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Editor in Chief

Carol Hunter

Managing Editor

Heidi Ledford

Copy Editor

Elissa Preston

Editors

Kristen DeAngelis

Dula Parkinson

Jessica Marshall

Chris Weber

Art & Web Editor

Tony Le

Printer

Metro International

© Berkeley Science Review. No part of this publication may be reproduced, stored, or transmitted in any form without express permission of the publishers. Published with financial assistance from the Office of the Vice Chancellor of Research, the Space Sciences Lab, the Graduate School of Journalism, the Graduate Division, the Physics Department, the College of Natural Resources, the Graduate Assembly, and the Associated Students of the University of California. Berkeley Science Review is not an official publication of the University of California, Berkeley, or the ASUC. The content in this publication does not necessarily reflect the views of the University or the ASUC. Letters to the editor and story proposals are encouraged and should be e-mailed to submissions@uclink.berkeley.edu or posted to the Berkeley Science Review, Eshelman Hall, Berkeley, CA . Advertisers: contact advertise@uclink.berkeley.edu or visit http://sciencereview.berkeley.edu

D E A R R E A D E R S ,

You may notice a few changes in this issue of the Berkeley Science Review. New, thicker paper stock. New layout and design from our new art director, former webmaster Tony Le. And, of course, a host of wonderful new contributors, from departments ranging from chemical engineering to neuroscience.

In this issue, you can read about Berkeley scientists who are stepping beyond academia to address global health problems in the developing world and about how tightened security has affected international students—and in turn, scientific research—at the university. Discover the state of our country’s endangered soils (yes, endangered soils), and speculate on Lawrence Berkeley Lab’s future relationship with UC. For a bit of fun, check out Quanta (heard on campus) or turn to the Back Page and find out how to search for life on Europa.

You can always find copies of the BSR distributed around campus and at local science museums. But this year the BSR has also been distributed in Washington, DC to members of Congress (thanks to former ed-in-chief Colin McCormick, currently a AAAS fellow in the nation’s capitol) and even sent overseas to Italy and Iraq. So I guess you could say we are now internationally known!

But as much as things have changed here at the BSR, our core mission remains the same: communicating the exciting scientific research, policy, issues and controversies going on at UC Berkeley to the campus community and beyond.

As our sixth issue goes to press, it’s good to look back on our humble beginnings. e biannual, -copy, -page, full-color, award-winning magazine you see before you started out as an innocent e-mail blipping across the Internet four years ago: an idea to produce a popular science magazine at the university. And a group of science and humanities graduate students took up that idea and, through creativity and hard work, turned it into a reality.

at’s another thing that hasn’t changed here at the BSR. We’re still written, edited, designed and published by a dedicated group of volunteers, most of them full-time Berkeley graduate students. And we’re always looking for more people to get involved. Send us your story ideas. Write a letter to the editor and let us know what you think of the issue. Tell us if you’re a writer, editor, cartoonist, designer, artist or photographer and want to help out. Or if you just want to send us money, that’s okay too! We’ll take checks or cash…

You can always e-mail us at sciencereview@yahoo.com, and you can find all of our content—plus information on our mailing list, science writing seminars and more—on our website atsciencereview.berkeley.edu.

Enjoy the issue!

Carol Hunter

FROM THE EDITOR

B E R K E L E Ysciencereview

4

S P R I N G I S S U E

FEATURES

24 Beyond the Ivory Tower

Cal academics rush in where

Pharma fears to tread

by Letty Brown

33 Creature Comforts

Field station provides a

window on the wild

by Annaliese Beery

38 The Ground Beneath

Your Feet

Exposing the states

of endangered soils

by Charlie Koven

B E R K E L E Ysciencereview

6

LABSCOPES LABSCOPESLABSCOPES

host etectors in the ky

THE AURORA—the ghostly lightshow sometimes visible in polar skies—is well known for its beauty. But

beauty can be treacherous: the same phenomenon that causes the aurora can also cause space storms that disrupt satellite communications and power grids. Both lights and storms

aking ense of cents

C LOSE YOUR EYES … and imagine the scent of strawberries. Did you take a sniff? According to a new

study from UC Berkeley’s Department of Psychology, you probably did. Researchers have long suspected a connection between motor function and the images created in the mind’s eye. For example, it is well known that when people are asked to imagine a visual scene, they make eye movements that mimic real viewing. But Moustafa Bensafi, a post-doctoral researcher in Noam Sobel’s lab, wondered whether the same connection exists in our sense of smell. e answer he found was a resounding “yes.” Bensafi conducted experiments where naïve subjects wore special masks which measured and recorded the air flow rate through the subject’s nose. When asked to imagine smells such as strawberries or rotten eggs, they not only took a noticeable sniff, the size of their sniffs depended on the type of odor they were imagining. is finding supports earlier work done in the Sobel lab which found that people experiencing a pleasant aroma intuitively take a big sniff, while a foul stench evokes a much more timid response. Sure enough, this effect holds for imagined smells as well. Bensafi also found strong evidence that a physical sniff is necessary to form a clear mental image.

Subjects were asked after each trial to rate their mental images. When their ability to sniff was blocked with a nasal clip during the imagination period, subjects rated their image much lower in vividness and intensity. — Jess Porter

Learn more at: ist-socrates.berkeley.edu/~borp/index.htm

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result from “magnetic reconnection,” the temporary opening of a gap in the Earth’s magnetic field. Magnetic reconnection occurs when a gust in the solar wind—the current of energetic, charged particles streaming from the sun—creates a magnetic field that in some place exactly cancels the Earth’s. Past research on magnetic reconnection has relied on local measurements by passing spacecraft, which provide only a fleeting glimpse of the phenomenon. Now, scientists at UC Berkeley’s Space Sciences Laboratory (SSL) have devised an ultraviolet detector flown aboard NASA’s IMAGE spacecraft to view changes in the Earth’s magnetic field continuously. e SSL team found that cracks in the Earth’s field stay open for hours rather than in sporadic bursts as predicted by some theories—new knowledge potentially valuable for space-weather forecasting. ough beauty is notoriously ephemeral, the cause of the aurora, it seems, is no flash in the pan. — Chris Weber

Want to know more?www.gsfc.nasa.gov/topstory//image_cluster.html

LABSCOPES

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reen nergy from utant lgae

I F PROFESSOR ANASTASIOS MELIS of the Department of Plant and Microbial Biology has any say about it, someday

the clean air, inexpensive fuel and open space might actually make it desirable to live next to a power plant. e Melis lab is engineering the unicellular green alga Chlamydomonas reinhardtii to make environmentally clean hydrogen gas for fuel. But C. reinhardtii has evolved to survive with limited access to sunlight, not in bright, man-made bioreactors. e “serious optical challenge,” as Melis puts it, is that the chlorophyll antenna molecules that C. reinhardtii uses to harvest the sun’s light work best in nature, where these algae live in dense mats many cells thick and shade each other from direct sunlight. As a result, these algae are sensitive to intense light, which can damage their chloroplasts and reduce their capacity for photosynthesis—and for hydrogen production. To avoid this waste of the sun’s energy, the Melis lab has made mutant algae that have smaller light-harvesting antennae, making the algal hydrogen production ten times more efficient. “My vision,” says Melis, “is mass cultures, millions of gallons, in a sterile bioreactor in tubes lying miles on end, where sunlight can penetrate through.” e algae also eat

ncoming

THE DAILY ROUTINE in the Dudley lab might involve gliding in wind tunnels and jumping from high posts—if

you’re one of graduate student Greg Byrnes’ flying squirrels, that is. Robert Dudley, a professor in the Department of Integrated Biology, recently moved his lab here from Texas, along with an assortment of aerial acrobatics equipment which the lab uses to study the biomechanics of flight. “We’re particularly interested in the unstable aspects of flight dynamics like maneuverability and acceleration,” says Byrnes. He is using flying squirrels to study aspects of gliding behavior that may give insight into the early stages of the evolution of flight in other species. For their part, the squirrels get rewarded with tasty pecans for making the leap to a distant, carpeted post, while Byrnes photographs them and analyzes their motion. He uses the lab’s wind tunnel in order to study the animals as they glide continuously. Members of the Dudley lab also study flight in hummingbirds, orchid bees and butterflies and are encouraged to ask a range of “idiosyncratic biomechanical and ecophysiological questions.” Not too big of a leap for Byrnes and his squirrels. — Annaliese Beery

Learn more at:ib.berkeley.edu/faculty/dudleyr.html

the greenhouse gas carbon dioxide and, as by-products, produce photoprotective pigments, such as zeaxanthin, that can be added to foods or taken as vitamin supplements for their beneficial antioxidant properties. Melis’ vision is still a long way from reality, but if he gets his way, he’ll give a whole new meaning to “green” energy. — Kristen DeAngelis

Learn more at: plantbio.berkeley.edu/profiles/newProfiles/melis.html

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W HILE INDUSTRIAL lobbyists and environmentalists bicker over

how global warming will affect ecosystems, Professor John Harte of the Energy and Resources Group and the Department of Environmental Science, Policy and Management proposes to settle the issue this way: let’s try it and see what happens.

Harte has been heating patches of a Colorado mountain meadow for years to determine how increased temperatures affect the ecosystem. Infrared heaters hang above -square-meter plots, increasing the amount of heat radiation that hits the ground below by three percent over unheated plots. is increase mimics the change expected from the pre-industrial atmospheric carbon dioxide concentration doubling, which climate change studies predict will occur by about .

“We turned on the heaters in January ,” says Harte, “and they’ve been on ever since.” For over a decade, Harte and his students have worked like a team of doctors hovering over their patient. ey keep tabs on a long list of vital signs, measuring soil temperatures and soil moisture, counting the number of each plant species, and recording when these species bud, flower, and disperse their seeds. ey analyze these and other measurements to track down the consequences of warming in the meadow.

Harte’s experiment was the first of its type. He began the research because the computer models used to predict climate change do not include an ecosystem’s crucially important responses to warming, which scientists call “ecosystem coupling.” If warming causes a change that leads to additional warming—known as a positive feedback response—small increases in temperature could lead to big effects. On the other hand, if warming causes a change that leads to decreased warming—a negative feedback response—the effects of heating will be kept in check, and the ecosystem should remain stable. While other researchers had investigated

ecosystem coupling via studies of warming in greenhouses, Harte wanted to monitor the effects of climate change in a more realistic environment. His experiment has identified feedback responses that he hopes can be used to improve climate change models.

Harte and his team were surprised at how quickly and dramatically their plots changed. e heaters caused winter snows to melt about two weeks early, raised soil temperatures by about º C, and dried the soil by to percent. ese changes altered the distribution of plant species in the plots, increased the amount of sunlight absorbed by the ground surface, and changed the rate that soil microorganisms consume and produce the greenhouse gases methane and carbon dioxide.

Harte’s team found that increased tempera-tures caused certain plants to thrive at the expense of others. As much as two-thirds of the forbs—non-woody, flowering plants

“like daisies and all the things you think of when you think of beautiful, flower-strewn mountain meadows”—have disappeared from the heated plots, says Harte. Meanwhile, he says, “Sage is growing like gangbusters.” Because sagebrush plants are darker than the more brightly colored forbs, more sage means a darker plot, which in turn absorbs more light energy and leads to more sage—a positive feedback to warming.

e early snowmelt causes a similar positive feedback response. Snow-covered ground reflects sunlight well, so a snowy surface absorbs much less energy than bare soil does. Since the heat lamps cause snow to melt earlier, the exposed ground begins trapping heat earlier in the season, increasing the effects of warming.

Not all the feedback mechanisms in the meadow experiment are as straightforward. e relationship between warming and

Rocky Mountain HighMeadow warming offers a sneak peek at climate change

Heaters simulate

global warming in this

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meadow. The heaters

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greenhouse gas flux varies under different conditions. Certain microorganisms in the meadow’s soil reduce warming by consuming methane from the atmosphere. Other microbes release heat-trapping carbon dioxide by degrading dead plant matter. Harte found that his heaters either accelerate or slow these processes, depending on the temperature, soil moisture, and kinds of plants in the plots.

ough Harte has observed both positive and negative feedbacks to warming in the meadow, he cautiously says that responses that increase the effects of warming are more common. He notes that his approach does not mimic climate change perfectly. For example, he has not increased the amount of carbon dioxide

in the meadow air. Nor has he changed the amount of rain that falls on the plots. ese two factors, which are expected in “real” global warming, could also affect the behavior of the ecosystem.

Harte also emphasizes that while he and his group have learned much about the effects of warming in a Rocky Mountain meadow, different environments—such as forests, deserts or tundra—may respond differently to climate change. “e experiment we’re doing is expensive and time consuming,” Harte says. “You can’t do this kind of experiment everywhere.”

Nevertheless, his study has yielded important results. “Everything we know about ecosystem coupling suggests that the [climate change] situation is more dire than models predict,” Harte says. e heaters will stay on for at least another five years. In the meantime, Harte and his students are using their results to develop simpler, more universal ways of predicting the ecological impact of climate change that other scientists can use beyond their mountain meadow.

J M is a graduate student in chemical engineering.

Want to know more?socrates.berkeley.edu/~hartelab

UC BERKELEY graduate students and postdocs under the direction

of Professor John Clarke are dancing a magnetic limbo. e bar is set extremely low. Using fields weaker than those produced by refrigerator magnets, Clarke’s team and their collaborators from Alex Pines’ group have been able to image samples with millimeter resolution. And Clarke hopes his novel magnetic resonance imaging (MRI) system—which uses fields , times lower than those currently used in clinical MRIs—will soon be available for cheap and reliable medical imaging.

An MRI system images “soft” tissues, which don’t show up on X-ray images, and is invaluable to doctors who need to see inside the human body before operating. e key to MRI is the hydrogen contained in water molecules in the patient’s tissue. e hydrogen nuclei give a magnetic resonance signal when they absorb or emit radio waves in a magnetic

field. An MR image—for instance, of someone’s brain—shows a three-dimensional volume as a series of slices, with each slice showing detailed information about the density of hydrogen atoms. Because hydrogen atoms in different tissues give different MR signals, doctors can use these images to pinpoint hairline fractures or torn cartilage and to distinguish healthy tissue from tumors. “e tumor lights up” in an MR image, says Clarke, because cancer breaks down cell membranes, giving a different structure to the tissues.

But this valuable tool is not without its prob-lems. Clinical MRI machines require a power-ful electromagnet—a coil of superconducting wire that carries a permanent, circulating current— to produce a magnetic field about , times that of the Earth. Seungkyun Lee, one of Clarke’s students, points out that a big superconducting magnet is “expensive, bulky, and in general very demanding of

e Low Ambitions of Mr. SQUIDAre weak magnets the future of MRI?

Magnetic resonance in the kitchen:

grad student Whit Myers slices bell

peppers with the Clarke low-field MRI

system and a trusty Ginsu.

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infrastructure.” MRI also requires that the magnetic field be very uniform; for commer-cial systems, typically to one part in a hundred million over the region imaged. Making the field uniform in a commercial MRI requires a set of superconducting “shim” magnets. ese magnets are also expensive, and the process of “shimming” takes a long time.

Clarke’s low-field plywood-and-wire prototype, however, does without the expensive monster bore magnet and shim coils of a commercial MRI system. e fields used in Clarke’s technique are low enough to be produced by an inexpensive pair of simple wire coils. And the low-field MRI magnet doesn’t require such a uniform field. “We haven’t done any shimming at all,” says Whit Myers, another student. e cost-saving advantages of low-field MRI are made possible by Clarke’s specialty: the superconducting quantum interference device, or “SQUID.”

Clarke drinks his tea out of a mug with a big blue squid painted on the side, but the “SQUID” in Clarke’s experiments is no marine mollusk; it is an extremely sensitive detector of magnetic flux. So many of Clarke’s contributions to the field of superconductivity have been in the application of SQUIDs to scientific and practical problems that he has earned himself the title of “Mr. SQUID” among his colleagues. e critical element in Clarke’s latest low-field MRI system is, of course, a SQUID, fabricated from thin layers of niobium and aluminum oxide and chilled to . Kelvin—well below the temperature at which air liquefies.

e sensitivity of the SQUID is critical for Clarke’s low-field MRI to work. For a standard MRI receiver, the strength of the detected signal increases with the radio waves’ frequency. A strong magnetic field means higher frequency radio waves, which in turn means a bigger signal. A conventional MRI needs its strong electromagnets to boost the radio frequencies up to MHz. A SQUID’s sensitivity, however, does not depend on frequency, so it is able to function in a much lower magnetic field; Clarke’s system can detect radio waves oscillating at only . kHz. is detection scheme works well: Myers, with postdoc Michael Moessle, has used

Clarke’s low-frequency, SQUID-detected MRI to image samples to a resolution of one millimeter and biological samples to four milimeters. Instead of scanning brains, he uses green peppers, which are far easier to obtain, and, according to Myers, much tastier.

Brain imaging, however, is low-field MRI’s next project. A Canadian company, CTF Systems, has bought commercial rights to an application of the Clarke group’s techniques. CTF makes extensive use of SQUIDs to image the magnetic fields produced by the brain. is procedure, “magnetoencephalography” (MEG), is used before excision of a brain tumor to map out the brain’s functional areas, ensuring that the tissue surrounding the tumor is cut in the places that are used the least. e CTF system uses SQUIDs, which completely cover the top of a patient’s head. CTF intends to integrate their MEG capability with Clarke’s low-field MRI system to map brain function onto a -D image of the brain itself. “With SQUIDs instead of

just the one that we have, CTF should be able to get far superior images to ours,” says Myers.

Currently, patients need to get the MEG done at one facility before traveling elsewhere for a brain MR image. Even though low-field MRI takes more time than high-field MRI, integrating MEG and low-field MRI will save patients time and money.

Clarke says he began his project “just because [low-field MRI] was there” and does not intend the technique to compete with high-field MRI. But having set his sights low—ultra-low—he may soon be able to watch his concept develop into medical reality.

K M is a graduate student in biophysics.

Want to know more?ist-socrates.berkeley.edu/~jclarke

T HE STUDY of human evolution is not for the faint of heart. With

heated debates surrounding each new discovery, there are few fields that are so charged with controversy. One long-standing debate concerns the “out of Africa” theory, which argues that Homo sapiens evolved in Africa. e theory has been vocally opposed by “multiregionalists,” who believe that modern man evolved in many different regions throughout the world. But recently, an international research team including Tim White of UC Berkeley’s Department of Integrative Biology and Laboratory for Evolutionary Studies, hit a home run for the “out of Africa” team by discovering the oldest known fossils of Homo sapiens in Herto, Ethiopia.

e Herto findings put to rest a predominant argument against the “out of Africa” theory. While genetic analyses have been providing mounting support for the theory, the fossil record in Africa remained incomplete. “e multiregionalists pointed to a lack of fossil

Out of AfricaTracing the origins of man

evidence in Africa to support their theory,” said White. “Post-Herto, that is no longer possible.” e findings are significant, White said, because they share characteristics of both archaic and modern humans. ey provide a missing link, in a sense, between us and our pre-Homo sapiens ancestors.

Herds of goat and cattle scatter present-day Herto, a village on the arid Bouri Peninsula of Ethiopia. Today, the animals barely subsist on patchy scrubs of vegetation, but , years ago, Herto surrounded a freshwater lake and was home to hippos and crocodiles. While the current dry and dusty conditions of Herto are challenging for its inhabitants, they are perfect for archaeologists. In fact, White’s research team was attracted to their site after noticing a prehistoric hippo cranium protruding from the sands—before any digging occurred. It was clear from the start that the hippos and bovines they found had been butchered, said White. But it would take five years to get a clear picture of the humans who did the butchering.

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en, one day in the early dry season of , White was setting up lunch at Herto while other team members were still surveying for exposed fossils. Before he could eat, the sur-veyors told White they had found a hominid bone in the peninsula’s eroding, ancient sands. Although the chunk of bone was only about half the size of a dollar bill, White and his team later determined it to be a piece of a skull from the earliest known sub-species of Homo sapiens. After uncovering more fossil-ized fragments, the team reconstructed skull fragments and teeth from seven individuals. e three most complete fossils, however, were one adult cranium (excluding the lower jaw), cranial fragments from another adult, and a less-complete child’s skull.

To determine the age of the fossils, White and his team turned to Paul Renne, of UC Berkeley’s Department of Earth and Planetary Sciences and the Berkeley Geochronology Center—a non-profit organization that dates geological events in the Earth’s history. Renne’s research group used argon-isotope dating to find the age of the Herto fossils. is process takes advantage of the radioactive decay of an isotope of potassium (potassium-) into argon (argon-). By knowing the rate of this decay and measuring the proportion of potassium- to argon-, Renne and his team determined the age of volcanic ash above and below the fossils. After correlating the make-up of the Herto fossils with the volcanic ash, they dated the skulls to about , years ago, chronologically placing them between pre-Homo sapiens and modern man.

“ey are by far and away the oldest known Homo sapiens,” said Renne. “ey clearly support the out-of-Africa hypothesis.”

e Herto individuals are not the only early humans found in Africa, but their relative wholeness makes them the most significant. Unlike remains dating from , to , years ago found in South Africa, Tanzania and Morocco, the Ethiopian fossils are “especially well preserved and clean,” said Renne. ey do not show evidence of disease or pathologies, which can sometimes misrepresent a species and mislead scientists.

e most unique quality of the crania is their combination of early and modern human features. For example, the wide-set eyes, anteriorly-placed teeth, and short occipital bone at the base of the skull are found in more ancient African crania. But the wide upper face, moderately domed forehead, and globular braincase resemble modern human fossils, like those found in Israel from about , years ago.

ese findings are so unique, in fact, that White and his colleagues have assigned them to a new subspecies of Homo sapiens. ey chose the name Homo sapiens idaltu, which means “old man” in the language of the Afar people who now inhabit Herto. It is meant to honor the people of the Bouri Peninsula, White explained, with whom he has become friends over the last years. In fact, Afar Chief Elema has two sons who are learning to be paleontologists, and White plans to

continue teaching them when he returns to Ethiopia to revisit the Herto site and venture into other nearby areas.

“ere is a lot we don’t know about human evolution,” said White. “Any chance we get, we want to know more.”

A R is a graduate student in journalism.

Want to know more?Pleistocene Homo sapiens from Middle Awash, Ethiopia. TD White et al., Nature (); Vol. , pages -.

Stratographic, chronological and behavioural contexts of Pleistocene Homo sapiens from Middle Awash, Ethiopia. JD Clark et al., Nature (); Vol. , pages -.

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Far right: As livestock graze in the

distance, researchers sweep sand from an

archaeological site in Awash, Ethiopia. This

site and others nearby yielded the oldest

remains of Homo sapiens ever discovered,

including the reconstructed adult skull

shown at near right. The discovery of these

fossils lends credence to the “out of Africa”

hypothesis. The skull is currently housed

in the National Museum of Ethiopia, Addis

Ababa. Bottom: Professor Tim White displays

his Cal colors while working in Ethiopia.

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IT TAKES A BOLD creature to stand between determined hordes of

thirsty California wine connoisseurs and the fruit of Napa’s fertile vineyards. But Nature, much to the chagrin of California vintners, has devised just such an organism. Meet Xylella fastidiosa: bacterium, agricultural pest, and wine-lover’s nightmare. is plant pathogen thrives in the tissue of susceptible plants such as grapevines, reducing them to withered, yellowed skeletons in an affliction known as Pierce’s disease.

California viticulturists, anxious at the prospect of barren vineyards and a devastated wine industry, have kept a wary eye on the mounting acreage claimed by Xylella. To combat the disease, they have recruited the help of Berkeley scientists. One is postdoc Karyn Newman of Steven Lindow’s lab in the Department of Plant and Microbial Biology. Her recent efforts clarify the molecular details of Xylella infection and suggest a new model of how communities of bacteria coordinate their behavior in different hosts.

Newman faced the challenge of unraveling Xylella’s complex interactions

with its two hosts. Because a grapevine’s tough epidermis normally excludes the pathogen from the nutrient-rich tissues within, Xylella hitches a ride in the gut of a second host, the sharpshooter leafhopper. is insect feeds on grapevines by plunging its stiletto-like mouthparts into the plant’s xylem (the system of tubes that carries water and minerals throughout the plant) in order to suck out a meal of nutritious sap. Berkeley’s Alexander Purcell, professor of insect biology and frequent collaborator with the Lindow lab, has shown that bacteria living in the sap of infected plants are sucked into the pumping chamber of the insect’s mouthparts. Once inside this compartment, called the foregut, Xylella adheres to the chamber’s walls and proliferates. “When you look inside the foregut of these insects,” Purcell explains, “you see single cells, then little tufts of bacteria…en you look again a week or so later, and it’s like shag carpeting!” ese Xylella colonies, which thrive off of the xylem sap that floods the insect’s mouth, provide a reservoir of infectious bacteria. Like a malarial mosquito, a single infected sharpshooter punctures vine after vine, spreading the disease to uninfected plants as it feeds.

Once inside a plant, Xylella initially infects only a single cell, causing few symptoms, then slowly spreads through-out the plant’s xylem. As the bacteria establish new colonies, they exude a coat of gummy polysaccharides and replicate, gradually forming dense obstructions throughout the vascular network. “e cumulative effect of all those plugs is to block sap flow,” says Newman. As peripheral tissues are deprived of water, the plant’s leaves yellow and scorch, and the fruit withers on the vine. In the end, severely infested vineyards look, in Newman’s words, “like moonscapes.”

ough farmers rigorously inspect every new plant for signs of disease, prune back infected limbs, and spray pesticides to curb the sharpshooter population, according to Newman, “You only need a couple of infected bugs in a vineyard to wreak havoc.” Understanding Xy-lella’s interactions with its hosts is therefore crucial in devising new strategies to protect vineyards fromthis plant pathogen.

Popular conceptions of infectious bacteria cast these organisms as single-celled barbarians at the gate: undisciplined,

The glassy-winged sharpshooter

feeds on California grapevines,

infecting them with the bacteria

that cause Pierce’s disease.

Xylella incites a viticultural vendetta

Trampling Out a Vintage

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uncoordinated hordes that overrun their hosts’ defenses by sheer numbers. However, Newman’s and other studies contradict this notion, showing instead that bacteria use chemical cues to execute highly organized group maneuvers during infection.

For example, Xanthomonas campestris, another plant pathogen and close relative of Xylella, releases a chemical signal into the environment. When enough bacteria are present, the signal accumulates above a threshold concentration, prompting the bacteria to produce disease-causing proteins and enzymes that degrade the plant’s cell walls. is type of density-dependent behavior, called quorum sensing, allows individual Xanthomonas bacteria to cooperate with one another, delaying expression of disease genes until the population is large enough to make the infection successful.

Quorum sensing in Xanthomonas is controlled by a family of rpf (Regulation of Pathogenicity Factors) genes. Upon completion of Xylella’s genome sequence in , researchers identified similar genes in its DNA, raising the possibility that the grapevine pathogen also uses quorum sensing when infecting its hosts. Newman investigated this hypothesis by selecting a putative quorum sensing gene, rpfF, and creating a Xylella strain lacking the gene. She then observed

the ability of these mutant bacteria to infect their hosts.

Newman found that deleting, or “knocking out,” the rpfF gene rendered Xylella unable to colonize the sharpshooter. Bacteria were sucked into the insect as usual, but rather than forming colonies, they were simply washed through its digestive system and, as Newman politely states, “into its honey-dew.”

Surprisingly, when Newman injected grapevines with the same rpfF knockout mutants, the plants sickened dramatically compared to those infected by bacteria with functional rpfF. us, says Lindow, “the same signal that promotes colonization in the insect host somehow inhibits exuberant growth or affects other virulence traits in the plant.”

Although the mechanism by which rpfF controls Xylella’s behavior remains unclear, one possibility is that the rpfF signal regulates the pathogen’s spread through the plant. For instance, once the signal has accumulated above a threshold level, it may instruct the bacteria to syn-thesize enzymes that dissolve plant tissues blocking Xylella’s entry into new cells. Pioneering bacteria could then abandon overcrowded colonies and establish new communities in uninfected parts of the plant. If the rpfF signal were absent,

Xylella bacteria clog water transport

vessels in grapevines, and the

water-starved plants wither and die.

The vines on the right are highly

susceptible pinot noir grapevines.

Those on the left are a less-

susceptible chenin blanc variety.

bacteria would be unable to disperse, causing established Xylella colonies to balloon ever larger, perhaps increasing xylem blockage and withering grapevines more severely. Similarly, the rpfF signal may trigger some crucial change in Xylella’s behavior or biochemistry that al-lows it to recognize or attach to its insect host. Deletion of rpfF would therefore curtail the bacteria’s ability to grow in the sharpshooter’s foregut.

Future research in the Lindow lab promises to test these speculations, and Newman continues to investigate Xylella as an intriguing new model for bacterial quorum sensing. Furthermore, her discovery that rpfF makes a signal that impedes Xylella’s growth in plants provides a tantalizing clue to controlling California’s vineyard scourage.

T P is a graduate student in plant biology.

Want to know more?Cell-cell signaling controls Xylella fastidiosa interactions with both insects and plants. K Newman et al., Proceedings of the National Academy of Sciences (); Vol. , pages -.

www.cnr.berkeley.edu/xylella gwss.ucanr.org

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W HEN CONFRONTED with that intractable knot, whether untying

the strings on a package or rescuing a sewing project, eventually you have to reach for the scissors to cut your way out. Living cells must also snip at the jumbles of DNA that are created as these stringy molecules are replicated or folded. Specialized enzymes act as the “scissors” of the cell and must not only cut and disentangle DNA, but also reassemble the strands correctly. How does an enzyme successfully resolve a knot and avoid creating an even bigger snarl? UC Berkeley graduate students Michael Stone and Zev Bryant from the Department of Molecular and Cell Biology (MCB) have employed cutting-edge single molecule techniques, laser tweezers, and even LEGOs to find out how one enzyme, topoisomerase, does the job.

A living cell is a crowded place, and an expansive molecule like DNA has to be compacted in order to squeeze in. Cells do this by tightly coiling their DNA, then further twisting the DNA coils around proteins to form the tight genetic package known as a chromosome. But what happens when proteins need to access genetic information to transcribe or replicate DNA? Proteins are much bigger than the thickness of DNA strands, and nothing but ions are small enough to cram into the spaces left from twisting the DNA into a chromosome.

e simplest way to make enough space to allow proteins to access DNA would be to pull the intertwined molecules of double-stranded DNA apart. But doing so produces extra twists in adjacent stretches—a phenomenon known as “supercoiling.” If you’ve ever idly twisted a telephone cord, you’ve probably

Double, Double, Coil and TroubleUnraveling your knotty DNA

witnessed supercoiling. Twists in the opposite direction of the coil are called negative supercoiling, whereas twists in the direction of the coil cause tighter coiling known as positive supercoiling. When the coils wind so tight that the cord buckles, the resulting loop is known as a plectoneme.

“Supercoiling changes continually. During every process you can think of—repair, transcription, replication—you have to unwind the DNA,” describes MCB professor Nicholas Cozzarelli. “When you have unwinding, it leads to supercoiling.” Whereas negatively supercoiled DNA is necessary for compacting DNA and aiding strand separation for transcription, positively supercoiled DNA is detrimental and must be selectively removed or vital functions

like transcription and cell division would grind to a halt.

ere are plenty of enzymes that can cut DNA, but simply snipping supercoiled DNA (or releasing the twisted telephone cord) would cause the structure to completely relax, regardless of whether it was negatively or positively supercoiled. Instead, cells use a specialized enzyme that removes one twist at a time by cut-ting a segment of DNA without letting go, passing another through the tempo-rary gap, and then resealing the cut seg-ment. is enzyme, called topoisomerase, must distinguish positively supercoiled DNA, which is selectively relaxed by the enzyme, from negatively supercoiled DNA, which is left alone. is feat is particularly remarkable considering that the chirality of the supercoil (positive or

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(positive) (negative)

E. coli topoisomerase IV uses crossing geometry to distinguish

positive from negative supercoiling. In this diagram, each ribbon

represents a double-stranded molecule of DNA. The angle (θ)

is determined by a counterclockwise rotation of the underlying

segment (black) to the overlying segment (white). An acute angle

signifies a left-handed, or positive, supercoil, whereas an obtuse

angle indicates a right-handed, or negative, supercoil.

15

BRIEFS

negative) depends on a DNA segment that is orders of magnitude larger than the size of the enzyme.

Stone and Cozzarelli could foresee two ways that a topoisomerase from Escherichia coli bacteria could be so selec-tive. In one model, the enzyme would examine one of the two individual seg-ments to be transposed and only cut the segment if the direction of local twisting were consistent with positive supercoil-ing. In the other model, topoisomerase compares the angle formed when one seg-ment of supercoiled DNA is crossed by another segment. e crossing segments form two angles, the smaller of which tends to be on one side of the enyzme or the other, depending on the supercoil sign. e problem was that the sign of supercoiling affects both parameters, local twist and crossing geometry, making it impossible to determine the effects of each parameter individually.

What Stone and Cozzarelli needed was a system that would allow them to both supercoil a molecule of DNA in a specific direction and to separate

local twist from crossing angle. ey teamed up with Bryant and his graduate advisor Carlos Bustamante, a professor in the MCB, chemistry, and physics departments at UC Berkeley and the Howard Hughes Medical Institute. Whereas most biochemists work with populations of molecules, the Bustamante lab has pioneered the application of single-molecule techniques to answer biological questions. “With single-molecule methods, you can follow the molecules in real time as they do their thing,” says Bustamante. In this case, the single-molecule methods would allow the researchers to manually coil DNA, specifying the degree and sign of supercoiling.

For this, they used laser tweezers. Laser tweezers work by focusing intense light on a small bead. e light refracts around the bead, and because light photons have momentum, the bent light pushes the bead towards the focus, optically trapping it in place. By attaching a single molecule of DNA at one end to the trapped bead, Bustamante’s group can manipulate the DNA by moving the laser

while simultaneously measuring the force pulling back on the bead.

To supercoil single molecules of DNA, Stone and Bryant modified this apparatus by tethering two molecules of double-stranded DNA in parallel to a bead at either end of the strand. e bead at one end was optically trapped, whereas the bead at the other end was sucked into a rotatable pipette. While initial experiments required both students to turn the pipette by hand, a postdoc later offered up a LEGO MINDSTORMS kit featuring modular motors and gears. Bryant says, “We had to go to Toys-R-Us to buy a second set because we didn’t have enough pieces.”

By turning the pipette clockwise or counterclockwise, Stone and colleagues could positively or negatively supercoil the two strands. To eliminate the effects of supercoiling on the single strands, each component strand was broken at one position to allow it to swivel on its axis, thereby relieving any local twisting. If the enzyme could still distinguish between positive and negative supercoiling, it

plectoneme

Laser tweezers allow manipulation

of single molecules. In this case, two

strands of DNA are attached to a bead

at either end of the strand. One bead

is held in place using a laser, while the

other bead is held in a rotatable pipette.

By rotating the pipette clockwise or

counterclockwise, Stone and coworkers

can dictate the sign of supercoiling

in their experiments. Further rotation

causes the supercoiled fragment to

collapse into a plectoneme.

16

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could only be by detecting the crossing angle of the two strands.

Turning the pipette in either direction caused a steady compaction in the DNA coils until reaching a critical twist that caused the supercoil to buckle into a plectoneme. Addition of topoisomerase selectively relaxed the positively supercoiled strands, but not the negatively supercoiled structures, implying that topoisomerase was in fact using both strands to determine the sign of the supercoil. Furthermore, in cases where negatively supercoiled strands buckle, the plectoneme that forms is positively supercoiled. Topoisomerase relaxed the positively coiled plectoneme but stopped when all that remained was negatively supercoiled, elegantly demonstrating sign specificity.

To Stone, these results illustrate “the inherent role that supercoil structure can have in dictating enzyme activity.” In fact, recent data has shown that several proteins that bind and remodel supercoiled DNA also respond to the crossing geometry of the DNA strands. While enzymes have long been known to manipulate DNA structure, this particu-lar role for DNA structure in dictating enzyme function is a newer twist.

S G is a graduate student in molecular and cell biology.

Want to know more?Chirality sensing by Escherichia coli topo-isomerase IV and the mechanism of type II topoisomerases. MD Stone et al., Proceedings of the National Academy of Sciences (); Vol. , pages -.

{ READ — WRITE — CONTRIBUTE }sciencereview.berkeley.edu

17

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BISMARCK ONCE SAID that the making of laws, like the making of sausages, should never be watched. Many

mathematicians have traditionally thought the same of theorems, as the intuition that suggests a theorem is rarely presented in texts and papers. While rigorous proof has been seen as the raison d’être of mathematics, some believe the desire for elegance and terseness in proofs has led to a bewildering style that can obscure underlying motivation. e result is a debate in which leading mathematicians can be found on either side. e Hungarian mathematician George Polya wrote that “rigorous proofs are the hallmark of mathematics; they are an essential part of mathematics’ contribution to general culture.” But according to Jacques Hadamard, “e object of mathematical rigor is to sanction and legitimize the conquests of intuition, and there was never any other object for it.”

e debate does not just concern how mathematics is presented, but also how it is done. Mathematicians in the Hadamard school of thought are sympathetic to a more experimental approach that uses computers to generate theorems. In fact, when invited recently by www.edge.org to suggest two rules-of-thumb for mathematics, Professor Steven Strogatz of the Center for Applied Mathematics at Cornell gave as his first law: “When you’re trying to prove something, it helps to know it’s true.” His second was: “To figure out if something is true, check it on the computer. If the machine agrees with your own calculations, you’re prob-ably right.”

In Mathematics by Experiment: Plausible Reasoning in the st Century, Jonathan Borwein of Simon Frasier University and David Bailey of Lawrence Berkeley National Laboratory provide an interesting addition to this debate. As the title suggests, the authors side with the experimentalists. Very sensibly, though, they avoid dry philosophical debate, arguing instead for the fruitfulness of the experimental approach in the most enjoyable way possible: through examples of how effective it can be.

e authors point out that the learning-by-calculating method has a distinguished history. ey quote th century mathematician Johann Gauss, who worked “through systematic experimentation.” ey also discuss the history of the Riemann hypothesis, one of the most famous unsolved problems in mathematics. While many have assumed that Riemann’s conjecture was due to pure insight, his papers show that he performed brute-force calculations to several decimal places.

Nothing handles brute-force calculations like a computer, and with the advent of the computer, the experimental method came into its own. Borwein and Bailey present many examples of how computers can be used to generate theorems. One method uses a computer to evaluate an infinite series to a high number of decimal places, then employs “constant recognition” software to see if this number is approximately equal to a well-known constant, like a fraction times a power of π, or a value of the Riemann zeta function. e resulting conjecture, that the equality holds exactly, can then be proved (one hopes) using more conventional means.

As well as extensive discussions of important problems, there are toothsome mathematical morsels at the end of several chapters. ese include quotations from mathematicians, pithy proofs of easily stated theorems, links to interesting Internet sites, and a discussion of the infamous π = chapter of the Bible. Although often lacking any obvious thematic structure, these sections are among the most enjoyable in the book.

Mathematics by Experiment is not a systematic exposition of any mathematical field, and the reader needs a reasonable knowledge of undergraduate mathematics—especially analysis and number theory—to fully enjoy the book. However, the mathematical ideas are always very good, and the reader is often encouraged to engage them by writing simple computer programs, which affords more pleasure than a passive read. e authors also present ten challenging problems, but one must be prepared to invest a significant amount of time to solve them (or, as the author of this review can attest, not to solve them). Whether you take sides in the debate about the validity of experimental mathematics or are not sure what all the fuss is about, the book is a rewarding read.

P M is a graduate student in physics.

Want to know more?For an abridged version of the book and a list of related links, visit: crd.lbl.gov/~dhbailey/expmath

athematics by xperiment lausible easoning in the st enturyBy Jonathan Borwein and David Bailey Reviewed by Padraig Murphy

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Cal academics rush in where Pharma fears

to tread

GLOBAL HEALTH IS A STUDY OF CONTRASTS. A baby girl born in Japan today can expect to live for years, while a girl born at the same moment in Sierra Leone has a life expectancy of only . While wealthy nations pursue drugs to treat baldness and obesity, depression and erectile dysfunction, elsewhere millions suffer from preventable or treatable infectious and parasitic diseases. Scourges such as malaria, tuberculosis, cholera, hepatitis B, and AIDS cause over percent of deaths annually in the developing world, while here in the developed world, clean water, vaccinations,

medications, and adequate nutrition push this figure to below eight percent.

e vory owe

by etty rown

25

How can we bridge this gap? Most for-profit companies are not interested in developing cures for people who cannot pay. And while governments and international aid agencies are doing important work, they are far from solving the global health crisis on their own. Academic researchers, who often have the expertise, flexibility and passion to address these needs, are also called upon to do their part. But it isn’t always easy. Research in the developing world is fraught with difficulties, from lack of resources and pressure from academic systems to the personal threat of war and disease. Fortunately, some are willing to step up to the plate. Professor Vince Resh, Professor Eva Harris, Dr. Tom Carlson, and others here at UC Berkeley have been willing take science beyond the ivory tower, demonstrating the range of research that can be used to control, diagnose, and treat these devastating diseases.

P H O T O C O U R T E S Y : O N C H O C E R C I A S I S C O N T R O L P R O G R A M M E /

W O R L D H E A L T H O R G A N I Z A T I O N

Village in West Africa, abandoned due to African river blindness.

An adult black fly

(Simulium dam-

nosum) taking a

bloodmeal on

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Bringing a River Valley Back to Life STANDING IN HIS OFFICE in the Wellman building on the Berkeley campus, Professor Vince Resh shows me a photograph. Resh stands with eight Africans, male and female, next to the river Pru in Ghana. Although the Africans are all adults, they appear childlike in size and stature, and Resh, at ’’’, towers above them. “Besides blindness, high parasite loads lead to a lot of stunting,” he explains. e people he stands with are victims of African river blindness.

African river blindness, caused by the nematode parasite Onchocerca volvulus, is so named because out of afflicted countries are in Africa; because it is transmitted by black flies, whose larval and pupal stages live in rivers; and because it leads to blindness in up to percent of adults in afflicted communities. Resh, a professor in the Division of Insect Biology in the Department of Environmental Science, Policy and Management, uses his expertise in entomology to help control African river blindness in sub-Saharan West Africa.

Resh is part of the World Bank-funded World Health Organization (WHO) program to control African river blindness, started in the mid-s under the leadership of the former US Secretary of Defense Robert McNamara. While traveling through West Africa, then considered the poorest part of the world, a French entomologist convinced McNamara that curing African river blindness would raise the standard of living of the area to that of the rest of the continent. “Because of this disease, the most fertile valleys for agriculture were being abandoned—and had been abandoned for hundreds of years,” says Resh.

It’s easy to understand why: when a black fly carrying the parasite bites a human, the tiny larval worms are injected

into the subcutaneous tissue, where they swim under the skin causing skin lesions and violent, intense itching. When the larvae mature, the parasitic nematodes concentrate around bony areas like the pelvis, forming golf-ball-sized cysts where the to centimeter long adults reproduce. During a parasite’s lifetime, averaging years, it can cause chronic suffering and disability: wrinkling and depigmentation of the skin, elephantitis of the genitals, stunting of growth, and blindness in to percent of infected adults.

e WHO decided that the easiest way to mitigate the disease was to control the black fly. Resh, a specialist in disease-carrying insects and freshwater ecosystem monitoring, was brought on board in the early s as one of five ecologists to serve as advisors to the program. Resh and his colleagues were in charge of the development of a selective insecticide and the evaluation of environmental damage. e panel chose a mix of pesticides, made up of percent Bacillus thuringensis israelenisis (Bti)—used in the United States for insect abatement in marshes—which is very selective towards black flies. “It has almost no non-target effects,” Resh explains. To avoid Bti resistance in the black flies, the team used percent other insecticides and a rotational scheme.

Resh’s position put him in charge of countries, where he oversaw the spraying of insecticide along , miles of river per week for what would be a total of years. Simultaneously, he was put in charge of resettlement issues. “You have these vacated river valleys, and suddenly you have hundreds of thousands of people moving in,” he says. “If their practices are non-sustainable, everything goes down the tubes.”

e project has been widely lauded. “It has been the success story of public health,” Resh says. “After years of spraying you find fish populations didn’t decline, fish diversity didn’t decline. e system has recovered. And from the development point of view, food is grown in this area now for at least million people who weren’t being fed before.”

“I had this great degree in biochemical sciences but what did it mean?” she said. “I wanted to work in something I was skilled in, and do something real, give something back to society.”

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Detecting Disease on a Shoestring Budget IN ANOTHER PART of the Berkeley campus, Assistant Professor Eva Harris of Berkeley’s School of Public Health attacks the global health crisis from another angle. Harris is one of a small number of professors on campus to have been honored with a MacArthur “genius award”—an internationally renowned prize given to a few people each year who display creativity and genius as they work towards the greater public good. “For years I’ve been setting up programs to develop scientific capacity in developing countries,” she tells me, “focusing on the poorest countries in Latin America.”

Scientific capacity-building means helping biomedical scientists in developing nations gain access to the training, funding, and equipment needed to diagnose, prevent, and cure infectious diseases: in other words, helping local people to help themselves. In a report, the Global Forum for Health Research stated that “strengthening research capacity in developing countries is one of the most effective ways of advancing health and development in these countries.” But it is a difficult road. In , Harris wrote for the British Medical Journal: “Global health relies on biomedical scientists and public health workers to solve infectious disease and other health problems at a local level. Yet investigators in developing countries face tremendous obstacles: scientific

isolation, insufficient technical training and research tools, a lack of up-to-date scientific information, and limited financial, material, and human resources.”

Harris became involved in this field after moving to Latin America before graduate school. “I had this great [undergraduate] degree in biochemical sciences but what did it mean?” she said. “I wanted to work in something I was skilled in and do something real, give something back to society.” She deferred graduate studies and began working in the Nicaraguan Ministry of Health, where, in the midst of the war between the contras and the Sandanistas and with roosters underfoot, she was charged with teaching molecular biology techniques to health clinic workers. “It was one of the most terrifying moments of my life,” Harris says. “Here I was, years old, fresh off the boat, clutching Xeroxes from Bruce Albert’s Molecular Biology of the Cell, thinking, ‘is is all I know. ese people have been running a revolution for years and I’m supposed to teach them? But,” she adds, “it resulted in years of incredible work together, and it really did change my life.” Soon after, while working on her PhD in UC Berkeley’s Department of Molecular and Cellular Biology, she extended this volunteer work and was soon teaching a suite of workshops.

Vince Resh standing beside the river Pru in Ghana with African villagers ,

all victims of African river blindness.

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In the late s, Harris and her team brought polymerase chain reaction (PCR)—a new method of copying DNA useful for detecting infectious diseases—to Nicaragua. e technique usually requires thermocyclers, machines costing about , each, but Harris found ways around this. “It was an incredible moment,” she describes. “With a beaker of

ice water in one hand and a pot of boiling water in another, we were elbowing each other to see the band of DNA. I saw what the power of this could be.” Despite intermittent electricity and a lack of running water most days of the week, Harris and team had successfully improvised water baths at different temperatures to manually amplify DNA. It was PCR, but without the expensive machinery. With these methods, they detected and speciated the Leishmania

protozoa—a parasite that can cause ulcerated lesions and swelling of the spleen and liver—and were able to start helping local people infected with the parasite. “is is where the vision came from for what I do: adapting fancy technologies from the North to the needs of the South,” she says. “But as a true partnership, in a respectful way.”

While she was a postdoc at UCSF, Harris published a book about the principles behind technology transfer called A Low Cost Approach to PCR: Appropriate Transfer of Biomolecular Techniques (Oxford University Press). She had helped start labs in many countries and was designing and personally teaching different courses in Bolivia, Ecuador, and other Latin American countries. With the money she earned from winning the MacArthur award in , Harris started a non-profit organization called the Sustainable Science Institute (SSI), which she still heads today. e institute has enabled her to hand over many of her responsibilities to a professional staff and to start scientific capacity building projects worldwide.

Now, Harris’ laboratory in the Division of Infectious Diseases in the School of Public Health is primarily focused on the dengue fever virus—a virus responsible for the most prevalent mosquito-borne viral illness in humans and a major public health threat worldwide. Also known as “breakbone fever,” the disease affects about million people each year, with , hospitalizations and , deaths annually. Harris was at first hesitant to study the disease as she was

A boy leads a woman

blinded by onchocerciasis

in a West African village.

As many as percent

of those afflicted with

the disease eventually

become blind.

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While these people break their backs to pay for Western pharmaceuticals—which cost, on average, half a billion dollars each to develop—Carlson believes that they could be growing plants in their backyards that could be just as or more effective.

Eva Harris (second from

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sample extraction in

preparation for PCR in a

workshop in Ecuador.

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RESH, HARRIS AND CARLSON aren’t the only UC Berkeley professors whose work benefits developing world health. In the Department of Electrical Engineering and Computer Science, there’s Bernhard Boser’s bio-chip that diagnoses infectious diseases, and in chemical engineering, Jay Keasling’s work on malarial drugs. Along with Eva Harris, the School of Public Health has Kirk Smith studying indoor pollution issues in the developing world and Joe Eisenberg studying the spread of waterborne diseases in northern coastal Ecuador. Kara Nelson in civil and environmental engineering works on wastewater treatment with an emphasis on controlling water-borne pathogens in the developing world. Others can be found here and there in departments throughout the university.

But they are in the minority. Of the billion per year that goes to health research worldwide, only billion of this is allocated to health research in the developing world. is statistic is called the / Gap: only percent of the worldwide expenditure on health research and development is devoted to the major health problems of percent of the world’s population. Meanwhile, according to the United Nations Development Program, billion a year is spent annually on cosmetics in the US and another billion on pet food. Big companies and other institutions aren’t addressing these disparities. e drug industry has shown no great interest in remedies for third-world ailments. Of the , drugs licensed between and , according to one report, only were for tropical diseases and only four of those were developed by the pharmaceutical industry.

When pharmaceutical companies do get involved in the developing world, they often use indigenous knowledge to identify genetic and biological resources in exotic plants that could be turned into a profitable drug or other product for Western markets. e companies then patent this “discovery,” and the local communities where this plant and

including what part of the plant was used, how much, and how it was prepared, and brought the plant back to the United States. ere, he designed scientific studies to test for bioactivity in cellular and animal models and conducted human clinical trials at UCSF and Stanford to test its safety and efficacy. e results, published in the American Journal of Physiology, showed that it can control secretory diarrhea, including traveler’s diarrhea and diarrhea in people living with AIDS. Carlson is now advising the San Francisco-based non-profit drug company One World Health on the low-cost development of this medication for the affordable treatment of diarrhea in infants and children in tropical countries.

ere is a sense of urgency to his work. e tropical rainforests—containing percent of the world’s vascular plants—are being cleared at a rapid rate. According to World Resources Institute, species each day—four every hour—go extinct due to tropical deforestation, and researchers estimate that pharmaceutical companies have looked at fewer than one percent of the world’s plants. Additionally, the cultures that hold the knowledge of plant-based medicines are increasingly threatened. Over different Amazonian tribes are thought to have gone extinct in the last century. With them went oral “libraries” of information passed down over time. In other communities, Carlson sees young people showing less interest in traditional healers. However, he says that is not always the case. When young people in indigenous communities where he works see Western doctors and scientists take interest in traditional healers, it almost always generates new respect for these elders. “It refuels interest in youngsters in the traditional ways,” he says. “It is very empowering to watch these traditional healers get respect.”

The 10/90 Gap

31

seen their fair share of action, from civil war in Nicaragua to cholera outbreaks in Peru.

While they are busy struggling with war and disease—and trying to save humanity in the bargain—these researchers still need to find time to be good professors and fulfill their academic role at the university. Some departments at UC Berkeley are especially good at encouraging such applied work. When I ask Resh how he was able to do what he did, he says, “I’ve been lucky, very lucky. Our department and division have been very supportive. Our college (the College of Natural Resources) supports work on applied problems.” Of course, he isn’t exactly shirking his professorial duties. Concomitant with his work with the WHO, Resh has managed to publish over papers, mentor over

knowledge originated seldom see any benefit. e companies call this bioprospecting, but others see it as biopiracy.

To avoid biopiracy in his work with traditional healers, Carlson always secures a clear agreement from the local communities as well as the host governments where he works, in compliance with the Convention on Biological Diversity (CBD). e CBD, a product of the Earth Summit in Rio de Janeiro, was ratified by countries as of , although not yet by the United States. e CBD sets up legal guidelines for the equitable sharing of benefits between all parties involved in exchanges of genetic resources and implements systems of funding that acknowledge rights over resources and technologies. Carlson found the literature about this to be scarce, so he has written numerous articles based on his own research in tropical countries to clarify bioprospecting principles addressed by the CBD.

When large institutions do become engaged, they often display a paternalistic attitude. As Harris explains, “ere is normally a horrible cycle, where there is a dependency, an imposed top-down approach, so people aren’t used to making their own decisions. Often with the NIH and other granting institutions, it is the agenda of the Northern partner.” She adds that this can sometimes work, but it is not a sustainable solution. Some of this paternalistic attitude may be slowly changing. Resh feels that in WHO/World Bank projects, at least, community involvement is emphasized and the leadership structure is becoming less “top down” and more locally led. “By the time I left,” he says, “I was the last non-African leader of the onchocerciasis program.”

Unfortunately, respect is not the norm. Researchers of developing world health see increasing disempowerment in poor populations. Loss of land—whether due to development projects, wars, or drought—is a tremendous health problem. Without land, families are not able to grow their own food or medicinal plants. Carlson states, “I see the largest mortality and morbidity in places where people have lost access to their land, where they are disenfranchised and their land is taken by others.”

The Cost of Doing the Right ThingFOR PROFESSORS WORKING in the developing world, physical hardships are a fact of life. As an advisor for the WHO, Resh has found himself in several life threatening situations, from civil war in the Ivory Coast to his own battle with infectious disease. “Five of us—three Africans and a French guy and myself—picked up something that went undiagnosed for two and a half years,” he says. “We all thought we were going to die.” Harris and Carlson have also

“These are people who are at the end of the road. Nobody gives a damn about them. They are the poorest, least politically powerful people in the world, and that’s what was relevant about this. That’s why you take a chance.”

graduate students and, in , win a Distinguished Teaching award—given to only a handful of professors campus wide—for his instruction of the introductory biology course Biology B.

Still, it is very difficult to fulfill both roles. Harris wonders about her record in the context of the metrics of success in the academic world. “I’m up for tenure this year and I don’t know what they’re going to do with me,” she says, candidly. “I have developed a very broad program and a really strong CV to back it up, and I’ve done high level work throughout. But it’s very unusual in the academic sphere because you are really supposed to specialize.” She adds, “I know I’m paying the price to do not just all the basic science but the work in developing countries and service to society as well. It’s really a negative in terms of the academic world.”

When facing a tenure review, Harris says, public service hardly matters. “What matters?” she says. “First and last author on publications and principal investigator on the grant. Period.” So even while people in the academic world wonder why there aren’t more collaborations and international partnerships, the truth is that the

33

AS THE FOG ROLLS across the hills, Ned Place prepares a cocktail of tranquilizers and draws it into a dart. He holds his blowpipe steady, waiting for the hyena to turn her back, then quickly takes a shot. Once the drugs take effect, Place rolls “Mtoto” onto a stretcher to carry her to a portable examination table.

by nnaliese eery

But this isn’t Africa. It is the Berkeley Field Station for the Study of Behavior, Ecology and Reproduction.e field station is a -acre enclosure in the hills above the UC campus, so close to Tilden Park that on a lucky hike you might make out the rising “whoooooop” of a hyena. e station was founded in the s by Frank Beach, then chair of the psychology department, for the purpose of studying animal behavior in a semi-natural environment. Since its inception, the station has been home to pigs, African frogs, macaques, flying squirrels, and more. Among the field station’s facilities are indoor and outdoor enclosures, an aquarium with a central observation platform, and covered pits connected by tunnels that have been used for population studies with voles.

Left: A hyena at the edge of one of

the outdoor enclosures. Bottom:

Berkeley hyena colony co-founder

Lawrence Frank bottle-rearing Tumo,

one of the few wild-born hyenas at

the station. Most of the hyenas at the

station were born and raised there.

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W HILE THE UC maintains several land reserves, the Berkeley field

station offers something truly unique: a way to combine the natural aspects of field studies with controlled conditions rarely available in the wild.

When Girls Will Be (like) Boys FROM THEIR SERIES of connected indoor-outdoor enclosures, the field station hyenas have one of the best bay views in town. Many of these hyenas are descended from the infants originally brought here from Kenya in the mid-s by Laurence Frank and his colleague Professor Steve Glickman, who now heads the field station and the Berkeley hyena project. Spotted hyenas (Crocuta crocuta) are fascinating animals with a whooping call and a dog-like appearance. But part of what makes them interesting to biologists like Glickman and Place is their unusual reproductive anatomy.

Since the time of the Greeks, hyenas have been mistakenly cast as hermaphrodites. According to the -volume Natural History (the world’s first encyclopedia) written by Pliny the Elder in the first century AD:

e Hyaena is popularly believed to be bisexual and to become male and female in alternate years, the female bearing offspring without a male; but this is denied by Aristotle ... a number of other remarkable facts about it are reported, but the most remarkable [include] that

… a female is seldom caught.

Perhaps the reason females were so seldom caught is that most people would be hard pressed to know that they had caught one because of the female’s large and phallic clitoris. e birth process through this penis-like structure is so difficult it often results in the death of first-born cubs.

In addition to their masculine anatomy, female spotted hyenas are aggressive and dominate males in nearly all social interactions. Newborn pups are espe-cially aggressive, and they attack their littermates within minutes of birth to establish dominance. Some believe that masculinized genitalia may be a side effect caused by the advantages of aggressive behavior in establishing and maintaining dominance.

Researchers have been studying hyena social interactions in the field for years in order to understand better the costs and benefits of female aggression. But some types of experiments can only take place in a more controlled setting. e field station allows researchers to monitor the hyenas intensively, group different combinations of individuals together for mating and group dynamics, and even alter their hormonal profiles by treating them with drugs that affect hormone synthesis or function. Researchers at the field station are currently studying the role hormones play in how hyena females end up so masculinized, but early results suggest that the process is more complicated than anyone expected.

Singing in the BrainJUST NORTH OF the hyena colony, shrouded in eucalyptus trees, is the road that leads to buildings five through seven and their aviaries. Many of these rooms were used in the early s by Peter Marler, a pioneer in the scientific study of birdsong. Now they are home to birds from Frederic eunissen’s lab in the psychology department.

e eunissen lab studies how sound is processed in the brains of zebra finches (Taeniopygia guttata). ese songbirds are known for the male’s ability to memorize a song and sing it unchanged throughout his lifetime. Males raised without hearing their father’s unique melody—called

“isolate” males—are known to sing unusual songs, which are typically shorter and contain fewer elements than normal songs. Graduate student Sarita Shaevitz and her colleagues wondered whether the daughters of these isolate males would show the most interest in songs similar to those of their fathers, and have devised an experiment to understand the role of

c r e a t u r e

The field station is a 23-acre enclosure in the hills above the UC campus, so close to Tilden Park that on a lucky hike you might make out the rising “whoooooop” of a hyena.

A group of zebra finch females in one of the

station’s flight cages. Only the older females

have orange beaks.

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early experience in the development of song preference.

e rooms of building five are now equipped with sound isolation chambers where female finches can be raised in one of three experimental conditions. e first enclosure will be used to raise females without their brothers and fathers, in the absence of any male song. In the second, females will be raised with their

“isolate” fathers, becoming familiar with his unusually short and simple song. e third condition will be a control, where females are raised in the presence of their father and brothers singing normal songs.

Once the young zebra finch females have matured, they will be helped into sexual receptivity with a dose of estrogen. e birds will then be exposed to different auditory stimuli, including isolate male songs, various normal male songs, and songs from Bengalese or Parson’s finches. e researchers will track which sounds elicit the “copulation-solicitation display” response in the females—a posture that the females adopt just before they mate.

Under normal circumstances, female zebra finches exhibit a behavioral preference for more complex songs over less complex songs. Whether females will prefer a simple song similar to their father’s song over a different, more complex song remains a mystery. It will also be interesting to see what happens in the case that females have never heard song.

“It would be really exciting if females raised without a dad prefer songs similar to the songs of the father they never heard over other more complex songs,” says Shaevitz.

“But no matter what their preferences, this study should provide insight about the role early auditory experience plays in adult behavior.”

The Palaces of RatsTHE FIELD STATION is also used to study some furry Berkeley natives. Sarah Cunningham, a graduate student working with Glickman, has spent the last six years studying the dusky-footed wood rat (Neotoma fuscipes) both in the field and in captivity. ese wood rats are native to about half of California and sport hefty bodies, cinnamon-colored fur, and large,

c o m f o r t s

rounded ears. ey also have a distinctive tail rattling noise, which, according to Cunningham, “sounds like dropping marbles onto a wooden table.”

Unlike many other rodents, wood rats do not dig. eir talent lies in building giant, above-ground nests, which can be up to six feet tall. ese can be found all around Tilden Park, once you know what to look for. In more than years of tromping around the park, this author never saw a single one until Glickman pointed out five nests among the poison oak and blackberry lining a short trail from the Little Farm parking lot.

Wood rat nests are made of sticks and twigs, which the rats assemble into palatial compounds. ey often have several platforms or verandas for lookouts and multiple entrances so the rats won’t get trapped by predators. Remarkably, each structure houses only a single rat. A female will typically stay in her nest permanently, and a male will visit when she is reproductively receptive. Once the babies are old enough, they disperse and build their own nests, either from scratch

Wood rats use

shredded leaves, grass

and other materials to

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or by resurrecting and adding onto an abandoned one.

is process is extremely difficult to observe in nature, so Cunningham trapped several female rats and, after a field ultrasound confirmed they were pregnant, brought them back to the station. She encouraged them to build their nests against an observation window by framing it with wire mesh, giving her a sneak peak into wood rat domestic affairs. “Extensively looking inside the nests is something no one has done before,” she says. “Here the rats can run around and build houses for themselves.” From these windows, Cunningham has recorded thousands of hours of wood rat nest behavior. As the pups get older, she is waiting to see the various ways in which life beyond the nest begins.

A Window on the WildIN THE YEARS since the Berkeley Field Station was created, its role has changed from a facility for purely behavioral work to one where researchers study a wide range of questions in behavior, neuroscience, reproductive physiology, and ecology. e square pits once dug for populations of voles have seen recent use as chambers for insects in a study of interactions between parasites and their hosts. e hyenas’ vocalizations are being analyzed in the eunissen lab, and even the wood rats may find themselves studied in new ways in an upcoming project on olfaction. Because of the amount of space, the unusual kinds of spaces, and

the ability to closely monitor organisms in a semi-natural environment, Glickman says, “the research opportunities are extraordinarily varied.”

Cunningham puts it simply: “ere’s no way I could do this work anywhere else.”

A B is a graduate student in neuroscience.

Want to know more?Students interested in conducting research at the Berkeley field station can contact Steve Glickman at:glickman@socrates.berkeley.edu

Unlike many other rodents, wood rats do not dig. Their talent lies in building giant, aboveground

nests, which can be up to six feet tall.

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Top: Wood rat nest in the field at

Hasting’s reserve. Left: Wood rat

perched on a ceiling fixture. In

nature, wood rats climb trees; in

their rooms at the field station

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LETTER FROM THE FIELDL I N E

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LStephanie Ewing is a graduate student in environmental science, policy and management. She works with Professor Ron Amundson and postdoc Kim Warren-Rhodes in the Atacama desert in Northern Chile.

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UC BERKELEY PROFESSOR Ron Amundson of the Department of Environmental Science, Policy, and Management ponders that last question quite a bit. He and his colleagues recently published a paper in the journal Ecosystems that catalogues which of the thousands of individual soils recognized in the United States are the most endangered by human activity and at the greatest risk for extinction. At first, the words “endangered” or “extinction” may sound odd, because scientists have not traditionally viewed natural soils as living entities in need of the same types of diversity conservation as plants or animals. But Amundson and his colleagues make a clear argument for the need to start changing

our thinking; like species, soils are unique and diverse assemblages whose natural life cycle is several orders of magnitude longer than humans’. At our frenzied pace, we are destroying much of this diversity. And while the extinction of plant and animal species is apparent, we are only now developing tools to perceive the extent of the destruction of our soils.

Soil vs. DirtMOST SOIL SCIENTISTS shudder a bit at the mention of the word “dirt.” To pedologists, those who study the structure and formation of soils, dirt is the components of soil—sand, clay, humus—taken out of context. Dirt is a pile of debris next to a construction site, while soil is the product of thousands of years of plant growth and decay, dissolution of minerals in rainwater, and burrowing by earthworms and gophers. Soil is what anything—granite bedrock, windblown dust, river muds—eventually turns into if left exposed at the earth’s surface. When pedologists classify soils, they seek to interpret this history; to do so they rely on characteristics such as the material from which a soil formed, the presence of layers rich in certain minerals, and the chemistry of a soil’s clay. In the process they reveal stories about the formation of the landscape we see today.

e roles that soils play in ecosystems, both natural and agricultural, are well known: storing water, providing mineral nutrients to plants, and hosting microbes’ recycling activities. Soil scientists have long promoted practices to sustain these soil functions on farmlands, but Amundson’s work broadens the discipline’s historically agricultural focus. “Traditional soil conservation has been to take land that has already been converted to some use

The Ground Beneath Your FeetE x p o s i n g t h e s t a t e s o f e n d a n g e r e d s o i l s

This acres mima mound/vernal pool

preserve near Visalia, CA is surrounded

by thousands of acres of citrus. Together,

these alternating mounds and pools

constitute a hummocky landscape

formed from soils that are about ,

years old, the remants of landforms that

once covered more than , acres in

the San Joaquin Valley.

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The next time the soles of your shoes rest on something softer than asphalt or tile, something older and wilder than the green lawn in front of the

library, stop and think about what you are standing on. Do you notice the soft aroma rising from subterranean fungi nourished by California’s winter rains, or the sound of water as it percolates through grains of sand? If you were to dig down deep enough, you would eventually encounter bedrock, but what would you dig through before you got there? And most important, would something irreplaceable and unique be lost if the place where you stood were unearthed by the plow or the backhoe?

by harlie oven

39

and maintain its quality and productivity, which I think is a really important issue,” he says. “But then there’s the question that I wanted to bring up, about preserving the undisturbed land that we still have, helping to minimize the impact of urbanization and cultivation on those areas.”

In the United States, scientists classify soils under a soil taxonomy developed by the US Department of Agriculture. e USDA system’s hierarchical structure is modeled after the Linnaean system in biology; instead of kingdom, phylum, etc., soil scientists have order, suborder, on down to series, the pedological equivalent of a species. e coarsest level of classification has orders. Examples include grassland soils (“mollisols”) and desert soils (“aridisols”). On the fine end of the system is the series, a unique soil type that has well-defined characteristics and is specific to a certain region. Currently, there are , soil series recognized in the United States, an example being the Valentine Series, which blankets most of Nebraska’s Sand Hills. California, with its varied topography and climate, is blessed with an abundance of soils. Its , series represent by far the highest soil diversity of any state, and , of those soils are unique to California.

e USDA system is designed to be insensitive to all but the most extreme changes in land use, grouping both soils in their natural condition and their agricultural counterparts under the same series. As a result, a soil map might show that a certain series covers an extensive area, even though very little is left in its natural state. Amundson and his colleagues confronted this ambiguity by using maps of land use compiled from satellite observations.

in only one state. ey compared these rare and unique soils to land-use maps and termed a soil “endangered” if more than half of its area is covered by agriculture or urbanization. ey found that the midwestern farming states have the highest numbers of endangered soils—in Indiana, for example, percent of the naturally rare soils are endangered. In certain cases, their results showed a real cause for alarm; of the nation’s soil series are so heavily used that they have effectively become extinct in their natural form.

The Human Impact on SoilsTO APPRECIATE WHAT IS LOST when these unique soils disappear, imagine standing in a grassy field and digging up a shovelful of soil to search for the organisms living in it. Plant roots and leaf litter are the most obvious; they form the food base of the soil ecosystem. Next you find large animals: rodents, earthworms, ants and the like, known to soil microbiologists as macrofauna. Now zoom in to look at smaller creatures, the soil mesofauna, roughly half a millimeter in length: a large diversity of tiny insects, arthropods, and roundworms. In your shovelful you probably have at least a thousand of each. Zooming in further you find the microfauna: millions of protozoa, algae, and fungi, billions of bacteria, trillions of viruses. ese microfauna do the most transformative work of recycling nutrients and forming soil organic matter, the dark-colored, carbon-rich substance that, by providing nutrients to plants and microbes, is truly the foundation of the ecosystem.

Map illustrating the distribution of agriculture

and urban land use in the US and the resulting

distribution of soil series that have lost per-

cent or more of their original area to land use.

Distribution of land use data were obtained from

National Land Cover Data, acquired in the early

s and compiled by the USGS and EPA.

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ese maps differentiate agricultural, urbanized, and relatively undisturbed land, and show the extent of the human footprint: two to three percent of our country is urbanized and nineteen percent is agricultural.

To measure the human impact on specific soils, Amundson and colleagues compared these land-use maps with a geographical database containing each soil series in the United States. ey first identified “rare” soils, which cover less than , hectares (roughly the size of Tilden Park), and “unique” soils, which occur C

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Remants of the

Great Plains

grasslands can be

seen in scattered

pioneer cemeteries,

such as this one near

Oberlin, Kansas.

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How do humans affect these ecosystems? According to UC Berkeley soil microbiologist Mary Firestone, “One of the most easily documented, well understood, and huge change is cultivation, plowing of soils. at reduces by orders of magnitude the presence of mesofauna and macrofauna: reduces diversity, reduces number, and to some extent eliminates their functional role. e function that’s being lost is in part the role of decompositon, but it’s also the role that they play in moving organic matter around and chopping up organic matter into smaller pieces.” In terms of long-term effects on the soil itself, continues Firestone, “the major impact of cultivation is the loss of soil organic matter.”

In addition to depleting what Firestone calls “the nutrient capital of the soil,” this loss has deleterious effects on the environment. Soils store a significant portion of the world’s carbon, and when it is lost from soils it is converted into carbon dioxide by respiration of soil microfauna. is carbon dioxide, along with that released by the burning of fossil fuels, is humanity’s main contribution to global climate change. Further, the loss of fertility that accompanies a soil’s loss of organic matter forces farmers to use more fertilizers to sustain productivity. But the nutrients in fertilizers are much more mobile than those locked up in soils; they drain off farmlands to pollute rivers, lakes, and coastal environments. Heavy use of nitrogen fertilizer also causes microbes to produce excess nitrous oxide, another greenhouse gas whose concentration in the atmosphere has risen almost percent in the past years. ese environmental effects raise the issue of the long-term role of natural, undisturbed soils in our nation’s landscape.

For Amundson, the greatest loss accompanying human transformation of a soil is that of the information and deep history the soil holds. He first looked into the problem of vanishing soil diversity when he realized, after years of teaching the same field class on California soils, that many of the sites to which he used to take students no longer existed. “Science and the preservation of the natural history of the state were the reasons that I got into this,” he explains. “I look at soils as reservoirs of earth history. By disturbing soils, irrigating them, mixing them up, you basically destroy this historical record.”

Ecosystems Growing on Ancient SoilsSOME OF THE MOST INTERESTING and rare soils are extremely old—millions of years rather than merely thousands. As Amundson explains, “Segments of the earth’s landscape that are geologically old are rare because the random rejuvenation through erosion or deposition on the landscape keeps the very veneer of the earth’s surface relatively geologically young. So any landscape segment that somehow manages to evade those rejuvenation processes is by default a rare occurrence on the earth’s surface.” e unique properties of these old soils make their conservation both important and difficult.

To see how soils and the ecosystems which rest upon them have developed over such long periods, one can drive a few hours north of Berkeley to the coastal terraces of Jughandle State Park in Mendocino County. Here, millions of years of plate-tectonic motion have slowly and constantly raised the earth’s surface. As these forces push up the land, ocean waves plane it to a flat wall, causing the landscape to rise like escalator steps. Today one sees a staircase of successively older landscapes rising from the coast, from young soils near the coast to ancient soils—over one million years old—on the highest terraces. e lower steps tell a pleasant story of plant succession as redwoods predictably displace the coastal scrub. But continuing up the staircase, this simple story turns stark. e oldest steps contain a strange forest of stunted trees instead of towering redwoods. If you dug you’d find the cause: shallow soil bleached white with red spots. e colors indicate an almost complete loss of nutrients, leached by acids

Map illustrating the distribution of

endangered plants and endangered

soils (see text for definition) in the

US. Data for plants are from Dobson

and others ().

Another example of

Great Plains grasslands,

this one in Loup City,

Nebraska. The soil pit

dug in the foreground

is used to examine the

soil layers.

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from roots and decaying pine needles until only pure white quartz sand and occasional red deposits of iron remain. In the s the great UC Berkeley soil scientist Hans Jenny first realized that this soil, the Blacklock Series, revealed the importance of time in forming soils. He fought to preserve the landscape, which is now protected by the UC Natural Reserve System.

But while old soils may be inhospitable to growth, they are hardly wastelands. As Amundson points out, “Old landscapes, even if they are in benign climates, can be considered to be extreme environments that have dictated or allowed evolution to produce rare plants and animals that have adapted to these locations.” e heavy hand of evolution can result in species that grow only on certain soils. e highest terraces of the Mendocino staircase, for example, are the sole habitat for several species of tree, including the Bolander Pine, Fort Bragg Manzanita, and Mendocino Cypress. e link between diversity of soils and of plants occurs across the nation; Amundson and his colleagues found strong geographic correlation between rare, endangered soils and rare, endangered plants.

All of these issues—rare, ancient soils with endemic plant species, encroachment of agriculture and urbanization, and conflicting ideas about how best to maintain natural diversity—recently came to a head with the planning of the new UC campus in Merced County. e county, on the broad, western flank of the Sierra Nevada south of the gold country, rests largely on terraces left behind by the meandering of rivers that once drained the mountains. Many of the soils are one to two million years old and harbor some of the last remnants of landscape features known as mima mounds and vernal pools that once pervaded California’s valleys. Together, these alternating mounds and pools constitute a hummocky landscape overlying a flat, concrete-like impermeable layer called a duripan. As the water level rises with winter rains the vernal pools fill with water, which recedes slowly throughout the spring. Botanists particularly admire the pools because they provide a habitat for a unique and beautiful assemblage of endemic wildflowers, which bloom along their margins.

“When the UC [campus] was proposed for that area I was concerned and frankly dismayed,” says Amundson, “because it was going to be on this wonderful, broad, million-year-old landscape that there isn’t really much left of.” e controversy which arose over the potential loss of the landscape, however, caused people to become more aware of this irreplaceable resource. e final location of the campus, moved over just a bit, “turned out to be a win-win situation,” Amundson says. “ey’re going to take a small and insignificant amount of this [native soil] out of its natural state for the campus, but the result is that the state and the Nature Conservancy went around and started paying ranchers for the development rights to their broad ranch regions that ring the entire campus. I don’t think that, without having the UC campus there to focus all this attention, there would have been

this coordinated effort to keep this broad remaining open area in its natural state.”

e relationships between soils, plants, animals, and humans can be critical to the success of such conservation plans. In this case, as Amundson describes it, the final plan “keeps the ranchers in business. It gives them a huge infusion of money and incentive to stay in ranching. Actually, ranching is needed to maintain the biology of the vernal pools now, because if you take cows away, the invasive grasses would grow so thick that they would choke out the native plants. So now cows are an integral part of the ecosystem, and you have to have ranchers there to keep the unique plants growing around the vernal pools.” For Amundson, these examples point to the fundamental role of soils in conservation plans: “We want not only to have contiguous areas, but areas that maintain the geological and pedological diversity of the area that allowed this mosaic of things to develop in the first place.”

Looking to the FutureTO SAVE THE LANDSCAPES that are most endangered, scientists and planners need first to identify the most endangered soils. Amundson and his colleagues’ research, then, is critical; theirs is the first systematic comparison of individual soils’ distributions against patterns of land use across the country. Perhaps their most important result is to reveal the strain that agricultural and urban land use places on natural soil diversity. is realization comes at a time when, as Amundson notes, “Our population is expanding, agriculture is expanding, and basically at the end of this century there won’t be much land left to convert to agriculture. So I’m not suggesting that every segment of these incredibly old parts of the earth’s surface be preserved, but I think keeping a healthy and interesting diversity of segments of these areas in their natural conditions would be warranted for future generations.”

Ultimately, for preservation to succeed, more people need to appreciate the value of soils. “is generation has the choice about what we’re going to leave in terms of the earth’s surface for the next generation and beyond. It’s a serious responsibility that I think we at least need to consider. I’m just here to provide data and raise the conceptual issues that I think are worth talking about,” says Amundson. “I guess my view is to approach these parts of the earth’s surface with some sort of awareness that they represent time beyond anything we can imagine in biology. You know, the oldest trees on earth are insignificant compared to some of these landscapes that we destroy without even a second thought.”

C K is a graduate student in environmental science, policy and management.Want to know more?Soil Diversity and Land Use in the United States. R Amundson et al., Ecosystems (); Vol. , pages –.

Online access to the journal Ecosystems can be obtained from:www.springerlink.com

Visit this USGS website to view Landsat images of land use in the US:mac.usgs.gov/mac/isb/pubs/factsheets/fs.html

“I look at soils as reservoirs of earth history. By disturbing soils, irrigating them, mixing them up, you basically destroy this historical record.”

“IMAGINE one hundred professors standing in a circle facing each other, not allowed to speak,” says UC Berkeley professor Adam Arkin. At the moment, he happens to be lounging in a well-worn leather armchair in his wedge-shaped office in Calvin Lab, talking about puzzles. Arkin loves puzzles.

A professor of bioengineering and chemistry and a Howard Hughes Medical Investigator, Arkin, at age , is in his own words “a relatively young upstart.” His achievements include being named “Young Innovator” by Technology Review in and winning a remark-able million Department of Energy grant in . His group develops computer programs that model and predict the behavior of cells and microbes, and his unconventional methods have garnered both praise and criticism from the scientific community.

“Atop each head,” he continues, “is placed

a black or white hat. en one by one each

professor is asked to guess what color hat

they’re wearing. If they guess correctly, they

live,” he says with a mischievous glimmer in

his eye. “If not, they’re shot to death by their

own graduate student.” He asks, “How many

professors have to die before they break the

code and each guess correctly?”

Adam Arkin

by udrey M. uang

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PROFILE

ife in theory

To Arkin, his research in systems biology, figuring out how organisms coordinate gene regulation to survive, resembles a complex

game. He and the members of his group model how cells respond to external stressors such as starvation and extreme temperatures. Most biologists study how cells respond to each of these stressors in isolation. But a living cell actually responds to many stressors at once, like a hungry person stranded in a blizzard: he can eat before seeking shelter, but he may freeze to death; if he doesn’t eat, will he have strength to seek shelter? How cells respond in such situations is poorly understood and difficult to study experimentally, so Arkin hopes that approaching these problems using computer models will yield clearer answers.

Building computer models of cell behavior presents huge challenges because, like people, cells within a population never behave identically. Arkin first encountered this variability of responses while he was a graduate student at MIT, generating mutations in a bacterial protein. One particular mutant protein was toxic and poisoned the cells that made it. Arkin noticed that genetically identical bacteria responded to the toxin differently in order to survive. is variability fascinated Arkin and led to his current research.

Survival, when stripped down to the basic molecular level, depends on genes working in networks very similar to electrical circuits. When genes in the circuit are “turned on,” they make proteins that turn on (or off) other genes, which in turn make different proteins that can go back and turn off (or on) earlier genes in the circuit. “ere’s an optimal way of controlling these circuits, and basically, we want to solve the puzzle for how we can win against these organisms,” says Arkin. Winning the game or solving the puzzle, according to Arkin, equals survival of the cell.

Taking this off-beat approach of treating genetic systems as electrical circuits, scientists like Arkin have begun to address biological questions with

engineering principles and are redesigning modeling software accordingly. Arkin and others have reworked the computer program known as SPICE (Simulation Program Integration Circuitry Evaluation)–originally developed to simulate electrical circuitry–into BioSPICE, which specifically simulates biological systems and genetic circuits. Berkeley BioSPICE comprises a collaboration of scientists from UC Berkeley, Lawrence Berkeley National Laboratory, Stanford Research Institute, and other institutions working together to develop large-scale simulation software. BioSPICE has grown into an open source software package where anyone can add to and improve on the simulation software.

In addition to improving computer software, many in Arkin’s lab use the models they build to address real life situations—what Arkin calls real “biosystems.” One large-scale collaborative effort stems from the million Genomes for Energy and Environment grant from the Department of Energy for the use of soil microbes to remove toxic heavy metals from drinking water. ese microbes naturally remove small amounts of heavy metals, but in quantities insufficient to purify a water source for human consumption. e goal of the national project is to engineer these microbes to work more efficiently.

For Arkin, it’s another puzzle to solve. rowing more heavy metals at them won’t make them work faster, he says. Instead, they respond as though they’re being poisoned. “Right now, we can get a certain degree of metal reduction, but they tend to stop and go into stress response,” Arkin explains. “If we can quell that stress response while increasing metal reduction, we’ll win.” To do this, Arkin’s group analyzed and compared the genomes of three uncharacterized microbes to learn more about the genetic circuitry involved in heavy metal reduction. Once they

Keeping HIV in latency could prevent AIDS indefinitely, without the need to eradicate HIV.

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PROFILE

understand how these particular microbial genetic circuits function, they can predict how the circuits are controlled and can coerce the microbes into cleaning up drinking water.

e DOE has proposed the building of four national research facilities where scientists can converge to collaborate on Genomes for Energy and Environment projects. “is is really, really exciting stuff. I’m impressed that the DOE has the vision to do this,” Arkin says. However, the DOE projects focus on environmentally relevant microbes, which aren’t necessarily the well-studied model systems that Arkin and others have invested a lot of time characterizing. Although somewhat annoyed by having to do more groundwork to establish these DOE projects, Arkin appreciates their long-range implications. “I don’t have the power to do what I’d like to do sometimes. For me, personally, it’s a pain in the ass, but it’s a national scientific mission,” he says, adding that he feels obliged to help for the greater good.

Arkin’s work for the greater good extends into other projects, such as controlling HIV. His group has developed a model that predicts the usefulness of infecting HIV patients with another virus—a smaller, non-pathogenic (yet probably still contagious) therapeutic virus that attacks and destroys HIV—to prevent the onset of AIDS. HIV-infected individuals, although still contagious, often do not show symptoms of AIDS for up to ten years after infection. Says Arkin, “is [latency] is a wonderful strategy for the virus,” allowing it to spread to more

hosts. He contrasts HIV with Ebola virus, which kills its host too quickly to spread very far. During the latent period of HIV infection, the immune system constantly battles HIV to keep the virus below a threshold level in the bloodstream. Some HIV lies in wait during this time and only multiplies when the immune system weakens, causing HIV levels to rise and leading to the onset of AIDS. Arkin thinks that keeping bloodstream HIV levels low may be the key to winning the game against the debilitating and frequently lethal symptoms of AIDS. Says Arkin, “If HIV is prone to go into latency as part of survival, can’t we exploit that?”

Arkin’s graduate student Leor Weinberger, in collaboration with David Schaffer from the department of chemical engineering, has constructed a model that expands on previous models of HIV. He predicts that injecting an HIV-positive person with this therapeutic virus and keeping that virus at times the level of HIV in the bloodstream could force HIV to remain in latency; keeping HIV in latency could prevent AIDS indefinitely, without the need to eradicate HIV.

Although the model predicts great promise in this therapeutic virus, Arkin points out that it is still only theoretical: “I could theorize forever, but we need validation.” Weinberger is currently building this therapeutic virus in the lab to test on living cells. However, many potential risks need to be considered before attempting viral therapy on live patients.

This graph shows how HIV viral load

can be reduced by addition of a gene

therapy virus, thus slowing or halting

progression to AIDS.

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ADAM ARKIN

Critics point out the same problem with much of Arkin’s research: the computer model looks great, but does it work in real life? “His work is very interesting,” says Gerry Rubin, UC Berkeley professor of molecular and cell biology and vice-president of the Howard Hughes Medical Institute, “but the jury is still out on the real applications.”

“e question is,” says Arkin, “how much use have we actually been in medicine?” He makes a zero shape with his hands. e problem, he says, is the lack of data. Building good models requires a large amount of exacting data. ese quantities exist for bacterial systems, but according to Arkin, bacterial models hold little interest outside the scientific community.

“Cancer grabs people. HIV, oh that’s terrible! Getting a staph infection? Who cares?” says Arkin.

Improvements in high throughput technology in the last five to ten years, especially microarrays, have yielded much more data. But Arkin declares most of this data useless because it comes from a mixture of cells behaving differently and represents an average. Average responses don’t interest Arkin nearly as much as the variability of individual cellular responses that harkens back to his graduate work. Building these models requires knowing exact protein concentrations and rates of gene activation in individual cells. “Microarrays don’t tell you anything about this variability,” Arkin says. “It may tell you that some genes are on or off in some cells, but this is all stochastic. Individuality matters!” Does he think microarrays are useless? “I love microarrays,” he says,

“It’s like meeting a very beautiful girl (in my case) and realizing she has no personality. It’s pleasurable… but it ain’t what you want.” Although microarrays do give rise to lots of interesting data, Arkin says, “It’s not as deep as I want.”

On the other hand, Arkin loves the Internet. “I think the best source of data is the years of literature that you can search via Medline,” he says. His work has benefited immensely from the ability to access scientific literature and mine it quickly. “Could you

imagine mining through papers for data before the Internet?” he asks, “Ugh! Horrifying! ” Even now, with technology advancing faster than ever before, Arkin credits bench scientists for generating the rigorous data he mines from Medline and uses to build his models: “Right now, the major source of a modeler’s data is the biochemists who have done the hard stuff, scientists who have done the beautiful screens and come up with the great kinetics that people don’t appreciate as much as the microarrays.”

Arkin says his critics accuse him of talking big without delivering—and he believes the criticism is valid. When pressed about the applications of his research, Arkin responds that he isn’t driven by the applications. He says that people don’t appreciate the modeling, the theory in and of itself, and acknowledges that every model needs an application as a selling point. What drives him, though, is winning the game or solving the puzzle. He feels that he’s cracked small pieces of the puzzle so far and he hopes that solving enough small pieces will eventually allow him to make a significant impact.

As for the earlier puzzle, what becomes of the Berkeley professors about to be shot by their graduate students? Like Arkin’s organisms, the professors need an optimal strategy for survival. Say they meet the night before and come up with a code: the first professor forced to answer will guess “black” if he sees an even number of black hats before him, or “white” if he sees an odd number of black hats. e others can then figure out what color their hats are, and only the first professor might have to die.

A M. H received her PhD in molecular and cell biology.

Want to know more?genomics.lbl.gov

“I love microarrays. It’s like meeting a very beautiful girl and realizing she has no personality.”

46

PROFILE

in unauthorized personal goods to lab accounts. Finally, last June, Los Alamos lost track of two vials of plutonium.

UC’s official line is that the problems are now under control. “ere were mismanagement issues,” says UC’s Washington-based spokesman, Chris Harrington. “Strong and effective practices have been put in place to prevent their recurrence.” He mentions new accounting oversight, more direct management, and an ongoing effort to bring in outside security contractors.

But most people close to the labs agree with -year LBL veteran and UC Berkeley physics professor Richard Muller, who calls the charges “overblown.” At least three of the scandals turned out to be more hype than substance. A federal judge apologized to Wen

last election—a total of ,. Lockheed-Martin also threw in , to House Commerce and Energy Committee Chairman Billy Tauzin, the member of Congress who, along with Domenici, has the most influence on the DOE spending bill. President Bush appointed Dale Klein, a former vice president of the University of Texas, to a top position with the National Nuclear Security Administration, which governs the nuclear labs.

Atkinson speculated to the Contra Costa Times about the companies’ possible motives for bidding on the labs: “ey think that by running the laboratories, they are going to get their hands on intellectual property. And maybe that’s the game, and maybe they’ll succeed at it. But I think it will be a terrible loss for the country.”

Most scientists at LBL seem to agree that private management would hurt the labs’ scientific endeavors. e labs, some say, already have a hard time attracting and retaining top talent. UC management is a selling point: scientists at the labs have the same benefits as university faculty, and transferring within the UC system is relatively easy. Under a private company, it might be harder to get top scientists to go to what UC Santa Cruz professor of astronomy George Blumenthal, a faculty representative to the UC Regents, calls “the middle of nowhere, especially at Los Alamos.” Muller believes that corporate management would sacrifice the open intellectual environment the labs have fostered. He recalls a situation in which a member of Congress wanted a lab scientist fired for making statements that the congressman found offensive. UC refused. Muller believes that a private company would have yielded, sacrificing science for politics. If politics gain more power over science, “the loser,” Muller says, “[will be] the United States of America.”

As for security, privatization has not proved to be Sandia’s panacea. Last summer, the federal General Accounting Office reported instances of sleeping guards and of a stolen van smashing through a security fence. Watchdog websites for privately managed labs show long lists of security breaches.

e good news for Berkeley is that LBL appears to be the least attractive of the five labs to outside bidders. e lab is on UC land. Of its scientists who have joint appointments with universi-ties, have appointments with a UC campus, while only one has an appointment anywhere else. Similarly, Berkeley graduate students are on the payroll, along with from other UC campuses and only from all other universities. Lab staff members are in UC pension and health care plans. “Logistically,” Kolb says, changing from UC to other management “would be an expensive transition.” In fact, no one contacted for this story

Ho Lee for his treatment after the federal case against Lee fell apart. (Lee pled guilty to a single misdemeanor charge of mishandling secrets.) Audits found the total improper spending by Los Alamos staff to be less than ,, about percent of the original claim. e plutonium turned up after an extended search.

So far only the University of Texas has confirmed an intention to bid for the contract. Lab scientists, university staff, and media, however, consistently mention the same private companies as pos-sible bidders. Military contractor Lockheed-Martin runs Sandia National Laboratory and ran the Idaho National Engineering and Environmental Laboratory in the s. e nonprofit Battelle Memorial Institute runs the National Renewable Energy Laboratory in Colorado plus Brookhaven, Oak Ridge, and Pacific Northwest National Laboratories. Bechtel, a large engineering firm that is not publicly traded, manages the Idaho lab and the Nevada Test Site.

e list of potential bidders for the management contract has led to murmurings that the management competition is just another example of the Bush Administration picking on California and sound science to the benefit of his corporate and Texan backers. Indeed, former UC President Richard Atkinson said to the Contra Costa Times last October, “I think much of the nonsense that has gone on is politically motivated.” Federal Election Commission records add some credibility to the suspicions: all three corporations have political action committees, and all three donated money to Senate Energy Committee Chairman Pete Domenici for the

48

POLICY

Research at LBL has produced nine of UC Berkeley’s 13 Nobel prizes in science.

50

QUANTA (HEARD ON CAMPUS)

“This is not the University of Novartis. It is the University of California.”

Ignacio Chapela, Department of Environmental Science,

Policy and Management. The Pulse of Scientific Freedom in

the Age of the Biotech Industry, 12/10/2003

“To err is human. To really screw up requires an economist.”

Andrew Gutierrez, Department of Environmental Science,

Policy and Management. The Science Behind Genetically

Engineered Plants, 12/2/2003

“After doing a long supercomputer calculation, the computer understands why quarks are confined, but we don’t.”

Edward Witten of Princeton’s Institute for Advanced Study.

Quark Confinement and String Theory, 1/26/2004

“Great question. We have no idea. We can barely do these experiments in mice, and they don’t meditate.”

David Presti, Department of Molecular and

Cell Biology, when asked whether meditation

practices change neurotransmitter signals in

the brain. Buddhism, the Brain, and the Mind,

2/22/2004