Volume 2, Issue 14 September 2005
A Postcard from Jurassic Park
Kevin Padian is the president of the National Center for Science Education (NCSE), a group that defends the teaching of evolution in public schools. (Photo by Jon Blair/National Geographic)
Picture a cockatoo and a crocodile. Which one is closer to a Tyrannosaurus Rex? If you guessed the latter, you were mistaken. The reality is that about 230 million years ago the lineage that produced crocodiles and their relatives split off from the evolutionary line leading to dinosaurs and, eventually, birds. So if birds are related to massive creatures like the T. Rex, how did they ever get off the ground? Answering these kinds of big evolutionary questions requires a trip deep into the fossil record. That's UC Berkeley integrative biologist Kevin Padian's favorite stomping grounds.
Thin sections of bone from a fossil coelophysus femur (above) and a modern moa tibia (below) reveal striking similarities in growth pattern. Both have an abundance of vessels running through the bone, indicating a good metabolism and fast growth. (courtesy the researchers)
"My work has always been about the events, patterns, and processes behind macroevolution," says Padian, curator of UC Berkeley's Museum of Paleontology. "How do things play out on a large stage over the very long term? Why do some species succeed and some die?"
Padian is particularly curious about what life on the planet was like at the end of Triassic period and beginning of Jurassic, more commonly known as the age of dinosaurs.
Perhaps most famously, Padian and his collaborators discovered that dinosaurs "grew like a house on fire." That's contrary to what paleontologists previously thought. In recent years though, the researchers have shown that dinosaurs underwent rapid growth, more akin to today's mammals like birds and elephants than reptiles like crocodiles. Indeed, some dinosaurs reached their massive adult size during their early teenage years.
How do we know? Since there are no living dinosaurs left, Padian and his colleagues looked at dead ones. Working with Museum of the Rockies curator John Horner and professor Armand de Ricqles of the University of Paris, Padian has spent the last dozen years examining the inside of fossil bones. It turns out that bones record their growth history in tissue similar to the way a tree's years can be counted in its rings. As the animal ages, certain kinds of tissue are deposited while others are eroded. Comparing the fossilized bone tissue with samples from juvenile and hatchling dinosaur bones and also samples from modern animals, the researchers pieced together the entire growth history of various dinosaurs.
By cracking open the dinosaur bones, the scientists learned a great deal about the animals' evolution on the macro-scale. Early in their lineage, dinosaurs developed the sustained elevated growth rates that led to their massive size while other lines from a common ancestor did not. According to Padian, that growth rate may have given dinosaurs an advantage 200 million years ago when other animals with more typical reptilian bone structures died off. Also, the research suggests that dinosaurs may have been warm-blooded creatures with basal metabolic rates comparable to today's birds.
Artist's conception of Stegosaurus stenops. (Image courtesy ©Melani McKim)
"Dinosaurs weren't sluggish, lumbering, overgrown crocodiles at all," Padian says. "They were actually closer to what you saw in Jurassic Park."
The biology of dinosaurs' enormity is only one evolutionary riddle that Padian has pondered using the fossil record as his guide. Several years ago, his team pursued the question of why birds are so much smaller than their extinct dinosaur cousins. Studying the bone tissue, the researchers determined that ancient bird species truncated their growth rate after an initial fast spurt.
"We don't know why this happened," Padian says, "but when they became smaller, the proportionately larger feathers gave them an aerodynamic advantage."
An acid-prepped fossil Scelidosaurus scute from the British Museum in which most of the rock matrix has been digested away, revealing the interior lattice-work trabeculae surrounded by relatively thin layers of compact cortical bone. The trabeculae are 'pinched' out at the top, leaving an upper keel of just cortical bone similar to the plates and spikes of Stegosaurus. Inset shows a histological section of a Scelidosaurus scute that exemplifies the light construction and structure of the scute, similar to what is seen in Stegosaurus. (Photos by Russell Main/UC Berkeley)
More recently, Padian and his collaborators' studies of bone histology have clued them in to secrets about the social life of dinosaurs. For instance, the spikes and plates running down the back of stegosaurs and the helmet-like structure on the heads of triceratops did not evolve as protection devices, sexual displays, or heat exchangers to keep the animals cool or warm, a popular assumption. According to the Berkeley research, the bizarre structures simply helped dinosaurs spot members of their own species. Once again, Padian says, it's evolution working in a way that's not obvious on first glance, but crystal clear upon closer inspection.
"We know more about dinosaurs than we've ever known," Padian says. "In fact, we know more about the life history of dinosaurs than that of some living animals because we've worked so hard to reconstruct it."
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Mapping Cellular Signals
UC Berkeley professor Kevan Shokat is a chemist who thinks like a biologist. He's developing chemical tools to understand and manipulate the complex communications system at the heart of every cell. Eventually, his research could lead to a pharmacological map of the human cell that would guide the rapid development of new drugs to combat diseases like cancer and diabetes.
Kevan Shokat is also a researcher with the California Institute for Quantitative Biomedical Research (QB3) (Majed photo)
"We look for biological questions that genetics and biochemistry can't easily answer and think of chemical tools to get at them," says Shokat, who is also a professor of cellular and molecular pharmacology at the University of California, San Francisco, and affiliated with the Howard Hughes Medical Institute.
Shokat's laboratory focuses on kinases, enzymes that transfer energy stored within the cell to other proteins. The kinases act as control switches for many cellular activities, from development to death. However, with more than 500 kinases in every cell, identifying a specific kinase's functionality and manipulating it without affecting others in the protein family is no easy task. The pay-off could be huge though.
"The ability to understand how a specific kinase regulates signaling pathways would permit the development of new drugs and new strategies to control almost all disorders including cancer, neurological disorders, autoimmunity, and tissue rejection," he says.
For example, Shokat explains, inhibiting a particular kinase in a cancer cell could stimulate the death of that cell. On the other hand, simultaneously knocking out another kinase could result in dangerous side effects. To help understand each kinase's role in the cell, Shokat developed a chemical-genetic tool to selectively mutate kinases so that they can be individually switched on and off by introducing a drug into the body.
"It's like we changed the lock on the switch that turns the kinase on or off and now we have the key to it," he says. "So we can determine whether inhibiting that kinase is going to stop the spread of cancer, for example, or cause the animal to lose weight, indicating that it's not a good target for therapy."
This looped animation shows the engineering of the active site of a protein kinase to introduce a new active site pocket (red) that can be accessed by a tailor-made inhibitor molecule (grey and blue). (courtesy Daniel Rauh/Shokat Laboratory)
Already, Shokat and his colleagues are mutating and testing more than one hundred kinases. Their aim is to identify the kinases that may be tied to asthma, diabetes, cancer, neurological disorders, and even drug addiction. The technique is generic in that it can inhibit any of the mutated kinases they're studying with little modification.
"If inhibiting a mutated kinase affects a disease in the way we hope, a pharmaceutical company could then make an inhibitor for the wild type form of the kinase as it exists in the body," he says.
In April, Shokat and two collaborators demonstrated that their chemical-genetic technique could also shed light on how cells in the brain develop. Understanding how the growth of neurons are regulated could provide insight into diseases like Alzheimer's, Shokat says.
"Kinases are involved in almost every aspect of physiology," he says. "Yet people have no idea about the function of even the most well-studied kinases."
To that end, Shokat is also perfecting another chemical-genetic tool similar to the inhibitor approach that can reveal kinase function. Instead of targeting a mutated kinase with an inhibitor, a "tagging" molecule is delivered to the kinase. Shokat can then track the kinase as it travels along the signal pathways in the cell.
"The first tool allows us to inhibit the kinase and see what function gets regulated, but with this approach we can watch all of the dynamic changes inside the cell," Shokat says. "Our ultimate goal is to link the two together."
Shokat hopes that someday, scientists wielding his chemical-genetic tools will build a map of all the kinases in the cell. Pharmacologists could then consult that map to determine the best drug therapy to fight a particular disease.
"We have the map of the human genome," Shokat says. "But we'd love to know the effect of inhibiting any human protein and link that to a disease. It's all about understanding biology in the context of chemistry."
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Geochemistry Underfoot
For most of us, the effects of a rainstorm fade shortly after the last drop falls. The sun shines through the clouds and the streets begin to dry. Dig a little deeper though and you'd realize that the end of a shower is really just the beginning of the Earth's interaction with the fallen water. Slowly, the rain seeps into the watershed and makes its way into nearby streams. UC Berkeley professor James Kirchner wants to know what happens along the way. His research on this and other earth and planetary science questions could someday aid environmental remediation efforts and inform decisions about sustainable land use.
James Kirchner at the San Rafael Reef in Utah
"If it happens between 10 meters above the surface and 10 meters below, I'm probably interested in it," says Kirchner, who also directs Berkeley's Central Sierra Field Research Stations.
These days, Kirchner has three major research thrusts that all fall within that relatively thin slice of the planet. Geomorphology is the study of how Earth's topography evolves to form mountains, river valleys, and other surface formations. Meanwhile, the rainwater project spans two fields of study: hydrology and aqueous geochemistry, the chemical reactions between water and rocks.
"If it rained in Berkeley today, maybe a trillion drops would fall on campus," he says. "Some fraction of those would reach the stream today, some fraction tomorrow, and more the day after. We'd like to measure that distribution of transit times and the reactions that occur as the water moves underground."
Kirchner and his colleagues are developing techniques to study the factors controlling rainfall and runoff both physically and chemically. Their approach is to measure environmental "tracer chemicals" such as chloride that occur naturally in rainwater. Then, they look for the same tracers in samples from the stream flow and compare the two measurements. The fluctuations in those measurements provide the researchers with a good sense of how long it takes the rainfall to get to the stream.
A view of a watershed at Stony Creek Fan near Orland, California
"Looking at the movement of rainfall can also tell us how long contaminants like pesticides, fertilizers, or industrial compounds might be retained underground in the watershed before they're released into the stream," Kirchner says.
In one experiment, the researchers analyzed the amount of chloride in rainfall and runoff from a headwater stream in Plynlimon, Wales. They showed that contaminants would initially flush out of the watershed quickly but that low-level contamination could continue to steep into streams for years. The next step is to determine how contaminated water chemically reacts as it moves through the ground. Kirchner and his colleagues are using chemical tracers and soil samples to identify possible reactions.
"The question is whether the water moves through highly channelized flowpaths or through the soil like it's a sandbox, contacting the surface of every grain of every mineral," Kirchner says. "It'd be wonderful to give the subsurface of the Earth an MRI, but it just isn't feasible. So all we can work from are the chemical tracers in the water to tell us where it's been."
Kirchner's second large research project is a bit closer to the ground we stand on. With collaborators from Lawrence Livermore National Laboratory's Center for Accelerator Mass Spectrometry and other institutions, Kirchner is honing new techniques to measure long-term rates of physical erosion and weathering at the Earth's surface. Various processes convert rock to soil that either dissolves or makes its way down hill slopes where it becomes sediment in streams. Scientists would like to understand how those processes are linked to variations in topography, climate, and ground cover.
"It's important to know how the Earth's surface evolves but it's also relevant to long-term sustainability questions of forest management, logging, and agricultural practices," Kirchner says.
Until several years ago, it was extremely difficult to approximate the speed at which the various processes occur, he says. Then, the researchers developed a novel method for calculating how fast the Earth's surface erodes.
Wide angle view of the Center for Accelerator Mass Spectrometry FN tandem accelerator and mass spectrometer that Kirchner used to measure cosmogenic particles in mineral samples. (courtesy LLNL)
The Earth is constantly being bombarded with particles such as gamma ray neutrons that stream down from the upper atmosphere. These particles can transform certain elements into rare isotopes. For example, when a gamma ray neutron hits the nucleus of a silicon atom, it becomes a particular aluminum isotope. That isotope only exists as a product of this cosmic ray reaction.
Minerals in the Earth's surface are usually shielded from these gamma rays by the mass above them. But as that shielding is naturally eroded away, the minerals are subjected to a stronger flux of the gamma rays. As a result, the concentration of the aluminum isotope, for example, increases.
"We can measure that concentration and know how fast or slowly the sample has ridden the erosional elevator to the surface," Kirchner explains. "Once you've got these measurements from many places, you can ask questions about whether steep slopes erode faster than gentle slopes or how erosion rates change when you go from dry climates to wet climates."
The next step is to combine those measurements with techniques to chemically analyze rock and soil. Then, Kirchner says, the researchers can learn how fast soil minerals are made from rock and the rate at which natural processes boost the fertility of soil. Chemical weathering of rock is also tied to the amount of carbon dioxide in the atmosphere and the greenhouse effect, albeit on timescales of millions of years.
"All of this work makes it more interesting to look out the window everyday," Kirchner says. "You don't just see the scene in front of you but you also have an idea of what's happening below the surface."
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Berkeley's Scientific Legacy
J. Robert Oppenheimer, Doctor Atomic
In October, UC Berkeley physicist J. Robert Oppenheimer will be immortalized as Doctor Atomic in a new production of the San Francisco Opera. To his Berkeley students in the 1930s though, he was known affectionately as Oppie. That was decades before Oppenheimer would go down in history as the leader of the Manhattan Project.
Robert Oppenheimer, Glenn T. Seaborg, and Ernest O. Lawrence (L to R) in early 1946 at the controls to the magnet of Lawrence's 184-inch cyclotron, which was at the time being reconverted from wartime use as a mass spectrometer to its original purpose as a cyclotron. (Courtesy of Lawrence Berkeley National Laboratory)
Oppenheimer was born in 1904, the son of Jewish immigrants from Germany. In 1925, he completed his undergraduate degree in chemistry at Harvard and immersed himself in theoretical physics at the University of Gottingen in Germany, a leader in the then-nascent field called quantum mechanics. After earning his Ph.D., Oppenheimer returned to the United States where he began a fellowship at the California Institute of Technology. Two years later, in 1929, he joined UC Berkeley's physics department. Oppenheimer called the University a "desert," but was dedicated to spreading the new theoretical physics he had brought from Germany.
"I didn't start to make a school," he later said. "I didn't start to look for students. I started really as a propagator of the theory which I loved, about which I continued to learn more, and which was not well understood and which was very rich. The pattern was not that of someone who takes on a course and teaches students preparing for a variety of careers but of explaining first to faculty, staff, and colleagues and then to anyone who would listen, what this was about, what had been learned, what the unsolved problems were."
Working alongside another new hire, experimentalist and eventual Nobel Laureate Ernest O. Lawrence, Oppenheimer quickly brought Berkeley to the forefront of theoretical physics. Meanwhile, Oppenheimer raised FBI eyebrows with his involvement in radical politics. This suspicion would later explode into a tragic witch-hunt.
In 1942, Oppenheimer's theories were brought to bear on a new application. With encouragement from Lawrence, the U.S. Army put Oppenheimer in charge of their Manhattan Engineer District project, an effort to build an atomic bomb. Oppenheimer organized a team of the brightest physics minds of the time — Edward Teller, Enrico Fermi, Richard Feynman, and others — and set up shop on a mesa near Santa Fe, New Mexico. On July 16, 1945, at the Trinity test site in Alamogordo, New Mexico, Oppenheimer observed the first detonation of a nuclear weapon.
Trinity: July 16, 1945
Words from the Bhagavad Gita later came into his mind: "I am become death, the destroyer of worlds." A month later, atomic bombs annihilated Hiroshima and Nagasaki.
The atomic annihilation of Hiroshima and Nagasaki brought an end to the war. Oppenheimer became the chairman of the General Advisory Committee to the new Atomic Energy Commission. On the Commission, he lobbied against developing a hydrogen bomb, having previously said, "If atomic bombs are to be added to the arsenals of the a warring world, or to the arsenals of nations preparing for war, then the time will come when mankind will curse the name of Los Alamos and Hiroshima.
"The peoples of this world must unite, or they will perish. This war, that has ravaged so much of the earth, has written these words. The atomic bomb has spelled them out for all men to understand."
In 1947, Oppenheimer left UC Berkeley for the position of director of the Institute for Advanced Study, in Princeton, New Jersey. Six years later, he was accused of Communist affiliations and un-American activities, stemming from his years at Berkeley and later disapproval of the hydrogen bomb research. His security clearance was denied and he was removed from his advisory position at the Atomic Energy Commission.
Robert Oppenheimer and brother Frank back at Berkeley in 1966.
Oppenheimer continued to lecture and, in 1963 as the political tides shifted, received the Fermi Award from President Lyndon Johnson. In 1967, he died of throat cancer. While the tension and tragedy of Oppenheimer's life is well-suited for an opera, it is his scientific legacy that keeps his name alive at UC Berkeley.
"The fact that Oppenheimer was here attracted other people who wanted to be around him, though they were a bit afraid of him," University Professor of Physics Marvin Cohen has said. "He was a star."
On Monday, September 26, the College of Letters & Science will present Science and the Soul: J. Robert Oppenheimer and Doctor Atomic. The free symposium will feature a dialogue with composer John Adams and director Peter Sellars, celebrating the opening of the San Francisco Opera's world premiere of Doctor Atomic. Panelists include Dean of Physical Sciences Mark Richards and University Professor of Physics Marvin Cohen.