STUDIES AT LBL'S BEVALAC WILL HELP RESOLVE UNCERTAINTIES ABOUT RADIATION RISKS TO ASTRONAUTS
MIDWAY THROUGH THE 20TH CENTURY, more than a decade before a human first rocketed into space, scientists at this Laboratory began exploring the biological hazards of cosmic rays. The work was an outgrowth of research that began in the 1930s, when the Laboratory became the birthplace of nuclear medicine, conducting seminal studies on the medical uses of radiation and on radiation safety.
In a 1952 paper, biophysicist Cornelius Tobias outlined the spectrum of radiation to which a human space traveler would be exposed and described potential effects, including cancer, brain and nerve-tissue damage-and a remarkable, optical phenomenon. When the nuclei of heavy elements that streak through space strike a human eye, a future astronaut would perceive ghostly flashes of light, Tobias predicted.
Twenty years after Tobias first described the phenomenon, the lunar crew of Apollo 11 reported seeing odd ''light flashes and streaks." So did astronauts aboard six subsequent lunar missions. Yet, back on Earth, many experts scoffingly dismissed these reports.
To confirm the existence of these effects, Tobias conducted a unique experiment at the Bevalac, an accelerator that can be likened to a cosmic-ray factory. The Bevalac can generate a stream of particles akin to those that flash across interstellar space. The machine strips electrons from heavy elements such as iron, accelerating and focusing the nuclei into a beam of particles traveling at nearly the speed of light.
Tobias, in a controlled experiment, was exposed to a beam at the Bevalac and observed a visual phenomenon never before seen on Earth.
''You see visual flashes," he later recalled. ''It is an exhilarating sensation. It is as though you are looking into the universe itself."
This visual effect remains puzzling. Scientists know what type of radiation causes the effect and what part of the eye is involved, but the physical and biological basis of the effect has been only partially explained.
While significant scientific progress has been made toward understanding cosmic rays since Tobias' 1952 prediction, much still remains to be learned. Scientists know that cosmic rays cause multiple biological effects. But the complex chain of molecular events triggered by these exposures is uncertain and the risk of cell damage, cancer, and genetic mutation unknown. Also, the best means and materials to shield astronauts, minimizing their risk, remains undecided.
Lawrence Berkeley Laboratory has proposed using its ground-based cosmic-ray factory to explore and resolve these mysteries. At this time, the Bevalac is the only facility in the country capable of simulating the spectrum of radiation native to space-from protons to highly energized particles as heavy as uranium. Under the proposal, the U.S. Departments of Energy and Defense and the National Aeronautics and Space Administration would join in dedicating LBL's Bevalac to a space radiation effects research program. The program is a prerequisite to the nation's plans for humans to eventually explore the planets.
Ben Feinberg, a physicist with the- Accelerator and Fusion Research Division and head of operations at the Bevalac, is the principal investigator on the LBL proposal to operate the facility for space research. Feinberg points out that for many years NASA scientists, along with researchers from LBL and elsewhere, have used the Bevalac to study how cosmic radiation interacts with matter-everything from electronics to spacecraft shielding to human cells. Feinberg says this research would gradually increase so that by the middle of the decade a comprehensive program would be under way at the Bevalac and the facility predominantly devoted to this space initiative.
Working at the Bevalac, scientists would use cell cultures and animal models to assess the biological consequences of exposures to the different particles that are components of the space radiation environment.
In the past, risk has been estimated by dosage, a measure that gives little insight into the precise, long-term health effects when low doses are involved. Researchers say they can improve on this approach and intend to develop detailed knowledge able to pinpoint the damage that can be caused by even a single particle.
Research would also be conducted on measures to counter radiation. When the charged particles (also known as ions) of heavy elements encounter a spacecraft, they are not stopped in their tracks. Instead, they either pass through, slowed but with their energy largely intact, or hit other ions and shatter into a shower of fragments. As heavy ions and their fragments pass through humans, damaging interactions can occur.
Experiments would be conducted at the Bevalac to examine how various materials that could be used in a spacecraft wall would alter the cascade of particles that would ultimately reach an astronaut. Since it is almost impossible to totally stop these particles, biologists must deduce what is the most benign spectrum of particle radiation achievable. Then other scientists must determine what combination of shielding materials would produce this minimal radiation field inside the spacecraft.
The payoff from shielding research could add up to several billion dollars in savings on an interplanetary mission.
As currently envisioned, an interplanetary spacecraft would weigh some 300 tons and include 30 tons of shielding material. According to Tom Ward, scientific and technical advisor to the Department of Energy's Office of Space, ''With research, it may be possible to redesign more effective, lighter-weight shielding using new composite materials. Conceivably, shielding could be reduced in weight down to between two and five tons. In terms of the cost of an interplanetary mission, we estimate that there will be a $50,000 savings for every pound of shielding weight that can be eliminated."
The studies at the Bevalac not only can reduce the costs of an interplanetary mission, but are vital to the well-being of the astronauts. Besides the extended duration of exposures on an interplanetary mission, the spectrum of radiation differs from past missions near Earth, and overall exposures and biological risks increase.
Stanley Curtis, a biophysicist with LBL's Cell and Molecular Biology Division, helped write the book on radiation exposures for astronauts and currently is busy rewriting the book on how to gauge the biological effects of cosmic rays. Since 1965, he has worked on understanding what happens to heavy ions as they travel through matter. Curtis is a member of the National Council on Radiation Protection and Measurements which in 1988, published guidelines that today govern astronauts' exposures in low Earth orbit. A committee on which he currently sits is revising these guidelines, incorporating what has been learned during the continuing analysis of epidemiological data
from the Japanese A-bomb survivors. Curtis notes that up until now human space travel has been confined to the proximity of Earth. Within this domain, astronauts are exposed to radiation from the trapped radiation belts but are largely protected by the Earth's magnetic field from galactic cosmic rays emanating from outside the solar system. Astronauts on a planetary exploration will be exposed to these galactic cosmic rays which consist of a different spectrum of energies.
Estimates by Curtis and the National Council on Radiation Protection and Measurements indicate that during a three-year Mars mission, astronauts would be exposed to roughly one sievert (100 rem) of radiation to their blood-forming organs. This is more than six times the maximum allowable dose equivalent over three years for nuclear workers in the U.S. By way of contrast, astronauts in low Earth orbit typically receive 1/1000th of the dose of a Mars voyage during their seven to 10-day missions.
The components that comprise solar and galactic cosmic rays include protons (85 to 95 percent), helium ions (five to 14 percent), and the more hazardous high-energy heavy ions. Importantly, up to one percent of galactic cosmic rays consist of heavy ions, whereas particulate radiation from the sun generally contains less than one-tenth this number.
Both protons and heavy ions can cause cell damage that results in tumors. However, because of the greater charge and ionizing power carried by a heavy ion, the likelihood of its causing a tumor may be roughly 10,000 times that of a proton, says Curtis.
Curtis has quantified the radiation that astronauts would be exposed to during a three-year Mars mission by each of its constituent elements. His calculations assume that astronauts are protected by relatively heavy spacecraft shielding but that no solar particle event occurs during the voyage. (On rare, sporadic occasions, certain types of solar flares generate extraordinary storms of radiation. Since this radiation consists of predominantly low-energy protons, astronauts can effectively protect themselves with emergency ''storm shelters.")
''Once a spacecraft is outside the Earth's magnetosphere," says Curtis, ''the probability is that any given cell nucleus within an astronaut will be hit once every three days by a proton and once a month by a helium ion. The heavier ions will hit less frequently. That same cell, for instance, will be hit once every six years both by a carbon and oxygen ion and once every 100 years by an iron ion. When the full spectrum of particle radiation is included, over a three-year mission a heavy ion with charge between 10 (neon) and 26 (iron) would hit one in every three cell nuclei."
Curtis' precise calculations are a state-of- the-art demonstration of contemporary space physics. Curtis is even able to predict that six percent of all cell nuclei will be hit two or more times by heavy ions with charges between 10 and 26 during this hypothetical mission.
But deducing the biological effects of these hits is another matter altogether. Whether a particular hit will be benign or perhaps result in a tumor, a cataract, or damage to neural tissue is unresolved.
The proliferation of standard measures used to quantify ionizing radiation and exposures-including roentgen, red, gray, absorbed dose, rem, sievert, and dose equivalent-testifies to the complexity of gauging the biological effects. Curtis believes he has a better way to assess and pinpoint risk, at least to astronauts traveling outside the Earth's magnetosphere.
''Galactic cosmic rays are unusual in that they are highly penetrating and will traverse virtually all the cells of the body as single parades," says Curtis. ''What we need is a gauge of risk that accounts for this and that gives us a handle on the catalytic biological events that, years later, can result in effects such as cancer."
The abnormal transformation of a cell that results from radiation begins with molecular events in the DNA, such as deletions of genes, translocations, and other genetic rearrangements. These events, which can be a precursor to cancer, are probably initiated by single traversals of cell nuclei by charged particles. For that reason, says Curtis, counting the incoming particles that traverse a given point should offer a more scientific basis to assess risk. Curtis' approach introduces a fluence-related risk coefficient. Fluence refers to the number of incoming particles per unit of area. The system is a departure from the standard measure of dose equivalent, which is a calculation of average energy deposition weighted to yield the equivalent dose of gamma rays that would produce the same biological effect. Instead, Curiis accounts directly for heavy-ion exposures, the critical component of the radiation field outside the Earth's magnetosphere. ''We have a lot to learn," says Curtis. ''What is the probability per unit fluence of triggering various triggering various biological responses- say, for instance, a cellular event that initiates or promotes the formation of a tumor, or cataracts, or neural damage? Different types of particles have different probabilities for inducing tumors.
''These are unknowns, and they imply an ambitious future research agenda. The understanding of how cancer is induced by this type of ionizing radiation will come from a study of the biological effects that occur along the tracks of single particles. This coupled with a better understanding by biologists of the succession of important molecular events in the carcinogenic process will allow us to estimate more confidently the risk of radiation exposure on long-term planetary missions."
Curtis is part of a collaboration of physicists, biologists, and educators that is about to undertake these studies at a NASA funded Specialized Center of Research and Training in Radiation Health. Led by Aloke Chatterjee of LBL's Cell and Molecular Biology Division, the center is teaming researchers at LBL and at Colorado State University's Department of Radiological Health Sciences. Work will focus on developing a better understanding of the health risks of heavy-ion exposures and on training a new generation of research scientists to serve the nation during the approaching era of long-term human space missions.
Heavy ions differ from other types of radiation in terms of the potential severity of their effects on human DNA. ''We may have never been subject to heavy ions during evolution," says Chatterjee. ''Had the Earth's magnetic field and atmosphere not protected us from the ions, I don't believe we would have evolved the same way."
To understand this, it helps to picture the architecture of DNA, the macromolecule which regulates the chemical activities of each cell as well as its ability to accurately duplicate itself. DNA consists of two strands that, like a spiraling staircase, wind around one another and are bound by stairstep-like connections. Each stairstep consists of a bound pair of two compounds called nucleotides. Altogether, there are four types of nucleotides, but the same two always pair off together. Thus, if one of the pair is damaged or broken away, the other can serve as a template, facilitating repair by an appropriate replacement nucleotide.
Other forms of radiation may result in breakages of a single strand of DNA, but heavy ions have a greater likelihood of causing double-strand breaks, disrupting ready repair.
Double-strand breaks have been linked to cell death, cell mutation, cell transformation, and carcinogenesis. These double breaks apparently can be repaired by cellular enzymes but to what extent remains unknown.
At the Bevalac, researchers will conduct experiments to see how repair varies following irradiation by different heavy ions. They will also explore the mechanisms for mutations.
Heavy ions can cause biological damage either indirectly or directly. Stripped of electrons as they travel across the galaxy, heavy ions carry a large positive charge. As they shoot through a human, they primarily interact electromagnetically, mainly with the water that comprises much of a human being. These indirect interactions with the electron clouds within volumes of water-electrons are ripped free, triggering a chaotic cascade of chemical changes-are the most common.
Direct interactions involve energy deposition directly in a DNA molecule. This phenomenon can cause various types of DNA damage, including double-strand breaks.
''We don't know whether both direct and indirect mechanisms are responsible for mutations," says Chatterjee. ''When we understand that, we will be in a position to resolve other questions: Can we mitigate DNA damage? Can we protect cells?"
Spacecraft shielding will provide a fortress of protection for the astronauts. But no conceivable spacecraft wall can completely shield out ionizing radiation.
What configuration of materials would most effectively shield astronauts? Jack Miller, a nuclear physicist in LBL's Research Medicine and Radiation Biophysics Division, is conducting studies and experiments that can help answer this question. Miller currently heads a program initiated by LBL's Walter Schimmerling, who is now on leave to NASA to head its radiation health program.
Miller says that a critical test for shielding on an interplanetary spacecraft will be how well it mitigates the biological effects resulting from iron nuclei. Among the heavier ions, iron is relatively abundant. When galactic cosmic-ray heavy ions are weighted both by their numbers and by their potential biological effects, iron is the most significant.
''We have a very complex problem," says Miller. ''For every different material and thickness of shielding, you get a different radiation environment inside the spacecraft.
''For instance, if you tell me that you have an iron nucleus coming in at a certain energy, I can compute how thick a piece of aluminum you would need to stop it. But a problem remains. Though you might be able to stop the iron particles, some of them are going to be involved with head-on collisions with the nuclei of aluminum atoms. When that happens, they will fragment into lighter nuclei that will continue to traverse the spacecraft. It is very difficult to predict what the products of those collisions will be. And it is impractical to have a spacecraft shield that can stop all these secondary particles."
Studies conducted by the Schimmerling-Miller group aim to measure this secondary radiation field, with the ultimate goal of minimizing its effect on astronauts.
In a typical experiment, a beam of heavy ions from the Bevalac is directed at a piece of shielding material, behind which detectors are placed to measure the complex radiation field produced by interactions between the beam and shield. In related work, similar detectors have been used to study the role of nuclear fragmentation in LBL's experimental cancer radiotherapy program, in which beams from the Bevalac are used to bombard tumors.
''Neon is one of the ions commonly used in the Bevalac radiotherapy program," explains Miller, ''but what happens as these ions traverse the body? A neon nucleus has 10 protons and 10 neutrons, and we know that some of the neon ions will fragment as they pass through bone and tissue. Neon can fragment in a number of ways-for example, into a carbon and two helium nuclei-with varying consequences for the surrounding healthy tissue. These studies have allowed us to begin to characterize and quantify this complex radiation field."
This knowledge about the particles' characteristics currently is being used to help NASA design spacecraft shielding.
Rather than test every conceivable material and thickness of shielding, NASA is relying on computer models. One such model has been developed by Stan Curtis and another by Lawrence Townsend and John Wilson of NASA's Langley Research Center. The models predict the radiation environment, given a specific particle energy and thickness of shielding material. The LBL group provides input to the model in terms of nuclear fragmentation cross sections, a mathematical expression of the probability of particular fragments resulting from nuclear collisions with the shielding.
The Bevalac makes it possible to verify and to refine the predictions about which shielding materials are most effective. Different materials can be irradiated and tested at LBL's cosmic-ray factory. Ultimately, through feedback from this research, efficient, protective shielding material will be fabricated.
Miller says this work represents the fruits of decades of theoretical work and scientific experimentation. ''In many respects," he says, ''we have developed a very sophisticated understanding of the effects of radiation. But n some areas, our understanding is still quite limited. We know a great deal about the effects of high doses and high dose rates, but much less about the lower dose rates typical from exposure to cosmic rays in space.
''By taking advantage of the synergy among scientists in many different disciplines, we can develop a more precise understanding of the space radiation environment. Our ultimate goal is to make extended human habitation in space a practical reality."
-JEFFERY KAHN
NEW NMR TECHNIQUES ARE CLARIFYING THE STRUCTURE OF SOLIDS
THE PHENOMENON KNOWN AS NUCLEAR MAGNETIC RESONANCE (NMR) takes place at a dimly lit crossroads of science where the ordered grid of geometry, the metaphysical maze of quantum mechanics, and the concrete highway of materials science all come together.
In that paradoxical place, scientists who work with NMR may find-like Alice's White Queen-that they have to think about six impossible things before breakfast. Members of LBL chemist Alex Pines' group, for example, are currently thinking about conundrums like the following:
Alex Pines began thinking about some of these conundrums more than 20 years ago, when he was a graduate student of chemist John W. Waugh at the Massachusetts Institute of Technology. A paper based on his thesis described the transfer of polarization from hydrogen nuclei (protons) to carbon-13, thus making possible the first high-resolution NMR study of carbon-13. Today, that germ of an idea is the basis of a promising new possibility for studying the surfaces of solids.
Another idea from Pines' student days-making time appear to run backwards, in a complex system with many interacting particles, by forcing the spins of nuclei into an earlier configuration-is proving useful in a new technique known as ''multiple pulse zero-field" NMR spectroscopy. And his lifelong love of mathematical puzzles and oddities turns out to have a lot of bearing on the study of glass and other amorphous materials.
Pines' interests may diverge in many directions, but his focus is results-oriented. Over the past decade, Pines' team, associated with LBL's Materials Sciences Division and the UC Berkeley Department of Chemistry, has become a leading center in the research, development, and use of NMR techniques. Among the group's pioneering advances in NMR spectroscopy are multiple-quantum NMR, zero-field NMR, and double-rotation NMR. All three techniques have greatly extended the applications of NMR to new materials.
Now, Pines' team-currently consisting of about 20 researchers, including postdoctoral fellows, foreign visitors, and graduate students-is hard at work on a number of new advances in NMR and the application of all the techniques to new problems.
There are three broad areas of activity under way. First and foremost (because it provides the foundation for all the other work) is pure science-experiments aimed at the understanding of such phenomena as the nature of the interaction between radiation and matter, chaotic behavior, nonlinear dynamics, topology and geometry, and dynamical symmetry. These studies are usually divorced from specific techniques but may have important implications for all of them.
Following closely in the trail blazed by the pure science experiments comes the development of new methods and technologies. There are currently a number of new techniques under development-including dynamic-angle spinning (DAS) and double- rotation (DOR) NMR; surface-enhanced NMR; multiple-pulse zero-field NMR; NMR imaging of flow and turbulence; SQUID (Superconducting QUantum Interference Device) NMR; and two-dimensional NMR correlation methods.
Finally, there is the application of the various techniques, old and new, to the study of materials (see sidebar, page 18).
Nuclear magnetic resonance is phenomenon that occurs when matter interacts with a magnetic field. It is based on the fact that the spinning protons (hydrogen nuclei) in matter oscillate like tiny gyroscopes when they are trapped inside a magnetic field.
In NMR spectroscopy, a sample is placed in a magnetic field, which forces the spins of the nuclei into alignment. The sample is then bombarded with radio-wave pulses. As the nuclei absorb energy from a pulse, they topple out of alignment with the magnetic field, and as they lose the absorbed energy they line up again. By measuring the specific radio frequencies that are emitted by the nuclei, and the rate at which realignment occurs, scientists can gain detailed information on the atomic structure and motion of the sample.
But magnetic and electrical interactions between atoms can blur the spectrum associated with the spinning nuclei. For a long time, the application of conventional NMR spectroscopy was limited to liquids (where the rapid, random motion of the molecules averages out blurring effects) and to certain crystalline materials.
Many of Pines' contributions, over the past decade, have been aimed at overcoming these limitations and extending the use of NMR to new areas and new materials- particularly solids and amorphous materials. Now, an approach involving surface-enhanced NMR is leading to an extension of the possibilities of NMR in the analysis of the surfaces of solids.
''Surfaces are important," says Pines, ''because lots of chemistry takes place there. But NMR has not proven useful in the study of surfaces, except in systems with very large surface areas. There are two main reasons-one absolute, one relative."
The ''absolute" reason is the fact that surfaces constitute only a tiny fraction of any material's volume. "NMR is a relatively low- sensitivity technique," notes Pines, "so when it's combined with the small percentage of surface, you don't get much signal."
Added to this ''absolute" problem is the ''relative" one that even if an NMR signal from the surface is detectable, it is overwhelmed by the signal coming from the bulk. And some phenomena-catalysis, for example-are strictly surface phenomena, scarcely involving the bulk material.
The way around both of these problems may lie in the fusion of two ideas. One is the optical-pumping technique developed by William Happer (now director of DOE's Office of Energy Research) and his co- workers at Princeton University. The other is the idea of transferring spin from one kind of particle to another-a phenomenon first demonstrated in Pines' ''cross-polarization" work with carbon-13 at MIT almost 20 years ago. In this case, cross-polarization-based on the pioneering work of Elwin Hahn and Sven Hartmann at Berkeley-is used to transfer spin from polarized light to a gas and then to the surface of the material of interest.
Happer developed a two-step, optical-pumping process that begins with circularly polarized light (photons) from a laser and transfers the angular momentum of the photons to the nuclear spin polarization of xenon gas, resulting in a highly polarized gas. Adapting Happer's technique, Pines' team then brings the gas into contact with the surface of interest. The gas is adsorbed to the surface, forming a thin film of solidified xenon that yields high-intensity, characteristic NMR signals.
Says Pines, ''The next-and crucial- step will be to see if we can transfer the spin one more time-from the adsorbed film of xenon to the protons of the surface we're interested in. The real pay-off, of course, will be to transfer the polarization and show that the NMR spectrum of the surface is now different from the spectrum of the bulk. If we can do that, we will have a way to distinguish surface from bulk, and focus in on what's happening on the surface."
Another major thread of research in Pines' group is aimed at improving the ability of NMR spectroscopy to be applied to solid materials of various types.
Zero-field NMR was pioneered in Pines' lab in the early 1980s. This technique allowed NMR to be applied to amorphous substances like glass, and polycrystalline ones, like zeolite catalysts. In conventional NMR spectroscopy these materials yield a broad, relatively featureless spectrum that contains little or no structural information. That happens because each 'crystallite,' or individual grain, of the substance has its own random orientation with respect to the magnetic field.
By means of zero-field NMR, in which orientation to an external field plays no role, one obtains sharp, crystal-like spectra, even in orientationally disordered materials.
Now, an extension of the technique, known as multiple pulse zero-field (MPZF) NMR spectroscopy, is under development in Pines' lab. The new technique involves manipulating the spinning particles in such a way that their spins-and, indirectly, the direction of time-seem to run backwards. While the sample is m the ''zero-field" condition (that is, out of the strong external field) a much weaker magnetic field is rapidly pulsed on and off. This pulse affects the internal dipole field and causes the spinning protons to precess-like tops winding down-in such a way that they reverse direction.
When the spectrum is finally measured in high field, the ''memory" of the time-reversed state causes a dramatic reduction of the number of lines in the spectrum, permitting scientists to see details of structure that were previously hidden.
Two other important new techniques- double rotation (DOR) and dynamic-angle spinning (DAS)-use ideas rooted in pure mathematics to extend NMR spectroscopy to a whole new class of important solid materials.
Like zero-field NMR, both DOR and DAS seek to ''make a solid behave more like a liquid"-that is, to give solid materials the symmetry with respect to an external magnetic field that liquids have by virtue of the rapid, random motion of their molecules.
DOR and DAS make use of complex spinning techniques to achieve the symmetry of the icosahedron-a geometric figure with 20 faces and 12 vertices that represents an appropriate approximation to the ideal symmetry of the sphere.
While the problem with NMR spectroscopy of solids is the broadening of spectral lines due to the fact that each atom has its own individual orientation to the external magnetic field, in a liquid symmetry is spherical: The tumbling of the atoms causes all the orientations to average out. But there is no way to make a ''lump" of solid matter spin so as to achieve spherical symmetry.
It turns out, however, that for nuclei that are themselves spherical, cubic (fourfold) symmetry is a close enough approximation to the sphere to yield satisfactorily narrow NMR lines. Cubic symmetry can be attained through a technique known as magic-angle spinning, originally developed by Raymond Andrew and Irving Lowe in the 1950s.
In magic-angle spinning, a sample is rapidly rotated around an axis that is inclined at a carefully chosen ''magic" angle (the angle between the body diagonal and the face of a cube, or 54.74 degrees), with respect to the external magnetic field. This spinning motion approximates the natural tumbling that would occur in a liquid.
The technique has proven extremely useful for those materials in which nuclei are spherical. In carbon-13 and silicon-29, for example, resolution is improved 100 times or more.
But in nuclei that are not spherical (also called quadrupolar nuclei), cubic symmetry is not enough. Such nuclei have electric as well as magnetic moments, which complicate the picture. In these materials (which include such important species as oxygen-17, sodium- 23, and aluminum 27), magic-angle spinning improves resolution only three or four times-usually not enough to permit the differentiation of atomic sites.
We realized that the logical next step was to go to higher symmetry," says Pines, "but we also knew that such symmetry could never be achieved by rotating the sample about a single axis." It became clear that one must rotate the sample around two axes, which can be carried out in two ways: double- rotation (DOR) NMR and dynamic-angle spinning (DAS), based on icosahedral symmetry.
In DOR, the sample is spun around two axes at the same time, like a top within a top. The result is two ''magic angles"- the conventional one of 54.74 degrees plus a new magic angle of 30.56 degrees.
In DAS, the sample is spun sequentially about two different axes, inclined to the magnetic field at angles of 37.38 and 79.19 degrees; the sample is rotated about the first axis, reoriented, and rotated about the second axis. A computer program then analyzes the data, providing a high-resolution spectrum.
Based as they are on basic mathematical principles of icosahedral symmetry, DAS and DOR may prove particularly valuable in the study of local order in glass and other disordered materials which are thought to involve ''frustrated" icosahedral structures. In theory, such structures shouldn't exist at all because icosahedrons, with their five-fold symmetry, can never uniformly fill a three-dimensional space-hence the ''frustration."
There is also considerable controversy about the structure of quasicrystals which involve icosahedral structures. X-ray diffraction (until now the only available technique) shows only the overall, long-range order of the whole system. Dynamic-angle spinning (DAS), on the other hand, can reveal areas of local order, and thus may soon provide answers to some important questions.
Pines switches easily between the ivory tower and the real world. He is particularly proud of his group's accomplishments in the area of technical innovation and technology transfer. He notes that two companies have already licensed systems based on DOR and DAS-just as instruments based on the earlier mass-polarization and multiple- quantum techniques long ago entered the marketplace. DOR was honored last year with an ''R&D-100" award, presented by the publication Research and Development for outstanding achievement in technology.
The most valuable form of technology transfer, though, may be a human one-the steady stream of former students and postdocs from Pines' team who enter industry. They are as likely to be found at AT&T Bell Laboratories, IBM, Exxon, Monsanto, Du Pont, Squibb, GE, or Lockheed as they are at UC Berkeley, Yale, MIT, Princeton, Caltech, or the Weizmann Institute.
-JUDITH GOLDHABER
While work proceeds in Alex Pines' research group in developing new methods of NMR spectroscopy, a parallel effort is aimed at applying the various techniques, old and new, to a wide variety of materials and problems. Double rotation (DOR) and dynamic- angle spinning (DAS) extend NMR spectroscopy to the analysis of many technologically important solid materials. In the important isotope oxygen-17, for example, the width of lines in the spectrum has been reduced by DOR to about 50 hertz (from, typically, 10,000 hertz for static NMR spectroscopy ). The results involving oxygen-17 are of particular importance because many oxi des (compounds of oxygen) exhibit superconductivity-the ability to carry electri cal current without loss due to resistance-at relatively high temperatures.
Studies with DOR may permit, for the first time, a detailed look at what is taking place at the oxygen sites in these materials. A novel application of DOR spectroscopy to oxygen-17 is being pursued by Pines collaborator Jonathan St ebbins, a geologist at Stanford University. Stebbins is interested in using DOR to study oxygen-rich minerals in the earth.
"You might be surprised to learn that there's a lot more oxygen in th e earth's crust than in the atmosphere we breathe," says Stebbins. "About 80 per cent of the crust and mantle is oxygen, mainly in the form of oxides of common m inerals."
To understand the properties of these materials-many of which have great technological importance-it is necessary to explore what Stebbins calls their s tructural environment: for example, exactly where does the oxygen atom fit into the crystal structure?
Currently, Stebbins' research is focusing on synthetic silicates rather than real minerals, for two reasons: first, in natural minerals, the proportion of oxygen-17 is low, while in synthetics, it can be boosted to useful levels; se cond, virtually all natural samples contain iron, which interferes with NMR beca use of its magnetic qualities.
"At the moment," says Stebbins, "we're interested in showing that the DO R technique can reveal the structural environment of oxygen, and so far we're ve ry encouraged that it can.
A high-tech material so "hot" that it featured on the cover of Science's special issue on new materials in February 1990 has been spectroscopically analyzed by members of Pines' team using DOR. The material, known as VPI-5, is a compound of aluminum and phosphorus, synthesized by M.E. Davis and co- workers at Virginia Polytechnic Institute.
The experiment with VPI-5, the first important commercial application of DOR spectroscopy, was conducted in collaboration with Davis (now at Caltech).
VPI-5 is exciting because its crystalline structure can take the form of an open sieve, containing molecule-sized systems of channels and cavities. During synthesis, "guest" elements such as metals or silicon can be incorporated into this "host" sieve, creating materials that could take part in a number of industrially important reactions.
VPI-5 is of special interest because its sieve openings are large enough (12 angstroms or greater) to permit the passage of large molecules. In petroleum refining, for example, VPI-5 might be used as a catalyst to crack large hydrocarbons that are currently discarded.
In order to develop such commercial applications, researchers require detailed information about VPI-5's crystalline structure. In particular, they have to be able to distinguish between different atomic sites-the locations and positions of atoms in the crystal lattice.
In the LBL experiment, a sample of VPI-5 was first dehydrated and then slowly allowed to absorb water from the air. DOR spectroscopy revealed that the water does not go into random locations in the lattice, as might have been expected, but instead seems to fit into certain specific locations. The research team also found that the aluminum is far more ordered than had expected and that the order is strongly preserved after incorporation of the "guest" molecules.
Now that high-resolution spectroscopy of VPI-5 has been successfully demonstrated with water as the "guest" molecule, the researchers are interested in extending their studies to more catalytically interesting materials. They are currently using DOR to investigate the incorporation of semiconductor clusters and of organic compounds such as para-nitro-aniline in the molecular sieve of VPI-5. These materials are considered top-rated candidates for the very fast optical switches that will be required for the next generation of high-speed computers. -JG
Materials Sciences Division researcher Gerard Chingas is generating NMR images of complex structures in materials, using statistical approaches to process the data derived from NMR signals. This method can not only provide a description of very fine details but also sharply reduces the time required for data processing.
"By characterizing properties statistically," says Chingas, "we retain much more information when we attempt to characterize smaller structures, since their number is correspondingly greater, and their aggregate volume is large."
A slice image (A) shows half-millimeter nylon fibers in a tube 6 millimeters in diameter (filled with water to give an NMR signal). By squaring the data, Chingas obtained NMR diffraction patterns (B) that reflect the average fiber arrangement. Fourier transformation of each diffraction pattern resulted in a third image (C), which indicates fiber size and spacing directly. By preprocessing enhancements, he produced a three-dimensional image (D) for 0.11 mm fibers, in which the center peak denotes the average fiber size, and the distance from the peak to the rings indicates the spacing between fibers.
Working with a team of students and postdocs, Chingas plans to examine spatial patterns in technologically important materials, such as ceramics, where the strength or weakness of the material can depend on very small features. Using the statistical approach, which permits the averaging of signals from rapidly fluctuating fields, he will also be able to characterize turbulent fluid flow fields, such as are encountered during polymer processing.
ON THE HOMEFRONT, the relationship between humans and mice has always been an ambiguous one, dependent upon the age of the relating human. As children, encouraged by books, cartoons, and a panoply of toys depicting mice as kind, comical, brave, and invariably cute, we cheer the tiny creatures on in their uphill struggle to survive. As adults, we continually seek better means of dispatching them.
No such ambiguity has existed in the scientific laboratory, however, where mice have always been looked upon favorably. Their small size makes them easy to maintain and handle in large numbers. They are fast-breeding-nearly 90 percent of all mouse- matings result in mouse pups. A lot is known about them, and, in many ways, their physiology closely mimics that of humans.
Over the years, the cultivation of genetic variations in mice has resulted in substantial populations of inbred strains and interstrain hybrids that are especially valuable for genetic research. This value was enormously enhanced with the development in 1980 of the transgenic mouse-a mouse that carries the DNA of another species. The combination of transgenic technology with specific strains of genetically altered mice has become a powerful tool for the study of genetic diseases in humans. Already, transgenic mouse models have been produced for the study of the AIDS virus, several forms of cancer, and Lesch-Nyhan syndrome, a neurological disorder that causes retardation.
In 1991, two new types of transgenic mouse were added to the list by LBL's Edward Rubin, a geneticist who has a joint appointment with the Cell and Molecular Biology Division (CMBD) and the Research Medicine and Radiation Biophysics Division (RMRBD). The first type of mouse provided medical researchers with a long-sought model for studying human sickle-cell anemia. The second furnished direct experimental evidence that the risk of heart disease depends on the balance between so-called good and bad cholesterol rather than the total amount of cholesterol.
Sickle-cell anemia affects about 50,000 black Americans-one out of every 500 persons of African ancestry in this country. The disease, which is believed to have evolved in Africa as a natural defense against malaria-spreading mosquitoes, is caused by a mutant form of hemoglobin, the iron- containing protein in red blood cells that is responsible for carrying oxygen from the lungs to the rest of the body. Under certain physiological stresses, such as a decrease in oxygen, this mutant protein-known as hemoglobin S-will polymerize, forming a rigid chain that may distort a blood cell into the shape of a ''sickle." Lacking the flexibility of normal disc-shaped cells, these sickled cells are unable to squeeze through capillaries. This impairs the flow of blood, reducing the body's supply of oxygen. Damage from the reduction in oxygen accumulates until tissue cells die and organs fail.
Although an estimated eight percent of black Americans carry the hemoglobin-S gene, only those who inherit it from both parents contract sickle-cell anemia. Intensive studies have resulted in a detailed understanding of the disease on both a cellular and a molecular level, but there is still no effective treatment-a failure medical researchers attribute in part to the lack of an animal model.
Rubin and his collaborators have developed transgenic mice which carry human genes that produce a rare but naturally occurring form of hemoglobin with a great propensity for sickling. The red blood cells of these mice will sickle under the same conditions that cause red cells to sickle in humans with the disease. This should enable researchers to track the progress of sickle-cell anemia and to test experimental treatments.
The collaborators working with Rubin on the sickle-cell anemia transgenic mice were Mohandas Narla, leader of CMBD's hematopoiesis research group, and Elizabeth Spangler and Shirley Clift of RMRBD Collaborators outside of LBL were Ewa Witkowska and Bertram Lubin, at Children's Hospital in Oakland, and Peter Curtin, with the Department of Medicine of the University of California at San Francisco.
Previously, Rubin and his collaborators had developed strains of transgenic mice whose blood cells would not sickle even though the animals carried human sickle-cell genes. The key to the induced ''in vivo" sickling obtained with the newest strain was the use of a gene that expresses a variant of hemoglobin-S called ''hemoglobin-S Antilles." Red cells containing this protein are much more likely to sickle than those containing hemoglobin-S, under similar conditions.
Explains Rubin, "Sickling occurs when hemoglobin proteins precipitate out of solution during a state of deoxygenation. Hemoglobin-S Antilles gives up its oxygen much easier and w ill precipitate from solution much _ more readily than hemoglobin-S."
A hemoglobin molecule is made up of two polypeptide chains-alpha and beta- that must also interact in order for cells to sickle. Unlike his previous transgenic sickle- cell mice which produced only human beta chains, Rubin's new mice contain genes for expressing both a human beta chain (S Antilles) and a human alpha chain.
Says Rubin, ''As a result of the presence of human beta S Antilles and human alpha chains in mouse red cells, these cells sickle when placed in a test tube or when an animal containing them is placed in a low oxygen environment. This is similar to what occurs in humans with sickle-cell anemia."
To create their mice, Rubin and his collaborators remove fertilized mouse eggs from the mother at a time while the pronuclei derived from the sperm and the pronuclei derived from the ovum are still separate. One of these pronuclei-usually the sperm-derived because its larger size makes it an easier target- is co-injected with cloned fragments of human DNA that contain the beta S Antilles and the alpha-globin microinjection, the eggs culture. Those that survive and divide into two-cell embryos are then implanted into a surrogate mother.
At birth, mouse pups are screened for human DNA. This is done by scraping cells from the tails of the mice and subjecting the cells to molecular biological analysis. Animals containing human DNA sequences are then tagged for study. These mice carry the human sickle-cell genes and produce human hemoglobin-S Antilles proteins in their red cells. They also pass the human genes on to their offspring.
''About one out of every 100 eggs we inject will become a transgenic mouse," says Rubin. ''About half of the offspring of these mice will also be transgenics."
Through continued breeding of their transgenics, Rubin and his colleagues have built up a permanent stock of mice that are ''homozygous," meaning all of their offspring will inherit the sickle-cell genes.
''We now have a mouse model with disease severity similar to that of an individual with a mild form of sickle-cell anemia," Rubin says. ''The next step is to further engineer the mouse to develop an accurate model for individuals with severe forms of this disorder."
Working with a second team of collaborators, Rubin demonstrated that ''good" cholesterol lives up to its name and does indeed offer protection against heart disease.
Heart disease remains the leading cause of death among all people in the United States, and the majority of these deaths are the result of atherosclerosis-the clogging of arteries through the buildup of plaque deposited primarily by low-density lipoprotein (LDL) or ''bad" cholesterol. Scores of epidemiological studies have suggested that for both humans and animals, the presence of atherosclerotic plaque and the resulting risk of atherosclerosis is reduced if there is a high ratio of high-density lipoprotein (HDL)-the ''good" cholesterol-to LDL. However, whether HDL is directly responsible for this reduction or only an indicator of some other process taking place has been the subject of much debate.
After several months on high-fat diets, the transgenic mice genetically engineered to have high levels of human HDL and apolipoprotein Al (ApoA-I), the main protein component of HDL, showed almost no signs of atherosclerosis. Non- transgenic mice fed the same diets developed numerous fatty deposits in their arteries-a precursor to atherosclerotic plaques.
''This direct study on the transgenic mice is consistent with indirect human epidemiological studies suggesting that therapeutic interventions which raise the level of ApoA-I and HDL in plasma may decrease the risk of atherosclerosis in susceptible individuals," Rubin says.
As with other genetically based diseases, the physiological similarities between mice and humans make mice a good model for studying atherosclerosis.
''Many of the proteins and processes involved in lipid transport and metabolism in mice are similar to those in humans, including the relationship of HDL levels to atherosclerosis susceptibility," says Rubin, whose collaborators in this project again included Spangler and Clift. Joining them were RMRBD's Judy Verstuyft and Ronald Krauss, a cholesterol expert who has studied lipoproteins and heart disease for more than a decade and was the first to link the disease to a genetic mutation (see Research Review, Spring 1987).
Using transgenic techniques similar to those employed to make the sickle-cell mice, Rubin and this second group of collaborators introduced human DNA containing the ApoA-I gene into a strain of mice that is extremely susceptible to diet-induced atherosclerosis. Transgenic and non-transgenic littermates were then housed in the same cages and fed either high-fat ''cookies" consisting of mouse chow and large amounts of dairy butter or very high-fat cookies of mouse chow and cocoa butter. The mice were kept on these atherogenic diets for up to 18 weeks. Afterwards, arterial vessels from each animal were examined for fatty deposits. On the dairy butter diet, the transgenics were completely free of such deposits. Small deposits did appear in the transgenics on the cocoa butter diet, but the quantity was about an eighth of what was observed in the non- transgenics.
Blood was also collected from each mouse for lipoprotein measurements. Analyses showed that HDL levels in the transgenic mice were nearly double that of the non- transgenics, while the levels of LDL and other non-HDL cholesterols were approximately the same for all the animals. In addition to HDL quantity differences, there were also differences in HDL composition and size distribution between the transgenic and non-transgenic mice.
Says Rubin, ''It is possible that alterations in the concentrations as well as the physical and chemical properties of HDL may be contributing to the resistance of the transgenic mice to the development of fatty deposits."
Rubin cautions that the relationship between the fatty deposits measured in this first study and the mature, life-threatening atherosclerotic plaques that can form in mice following longer dietary exposure has yet to be examined.
''We've shown that a high plasma concentration of human ApoA-I and HDL in transgenic mice has a direct inhibitory effect on the early stages of atherogenesis," he says. ''Long-term studies will be necessary to assess the impact of ApoA-I and HDL on the formation of mature atherosclerotic plaques."
Rubin s newest line of transgenic mice should not only help researchers carry out such studies but should also be useful for investigating the roles played by individual genes in human atherosclerosis.
-LYNN YARIUS
ATOMS ROTATE AND MOLECULES STRETCH IN AN EMERGING PICTURE OF DYNAMIC SURFACES
FOR YEARS, GABOR SOMORJAI was certain that surfaces involved in catalysis were not rigid, as the theory had it, but dynamic. Until recently, however, when techniques for observing surfaces at the atomic level became available, he did not have the tools to prove it. Until he could prove it, says the head of LBL's Surface Science and Catalysis Program, his perception was "religion, not science."
Now, scientists here and elsewhere have proven that surfaces distort when they absorb, or bind, atoms and molecules of gas. Somorjai and his talentd international group at the Materials Sciences Division's Center for Advanced Materials are studying these dynamic surfaces on an atomic scale to understand their chemical structure and bonding, with important phenomena, such as the synthesis of gasolne. They are working on a new model in which a good catalyst is one in which the surface is not only not rigid but restructures easily
A catalyst is a substance that can accelerate and steer a chemical reaction without being consumed in the process. Catalysts have a host of industrial uses, from producing plastics to making a better fuel out of coal. They are widely used in the commercial production of fuels, chemicals, foods, and medicines. The $292 billion chemical industry and $140 billion petroleum industry rely heavily on catalysis. In fact, products manufactured with the help of catalysis account for one-sixth of the value of goods produced in the United States. Without a catalyst, a particular reaction may happen naturally but too slowly to be of use in industrial production.
There are three types of catalysts: homogeneous, heterogeneous, and enzymatic. In a heterogeneous catalyst-the kind Somorjai is most interested in and which accounts for 80 percent of U.S. catalyst sales-the active component is located on the surface, at the interface between a solid catalyst and a reactive fluid or gas.
''Surfaces have a special significance in science," says Somorjai. ''They have very special chemical, mechanical, and electrical properties.
''What intrigues me is that in most energy-conversion processes, surfaces play a unique role. For example, in photosynthesis, the green leaf is all surface."
Knowledge of the chemical, mechanical, and electrical properties of surfaces is very important to technology. ''If we understand these properties on a molecular level," says Somorjai, "we can make a better catalyst, coating, lubricant, or electronic device."
For many years, scientists assumed surfaces were rigid because they did not have the tools that are available now-such as low- energy electron diffraction (LEED)-to see the adsorbed molecules and the atoms of solid surfaces rearranging. And the theory of catalysis was not refined enough to allow for accurate interpretation of what was being seen.
''The fact that everything restructures wasn't noticed before, because the theory wasn't good enough," says Somorjai.
A CAM colleague, theoretical physicist Michel Van Hove, went to work on the theory. Says Somorjai: ''Michel improved the theory to the point where we could see all the restructuring. Once we saw this, we had an entirely different picture of catalysis."
The picture had begun to come into focus as early as 1979, when a group of researchers at the University of Warwick, England, observed what happens when carbon atoms are placed on top of a clean nickel surface in a vacuum. Using LEED, the researchers were able to see the usually square, uniform pattern of the nickel atoms rearrange itself to accommodate the carbon atoms. The nickel atoms rearranged to make stronger bonds with the carbon atoms, thus weakening the bonds between the nickel atoms. As the nickel grid opened up, the atoms pushed each other and then rotated to get out of each other's way. The rotation of the nickel atoms created a new pathway for the carbon atoms to react, move, and recombine into a new molecule.
Restructuring has also been observed at LBL, where scientists in the Surface Science and Catalysis Program are studying the reactions of ethylene and benzene, organic molecules used in the preparation of important industrial chemicals and products such as alcohols, acids, polymers, dyes, paints, and drugs. Characterization of how these two molecules react with metal surfaces serves as a model for reactions of organic molecules in general, says Van Hove.
A molecule of benzene is composed of a ring of six carbon atoms, each with a hydrogen atom attached. An ethylene molecule has two carbon atoms, each with two hydrogen atoms attached. In the gas phase, the bond lengths, or distances between atoms, are well known. But when scientists put these molecules on platinum or rhodium surfaces similar to the catalysts used in the catalytic converters of automobiles, the bond lengths changed and the molecules rearranged.
''The benzene molecule distorted quite strongly," says Van Hove. ''In fact, it seemed to be stretching and ready to fall apart." The ethylene molecule lost a hydrogen atom and completely rearranged, compared to its structure in the gas phase; the metal surface restructured as well.
These catalysis studies aid in understanding how chemical bonds are broken and new ones made. If the model of the heterogeneous catalyst as a dynamic surface is correct, the movement of the atoms of the catalyst may be providing unique sites or pathways for chemical reactions to take place-pathways which would not be there if the surface of the metal catalyst were rigid, says Van Hove. Knowing how to arrive at these unique sites or pathways and selectively break bonds will enable industrial scientists to obtain one particular molecule and not another.
Materials scientists from all over the world are painstakingly examining reactions such as the hydrogenation of ethylene to understand its individual steps.
''In a reaction like this," says Van Hove, ''there are many individual steps. We can really only study one step at a time in this whole sequence of steps. And each step is a lot of work to figure out. Once you have done them all-which no one has done for any reaction so far-then only can you start piecing all the steps together to get a complete history of a reaction. And only then can you calculate selectivities and reaction rates, which are the really important quantities in industry. Industrial scientists want the highest reaction rates and the highest selectivities they can get."
Because of the complexity of chemical reactions, surface scientists prefer to choose the simplest reaction and study it under the simplest conditions. Scientists at LBL began their study of ethylene by first studying the behavior of one hydrogen molecule on a very uniform, single-crystal metal surface in a vacuum chamber. Then they studied carbon monoxide by itself, observing how it sits on the surface and under what conditions it falls apart. Only then did they study more complex molecules, such as ethylene, with its four hydrogens and two carbons. On a rhodium catalyst, the ethylene rearranges and loses a hydrogen atom to become ethylidyne, an intermediate step on the way to becoming ethane. A valuable compound used in the production of plastics, ethane is composed of two carbons, each with three atoms of hydrogen attached. The question remains: What are the individual steps that result in atoms rearranging in this desirable manner?
The LBL team has a host of techniques to measure the properties of molecules at different stages of reactions.
When Somorjai came to LBL in the early 1960s, he brought expertise in LEED technology with him. Perfected over the years since then, LEED is still the most successful and widely used method for obtaining information about surfaces on an atomic level. Unlike x-ray diffraction, in which the rays penetrate an object's surface and give information about the inside of the material, electrons hit every atom they encounter and have a high probability of being scattered-or diffracted- by surface atoms. LEED enables scientists to measure bond lengths and angles.
Another tool, Auger electron spectroscopy (AES), monitors chemical composition-for example, how much hydrogen, carbon, oxygen, nickel, and platinum might be on a given point on the surface at any given moment. High-resolution electron energy loss spectroscopy (HREELS) is a vibrational technique which provides the vibrational spectrum of the molecule or atom and allows the scientists to identify it, as an ethylidyne molecule, for example, as opposto an ethylene molecule or an ethane molecule.
Among the other techniques that help reveal the condition of surfaces are ion-scattering spectroscopy (ISS), temperature-programmed desorption (TPD), and photo-emission techniques, such as ultraviolet photoelectron spectroscopy (UPS) and x-ray photoelectron spectroscopy (XPS). "These techniques give valuable information about what happens in the electronic orbitals that actually do the bonding between atoms at the surface," says Van Hove.
Members of the Surface Science and Catalysis Program are also developing new techniques for learning more about the structure of surfaces and surface interactions. CAM physicist Miquel Salmeron and his group, for example, are developing the scanning tunneling microscope (STM)-created 10 years ago by a group of IBM scientists in Switzerland-into a tool that can actually observe surface reactions as they take place.
''This is revolutionary," says Van Hove. ''It's the first technique that gives us atomic resolution to look at disordered surfaces and individual atoms reacting. It is especially good for conditions where you have roughness, unusual sites, or defects that may play an important role in reactions."
One version of the microscope being developed at LBL looks at the gas/solid interface at high gas pressure-a condition that would pertain in an industrial setting but is not often seen in a laboratory for fundamental studies, where reactions are typically done at low pressures.
An optical technique called second- harmonic generation, which is used for relatively large molecules, has been developed by Ron Shen, another member of the Surface Science and Catalysis Program. This and another technique he developed called sum- frequency generation can be used when a catalyst is in contact with a high-pressure gas or liquid-a situation most of the other techniques, which require a vacuum, cannot handle. Shen also plans to use optical techniques to study surface reactions on a very short time scale.
In the future, says Somorjai, LBL's Advanced Light Source may be used as a time-resolved technique to enable researchers to see the individual steps of a particular reaction, rather than the result of what might be several reactions.
"These are techniques that are being developed," says Van Hove, "and we are trying to understand what they are telling us by comparing the results of one technique with the other."
A more complete understanding of the exact role of the catalyst is emerging rapidly. ''Because we have better methods of observation, it's become obvious that whenever you put an atom or molecule on a metal, not only will the atoms move in the molecules, but the metal atoms will also move and the structure will change," says Van Hove. ''The conjecture is that these displacements affect the reaction."
The fact that the industrial stakes are high doesn't hurt the search for better understanding. ''Lots of people from all over the world are working on this new model of catalysis to prove or disprove it," notes Somorjai.
Understanding catalysis and the restructuring of surfaces involves very fundamental research. Scientists in the Surface Science and Catalysis Program also do research that is focused more directly on systems and materials important to industry. But, Somorjai notes, to interact effectively with industry, "we have to do research at a more basic level than they would do.
''If you just do the industrial applications, after a while you cannot generate new knowledge," says Somorjai. ''If you just generate new knowledge and don't focus on specific systems important to industry, then it will take a long time for that knowledge to be applied.
''We are in the bridge between fundamental, unrestricted, broad research and industrial, applied development. That is a niche that is so important to have-long range basic research, but in a way that is focused."
One such project in the Surface Science and Catalysis group is being funded by a French chemical and pharmaceutical company, Rhone-Poulenc, which has provided a grant for graduate student Denis Gardin to work on his Ph.D. in chemistry. Gardin is studying the catalytic process involved in the production of nylon from petroleum products, specifically the process of hydrogenating nitriles into amines.
The company uses a powdered nickel aluminum alloy and other compounds that improve the catalyst. ''Their work is limited by the fact that they use a very complicated catalyst," says Gardin.
To understand the catalytic mechanism, Gard in has simplified the catalyst to a single crystal of nickel, preparing a small, shiny, flat disc about the size of a fingernail. He introduces the catalyst into an ultrahigh vacuum system and cleans the surface by sputtering ions across it to remove the top several layers of atoms. He then characterizes the surface, using Auger electron spectroscopy and low-energy elec tron diffraction, to be sure there are no contaminants on it.
After he characterizes the nickel surface, Gardin introduces the amines, which stick to the surface. Using HREELS vibrational spectroscopy, he is able t o tell how they bond to the surface. He is also able to identify intermediate re actions that may help him understand the reaction's selectivity. ''With our tech niques we can control the surface," he says. ''We can deposit a small concentrat ion of aluminum on the surface to see whether pure nickel does the same chemistr y as nickel and aluminum."
Besides doing the reaction with gases, Gardin is building a system to tr ansfer a single-crystal catalyst to a liquid-phase reactor. This is a new field of study, he says: ''A lot of interesting reactions are done in liquid. This is the next step in the field of heterogeneous catalysis. "
Rhone-Poulenc uses numerous liquid phase reactions, Gardin says, but at present they have a limited understanding of the catalyst and make improvements mainly by trial and error. ''If they understood the precise mechanism," says Gar din, ''they could design a new catalyst with better reactivity and selectivity."
Of great interest to industry is the methane conversion process being de veloped by CAM scientist Heinz Heinemann in collaboration with Somorjai and visi ting Venezuelan chemist Pedro Pereira. For the first time, scientists have found a way to convert the abundantly available methane, the primary constituent of n atural gas, to ethylene, propylene, and other valuable hydrocarbons without the production of unwanted carbon dioxide. Ethylene and propylene are major starting materials for the chemical industry, used in manufacturing plastics, solvents, synthetic fibers, and drugs. The technique uses a catalyst of calcium, nickel, a nd potassium oxide in the presence of steam.
LBL recently signed its first Cooperative Research and Development Agree ment (CRADA) with Orion A.C.T., Inc., a Wilmington, Delaware-based company, to j ointly develop the methane-conversion technology. CRADAs were established by the U.S. government as a means of enabling federally funded laboratories to work wi th private industry to develop technology with a high potential for commercial a pplications. The agreement with Orion calls for a total _ expenditure of approxi mately $1 million over a two-year period to determine whether the technology can be scaled up to a commercial level, and whether it is worth doing so.
''A great deal of work will have to be done on the variables, such as ca talyst composition and the preparation necessary to maintain the catalyst's capa bilities, before we will know if we have a commercially viable catalytic process ," says Heinemann. Compared to an industrial company, ''we have been working on a very small scale at LBL," he says. ''We use one gram of catalyst, and the indu strial scientists will, at some stage, have to work with a few pounds of catalys t." If the project goes well, Heinemann predicts that a commercially viable proc ess could be in place in five to seven years.
Understanding surfaces and solving the problems of catalysis is a comple x, demanding task. But the diverse group of scientists who work in LBL's Surface Science and Catalysis Program are not daunted by the difficulties. In fact, the y seem to relish meeting the challenge head on. ''I like to solve problems," say s Somorjai. ''I take a big problem and use a combination of techniques and a com bination of backgrounds to solve it."
-DIANE LAMACCHIA
International technology transfer is a two-way street. The Surface Science and Catalysis Program in LBL's Center for Advanced Materials attracts an international crowd of scientists with their own knowledge and methods, who come to trade their wares at LBL. "They take some information with them, and they impart a great deal," says Gabor Somorjai, who leads the program.
Somorjai himself is a drawing card for many of the international visitors. An LBL staff scientist and member of UC Berkeley's chemistry department faculty since 1964, he is particularly interested in how surfaces work on an atomic scale and how this information can be used to understand heterogeneous catalysis and other chemical reactions on surfaces.
"Somorjai's group is very famous, especially in the field of catalysis," says visiting Hungarian chemist Janos Rasko.
Visiting British postdoctoral physicist Adrian Wander agrees. Wander works in the Surface Science and Catalysis Program with theoretical physicist Michel Van Hove, an expert on the theory of low-energy electron diffraction (LEED)-a method for evaluating the structure of surfaces at the atomic level. "You learn a lot of surface physics working with people like Gabor and Michel," says Wander. "This group is extremely good."
Somorjai is proud of his role as a teacher. "What makes a researcher effective is training other people. I've had about 70 graduate students, out of which 20 are now professors, and 50 are industrial and national lab scientists."
Somorjai provides his students and the other scientists in his group with a fertile meeting ground; in turn, the diversity of the group provides an excellent means of solving problems. "This is a group of fantastically creative scientists who are secure enough in their own knowledge to collaborate effectively with one another," he says.
Rasko, who came to LBL for a one- year visit from his position as head of a biotechnology lab in Hungary, has worked in the field of heterogenous catalysis for 18 years, using infrared spectroscopy to detect what happens on a solid surface. The project he joined at LBL is investigating oxidative methane coupling, a special kind of catalysis in which methane oxidizes at a much lower temperature than usual. The idea is to transform methane gas to more valuable hydrocarbons, such as ethylene, which are easier to use in industrial processes. "People here do research work with one eye to practical applications-more so than in my country," he says. Another recent visitor was Fulbright scholar Marie-Paule Delplancke of the Free University of Brussels, who spent 18 months here learning to prepare thin films of silicon carbide by a method called "plasma assisted chemical vapor deposition." Once perfected, the plasma deposition method of hard coating may be applied to mechanical devices such as cutting tools, to optical coatings, and to electronic devices. It does not require high temperatures and is therefore less expensive.
'`The spirit of research is different between here and my country," said Delplancke. "Here there is a lot of interaction between different groups--the engineers, physicists, and chemists. Also, there are a lot of nationalities, and everyone brings a small part to the research."
When Delplancke left, she took with her not only the knowledge new methods but a collaboration I between LBL and her university on the deposition of hard coatings.
"This is an international enterprise," says Somorjai. "Every country has a different technological interest, and each person brings in a different point of view. Then we come out with a picture that we couldn't get any other way."
John Lawrence, distinguished pioneer in nuclear medicine, died September 7, 1991, at the age of 87. In 1935 John joined the laboratory founded by his brother Ernest four years earlier He became the first doctor to treat patients with radioactive isotopes, neutrons, and heavy-ion beams. His work was a catalyst for the introduction of the physical sciences into the education of physicians. For more than 20 years, he served as director of Donner Laboratory, which became a major center for directing experimental medicine into new channels.
He was also a professor of medical physics at UC Berkeley. Lawrence won numerous awards and honors, including, in 1983, the Department of Energy's Enrico Fermi Award for his "pioneering work and continuing leadership in nuclear medicine."
This tribute is offered by Cornelius Tobias. Lawrence's friend and colleague for more than 50 years.
In the summer of 1935, John Lawrence, an instructor in medicine at Yale University, decided to spend a few weeks in Berkeley. He wanted to do some studies with radioactive phosphorous, one of the first artificial isotopes produced by the beams of his brother's cyclotron.
John injected soluble radioactive phosphorus into a group of leukemic mice. A few weeks later, the mice were much improved, no doubt due to the beta radiation they received.
The excitement of this discovery was too much for John to resist. With the encouragement of his Harvard mentor, Harvey Cushing, he left Yale for Berkeley. Cushing had told him, "You are pioneering in a very exciting new field, which will have a tremendous impact on medicine. Go to it!"
On Christmas Eve of 1936, John administered a dose of radiophosphorus to a 28-year-old woman suffering from leukemia-the first time that a radioactive isotope produced by the 27-inch cyclotron was used to treat a patient.
In the years to come, the method became a standard treatment for certain blood diseases, particularly polycythemia vera,, an uncontrolled proliferation of red blood cells in the body. Among those successfully treated was Cardinal Aloysius Stepinac of Yugoslavia, who spent five years under house arrest by the Tito government. In 1953, John was asked by the archbishop of San Francisco to travel to the cardinal's home in Yugoslavia, where he administered radioactive phosphorus that he had brought from Berkeley. In recognition, John received a medal from Pope Pius XII.
Another area in which John increased basic knowledge was the biological effects of neutrons. The cyclotron was potentially capable of producing copious quantities of neutrons, which initially were considered relatively harmless compared to x-rays. For about two years, the physics staff moved freely about their unshielded machine. Then, in 1935, John conducted experiments in collaboration with Paul Aebersold, one of Ernest's graduate students, and found that neutrons were much more harmful than x-rays. Since lead shielding proved ineffective, a large number of water-filled cans were piled around the accelerator. These were among the first steps in a new field: health physics.
Two years later, John made another startling observation: He found that a tumor was more sensitive to neutron radiation than were normal tissues. John and Ernest Lawrence then proposed that neutrons be tested in cancer therapy. In response, the Rockefeller Institute provided a grant to finance the first "medical" accelerator, the 60-inch cyclotron. It was soon demonstrated that neutrons were effective in killing tumors but, unfortunately, produced deleterious side effects.
The experiments with neutrons got the attention of Dr. Robert Stone, a professor of radiology at UC San Francisco and, coincidentally, led to treatment of another patient: John and Ernest's mother. In 1937, she was diagnosed with inoperable cancer. John took her to see Dr. Stone, who decided to treat her with an enormous dose of one MeV x-rays, produced by equipment developed by one of Ernest's graduate students, David Sloan. Over the following months, hercancer disappeared. Unfortunately, treatment of other patients was not always so successful.
The early treatment of patients attracted the interest of William Donner, a Philadelphia industrialist and philanthropist whose son had died of cancer. Donner contributed funds for the construction of the building that bears his name. Donner Laboratory was dedicated in 1942 to the "applications of the physical sciences to biology and medicine."
During World War II, John elected to apply the new science to the important field of aviation medicine-an effort in which Hardin Jones, a physiologist, and 1, a physicist, assisted. Working with nitrogen analogs-radioactive argon, krypton, and xenon- we proved that "preoxygenation" was a way to overcome the bends, a debilitating condition that limited the altitude ceiling of aviators.
After the war, an interdisciplinary faculty group was formed under Jones, offering Ph.D.s in biophysics and medical physics. During the next decades, hundreds of people came to Berkeley to study with John and his staff, many of them from other countries.
The years following the war also saw the beginnings of several important research programs. John and a group of young physicians used long-lived radioiron to label hemoglobin in red blood corpuscles and demonstrated that iron was transported to the bone marrow by a protein; they also were able to measure the cell life of red blood cells. Later, with Laboratory scientist Will Siri, John made expeditions to the Andes to study red cell production at high altitudes. This work led to pioneering studies of erythropoietin, the hormone that controls the production of red blood cells.
Another program began when John and I became interested in using high- energy protons in cancer therapy, following a suggestion from Robert Wilson (who later became director of Fermilab). With beams from the 184-inch cyclotron, we found that the effects of helium ions were more profound than those of protons and decided to explore the properties of still heavier ion beams.
John was compassionate and dedicated to his patients, and saw to it that each received the best that medical science could offer. Eventually several hundred patients were treated, most of them with acromegaly, caused by a tumor of the pituitary gland. it was shown that radiation can produce tumor regressions lasting for many years. The avalanche of scientific and medical investigations that followed is still in progress today.
Many important developments in instrumentation also grew out of work at Donner Laboratory, including the gamma-ray camera invented by Hal Anger that made it possible to visualize the distribution of radioactive isotopes inside the body. Hundreds of hospitals around the world wanted such a camera, and the discipline of nuclear medicine was born. The field continues to grow, with LBL researchers contributing significant new developments in positron emission tomography.
After 1948, when John became associate director of the Radiation Laboratory, much of his time was occupied with planning new developments here and in the programs of the Atomic Energy Commission. In 1955 he was one of the leaders at the Atoms for Peace conference in Geneva.
Over the years, he traveled much, gave many lectures, and received numerous awards and honorary degrees. At home, his office was always open for individuals with new scientific ideas. Leaders in medicine, science, and education mingled with students while participating in discussions at the Lawrence home.
When John retired as director of Donner Laboratory in 1970, he was asked by then-Governor Ronald Reagan to become a member of the University of California Board of Regents. During the 13 years he served as a Regent, he was instrumental in the development of advanced education in the medical sciences.
John's interest in cancer and atomic research never flagged. During the last few years of his life, he kept a table next to his bed, filled with scientific and medical books. When unable to sleep, he used to get up to read at any time of the night. It is this indomitable spirit that I admired most in John Lawrence. He had a sensitivity for human suffering, and he was a believer that humans can solve many of their problems through the use of science.
Edwin Mattison McMillan, one of the brilliant scientists who helped lead the Laboratory to its fame, died September 7, 1991, at the age of 83. Nobel laureate, former director of LBL, and professor emeritus of physics at the University of California, Berkeley.
McMillan received the last of many honors just a year before his death: the National Medal of Science. McMillan's "important and versatile scientific contributions spanning physics, chemistry, and engineering, and his great human qualities, form an important chapter in the history of science," said Glenn Seaborg, with whom McMillan shared the 1951 Nobel Prize in Chemistry.
This tribute is adapted from a talk by Edward Lofgren, McMillan's longtime friend and colleague, at a memorial service in Berkeley on September 14, 1991.
In January 1932, Ernest Lawrence wrote to Edwin M. McMillan at Princeton University: "We all would welcome your coming to California on a National Research Fellowship next year. We are busy installing equipment in our new Radiation Laboratory. If you wish to join in OD the work, we would be only too glad."
Who was this young man who was so cordially invited to the new Laboratory? He was the schoolboy whose toys were mechanical and electrical gadgetry, chemicals, rocks, minerals, and botanical oddities. He was the eager high- school student who lived in the shadow of Caltech, walked its hallways, attended lectures, and glimpsed the fabulous world of science.
He was the graduate of Caltech, greatly influenced by close association with Linus Pauling. He was the new Princeton Ph.D. and a holder of the most sought-after prize: a two-year National Research Council Fellowship.
Ed accepted the invitation of Lawrence to come to Berkeley but chose to do his research in the Physics Department on his own projects in molecular beams and hyperfine structure rather than in the new Radiation Laboratory. However, he was a close observer of the Radiation Laboratory and felt the excitement as Lawrence and his co-workers struggled with the powerful but temperamental cyclotron to make it work and to produce solid physics results. The attraction was irresistible; his interested observer status grew first to a part-time and then, in 1934, to a full-time commitment to the Radiation Laboratory that was destined to be his intellectual home for the rest of his life.
In those earliest days, Ed brought to the Laboratory a technique of meticulous experimentation combined with a mastery of nuclear theory that it did not have before. He discovered new isotopes-oxygen15 with Stanley Livingston and beryllium-10 with Samuel Ruben, and he provided the first unambiguous verification of electron pair production by gamma-ray absorption. He also took a keen interest in the operation and improvement of the cyclotron and was responsible for substantial improvements in ion sources, magnetic-field shaping, beam extraction, and power and control systems. He played an especially valuable role in the construction and initial operation of the 60-inch cyclotron.
As the decade of the 1930s drew to a close, momentous events in the world had their repercussions at the Laboratory. In the first days after January 29, 1939, when the discovery of fission became known, a number of verifying experiments were carried out at the Laboratory. Ed chose, he said, "to do an experiment of a very simple kind"-a measurement of the range of the fission fragments using a foil technique. Ed, ever the careful observer, noticed that the residue in a thin layer of uranium compound showed "something very interesting." The something-after a long series of exacting experiments in collaboration with Philip Abelson-was proven to be an isotope of element 93, the first element beyond uranium.
Ed named the element neptunium and had ready the name plutonium for the next element. Indeed, he prepared a sample of element 94, but the final chemical proof of its identify eluded him, as he was called away to help organize a new laboratory at MIT for research in radar. The chemical identification of element 94
was carried forward by a team including Glenn Seaborg, Joseph Kennedy, and Arthur Wahl. A paper co-authored by these three, along with McMillan, recorded the result in 1940, but wartime secrecy held up the announcement until 1946. Five years later, the Nobel Prize was awarded jointly to McMillan and Seaborg "for their discoveries in the chemistry of the transuranium elements."
Ed's mastery of physics-both theory and experiment-was such that he could contribute to almost any line of research. When Robert Oppenheimer was designated to head what became the Los Alamos Laboratory, the first person he called on, in November 1942, to help organize the laboratory was Ed McMillan. He assumed major responsibilities both in weapons development and in testing and instrumentation.
In the summer of 1945, activity at Los Alamos reached a climax in the test shot at Alamogordo. With the end of the war in sight, Ed's thoughts reverted to the central problem of cyclotrons: the energy limit imposed by the relativistic increase of mass of the ions as they gain energy. The highest energy accelerator at this time was the 60-inch cyclotron in Berkeley, with a beam of 16 MeV. The next projected cyclotron was to produce beams of 100 MeV.
Although the huge magnet had been built, the machine's operation was doubtful. Unless there was a new idea, further progress would be absolutely blocked.
McMillan had such a new idea. His principle of phase stability was as startling in its elegant simplicity as it turned out to be far-reaching in practice. He showed that under certain conditions, ions in cyclotron orbits collect in stable, zero- energy-gain bunches. The frequency of the accelerating field and the strength of the magnetic field may then be slowly altered to increase the energy of the stable bunches without limit. This is the principle of phase stability, which, together with strong focusing, provides the basis for the design of all the great high-energy accelerators today.
The principle of phase stability had also been determined by Vladimir Veksler in Russia, but due to the breakdown of communication during the war, the work of the two scientists was entirely independent. In 1963 McMillan and Veksler shared the Atoms for Peace Award for their contribution.
Returning to Berkeley when the war ended, Ed had a leading role in the program of the Laboratory to build new accelerators based on the principle of phase stability: the 184-inch cyclotron, the 300-MeV synchrotron, and the Bevatron.
In parallel with his remarkably productive career in research and in accelerator development, McMillan taught as a faculty member of the UC Berkeley Physics Department, becoming a full professor in 1946. He was chosen Faculty Research Lecturer in 1954, with the citation: "His teaching is notable for the clarity and simplicity with which he presents even the most complex scientific facts and theories."
McMillan was named associate director of the Laboratory and head of the Physics Division that same year. With the untimely death of Lawrence in 1958, he was appointed director of the newly named Ernest O. Lawrence Radiation Laboratory. Few scientists could have managed such a large and diverse scientific enterprise at all; McMillan did it well. He directed with a light touch, giving scope to individuals and making it possible for persons of great talent, but with sometimes very different styles, to work side by side. The years were very productive ones for the Laboratory.
McMillan held this position with distinction until his retirement in 1973. In retirement, he was an active participant in an experiment at CERN in Geneva, Switzerland; he maintained an interest in Laboratory affairs; and he contributed several important papers on aspects of the history of science.
Ed McMillan was one of the great scientists of the century. His colleague and fellow Nobel laureate, Luis Alvarez-a tough judge of scientific worth-summarized Ed's stature this way:
"Many people agree with me that Ed McMillan certainly earned two or three Nobel Prizes in physics, but only got one."
Great scientist and scholar, superb teacher, fine gentlemen. . . it was a privilege to have Ed McMillan as a friend.
Distinguished honors bestowed on members of the LBL scientific staff during July through November 1991 include the following:
Glenn T. Seaborg, associate director at large at LBL and University Professor at the University of California, received the National Medal of Science in September 1991. He was cited for his outstanding work as a nuclear chemist and as a teacher. The Medal of Science, the nation's highest award for scientific achievement, was the latest of numerous awards that Seaborg has won over the years. In 1951, he shared the Nobel Prize in Chemistry with the late Edwin McMillan for work on the chemistry of the transuranium elements, a field that still holds his interest.
John Newman,a researcher in LBL's Chemical Sciences Division and professor in UC Berkeley's Department of Chemical Engineering, was awarded the 1991 Olin Palladium Medal by the Electrochemical Society, Inc., for his contributions to electrochemical science and technology.
Morton Denn of LBL's Center for Advanced Materials and UCB's Department of Chemical Engineering, was named a Fellow of the American Institute of Chemical Engineers for his "outstanding work as an educator and researcher in polymer processing and rheology, as well as fluid mechanics, reaction engineering, and process optimization and control."
Miklos Gyulassyof the Nuclear Science Division was elected a Fellow of the American Physical Society in recognition of his "innovative work on the space-time aspects of nuclear collision dynamics, pion interferometry, quark-gluon plasma formation and hadronization in relativistic and ultra-relativistic nuclear collisions."
Wladyslaw Swiatecki of the Nuclear Science Division was awarded the Polish Physical Society's Marian Smoluchowski Medal for his outstanding contributions to science and to development of international scientific cooperation. The medal is the highest scientific distinction granted by the society.
Erik Anderson of the Center for X-ray Optics was a member of a team that won a 1991 R&D-100 Award for the development of a high-resolution scanning photoelectron microscope. The awards go to Research and Development magazine's choices for the year's top 100 achievements in technology.
Gareth Thomas, scientific director of the National Center for Electron Microscopy, received the 1991 Albert Sauveur Achievement Award from the American Society for Materials. He was cited for his "pioneering efforts in the development and applications of electron microscopy and for fostering the universal acceptance of this technique in the evolution of modern materials science."
Thomas Budinger, director of LBL's Research Medicine and Radiation Biophysics Division, received the 1991 Distinguished Scientist Award from the Society of Nuclear Medicine. The award recognizes Budinger's "distinguished contributions to nuclear medicine."
Dariush Arasteh, Brent Griffith, and Steve Selkowitz of the Energy and Environment Division were recognized by the magazine Popular Science for their work in developing a new gas-filled panel insulating material. The material was chosen as the year's best new product in the home technology arena and was one of 10 grand winners on the magazine's list of the 100 best new products and inventions of 1991.
Patents were awarded recently for inventions by these LBL researchers:
Tim Renner, Mark Nyman, and Ronald Stradtner for an ionization chamber dosimeter for measuring the radiation dose delivered to a patient; and Steve Selkowitz for a thermal insulated glazing unit.
The first step in the chemical process that enables the eye to detect light has been time-resolved by a team of LBL and UC Berkeley scientists. This reaction, which takes place within 200 millionths of a billionth of a second, is believed to be the fastest ever measured.
LBL's Robert Schoenlein and Charles V. Shank, and UCB's Linda Peteanu and Richard Mathies used strobelike flashes of blue-green laser light to stop the action on the twisting of a chemical bond that triggers the process of sight. The bond is between carbon atoms m a protein called rhodopsin, the main constituent of the rod and cone cells in the eye's retina.
"Our observations have important implications for the development of such things as artificial vision or solar converters," Mathies says. "In order to control a chemical reaction and dictate its outcome, we must first understand its dynamics."
Vision starts when photons of light enter the eye and are focused onto the retina. Absorbing the energy of even one photon causes a specific carbon-carbon double bond within the rhodopsin molecule to twist a full 180 degrees. Like a key unlocking a door, the twisting of the bond opens the way for converting photons into signals that are transmitted via the optic nerve to the brain for interpretation.
Scientists have long known that the twisting or "isomerizing" of the rhodopsin molecule is the primary step in vision but, until now, did not know how quickly it takes place. The LBL-UCB team was able to record-in a sequence of spectral snapshots-the entire reaction from start to finish using laser spectroscopy techniques they developed that operate on a femtosecond time scale. (A femtosecond is a millionth of a billionth of second.)
The LBL-UCB team obtained their measurements working with samples of rhodopsin extracted from cow retinas. First, a unique blue- green laser beam that flashed in pulses of only 35 femtoseconds duration was used to "pump" rhodopsin with the energy needed to make it twist. A second beam, with a broader spectrum and pulse length of only 10 femtoseconds, was then used to measure the spectral absorption patterns of the molecule as it changed shape.
Says Schoenlein, "In its original form, rhodopsin absorbs mostly green light. However, as it twists, the molecule starts to absorb light which is more in the yellow and red parts of the spectrum. By measuring the changes in the colors absorbed by the molecule, we can tell how fast the molecule is isomerizing."
The speed of rhodopsin's isomerization is considerably faster than anyone expected and helps explain why the eye is so efficient at collecting light.
"The energy of a photon is converted to mechanical motion so quickly that there is no time for any energy to dissipate or leak away," Schoenlein says. "As a result, the vision system is so sensitive that under ideal conditions it can detect a single photon."
Rhodopsin's light- sensitive region, called the "chromophore," is a form of vitamin A, consisting of a chain of carbon atoms. The twisting takes place at a double bond between the 11th and 12th carbon atoms in the chain, transforming the chromophore from what is called an "11-cis" configuration to what is called an "all-trans" configuration. This change in the chromophore leads to a change in shape of the rhodopsin molecule that initiates a cascade of enzymatic events which excite the retinal rod cell.
Says Mathies, "If the transformation of the chromophore did not take place as fast as it does, competing processes would prevent the detection of light. As it is, generally about two-thirds of the incoming photons are converted to reactions that yield the all-trans photoproduct."
The isomerization of rhodopsin is irreversible. After the protein changes shape, it eventually loses its retinal chromophore. The eye must then construct a new protein using part of the old molecule and a fresh supply of 11-cis vitamin A. This is why vitamin A deficiency reduces the eye's ability to detect light.
The next step in this research, the team says, will be to study the twisting reaction when the rhodopsin or the vitamin A chromophore has been modified. This, they say, will help them to better understand how and why the mechanism works, which, in turn, may provide clues for making light detectors and photon switches that could be used in photosensors, biological solar energy converters, and optical computers.
Jasper Rine, director of LBL's Human Genome Center and professor of genetics at UC Berkeley, and LBL biologist Elaine Ostrander are setting out to produce a high-resolution map of the dog genome-the full complement of canine DNA material-that can be used to identify the genes responsible for physical and behavioral variations between different breeds.
Why the dog genome?
"For over 2500 years, scientists and philosophers alike have argued that some elements of human behavior must be genetically determined," says Rine. "But because there is so much variety in how humans display even the simplest of behavior patterns, it has been hard to discern the genetic components."
Such is not the case with dogs. Just as all Chihuahuas are tiny and all Saint Bernards are huge, most basset hounds are docile while most pit bull terriers are not. The similarity of form and behavior in dogs of the same breed and the often dramatic differences between one breed and another are largely the results of intense selective breeding during the past 150 years, the time when most of the modern breeds came into existence. This indicates that in dogs not only are form and behavior genetically controlled but the number of genes responsible is small enough to be experimentally manageable.
Says Rine, "No other mammal is as well-suited for studying the genetic basis of form and behavior as the modern domestic dog. Dogs offer a wealth of genetic opportunities. "
The dog genome is approximately the same size as the human genome, which means it contains about 3 billion base pairs of nucleotides-the chemical compounds that bind together the double helix of DNA and serve as the building blocks for genes. Rine and Ostrander plan to construct a genome map with a resolution of 5 to 10 centimorgans (equivalent to about 10 million base pairs) based upon the physical location of approximately 400 randomly spaced markers-genetic landmarks whose inheritance can be monitored.
These markers will be identified through the crossbreeding of Border collies with Newfoundlands, dogs that share gentle dispositions but otherwise are quite different. Border collies are white and black or tan, average 35 to 45 pounds, and are compulsive herders. They will attempt to herd sheep, cattle, or children-even a collection of objects such as tennis balls-in a display of behavior that Rine likens to an obsessive-compulsive personality in humans. Newfoundlands are usually black, average 120 to 150 pounds, and are born water- rescuers. These dogs have been known to jump from boats or swim long distances from shore to reach drowning victims and deliver them to safety.
In the first cross, two small Border collies with well- established herding instincts will be mated with two large Newfoundlands that have shown exceptional water-rescue skills. Progeny from these matings should be medium sized dogs (70 to 80 pounds) with mixed behavior. They will be mated to either Border collies or Newfoundlands-a technique called backcrossing-in order to isolate and identify those genes that are responsible for size and behavioral differences.
"Informative crosses are assured since parental animals are chosen for extreme traits," Rine says. "Also, since most of the mapping information is derived from extreme individuals, selective genotyping can be used which drastically reduces the number of progeny that must be studied."
In addition to helping scientists determine the genetic basis for physical appearances and some extreme forms of behavior, Rine and Ostrander say that a map of the dog genome should be useful for studying diseases that dogs and humans share, such as prostate cancer and a number of neuromuscular diseases, including Duchenne muscular dystrophy.
"It is absolutely clear that locating a gene in the dog genome can be used to find the corresponding gene in the human genome," says Rine. "What is not clear is whether the gene that controls something in a dog will also control that same thing in a human being."
Rine and Ostrander anticipate needing about 100 dogs to make their map. Blood samples will be drawn to obtain the DNA required to identify genetic markers, and x-rays will be used to measure the shape, form, size, and density of their bones. Otherwise, the animals will not be stressed.