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Also in this issue:• Adaptive Optics Bring the Cosmos into Sharper Focus• Solving the Mystery of Comet X-Ray Emissions• 50th Anniversary Highlight: The Enduring Contributionsof Chemistry and Materials ScienceLivermore bioscientists are designing
synthetic molecules known as high-affinity
ligands that bind strongly to the proteins ofpathogens. These new molecules will be used to
identify biowarfare agents and, when armed witha radionuclide, have potential applications forfighting cancer. On the cover, synthetic chemist
Julie Perkins develops a two-pronged moleculethat will bind securely to a specific toxin protein.
In the background is a simulation of a
Clostridium neurotoxin tetanus protein, one of
the biowarfare agents that high-affinity ligands
will be used to identify. The article reporting on
this new approach to fighting bioterrorism anddisease begins on p. 4.

About the Review
Lawrence Livermore National Laboratory is operated by the University of California for the
Department of Energy’s National Nuclear Security Administration. At Livermore, we focus science andtechnology on assuring our nation’s security. We also apply that expertise to solve other importantnational problems in energy, bioscience, and the environment. Science & Technology Review is published
10 times a year to communicate, to a broad audience, the Laboratory’s scientific and technologicalaccomplishments in fulfilling its primary missions. The publication’s goal is to help readers understandthese accomplishments and appreciate their value to the individual citizen, the nation, and the world.
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S

National Nuclear Security Administration••

Prepared by LLNL under contract
No. W-7405-Eng-48

This document was prepared as an account of work sponsored by an agency of the United States Government. Neither
the United States Government nor the University of California nor any of their employees makes any warranty,
expressed or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any
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Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, orotherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States
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product endorsement purposes.

Cover design: George Kitrinos

About the CoverJune 2002
Lawrence
Livermore
National
Laboratory

Contents
S&TR Staff

FeaturesSCIENTIFIC EDITOR
Kimberly S. Budil

3 Fighting Bioterrorism, Fighting Cancer

MANAGING EDITOR
Ray Marazzi

4

PUBLICATION EDITOR
Dean Wheatcraft
WRITERS
Arnie Heller, Ann Parker,
Katie Walter, and Dean Wheatcraft
ART DIRECTOR AND DESIGNER
Lew Reed

Commentary by Bert Weinstein

A Two-Pronged Attack on Bioterrorism
Synthetic two-legged molecules will be excellent
detectors of biowarfare agents and cancer cells.

12 Adaptive Optics Sharpen the View
from EarthAstronomers are obtaining images with
unprecedented resolution, thanks to telescopes
equipped with adaptive optics developed at
Livermore.

INTERNET DESIGNER
Kitty Tinsley
COMPOSITOR
Louisa Cardoza
PROOFREADER
Carolin Middleton

S&TR, a Director’s Officepublication, is produced by theTechnical Information Department
under the direction of the Office of
Policy, Planning, and Special Studies.
S&TR is available on the Web
at www.llnl.gov/str/.

Printed in the United States of America
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National Technical Information Service
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Distribution Category UC-99
June 2002

Research Highlight
20 Experiments Re-create X Rays from Comets
Experiments using the Laboratory’s electron
beam ion trap and an x-ray spectrometer
designed by the National Aeronautics andSpace Administration are shedding light on
how comets emit x rays as they pass the Sun.

50th Anniversary Highlight
24 Chemistry—50 Years of Exploring
the Material World
From isotopic analysis to atomic-level simulationsof material behavior, Livermore’s chemists andmaterials scientists apply their expertise to fulfill
the Laboratory’s mission.

Departments
2 The Laboratory in the News
31 Patents and Awards
33 Abstracts

2

The Laboratory in the News

S&TR June 2002

Stroke treatment by wire
A springy plastic wire that changes shape at the flick of a switch
could provide a safer treatment for strokes caused by blood clots.
Developed by engineers at Livermore, the wire, made from shapememory polymer, will allow surgeons to remove blood clots fromthe brain without using potentially dangerous clot-busting drugs.
The shape-changing wire is made from two types ofpolyurethane bundled into one. One type is harder than the other.
Team member Duncan Maitland explains that the wire’s main
body is constructed from the softer material, with chunks of theharder material distributed though it.
The wire is first heated to allow both its hard and softcomponents to become malleable. The end of the wire is thentwisted into a coil and cooled, fixing the shape of the coil into thepolymer. Next, the wire is reheated but to a lower temperaturethan it was initially, so that only the softer part is deformed. The
coil is pulled to straighten it and then cooled again to harden it. It
becomes too rigid to spring back into the coiled shape. However,when heated again to 60°C, the plastic softens sufficiently for theend of the wire to spring back into a coil.
Maitland and his colleagues have tested their invention by
conducting in vitro experiments using pig’s blood. They fixed thewire to the end of an optical fiber and inserted both into a narrowcatheter. They speared a clot with the wire, withdrew the catheter,
and heated the wire with infrared light transmitted through thefiber. “The wire changed into a coil in a fraction of a second,”says Maitland. It grips the clot from behind, and the clot is pulled
out with the wire.
Contact: Duncan Maitland (925) 423-6697 (maitland1@llnl.gov).

New combustion method lowers power plant emissions
Livermore engineers have developed a unique combustion
method that combines staged combustion with nitrogen-enriched
air to lower power plant pollutant emissions.
The new technology, called staged combustion with nitrogenenriched air (SCNEA), could help power plants comply withstrict Environmental Protection Agency (EPA) requirements for
decreasing power plant emissions. “As EPA requirements becometighter and tighter on emissions, most solutions become moredifficult and more expensive to implement,” says Larry Fischer,principal investigator for SCNEA. “With our technology,
consumers will see cleaner air at a miniscule increase in theirutility bills.”
Before concerns about oxides of nitrogen (NO and NO2, often
called NOx) and their relationship to photochemical smog and acidrain arose in the late 1980s, power plants typically burned fuel inboilers and furnaces with single-stage combustion using air as theoxidant. Today, NOx emissions are regulated under provisions of
the Clean Air Act and its amendments. Those regulations will
become tougher by 2005, which means that the technologies used
to lower NOx emissions must be improved.

SCNEA lowers NOx emissions with a combustion methodthat burns fuels in two or more stages. In the first stage, fuel iscombusted with nitrogen-enriched air. The fuel remaining after
the first stage is combusted in the remaining stage(s) with air or
nitrogen-enriched air. This method substantially reduces NOx
emissions without significantly reducing power plant efficiency
and is applicable to many types of combustion equipment andmany types of fuels.
Livermore is working to form a consortium ofrepresentatives from the U.S. EPA, utility companies, boiler
manufacturers, emission control equipment companies, and acompany that produces nitrogen-enriched air to further develop
SCNEA. The next stage is a small-scale pilot program.
Contact: Larry Fischer (925) 423-0159 (fischer3@llnl.gov).

Laser communication link completed
A Livermore team has completed a 28-kilometer, highcapacity laser communication link between the Laboratory andMount Diablo. “This represents one of the longest terrestrial
high-capacity air-optics links in existence,” says Tony Ruggiero,principal investigator on the project to develop an opticalwireless testbed for evaluating new laser communication
technologies.
Laser communication consists of an optical system in which
information is encoded on a laser beam and transmitted to areceiver telescope. Functionally similar to radiofrequency or
microwave communications, lasers use the optical part of theelectromagnetic spectrum. The laser communication beam is
not visible or harmful in any way.
The initial Laboratory–Mount Diablo link transmitted data ata single-channel data rate of 2.5 gigabits per second—theequivalent to the transmission of 1,600 conventional T1 datalines, 400 TV channels, or 40,000 simultaneous phone calls.
The experiments are being conducted as part of the Secure
Air-Optic Transport and Routing Network (SATRN) program,which is cosponsored by the Nonproliferation, Arms Control,and International Security Directorate and Laboratory Directed
Research and Development to provide advanced technologies
for long-range laser communications.
Proliferation detection, counterproliferation, arms control,counterterrorism, and warfighting all require the timely andsecure communication of information in situations where
fiber-optic cable is physically or economically impracticaland data requirements exceed radiofrequency or microwave
wireless capacity.
Ruggiero says that the next challenge for the SATRN team istransmitting data long distances for longer periods of time toestablish a solid baseline for the availability, accessibility, andacceptability of the system’s single-channel long-range link
performance.
Contact: Tony Ruggiero (925) 423-1020 (ruggiero1@llnl.gov).

Lawrence Livermore National Laboratory

Commentary by Bert Weinstein

3Fighting Bioterrorism,
Fighting Cancer
T

HE anthrax attack last fall spotlighted the need for fast,accurate, inexpensive methods to detect weapons ofbioterrorism. Fortunately, long before this attack, Livermore
was a leader in developing innovative methods andtechnologies for early detection of bioterrorism threats. Since
the attack, the Laboratory has intensified its efforts in this area
vital to national security. This month’s issue of S&TR features
Livermore’s leading-edge biotechnology research withimmediate applications for detecting the agents of bioterrorism
and long-term possibilities for fighting disease, especiallycancer.
Pathogens can be detected in two basic ways: look for their
DNA, the genetic blueprint for the organism, or look for theprotein building blocks that are generated from this genetic
blueprint and make up the structure and machinery of theorganism.
Lawrence Livermore is well known for its DNA detection
capabilities. For the past decade, we have been developing
both the technologies and science for fast, accurate detection
and characterization of bioterrorism pathogens from their
DNA. We have licensed a series of technologies to industry,
most recently the Handheld Advanced Nucleic Acid Analyzer.
Our DNA analysis capabilities were deployed at the 2002
Winter Olympics as the analysis core of the Bological Aerosol
Sentry and Information System used for air-monitoring.
These DNA detection methods are highly sensitive andspecific but require skilled personnel and sophisticatedequipment to deploy them. As the article beginning on p. 4
reports, Livermore is also developing protein detection
methods to identify pathogens. As with most protein
recognition methods—home pregnancy tests, for example—our
methods will be fast and easy to use. But they must also be
more sensitive and specific than home pregnancy tests—more
like DNA detection systems. Livermore’s technique uses
carefully designed antibodylike molecules, called high-affinity
ligands, to identify pathogens. Our approach seeks to combine
the best of both worlds—fast and easy to use as well as highly
sensitive and specific.
In addition to applications in countering bioterrorism, thistool will also find widespread applications in the field of

public health. Livermore researchers have already begun todevelop a high-affinity ligand that will search out nonHodgkin’s lymphoma, a form of cancer. Cancer cells
produce specific protein building blocks that properly
designed high-affinity ligands can target. Arming theligands with radionuclides to kill the cancer cells may resultin an effective cancer treatment with minimal side effects.
Designing these high-affinity ligands draws on aspectrum of Livermore capabilities—bioscience research,high-performance computational modeling, synthesis of
new molecules, and an array of molecular diagnostics suchas nuclear magnetic resonance spectroscopy and mass
spectroscopy. The ability to bring together thesecapabilities allows us to make advances that would be
difficult or impossible anywhere other than at a national
laboratory.
This high-affinity ligand technology has many otherpotential applications. At some time in the not-too-distantfuture, doctors, other public health workers, and food safety
experts could use the same methodology to quickly detect
proteins from pathogens such as streptococcus, salmonella,flu, foot and mouth disease, and E. coli. With fasterdetection will come more timely, effective intervention andtreatment. The next generation of pathogen detectors—forfighting bioterrorism specifically and disease in general—
will likely combine DNA and protein recognition for evengreater speed and accuracy.
As part of the National Nuclear Security Administration’s
Chemical and Biological National Security Program,
Livermore has for a decade been at the forefront of research
to counter the effects of deadly weapons of biologicalterrorism. We are finding that almost every step forward inthis research produces know-how that can benefit the
everyday health of the general public. The specter ofbioterrorism is frightening, and the world is never likely tobe free of disease. Fortunately, we are finding better ways tofight both, and they often go hand in hand.
 Bert Weinstein is acting associate director of Biology and Biotechnology
Research Programs.

Lawrence Livermore National Laboratory

4

S&TR June 2002

Livermore scientists
are designing tiny
synthetic molecules
to detect biological
warfare agents andfight cancer.

N

EWLY
EWLY designed molecules thatbind to and capture biowarfare
agents are on the drawing board at
Livermore. The goal is for thesemolecules to quickly and efficiently
detect such deadly pathogens as
botulinum toxin, anthrax spores, or
smallpox. Using synthetic chemistry,scientists produce these new moleculesthat bind to unique sites on the surfaceof the toxin or organism. Their twopronged, or bidentate, structure is
critical. When a small molecule binds toa protein, the attachment is usuallyweak, and the interaction between thetwo is short-lived. If, however, two or
more small molecules that bind to theprotein are linked together, their

Lawrence Livermore National Laboratory

binding to the same protein may bethousands, even millions, of times
stronger. By targeting specific proteins,
the synthetic molecules will mimic
some of the behavior in our immune
system where antibodies recognize
molecular foreign entities in our bodies
and abnormalities such as cancer cells.
A single detector armed with manyof these synthetic targeting molecules
could simultaneously recognize an
equal number of harmful biologicalagents that might be used in a terrorist
attack. Assays using antibodies, known
as immunoassays, are widely used to
identify pathogens in the laboratory andform the basis for many biowarfare
detection systems fielded to date.

S&TR June 2002

However, only seven good antibodies
are currently available for pathogen
detection. Other detectors depend onrecognizing the bioagent’s DNA. “Butsome pathogens, such as viruses, require
human exposure to only a small numberof organisms to be acutely toxic,” says
Livermore biochemist Rod Balhorn.
“With so little DNA present in eachvirus and given the rapid variation that
occurs in the base sequences that makeup the DNA, those pathogens are
typically very difficult to detect.”
Similarly designed targeting
molecules could zero in on defective or
overactive proteins in our bodies andpoison them, just as our natural
antibodies do. These antibodylike
molecules can lock on to cancer cells orother pathogens and kill them—and only
them. By targeting unique sites on otherproteins that cause disease—for
example, the proteases that cause
inflammation in arthritis or enable HIV
to function—the synthetic molecules
would block the activity of the protein
without entering its active site. The
active site is a cavity on the surface of aprotein that is used by the protein to
perform its function. Similar active sites
can be present in many proteins, boththose that are essential to cell function
and others that cause disease.
The pharmaceutical industry has
already begun using this approach todevelop drugs that function as intended
without blocking the activity of healthy
cells or proteins. Molecules that target
unique sites on the surfaces of specificproteins may soon lead to a newgeneration of drugs that have minimalside effects.
Balhorn is leading the program at
Livermore to design synthetic molecules
for bioagent detection and cancer
treatment. He and a team of Livermore
investigators are collaborating with
scientists at Brookhaven and Sandia

Synthetic Molecules

national laboratories and the Universityof California at Davis Cancer Center.
Together, they are developing themethods needed to produce the first ofthese synthetic antibodylike molecules.
“Terminology is a little tricky,” henotes. “It is tempting to call our new
molecules ‘synthetic antibodies.’ But
we are designing small molecules thatfunction like antibodies, not large
proteins that are synthetic versions ofantibodies. So we use the term ‘highaffinity ligands’ to describe ourmolecules.”“Ligand” is a general term used todescribe a small molecule that binds toproteins or other large molecules.
The higher the affinity a ligand has fora specific protein, the more tightly itbinds to it. Research by others has
demonstrated that bidentate ligands
have a vastly increased affinity for thetarget protein, anywhere fromthousands to millions of times greater.
Polyvalent ligands—molecules that bindto multiple sites on the surface of aprotein—are observed in many
biological interactions that require very

tight binding. The seek-and-destroy
antibodies of our immune system, which
normally operate quite successfully, areone example.
“What we’re doing is searching fortwo molecules that bind to two sites
next to each other on the surface of aprotein,” says Balhorn. “Then our
synthetic chemist joins them together
using a third molecule, called a linker.
The linker must be both flexible androbust, or the new molecule will fallapart. This new synthetic ligand willthen behave pretty much like anantibody, binding tightly to the protein.”
The new bidentate molecules, called
high-affinity ligands (HALs), will haveseveral advantages over naturally
occurring antibodies. They can betotally inorganic (nonprotein) and canbe synthesized in large quantities
using methods to ensure that each batchis structurally and functionallyidentical. They will also be stable
over a long period, making themexcellent candidates for long-term
deployment in detectors for agents ofbiological warfare.

This schematic diagramshows how a linker
molecule will connect
molecules that bind to twosites on a protein. The
goal is to develop a
process for designing andproducing high-affinity
ligands for any structured
surface. When two
molecules are connectedwith a linker, they bindwith up to a million times
higher affinity than does
each molecule alone.

Lawrence Livermore National Laboratory

5

6

Synthetic Molecules

S&TR June 2002

The Toxic Targets
As bioagent detectors, HALs can be
designed to target protein toxins
produced by pathogens as well as any
major protein component of pathogenicorganisms. For the National Nuclear
Security Administration’s Chemical
and Biological National Security
Program, work is under way to develop
HALs that bind to the Clostridium
neurotoxins, which include botulinum
and tetanus, the most toxic substances
known. The Clostridium toxins attack
the central nervous system and cause
spastic paralysis in the case of tetanus
and flaccid paralysis in the case of
botulinum.
Balhorn’s team is laying the
groundwork for future development of
HALs to target the Staphylococcus
enterotoxins, which cause acuteintestinal symptoms such as those
associated with food poisoning, andricin, a residue of castor bean

processing that causes major intestinalor respiratory complications. The
body’s response to toxic quantities of
either of these substances is swift andoften fatal.
Work is also scheduled to begin in
the near future on HALs that bind toproteins in the spores of Bacillus
anthracis (anthrax) and in Yersinia
pestis (plague). Once these HALs arecompleted, efforts will focus on thenext highest priority agents: smallpox,
Francisella tularensis (a plaguelike
illness), and Brucella melitensis (anorganism whose infections, often called
Mediterranean fever, cause spontaneousabortions). Creating synthetic ligands
even for proteins with a known
structure is still a research project.
Work began in 2000, and Balhorn
estimates that high-affinity ligands
for these eight bacterial toxins andthreat organisms can be delivered inabout 2005.

Catalytic domain

Targeting domain

Clostridium
neurotoxins havethree parts: thetargeting domain and thetranslocation domain, which together
make up the heavy chain, and thecatalytic domain, which makes up the light chain
and is the toxic part of the molecule.

Translocation domain

Lawrence Livermore National Laboratory

Got Structure?
If the structure of the target protein is
known, the team uses that structure todevelop a HAL. Work on thesemolecules is a logical progression from
Livermore’s protein structure andcomputational biology effort, withwhich Balhorn has been involved since
its inception. (See S&TR, April 1999,
pp. 4–9.) Using x-ray crystallography
and nuclear magnetic resonance (NMR)
spectroscopy, high-resolution structures
for many proteins have been determinedat laboratories around the world,
including Livermore. These include
several types of Clostridium toxins(botulinum and tetanus) and the
Staphylococcus enterotoxins.
All toxins in the Clostridium family
have three parts. The targeting (orbinding) domain, which binds toreceptor molecules on the nerve cell
membrane, and the translocation
domain, which makes a pore in the cellthrough which the toxin passes, together
make up what is known as the heavy
chain. The light chain, which contains
the catalytic domain, is a protease that is
injected into the nerve cell and disrupts
its functioning.
For the Clostridium neurotoxins, theteam is developing a HAL to bind to thetargeting domain, that fragment of theprotein that recognizes and binds tomotor neurons. Of these neurotoxins,
botulinum is considered a greater threat
than tetanus, but tetanus is easier towork with. Fortunately, its targetingdomain is sufficiently similar in
structure to botulinum’s that it serves asa model for botulinum.
In 1998, Livermore’s x-ray
crystallography group completed a highresolution structure of the binding domainof the tetanus toxin. Researchers thencomputationally calculated the molecularsurface of the protein to identify sites
where binding is likely to occur. “We look

S&TR June 2002

for pockets on the surface of the folded
protein, places where another moleculewould be able to fit tightly,” says
computational chemist Felice Lightstone.
For the tetanus toxin, Lightstone found two
appropriate sites adjacent to one another on
the binding domain.
For a HAL to be effective, the sites
designated for binding must be on a partof the toxin that is “conserved,” meaningthat these regions remain essentially
identical across all strains of a toxin.
When bioagents are being geneticallyengineered, areas such as these are
difficult to modify without altering thetoxicity of the agent. Ideally, a highaffinity ligand for tetanus toxin will beable to recognize engineered and otherunknown or related Clostridium toxins.
The next step involved selecting
compounds that might fit into the twosites. All of the 300,000 compounds in
the Available Chemicals Database, alisting of all commercially available
compounds, were computationallyinserted (docked) into each site. The
potential fit and interactions were thenassessed. The top 1,000 compounds
were run again using a range of(a)Synthetic Molecules

structures for each compound
representing the different bondorientations and shapes, known as
conformations, that each molecule islikely to adopt. In this manner, the top
100 compounds were identified. The
calculations for each site took about
3 weeks on a Linux cluster of 40 dualprocessor personal computers.
Sandia National Laboratories inLivermore has recently written new
programs to expedite this timeconsuming process. Each compound istested in 10 different conformations to
see which fits best into the rigid
protein. This provides a more realistic
test of binding, because many of thesesmall molecules are not rigid and canadopt different conformations.
“Computational docking projects
typically have success rates ofanywhere from 10 to 40 percent,” says
Lightstone. “Even before we started
using our new version of this program,
our success rate of identifying
molecules that actually bind to theprotein was in the 40- to 65-percent
range. Now, the likelihood of getting a
fit may be even greater.”Into the Laboratory
Once possible ligands have been
identified computationally, they must
be tested in the laboratory to see
whether binding actually occurs.
Mass spectrometry (MS) and NMR
spectroscopy are both effective fortesting ligand–protein binding.
NMR examines binding in the solution
state, while MS looks at binding in
the gas phase. MS typically requires
much smaller samples, but it
cannot handle certain compounds or
chemical buffers. NMR can examine
mixtures of compounds moreeasily and determine which
combinations bind best in solution.
Both techniques can identify whereon the target protein binding isoccurring.
The initial computational screening
process to find new compounds thatbind to tetanus neurotoxins resulted in
100 possible ligands that were predicted
to bind to one of two sites (site 1 andsite 2) on the tetanus neurotoxin’s
targeting domain. Experiments
using electrospray ionization–massspectrometry (ESI–MS) suggested that(b)

Site 1Site 2(a) The x-ray crystal structure for the tetanus toxin showing how the amino acid chain is folded and (b) its calculated molecularsurface showing sites 1 and 2, predicted binding sites for ligands.

Lawrence Livermore National Laboratory7

8

Synthetic Molecules

S&TR June 2002

The predicted structure of the tetanus–lavendustin A complex. Lavendustin A is shown in purple
binding to site 2.

7 of the first 13 tested compounds boundto the toxin. With ESI–MS, ligand
binding is confirmed when a new mass
peak appears at the expected mass-tocharge ratio for the ligand–tetanus
complex.
The antitumor drug doxorubicin was
discovered to be the best fit at site 1.
The binding of this ligand to site 1 waslater confirmed by x-ray crystallographyof doxorubicin–tetanus toxin anddoxorubicin–botulinum toxin complexes.
For site 2, the same MS method wasused to screen 1 of 100 compounds, sixof which were observed to bind. The
figure above shows one of these ligands,
lavendustin A, docked into site 2 in thepredicted structure of the tetanus–
lavendustin A complex.
The six ligands predicted to bind tosite 2 were then screened for binding to
the targeting domain using NMR. The
six molecules were tested individually,
as mixtures of different combinations of
the compounds, and in the presence orabsence of the known site 1 binder,
doxorubicin.

When examined by NMR, small
molecules exhibit weak, negative
signals referred to as NOEs (nuclear
Overhauser effects). Large molecules
such as proteins exhibit strong, positive
NOEs. When small molecules bind toproteins, the characteristics of the NOE
for the large molecule are transferred tothe small molecule. Thus, strong NOEs
are detected for ligands that bind to
the protein.
The NMR screening of mixturescontaining the six predicted site 2
ligands confirmed that four bind totetanus toxin in solution. Using a noveltransfer NOE (trNOE) competition
assay, researchers have determined thatthree of these ligands bind in the same
site, presumably at site 2. The fourth
ligand was determined to bind in a thirdsite distinct from site 1 and site 2.
NMR experiments were also
performed to evaluate how possible
structural changes induced by thebinding of one ligand in site 1 could
influence the binding of the second
ligand in another site. In these

Lawrence Livermore National Laboratory

experiments, doxorubicin, which wasadded first, remained bound to site 1
throughout the additions of all six ofthe predicted site 2 ligands. The
mixture containing doxorubicin andlavendustin A produced the strongest
positive trNOE signal in the presenceof the tetanus toxin. This experimentconfirmed that both lavendustin A anddoxorubicin bind simultaneously tothe toxin, indicating that each mustbind to a different site.
“Unfortunately, this assay cannot
define the location of the binding
site,” says physical chemist Monique
Cosman, leader of the NMR group at
Livermore. “But since doxorubicin is
known to bind to site 1, we know thatlavendustin A must bind to a different
site, which may be site 2.
By performing these trNOE binding
experiments with pairs of moleculesthat were determined to compete forbinding to the same site, Cosman
developed a new NMR method for
identifying the relative strength ofbinding of each ligand to a particularsite on the protein. MP-biocytin,
another molecule that binds to site 2,
did so with a relatively lower affinity
than lavendustin A. The affinity of thethird ligand is similar to that oflavendustin A, but it was not studied
further because it is too perishable.
Mass spectrometry was then used toverify where the molecules arebinding. Chemist Sharon Shields
developed a new method thatcombines MS with proteolysis, a
process in which a protein is digested
by enzymes. “This is unique,” shenotes. “Now we can study solutionphase biological processes using a
gas-phase mass spectrometricmethod.”She first treated the targetingdomain of tetanus toxin with proteases
that make clips in the amino acidchain either alone or on the tetanus–

S&TR June 2002

doxorubicin complex using various
ratios of doxorubicin to the neurotoxin.
Then she used matrix-assisted laser
desorption ionization and ESI–MS todetermine the pattern of enzymatic
degradation that had occurred. In thetetanus–doxorubicin combinations,doxorubicin prevented the enzyme fromdigesting the protein at the binding siteby limiting access to the amino acids
located in that region.
The figure below shows a map of
peptides (amino acid chains) produced
by digesting the tetanus–doxorubicincomplex compared to the tetanus toxin
alone. In this experiment, Shields usedthe enzyme trypsin. The decreased
abundance of peptides indicates thelocation where binding is occurring.
That location contains amino acids
299–304, 351–376, and 394–434.
Molecular docking calculations had
predicted that doxorubicin would residenear amino acids 356, 358, 359, 407,
409, 419, 427, and 437. These
predictions are a close match to MS(a)Synthetic Molecules

results. Comparable locational
experiments using other enzymes had
similar results.
Shields also found that the presenceof doxorubicin induces subtle changes
in the tetanus toxin’s three-dimensional
structure, suggesting that the protein
may envelope, or wrap around,doxorubicin when it binds. Further
experiments are needed to confirm
these results.
Creating a New Molecule
Synthetic chemist Julie Perkins has
the job of linking the two molecules thatbind to sites 1 and 2 to create a new
HAL. This is the critical step. She isexperimenting with linkers that willconnect doxorubicin and MP-biocytin as
well as doxorubicin and lavendustin A.
“We know that each of these compounds
binds individually to sites 1 and 2, but
because they bind weakly, they can also
float away,” Perkins says. “When thecompounds are linked together, they aremuch more likely to stay bound.

She is starting with the amino acidlysine as a linker. Lysine is an ideal
building block because it has three
distinct functional groups upon which
she can perform synthetic chemistry
experiments. Many derivatives oflysine are commercially available aswell. The molecules that have been
identified to bind into site 1 and site 2
can either be attached directly to lysine,resulting in their close proximity, orwith a linker, which increases the
distance between them. Increasing the
distance between the two compoundswith a flexible chain may also help
increase the affinity of the ligand forthe protein.
“To achieve maximum affinity of
the ligand for the protein, we have tofind the optimal length and rigidity of
the linker,” says Perkins, “and that can
only be done experimentally.” She isexperimenting with a flexible glycol
chain that can be attached to the lysine
to increase the distance separating thetwo ligands.

(b)(a) This map of peptides (amino acid chains) compares the doxorubicin–tetanus toxin complex to the tetanus toxin alone. Amino acids in yellow
represent the peptides that showed a decreased abundance, which indicates that binding is occurring. (b) Computational docking studies
predicted that binding would occur at the location shown. The two match quite well.

Lawrence Livermore National Laboratory

9

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Synthetic Molecules

S&TR June 2002

Synthetic chemist Julie Perkins works to link two molecules, each of which binds to two protein
binding sites. The new molecule will bind more strongly and securely to a specific toxin protein
than the individual molecules can.

Targeting Cancer
For cancer therapy, the challenge isto synthesize molecules that bind withhigh affinity to each cancer cell without
themselves generating an immune
reaction from the body. Targeting
molecules therefore must be smaller
and more specific and have higher
affinities than natural antibodies. They

Once she has synthesized each newcompound containing the two linked
ligands, conventional binding studies
will identify the highest affinity andmost selective ligand combinations.
These studies will determine how
tightly the HALs bind and confirm
that they selectively bind only to
Clostridium neurotoxins.

Sites 1 and 2 on the HLA-DR10
molecule (a protein receptor for nonHodgkin’s lymphoma) have been
identified.

Site 1Site 2

Lawrence Livermore National Laboratory

should also not be made of proteins,which elicit an immune response fromthe body.
The goal is to use these small,
exceptionally high-affinity molecules
to deliver a lethal radiation dose
directly to a tumor. In this case, the
HALs would be tagged withradioactive isotopes and introduced
into the body. Research all over theworld is focused on this newtechnique, known as isotopicallyenhanced molecular targeting.
To create new HALs for cancer
treatment, Livermore is using the sameprocess developed for producing HALs
that bind to toxins and pathogens. The
first project will be a HAL for a
receptor protein found on the surface
of non-Hodgkin’s lymphoma,
HLA-DR10. The crystal structures offour HLA-DR molecules are known,
and unique binding sites on the HLADR10 protein have been identified
using computer models of the protein
generated by computational
biochemists Adam Zemla and Daniel
Barsky. Computational docking
experiments are under way.
The HAL developed for binding
HLA-DR10 and targeting human
lymphomas will be designed to rapidly
pass through the liver and kidney andthus minimize the systemic damage
that can occur when antibodies carryradionuclides. “We are striving toconvert the meaning of the word
‘cancer’ from ‘fear, pain, suffering,and death’ to ‘just another treatabledisease,’” says Balhorn.
Targets of Unknown Structure
When a target protein’s structure is
not known, the team will use a
different route to design and synthesize
HALs. Computers cannot be used to
predict the binding of molecules toS&TR June 2002

sites on these proteins. But NMR and
MS processes that are being developed
and fine-tuned now for identifying
ligands that bind to known protein
structures will identify ligands that bindto unknown structures.
Libraries of molecules will be
experimentally screened for theirability to bind to the protein using a
combination of Cosman’s NMR
technique and mass spectrometry
methods being developed by chemist
Lori Zeller. The molecules that bindwill be segregated into sets that bind todifferent sites. Perkins will thensynthesize all possible combinations ofpairs of these small molecules using aseries of different-size linkers. With
Livermore’s new Fourier transform ion
cyclotron resonance mass spectrometer,
mixtures of the HALs and protein canbe quickly screened to identify theparticular combination of ligands andlinkers that produce HALs that bind to
the protein. This approach should work
well for creating detection reagents forpathogens. In collaboration with groups
at Porton Down Defense Science andTechnology Laboratory in England,
Livermore researchers will design thefirst HAL for a protein with an
unknown structure to bind to a proteinon the coat of the anthrax spore.
Measuring Success
The Livermore team will soon
produce its first HAL for the
Clostridium neurotoxins. To knowwhether this work has been

Synthetic Molecules

Livermore will design a high-affinity
ligand to bind to protein in the spore
coat of Bacillus anthracis (anthrax).
Innermembrane

Exosporium

CortexCoats

successful—whether the ligand works
as designed in a bioagent detector—
the team will send its results to the
Department of Defense’s Critical
Reagent Program to be assessed for
quality and specificity.
In the war against bioterrorism, thebest defense begins with having thebest possible data. Work has begun on
docking studies to identify bindingsites on the light chain of botulinum
toxin. In this case, the goal is tosynthesize HALs that can distinguishbetween the different types of
Clostridium neurotoxins. That kind offine-tuning is essential for accuratebioagent detection and identification
during a crisis.
—Katie Walter

Lawrence Livermore National Laboratory

Key Words: antibodies, bioterrorism,
botulinum toxin, cancer treatment,
Clostridium neurotoxins, high-affinity
ligands (HALs), mass spectrometry (MS),nuclear magnetic resonance (NMR), protein
structure, synthetic chemistry, tetanus.
For further information contact
Rod Balhorn (925) 422-6284(balhorn2@llnl.gov).

11

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S&TR June 2002

Blur-free images reveal a wealthof astronomical detail.

F

ROM a remote outpost on thesummit of Hawaii’s dormant Mauna
Kea volcano, the world’s two mostpowerful telescopes, located at theW. M. Keck Observatory, are probing
the deepest regions of the universe.
Thanks to a Lawrence Livermore–Keckteam of scientists and engineers,
astronomers are obtaining images on the
10-meter Keck telescopes withresolution greater than that of otherland-based telescopes or even theorbiting Hubble Space Telescope.
Many of the Keck images, together
with those from the smaller Shane
telescope at the University ofCalifornia’s Lick Observatory near
San Jose, are being taken by Lawrence

Livermore astronomers working withcolleagues from University ofCalifornia (UC) campuses and theCalifornia Institute of Technology(Caltech). The images are shedding
new light on the formation of stars andgalaxies, revealing unexpected features
on planets and moons in our solar
system, and yielding new information
on black holes in the centers of distantgalaxies.
The key to the unsurpassed image
clarity is adaptive optics that remove
the blurring of starlight caused byturbulence in Earth’s atmosphere,
resulting in a tenfold improvement in
resolution. Adaptive optics measure thedistortions of light from a natural star

The W. M. Keck Observatory, located on Hawaii’s dormant Mauna Kea volcano at an altitude ofover 4 kilometers, houses the world’s two most powerful telescopes. The Keck telescopes areseen with their domes open for observation.

Lawrence Livermore National Laboratory

S&TR June 2002

or one manufactured by a powerfullaser, and then remove the distortions
by reflecting the light off a deformablemirror that adjusts several hundred
times per second to sharpen the image.
A Livermore-designed adaptive
optics system was installed on Lick’s
3-meter Shane telescope in 1994, andLivermore’s sodium-layer laser guidestar system was added in 1996. In
September 1996, Lick obtained the firstsignificant image improvement using
adaptive optics with a laser guide star.
Routine astronomical observation withthe laser guide star began in August
2001, and the guide star was turned
over to the observatory for operation inspring 2002.
Keck’s adaptive optics system, forwhich Livermore scientists andengineers working with their Keckcolleagues provided the wavefront
control system, made its firstobservations in 1998 and began generaluse in late 1999. Its laser guide star, a
Livermore–Keck project, was installedin fall 2001 and achieved “first light” on
December 23, 2001. “We asked for an
early present this year, and just before
Christmas, we were given a virtual starthat will dramatically increase theresearch capabilities of the world’s
largest telescope,” announced Frederic
Chaffee, director of the KeckObservatory. The laser guide starshould be fully integrated with theadaptive optics system by autumn 2002,
with the first astronomical observation
following shortly thereafter.

Adaptive Optics

scientist Deanna Pennington, “People
are extremely pleased with the adaptive
optics systems.”
Pennington, who served as laser guidestar project leader at both Lick andKeck, says astronomers are clamoring
to use the Keck laser guide star because“It makes possible entirely new kindsof observations that astronomers simply
couldn’t access before.”
Livermore astronomers have beenamong the first to use the adaptive optics
systems. Most of them are part of theLivermore branch of the University ofCalifornia’s Institute of Geophysics andPlanetary Physics. Since its
establishment in 1983, the Livermore
branch has been the focus of mostastronomical activities at the Laboratory.

No adaptive optics

Livermore astrophysicists Claire
Max, Bruce Macintosh, and Seran
Gibbard have been observing objects
within our solar system using both Lickand Keck adaptive optics. At Lick, they
have been aided by Livermore’s Don
Gavel, lead engineer for the adaptive
optics system. The Livermore efforts
focused on observations of Io, Jupiter’s
largest moon; Titan, Saturn’s largest
moon; the planets Uranus and Neptune;
and various asteroids.
Surprising Storms on Neptune
Astronomers using the Kecktelescopes have obtained the best
pictures yet of the planet Neptune, theeighth planet from the Sun. Thanks toadaptive optics, the images reveal aWith adaptive optics

Intensity

With adaptive optics
No adaptive optics

Exceptionally Clear Images
Astronomers are reporting
exceptional results from the adaptive
optics systems installed at the two
observatories. At Lick, roughly
50 percent of images are taken using
adaptive optics, and about half of thoseimages are made with the laser guidestar. At Keck, reports Livermore laser

Adaptive optics sharply increase the resolution of images taken at the Lick Observatory near
San Jose, California.

Lawrence Livermore National Laboratory

13

14

Adaptive Optics

wealth of small-scale features in
Neptune’s atmosphere, including
narrow, bright bands encircling theplanet, similar to those observed on
Jupiter. There appear to be waves
within the bands and regions where
the bands move apart and cometogether as if they are separated bya vortex.
The images suggest violent methanestorms with wind speeds reaching more

S&TR June 2002

than 1,770 kilometers per hour. The
imaging team, which has included
astronomers from the UC campuses at
Berkeley and Los Angeles (UCLA) andfrom Caltech, is working to understandwhat might be the source of the energy
driving the extreme weather.
Working with UC Berkeley’s Imkede Pater, the team has also captured
near-infrared pictures of the planet
Uranus, which mark the first ground-Time-lapse photograph of the Lick Observatory and the laser guide star.

(a)

(b)

(a) Astronomers using Keck’s adaptive optics have obtained the best pictures yet of the planet
Neptune. The images show bands encircling the planet and what appear to be fast-moving
storms of haze. (b) The same image without adaptive optics.

Lawrence Livermore National Laboratory

based detection of the faint rings aroundthat planet. Also clearly visible is alayer of methane haze on Uranus’s
south polar cap, tiny cloud features athigh northern latitudes, and, inside
the planet’s bright epsilon ring, three
fainter rings.
Keck images of Io have revealed
many glowing volcanoes. Macintosh
took the images in the infrared band to
detect sources of heat on the moon.
Other striking images, taken by Gavel,
are of the asteroid Kalliope with its own
moon. Gibbard has been using Keck to
obtain images of Titan, the only solid
body in the solar system besides Earthto have a substantial atmosphere (mostly
nitrogen, with about 3 percent methane).
Some astronomers believe that Titan’s
atmosphere may be similar to that ofEarth’s during our planet’s early
development. Methane haze in theupper atmosphere obscures Titan’ssurface features at visible wavelengths.
However, in some narrow “transparency
windows” in the near-infrared band,surface features can be seen throughthe haze.
Without adaptive optics, says Gibbard,“Titan looks like a fuzzy star.” She has
been analyzing a large series of images
to assemble the first map of Titan’ssurface. “By taking many images overtime, we can see which features do notchange, and these belong to thesurface,” she says. The use of adaptive
optics has replaced a process calledspeckle imaging, which involved taking
hundreds of very fast exposures andassembling them. “Adaptive optics ismuch simpler,” Gibbard says.
Imaging Stellar Nurseries
Macintosh and astronomers from
UCLA are using adaptive optics on
Lick and Keck to study the formationand evolution of planetary systems in
the Trapezium (sword) region of theconstellation of Orion. This region, theS&TR June 2002

closest large-scale star formation to ourSun, serves as a stellar nursery.
“One of the most fundamental
questions in modern astronomy is thepossibility of the existence of othersolar systems like our own, those withpotentially habitable planets,” Macintoshsays. He notes that although planetarysystems have been detected throughindirect methods, all are different fromour solar system because they havemassive, Jupiter-like planets occupying
the inner part where Earth is located inour system. “It is unclear which type ofsystem is more common in theuniverse,” says Macintosh.
The astronomers first use Lick toscout for promising young stellar
systems and then travel to Keck to
obtain high-resolution images. Brightstars found in the constellation serveas handy natural guide stars for theadaptive optics system.
Macintosh says that large planets(about the size of Jupiter) that are
10 million years old or younger radiatesignificant near-infrared light. Keck’s
adaptive optics system can detect theseplanets even though they are a million
times dimmer than the star they orbit.
Macintosh has also imaged several of
the Orion proplyds—protoplanetary
disk envelopes surrounding youngstars—that are being disrupted byintense radiation from nearby
supermassive stars.
“Keck could be the first telescope to
image a planet orbiting a star outside ofour solar system,” Macintosh says. He
adds, “Keck’s adaptive optics systemrepresents the most significant advancein astronomical capabilities since thelaunch of the Hubble Space Telescope.”
Jennifer Patience is studying thebinary star systems that are foundamong the young stars in Orion’s
Trapezium. “We want to know how
common it is for planets to form inbinary systems,” she says. Astronomers

Adaptive Optics“First light” from the laser guide star on the Keck II telescope, December 23, 2001.

believe that the presence of a nearby
companion star may disrupt
circumstellar disks surrounding youngstars (circumstellar disks provide theraw materials for planet formation).
Working with astronomers from UC
Berkeley and UCLA, she uses Keckand Lick adaptive optics systems tolook at star systems in the near-infrared
spectrum and to see through clouds ofgalactic dust and gas that mask images
in visible light.
The team has imaged 150 stars inOrion with resolution never before
attained. Keck’s adaptive optics makeit possible to resolve binaries withseparations comparable to the distance

Lawrence Livermore National Laboratory

This image of Io, Jupiter’s largest moon,reveals volcanic activity. (Image courtesy of
Keck Observatory.)

15

16

Adaptive Optics

S&TR June 2002

Astronomy Benefits from Laser Advances
Since their invention, ground-based telescopes have suffered fromblurred images caused by Earth’s fast-moving and turbulent
atmosphere. However, advances in optics and computer technology
have made it possible to sharply reduce this blurring by the use ofadaptive optics that correct atmospheric distortions and allow groundbased telescopes to reach their theoretical maximum resolution.
Adaptive optics systems have traditionally required the astronomer
to find a bright star as a reference point of light. However, less than
1 percent of the sky contains stars sufficiently bright to be of use as areference light. To extend the usefulness of adaptive optics, Livermore
scientists developed a laser system that creates a virtual reference starhigh above Earth’s surface to guide the adaptive optics system. The
laser guide star is created by projecting light from a dye laser on a layerof sodium atoms that are in the atmosphere 90 to 100 kilometers above
Earth.
The main components of an adaptive optics system using a laser
guide star are a wavefront sensor camera equipped with a chargecoupled device detector, a control computer, a deformable mirror, apulsed dye laser that is tuned to the atomic sodium resonance line at awavelength of 589 nanometers, and a set of solid-state lasers to pump,or energize, the dye laser. The dye laser, similar to that pioneered at
Livermore for its Atomic Vapor Laser Isotope Separation program,creates a glowing star of sodium atoms measuring less than 1 meter indiameter at an altitude of about 100 kilometers above Earth’s surface.
This artificial reference can be created as close to the astronomicaltarget as desired so that the light from the laser star and the observed
object pass through the same small part of the atmosphere.
At the telescope, wavefront sensors measure distortions due toatmospheric turbulence, using light from the guide star as a reference.
The sensors relay this information to a computer, which in turncontrols the movements of tiny actuators attached to the back of adeformable mirror. The mirror changes its shape hundreds of times per
second to cancel out atmospheric distortion.
Near-infrared images obtained with the adaptive optics systems on
the telescopes at the W. H. Keck Observatory in Hawaii are superior toimages obtained with the Hubble Space Telescope because Hubble’s
light-gathering mirror is much smaller. (Adaptive optics will not,however, replace space-based observatories, many of which aredesigned to sample certain bands of electromagnetic radiation such as
ultraviolet light that are blocked by Earth’s atmosphere.)
Lick’s dye laser projects light into the sky through a 30-centimeter
refractive telescope that is mounted on the side of the main telescope.
The laser was designed and built by Livermore’s Herbert Friedman.
The deformable mirror has 127 actuators to raise or lower a tiny part of
the front surface by up to 4 micrometers.
The laser guide star at the Keck II telescope uses a 20-watt dyelaser, the most powerful laser in use at a telescope. The laser light isprojected onto the sky by a telescope with a 50-centimeter lens
attached to the side of the 10-meter Keck II telescope. A 15centimeter-diameter deformable mirror is adjusted continuously by
349 actuators.
Keck’s laser guide star was built at Livermore and thenreassembled at the observatory’s headquarters in Waimea, Hawaii,
which is slightly less than 1 kilometer above sea level. The
observatory’s telescopes are located at the summit of the Mauna Kea
volcano, over 4 kilometers above sea level. Scientists observe on thesetelescopes remotely from the Waimea headquarters to avoid the risk ofsickness from extended exposure to Mauna Kea’s high altitude.
During the two-year temporary installation at headquarters, theLivermore team of Deanna Pennington, Curtis Brown, Pam Danforth,and Holger Jones made extensive improvements. “We installed asignificant level of automation and diagnostics on the laser guide starsystem to make it more reliable and robust and permit it to be operated
remotely from Waimea,” says Pennington, laser scientist and systems
engineer at both Lick and Keck. She notes that installing the adaptive
optics system and laser guide star at Lick gave the Livermore teamvaluable experience in designing the larger system at Keck. The laser
system was installed and activated on the telescope at the 122kilometer summit over a 6-month period, culminating in the “firstlight” demonstration on December 23, 2001.
Keck’s adaptive optics and laser guide star embody more than two
decades of Livermore experience in adaptive optics technology.
Adaptive optics systems with adjustable mirrors have been used on a
succession of increasingly powerful lasers at Livermore, and they will
be used on the National Nuclear Security Administration’s National
Ignition Facility (NIF), under construction at Livermore.
Claire Max and Friedman started Livermore’s work on laser guidestars in the early 1990s. Feasibility tests conducted at Livermore in
1992 demonstrated the first laser guide star at usable power levels anddetermined the requirements for a telescope version.
Livermore scientists are working on the next generations ofadaptive optics. About 20 Livermore employees belong to the
Adaptive Optics program within the Physics and Advanced
Technologies Directorate. One team is developing more reliable
deformable mirrors based on microelectromechanical technology.
With funding from the Center for Adaptive Optics (see the box on
p. 19) and the European Southern Observatory in Chile, Pennington
will lead another group of Livermore scientists within the NIF
Programs Directorate who are investigating fiber lasers to replace thecurrent dye laser. Fiber lasers, widely used in the telecommunicationsindustry, will be part of the NIF front end and will produce the laser
beam before it is amplified. Pennington says that fiber lasers provide
an “elegant solution” for generating 589-nanometer light because they
are compact, efficient, and robust.

Lawrence Livermore National Laboratory

S&TR June 2002

Adaptive Optics

An overview of the layout within the domeof the Keck II telescope. (a) The laser
equipment room on the dome floor houses
the pulsed dye laser master oscillator,
yttrium–aluminum–garnet pump lasers, andcontrol systems. (b) The laser room on theelevation ring of the telescope houses anoptics bench containing two stages of dyeamplification, numerous diagnostics, andthe bottom half of the projection telescope.
(c) The 50-centimeter projection lens islocated at the top end of the telescope.

Infrared bore-site
camera(c) Projection lensTelescope

Beam tube(b) Laser enclosure

Telescopefoundation
Domefoundation

Controlroom(a) Laser
equipmentroom

Lawrence Livermore National Laboratory

17

Adaptive Optics

S&TR June 2002

between our Sun and Uranus, a distancethat is less than the diameter ofcircumstellar disks. “We now have thecapability of resolving most binary
systems, including a range inaccessible
to previous surveys,” Patience says.
She notes that with the resolving powerof Keck’s adaptive optics system, aperson standing on Mauna Kea, locatedon the big island of Hawaii, could see
objects as small as 1 centimeter tall on
the island of Oahu, approximately
400 kilometers away.
Peering into Black Holes
Max, her colleague Gaby Canalizo,
and astronomers from UC Santa Barbara,
are using adaptive optics on Lick andKeck telescopes and Lick’s laser guidestar to observe nearby active galactic
nuclei, which are small, extremely

bright central regions in some galaxies.
Very distant and bright active galactic
nuclei are known as quasars. Active
galactic nuclei are thought to contain
black holes at their centers, which suckup stars, planets, and gas from thesurrounding galaxy in a process calledaccretion. In some cases, the material isthen shot out from the region surrounding
the black hole at high speeds in outflows
known as jets.
Max notes that for 30 years, Departmentof Energy laboratories have been doing
pioneering work on the high-energy
processes involved in black-holeformation and emission. However, onlyin the past few years has direct evidence
for black holes begun to emerge—in theform of high-resolution observations thatprobe the active galactic nuclei close to
the central black hole.

+90

Latitude18

Max and Canalizo’s team isobserving energy outflow from theprocess of accretion of matter into themost massive black holes in nearby
galaxies. The images enableastronomers to explore the region
nearby and the evolution of the central
black holes. In the process, theastronomers have found double active
galactic nuclei suggestive of galaxy
mergers, which are believed to be acause of black hole formation.
Looking to the Future
When the Keck laser guide star
becomes available for viewing,
Livermore scientists will be among thefirst to use it and thereby help to makelaser guide stars a more accepted toolof astronomical research. Pennington
notes that a National Academy of
Sciences panel has identified laser
guide stars as a key technology foradvancing astronomy. Most experts saythat the next generation of giant
telescopes will not be feasible without
adaptive optics systems equipped withlaser guide stars.

0

–90
360

270

0

180
Longitude

0.04

0.08
Reflectance

90

0.12

0

0.16

The first map of the surface of Titan, Saturn’s largest moon, is being assembled with the help ofadaptive optics. Colors denote reflectance, with 1.00 corresponding to the reflectance of aperfect mirror. Data from current observations are filling in the blank areas.

Lawrence Livermore National Laboratory

Keck adaptive optics image of a protoplanetary
disk envelope surrounding a young star in the
Trapezium region of the constellation Orion.

S&TR June 2002

Adaptive Optics

New Center Spreads the Word
Lawrence Livermore is a major partner in the Center for
Adaptive Optics, which is headquartered at the University ofCalifornia (UC) at Santa Cruz. The center, funded by the National
Science Foundation, began operations in November 2001. The
27 partner institutions in the center also include several other UC
campuses, the University of Chicago, the California Institute ofTechnology, the University of Rochester, the University of
Houston, Indiana University, and 17 other partners.
The center’s director is Jerry Nelson, professor of astronomy
and astrophysics at UC Santa Cruz. Nelson designed the twin
telescopes at the W. M. Keck Observatory in Hawaii. Livermore
scientists Claire Max and Scot Olivier are associate directors, andLivermore scientists play important roles in center activities andsponsored research.
The center coordinates the efforts of researchers across thecountry involved in the growing field of adaptive optics for
astronomical and vision science. The center also operates scienceeducation and outreach programs for scientists and college students.
“Our goal is to provide the sustained effort needed to bring
adaptive optics from promise to widespread use by astronomers
and vision researchers,” says Max. She predicts that most large
ground-based telescopes will have adaptive optics systems within
the next few years. Relatively few astronomers, however, haveexperience with adaptive optics, let alone laser guide stars. “We

However, as a telescope gets larger,
the requirements for an adaptive optics
system become increasingly rigorous.
The proposed California Extremely
Large Telescope (CELT), a
collaboration between UC and Caltech,is designed to have a 30-meterdiameter mirror, three times the size of
Keck’s. CELT’s adaptive optics system
will probably require multiple laser
guide stars with several mirrors working
together to correct for different layers of
atmospheric turbulence. Each mirror
may require about 5,000 actuators.

want to inform the broader astronomical community about adaptive
optics through conferences and workshops,” she says.
Max points out that adaptive optics are also used in vision
science to compensate for aberrations in the eye that affect visionand impede efforts to study the living retina. Adaptive optics has
made it possible to obtain images of the living human retina with
unprecedented resolution, enabling researchers to see individual
light receptors. Adaptive optics may also provide normal eyes withsupernormal vision. A team of Livermore researchers led by
Olivier is developing a high-resolution liquid-crystal adaptive
optics system for human vision correction that will be used at UC
Davis to study the limits of human visual acuity.

Thanks to increasingly powerfultelescopes, more capable adaptive
optics systems, and advanced guide-starlasers, the heavens are sure to berevealing more of their secrets in the
new millennium.
—Arnie Heller

For further information contact
Deanna Pennington (925) 423-9234(pennington1@llnl.gov).

Key Words: active galactic nuclei, adaptive
optics, atomic vapor laser isotope separation,
binary star, black hole, California Extremely
Large Telescope (CELT), deformablemirror, dye laser, Hubble Space Telescope,laser guide star, Lick Observatory, W. M.
Keck Observatory.

For online information on the
Lick Observatory:
www.ucolick.org/

Lawrence Livermore National Laboratory

For online information on theW. M. Keck Observatory:
www2.keck.hawaii.edu:3636

For online information on theCenter for Adaptive Optics:
cfao.ucolick.org/

19

20

Research Highlights

Experiments Re-create X Rays from Comets
E

ARTH is continually showered by x rays traversing theuniverse from our Sun and other hot stellar objects. A major
branch of astronomy is devoted to detecting and studying x raysfrom distant stars and galaxies, and Lawrence Livermore
scientists have long studied the x rays that are produced from
nuclear detonations.
However, it came as quite a surprise to scientists in 1996
when the Rosat X-Ray Satellite detected low-energy (less than
1 kiloelectronvolt) x rays streaming from the comet Hyakutake.
X-ray emission is usually associated with hot plasmas fromstars, nuclear reactions, and black holes, not from ice-cold
objects such as comets. Since the original discovery, other x-ray
satellites have established that several other comets travelingthrough our solar system emit x rays with fluxes, or intensities,
as high as 1025 photons per second.
To help resolve the apparent contradiction, a national team ofscientists headed by Lawrence Livermore physicist Peter
Beiersdorfer is working on the laboratory production of lowenergy x rays identical to those produced by comets travelingnear the Sun. The team is using Livermore’s electron beam ion
trap (EBIT) to produce the x rays and an x-ray spectrometer

The current explanation for comet x rays iscalled charge exchange. This process isbelieved to occur when heavy ions (Aq+)
from the solar wind flowing from the Sun(right) collide with electrically neutral atoms
and molecules (B) in the comet’s
atmosphere (left). During a collision, a heavy
ion captures one or more electrons from acomet’s atmospheric atom, ionizing it toB(q–p)+. The solar wind ion, now Ap+,
momentarily enters an excited state andkicks out an x ray as the electrons return to alow-energy state. The x ray can be detectedby a spacecraft (lower left).

(XRS) designed by the National Aeronautics and Space
Administration (NASA) to detect them.
The research is providing much greater understanding about
the x rays that are emitted by comets as they pass the Sun. The
effort is also providing scientists with valuable information thatwill help them interpret data to be collected by a joint
U.S.–Japan x-ray satellite mission scheduled for launch in 2005.
Primordial Chunks of Ice
Comets are odd-shaped chunks of ice (water and frozen gas)and dust a few kilometers to a few tens of kilometers indiameter. They are the oldest, most primordial objects in thesolar system. X rays emanate from a comet’s nebulous
atmosphere called a coma, which can stretch tens of thousandsof kilometers in front of or behind the comet. The coma isformed when the comet gets close enough to the Sun so thatsome of the ice is vaporized.
More than a dozen theoretical models were first proposed to
explain why comets give off x rays. Some models predicted thatcomet x rays are reradiated x rays from the Sun. Other models
were based on some kind of interaction between the molecules

Solar windion

Comet’s
atmosphere
Ap+

Aq+

X ray
B
Neutral cometary
gas atomSpacecraft
detector

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B(q–p)+Sun

S&TR June 2002

Re-creating Comet X Raysin the comet’s thin atmosphere and ions or electrons from theSun’s solar wind, the stream of particles that blow off the Sun’scorona at 400 kilometers per second.
The current leading explanation is called charge exchange.
This process is believed to occur when solar wind forces heavy
ions of carbon, nitrogen, oxygen, and other elements to collidewith the electrically neutral atoms and molecules found in acomet’s atmosphere. During a collision, a heavy ion from thesolar wind captures an electron from a comet’s atmospheric atom
or molecule and momentarily enters an excited state. The ion
immediately kicks out an x ray as the electron returns to a lowenergy state.
“Very little experimental data are available on chargeexchange-induced x rays and what the spectrum emission lines
look like,” says Beiersdorfer. “The goal of our research is to
re-create, in the laboratory, the same x-ray emissions that are
produced when the solar wind and comets interact. In this way,
we can better understand the nature of charge exchange and help
other scientists interpret data taken by x-ray satellites.”
The research, supported by Laboratory Directed Research andDevelopment funding and NASA, is a collaboration between
scientists from Livermore, NASA’s Goddard Space Flight
Center, and Columbia University. The investigators include
Daniel Thorn, Mark May, and Hui Chen from the Laboratory;
Richard Kelley, Scott Porter, Caroline Stahle, Keith Gendreau,
Gregory Brown, Andy Szymkowiak, and Kevin Boyce from

Goddard; and Steven Kahn from Colombia. In addition, spaceresearchers Casey Lisse from the University of Maryland andBradford Wargelin from the Harvard Smithsonian Observatory
are aiding the research effort.
The team is using Livermore’s EBIT, which produces andtraps highly charged ions by means of a high-current-density
electron beam instead of traditional high-energy particle
accelerators. The instrument was developed in 1985 byLaboratory physicists Mort Levine and Ross Marrs. Other
electron beam ion traps, most of which are based on
Livermore’s design, are used at research centers in the U.S.,
Europe, and Japan.
EBIT’s electron beam collides with selected ions to strip
them of one or more electrons, depending on the beam’s energy.
The current version, named SuperEBIT, can produce an electron
beam energy of up to 250 kiloelectronvolts, enough to makeuranium (U92+) ions. “SuperEBIT can produce virtually any ion,
x ray, or visible photon desired,” says Beiersdorfer.
New Generation of Spectrometer
The XRS was designed by NASA for Japan’s Astro-E X-Ray
Satellite, but a failed rocket launch in February 2000 means a
wait of five years before its replacement, the Astro-E2 Satellite,
can be placed in orbit. Fortunately, the Astro-E’s engineeringspare XRS was still available for laboratory x-ray astrophysics
measurements. It was sent to Livermore after the failed launch

At Livermore’s electron beam ion trap (EBIT)
facility, scientists study the charge-exchange
process and the effects of different ions andinteraction gas molecules on the x-ray
emission patterns recorded by the x-ray
spectrometer (XRS) (front). The EBIT (inback) provides a source of ions to re-create
solar wind particles. At the left is an old-stylespectrometer. Also shown is the intersectionof the XRS and EBIT.

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Re-creating Comet X Rays

S&TR June 2002of Astro-E. The Livermore–Goddard team adapted the
instrument to fit on EBIT and uses it to study x-ray detection.
The XRS, a new generation of spectrometer, uses
microcalorimeter detectors that are so sensitive they can detect
the heat produced by the energy of an individual x-ray photon.
To accomplish this, its microcalorimeter array is cooled to an
extremely low temperature of –460°F (0.060 kelvin). (Theabsence of all heat, called absolute zero, is 0.0 kelvin, and has
never been achieved.) The XRS has an energy detection rangeof 0.4 to 10 kiloelectronvolts with an energy resolution of
10 electronvolts, which allows scientists to see much finer detailin the x-ray spectrum.
At the Livermore EBIT facility, scientists study the detailsof the charge-exchange process and the effects of different ionsand interaction gas molecules on the x-ray emission patterns
recorded by the XRS. The EBIT facility provides a source ofions to re-create solar wind particles interacting with atoms andmolecules in a comet’s atmosphere. The XRS records the x-ray
spectra, and diagnostic detectors characterize the experimental
conditions. In effect, says Beiersdorfer, the EBIT facility has
become a test stand for the Astro-E2 satellite, which will carryan enhanced XRS.

Experiments Mimic Space Interactions
The EBIT experiments begin with the production of several
million ions of either carbon, oxygen, neon, magnesium, silicon,
or iron. These ions are found in the solar wind and are believed
to be involved in charge-exchange reactions with comets. The
beam is then turned off, and the trap is operated in the so-called
magnetic mode, in which the ions are confined by a magnetic
field to a volume of about 2 cubic centimeters. At this density,
the physics is the same as that found in the vicinity of a cometpassing close by the Sun. (A greater density of ions would
introduce completely different physics regimes.) Next, neutral
molecules of water, methane, nitrogen, or carbon dioxide, all ofwhich have been identified in comets’ atmospheres, are injected
into the trap.
For a few hours, the XRS records the x rays produced bycharge-transfer collisions between the ions and the neutral
molecules. The result is a catalog of emission lines that serve as
tell-tale fingerprints of a particular ion’s x-ray-producing
collision. Beiersdorfer says that the experiments are validating
the hypothesis that charge exchange is a viable mechanism forproducing comet x rays, although the exact mechanics of theprocess are probably more complex than is known.

100
60
80

EBIT
with XRS

60

40CountsCounts22

Old-styleinstrument

40

20

20

0
700

900
1,100
1,300
X-ray energy, electronvolts

1,500

Data on charge-exchange-induced x-ray emissions supplied byelectron beam ion trap (EBIT) experiments with the x-ray spectrometer(XRS) are enormously more detailed than data supplied by old-styledetectors. This graph compares the data supplied by each instrument
in registering x-ray emissions caused by charge-exchange reactions
involving an ion of neon (Ne9+).

0
550

650

750
850
X-ray energy, electronvolts

950

Plots of x-ray emissions from an ion of oxygen (O7+) caused byinteractions of O8+ with methane (CH4, the green trace) or with nitrogen(N2, the red trace) reveal subtle changes in the x-ray emission lines
when these different neutral gases collide with the heavy ions. Thechanges are found near 850 electronvolts.

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S&TR June 2002

Re-creating Comet X Rays

The researchers discovered that the x-ray emission patternchanges with the kinetic energy of the ions. They found that the
average x-ray energy emitted by the ions shifts to higher values
as the kinetic energy of the ions is lowered. They also uncovered
subtle changes in the x-ray emission lines when different neutral
gases collide with the heavy ions. “The composition of theinteraction gas is another important variable,” says Beiersdorfer.
Comets as Probes
Beiersdorfer predicts that careful detection and measurementof x rays produced by the interaction between the solar wind andcomets will one day provide a powerful means to monitor space“weather” inside the solar system without the need for spacecraft
circling the Sun. In this way, he says, comets could be used asprobes to measure the intensity, speed, and composition of thesolar wind, its intermittent “quiet time,” and the chemicalcomposition of comet gases.
“Given that more than three bright comets with appreciable
x-ray emissions enter the inner solar system each year, their x rays
can provide a valuable diagnostic of the solar wind. This capability
has opened up a whole new window to our solar system; it’s avery rich field.”Some astronomers have conjectured that as the solar windslows down throughout the heliosphere, it may generate weak
x rays through charge-exchange reactions with natural gas
streaming in from the interstellar medium (mostly hydrogen atoms).
If this hypothesis is borne out by x-ray satellite data, astronomers
will have to revise their assumption that the soft x-ray backgroundthat seems to permeate the universe may in fact be partly due tocharge-exchange reactions from the solar wind.

Small Handbook on Comet X Rays
The result of the EBIT experiments will likely be a small
handbook for scientists to guide their interpretation andunderstanding of the comet x-ray data sent back by Astro-E2,
beginning in 2005. “The scientific community will be well
prepared when Astro-E2 launches,” says Beiersdorfer. In themeantime, NASA has committed a second, advanced XRS for
the EBIT team’s research.
As the EBIT experiments continue, other scientists arelooking at the theoretical model of charge exchange. Atomic
theorists Ronald Olson from the University of Missouri at Rolla;
Jim Perez from Luther College in Decorah, Iowa; Charles
Weatherford from Florida A&M University in Tallahassee; andBurke Ritchie from Livermore are aiding the research effort.
Lawrence Livermore researchers have extensive experience inmodeling short-wavelength radiation phenomena, and physicist
Ritchie is using high-performance supercomputers to elucidatein greater detail charge-exchange reactions using the quantum
theory of atomic collisions.
Clearly, primordial chunks of dirty ice still hold a few
surprises for scientists.
—Arnie Heller
Key Words: charge exchange, comets, electron beam ion trap (EBIT),
microcalorimeter, solar wind, x rays, x-ray spectrometer (XRS).
For further information contact Peter Beiersdorfer (925) 423-3985(beiersdorfer1@llnl.gov).

Lawrence Livermore National Laboratory23

50th Anniversary Highlight

24

O

S&TR June 2002

F the 70 or so people who came to work at the Livermore
branch of the University of California Radiation
Laboratory in September 1952, nearly a third were chemists,chemical engineers, and material scientists, hired to support
the Laboratory’s fledgling nuclear weapons program. These
personnel had two immediate tasks. At the front end of aweapon’s development, Livermore chemists had to be able toform parts out of unusual materials such as plutonium anduranium for nuclear test devices. Then after each device wastested, they had to be able to analyze the radioactive
components of the leftover debris and gases to help determine
the weapon’s performance.
Livermore’s chemists wasted no time setting up aprocessing laboratory in the only available room equippedwith running water: the women’s restroom of the bachelor
officers’ quarters of the former naval air station that was thehome of the new “Rad Lab.” By spring 1953, they had also
put a laboratory in the former dispensary and set up achemical fabrication capability in the assembly hall. The
women’s restroom and the assembly hall were merely
temporary measures. The first permanent building at theLivermore site, completed in 1954, was built for thechemistry organization.
As the Laboratory grew and evolved, so did its chemistryorganization. From studies of isotopes—particularly in theactinide group of elements—Livermore chemists built a firstclass institute to study heavy elements and helped discover
new elements. They developed high explosives that were
safer but still delivered the power needed by weapons
designers, and they tailored other special materials for
specific applications. Chemists were the first at theLaboratory to use computers to automate laboratory
processes. And their involvement with the computational

world didn’t stop there. With the explosion in computational
abilities and sophisticated experimental capabilities of thepast decade, chemists and material scientists are gaining amore complete and fundamental understanding of the
behavior of materials as esoteric as aging plutonium and ascommon as the surface of water.

Nothing in life is to be feared.
It is only to be understood.
—Marie Curie, physicist and winner of theNobel Prize for physics (1903) andchemistry (1911)
Of Yields, Isotopes, and Heavy Elements
In his preliminary plan for the Laboratory, Herb York,the young physicist whom Ernest O. Lawrence designatedto get the Livermore project up and running, madespecific note of the need for a radiochemistry group.
Radiochemistry, a fairly new field in 1952, is the study ofradioactive substances and is closely tied to nuclear
chemistry, which is the study of the atomic nucleus,
including fission and fusion reactions and their products.
Radiochemical diagnostics were crucial to determining how
well a device performed in a test. An exploding device
produces large neutron fluxes. Those neutrons interact withthe device materials, creating different isotopes and otherelements. By determining the differences between thematerials in the weapon before the explosion and those
produced by the explosion, scientists can deduce what
happened during the test.

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S&TR June 2002

50 Years of Chemistry and Materials Science

Obtaining those results was a long, extremely complex
process, and not without its hazards. (See the box on p. 27.)
Livermore conducted nuclear experiments for nearly four
decades, at first in the atmosphere and later underground.
Throughout that time, radiochemists examined fission
products, heavy elements, products resulting from neutron
capture, products from other neutron interactions, and shortlived gases. Their results—when combined with results fromnonchemical diagnostics (such as those described in S&TR,
April 2002, pp. 22–24)—gave weapon designers a picture of
how well the device worked.
For example, to determine the fusion yield of a device,chemists would add detectors—small quantities of specificelements, such as yttrium—to various parts of a device as it
was being made. Radiochemist David Nethaway, who started
his Laboratory career during the early days of atmospherictesting, explains, “Certain reactions between neutrons anddetector materials such as yttrium only occur when theneutron energies are above a particular threshold.” For
instance, the reaction that converts an atom of yttrium-89 to
an atom of yttrium-88 plus two neutrons only occurs when aneutron with an energy greater than 12 megaelectronvolts(MeV) smashes into the yttrium-89 atom. “By measuring theamount of yttrium-88 in debris samples recovered from thetest, we could determine the fluence of 14-MeV neutrons, andfrom that we infer a fusion yield,” says Nethaway. (SeeS&TR, May 2002, pp. 16–21.)
Over time, Livermore’s radiochemical expertise wasapplied to other projects as well. In the early 1970s,
radiochemists performed radiological surveys of Enewetak
Atoll in the Pacific Ocean to prepare for the islanders’ return
after the atmospheric tests of the 1950s. The initial focus wason elements of particular use to nuclear weapons research andtesting, including the set of elements known as actinides. This
work led to the establishment of the University of California’s
Glenn T. Seaborg Institute for Transactinium Science at
Livermore in 1991. Since the Laboratory’s early days,
Livermore chemists have also been involved in searches for
new elements to add to the periodic table. This work includes
detailed studies of debris from the Hutch Event, a 1969
underground test specifically designed to produce superheavy

A 1957 photo of Livermore’s chemists setting up equipment in a gas
analysis laboratory. Rare gases such as krypton and xenon wereregularly analyzed as part of the chemical diagnostics for nuclear
weapon tests.

In the mid-1950s, inhabitants of Enewetak Atoll in the South Pacificrelocated when the U.S. began conducting atmospheric nuclear tests
nearby. When the islanders were preparing to reinhabit Enewetak,
Livermore led a research force, members of which are pictured here,
drawn from 19 federal and scientific organizations to perform a radiologicalsurvey of the soils, plants, and marine environment of the islands.

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50 Years of Chemistry and Materials Science

S&TR June 2002

elements, and culminates with the recent synthesis of elements
114 and 116. (See S&TR, January/February 2002, pp. 16–23.)
After a decade of underground testing at the Nevada Test
Site, Livermore’s radiochemists began studying the movementin groundwater of radioactive elements from those tests. Using
both radioactive and stable isotope tracers, these scientists
investigated groundwater sources, ages, travel times, and flow
paths. Having proved their usefulness at the Nevada Test Site,
isotope tracer methodologies have since been applied to otherwater resource projects, including one for the Orange County
Water District in southern California. (See S&TR, November
1997, pp. 12–17.)
Today, radiochemists and nuclear chemists are also
contributing their skills in radiation detection, gamma-ray
spectrometry, and mass spectrometry to programs aimed atpreventing nuclear proliferation. For example, sophisticatedcodes originally developed to analyze the complex gamma-ray
emissions from nuclear explosion debris now form thestandard for analyzing samples collected by the International
Atomic Energy Agency (IAEA) and other internationalorganizations. Nuclear chemists are also developing gammaray imaging technology that can be applied to a range ofcounterterrorism applications.
Developing Safe Explosives, New Polymers, and MoreIn the division assigned to develop and design
thermonuclear weapons and testing devices, York also
sketched in spots for chemists and metallurgists, noting,

A collaboration with Lawrence Berkeley researchers resulted in the
discovery of element 106 in 1974. A separate collaboration (pictured
above) with the Joint Institute for Nuclear Research in Dubna, Russia, thatbegan in 1989 led to the discovery of several new isotopes in the early
1990s and in the recent synthesis of superheavy elements 114 and 116.

“[C]ertain unusual mixtures of materials are very frequently
needed . . . and are normally unobtainable outside.” Over theyears, Livermore’s material specialists have dealt with nearly
every element in the periodic table. Sometimes they created
new materials, and sometimes they synthesized existingmaterials in unusual or exotic ways or combinations.
At the start, new materials development was strictly related
to nuclear weapons and mostly involved unusual alloys(including a corrosion-resistant “stainless” uranium) andplastics. About those earliest days, chemical engineer Barney
Rubin recalled, “ A major activity was becoming expert inmaking plastic parts or fabricating components out of weird
exotic materials that used plastics as binding agents. We also
got heavily into metallurgy. We weren’t material scientists inthe sense that they are known now. We were sort of kludging
things together as best we could—sometimes by intuition andblack art, sometimes by science, and sometimes by a
combination of the two.”In the area of high explosives (HE), Livermore started
pretty much from scratch. The chemists turned for assistanceto the centers for HE expertise —Los Alamos and certain
Department of Defense laboratories. Livermore’s chemists
worked closely with weapon designers to develop an HE
program that made sense for the design effort, eventuallycreating the LX series of explosives for Livermore’s weapons.
“We had a general goal of trying to get more bang per unit
volume,” says Gus Dorough, an early leader of the chemistryorganization. “It was a point that clearly interested the nuclear

Fran Foltz examines crystals of the insensitive high explosive triaminotrinitrobenzene (TATB) under the microscope. The background shows
TATB crystals at high magnification.

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S&TR June 2002

50 Years of Chemistry and Materials Science

designers, and it turned out to be a very sophisticated andsubtle subject. It’s not just a matter of more potential energy
per unit volume; it’s a matter, for instance, of how that energy
is released, what kind of chemical detonation products areformed, and the equations of state of those products. Justdeveloping a good technique to measure energy release so we
could screen new compounds was no simple matter.”Several empirical tests for measuring HE energy andsensitivity were developed, including the Susan Test (named
after Dorough’s daughter), which measured safety propertiesof explosives under simulated accident conditions. Livermore
also developed insensitive HE that met the designers’
requirements while significantly improving the safety andsurvivability of munitions, weapons, and personnel. One such,
triamino-trinitrobenzene (TATB), is nearly invulnerable tosignificant energy release in plane crashes, fires, andexplosions or to deliberate attack with a small firearm. (SeeS&TR, November 1996, pp. 21–23.)

Polymers—substances made of giant molecules formed by
the union of simple molecules—have long been of interest to
the Laboratory. In the 1980s, a low-density lightweight
polymer called aerogel, first invented in the 1930s, caught theattention of Livermore chemists who went on to create
superlight silica aerogels and organic aerogels for theStrategic Defense Initiative. (See Energy & Technology
Review, November 1994, pp. 16–17.)
Since then, Livermore has developed and improved
aerogels for national security applications and synthesized
electrically conductive inorganic aerogels for use as
supercapacitors and as a water purifier for extracting harmful
contaminants from industrial waste or for desalinatingseawater. Recently, chemist Glenn Fox led a desalinating
project to bring atomic-level control to the design andsynthesis of organic aerogels. (See S&TR, June 2000,
pp. 23–25.) A team headed by chemist Randy Simpson
created aerogellike energetic materials with structures that can

Samples from the Sky—Radiochemistry in the Era of Atmospheric Tests
The atmospheric tests of nuclear weapon devices presented
unique challenges in data gathering for radiochemists. Right after an
atmospheric test, much of the material—radioactive particulates andgases—resides in the signature mushroom cloud. The objective ofresearchers was to get representative samples of this cloud for analysis.
In an interview conducted nearly 20 years ago, the late Harry
Hicks, one of the early radiochemists at Livermore, described what
was involved in collecting and processing the samples. The first step
was to look at the expected yield of an upcoming test to estimate thesize of the cloud and its altitude. “Then you look at the mix offission and fusion,” said Hicks. “The fission products tell you what
the radiation level is in the cloud. What you want to do is to send
the aircraft in to get your samples, but you don’t want to overexpose
the crews.”
A plane with a Laboratory chemist would be in the air before shot
time. After the shot went off, the chemist would observe the cloudand its formation. “If you saw a wisp of cloud or a likely spot,” said
Hicks, “you’d go over and find out whether it was radioactive or notby flying through to see if you wanted to sample the thing.” If the

Chemist Harry Hicks readyto board an Air Force RB-57
sampling plane.

cloud appeared promising, an Air Force sample plane would fly inand obtain a sample. Particulates were captured on large filter papers
mounted in pods on each wingtip. Short-lived gases were drawn
through the filter, compressed, and stored in 30-centimeter spheres.
Radioactive elements decay constantly, so time was of the essence.
Planes landed immediately after obtaining samples, and the samples
were removed, packaged, and rushed back to Livermore by courier
plane. The samples from Pacific tests normally came in at seven oreight o’clock at night, and the chemical analysis—which took place
inside gloveboxes in a building without air-conditioning—began.
First, a chemist dissolved the filter papers, a nasty business involving
beakers, hot plates, red fuming nitric acid, and hot perchloric acid.
Once the papers were dissolved, each desired chemical element had
to be completely separated out and completely cleaned of othermaterials. “Our procedures were relatively new,” noted Hicks, “andthey weren’t exactly reliable, so we would do everything in
quadruplicate, hoping we got three, or two, to agree. It just took
a long time to be able to say, ‘I’m sure that there’s nothing but thatelement there.’”As the shots got larger, the test clouds got larger and higher, so
planes could only sample the tail end of the cloud. In the early 1960s,
Livermore researchers had the unique idea of using rockets todetermine how representative such samples were. “With remotely
controlled rockets, we were able to get samples from higher up andearlier than we could with planes flown by pilots,” says retired
Livermore chemist John Kury. Results from the rocket tests showedthat plane samples—taken later and lower—were indeed representativeof the clouds. “At the time, this project made a real difference in our
understanding of the radiochemistry needed to analyze device
performance,” notes Kury, “and it made a real difference for years
after, by validating the samples done in earlier tests.”

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50 Years of Chemistry and Materials Science

S&TR June 2002

be engineered at the nanometer scale. (See S&TR, October
1999, pp. 19–21.)
Aerogels aside, polymers have long been used byLivermore’s material scientists to create smooth, spherical thinwalled shells or coatings for targets used in laser fusion
experiments. (See S&TR, June 1997, pp. 22–24.) Anotherorganic polymer, Mercaptoplex, was originally developed at
Livermore for use in processing nuclear fuel rods.
Mercaptoplex has found another application in removing toxic
mercury from industrial waste streams and public watersupplies. (See S&TR, November 1999, pp. 17–19.)

A piece of extremely lightweight aerogel
poised on soap bubbles. Aerogels havethe highest internal surface area pergram of material of any known material
and also exhibit the best electrical,
thermal, and sound insulation
properties of any known solid.

Multilayers—exceedingly thin alternating layers ofmaterials—are another example of the Laboratory taking an
existing material, developing it further, and expanding its
applications. First demonstrated more than 50 years ago,
multilayers offer extraordinary strength, hardness, heatresistance, and unexpected new properties. In 1987, chemist
Troy Barbee led a team that designed and synthesized
multilayer optics for the soft x-ray and extreme ultraviolet
regions of the spectrum. Telescopes with these multilayer
x-ray optics were used to capture high-resolution, wide-field
x-ray images of the Sun. (See S&TR, December 1997,
pp. 12–19, and December 1999, pp. 11–13.) Multilayer
optics are also used in electron microprobes, scanningelectron microscopes, and particle beamlines in accelerators.
Multilayer optics are crucial to the current collaboration
among Livermore, other Department of Energy laboratories,
and private industry to develop extreme ultraviolet
lithography for manufacturing the next generation of
microcomputer chips. (See S&TR, November 1999,
pp. 4–9.)

Tools of the Chemistry Trade
The tools of Livermore’s chemists and material scientists
extend beyond the typical array of glassware and general chemistry
apparatus to include nuclear radiation counting instruments,
accelerators, vapor deposition equipment, a variety of microscopes
and mass spectrometers, and, of course, computers.
Chemists were the first at the Laboratory to integrate computerswith laboratory equipment using a PDP-7 in the gas-analysis
laboratory in 1965. By 1971, the computer was simultaneously
controlling an assortment of experimental equipment including avacuum-fusion device, a mass spectrometer, an emission
spectrograph plate reader, and an automatic sampling atomic
absorption system.
As computers evolved, so did the chemistry organization’s
applications of them. In the mid-1970s, chemistry designed thefirst completely computerized triple-quadrupole mass
spectrometer, a marvel of its time. The system allowed chemists todetect and measure less than 1 nanogram of a sample and was used
to analyze trace sulfur compounds in processing oil shale and toinvestigate the thermal decomposition kinetics of high explosives.
Today, massively parallel computers are a mainstay of efforts
to understand material properties and behaviors. For instance,computer simulations of energetic material properties led
theoretical chemist Riad Manaa to propose a novel energetic

material consisting of a nitrogen analog of the familiar carbon
buckyball. (See S&TR, June 2001, pp. 22–23.) Chemists are also
supporting efforts to model chemical warfare agents by developing
kinetic models for surrogate and actual agent chemicals, which
could then be used in atmospheric dispersion and other accident
and terrorist scenarios. As part of this effort, chemists recently
developed the first detailed kinetic model for the agent sarin andmodeled comparisons of the chemistry of sarin and its surrogates.

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Kinetic
model for theagent sarin.

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50 Years of Chemistry and Materials Science

Delving into Material Behavior and Properties“Exploratory, basic scientific research is key to the
Laboratory’s success in fulfilling its missions,” explains
Hal Graboske, associate director for Chemistry and Materials
Science (C&MS). “In all of our work, we are pushing thefrontiers of science and often must know the basics before
we can proceed with the more complex.” To meet theLaboratory’s programmatic needs, Livermore’s chemists
and material specialists have often returned to the basics,
investigating the behaviors and properties of elements andvarious materials in ever-increasing detail and at more
encompassing scales.
Nuclear weapons include highly reactive metals—
plutonium and uranium—as well as organic compounds that
degrade over time from exposure to radiation, hightemperatures, and accumulated gases. In the past, scientists at
Livermore studied how various materials aged and interacted
under stockpile conditions to guide the selection and use of
the best available materials for new weapons. They developed
accelerated aging tests, subjecting small samples of candidate
materials to elevated temperatures for a day to several
months. These tests measured gas evolution, weight loss, andchemical reactions with contacting materials. Materials thatpassed this screening were assembled into configurations thatmodeled the material interfaces in the weapon design andtested at temperatures appropriate to service conditions formonths or even years.
With the advent of stockpile stewardship in the 1990s,
material scientists looked for ways of predicting the lifetimeof key weapon materials and developing “age-aware” material
models for use in codes that predict the lifetime of the overall
weapon system. (See S&TR, September 1999, pp. 4–11.) For
example, metallurgist Adam Schwartz is part of a teamconducting experiments to measure the structural, electrical,
and chemical properties of plutonium and its alloys anddetermine how these materials change over time. (See S&TR,
March 2001, pp. 23–25.) “Plutonium is a complex andperplexing element,” notes Schwartz. “For instance, it has
seven temperature-dependent solid phases—more than any
other element in the periodic table. Each phase has a different
density and volume and its own characteristics.” Instruments
such as the transmission electron microscope image themicrostructure, allowing researchers like Schwartz to see notjust the surface, but the internal structure of the material at theatomic scale, providing the measurements needed forLivermore’s material models.
It’s not just exotic materials such as plutonium that get theclose scrutiny. Water, for instance, was the subject of a recent
collaboration between Lawrence Livermore and Lawrence

The Sun’s corona seen with x-ray optics designed at Livermore.

Berkeley chemists. (See S&TR, November 2001, pp. 20–23.)
Any system involving liquid water—hemoglobin in blood,
proteins in water—is affected by the way that hydrogen bonds
to the oxygen atoms. The researchers developed a techniqueusing synchrotron radiation to determine for the first time thedistance of bonds between hydrogen atoms and oxygen atoms
at the surface of liquid water.
The properties and behaviors of materials are also greatly
affected by the processes they undergo—whether the process
is welding metals or growing crystals. Livermore metallurgist
John Elmer has researched details of the welding processsince the early 1990s. Dependable welds are important for
maintaining the performance and safety of nuclear weapons
and play a key role in the long-term storage of nuclear
wastes. Recent experiments using x-ray synchrotron radiation
have revealed second-by-second changes in a metal’s
microstructure during welding, providing the first real-timelook at the welding process. (See S&TR, November 2001,
pp. 4–11.)
In the mid-1980s, C&MS researchers began to investigate
ways to rapidly grow the crystals used for optical switching
and frequency conversion on high-power laser systems. (SeeEnergy & Technology Review, November 1994, pp. 3–5.)
With the advent of the powerful atomic force microscope in
the 1990s, Livermore researchers began to clarify on the

Lawrence Livermore National Laboratory

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50 Years of Chemistry and Materials Science

S&TR June 2002

nanometer scale the growth mechanisms and threedimensional structures of widely different solution-based
crystals. (See S&TR, November 1996, pp. 12–20.)
In the past, advances in materials were accomplished byextensive laboratory testing combined with a healthy dose ofguesswork, a time-consuming and often costly approach. As
experimental tools such as microscopes have become
increasingly powerful, so have the computers used to modeland predict material behavior. At Lawrence Livermore, home
to some of the most powerful massively parallel computers inexistence, C&MS researchers are linking computer
simulations to laboratory experiments. (See the box on p. 28.)
Codes are now so sophisticated that Livermore researchers are
beginning to predict what scientists will see when imaging
materials through electron microscopes.
Chemistry’s Future Grows with the Laboratory
It’s been a long journey for Livermore’s chemistryorganization from the women’s restroom in the old barracks totoday’s highly sophisticated state-of-the-art laboratories andequipment, from analyzing radiochemical diagnostics forweapon tests to simulating the behavior of materials at theatomic level using supercomputers.
“For the past half-century, our goals have been to provide
the right people for the Laboratory’s programs and a research
environment that fosters growth,” says Graboske. “Thepeople have always risen to the challenge, meeting thechanging needs and seizing emerging opportunities over the
decades.” From continued support of the weapons program todealing with the nation’s recent threat of terrorism, theLaboratory’s chemistry and materials science experts remain
at the cutting edge of scientific discovery.
—Ann Parker
Key Words: actinides, aerogels, atmospheric tests, chemistry,computer simulation, crystal growth, high explosives, isotopes,
materials aging, material science, metallurgy, multilayers, multiscalemodeling, plutonium, polymers, radiochemistry, radiochemical
sampling, welding.
.
For more information about the Chemistry and Materials Science
Directorate:www-cms.llnl.gov/
For more about the history of the chemistry organization at
Livermore:
www-cms.llnl.gov/50_year_anniversary/(a)

For further information about the Laboratory’s 50th anniversarycelebrations:www.llnl.gov/50th_anniv/(b)(a) An 8- by 8-micrometer scanned image of the face of apotassium dihydrogen phosphate (KDP) crystal. The
morphology and dynamics of crystal growth are relevant to
the National Ignition Facility (NIF) as well as to projects
that study biomaterials. (b) An example of a large KDP
crystal grown for the NIF laser.

Lawrence Livermore National Laboratory

Patents and Awards

Each month in this space we report on the patents issued to and/or
the awards received by Laboratory employees. Our goal is to
showcase the distinguished scientific and technical achievements ofour employees as well as to indicate the scale and scope of thework done at the Laboratory.

Patents
Miniature X-Ray Source
James E. Trebes, Gary F. Stone, Perry M. Bell,
Ronald B. Robinson, Victor I. Chornenky
U.S. Patent 6,353,658 B1March 5, 2002

A miniature x-ray source capable of producing a broad spectrum
x-ray emission over a wide range of x-ray energies. The miniature
x-ray source comprises a compact vacuum tube assembly
containing a cathode, an anode, a high-voltage feedthrough fordelivering high voltage to the anode, a getter for maintaining highvacuum, a connection for an initial vacuum pumpdown andcrimpoff, and a high-voltage connection for attaching a compact
high-voltage cable to the high-voltage feedthrough. At least a
portion of the vacuum tube wall is highly x-ray transparent andmade, for example, of boron nitride. The compact size andpotential for remote operation allow the x-ray source, for example,
to be placed adjacent to a material sample undergoing analysis or
for medical applications in proximity to the region to be treated.
Sputtering Process and Apparatus for Coating Powders
Daniel M. Makowiecki, John A. Kerns, Craig S. Alford,
Mark A. McKernan
U.S. Patent 6,355,146 B1March 12, 2002

A process and apparatus for coating small particles and fibers. The
process involves agitation by vibrating or tumbling the particles orfibers to promote coating uniformly, removing adsorbed gases andstatic charges from the particles or fibers by an initial plasma
cleaning, and coating the particles or fibers with one or morecoatings. The first coating is an adhesion coating, and subsequentcoatings are deposited in situ to prevent contamination at layerinterfaces. The first coating is of an adhesion-forming element(tungsten, zirconium, rhenium, chromium, titanium) and is 100 to
10,000 nanometers thick. The second, or final, coating is multiple
elements (copper or silver, for example, for brazing processes, orother desired materials). It is 0.1 to 10 micrometers thick anddefines the new surface-related properties of the particles. An
essential feature of the coating process is the capability to deposit
the coating in situ without interruption to prevent the formation ofa contaminated interface that could adversely affect the coating
adhesion. The process may include screening of the material to becoated and either continuous or intermittent vibration to prevent
agglomeration of the material to be coated.
System and Method for 100% Moisture and Basis Weight
Measurement of Moving Paper
Jose E. Hernandez, Jackson C. Koo
U.S. Patent 6,355,931 B1March 12, 2002

A system for characterizing a set of properties for a moving
substance. The system includes a first near-infrared linear array, asecond near-infrared linear array, a first filter transparent to a firstabsorption wavelength emitted by the moving substance andjuxtaposed between the substance and the first array, a second filter

blocking the first absorption wavelength emitted by the moving
substance and juxtaposed between the substance and the second
array, and a computational device for characterizing the resulting
data from the arrays. The method includes the steps of filtering out afirst absorption wavelength emitted by a substance, monitoring thefirst absorption wavelength with a first near-infrared linear array,blocking the first wavelength from reaching a second near-infrared
linear array, and characterizing data from the arrays into information
on a property of the substance.
Colloidal Spray Method for Low Cost Thin Coating Deposition
Ai-Quoc Pham, Robert S. Glass, Tae H. Lee
U.S. Patent 6,358,567 B2March 19, 2002

A dense or porous coating of material is deposited onto a substrateby forcing a colloidal suspension through an ultrasonic nebulizer andspraying a fine mist of particles in a carrier medium onto asufficiently heated substrate. The spraying rate is essentiallymatched to the evaporation rate of the carrier liquid from thesubstrate to produce a coating that is uniformly distributed over thesurface of the substrate. Following deposition to a sufficient coating
thickness, a single sintering step may be used to produce a dense
ceramic coating. This method allows coatings ranging in thickness
from about one to several hundred micrometers. Also, because themethod uses a plurality of compounds in the colloidal suspension,
coatings of mixed composition can be obtained. Because the method
uses a plurality of solutions, separate pumps, a single or multiple
ultrasonic nebulizers, and varying individual pumping rates and/or
concentrations of the solutions, a coating of mixed anddiscontinuously graded (stepped) or continuously graded layers may
be obtained. This method is particularly useful for depositing dense
ceramic coatings on porous substrates for improving electrode
performance in high-power-density solid-oxide fuel cells and on gas
turbine blades, sensors, and steam electrolyzers. The invention has
general use in preparation of systems requiring durable andchemically resistant coatings and for coatings having other specificchemical or physical properties.
Chimeric Proteins for Detection and Quantitation of DNA
Mutations, DNA Sequence Variations, DNA Damage and DNA
Mismatches
Sandra L. McCutchen-Maloney
U.S. Patent 6,365,355, B1
April 2, 2002

Chimeric proteins having both DNA mutation binding activity andnuclease activity are synthesized by recombinant technology. The
proteins are of the general formula A-L-B and B-L-A, where A is a
peptide having DNA mutation binding activity, L is a linker, andB is a peptide having nuclease activity. The chimeric proteins areuseful for detection and identification of DNA sequence variations,such as DNA mutations (including DNA damage and mismatches)by binding to a mutation and cutting the DNA once the mutation
is detected.

Lawrence Livermore National Laboratory

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32

Patents and Awards

S&TR June 2002

Tiltmeter Leveling Mechanism
Steven L. Hunter, Carl O. Boro, Alvis Farris
U.S. Patent 6,370,784
April 16, 2002

Plates for Vacuum Thermal Fusion
James C. Davidson, Joseph W. Balch
U.S. Patent 6,372,328 B1April 16, 2002

A tiltmeter device having a pair of orthogonally disposed tilt
sensors that can be leveled within an inner housing containing thesensors. An outer housing can be rotated to level at least one
sensor of the pair while the inner housing can be rotated to level
the other sensor. The sensors are typically rotated up to±100 degrees. The device is effective for measuring tilts of wells at
various angles of inclination and can be used to level a platform
containing a third sensor.

A process for effectively bonding plates or substrates of arbitrary sizeor shape. The plates or substrates can be glass, plastic, or alloy with amoderate melting point and a gradual softening point curve. The
process incorporates vacuum pull-down techniques to ensure uniform
surface contact during the bonding process. The essence of theprocess involves the application of an active vacuum source toevacuate interstices between the substrates while providing a positive
force to hold the parts to be bonded in contact. This process allows
the temperature of the bonding process to be increased to ensure thatthe softening point has been reached; it also permits small void areas
to be filled and come in contact with the opposing plate or substrate.
The process is most effective when at least one of the two plates orsubstrates contains channels or grooves that can be used to apply
vacuum between the plates or substrates during the thermal bonding
cycle. Also, providing a vacuum groove or channel near the
perimeter of the plates or substrates is beneficial to ensure bonding of
the perimeter of the plates or substrates and to reduce the unbonded
regions inside the interior region of the plates or substrates.

Ultrashort Pulse Laser Deposition of Thin Films
Michael D. Perry, Paul S. Banks, Brent C. Stuart
U.S. Patent 6,372,103 B1April 16, 2002

Short-pulsed laser deposition is a viable technique for producing
high-quality films with properties close to those of crystalline
diamond. The plasma generated using femtosecond lasers is
composed of single-atom ions with no clusters producing films
with high diamond-to-graphite content. Using a high-averagepower femtosecond laser system, this invention dramaticallyincreases deposition rates up to 25 micrometers per hour (which
exceeds the rate of many chemical vapor deposition processes) andproduces particulate-free films. In the present invention, deposition
rate is a function of laser wavelength, laser fluence, laser spot size,
and target–substrate separation. The relevant laser parameters
ensure particulate-free growth, and characterizations of the films
grown are made using several diagnostic techniques, including
electron-energy-loss spectroscopy and Raman spectroscopy.

AwardsClaire Max, founding director of Livermore’s Instituteof Geophysics and Planetary Physics (IGPP), has been namea fellow of the American Academy of Arts and Sciences.
Founded during the American Revolution by John
Adams, James Bowdoin, John Hancock, and other early
U.S. leaders, the academy is today an international society
with the dual function of electing to membership individualsof exceptional achievement, drawn from science,scholarship, business, public affairs, and the arts, and of
conducting projects and studies responsive to the needs andproblems of society.
Max was selected in the physics division of the academy.
She joined Livermore as a physicist in 1974, founded IGPP

in 1983, and became director of University Relations in 1995.
She now serves as associate director for the National Science
Foundation’s Center for Adaptive Optics at the University ofCalifornia at Santa Cruz, in which Livermore plays asignificant role. She is also a professor of astronomy at UC
Santa Cruz.
Max’s most recent work focuses on the use of adaptive
optics on the telescopes at the W. M. Keck Observatory in
Hawaii. (See the article beginning on p. 12.)
Edward Teller is the only other academy member from theLaboratory. Others selected as fellows in 2002 include
Senator Edward Kennedy of Massachusetts and Academy
Award–winning actress Anjelica Houston.

Lawrence Livermore National Laboratory

Contact:
Rod Balhorn (925) 422-6284 (balhorn2@llnl.gov).

Adaptive Optics Sharpen the View
from EarthAstronomers are reporting exceptional results from theadaptive optics systems installed at the W. M. KeckObservatory in Hawaii and the University of California
Lick Observatory near San Jose. The images are shedding
new light on the formation of stars and galaxies, revealing
unexpected features on planets and moons in our solar
system, and yielding new information on black holes
residing in the centers of distant galaxies. Adaptive optics
measure the distortions of light from a natural star or one
manufactured by a powerful laser, and then remove thedistortions by reflecting the light off a deformable mirrorthat adjusts several hundred times per second to sharpen theimage. Livermore researchers have been among the leaders
in designing and using adaptive optics systems on
astronomical telescopes. Livermore also has been the leader
in designing laser guide stars to allow adaptive optics to be
used over more of the sky. The next generation oftelescopes almost certainly will require laser guide stars andadaptive optics systems.
Contact:
Deanna Pennington (925) 423-9234 (pennington1@llnl.gov).

U.S. Government Printing Office: 2002/783-051-70019

Livermore climate scientists areusing supercomputers to clarify
some issues in the global warming
debate.
Also in July/August• Experiments guide development of codes forpredicting metal failure.
• Statistical tool provides more meaningful
data interpretation.
• 50th Anniversary Highlight: The
Nonproliferation, Arms Control, andInternational Security Directorate had its
beginnings in work to understand andcounter the nuclear threat. Today, thedirectorate’s responsibilities must also
encompass technology and intelligence inbiological and chemical terrorism.

M o n t h

New synthetic molecules known as high-affinity ligandsthat bind to and capture biowarfare agents are being
designed at Livermore. With a bidentate (two-pronged)
structure, their binding strength will be thousands tomillions of times stronger than molecules that join at justone place. The first such ligand is being designed for a
Clostridium neurotoxin tetanus protein, using its structure
as a starting point. Using computational techniques,
researchers have located two adjacent binding sites on thetetanus targeting domain and also identified numerous
compounds that would fit into the sites. Laboratory
experiments using nuclear magnetic resonancespectroscopy and mass spectrometry narrowed the choicesof molecular compounds by determining which compounds
actually bound to the two sites. The two best choices will
be joined by a third linker molecule to create a ligand tobind tightly to the tetanus toxin. Similarly designed
molecules can also be used to target proteins that cause
disease and block their activity. Armed with theradionuclide used in radiation therapy, such molecules
could make excellent cancer-fighting tools. Work has
begun on a high-affinity ligand for a surface receptor for
non-Hodgkin’s lymphoma.

33

N e x tA Two-Pronged Attack on Bioterrorism

Simulations
Explore theCauses andEffects of
Climate Change

C o m i n g

Abstracts

University of California
Science & Technology Review
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June 2002

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Also in this issue:• Adaptive Optics Bring the Cosmos into Sharper Focus• Solving the Mystery of Comet X-Ray Emissions• 50th Anniversary Highlight: The Enduring Contributionsof Chemistry and Materials Science