
were observed for 1 hour during the decline phase. The authors
suggest the observations are incompatible with the fireball and
afterglow models of gamma ray bursts, and that another physical
mechanism may be responsible for the constant phase seen the
first few hours after the burst occurs. QY: T. Broadhurst, Univ.
of Calif. Berkeley, Dept. Astronomy 510-643-8520
(Science 13 Feb 98)
-------------------
Related Background:
OPTICAL STUDIES OF A GAMMA-RAY BURST SUGGEST FIREBALL MODEL
Studies of the mysterious gamma-ray bursts seen in every part of
the sky daily continue to be reported. This week we have the
results of observations of gamma ray burst (GRB) GRB970508, which
occurred on May 8, 1997 (hence the name). Optical studies of the
source of the burst by M. R. Metzger et al (California Institute
of Technology, US; National Radio Astronomy Observatory, US;
Institute of Space Astrophysics, Frascati IT; University of
Ferrara, IT) using data from the recently orbited Italian-Dutch
satellite BeppoSAX indicate the source of the GRB is extra-
galactic at a distance of 5 billion parsecs (1 parsec = about 20
trillion miles). Taking into account the recorded energy and its
loss by intervening absorption across that distance, we are
considering an initial energy burst with a magnitude equal to
the total radiation from our Sun during the entire age of the
universe. The computed energy figure is 10^(51) ergs of
gamma-rays. A consensus among astrophysicists is forming that
these GRBs involve "relativistic fireballs" produced by
colliding neutron stars, either two neutron stars colliding with
each other, or single neutron stars colliding with black holes.
The various radiant energy data are coming in so rapidly now,
there is a feeling the physical nature of GRBs will soon be
completely understood.
(Nature 26 Jun 97)
-------------------
Related Background:
GAMMA RAY BURSTS AND POSSIBLE TERRESTRIAL DISASTER
... Neutron stars are one of the possible end-products of
stellar evolution. If, following its terminal stages, the remnant
mass of a star is between 1.4 and 2 to 3 solar masses, the star
will collapse into a neutron star, a body with a radius of 10 to
15 kilometers, with a core so dense that its component protons
and electrons have merged into neutrons. The average density of a
neutron star is 10^(15) grams per cubic centimeter, and the
weight of an object on the surface of a neutron star would be
10^(11) its weight on the surface of the Earth. Neutron stars
apparently have an outer shell of iron, but it is iron like no
Earth iron, an iron of 4 orders of magnitude greater density.
Theory predicts that a neutron star should rotate very rapidly,
be extremely hot, and have an intense magnetic field.
... ... Leonard and Bonnell (US National Aeronautics and Space
Administration, US), in a review of gamma ray bursts and the
important data on these phenomena collected during 1997, point
out the following: 1) The current consensus is that gamma ray
bursts are produced by the merger of two neutron stars; 2) up to
this point, the bursts that have been noted apparently originate
outside our own galaxy; 3) considering the known neutron stars
inside our own galaxy, a case can be made that evolutionary
disjunctions in Earth's past may have been caused not only by
asteroid impacts, but also by gamma- ray bursts from merging
neutron stars a few thousand light years distant in our galaxy.
QY: Peter J.T. Leonard, NASA Goddard Space Flight Center,
Greenbelt, MD US (Sky & Telescope February 1998)
-------------------
Related Background:
EVIDENCE FOR DISTANT SOURCE OF GAMMA RAY BURSTS
Gamma Ray Bursts have been much in the news recently. They were
first accidentally discovered some 30 years ago by military
satellites, and then interest was rekindled when the Compton
Gamma Ray Observatory was launched by NASA in 1991. The Compton
orbiting device has been detecting Gamma Ray Bursts in all parts
of the sky on a daily basis. One controversy among astronomers
is whether the source is within our galaxy or extra-galactic.
Now Mark R. Metzger, leader of a team at the California
Institute of Technology (Pasadena CA US), reports that the
bursts detected here are coming to us through a stellar gas
cloud about 7 billion light-years away, which means the source
of the bursts must be at least that far, certainly
extra-galactic, and travelling to us for about half the age of
the universe. At least one part of a 30 year old puzzle has
apparently been solved -- the source of the bursts.
(UPI 15 May 97)
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DETECTION OF X-RAY AFTERGLOW ASSOCIATED WITH GAMMA-RAY SOURCE
Gamma ray bursts (GRBs) continue to tantalize astrophysicists.
The distribution of these bursts is isotropic across the sky, but
inhomogeneous in space, and with a deficit of faint bursts. The
problem is that present gamma ray telescopes have poor imaging
capabilities, and the phenomenology is unusual in that the bursts
last only from a fraction of a second to hundreds of seconds. At
present, it is not clear whether the bursts are produced in our
own galaxy or at cosmological distances. This week Costa et al (a
team of 26 researchers in IT and NL) report an analysis of a GRB
of 28 February 1997 (GRB970228). The major discovery is that of
an associated x-ray afterglow which fades within a few days
according to a power-law decay function (empirical). The authors
suggest that for the first time since the discovery of GRBs, it
will now be possible to correlate gamma-ray, x-ray, optical, and
radioastronomy observations. (Nature 19 Jun 97)
---------------------
AN HISTORIC MEETING DEVOTED TO GAMMA RAY BURSTS
Gamma ray bursts (GRBs) have been much in the news the past 10
months, principally because of correlative data from x-ray,
optical, and radio instruments. Last month saw the Fourth
Huntsville Symposium on Gamma Ray Bursts (15-20 Sep 1997,
Huntsville AL US), and the meeting is being called "historic".
There is apparently now a consensus that GRBs are cosmological
rather than galactic in origin, in other words from outside our
Milky Way galaxy. So that part of the 30-year puzzle concerning
GRBs is evidently solved. The other part of the puzzle concerns
the physical events producing the bursts, and for that part of
the puzzle there is apparently no consensus yet. It has recently
been proposed that GRBs are associated with the cataclysmic end
of massive stars, and if this is true, it is believed the
appearance of GRBs should provide data concerning the rate of
formation of such stars, a critical parameter that has evidently
been established by observation. In any case, the gamma ray burst
field has apparently now shifted to data analysis at new
wavelengths of the electromagnetic spectrum, with the emphasis
now on x-ray, optical, and radio observations from several
instrument sources, including the valuable BeppoSAX satellite,
the Hubble Space Telescope, and the Burst and Transient Source
Experiment (BATSE) aboard the Compton Gamma Ray Observatory.
QY: Bohdan Paczynski (Nature 9 Oct 97)
3. A SINGLE-WALL CARBON NANOTUBE ROOM-TEMPERATURE TRANSISTOR
Carbon nanotubes are similar to fullerenes, except their shape is
tubular. They were first discovered by Sumio Iijima (NEC
Laboratories, JP) in 1991, they come in both multi-walled and
single-walled versions, and they have diameters of the order of
10 to 30 nanometers. The use of individual molecules as
functional electronic devices was first proposed by Aviram and
Ratner in 1974. Since then, molecular electronics has attracted
much interest, particularly because it could lead to conceptually
new miniaturization strategies in the electronics and computer
industry. But the realization of single-molecule devices has
remained a challenge, largely owing to difficulties in achieving
electrical contact to individual molecules. Recent advances in
nanotechnology, however, have resulted in electrical measurements
on single nano-scale molecules. ... ... Tans et al (3 authors at
Delft University of Technology, NL) report the fabrication of a
field-effect transistor -- a 3-terminal switching device -- that
consists of one semiconducting single-wall carbon nanotube
connected to 2 metal electrodes. By applying a voltage to a gate
electrode, the nanotube can be switched from a conducting to an
insulating state. The device operates at room temperature,
thereby meeting an important requirement for potential practical
applications. Electrical measurements on the nanotube transistor
indicate that its operation characteristics can be qualitatively
described by the semi-classical band-bending models currently
used for traditional semiconductor devices, an unexpected result.
The authors suggest the fabrication of this 3-terminal switching
device at the level of a single molecule represents an important
step towards molecular electronics.
QY: Cees Dekker (dekker@qt.tn.tudelft.nl)
EMAIL
(Nature 7 May 98 393:49)
(continued in Part 2)
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SCIENCE-WEEK - Part 2/3
A Free Weekly Digest of the News of Science
May 29, 1998
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4. ON MODULAR COGNITIVE SYSTEMS IN THE HUMAN BRAIN
One of the central challenges of cognitive neuroscience is to
unmask the apparent unitary nature of perceptual, memorial, and
cognitive systems. Neuropsychological analyses, functional brain-
imaging methods, and analyses of normal reaction times have
revealed that apparently unitary processes consist of multiple
components. Frequently, these multiple components are distributed
across the cerebral hemispheres, but appear unified because of
the integration possible via the corpus callosum.
... ... Baynes et al (4 authors at 3 installations, US) report a
case of elective surgery for a severe epileptic disorder, the
surgery involving a resection of the corpus callosum in a left-
handed woman with left-hemisphere dominance for spoken language.
The patient demonstrated a dissociation between spoken and
written language. Words flashed to the dominant left hemisphere
were easily spoken out loud, but could not be written. When words
were flashed to the patient's right hemisphere, she could not
speak them out loud but she could write them with her left hand.
The authors suggest this marked dissociation supports the view
that spoken and written language output can be controlled by
independent hemispheres, even if before hemispheric disconnection
spoken and written language appear as inseparable cognitive
entities.
QY: Kathleen Baynes (kbaynes@ucdavis.edu)
EMAIL
(Science 8 May 98 280:902) (Science-Week 29 May 98)
-------------------
Related Background:
BRAIN PLASTICITY IN CHILDREN AFTER HEMISPHERECTOMY
Epilepsy is a term unhappily applied to several dozen different
seizure disorders, their commonality being central nervous system
seizures rather than identical pathological processes causing the
seizures. From a neurophysiological standpoint, a seizure is the
end result of a massive discharge of nerve cells, often the motor
neuron pathways that activate muscle cells. Seizures can be
produced by various central nervous system infections, metabolic
disturbances, toxic agents, cerebral oxygen deficiency, expanding
brain lesions, cerebral trauma, cerebral hemorrhage, and so on.
In general, any physiological event or series of events that
produces a wide disruption of central nervous system activity has
the potential for production of seizures of one sort or another.
Most patients who for reasons known (symptomatic epilepsies) or
unknown (idiopathic epilepsies) are chronically subjected to
seizures can be helped with various pharmacological agents such
as phenytoin or cloneazepam, but 10% to 20% of patients have
seizures that cannot be managed by drugs. If the seizures are due
to a specific damaged locus in the brain (the "epileptic focus"),
the recourse for these patients, if the locus can be determined,
is surgery. What is done is to completely remove the epileptic
focus, sometimes an area no larger than a small coin, and if the
surgery is successful the cure is immediate and permanent. There
are cases, however, in which the affected part of the brain is
quite large, the seizures completely unmanageable, and the only
recourse is radical surgery. Since severe chronic epilepsy due to
brain lesions is usually first diagnosed in young children, it is
such children who are the usual patients in radical brain surgery
for epilepsy. The most radical and fairly common procedure is
hemispherectomy, removal of an entire half of the brain, and the
most remarkable aspect of this is that when the surgical
procedure is successful, not only are the seizures eliminated,
but the child can function as well or almost as well as any other
child. It is an example of a phenomenon well-known to neuro-
biologists called "brain plasticity", the ability of the brain to
recover the function of a damaged or removed region by assignment
of the function to an undamaged location. The language area of
the brain, for example, is often considered to be fixed on the
left side of the brain by genetics, but in truth it is not so
fixed, and if the left side of the brain is removed at an early
age, the right side of the brain will quickly develop a language
center and there will be little functional impairment. In a
recent publication, Eileen P. G. Vining (Johns Hopkins Univ-
ersity, Baltimore MD US) reports the progress of 54 children who
underwent hemispherectomy for recurrent severe epileptic
seizures. The majority of the patients were seizure-free
following surgery, no longer needed drugs, and many of the
patients are now in school. One of the most significant facts
about the human brain is that its histological development
continues at least until adolescence, and the dynamism of this
histological development is what is responsible for its
remarkable plasticity. QY: E. Vining, Johns Hopkins University
(410) 516-8171 (Pediatrics August 1997)
5. CELL RECEPTOR CLUSTERING AS A MECHANISM TO CONTROL SENSITIVITY
Chemotactic bacteria such as Escherichia coli can detect and
respond to extremely low concentrations of chemical attractants,
concentrations less than 5 nanomolar in the case of aspartate.
They also sense gradients of attractants extending over 5 orders
of magnitude in concentration (up to 1 millimolar aspartate).
... ... Bray et al (3 authors at Cambridge University, UK) report
an analysis of the possibility that this combination of
sensitivity and range of response depends on the clustering of
chemotactic receptors on the surface of the bacterium. The
authors examine what will happen if ligand binding changes the
activity of a receptor, propagating this change in activity to
neighboring receptors in a cluster. Calculations based on these
assumptions indicate that sensitivity to extracellular ligands
increases with the extent of spread of activity through an array
of receptors, but that the range of concentrations over which the
array works is severely diminished. However, a combination of low
threshold of response and wide dynamic range of response can be
attained if the cell has both clusters and single receptors on
its surface, particularly if the extent of activity spread can
adapt to external conditions. The authors suggest a mechanism of
this kind can account quantitatively for the sensitivity and
response range of E. coli to aspartate, and that given the
simplicity of this mechanism, they anticipate that it will be
widely used by cells other than bacteria and for purposes other
than chemotaxis.
QY: Dennis Bray (d.bray@zoo.cam.ac.uk)
EMAIL
(Nature 7 May 98 393:85) (Science-Week 29 May 98)
6. ON DRUG DELIVERY AND TARGETING
R. Langer (Massachusetts Institute of Technology, US) reviews the
current status of drug delivery and target systems. When a
pharmaceutical agent is encapsulated within, or attached to, a
polymer or lipid, drug safety and efficacy can be greatly
improved and new therapies are possible. This has provided the
impetus for active study of the design of degradable materials,
intelligent delivery systems, and approaches for delivery through
different portals of the body. Delivery systems that could target
drugs to specific body sites or precisely control drug release
rates for prolonged times have long been dreamed of, but only in
recent years has the development of such systems become
practical. In a short time, new drug delivery systems have had an
impact on nearly every branch of medicine. There are 3 general
mechanisms by which drugs are delivered from polymer or lipid
systems: 1) diffusion of the drug species from or through the
system; 2) a chemical or enzymatic reaction leading to
degradation of the system, or cleavage of the drug from the
system; 3) solvent activation, either through osmosis or swelling
of the system. The author suggests that with the progress being
made in biology, chemistry, biomaterials science, and engineering
and pharmaceutical sciences, this field should have a bright and
rapidly evolving future.
QY: Robert Langer, Mass. Inst. of Technology 617-253-1000.
(Nature 30 Apr 98 392/supp:5) (Science-Week 29 May 98)
7. NEW DIRECTIONS FOR ORGAN TRANSPLANTATION
J. Platt (Duke University, US) reviews the current status of
organ transplantation and the various strategies being developed
to overcome the relevant problems. Organ transplantation is in
many cases the preferred treatment for the chronic failure of the
major organs. There has been considerable success in preventing
the rejection of transplanted organs, and further improvements in
the outcome of transplantation will occur. However, the main
limitation on the fullest possible use of organ transplantation
is the shortage of donated human organs. One solution to this
problem would be xenotransplantation, the use of animals instead
of humans as the source of organs and tissues for transplant. The
immunological barriers to this procedure are now well-defined,
and promising strategies such as the use of transgenic animals as
the source of organs, are being developed to overcome them.
Still, the problem of acute vascular rejection may not easily
yield to currently available therapies, and there is always the
possibility that some unforeseen hurdle remains to be detected.
Thus, xenotransplantation will probably enter clinical practice
gradually, in well-defined steps.
QY: Jeffrey L. Platt, Duke University 910-716-4264.
(Nature 30 Apr 98 392/supp:11) (Science-Week 29 May 98)
(continued in Part 3)
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SCIENCE-WEEK - Part 3/3
A Free Weekly Digest of the News of Science
May 29, 1998
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8. ON CELL THERAPY
F. Gage (Salk Institute, US) reviews cell therapy as a strategy
for the treatment of human disease. Because no single cell or
universal donor is likely to be useful for all diseases, it is
the source and desired function of the cell that will dictate
which cell type is most useful for each disease. The aim of cell
therapy is to replace, repair, or enhance the biological function
of damaged tissue or organs. This can be achieved by the
transplantation of isolated and characterized cells to a target
organ in sufficient number and quality for them to survive long
enough to restore function. The success of this therapy at a
clinical level requires an integration of many disciplines,
including cell biology, immunology, tissue engineering, molecular
biology, materials science and transplantation biology, and the
clinical expertise relevant to the disease being treated. Thus,
developments in any of these disciplines can have a major impact
on the success of cell therapy. For example, the identification
of a growth factor that could induce the expansion of the most
primitive hematopoietic stem cells would have a large impact on
the practicality of many cell and somatic gene therapy
strategies. So too would the identification of specific immune
suppression strategies that protect only the grafted cells
without compromising the host's immune system. These and other
discoveries are on the horizon, and they will facilitate the
usefulness of cell therapy in clinical medicine.
QY: Fred H. Gage, Salk Institute, 10010 N. Torrey Pines Road, La
Jolla, CA 92037 US.
(Nature 30 Apr 98 392/supp:18) (Science-Week 29 May 98)
9. ON HUMAN GENE THERAPY
The first approved clinical protocol for somatic gene therapy
began trials in 1990. Since then, more than 300 clinical
protocols have been approved worldwide, and over 3000 patients
have carried genetically engineered cells in their body. The
conclusions from these trials are that gene therapy has the
potential for treating a broad array of human diseases, and that
the procedure appears to carry a very low risk of adverse
reactions. However, the efficiency of gene transfer and express-
ion in human patients is still disappointingly low. Except for
anecdotal reports of individual patients being helped, there is
still no conclusive evidence that a gene-therapy protocol has
been successful in the treatment of a human disease.
... ... W. Anderson (University of Southern California, US)
reviews the status of the field and the difficulties that have
delayed advances, the author making the following points: 1) Gene
therapy is a powerful new technology that will require several
years before it will make a noticeable impact on the treatment of
disease. 2) Several major problems still exist, including poor
delivery systems, both viral and non-viral, and poor gene
expression after genes are delivered. 3) The reason for the low
efficiency of gene transfer and expression in human patients is
that we still lack a basic understanding of how vectors should be
constructed, what regulatory sequences are appropriate for which
cell types, how in vivo immune defenses can be overcome, and how
to manufacture efficiently the vectors that we do make. 4)
Although it not surprising that we have not yet had notable
clinical successes, the lessons we are learning in the clinic are
invaluable in illuminating the problems that future research must
solve. 5) Despite our present lack of knowledge, gene therapy
will almost certainly revolutionize the practice of medicine over
the next 25 years. In every field of medicine, the ability to
give the patient therapeutic genes offers extraordinary
opportunities to treat, cure, and ultimately prevent a vast range
of diseases that now plague mankind.
QY: W. French Anderson, Univ. of Southern California 213-740-2311
(Nature 30 Apr 98 392/supp:25) (Science-Week 29 May 98)
-------------------
Related Background:
THE PROSPECTS FOR GENE THERAPY
At the present time, more than 200 clinical trials of gene
therapy are apparently in place worldwide, with hundreds of
patients enrolled, but there is still not a single case of gene
therapy that can be called an unequivocal success. The major
problem is evidently gene delivery, getting the therapeutic gene
or genes or bits of DNA into cells in a way such that the new
genetic materials will be allowed to express their proteins in an
enduring cellular environment. There are basically two methods
for gene delivery, viral and non-viral, and neither method has
yet proved satisfactory. Success with either method, absent some
serendipitous laboratory or clinical discovery, will most likely
depend on further basic research. This has not been a good year
for the gene therapy community, considering the publicized lack
of clinical success, and considering that in Germany one of the
foremost gene therapy researchers has been accused of long-term
fraud and suspended from his professorship. But there are still
optimists, and this is still a field of vital importance to
medicine. In a recent review, Inder M. Verma and Nikunj Somia
propose that "in the not too distant future, gene therapy will
become as routine a practice as heart transplants are today." QY:
I. M. Verma, Laboratory of Genetics, The Salk Institute, La
Jolla
CA 92037 US (Nature 18 Sep 97)
-------------------
Related Background:
A RECOMBINANT GENE THERAPY FOR HUMAN RHEUMATOID ARTHRITIS
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, and
one would expect that if we could synthesize the receptor and
introduce the synthesized product into the extracellular fluid,
the cytokine for which this receptor is specific would bind to
the receptor and be prevented from delivering its chemical signal
to the cells. Test-tube synthesis of most complex proteins
produced by biological cells is not yet possible, but what one
can do, after calculating the DNA code for the active part of the
receptor protein, is incorporate the necessary DNA sequence into
the genome of some mammalian cell line, and have these cells act
as chemical factories to produce the cytokine receptor that we
are unable to synthesize otherwise. We then gather the factory
product, administer it to the patient, and expect the cytokine
receptor to bind its specific cytokine in extracellular fluid and
thus reverse the course of the disease. This is essentially what
"recombinant gene therapy" is all about. It is a field less than
a decade old, and like all fields involving clinical medicine, it
moves slowly because procedures that involve human patients must
be carefully developed. This week, Larry W. Moreland et al (12
authors at various installations, US) report the successful
treatment of rheumatoid arthritis with a recombinant human
cytokine receptor complex produced by the method outlined above.
It is a beginning. Like all treatments involving recombinant gene
therapy, much work needs to be done. But the path ahead is clear,
and there is an expectation of important results from this area
of clinical medicine. (New England Journal of Medicine 17 Jul 97)
-------------------
Related Background:
GENE-BASED IMMUNOTHERAPY FOR CERTAIN CANCERS EXPECTED SOON
Theodore Friedmann, director of the gene therapy program at the
University of California San Diego (US), points out that at
present no gene therapy approach has definitely improved the
health of a single one of the more than 2,000 patients who have
enrolled in gene therapy trials worldwide. Nevertheless,
Friedmann predicts that in the future gene therapy will be a
standard form of treatment for many diseases. In particular, he
says it seems likely that gene-base immunotherapies will succeed
with some malignancies such as neuroblastoma and melanoma in the
next few years, and will become helpful additions to existing
therapies for these diseases. (Scientific American June 1997)
10. ADOLESCENT BEHAVIOR: A NEW SURVEY TECHNOLOGY
Surveys of risk behaviors have been handicapped by their reliance
on respondents to report accurately behaviors that are highly
sensitive and may be illegal. There is a consensus among
specialists that face-to-face interviews, in particular, never
reveal more than a small fraction of such behaviors, and that
even paper questionnaires significantly underestimate prevalence.
... ... Turner et al (6 authors at 3 installations, US) now
report an audio computer-assisted self-interviewing technology
for measuring risk behavior, the technique tested in 1690
respondents in the 1995 US National Survey of Adolescent Males.
The respondents were randomly assigned to answer questions using
either the new technique or a more traditional self-administered
questionnaire. Estimates of the prevalence of male-male sex,
injection drug use, and sexual contact with intravenous drug
users were higher by factors of 3 or more when the new technique
(denoted as audio-CASI) was used. Increased reporting was also
found for several other risk behaviors, including violent
behaviors. The authors suggest their results, and complementary
evidence emerging from smaller studies using local samples,
indicate that the estimates of prevalence of risk behaviors
obtained with the new technique are more accurate than previous
estimates derived from data collected in less private interview
contexts. The authors further suggest that their estimates
present a disturbing picture of the biological and social risks
that confront young males in the US at the end of the 20th
century.
QY: C.F. Turner, Research Triangle Institute, 1635 M Street NW,
Washington, DC 20036 US.
(Science 8 May 98 280:867) (Science-Week 29 May 98)
11. AN ANALYSIS OF DEMOGRAPHIC TRAJECTORIES OF HUMAN LONGEVITY
Human old-age survival has increased substantially since 1950,
and this evidence of extended post-reproductive survival is
apparently puzzling biodemographers. Vaupel et al (14 authors at
10 installations, DE US DK MX CN) review current questions and
results in this field, presenting data from various sources. The
reduction in death rates at older ages has increased the size of
the elderly population considerably. In developed countries in
1990 there were about twice as many nonagenarians and 4 to 5
times as many centenarians as there would have been if mortality
after age 80 had stayed at 1960 levels. Reliable data for various
developed countries indicate that the population of centenarians
has doubled every decade since 1960, mostly as a result of
increases in survival after age 80. Here are selected data for
people 60 years and older in 1997 and projections for 2025:
----------------------------------------------------------------
1997 2025 percent of pop. in 2025
World 530 million 1200 million 15
Italy 13 18 33
Sweden 2 2.7 29
Germany 18 28 32
Japan 27 40 33
US 44 83 25
China 118 290 20
India 64 165 12
Mexico 6.5 18 13
----------------------------------------------------------------
QY: James W. Vaupel (jwv@demogr.mpg.de)
EMAIL
(Science 8 May 98 280:855) (Science-Week 29 May 98)
12. A SUGGESTED REVISION OF CREUTZFELD-JAKOB DISEASE NOMENCLATURE
Creutzfeld-Jakob disease is a rare, progressive, and always fatal
transmissible spongiform encephalopathy now considered to be a
prion disease, and recently in the public arena due to the
outbreak of apparently related "mad cow" disease (bovine spongi-
form encephalopathy) in the UK. In 1921 and 1923, Alfons Maria
Jakob (1884-1931) published 4 papers on an apparently newly
identified neurological disease, and in one of these papers,
Jakob refers to a previous paper in 1920 by Hans Gerhard
Creutzfeld (1885-1964), in which, according to Jakob, Creutzfeld
identifies a similar disease. Since the Creutzfeld paper appeared
first, this new disease entity came to be called Creutzfeld-Jakob
disease. In a letter to the journal *Nature*, F. Katscher now
points out that analysis of the case reported by Creutzfeld
indicates his case does not belong to the transmissible
spongiform encephalopathy group, that Creutzfeld himself stated
this sometime between 1945 and 1964, and that Creutzfeld-Jakob
disease should really be called Jakob disease, but since that
would suggest a new disease, a compromise solution is to
rearrange the order of the names to Jakob-Creutzfeld disease. But
there is more: Jakob's original slide preparations still exist,
and of the 5 cases originally presented by Jakob in his first 4
papers, Katscher points out that present analysis indicates that
only 2 of these cases are what we currently understand as
Creutzfeld-Jakob disease.
QY: Friedrich Katscher, Mariahilfer Str. 133, A-1150 Vienna, AT.
(Nature 7 May 98 393:11) (Science-Week 29 May 98)
----------------------------------------------------------------
BOOK NOTES:
P. Erlich and A. Erlich: BETRAYAL OF SCIENCE AND REASON
How Anti-Environmental Rhetoric Threatens Our Future Island
Press, 1998, 320p, US24.95, paper US16.95 ISBN 1-55963-483-9
(hc); 1-55963-484-7 (p) An account of the corporate backlash
against environmental policies, the backlash that "distorts and
denies mainstream scientific thinking in an effort to roll back
environmental policies in favor of immediate economic interests."
Natural resources, toxic substances, ozone depletion, global
warming, acid rain, biodiversity loss, flood production,
population growth. Paul R. Erlich is Professor of Population
Studies at Stanford University (US); Anne H. Erlich is a senior
research associate in biological sciences at Stanford University
(US).
Brian Fagan: FROM BLACK LAND TO FIFTH SUN
The Science of Sacred Sites
Perseus/Addison-Wesley, 1998, 403p, US26
ISBN 0-201-95991-7
An anthropologist and archeologist examines the spiritual lives
of ancient peoples in the light of archeological data and the
most recent archeological techniques. This is an authoritative
and well-written introductory account for anyone with a serious
interest in archeology or anthropology and the interface between
these disciplines. Indexed, with a wide-ranging list of
references. Cro-Magnon caves, San rock art, Jericho, Catalhoyuk,
Ain Ghazal, Avebury, Stonehenge, Chaco Canyon, North American
moundbuilders, Cyclades Islands, Knossos, Pyramids of Giza,
Nekhen, Saqqara, Mayan sites, Aztec sites. The author is
Professor of Anthropology at the University of California Santa
Barbara and has written many popular books about archeology.
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