ScienceWeek

SCIENCE-WEEK - Part 1

A Free Weekly Digest of the News of Science

January 2, 1997

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"Our loyalties are to the species and the planet.
We speak for Earth. Our obligation to survive is
owed not just to ourselves but also to that Cosmos,
ancient and vast, from which we spring."
-- Carl Sagan

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Contents of This Issue:

Part 1
1. A Nobel Laureate Comes Out Against Block Research Grants
2. On the Continuing Disintegration of Russian Science
3. The Beginnings of the Battle Over Breast Cancer Genes
4. X-ray Emissions and Outbursts from Massive Star Eta Carinae
5. Predicting the Course and Consequences of El Nino
6. Experimental Approaches to the Analysis of Earth's Core
7. Isotope Effects: 50th Anniversary of a Classic Paper
8. Experimental Quantum Teleportation
9. Origin of Life: The Present Status of Chemical Theory

Part 2

10. Virtual Symbiosis in Higher-Order Peptide Self-Replication
11. Enzyme Optimization by Test-Tube Evolution
12. Synthesis of Peptides Without Formation of Peptide Bonds
13. Mechanism of RNA Polymerase Nucleosome Transcription
14. Crystal Structure of a G Protein Complex
15. Details of Dynein Motor Domain Mechanisms
16. Complete Genome Sequence of Lyme Disease Pathogen
17. Regeneration of Motor Neurons: Identification of a Mitogen
18. Synchronization and Rate Modulation in Motor Cortex Neurons
19. Inhibition of Kaposi's Sarcoma by Ribonuclease
20. Cumulative Medical Impact of Sustained Economic Hardship

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1. A NOBEL LAUREATE COMES OUT AGAINST BLOCK RESEARCH GRANTS In
general, there are two methods for providing financial support
for scientific research. One method involves awarding funds to an
institution, or to departments within an institution, with the
idea that bureaucratic entities within the institution will then
disburse funds to individual investigators heading particular
research programs. Such awards are called "block grants", the
awarding of funds en bloc to an institution or institutional
department. The other method is to simply award research funds to
individual researchers, usually on the basis of competitive
individual applications. It is easy to provide arguments and
counter-arguments for either method, and as usual in areas of
public policy where no one has ever done a controlled public
policy experiment, the result is a vacillation of public policy
from one era to another depending on the public mood and public
priorities and the efficacy of public rhetoric. In fact, what
works in one place and time may not work in another place and
time, and even if everyone knows this, the debate continues and
has continued for the past 50 years. In the US, the tendency has
been to favor individual competitive research grants over block
grants, while in some other countries the opposite has been true.
Nobel Laureate Arthur Kornberg, in an editorial in the journal
Science, notes that recently the US National Institutes of Health
budget allocations have been shifting in favor of block grants,
"program projects in some of which a director can select the
investigators and choose projects that might not withstand peer
review." Kornberg says it is a common illusion that "strategic"
objectives are necessary to solve the problems of major diseases,
but the idea is misguided. "Basic research," Kornberg says, "has
been the province of the individual investigator and remains the
lifeline of medicine." QY: Arthur Kornberg, Stanford Univ., Dept.
of Biochem. 415-723-2300 (Science 12 Dec 97)

2. ON THE CONTINUING DISINTEGRATION OF RUSSIAN SCIENCE The
situation of science in Russia is simply stated: Science is
dying. No matter the impressive past or the optimistic statements
by Russian bureaucrats concerning the future of Russian science,
the evidence indicates a disintegration of all the scientific
disciplines. The funding of science is now 10% of what it was
before the breakup of the Soviet Union, scientists receive on the
average US$100 a month in salary, cannot afford to eat in a cheap
restaurant, must work at non-science jobs to survive. A recent
review of conditions states, "The scientific community in Russia
has been scrapping for morsels from a free-market economy riddled
with corruption." There is a constant struggle by scientists to
find adequate research funds, a scarcity of materials, decrepit
equipment, lack of foreign scientific journals, low esteem by the
public, and pitiful salary levels. A research scientist at the
Institute of Theoretical and Experimental Physics in Moscow
supplements his income by driving his car as a taxi. Approxi-
mately 80,000 scientists emigrate from Russia each year, typic-
ally 30 to 45 years of age, and there is no incentive for young
people to choose science as a career. Mikhail P. Egorov, a
research scientist at the Zelinsky Institute, says, "Without
science, Russia will become a Third World country." (Chem. & Eng.
News 22 Dec 97)

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Related Background:

CONTINUING COLLAPSE OF SCIENCE IN RUSSIA Following the departure
of the Soviet regime in Russia, and the transformation of Russia
to a private-enterprise market economy, Russian science
effectively collapsed. The two chief character-istics of Soviet
science policy were the use of a command and control structure,
with various governmental departments tightly controlling various
areas of scientific research, and a severe restriction of both
publication of results and contacts with the international
scientific community. These aspects no longer exist in what is
called "Russian science". The new problem is the national budget
crisis, which has resulted in a severe shortage of funds, coupled
with a tangle of bureaucratic difficulties in the government
administration of large scientific projects. There has also been
a severe brain-drain, as the average income of Russian scientists
has dropped from 10% to 20% above the national average under the
Soviet regime to 20% below the national average in 1996.
Detailing the situation, physicist Boris G. Saltykov, the
Minister of Science and Technology Policy 1991 - 1996, is
nevertheless optimistic "that Russia's scientific community will
find both the strength and ability to overcome its present
crisis." (Nature 3 Jul 97)

3. THE BEGINNINGS OF THE BATTLE OVER BREAST CANCER GENES
Legal papers filed in two different court jurisdictions in the
past 6 weeks indicate that a significant battle is looming
concerning exploitation rights for discoveries of two breast
cancer genes, BRCA1 and BRCA2. The major litigants are
Oncormed Inc. of Gaithersburg, MD US, and Myriad Genetics of Salt
Lake City, UT US. Each company holds patent rights from
independent research teams, and each company sells genetic tests
used to estimate a woman's risk of breast or ovarian cancer.
These legal entanglements highlight the questions that are being
raised about the value of gene patents in general. In this
particular case, there has been criticism of the US Patent
Office, which has apparently awarded patents to two different
groups for the same use of the gene BRCA1, albeit with vari-
ations of the gene involved in the methodology. One geneticist
calls the Patent Office decision "just crazy". The US Patent
Office is headed by Bruce Lehman, who has also come under fire
from scientists and librarians for his support of restrictive
electronic database copyright protection legislation promulgated
by commercial interests. (Science 12 Dec 97)

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Related Background:

CONSTRAINTS IMPOSED IN USE OF BREAST CANCER GENE PATENTS
BRCA1 and BRCA2 are known breast cancer susceptibility genes,
discovered in 1994 and 1995, and it has been reported that a
protein made by BRCA2 plays a critical role in cell repair of
DNA damage. Both cancer genes are apparently somehow involved in
tumor suppression or in the production of proteins vital for DNA
repair and the suppression of mutations. Patents for both genes
have been awarded to university-industry consortiums. From the
commercial standpoint, the value of such a patent is the
potential for making profit from diagnostic tests, since if one
has a patent on an important gene, one also has exclusive rights
to market diagnostic tests for disease-producing mutations of
that gene. Since breast cancer kills many millions of women
worldwide each year, there are many millions of women who are a
potential market for a diagnostic test that will tell them if
they are at risk. A similar paradigm applies to many other
patents that have been awarded or will soon be awarded for genes
in the human genome. That is the commercialization aspect of the
story. The scientific aspect is that identifying genes in the
human genome, their expressed proteins and the function of their
expressed proteins, and coupling such genes to specific disease
entities -- all of it is enormously expensive. So for the past
decade such research projects have been deliberately opened to
venture capital from private interests with the idea that
exclusive patents would be used to recoup the initial investments
with a profit. The basic science of the human genome has thus
been commercialized. A reasonable analogue would be the use of
private venture capital in particle physics to identify a new
elementary particle with the arrangement such that the private
commercial interest would have an exclusive patent on that
elementary particle. In any case, this is the current situation
in molecular biology. Now a British patent for the BRCA2 gene
has been awarded to a consortium of the Cancer Research Campaign
Technology (UK) and Duke University (US), and this consortium has
in turn granted an exclusive worldwide license to the patent for
diagnostic services and products to the company Oncormed of
Gaithersburg, MD US. What is apparently a new wrinkle in this
game is that Oncormed must apparently meet certain strict
conditions in exercising its license: broad sub-licensing of
diagnostic tests to other concerns, a requirement for pre- and
post-test counseling for women tested, a ban on direct advertis-
ing to the public for screening tests, and no charge for use of
the techniques by the UK National Health Service. Everyone agrees
that genetic testing ought to be conducted ethically and
responsibly, but apparently not everyone agrees that agreements
with private companies can effectively replace government
regulation. The story of the commercialization of molecular
biology has yet to unfold its denouement. (Nature 27 Nov 97)

4. X-RAY EMISSIONS AND OUTBURSTS FROM MASSIVE STAR ETA CARINAE
X-ray radiation energies range from approximately 10^(2) elec-
tronvolts to 10^(5) electronvolts, and "hard" x-ray emissions
is simply another term for high energy emissions. Eta Carinae
(also called "Eta Car") is a variable star in our galaxy, the
star at a distance of about 9000 light years from Earth. The
star's brightness suddenly increased in 1833, and for the next
decade was the second brightest star visible to the naked eye.
For the past 150 years there have been large variations in
brightness of the star at irregular periods. A binary stellar
system consists of two stars revolving about a common center of
mass under the influence of their mutual gravitational attract-
ion, and periastron refers to the closest approach of the two
stars in a binary system. The term "stellar wind" refers to the
steady stream of matter ejected from many types of stars,
including our own Sun (solar wind). Now Corcoran et al (6 authors
at 4 installations, US DE) report a 1.5 year study of the hard x-
ray emission from Eta Car indicates there has been an overall
increase in the mean x-ray flux that has accelerated since
January 1997, with small-scale periodic outbursts occurring every
85 days. Since it has been argued that Eta Car is in fact a
binary stellar system whose components are approaching periastron
near 1 January 1998, the authors suggest the hard x-ray emission
may be produced by collision of the stellar winds from the two
stars, and that monitoring the changes in x-ray emission through
periastron should test this wind-collision model. QY: Michael F.
Corcoran  (Nature 11 Dec 97)

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Related Background:

... Many astronomers believe Eta Car is a blue variable star
whose periodic gas ejections obscure its radiations. Variable
stars are stars whose physical parameters vary, usually
periodically, with the cause of the variation either intrinsic
(produced by the internal physics of the star) or extrinsic
(produced by the proximity of another star). A "blue" variable is
a variable star thought to be a member of a binary system, the
blue variable remaining on the Main Sequence long after stars of
similar or lower mass have diverged into red giants. The key
question concerning Eta Carinae is whether it is a binary star or
a single massive star, perhaps a blue variable, with periodic gas
ejection. Recently, analysis has revealed a 5.5 year cycle in
certain spectroscopic parameters of Eta Carinae, and it hoped
that within the next few months the periodicities will be
confirmed and explained. K. Davidson (Univ. of Minnesota, US)
reviews what is known concerning Eta Carinae and the observations
that may be made in the near future. The author suggests the
binary theory concerning the star may be confirmed or disproved,
and perhaps its fundamental structure and instability revealed.
QY: Kris Davidson, Univ. of Minnesota 612-624-0211 (Sky &
Telescope January 1998)

5. PREDICTING THE COURSE AND CONSEQUENCES OF EL NINO
El Nino is an aperiodic intermittent (2 to 10 years) flow of
unusually warm surface water along the western coast of South
America, the flow capable of causing abnormally high rainfall in
usually dry areas and severe local ecosystem dislocations -- what
is termed an El Nino "event". El Ninos are regional phenomena,
but they have global consequences. The name "El Nino" ("The
Child") arose because the phenomenon usually occurs around
Christmas. In 1986, M.A. Cane and S.A. Zebiak proposed a model
for making forecasts of El Nino several seasons ahead by applying
Newton's equations of motion and the laws of thermodynamics to
the dynamics of the ocean and atmosphere of the tropical Pacific.
Webster and Palmer (Univ. of Colorado, US; European Center for
Medium Range Weather Forecasts, UK), in a short review of the
past behavior and possible future behavior of El Nino, summarize
the use of the Cane-Zebiak model in making global weather
predictions, and suggest that the present El Nino may be
approaching a climax, with increased rainfall in the southwestern
US and on the Pacific coast of Peru and Ecuador, drought
continuing over Indonesia and New Guinea and increasing over
Australia. QY: Peter J. Webster 
(Nature 11 Dec 97)

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

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Related Background:

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

7. ISOTOPE EFFECTS: 50TH ANNIVERSARY OF A CLASSIC PAPER
In general, the isotope effect refers to differences in
reactivity of a compound when in the compound one isotope of an
element is substituted for another isotope of the element. The
carbon-hydrogen bond energy, for example, is less than that of
the carbon-deuterium bond energy, so reactions involving the
breaking of these bonds will differ in various parameters. The
effect, apparently involving differences in vibrational energies
of the isotopes, differences that in turn are mostly dependent on
differences in isotope masses, was first described in a quantum
mechanical formulation in a classic paper by Jacob Bigeleisen and
Maria Goeppert-Mayer in 1947. Goeppert-Mayer is one of the more
interesting personages of 20th century science. She received her
PhD in physics at the University of Gottingen in 1930, emigrated
to the US in 1933, married the chemist Joseph Mayer, as a woman
was consistently refused employment by American universities
except at levels of that of a teaching assistant, and she more or
less worked independently until the 1940s. But her brilliance was
recognized, she was part of the Columbia University Manhattan
Project (working with Bigeleisen), she later assisted Enrico
Fermi, and she eventually won a Nobel Prize in Physics in 1963
for her shell model of the atomic nucleus, which supposedly she
devised in 10 minutes while sitting in Fermi's office at the
University of Chicago. She is one more example of a brilliant
women denied a solid career in science for reasons that seem
absurd. She was finally appointed Professor of Physics at the
University of California San Diego in 1960. In chemistry, the
applications of the isotope effect have been profound, and all
chemists are aware of her classic paper with Bigeleisen, who
after 1947 continued work in the field, particularly on kinetic
isotope effects. To celebrate the 50th anniversary of the
influential paper by Bigeleisen and Goeppert-Mayer, the Journal
of Chemical Physics, in which the paper first appeared in 1947
(15:261), has authorized a reprinting of the original to be
distributed to participants at the forthcoming Gordon Research
Conference on Isotopes in Biological and Chemical Sciences.
Bigeleisen has stated the original isotope effect formulation was
in fact due to a flash of insight by Goeppert-Mayer, and an
argument can be made that Goeppert-Mayer deserved a Nobel Prize
in chemistry as well as one in physics. (Chem. & Eng. News 22 Dec
97)

8. EXPERIMENTAL QUANTUM TELEPORTATION
Quantum teleportation is the transmission and reconstruction over
arbitrary distances of the state of a quantum system, an effect
first suggested by Bennett et al in 1993 (Phys. Rev. Lett.
70:1895). The achievement of the effect depends on the phenomenon
of entanglement, an essential feature of quantum mechanics.
Entanglement is unique to quantum mechanics, and involves a
relationship (a "superposition of states") between the possible
quantum states of two entities such that when the possible states
of one entity collapse to a single state as a result of suddenly
imposed boundary conditions, a similar and related collapse
occurs in the possible states of the entangled entity no matter
where or how far away the entangled entity is located. Polarizat-
ion is essentially a condition in which the properties of photons
are direction dependent, a condition that can be achieved by
passing light through appropriate media. Bouwmeester et al (6
authors, Univ. of Innsbruck, AT) now report an experimental
demonstration of quantum teleportation involving an initial
photon carrying a polarization that is transferred to one of a
pair of entangled photons, with the polarization-acquiring photon
an arbitrary distance from the initial one. The authors suggest
quantum teleportation will be a critical ingredient for quantum
computation networks. Dik Bouwmeester
 (Nature 11 Dec 97)

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Related Background:

REPORT OF FIRST QUANTUM MECHANICAL ENTANGLEMENT OF ATOMS
... In the past, evidence of quantum mechanical entanglement has
been restricted to elementary particles such as protons,
electrons, and photons. Now E. Hagley et al, using rubidium
atoms prepared in circular Rydberg states (which means the outer
electrons of the atom have been excited to very high energy
states and are far from the nucleus in circular orbits), have
shown quantum mechanical entanglement at the level of atoms.
What is involved is that the experimental apparatus produces two
entangled atoms, one atom in a ground state and the other atom
in an excited state, physically separated so that the
entanglement is non-local, and when a measurement is made on one
atom, let us say the atom in a ground state, the other atom
instantaneously presents itself in the excited state -- the
result of the second atom wave function collapse thus determined
by the result of the first atom wave function collapse. There is
talk that before long quantum mechanical entanglement may be
demonstrated for molecules and perhaps even larger entities.
[Phys. Rev. Lett. 79:1 (1997)]

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QUANTUM PHOTON ENTANGLEMENT AT A DISTANCE OF SEVEN MILES
Whether or not the quantum mechanical behavior of elementary
particles is called mysterious depends, more or less, on the
attitude one has. If there is a demand that the behavior of these
particles be explainable with the logistic structure of human
language, then some aspects of their behavior seem mysterious
indeed. On the other hand, if there is a willingness to admit
that the logical structure of human language may not at present
be isomorphic with the logical structure of the laws that govern
the behavior of these particles, then it is probably best to put
off notions of mysteries and take the behavior for what it is.
This week there was announced to the popular press, before
publication, the results of a twin-photon experiment in
Switzerland. Nicolas Gisin et al (University of Geneva, CH)
reported that a pair of twin photons split and sent along two
diverging paths, when arriving at terminals seven miles apart,
exhibit the phenomenon of quantum "entanglement". The gist of it
is that the detection of one of the photons effectively causes
the collapse of the spectrum of its wave-function solutions to a
single solution, and this collapse instantaneously causes the
collapse of the possible quantum states of the other photon, in
this case seven miles away. The melodramatic notion (purveyed by
the press) is that information has somehow travelled from one
photon to the other at a speed greater than the speed of light,
with the result that great canons of thought are thereby
destroyed. But perhaps the more prosaic reality is that any
attempt to describe non-classical events with language based on
classical laws and perceptions cannot succeed.
(New York Times 22 Jul 97)

9. ORIGIN OF LIFE: THE PRESENT STATUS OF CHEMICAL THEORY
The essential question involved in the origin of what we call
life is how can order arise from disorder? At the present time,
this question is approached on two fronts: 1) study of the
principal features of self-organizing systems, systems in which
order does arise from disorder, systems in which order is indeed
demanded from disorder on thermodynamic grounds; and 2) study of
the detailed chemistry of such systems, the chemistry of
organization and the chemistry of components. In the case of
components, it is essential that appropriate self-organizing
components exist in the first place if they are to become self-
organized, and such candidate components are thus the focus of
much chemical research in this area. In 1953, the chemist Stanley
Miller reported what soon became a famous experiment. To water
under a gas mixture of methane, ammonia, and hydrogen, he added
an electrical discharge. After one week of continuous electrical
discharge, he found that a number of important biological
molecules, including amino acids, had been formed. Miller
proposed his experiment as a model for the conditions under which
the essential compounds necessary for life originated . The
Miller experiment was a watershed, and it began a new era of
experimentation and analysis of possible primordial components.
Coupled with this, were the new important discoveries by
astrophysicists of the presence of organic molecules in the
interstellar medium and in meteorites. In a review of origin of
life theories, P. Radetsky (Univ. of California Santa Cruz, US)
points out that the Miller theory is no longer the consensus
theory, that contemporary geologists believe the primordial
atmosphere consisted primarily of carbon dioxide and nitrogen,
which are less reactive than the gases in the Miller experiment,
and that the field is currently embroiled in controversy fueled
for the most part by an absence of hard fact. QY: Peter Radetsky,
Univ. of California Santa Cruz 408-429-4008 (Earth February
1988)

(continued in Part 2)

=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=

SCIENCE-WEEK - Part 2

A Free Weekly Digest of the News of Science

January 2, 1998

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Contents of Part 2:

10. Virtual Symbiosis in Higher-Order Peptide Self-Replication
11. Enzyme Optimization by Test-Tube Evolution
12. Synthesis of Peptides Without Formation of Peptide Bonds
13. Mechanism of RNA Polymerase Nucleosome Transcription
14. Crystal Structure of a G Protein Complex
15. Details of Dynein Motor Domain Mechanisms
16. Complete Genome Sequence of Lyme Disease Pathogen
17. Regeneration of Motor Neurons: Identification of a Mitogen
18. Synchronization and Rate Modulation in Motor Cortex Neurons
19. Inhibition of Kaposi's Sarcoma by Ribonuclease
20. Cumulative Medical Impact of Sustained Economic Hardship

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

10. VIRTUAL SYMBIOSIS IN HIGHER-ORDER PEPTIDE SELF-REPLICATION
In biology, symbiosis is an intimate and protracted association
of individuals of different species, and mutualism is a type of
symbiosis in which both participants receive benefits from the
association. The two terms are sometimes used interchangeably,
with symbiosis referring to a mutually beneficial association.
The concept of a "hypercycle" was first formulated by Manfred
Eigen (in collaboration with P. Schuster) 20 years ago. A
hypercycle is essentially an interrelationship of two or more
self-replicating molecular species interlinked through a cyclic
catalytic network. In a bipartite arrangement, for example, self-
replicating molecule A may produce as a by-product X, and X
catalyzes the self-replication of B, which produces the by-
product Y, and Y catalyzes the self-replication of A, and so on.
Many permutations of the idea are possible, and if one considers
the bipartite arrangement outlined above as a single system, it
is evidently a higher-order single system that is reproducing via
autocatalysis. In the replication of biological macromolecules,
genotypic replication refers to the genomic replication of DNA
and RNA, while phenotypic replication refers to the replication
of the proteins said to be "expressed" by the genomic elements
(genes), i.e., the expression of the nucleic acid information.
Lee et al (Scripps Research Institute, US) report a chemical
system that is an apparent example of a minimum hypercyclic
network, the system involving two otherwise competitive self-
replicating peptides "symbiotically" catalyzing each other's
production. The authors suggest this example of a hypercyclic
peptide network supports the idea that peptides could play a role
in early darwinian evolution involving selection based on
feedback processes of genotypic replication, and that molecular
genotypes and phenotypes may have been the same molecules.
QY: M. Riza Ghadiri  (Nature 11 Dec 97)

11. ENZYME OPTIMIZATION BY TEST-TUBE EVOLUTION
In chemistry, an enantiomer is a compound whose structure is not
superimposable on its mirror image, the compound being one of a
pair of optical isomers, each of which interacts differently with
polarized light (i.e., shows optical activity). A mixture of two
optical isomers in equal amounts is called a racemic mixture, and
racemic mixtures do not show optical activity. A reactant or
process that produces selects an enantiomeric excess is simply a
reactant or process that produces or selects one enantiomer in
excess over the other enantiomer. Hydrolysis is a reaction
between a compound and water, for example, the salt of a weak
acid reacting with water to form a base and the acid. A lipase is
an enzyme that acts upon the fatty acid esters of glycerol, the
triglycerides, diglycerides, and monoglycerides.  Polymerase
chain reaction (usually denoted as PCR) is a synthetic method
allowing bulk replication of minute quantities of a chosen
segment of a nucleic acid to take place accurately and effic-
iently in vitro. Combinatorial testing is an automated technique
used in combinatorial chemistry to screen large numbers of
compounds involving structural permutations for specific
properties. M. Reetz et al (Max Planck Institute for Coal
Research, DE; Univ. of Bochum, DE) report the creation of an
enantioselective enzyme by evolution in a test-tube. The work
involved the hydrolysis of racemic p-nitrophenyl 2-methyldecan-
oate, starting with a lipase that produced only 2% enantiomeric
excess, then subjecting the enzyme gene to error-prone polymerase
chain reaction to obtain 1000 mutants for combinatorial testing.
After 4 generations of the mutation process, they obtained an
enzyme that produced 81% enantiomeric excess. QY: Manfred T.
Reetz, Max Planck Inst. Coal Res., Mulheim, DE (Angew. Chem. Int.
Ed. Engl. 36:2830 1997)

12. SYNTHESIS OF PEPTIDES WITHOUT FORMATION OF PEPTIDE BONDS
Amino acids are the building blocks, the monomers, from which all
proteins and other polypeptides are assembled, and polypeptide is
merely a generic term for a polymer composed of amino acids
linked by peptide bonds. A peptide bond, the bond linking two
adjacent amino acids in a chain, is formed by the reaction
between the carboxyl group on one amino acid and the amino group
on the adjacent amino acid. An amide of an amino acid is any
compound obtained by substitution of an -NH(2) group for the -OH
group of the amino acid. Moody et al (Univ. of Exeter, UK) now
report a technique for synthesis of polypeptides without de novo
formation of peptide bonds. The technique involves the prepar-
ation of dihydropeptides by insertion of an acid residue into a
nitrogen-hydrogen bond of the amide of a nitrogen-protected amino
acid. Synthetic chemists apparently believe the method may be
important for drug design, particularly for the combination of
natural with non-natural amino acids in small polypeptides. QY:
Christopher J. Moody, Univ. of Exeter, UK (Chem Commun.
1997:2391)

13. MECHANISM OF RNA POLYMERASE NUCLEOSOME TRANSCRIPTION
Transcription is the process by which genetic information in DNA
is converted into RNA, and RNA polymerase is an enzyme that
polymerizes ribonucleoside triphosphates into RNA in the order
dictated by a DNA or RNA template. RNA polymerases are found in
all living cells, with one type found in prokaryotes (cells
without a cell nucleus and other membrane-bound organelles), and 
3 types found in eukaryotes (cells with a cell nucleus). RNA
polymerase type III is specific to transfer RNA (tRNA) and
ribosomal RNA (rRNA). Transfer RNA is a class of small RNA
molecules that transfer individual amino acids to a growing
polypeptide chain during protein synthesis, and ribosomal RNA is
a class of RNA molecules that have an important role in the
structure of ribosomes, the large molecular entities that carry
out protein synthesis in all cells. All the RNA polymerases are
large and complex molecules with molecular weights of approx-
imately 500,000 daltons. Nucleosomes are higher order structures
of eukaryotic chromosomal DNA, the structures composed of coils
of the DNA double helix around a complex of 8 small basic
proteins called histones. Studitsky et al (4 authors at 2 instal-
lations, US) report that the large yeast RNA polymerase III
transcribes through a single nucleosome, with direct internal
nucleosome transfer in which histones never leave the DNA
template. The authors suggest their results show that a eukary-
otic polymerase is capable of transcribing through a nucleosome
without displacing it from the template, and that this ability
may reflect a property of importance for the transcription
process in vivo. QY: Gary Felsenfeld, US Nat. Inst. of Health,
Bethesda, MD 20892-0148 (Science 12 Dec 97)

14. CRYSTAL STRUCTURE OF A G PROTEIN COMPLEX
ATP (adenosine triphosphate) is the most important chemical
energy source in all living cells, intimately involved in various
cell functions and cell metabolism, and an entity in numerous
cyclic chemical pathways involved in the synthesis of components.
One of the reaction products of ATP is cAMP (cyclic AMP, or
adenosine 3,5-monophosphate), which acts as an intracellular
hormone (i.e., a chemical messenger). Cyclic AMP is derived from
ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also
called adenyl cyclase and adenylate cyclase). Cyclic AMP is
called the second messenger; the first messenger is the hormone
that interacts with its receptor on the cell surface. G-proteins
are a family of signal-coupling proteins that act as intermed-
iaries between activated cell receptors and effectors, for
example, the transduction of hormonal signals from the cell
surface to the cell interior, and certain G-proteins are known to
interact with adenylyl cyclase. The G-protein is apparently
embedded in the cell membrane with parts exposed on the outside
surface and inside surface. The outside moiety is activated by
the first messenger, and the inside moiety activates the second
messenger, the G-protein thus acting as a trans-membrane signal
transducer. Forskolin is a diterpene that apparently activates
various isoforms of adenylyl cyclase. Tesmer et al (4 authors at
Univ. of Texas Southwestern Medical School) report the crystal
structure of a soluble catalytically active form of adenylyl
cyclase in complex with its G protein subunit and forskolin to a
resolution of 2.3 angstroms. The active site of adenylyl cyclase
was located and substrate elements important for substrate
recognition were identified. The authors discuss in detail
possible molecular mechanisms for the activation of adenylyl
cyclase by its G protein subunit as suggested by the structural
analysis. QY: Stephen R. Sprang 
(Science 12 Dec 97)

15. DETAILS OF DYNEIN MOTOR DOMAIN MECHANISMS
Microtubules are part of the cytoskeleton of biological cells,
the quasi-rigid matrix that among other things determines cell
shape. The microtubules are 25 nanometers in diameter, and
composed of the protein tubulin. They occur in regular arrays in
cilia, flagella, the mitotic spindle, and in the cytoplasm in
general, and they contribute not only to cell shape, but also to
cell motility. Microfilaments are 4 to 6 nanometers in diameter,
highly variable in length, and are found in all eukaryotic cells.
They are composed of a protein called "actin" and several other
accessory proteins, and they are important in cell locomotion and
in the molecular dynamics of muscle cells. "Motor proteins" are
mechanico-chemical enzymes involved in locomotion or transport,
and there are three families of such proteins: kinesins, dyneins,
and myosins. Kinesins and dyneins are microtubule based motor
proteins, while myosin is a microfilament based motor protein. In
general, as mechanico-chemical enzymes, motor proteins convert
energy from hydrolysis of nucleotides to mechanical force, and
since they are involved in many important cellular events, the
molecular details are currently the focus of intensive research. 
Gee et al (3 authors at 3 installations, US) report that the
entire carboxy-terminal two-thirds of the 532K dalton force-
producing heavy chain subunit of dynein is required for ATP-
binding activity. They have also identified a distal microtubule-
binding domain that apparently forms a hairpin-like stalk. The
authors suggest the mechanism for dynein force production differs
substantially from that of other motor proteins.
QY: Richard B. Vallee  (Nature 11 Dec 97)

16. COMPLETE GENOME SEQUENCE OF LYME DISEASE PATHOGEN
Lyme disease is caused by a spirochete bacterium, Borrelia
burgdorferi, a spirally coiled organism in which 2 to 100
flagella (contractile strands that are responsible for bacterial
motion) are wound beneath a flexible outer cell wall, enabling
the spirochete to move by rhythmic flexing that causes a cork-
screw motion through the surrounding medium. The pathogen that
causes syphilis is also a spirochete. In humans, Lyme disease is
contracted through the bite of small ticks such as the minute
tick Ixodes dammini. The disease was first recognized in 1975 as
a result of an unusual clustering of cases in the small community
of Lyme, Connecticut (US), and hence the name. It has since
appeared in more than half the states in the U.S., especially the
northeastern coast, and in California and Oregon, and it has also
appeared abroad. In the U.S., 18,461 cases of Lyme disease were
reported in 1996, a 41% increase over 1995. This disease is now
the most commonly reported tick-borne illness in the U.S., and it
is an insidious pathological entity that if not treated early may
lead to severe arthritis, various serious neurological complic-
ations when the organism invades the central nervous system, and
in some cases death. Plasmids are small, often circular, extra-
chromosomal genetic entities that replicate independently of
nuclear DNA. They are common in bacteria and in certain eukary-
otes. Translation is protein synthesis, the process during which
polypeptides are synthesized on ribosomes. Fraser et al (38
authors at 3 installations, US) now report the complete genome
sequence of B. bergdorferi, the pathogen that causes Lyme dis-
ease. The genome is comprised of a linear chromosome containing
910,725 base pairs plus at least 17 linear and circular plasmids
with a combined 533,000 base pairs. The chromosome contains 853
genes encoding a basic set of proteins for DNA replication,
transcription, translation, solute transport, and energy metabol-
ism, but no genes for cellular biosynthetic reactions. Of 430
genes on 11 plasmids, most have no known biological function. The
authors suggest this elucidated genome sequence will provide a
new starting point for the study of the pathogenesis, prevention,
and treatment of Lyme disease. QY: Claire M. Fraser
 (Nature 11 Dec 97)

17. REGENERATION OF MOTOR NEURONS: IDENTIFICATION OF A MITOGEN
Motor neurons are nerve cells that transmit nerve signals from
the brain or spinal cord to muscle or gland tissue, and sensory
neurons are nerve cells that carry signals from various parts of
the body to the brain or spinal cord. High signal propagation
velocities in motor and sensory neurons in vertebrates are
achieved by association of the nerve fiber with an enfolding
sheath called myelin. The myelin sheath consists of concentric
layers of electrically insulating lipid material, but the sheath
is periodically interrupted, and at the points where the sheath
is interrupted so is the electrical insulation interrupted. The
result, predictable from the classical physics of electrical
transmission lines and the electrical parameters of nerve fibers,
is that the propagation of an electrical pulse along such nerve
fibers occurs at a velocity much higher than that found in
unmyelinated fibers. Glial cells are the cells of the central and
peripheral nervous system that produce the multiple membrane
layers called myelin and enfold nerve cell axons with it, and
Schwann cells are a particular type of glial cell. A mitogen is
any compound that stimulates mitotic cell division. Livesey et al
(6 authors at 3 installations, UK CA) report the identification
of an extracellular signaling molecule, previously described as
the pancreatic secreted protein Reg-2, that is expressed solely
in regenerating and developing rat motor and sensory neurons,
with Reg-2 a potent Schwann cell mitogen in vitro. In vivo, Reg-2
is apparently transported along regrowing axons, and inhibition
of Reg-2 significantly retards the regeneration of axons
containing the protein. The authors suggest that Reg-2 is an
essential component of the neuron-glia interactions underlying
development and regeneration of mammalian motor neurons.
QY: Frederick J. Livesey 
(Nature 11 Dec 97)

18. SYNCHRONIZATION AND RATE MODULATION IN MOTOR CORTEX NEURONS
Cognitive motor processes are task-oriented behaviors involving
voluntary muscle movements, for example, the deliberate reaching
out for and lifting of an object in response to a stimulus. In
the mammalian brain, the primary motor cortex is the area of the
cerebral cortex containing nerve cells and neural circuits
responsible for voluntary movement, the signaling to peripheral
muscles involving the propagation of electrical changes (action
potentials) the length of long nerve fibers from the brain to the
spinal cord. The neurons of the motor cortex are themselves
responding to inputs of action potentials from neurons elsewhere
in the brain, so the output of the motor cortex is a result of
complex interactions of neurons within the motor cortex and of
these neurons with neurons outside the motor cortex. Since it is
possible to fix electrodes in the motor cortex and record the
local electrical activity of nerve cells in that region, there
has been extensive research to delineate the interactions between
motor cortex neurons and the relation of these interactions to
behavior. Two important parameters in this context are the
discharge rate of action potentials by neurons and the degree of
synchronization of activity of connected nerve cells. Riehle et
al (4 authors at 3 installations, FR IL DE) report that simultan-
eous recording of neuron activity in primary motor cortex of
monkeys during task performance reveals context dependent rapid
changes in patterns of coincident action potentials. Spike
synchronization and discharge rate modulations occur in relation
to external events, but the latter are not precisely time-locked.
Spike synchronization also occurs in relation to internal events
(stimulus expectancy) where firing rate modulations are absent.
The authors suggest their findings indicate that internally
generated synchronization of individual spike discharges may be
involved in the cortical organization of cognitive motor
processes. QY: Alexa Riehle 
(Science 12 Dec 97)

19. INHIBITION OF KAPOSI'S SARCOMA BY RIBONUCLEASE
Ribonuclease (also called RNase), found in all living systems, is
a family of enzymes that degrade RNA (ribonucleic acid) by catal-
yzing the hydrolysis of the sugar-phosphate bonds in the RNA
backbone. Chorionic gonadotropin is a hormone secreted by the
placenta of higher mammals, and its detection in urine is a
common pregnancy test. Kaposi's sarcoma is an ordinarily rare
cancer that can be common in humans with compromised immune
systems (for example, in AIDS). Apoptosis is programmed cell
death produced by control mechanisms designed to destroy
defective cells. Griffiths et al (3 authors at 2 installations,
UK) now report the purification of a ribonuclease from a
commercial human urinary chorionic gonadotrophin, with the pure
enzyme killing Kaposi's sarcoma cells in vitro, apparently by
apoptosis. The authors suggest that effects of commercial human
chorionic gonadotrophin on these cancer cells and tumors may be
partly due to ribonuclease present as a contaminant in these
preparations. They also suggest it may be possible to exploit the
anti-neoplastic properties of this enzyme in the treatment of
AIDS-related Kaposi's sarcoma and other tumors.
QY: David J. Adams  (Nature 11 Dec 97)

20. CUMULATIVE MEDICAL IMPACT OF SUSTAINED ECONOMIC HARDSHIP
Although it has been generally recognized that a correlation
exists between economic hardship and health, the existing data is
a result of correlation studies at one particular time, and
apparently no studies have been reported to show a correlation of
poor health with sustained economic hardship in individuals.
Lynch et al (3 authors at 2 installations, US), in a study of
1100 people with a median age of 65 years in 1994, with income
information collected in 1965, 1974, and 1983, now report that
after adjustment for age and sex, there is a significant assoc-
iation between sustained poverty level and all measures of
functioning except social isolation. The authors conclude that
sustained economic hardship leads to poorer physical, psycholog-
ical, and cognitive functioning, and they suggest that increases
in economic inequality that push large proportions of the popul-
ation into low-income groups may have serious short-term and
long-term health consequences. QY: John W. Lynch, Univ. of Mich-
igan, Dept. of Epidemiology 313-764-7433
(New England J. Med. 25 Dec 97)

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

BOOK NOTES

G. Burbridge, A. Sandage, F. Shu (eds.):
ANNUAL REVIEW OF ASTRONOMY AND ASTROPHYSICS
1997 Volume 35
Annual Reviews, 1997, 699p, US70
16 reviews by experts in the various fields. Eta Carinae, high-
velocity clouds, compact galaxy groups, active galactic nuclei,
very low mass stars, etc. Required reading for all specialists
and graduate students, the Annual Reviews in all the scientific
disciplines have been unmatched in importance for the past 50
years.

J. Cruse and R. Lewis: ATLAS OF IMMUNOLOGY
CRC Press, 1997, 352p, US69.95
A pictorial reference containing more than 1000 illustrations.
Designed for students, basic scientists, and clinicians.
Historical figures, cytokines, histocompatibility complex
molecules, immunoglobulins, transplantation, autoimmunity,
antigen presentation, the T-cell receptor, etc. The focus is on
visual presentation of information.

George Greenstein: PORTRAITS OF DISCOVERY
Profiles in Scientific Genius
Wiley, 1997, 232p, US24.95
Rambling personal profiles of ten "enigmatic" scientists.
Feynman, Boltzmann, Gamow, Payne-Gaposchkin, Alvarez, etc.
Discussions range from Richard Feynman's bongo drums and sex life
to Ludwig Boltzmann's manic-depression and suicide. The author
is
an astronomer at Amherst College.

George E. Harlow (ed.): THE NATURE OF DIAMONDS
Cambridge Univ., 1997, 224p, US74.95, paper US29.95
This is a large-format show-and-tell type book, but the articles
are by experts and cover the subject: geology, gemology, physics,
culture, economics, technology, the history of diamond mining,
diamond rushes, etc. An authoritative illustrated summary.

P. Lloyd-Williams, F. Albericio, and E. Giralt:
CHEMICAL APPROACHES TO THE SYNTHESIS OF PEPTIDES AND PROTEINS
CRC Press, 1997, 304p, US89.95
A reference compendium for organic chemists. Descriptions of
state of the art methods for synthesis of natural and artificial
large peptide and protein molecules. Introduction to basic
topics, solid-phase peptide synthesis, peptide synthesis in
solution, convergent approaches, formation of disulfide bridges,
peptide libraries.

W. Wu, M. Welsh, P. Kaufman, and H. Zhang:
METHODS IN GENE BIOTECHNOLOGY
CRC Press, 1997, 416p, US79.95
Underlying principles, latest techniques and methods,
applications, protocols, trouble-shooting guides, etc. For anyone
working with genes who needs a source of current biotechnology
methods. 18 chapters and an index.

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