berkeley science review - spring 2005

B E R K E L E Ysciencereview

Spring 2005 Issue 8

R e a c h n e w h e i g h t s w i t h BSR

Are you fascinated by the world of science? Do you want to write about scientifi c discoveries happening at Berkeley? Th en join the Berkeley Science Review! We’re a graduate student publication

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BERKELEY SCIENCE REVIEW 3

Editor in Chief

Kaspar Mossman

Managing Editor

Dula Parkinson

Editors

Michelangelo D’Agostino

Charlie Emrich

Padraig Murphy

Jess Porter

Tracy Powell

Sarita Shaevitz

Art Director

Kaspar Mossman

Assistant Art Director

Stephanie Cady

Layout Editors

Wendy Hansen

Allon Hochbaum

Bryan Jackson

Jess Porter

Tracy Powell

Proofreader

Amber Wise

Printer

Sundance Press

© 2005 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; Lawrence Berkeley National Lab; the Department of Physics; the Office of the Executive Vice-Chancellor and Provost; the Graduate Division; the College of Natural Resources; the Space Sciences Laboratory; the School of Journalism; the Biological Sciences Division, College of Letters and Sciences; and the Associated Students of the University of California (ASUC). 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 [email protected] or posted to the Berkeley Science Review, 10 Eshelman Hall, Berkeley, CA 94720. Advertisers: contact [email protected] or visit http://sciencereview.berkeley.edu

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

At a recent lab meeting, before moving on to weighty scientific matters, we were discussing popular music. More specifically, we were discussing unpopular music.

“Steely Dan,” said Amber, who as it happens is the BSR’s proofreader. “They’re the band no-one likes.”

But I like Steely Dan, I said.“You don’t count,” said Amber.Perhaps. But as I write this I have some Steely Dan lyrics going around in my head:

“The weekend at the college didn’t turn out like you plannedThe things that pass for knowledge, I can’t understand.”

If you’re a graduate student, you’ve spent considerably more than a weekend in pursuit of your degree, and you may start reeling when you contemplate the years that have passed and the years that remain (definitely not like you planned). You’ll find you’re in good company when you read Loren Bentley’s feature “Prisoners of the Ivory Tower,” on page 42. Every time I look at it, I want to quit the BSR and rush back to my lab bench.

But all those weekends of research do add up to some spectacular science at UC Berkeley and LBL, and the mission of the BSR is to bring those stories to a wide audience. Our authors are experts in their fields and writers who excel at telling the story of Berkeley science, making it accessible to non-specialists like you and me. Here are just a few stories you’ll find in this issue:

On page 34 you can read how LBL’s new synthetic biology department may one day create wholly new forms of life to produce medicines that cure major human diseases.

For all the times you wondered what it would be like to have taste receptors all over your body (it won’t take you long to realize it’s a bad, bad idea), the story on page 10 is for you. Some animals do have taste receptors all over their bodies, and surprisingly, the way these tastes map into their brains is the same as it is in mammals.

UC Berkeley’s new chancellor Robert Birgeneau is a physicist who is still active in research despite his administrative duties. The BSR interviewed him to find out how he balances work and…well, more work, and to find out exactly what “smectic” means. You’ll find the interview on page 32.

The BSR is still produced entirely by volunteers, most of whom are UC Berkeley graduate students. We welcome contributions from aspiring writers, artists, designers, and editors—check out our website at sciencereview.berkeley.edu, then email us at [email protected]. And of course, there’s no better way to support our great coverage of Berkeley science than to send money!

Enjoy the issue,

Kaspar Mossman

p.s. Steely Dan rocks.

from the editor


C O V E R : A P E A C O C K M A N T I S S H R I M P S M A S H E S A P A N E O F G L A S S W I T H I T S T R A D E M A R K S T R I K E . S T O R Y O N P A G E 6 . [ P H O T O : R O Y C A L D W E L L ]

4 BERKELEY SCIENCE REVIEW

S P R I N G 2 0 0 5 I S S U E 8

FEATURES

26 Zoom with a View

A tour of the Golub antique

microscope collection

by Angie Morey

34 Intelligent Design

Playing with the building blocks

of biology

by Alan Moses

42 Prisoners of the

Ivory Tower

Serving five to life

in academia

by Loren Bentley



FEATURES

C U R R E N T B R I E F S

8 In the Garden of Good and EvilMushroom hunters can tell the differenceby Jennifer Skene

10 Flies Taste Like MammalsVertebrates, invertebrates encode taste with the same “molecular logic”by James Endres Howell

12 Pull My DNA...with the world’s smallest tweezersby Merek Siu

13 Sweeping CO2 Under the RugThe science of geologic sequestrationby Rebecca Sutton

15 Who’s Your Daddy?Survival of the fittest means something different to frogsby Allison Drew

17 BOINC!Do try this at homeby Michelangelo D’Agostino

DEPARTMENTS

6 Labscopes

Kapow!

Bold Vision

Fat is Beautiful

Like a Rock

41 Book Review

Race: the Reality of Human Differences

49 Read any good books lately?The shocking reason for the success of The Da Vinci Code

50 Letter From EcuadorWater, water everywhere...but what’s the fecal coliform count?

P O L I C Y

19 Strange FruitCalifornia counties have a love-hate relationship with GMOsby Cheryl Hackworth

U N I V E R S I T Y

32 Meet the ChancellorThe BSR puts the Birge back in Birgeneauby Tracy Powell and Steven Bodzin


LABSCOPES LABSCOPESLABSCOPES

Kapow! {COVER STORY}

ALTHOUGH crustaceans may get a bit punchy as they approach their stovetop demise, few would have thought to ask the

mantis shrimp—a distant cousin of the lobster—for insight into the fine art of the uppercut. But as Sheila Patek, Wyatt Korff, and Roy Caldwell in the Department of Integrative Biology have discovered, the mantis shrimp strike, which packs the equivalent force of a .22 caliber gunshot, may be one of the fastest animal movements ever observed. Mantis shrimp use their strike to smash open hard-bodied prey such as snails and crabs. In order to glimpse this feat, Patek’s group negotiated with the BBC to borrow equipment capable of recording these animals at a whopping 5000 frames per second. The resulting observations solved the long-standing puzzle of how these creatures are able move so quickly: they use a unique spring-loaded click mechanism, which “looks basically like a Pringle” according to Korff, a graduate student involved in the project. The researchers also observed a rare phenomenon known as cavitation, which, Patek says, “occurs when water vaporizes under low pressure, releasing both light and sound—a consequence of the extreme speed.” Next time you stop in at the Monterey Bay Aquarium, be sure to take a closer look at these remarkable critters, but remember to keep your hands away from the glass.—Brendan BorrellWant to know more? Check out movies of the shrimp strike at ist-socrates.berkeley.edu/~patek/shrimpMechanics

Bold Vision

LIKE couch potatoes everywhere, neuroscientists can now grumble if they have to get up, because three Berkeley researchers

just handed them their own remote control. Rich Kramer and Ehud Isacoff from the Department of Molecular and Cell Biology and Dirk Trauner from the Department of Chemistry have come up with a way to control neuron signaling from a distance, using a synthetic ion channel that they can switch on with a beam of light. Embedded in the cell membrane of a neuron, the channel is blocked by a molecular gate until it’s exposed to ultraviolet light. The gate then folds back like an accordion, triggering the neuron to begin signaling. Kramer, Isacoff, and Trauner will use their invention to study the way neurons talk to each other. This is also an exciting step toward artificial vision: in certain forms of blindness, photoreceptors in the retina cannot respond to light, although the rest of the vision pathway remains intact. Patients would rely on an electronic eyepiece to translate natural light into patterns scanned onto the retina. Synthetic channels could then be used to restore light sensitivity to neurons in the retina, bypassing failing photoreceptors and restoring visual function. —Jess Porter

Want to know more? “Light-activated ion channels for remote control of neuronal firing,” Banghard et al., Nature Neuroscience 7, pp. 1381-1386 (2004).

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Like a Rock

LIKE a desert wanderer, UC Berkeley astronomer Geoff Marcy seeks water, but his search is not on this planet. Using the

powerful Keck Telescope atop a dormant Hawaiian volcano, Marcy searches for new planets by detecting small, cyclical shifts in the wavelengths of starlight. These “Doppler shifts” are caused by compression and expansion of light waves that stream from stars as they wobble, drawn ever so slightly toward an orbiting planet. Recently, Marcy discovered a planet the size of Neptune—small enough to have an Earth-like, rocky surface—circling a dim red star near the constellation Leo. Planet and star are separated by just 3% of the distance from the Earth to the Sun. Because they’re so close, the orbiting planet exerts its own tiny gravitational tug on the star, pulling it in small circles at just 40 mph. (Remarkably, astronomers can distinguish subtle changes in the light of a star 33 light years away, as it wobbles at speeds too slow for our highways.) The light side of the planet sizzles at 340°C, while the dark side endures a chilly –100°C or below. “The most intriguing aspect,” notes Marcy, “is the possible domain in between the hot and the cold side, where the temperatures, as Goldilocks would say, are just right.” Just right for liquid water, and perhaps even life, to exist. —Rebecca SuttonWant to know more? Learn more about this and other rocky planets at www.exoplanets.org

Fat is Beautiful

THOUGH reminiscent of the tie-dyed T-shirts on Telegraph Avenue, patterns like this arise from a very different

source—interactions among proteins and fats (lipids), biological molecules found in all living cells. Raghuveer Parthasarathy, a Miller Postdoctoral Fellow in Jay Groves’s lab in the Department of Chemistry, investigates the relationship between proteins and cell membranes, which are double-layered lipid structures richly studded with proteins, sugars, and other molecules. When two cells come together—as in some types of immune responses—their membranes interact to form a junction. To better understand these interactions, Parthasarathy creates an artificial cell-cell junction out of two lipid bilayers sandwiched together. Labeled proteins within one of the layers get pushed into dense zones radiating out from the point of contact, which can then be photographed. The pattern formation is quick and stable, taking only about 100 milliseconds and lasting for tens of minutes. Beyond looking cool, these patterns may help shed light on the complex protein reorganizations that occur when real cells come together. —Sarita ShaevitzSee more phat pictures at: groveslab.cchem.berkeley.edu

poisonous varieties are often dead ringers for other edible, tasty species. True mushroom hunters know their mushroom biology, and are well aware that the size, color, texture and odor of the stalk, cap, or gills can be used to distinguish between species. Some species change color when they are bruised or sliced in half and their juice oxidizes. Other species can only be identified after microscopic spore analysis. It’s a tricky business, which requires more than just a simple key or field guide.

How can you join these mushroom hunters and dine on wild porcini risotto without worrying about getting sick or dying? The most interesting option by far is to sign up for Tom Bruns’s course, California Mushrooms, PMB 3. Offered in the fall, the course takes advantage of the early part of the mushroom season (which stretches from October through March, peaking in December and January). Students collect and learn to identify over 50 genera and build their own extensive collections throughout the semester.

Mushrooms are the fruiting bodies of fungi and exist to produce and disperse spores. The many types of fungi in the

THE Bay Area is the perfect habitat for mushroom hunters. The culture of

culinary obsession, the warm and moist winter climate, the abundance of conifers and hardwood trees, and even the region’s relaxed attitude toward experimenting with mind-altering substances... But who are the mushroom hunters, and how can you, the aspiring mushroom hunter, join their ranks?

Mushroom hunters come in all ages, with varying degrees of affinity for mushroom-themed clothing. They seek wild fungi for their taste, medicinal qualities, or psychoactive effects. For them, mushroom hunting is more than a hobby. It has to be, explains Tom Bruns, a professor in the Department of Plant and Microbial Biology: “Calling them amateurs doesn’t do them justice. These people are very well informed.” Mushroom hunters must be good at what they do, because misidentifying a mushroom could be fatal.

While the East Bay is home to edible wild chanterelles and porcinis, it is also home to a number of toxic mushrooms, which will make you sick, and poisonous mushrooms, which can kill you. The

wild have diverse methods of obtaining food. Mycorrhizal fungi form symbiotic relationships with trees, providing them with nutrients and receiving carbon in exchange. Parasitic fungi get carbon from plants but give nothing in return. Saprophytic fungi obtain their carbon from dead or rotting debris.

Many species of saprophytic fungi, such as oyster mushrooms and common button mushrooms, can be easily cultured. Mycorrhizal species, which require a host tree, must be found in the wild; hence the high price of chanterelles at Monterey Market. However, mushroom hunters who know the locations of blewit and porcini patches can eat like kings—for free. You can dine with them if you join the Mycological Society of San Francisco and attend the Culinary Group’s monthly dinners. The Society publishes a newsletter and hosts forays to regional parks where seasoned hunters pass on their knowledge (though

Amanita calyptrata—photo taken in the Jackson State

Forest, on a fieldtrip for California Mushrooms, PMB 113.

Mushroom hunters can tell the difference

In the Garden of Good and Evil

Ramaria sp., Jackson State Forest.

P H O T O C O U R T E S Y : T O M B R U N S

CURRENT


off their skills in other regions: “This knowledge doesn’t travel to other places.” Perfectly edible mushrooms from the East Coast, Europe and Asia have toxic or poisonous look-alikes here in the Bay Area. Recently, an Oakland resident died after eating Amanita phalloides, the Death Cap mushroom, which she mistook for

perhaps not the locations of their secret porcini patches).

Another way to become familiar with mushrooms is to visit the Mycological Society’s annual Fungus Fair—this year, it was held at the Museum of California in Oakland. Here, chefs from renowned Bay Area restaurants give cooking demonstrations. Local mushroom experts, including Bruns, give talks. There are also booths where you can try your eye at identifying mushrooms, peruse fabrics colored with mushroom dyes, learn about medicinal mushrooms, and, at perhaps the most popular table, learn about the psychoactive mushrooms that can be found in nearby parks.

One group of psychoactive mushrooms contains a chemical called psilocybin, which, when ingested, is converted to psilocin. Psilocin is structurally similar to serotonin, a chemical naturally present in the brain. It is thought that psilocin changes the brain’s signal-to-noise ratio. Stimuli that the brain usually considers to be noise are instead considered to be signals, resulting in synesthesia, the simultaneous perception of more than one sense. Two species of mushrooms that contain psilocybin grow in the Bay Area: Psilocybe cyanescens and Psilocybe fibrilosa. Both are small and brown, and resemble several species of poisonous mushrooms.

The psychoactive Amanitas, those Alice-in-Wonderland-ish red mushrooms with white polka dots, comprise a separate group. Their active ingredient is the chemical muscimol. Amanita muscaria can be found in the Bay Area, but they contain a small amount of muscimol and a large amount of toxic compounds that make people sick. Amanita muscaria from Eastern Europe contains more muscimol, resulting in stronger psychoactive effects and greater popularity.

At a talk at this fall’s Fungus Fair, amateur mycologist Debbie Viess warned that while mushroom hunters may be familiar with the species present in the Bay Area, they shouldn’t attempt to show

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an edible species common in her native Taiwan. “Posters to warn people about the Death Cap mushroom are printed in many languages to target immigrant communities,” says Anne Pringle, a UC Berkeley post-doctoral fellow.

Recent work by Pringle has shown that the Death Cap mushroom was actually introduced from Europe. “There is a great oral tradition in the amateur community here,” explains Pringle. “They thought Amanita phalloides was introduced—and it turns out they’re

absolutely right.” Investigating historical descriptions, herbarium specimens, and genetic data, she found that the first confirmed California specimen of the Death Cap was collected in 945. “There were probably multiple introductions of this species,” she says, because Amanita phalloides in California are not genetically

similar enough to have come from a single introduction.

Because of the severe consequences of a misidentified mushroom, aspiring mushroom hunters are encouraged to learn their lessons well. At the final exam for California Mushrooms, says Bruns, completely deadpan, “the students are presented with three mushrooms, one of which is poisonous. They have to eat two.”

JENNIFER SKENE is a graduate student in integrative biology.

Want to know more?Visit the Mycological Society of San Francisco’s website at www.mssf.org

Visit the Oakland Museum of California online atwww.museumca.org

Good...or evil? The experts at the Mycological Society

of San Francisco’s annual Fungus Fair will tell you.


BRIEFS

Kristin Scott and colleagues used the proboscis

extension reflex (triggered when a leg touches

a droplet of sugar water, right) to characterize a

sweet taste receptor gene in fruit flies.

Flies Taste Like MammalsVertebrates, invertebrates encode taste signals with the same “molecular logic”

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On the second floor of LSA, postdoc Zuoren Wang glues a fruit fly to

a glass slide, its legs wriggling in the air. Working under a microscope, he dunks its feet into a spherical drop of a sugar solution and watches it extend its proboscis in a reflexive feeding maneuver. Around the corner, PhD student Aakanksha Singhvi examines transgenic flies in which fluorescent proteins illuminate individual taste cells. This technique allows her to trace those cells’ projections into the fly’s tiny brain and document the neural anatomy of taste in unprecedented detail.

Those experiments and others—carried out in Kristin Scott’s laboratory in the Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute and published last summer in Cell—produced two remarkable conclusions.

First, the insect taste system is organized in much the same way as that of vertebrates. On any particular taste neuron, the taste receptors—surface proteins that bind to small “tastant” molecules—will bind only to bitter or sweet tastants, for example, but never to both. Flies have, in other words, dedicated sweet and bitter taste neurons, just like we have on our tongues.

Moreover, the parts of the fly brain responsible for taste perception likewise appear to be segregated not only by sweet or bitter, but also by the location of the taste on the fly’s body.

Taste ranges over only a handful of “qualities”, each corresponding to a particular type of receptor protein: sweet, recognizing sugars and related compounds; bitter, recognizing a wide range of plant alkaloids and related compounds; salty, recognizing sodium and potassium ions; and sour, recognizing hydronium ions from acids. Mammals also have a receptor for “umami”—“yummy taste” in Japanese—recognizing the amino acid glutamate, which in nature signals a protein source.

Scott and her colleagues propose that this relatively simple system leads to a simple pair of behavioral responses: to eat sweet or moderately salty food sources and reject bitter, acid, or very salty food sources. But in flies there are two anatomical twists that Scott’s group has exploited. First, flies have taste neurons on their wings and legs, so they taste food at the ends of their appendages and then turn toward desirable sources to feed. (Fish, incidentally, have taste receptors all over their bodies; taste researchers like to call them “swimming tongues.”)

Second, the female fly’s egg laying organ also has taste cells, so egg-filled mothers can deposit their broods directly onto food sources. “Time flies like an arrow,” according to Groucho Marx, “and fruit flies like a banana.”

Clues to how sensory perceptions are represented in the brain have previously been found in various sensory systems in diverse animal models. The neurons at the center of the vertebrate retina, for example, make projections to the center of a certain brain area, while neurons from the left and right edges of the retina make connections on opposite edges of that area. Thus the brain tissues that process visual signals embody a map of the retinal image. Similarly, our sense of touch is represented as a distorted map of the body surface stretched over the touch center of the brain. How taste circuits in vertebrate brains are organized remains unknown. But researchers presume that, since the cells of the tongue are organized by taste quality, the taste center in the brain is likewise segregated anatomically by taste quality. The hypothesis, in other words, is that there are distinct brain areas that process sweet, bitter, salty, sour, and umami stimuli.

Scott’s team showed that the fly’s brain anatomy encodes two qualities of taste

CURRENT


in parallel: what it tastes like, and where it is on the fly’s body. They observed, for example, that taste cells on the end of a fly’s leg send projections further towards the hind end of the fly’s brain than taste cells on its proboscis. Furthermore, a bitter and sweet cell side by side on the proboscis will project to distinct targets within the proboscis taste area of the brain. In general, each taste organ sends nerves to distinct targets in the brain, and within those areas, bitter and sweet neurons seem to connect to distinct groups of target neurons.

So much for taste representation in the brain. How does each taste neuron genetically encode taste sensitivity? The proboscis extension reflex Wang observes has been known for 30 years. But he put it to new use in order to characterize the function of specific taste receptor genes. Sixty-eight taste receptors have been identified in the sequenced genome of the fruit fly. Scott’s group removed specific taste neurons by genetically programming them for death—they drove a diphtheria toxin gene only in cells that produce that taste receptor, eliminating all cells that contain a certain receptor, one at a time. Then they put these flies to a sweet and bitter taste test. Using this method they characterized one bitter and one sweet receptor. The remaining 66 gene products are presumed to include sour and salty receptors, as well as other sweet and bitter receptors, but none have been characterized except the two in Scott’s studies.

With only four taste categories, why does the fly genome contain so many taste receptor genes? Probably because of the molecular diversity of tastant molecules. While sugars, chemically speaking, are a relatively simple class of molecules, the compounds that evolution has dictated animals avoid—the bitter tastants, in other words—are remarkably diverse. It’s now known that in both flies and mice a single bitter taste cell contains many different types of bitter receptors. “This organization,” Scott explains, “would allow animals to recognize many

different compounds as bitter, without being able to tell them apart.”

Scott started her career at Berkeley only two years ago, after a postdoctoral fellowship in the laboratory of Richard Axel at Columbia. Axel shared last year’s Nobel Prize with another former postdoc, Linda Buck, for the identification of the genes encoding olfactory (smell) receptors.

“Our long term goal,” Scott says, “is to understand the neuronal circuits in the brain” that underlie taste. In order to begin to explain taste behavior in terms of connected groups of neurons, they aim to identify the individual neurons in the brain that receive input from taste cells, and then determine which neurons they connect to in turn. To trace these neural circuits, postdoctoral fellow Sunanda Marella and PhD student Walter Fischler have been using transgenic flies with neurons whose fluorescence intensity changes when they become active. Instead of having to poke randomly around the tiny fly brain with electrodes, recording taste response activity in one cell at a time, their method will allow real time microscopic observation of the activity of whole groups of neurons in the taste areas of the fly brain—a technique known as “functional imaging.”

Meanwhile, Scott’s group is screening for mutants with defects in taste-mediated behavior. Ultimately, they hope to identify genes required in the fly brain for those behaviors and uncover more clues to the underlying neural circuits and how they function. “Functional imaging,” Scott explains, “will be the platform for all of these studies.”

JAMES ENDRES HOWELL is a graduate student in molecular and cell biology.

Want to know more?Check out “Taste representations in the Drosophila brain”: Wang Z. et al, Cell. 117, pp. 981-991 (2004).

Visit Kristin Scott’s lab at mcb.berkeley.edu/labs/scott


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Laser tweezers: a glass micropipette holds onto a polystyrene bead via suction. The “trap” bead is held in place by focused laser beams. A strand of DNA joins the two beads.

other, the “trap bead,” hovers above it. The pipette is linked to a stage Smith controls via a red trackball; the trap bead is held in place, not by a physical object, but by light from a focused laser beam, the heart of the laser tweezers. When Smith moves the pipette bead, the trap bead starts to follow—it’s as if an invisible tether is linking the beads.The tether is a single strand of DNA, with its ends modified so that it sticks to proteins that coat the beads. While the pipette bead is solidly anchored, the laser tweezers hold the trap bead somewhat loosely, as if the bead were on a spring. Researchers observe how the DNA linking the two beads stretches when they pull on it. By studying how the trap bead deflects the laser beam, they can measure the force on the tethered DNA in piconewtons (a millionth of a millionth of the force needed to hold a baseball) and how far it stretches in nanometers.

Laser tweezers have been especially useful in the study of proteins that move along DNA, doing things like reading, copying, cutting, and unwinding it. Each

of these proteins physically moves along a DNA double strand as it performs its function. By attaching a bead to one of these proteins, researchers can use laser tweezers to play friend or foe by mechanically helping or hindering the motor’s motion.

Measuring how speed varies with force and chemical fuel supply allows researchers to investigate the fascinating coupling between the physical mechanism and the underlying biochemistry. A good example is the “packing” motor of the virus phi29, which is able to stuff a long strand of DNA into a tiny virus shell while preparing to infect other cells (imagine putting a ten foot length of stiff wire in a box the size of a walnut). Using laser tweezers, Bustamante’s group

showed that this is possible because

the motor responsible for this task is extremely powerful, able to work against a pressure of about sixty atmospheres—ten times the pressure stored in a bottle of champagne! These experiments,

Smith says, “take a big collaboration…You need a biologist or a biophysicist to tell you what the problem is that’s worth solving…You need a physicist to build the optics and to interpret the data… and you need an architect and a building manager to build you a basement room on bedrock.” Since laser tweezers are so sensitive, “you have to practically build your building around [them].”

Although on campus versions of Smith’s tweezers reside in the Bustamante lab, Ignacio Tinoco’s lab in Chemistry, and Jan Liphardt’s lab in Physics, the infrastructure requirements prohibit standard biology labs from using laser tweezers. That’s something Smith wants to change, so he has built the “Mini-Tweezers,” which take the 4 by 6 foot optical table and associated optics and cram them into a basketball-sized package. This portability enables your “collaborator someplace across the world to send it back to you in a box.” Smith expects a commercial version of the instrument to cost between $00,000 and

Pull My DNA...with the world’s tiniest tweezers

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Steven Smith is a research scientist in Carlos Bustamante’s lab in the Departments of Physics, MCB, and Chemistry.

MOST people take it on faith that molecules exist, while a few others

aren’t satisfied until they have seen them imaged by a microscope. But as Steven Smith says, “after you’ve looked at these molecules for a long time you really want to get your hands on them.”

A fine concept, but a challenging task if the molecules you’re talking about are only two nanometers in diameter ( 20,000 times smaller than a human hair). Despite these minuscule dimensions, Smith, a research scientist in Carlos Bustamante’s lab in the physics, chemistry, and molecular and cell biology departments, can stretch, twist and probe all kinds of molecules with an instrument called laser tweezers.

Watching Smith work with laser tweezers is like watching him play a video game. A monitor shows a view through a microscope of the two beads he controls: one is perched atop a pipette, and the

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$200,000, or about the same price as an atomic force microscope (AFM). Labs that would consider AFMs for imaging or high force mechanical manipulation are the intended market. A prototype of the Mini-Tweezers is already being used with improved resolution and reduced drift in what must be one of the worst rooms for tweezers on campus. By simply dangling from the ceiling on a single bungee cord, the Mini-Tweezers achieves excellent vibration isolation. Now, the key to understanding nature’s rubber bands is Smith’s “basketball” hanging from a bungee.

MEREK SIU is a graduate student in biophysics.

Want to know more? Visit the Bustamante lab website at alice.berkeley.edu for articles, movies, and more.

Smith’s “Mini-Tweezers” compress the essentials of optical tweezers into a package the size of a basketball.

Sally Benson, an LBNL engineer, coordinates joint public-private research on carbon sequestration.

Sweeping CO2 Under the RugThe Science of Geologic Sequestration

SALLY BENSON was skeptical. Five years ago, when the US Department

of Energy asked this Lawrence Berkeley National Laboratory engineer to develop a program to study geologic carbon sequestration, she described herself as “agnostic.” Could the capture and underground storage of carbon dioxide emitted from refineries and power plants really loosen the chokehold of this gas on our climate? Would it be safe? And could we afford it?

In the end, Benson could not ignore any means of combating global warming. By burning fossil fuels over the last 250 years, we have injected nearly 300 billion tons of carbon, most of it carbon dioxide, into our atmosphere. Carbon dioxide traps the sun’s heat near the Earth’s surface in a process known as the greenhouse effect. In the 990s, record-breaking heat and devastating storms triggered international alarm about the effects of global warming. With renewable energy production still in its infancy, geologic carbon sequestration

has been touted as a way to reduce the impact of fossil fuels on our climate using existing technology from the oil and gas industry.

Five years later, scientific evidence has created a new convert. Benson easily admits, “the longer I’ve worked on [geologic carbon sequestration], the more persuaded I’ve been that this can really work.” As director of GEO-SEQ (pronounced “geo-seek,” for Geologic Sequestration), she guides public-private research focusing on the storage end of this capture-and-storage technology. While other groups design energy production facilities and gas separation methods for carbon dioxide capture, the GEO-SEQ team explores ways to get the gas underground and keep it there.

The first step in carbon sequestration is the selection of a site with an appropriate underground mineral formation. A good formation is like a loaf of crusty bread —a dense, impermeable layer topping a mass of porous material. The dense layer, known as the caprock, keeps the buoyant

carbon dioxide below ground. Fortunately, many good sequestration

sites are easy to spot. Because oil and natural gas are buoyant, reservoirs that store these fluids can store carbon dioxide as well. Even more carbon dioxide can be stored within saline formations —common mineral deposits permeated with very old, salty water, and topped by caprocks. Worldwide, depleted oil and gas reservoirs and saline formations

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Like the Texas oil reservoir that Benson studies, underground saline formations can store CO

2,

preventing this pollutant from entering our atmosphere. Statoil’s Sleipner West natural gas production facility (above) pumps 2800 tons of CO

2 each day into a saline formation beneath

the floor of the North Sea.

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could hold nearly two trillion tons of carbon as carbon dioxide—six times what we’ve produced since the rise of industrialization.

To study carbon sequestration, Benson and her team have injected 700 thousand gallons of carbon dioxide into a depleted oil reservoir near the town of South Liberty, Texas. Sensors above and below ground detect trace amounts of the gas, or minute changes in pressure, seismic motion, or electromagnetic properties. These measurements reveal the effects of natural and operational variables (like reservoir geology and rate of injection, respectively) on the flow of carbon dioxide within the reservoir. As scientists improve predictions of the underground behavior of the gas, they advance their ability to find and fill storage sites.

By testing a variety of sensors, Benson determines which can be used to detect leaks for commercial sequestration projects. Seepage through microfractures within caprocks presents the largest monitoring challenge, notes Scott Klara, sequestration technology manager for the Department of Energy. However, without

carbon storage, “we are leaking 00%.”While Benson initially questioned

the security of sequestration, she is now satisfied that storage can be quite safe. It turns out that storing carbon dioxide underground is a lot like storing natural gas underground, something industry has been doing for decades. Existing methods to control potentially disastrous natural gas leaks work just as well for carbon dioxide, though as Benson cautions, “that doesn’t mean it would be cheap.”

And while most forms of waste disposal grow more dangerous as containment structures age, Benson points out that for sequestration, “it’s actually the reverse; the carbon dioxide storage actually gets more and more stable over time.” Although sequestration initially depends on the caprock to physically trap the gas, chemical reactions eventually transform carbon dioxide into carbonate minerals, permanent residents of the reservoir.

Benson and her GEO-SEQ team are not alone. Already, three commercial projects each store at least a million tons of carbon dioxide annually. But how much does geologic carbon sequestration

cost? If power plants used existing sequestration technology, the cost to produce electricity would increase by 30 to 70%. With more advanced technology, the Department of Energy hopes to reduce the cost of storage to less than 0% of the cost of electricity production. Measured against the climatic disasters that may result from global warming, geologic carbon sequestration should prove to be an exceedingly wise investment.

REBECCA SUTTON is a postdoctoral researcher in environmental science, policy, and management.

Want to know more?Visit the GEO-SEQ website at esd.lbl.gov/GEOSEQ


BRIEFS

During amplexus, the female frog deposits her eggs while the male frog—clasped to her

back—fertilizes the clutch.

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Who’s Your Daddy?Survival of the fittest means something different to frogs

ELEVEN months of the year the European common frog’s life is

a bit dull. But for a few weeks each spring some of these usually bashful amphibians drop their mild manners to go on a carnal free-for-all. David Vieites, a postdoctoral fellow in UC Berkeley’s Department of Integrative Biology, had been studying Rana temporaria for over ten years before he was treated to a rare first glimpse into their unusual sexual strategies.

Interested in the special adaptations amphibians must make to survive in extreme environments, Vieites chose a study site high in the Spanish Pyrenees. He worked with this population throughout his undergraduate and graduate careers at the University of Vigo in northwestern Spain. However, it was not until he finished with his coursework as a graduate student, and finally freed from exams in the first weeks of May, that he witnessed a behavior never before reported among amphibians.

Most populations of R. temporaria breed at night, but the low temperatures at Vieites’s alpine site force these frogs to breed during the day. This allowed Vieites to take a front row seat during mating season.

R. temporaria is an explosive breeder. Just after the ice melts in the spring, enormous numbers of male frogs gather at ponds to mate. Over the next several days, females will wander by a few at a time, drawn to the cacophony of croaks from the males. Males typically outnumber females by 10 to 1 which means only a small fraction of the males (10–20%) will get an opportunity to mate. The rest will have to wait,

frustrated, for next year. For frogs, egg fertilization usually takes

place while the male and female are in amplexus—while the male is clasped to the female’s back and releases sperm on her eggs as she lays them. Vieites ob-served something quite different. While some males were behaving “normally” —clasping females and fertilizing eggs in the usual way—other “pirates” were sneaking after mating pairs and making off with their freshly laid egg clutches. At times, the pirates banded together into groups, patrolling the pond for unattend-ed eggs. Unsatisfied with simply grasping the clutch, some pirates would crawl into the heart of an egg mass so their sperm could penetrate every last egg. On aver-age, pirate sperm fertilized one quarter of the eggs, but in some cases accounted for nearly all the fertilization in clutches.

While this behavior clearly confers an evolutionary advantage on the pirates, who would otherwise fail to pass on their genes, it also benefits the females in two key ways. First, the fertilization rate of pirated clutches can approach 100% compared to just 70% in singly

fertilized clutches. More fertilized eggs is good for mom because it means more of her DNA is passed on. Second, these higher yield clutches have the advantage of increased genetic diversity, with some portion fertilized by the original male and the remainder fertilized by the pirate(s). This is also good for mom, since a more diverse clutch will likely produce more fit offspring with a greater chance of surviving to pass on her genetic information.

The only ones who don’t seem to benefit from the pirate behavior are the original males pursuing the “normal” mating strategy. Quantifying the relative fitness of the “normal” strategy versus the pirate strategy will be Vieites’s next task.

Only five or six other species of amphibians are known to exhibit multiple paternity, but Vieites believes that this number greatly underestimates the actual prevalence of this type of behavior. Very little is known about the great majority of amphibian species. R. temporaria is one of the best-studied species—over 4000 scientific articles have been published about it over the past 100 years—and yet


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this behavior remained unknown, and it would be unknown today if Vieites had not finally made it up to his study site for that one crucial week in May.

Unfortunately, our time to fill in the many gaps in our knowledge about amphibians may be running out. Vieites emphasized that while his studies of amphibians have resulted in many interesting findings that may have much to teach us about sexual selection and evolution, these are overshadowed by a looming crisis. The World Conservation Union Global Amphibian Assessment, a major project on the conservation status of 5743 species of amphibians, has discovered that the populations of over 40% of species are decreasing.

Even more troubling, for almost half of the most rapidly declining species, populations are dwindling for no identifiable reason. It is possible to

develop strategies for conserving species when the decline is due to identifiable factors such as habitat loss. Without knowledge of the cause, little can be done to reverse the slide. Only with further research can we hope to uncover the causes, and in so doing, the solutions. Clearly, there is a wealth of knowledge still waiting to be mined from further study—if behaviors such as clutch piracy are only now coming to light in our most well-known amphibian species, imagine what awaits us in unfamiliar places.

ALLISON DREW received her MS in environmental science, policy, and management from UC Berkeley.

Want to know more?Check out “Post-mating clutch piracy in an amphibian”: Vieites, D. R., et al., Nature 431, pp. 305-307 (2004).

David Vietes first observed this strange mating

behavior at a site high in the Spanish Pyrenees.

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BOINC!Do try this at home

it’s happening.As crazy as it might at first

have seemed, SETI@home captured people’s imaginations. It’s been downloaded by over 5 million users in 226 countries, some 600,000 of whom still remain active. Together, they’ve contributed over 2 million years of computing time. Its message boards form an online community where people can socialize (several couples have met through SETI@home and married) and keep track of how much work their computer accounts have completed. The “leader board” generated so much attention that some users began selling completed units and successful accounts on eBay for as much as $275.

While working on the original version of SETI@home, Anderson quickly discovered that he and his coworkers were spending most of their time building infrastructure to manage the project: writing code to send out data packets to people’s computers, running servers and databases, keeping track of completed work sent back to the project, and making sure that nobody submitted fraudulent results. They lost a year of science in just setting up the basics. But in the process, Anderson had a realization: “Infrastructure is totally independent of application. Wouldn’t it be better if we just developed one [system so that other] projects could start up with minimal infrastructure?” And so BOINC was born.

BOINC handles all of the behind-the-scenes tasks so that scientists can quickly and easily set up public computing projects of their own. It’s available free of charge for researchers and for the general public to download, and it runs on Windows, Apple, and Linux platforms. “The goal of BOINC is that someone can set up one of these projects really easily,” Anderson says.

And so far, scientists and the public have been quick to respond. SETI@home has switched over to the BOINC plat-

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IN THE old days, if you wanted to be a tiny contributor to the onward

march of scientific progress, you might have donated your body to science. But if David Anderson has his way, you won’t have to wait until you’re pushing petals to advance the frontiers of human knowledge—you just have to donate your dead computer time.

Anderson, a scientist at the Berkeley Space Sciences Laboratory (SSL) and former professor in the Department of Computer Science, directs BOINC—the Berkeley Open Infrastructure for Network Computing (boinc.berkeley.edu). BOINC is a software platform that makes it easier for scientists to harness the massive computing resources that often lie dormant in people’s homes and offices. In this new paradigm, called public computing, computational tasks are chopped into small pieces and sent to individual members of the public. Your computer can be looking for aliens or calculating the temperature of the Indian subcontinent in the year 2050 while you sip a cup of tea or cook dinner.

Without a doubt, the best-known public computing project is SETI@home. SETI, the Search for Extraterrestrial Intelligence, looks for signals from intelligent extraterrestrials in data from the Arecibo radio telescope in Puerto Rico. SETI@home was created in 1995 by Anderson and David Gedye, then a UC Berkeley computer science graduate student. It was the 25th anniversary of the Apollo moon landing and Gedye was, as Anderson puts it, looking for a way to rekindle the public’s interest in science in the same way that “Apollo got the public really galvanized.” SETI@home was their answer: let people search through the mountains of Arecibo data on their home computers, a chunk at a time, and give them a glitzy screen saver to look at while

form. In August, Climateprediction.net signed up to use BOINC as well. Based in the UK, Climateprediction.net aims to improve long-range climate model-ing by making very small tweaks to a model’s parameters and running it again and again. Thus far, 20,000 users have crunched through over 2 million years of Earth’s imaginary future. Their efforts culminated in a January publication in Nature showing that the Earth’s response to increases in greenhouse gases may be far more dramatic than scientists had pre-viously expected.

As part of the World Year of Physics in 2005, Einstein@home has been designed to run on BOINC to search for gravity waves, the ripples in the fabric of space-time predicted by Einstein’s general theory of relativity. If that doesn’t interest you, you can help design magnets for the Large Hadron Collider, the world’s next great particle accelerator at the CERN lab in Switzerland with LHC@home, or help figure out how proteins fold with the Predictor@home project.

From the beginning, Anderson made it one of BOINC’s goals to allow users to choose how to allocate their resources between projects, especially with so many to choose from. For example, you can choose to search for gravity waves ten percent of the time and fold proteins the other ninety percent. His hope was that

Is ET trying to phone home? The answer may be

hidden in this noise.


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Quanta{heard on campus}

BOINC could “get people to invest some thought” in the experiments they were choosing between and ask themselves, “Is this something benefi cial to humanity?”

Dan Wertheimer, an astronomer at SSL and chief scientist of SETI@home, calls BOINC “a tremendous way to get the public involved in science.” Karl Chen, who worked on BOINC as an undergraduate and is now a graduate student in computer science, concurs. “I ran SETI@home when I was a kid and my science teacher had it at one point…It’s good publicity and marketing.” Individual projects work hard to put up materials explaining their science to participants. Th e Lawrence Hall of Science has even developed a curriculum unit for schools based on SETI@home.

Not everyone is in love with the idea of public computing, though. To Anderson, many in the supercomputing community might “equate public computing with searching for little green men” or scoff that “you can’t get real work done that way.” Th ey prefer large centralized supercomputers or national lab and university consortia. “Livermore does testing on nuclear weapons,” Chen says. “Th at’s something they won’t run on people’s home computers.”

“All these things have their place,”

Anderson cautions. While your computer won’t be designing next generation nukes, it may give scientists access to unprecedented computing power at a very low cost, thereby breathing life into projects that might not otherwise have been feasible or might not have been attractive to government funding agencies.

As computers get faster and faster and storage space gets cheaper and cheaper, a larger share of the world’s computing resources will lie scattered in homes and offi ces rather than in centralized facilities. But when it comes to harnessing this power through public computing, as Anderson puts it, “You can’t really buy it—you have to convince people you deserve it.” In this way, Anderson and BOINC may give the public a larger share and a larger voice in how science gets done.

MICHELANGELO D’AGOSTINO is a graduate student in physics.

Want to know more?Visit BOINC: boinc.berkeley.edu

Check out “Uncertainty in predictions of the climate response to rising levels of greenhouse gases”: Stainforth, D. A. et al. Nature 433, pp. 403-406 (2005).

“Sleep with your ideas. Don’t marry them.”Annelise Barron of Northwestern University. Center for Analytical Biotechnology seminar, 1/13/2005

“Twinkling of stars may be beautiful, but it is very objectionable in astronomy.”Charles Townes, emeritus professor of physics. IR Interferometry on Old Stars, 3/4/2005

“We built the world’s most expensive low-fi delity sound system.”Steve Block of Stanford University, explaining how he reconstructed “The Girl From Ipanema” from angstrom-scale oscillations of a bead in his laser trap—the bead had picked up the signal from the stereo playing in the next room. Optical Tweezers: Biophysics, One Molecule at a Time, 10/12/2004

“Those are the units Einstein used. Dynes per centimeter, buddy!”Harden McConnell of Stanford University, responding to a request that he translate the archaic units of pressure in a phase diagram, How Cells Handle Cholesterol, 10/26/2004


Strangef r u i t

California counties have a love-hate relationship with GMOs

Home from the GMO warsGMOs, THOUGH broadly shunned by the European public, are common in the US marketplace. But even here on the complacent side of the Atlantic, they have become increasingly con-troversial. Simply defi ned, GMOs are organisms (most commonly bacteria or plants) that contain genetic material from more than one source. For ex-ample, “Bt corn” is a corn plant with a bacterial gene integrated into its DNA; “Golden Rice” is a rice plant that con-tains daff odil and bacterial genes.

Th ough often touted as solutions to agricultural, nutritional, and ecological problems, GMOs have also inspired a variety of criticisms. Th ese range from ethical objections to DNA manipulation, to concern about the boundaries of intellectual property rights, to fears of unintended environmental or human health eff ects. But in the end, both those who reject these organisms and those who defend them struggle with two central questions: who is qualifi ed to

evaluate the eff ects of GMOs, and who is responsible for such evaluations? On whom do we place the burden of ensuring the safety of our Bt corn or Golden Rice?

As it stands, no one governmental agency regulates all aspects of GMOs. Th is lack of comprehensive, mandatory federal regulation is disquieting to environmental and food safety advocates. Th at is why, in March 2004, Mendocino County in northern California passed Measure H, making

by Cheryl Hackworth

art by Jennifer Bensadoun

I N SEPTEMBER 1999, a group of local activists raided UC Berkeley property. Th eir mission: to save humanity and the environment from genetically modifi ed organisms, or GMOs. Th e target: two small plots of agricultural land near the university campus.

Th e damage: row after row of uprooted corn plants. In the end, it was an empty victory; the guerrillas had mistakenly victimized not genetically modifi ed crops but the innocent off spring of traditional breeding between conventional parents. Today, the grassroots struggle to uproot California GMOs continues, but the covert activism of fi ve years ago has been replaced by sweeping legislative measures voted on by the public at large.


it the first county in the United States to render it “unlawful for any person, firm, or corporation to propagate, cultivate, raise, or grow genetically modified organisms.” Trinity County, also in northern California, quickly followed suit, starting a trend in California counties to pass this type of measure.

To counter the anti-GMO push, Fresno County launched a trend of its own. Located in the center of California’s commercial agriculture belt, Fresno grows a large number of genetically engineered crops; as a result, the Fresno Board of Supervisors passed a resolution “that the County of Fresno will make every effort to preserve the choice of using biotechnology in its county and encourage the establishment of a state or national biotechnology policy.” Kings County, neighbor to Fresno, passed a similar resolution, emphasizing farmer choice in the use of GM crops.

As counties rush madly for one bandwagon or the other, California’s famously chaotic, grass-roots approach to legislation is once again breaking

new ground. Voters have begun to legislate scientific issues directly, and the effects may eventually ripple through UC Berkeley research programs and then the state (and world) agricultural communities.

The Letter of the LawTHE measures that made it onto No-vember 2004 ballots in counties across the state were a motley bunch. Some prohibited all GMOs, while others attempted to outlaw only GM food crops, making exceptions for GMOs used in medicine and research. The penalties for contraband organisms also differed, some giving the Agricultural Commissioner power to dole out ap-propriate punishments. Others, like Humboldt’s, would have punished offenders by “confiscation and destruc-tion of any organisms found to be in violation,” and imposition of “a mon-etary penalty and/or imprisonment,” in essence, turning the cultivation of GMOs into a criminal act.

Unfortunately for their creators, these measures were written without much scientific or legal advice. The lack of

scientific input was evident in such bloopers as “DNA, or deoxyribonucleic acid, means a complex protein,” a quote common to over half of the voter initiatives. (DNA is composed of nucleotides, not amino acids.)

In other cases, the legality of some ordinances was questionable. The criminalization of growing GMOs in Humboldt County’s measure was illegal and resulted in a lack of support from both sides; it failed to gain voter approval. Similar measures on the November ballots in Butte and San Luis Obispo Counties, despite heavy financial support from anti-GMO groups, also failed. In fact, the year’s three anti-GMO successes were largely symbolic: Marin county, for example, has only minimal commercial farming,

The tassels of a GM corn plant, flowering in a research plot in northern California.

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almost all of which is organic. Similarly, there were no GMOs growing in Mendocino or Trinity Counties when they voted to ban such organisms.

Beyond the shaky scientifi c wording and legality of the California county ordinances, questions of practicality lurk. Whether these laws can even successfully function on a county-by-county basis is an open question. Peggy Lemaux, a professor in the department of Plant and Microbial Biology, doesn’t think it will work at all. Th e government “used to do [county-by- county regulation] with pesticides and it was so horrible because [the farmers’] land would go from one county to the next. It’s a very diffi cult situation for farmers to deal with.”

But if these measures were created quickly, with little advice from scien-tists or lawyers, and they were passed as a purely symbolic move, why were people so eager to act? Lemaux thinks the reason is because the public wants the government to have a system in place to regulate this new technology. “It was born out of people’s frustration because they don’t know…how to get the state to move on this. Th is is their

way to force it.”Th is has some farmers in Califor-

nia worried that this series of events has set a precedent for future action. Sarah Hake, a professor in the Depart-ment of Plant and Microbial Biology whose husband owns an organic farm in Marin County, is disturbed by this trend: “I don’t think California coun-ties should be setting protocol in the state or the nation.” She thinks these laws should be created at the state level by legislators with help from informed scientists.

In the midst of this controversy, bio-tech companies continue to produce new genetically modifi ed organisms, and farmers continue to plant more and more land with these crops. Given a choice, with no pressure from non-governmental organizations, farmers choose genetically engineered crops time and again.1

Why have most scientists and farm-ers welcomed this technology, even in the face of growing public opposition? Genetic engineers claim that their new techniques are no diff erent from clas-sical breeding and affi rm that farmers have been manipulating plant and

animal characteristics for thousands of years. GMOs can also yield new crop lines in a much smaller time frame than classical breeding. Additionally, many biotech companies vow to engineer plants with increased nutrient composition and greater fruit yield. But op-ponents counter these claims with vehement criticisms of the eco-nomics and ecology of GMO-based

Gene fl ow is a result of the pollination of one plant line by another. This is not normally cause for concern, but it can become a problem if pollen from a GMO fertilizes an organic plant or a native, “landrace,” variety. Farmers have several options to control gene fl ow into or out of their fi elds.

To limit the risk of pol-len contamination, organic crops are restricted to grow on land surrounded by a substantial buff er zone. The minimum buff er distance is set by the federal Associa-

tion of Offi cial Seed Certify-ing Agencies. But no matter how wide the buff er zone, there can never be 100% certainty that no contami-nation will occur.

To reduce the risk of gene fl ow below what a buff er zone permits, two tech-niques are in the pipeline. In the fi rst, scientists insert the foreign gene into a cell’s chloroplast, the photosyn-thetic compartment in a plant cell, rather than its nu-cleus. Transgenes inserted into this cell compartment can still produce the de-sired plant characteristics.

However, the chloroplast is naturally excluded from a plant’s pollen. This means that foreign DNA inserted into the chloroplast would remain only with the sta-tionary, female portion of the plant body, reducing the chance of genetically “polluting” other plants. Currently, no commercially sold GM plant utilizes this technology.

A second technique involves the insertion of a “terminator” gene into the GMO. This gene renders the pollen from a GMO plant infertile, preventing it

from forming a new seed in the event that it does fi nd its way to another plant. Farmers’ rights groups were outraged at the initial introduction of this technology, as it was seen as a way of maintaining proprietary rights over GM seeds, forcing farmers to buy new seed each year. As a result of the outcry, the company that developed the terminator technology promised not to use it, even though this method would drastically reduce the possibility of gene fl ow from GMOs to other plants.

Blowin’ in the wind


agriculture (see sidebars).Opinion among the faculty at UC

Berkeley varies as much as it does internationally. In the Departments of Molecular and Cell Biology (MCB) and Plant and Microbial Biology (PMB), researchers regularly genetically engineer species of bacteria, fungi, and plants, mostly for research, but some for eventual commercial use. Peggy Lemaux and Sarah Hake both make it a priority to speak to the public about both sides of the issue. Hake, in a letter to the residents of Marin County, wrote that “investigating the benefits and risks of each GM crop would be much more prudent than simply saying no based on fear of the unknown.”

Voicing the opposite side of the issue are Andrew Gutierrez and Ignacio Chapela, professors in Environmental Science and Policy Management (ESPM), who frequently address the public about possible problems with these new crops. Gutierrez, who studies “non-target” effects of GMOs, constantly returns to his most basic argument against these crops: “You

need to ask: are they needed, are they efficacious, and are they economic. In most cases, you’ll find they are not.”

A pound of prevention? TO MANY who are concerned with GMO safety, one of the most significant regulatory problems is that the GMO market is dominated by a few very large companies like Monsanto and DuPont. These companies own not only the genetically modified plants themselves, but also the technology and information used to create them for at least the next 20 years. With this monopoly and little government oversight, such companies can set their own standards for product regulation. Many people fear that as a result, the proper tests are not done and possible problems with human health and environmental safety are not discovered.

Indeed, there is very little enforced regulation by either the state or the federal government. As long as the company selling the product can demonstrate that the genetically engineered crop is “substantially

equivalent” to its closest classically bred relative, no additional testing is required.

Nonetheless, many companies exten-sively test their products, regardless of government pressure, for fear of litiga-tion. In fact, GMOs are tested with greater rigor than any classically bred crop currently produced, even though an overwhelming majority of cur-rent peer-reviewed data indicates that GMOs are no more harmful than clas-sically bred crops.

Frustrated by the success of anti-GMO initiatives, industry representatives assert that the public should be championing less regulation, not more. Neal Gutterson, a graduate of UC Berkeley and Chief Operating Officer of Mendel, a private biotechnology research company in the East Bay, thinks genetically modified crops are already overregulated. He points to a five-hundred-page dossier sent by Monsanto to the US government in support of a new product. To clear a classically bred crop for sale, the government requires far less paperwork. Gutterson argues,

Peggy Lemaux examines some GM sorghum, engineered to be more easily digestible.

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“[introduction of GMOs to market] is overregulated based on what is required to demonstrate safety.” Since there has been no verifi able demonstration of any harm to human health,2,3 GMOs should be regulated at the same level as classically bred crops.

In contrast, UC Berkeley’s Andrew Gutierrez supports the implementation of the precautionary principle, which questions the ethics of blindly implementing a new technology. Th is principle asserts that if the eff ects of a new technology are unknown but are judged by some scientists to have negative risks, then it is better not to carry out the action at all rather than risk uncertain consequences. In essence, the precautionary principle would thus prohibit any further development or use of GMOs until they could be shown to be irrefutably safe for the environment and for human health.

Of course, the demonstration of irrefutable safety is impossible, but to help quiet public concerns, many researchers continue to study the

human health and environmental safety of these crops. But, according to Gutierrez, “it’s diffi cult to get resources to do those studies. Who provides the money? Th e USDA and industry provide the money,” and these groups have a vested interest in benign results.

Opponents of the precautionary principle point out that the principle can limit any technology because

there are possible negative eff ects associated with any new advancement in science. Th e principle ignores any possible benefi ts of GMOs. Gutterson claims, “our society would never have gained wheels if it had been for the precautionary principle.”

Something that both sides of the GMO debate agree on is that the general voting public should not

Human rights groups are concerned that the rights of farmers, especially those in the developing world, will diminish as the popularity of GMOs increases. The ownership of these plants remains with the company that creates them, not with the farmers who plant them.

Because of patents, farmers are prohibited from planting saved GM seed. Most industrial farmers in the United States who grow corn or other grasses already purchase new seed at the beginning of every growing season. But

farmers who rely on saved seed, many of whom are in the developing world, may fi nd themselves in legal trouble with agricultural companies.

Percy Schmeiser, from Saskatchewan, Canada, is one such farmer. He blames the Monsanto Company for contamination of his canola fi elds. During a regularly scheduled random check, Monsanto found that at least 95% of Schmeiser’s 1,000 acres contained Round-Up Ready canola (canola that can grow in the presence of the herbicide Round-Up, also sold by

Monsanto). The company promptly

sued Schmeiser for the profi t he had made on his herbicide-resistant canola. Schmeiser countered Monsanto by claiming that he gained no advantage from the GM canola since he had never sprayed it with Round-Up. Schmeiser also emphasized that most patents do not uncontrollably fi nd their way into the possession of an unlicensed individual. But Monsanto insisted that regardless of how the gene found its way into Schmeiser’s canola, the

farmer had infringed on its patent.

After listening to both sides, the judge ruled that the only way Schmeiser’s fi elds could contain 95% GM crops was if he had in fact sprayed them with Round-Up and then looked for resistant plants. Even if the crops were initially the result of contamination, Schmeiser had intention-ally selected for Monsanto’s proprietary organisms. The precedent is clear: in Canada, the company owns the rights to any plant con-taining a patented gene, re-gardless of how it got there.

Old Macdonald had a right

Sarah Hake’s husband, Don Murch, at Gospel Flats, his organic farm in Marin County.

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directly decide how to regulate GMOs. Rather, scientists and legislators should work together to create these laws. As Gutierrez states, “I don’t think the public is sufficiently informed on the issues.” Gutterson agrees, saying, “it’s an act of democracy, so you can’t argue with that, but you need a more expert, informed view. The voters can be misguided.” Instead, he thinks “we look to the federal government to regulate complex issues and I think that’s the right place to go. The USDA and FDA need to be given a mandate.”

The gene’s out of the bottleANOTHER major concern surrounding GMOs is the possibility that they will genetically contaminate other crops, be they organic plants grown in a nearby field or wild relatives of a genetically

modified species (see sidebar “Blowin’ in the wind”). Contamination could occur if a genetically engineered plant pollinated a non-GMO plant, thereby creating fruit or grain containing a genetically engineered gene. This process is known as “gene flow.” Contaminated fruits or grains would be grown and shipped as non-genetically engineered foods, and without complex biological tests, consumers would be none the wiser. Understandably, this makes many farmers

uneasy, especially those who farm organically. With even the possibility of this contamination happening, organic farmers stand to lose value in US and European organic markets.

The threat to wild relatives may be even more serious. Wild relatives of cultivated plants are considered unlimited reservoirs of genetic diversity that can be bred into contemporary crop lines. Genes stored in natural relatives can confer traits such as increased flavor or enhanced disease resistance to a new pest. Farmers have resorted to these wild relative gene reservoirs during the entire history of agriculture, and they continue to do so today.

Ignacio Chapela was one of the first scientists to address concerns over gene flow. Chapela believed that pollen from

illegally grown GM plants imported from the US could contaminate indigenous plant lines in Central America, where many varieties of corn are grown on small family farms. These plant lines, known as landraces, are genetic warehouses for traits that could be classically bred into US corn lines to confer desired characteristics. After random sampling in the maize fields in Central America, Chapela discovered that genetically engineered traits had already found their way into Mexican landraces.

Although Chapela’s scientific methods have been extensively criticized, few scientists would dispute his conclusion that contamination of the land races in Mexico has already occurred. The extent of the contamination, whether it can be stopped, and how to eliminate the genetic pollution that exists, are all areas that require further study.

Closer to homeTHE city of Berkeley, located in Alameda County, includes UC Berkeley as well as a large number of private biotechnology companies that may be affected by new laws regulating genetically modified organisms. Berkeley residents do not grow genetically modified crops and most are fairly liberal in their political leanings; the culture in this county has more in common with Marin than with Fresno. This may be why groups such as GMO-Free Alameda are taking hold here.

The main goal of GMO-Free Alameda is to “protect the county’s agriculture, environment, and private property from genetic contamination and to safeguard residents’ health and the economy from the ill effects of genetically modified organisms.” GMO-Free Alameda plans to start just as Mendocino and Marin Counties did, with a ballot measure supported by a collected list of supportive voters.

The granules of GM sorghum tissue in this petri dish will be treated with hormones and develop into full-grown plants.

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Sonoma, a neighboring county, has already collected the necessary number of signatures to put it on the next ballot, and Alameda County may soon follow.

Th ese county-based initiatives would not directly aff ect research at UC Berkeley, but the eff ects on private companies and farmers in northern California would still be felt at the university. Peggy Lemaux conducts research on genetically modifi ed grains, and some of her research is done through contract with local farmers. If the farmers were prohibited from growing genetically modifi ed organisms, this research couldn’t be done and, says Lemaux, “[I] couldn’t assess the impact of GMOs because I couldn’t do the experiment[s].”

Biotech businesses like Neal Gutterson’s Mendel fear that local legislation against GMOs may limit or even reduce the fi nancial stake the government and private companies have in the biotech industry and university research in California. Currently, California has a large biotechnology sector in both the public and private arenas, and a majority of cotton farmers in California also grow genetically modifi ed plants. However, all of these industries could easily decline if California’s legislative climate discouraged the research or use of GMOs.

It’s a good sign that activist groups have shifted tactics from guerrilla war-fare to working within the legal sys-tem—introducing ballot initiatives is a far more civilized way to work change. However, good democracy requires in-formed voters, and the GMO debate is too complex to be reduced to a simple yes or no vote by a public generally uneducated in science, agriculture, eco-nomics, or technology. Th e people we elect, Hollywood action heroes or oth-erwise, should appoint qualifi ed scien-tists and legislators to introduce state or

federal laws—laws that exercise proper caution, while still allowing farmers the advantages of technology. Th ese scien-tists and legislators need to understand both the risks involved with gene fl ow and the social cost of patenting farm-ers’ seeds, while at the same time taking into account the tremendous benefi ts this new science promises.

CHERYL HACKWORTH is a graduate student in molecular and cell biology.

Want to know more?Check out the UC Biotech website:www.ucbiotech.org

The Pew Initiative website:www.pewagbiotech.org

And for some activist viewpoints:www.calgefree.orgwww.organicconsumers.org

References1. USDA-NASS Censuses; Pew Initiative on Food and Biotechnology Study, 2004.2. Hammond, B. G., et al., “The feeding value of soybeans fed to rats, chickens, catfi sh, and dairy cattle is not altered by genetic incorporation of glyphosate tolerance,” J. Nutrition 126, pp. 717-727 (1996).3. Hammond, B. G., et al., “Results of a 13 week safety assurance study with rats fed grain from glyphosate tolerant corn,” Food and Chemical Toxicity 42, pp. 1003-1014 (2004).

Rajvinder Kavr, assistant specialist, and Erica Moehler, undergraduate, work with GM sorghum in Peggy Lemaux’s lab.

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The Eran Karmon Editor’s Award honors the memory of Eran Karmon, co-founder and fi rst editor-in-chief of the Berkeley Science Review. It is donated by the Karmon family, to be awarded annually to the editor-in-chief of the BSR. The BSR would like to thank the Karmon family for this generous donation.

by Angie Morey


a tour of the Golub antique microscope collection

ACTION figures, dolls, coins, stamps, baseball cards—hobbyists collect all kinds of things these days. But if you’re Orville J. Golub your hobby is anything but typical. Golub, a graduate of UC Berkeley’s doctoral program in Bacteriology (PhD 944), has

been collecting microscopes of historic and scientific significance since the 960s. A testament to the centuries of scientific work that have preceded us, these relics are both fascinating and aesthetically beautiful.

ZOOM with a View

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For years, Golub’s collection was displayed in his house, viewable only to those who had the pleasure of visiting him and his wife at their home in Los Angeles. However, thanks to the generosity of the Golubs, UC Berkeley students, affiliates, and visitors can now view a portion of the glorious microscope collection here on campus. The Golub Collection, bequeathed to the Regents of the University of California by Dr. Golub and his wife, Ellina Marx Golub (BA 939), now rests in the Onderonk Lobby of the Valley Life Sciences Building. At last count, the collection contained forty-eight microscopes from the 7th through 20th centuries.

An affair beginsHOW does one ignite a love affair with microscopes? Like many of its kind, this relationship began as a consequence of circumstance. Golub entered graduate school in the Bacteriology Department at UC Berkeley in 937, a time that he concedes “seems prehistoric.” Perhaps not surprisingly, Golub’s teaching assistantship in bacteriology required the frequent use of microscopes. Gazing into the secret worlds of tiny bacteria became a pleasant daily routine. However, Golub’s routine was briefly interrupted when he was sud-denly called into active duty a year before America entered World War II. Having completed his graduate courses but

The Golubs in their microscope museum den.


1609 Galileo improves the design of the compound microscope with better glass polishing and finer focus ad-justment.

1590 Hans Janssen and his son Zacharias Janssen claim to invent the first compound microscope, introducing a second lens for increased magnification.

A single piece of glass, thicker in the middle than around the edges, comprised the first “lens”, so-called because of its lentil shape.

A Brief History of Microscopy

1670-1680 1750-1800

c. 1745

not the research required for his PhD, he was fortuitously assigned to work in the US Navy Research Unit on the 5th floor of the Valley Life Sciences Building under the guidance of his graduate advisor, Dr. Albert Krueger. Golub worked with the Navy Research Unit throughout the war, managed to complete his thesis on the influenza virus, and was awarded his PhD in 944.

After the war ended in 945, Golub accepted a position in the Virus Division at Fort Detrick, Maryland, which was then the headquarters for the government’s work

on biological warfare with Army, Navy, and civilian scientists. While there, Golub became friends with three other men who, after a couple of years, were anxious to apply their skills and innovative minds to something new. Their common desire to explore ideas without the red-tape rigors of working for the government led to the development of a Los Angeles-based company called Bio-Science Laboratories in 948. This was not your typical 940s lab, but rather an innovative and progressive reference clinical laboratory. While many clinical labs

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A. Guillaume Menard box microscope (probably from France) B. John Cuff compound microscope (England) C. Simple brass microscope (origin unknown)

1674 Anton van Leeu-wenhoek creates a powerful single-lens microscope by in-creasing the curvature of the glass.

1826 Joseph Jackson Lister (whose son pioneered anti-septic technique) perfects the achromatic lens, reducing both chromatic and spherical aber-rations.

1931 Ernst Ruska builds the first electron microscope. Image resolution is now lim-ited by the wavelength of electrons, rather than visible light.

1757 John Dollond com-bines two types of glass to create the first achromatic lens.

1674 Anton van Leeu-wenhoek creates a powerful single-lens microscope by in-creasing the curvature of the glass.

c. 1840

c. 1890

1905

performed standard laboratory procedures, Bio-Science Laboratories took the task a step further by carrying out new research and publishing frequently in the scientific literature. The Laboratory rose to be a leader in the clinical field and was called upon by doctors and hospitals both nationally and overseas to perform procedures such as hormone, toxicological, and chromosomal analyses as well as bacteriological and immunological assays. Although most of these procedures are commonplace in the medical field today, Golub reminds us that “lab life was different

back then” and these now-common procedures required a specialized laboratory, a niche for which Bio-Science Laboratories was perfectly designed.

Continuing with their trend of originality, the company began to build a collection of old laboratory equipment for the aesthetic enjoyment of their clients and employees. They envisioned that this collection would include blood counting equipment, balances, glassware, specialty books, and microscopes. As avid travelers, Golub and his wife were already accustomed to acquiring laboratory relics on

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D. Chevalier universal microscope (France) E. W. Watson & Sons of London compound microscope (England) F. Leitz compound microscope (Germany)

Ruzin sometimes imagines “what the original owner must have thought and felt when they used the instrument .”


their trips to Europe. For this reason, collecting mementos for the Laboratory’s collection was merely an extension of their chief diversion. However, as the “lab equipment” collection grew, it soon became clear that the pair was showing signs of favoritism for the microscopes. One of Golub’s partners noticed this trend and suggested that he “try to get more variety.” As the Laboratory’s collection neared completion, Golub approached a crossroads. He could either put his collecting career to rest, or continue in his keen pursuit of rare relics. Not one to deny his passions, Golub’s choice was simple. He “had fallen in love with old scopes” and decided to pursue his penchant for collecting with full force.

Collecting microscopes in the 960s, before the advent of eBay or Google, required more than just a few clicks on the Internet. Fortunately, on their many vacations abroad, the Golubs had established the connections necessary to acquire rare specimens of historical and scientifi c merit. Alain Brieux, a Parisian dealer of scientifi c antiquities, was one such connection who became instrumental in the expansion of the Golubs’ personal microscope collection. Th e Golubs also made purchases for their personal collection from other private dealers, as well as from Sotheby’s and other auction houses both in the United States and Europe.

By the late 960s the Golubs had amassed a substantial

number of microscopes. Luckily, the Golub family had a sizable home near the University of California, Los Angeles and the time was ripe to create a dedicated space for their prized microscopes. Th ey hired an architect to redesign two spare rooms, one of which Golub had been using as a dark-room to develop his own photographs. With fi ve children, Golub recognized that he “couldn’t do both—develop pictures and have a room for an extensive microscope collection.” In the end, the dark-room was sacrifi ced for what could best be described as a “museum den”. Th e room’s museum-like features included walls

lined with glass shelves containing the growing collection of instruments, illuminated on one side by natural light from an overhead skylight. Th e room’s den-like features included comfortable chairs, an entertainment system, and a variety of books on optics and microscopy stacked on the shelves of an antique bookshelf. With a proper home for his microscopes, Golub continued collecting microscopes even after his retirement from the Laboratory in 980. In 995, through discussions with then-Chancellor Ira Michael Heyman, Golub arranged to donate part of the collection to UC Berkeley, to be housed in a special case in the Valley Life Sciences Building. It is here that the collection remains and continues to grow. Since its establishment, Golub has added microscopes to the collection and plans to make other donations in the near future.

The collection’s curatorSINCE their arrival on the Berkeley campus, the remark-able Golub microscopes have seen several curators—but none quite as attentive and talented as their current caretaker, Steve Ruzin. Ruzin is fueled by both a gift for gadgets and machinery and a long-standing fascination with microscopes. A photo of twelve-year-old Steve with his fi rst microscope eerily predicts his future as a scientist and innovator in the world of microscopy.

Ruzin’s aff ection for microscopes has found a perfect fi t here on the UC Berkeley campus. He not only serves

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A life-long passion appears early: 12-year old Steve Ruzin (far right)

poses with his fi rst microscope.


as curator of the Golub Collection, he is also director of the College of Natural Resources Biological Imaging Facility, which functions as an instructional and research laboratory for all aspects of modern biological light mi-croscopy and computer image processing and analysis. In both arenas, Ruzin has been characteristically attentive and detail-oriented. In curator mode, Ruzin takes apart, cleans, reassembles, and photographs each microscope. He is continually astonished by the microscopes and loves “being able to hold and study instruments that were used by some long-deceased scientist.” As he selects one mi-croscope each month to be showcased as the Microscope of the Month (MOM) on the collection’s website (mi-croscopy.berkeley.edu), Ruzin sometimes imagines “what

the original owner must have thought and felt when they used the instrument to look at specimens they knew nothing about.”

Hands-on experienceAS IF their presence alone were not remarkable enough, these noteworthy relics of our scientifi c past have found a place in the classroom due to the ingenuity of Steve Ruzin and bioengineering professor Daniel Fletcher. “Bringing the scopes into the Principle of Optics and Microscopy course provides students with a rare and wonderful opportunity to apply textbook and classroom lessons to a real analysis of historically relevant microscopes.” Fletcher goes on to describe the main project for the course. “Th e students work together in groups to care-fully analyze the functionality of their selection from the Golub Collection.” Like photo albums made by proud parents, the students’ fi nal projects include pictures of their microscopes, descriptions of their magnifi cation power, as well as photographs of images produced by their microscopes.

Th e students’ ray diagrams, focal length estimations, and magnifi cation calculations are a beautiful display of education at its best. Th anks to Golub, Ruzin, and Fletcher, the collection’s microscopes continue to play a role in twenty-fi rst century science. And while researchers from eras past may never have imagined the work that would be done in subsequent centuries, they would likely be pleased that their microscopes are not just gathering dust; instead, these instruments participate in a living sci-entifi c legacy, touching and shaping the minds of future innovators.

ANGIE MOREY is a graduate student in the psychology department’s program in cognition, brain, and behavior.

Want to know more?Visit the Golub collection online at golubcollection.berkeley.edu

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Students in Dan Fletcher’s Optics and Microscopy class experience the

Golub Collection hands-on.


As a magazine devoted to science on campus, we were pleased to hear the university has a scientist at the helm. How do you balance your roles as researcher and university administrator? First of all, I have to tell the truth; it is diffi cult to balance it all. I get paid to be a chancellor and previously as a president and that’s what I do most of the time. But I have managed to maintain a research laboratory. Frankly, that has rested strongly on having really talented postdocs.

What questions do you pursue in your scientifi c life?Fundamental questions in materials physics. Th ese days, the two main areas we work on are high-temperature superconductivity, which remains unsolved after nearly 20 years, as well as something very diff erent, which is soft condensed matter physics. Th is involves looking at the physical properties of liquid crystal materials in unusual environments.

Physics pop-quiz: can you give us a layman’s defi nition of the word “smectic”?Smectic derives from the Greek word “smegma”, which means “soap”. Smectic liquid crystals are materials which

function like soap—that is, they form layers. Th e way that a detergent works is that the molecules form a fi lm, then the fi lm surrounds the dirt particle and carries it off , so detergents are examples of smectic liquid crystals.

In addition to being chancellor, are you an offi cial member of the physics department?Yes, my appointment as professor of physics has been approved. I went through the same process that everyone else goes through. I’ve already identifi ed an offi ce for myself over in Birge, which is currently being cleaned up, as well as a couple of rooms which will become my laboratories. I also anticipate doing some work up at LBL.

An article in the San Francisco Chronicle a year or so ago claimed that the physics deparment was in “genteel decline,” and was losing talented physicists to private universities. As a physicist yourself, do have any special plans to keep the physics department competitive?First of all, as chancellor it would be inappropriate for me to interfere in the workings of individual departments. Let me just say that, generally, departments go through peaks and valleys. Part of a department’s normal evolution is to have people who achieve a phenomenal level, as they did in our department here at Berkeley, who then mature and are replaced. I think the review [you refer to] was done in the middle of a transition period for the department. Recently, [the department] has hired a number of really talented young people doing nontraditional kinds of research that I think will help reestablish the preeminence of the physics department.

Additionally, I knew the two [researchers that the department] lost personally from my research life, and they left in good part because of limitations in the facilities here on campus for the kind of research they were trying to do. Th e new facilities which we hope to build during my time as chancellor should help to solve that problem. Th ese facilities include new, low-vibration laboratories – the kind of modern laboratory space that you need to do state-of-the-art research – especially of the sort that they were doing, which was in the nano fi eld and required extreme delicacy and extreme stability.

Public-private partnerships seem to be a new trend in public university research. Some of these partnerships,

Meet the Chancellor The BSR puts the Birge back in Birgeneau

The arrival of the University’s new chancellor last September was greeted with much fanfare; less well-publicized was the fact that our new administrator-in-chief is a pre-eminent physicist. In an interview earlier this spring, Tracy Powell and Steve Bodzin asked Chancellor Birgeneau to step aside, giving Professor Birgeneau a chance to weigh in on topics ranging from stem cell research to the state of the physics department.


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How do you address fears that this research will advance an era of human cloning or germline modification? Do you have any personal ethical guidelines that you’ve developed as a result of your particular experiences as a scientist?These are very complicated issues, so of course we all have our own ethical values. I think that in the particular case of a person who was going to use stem cell research very directly to try to clone a human being, then we would reject that. On the other hand, you can’t stop the progress of science just because some person out there may try to use the results of science for an unethical reason; it’s just not possible.

How optimistic are you that the aims of Proposition 71 will be successful?In the long run, I’m very optimistic. I happen to have some motivations for this. One of my close friends, a great physicist in my field, died of Lou Gehrig’s disease last year. I watched him deteriorate over a two-year period and he kept doing research until almost the last day. It was amazing, and it was courageous on his part that he would refuse to give in, but it’s a horrible thing to watch. As you know, this is a neurodegenerative disease for which stem cells may offer a promise, and so one only needs that kind of personal experience [to be convinced] that we really must go forward with this kind of research. Is it 5 years or is it 10 years… you’re a biologist, you can probably count better than I can! But certainly this is a very promising approach and we need a breakthrough for neurodegenerative diseases. We must have a breakthrough.

TRACY POWELL is a graduate student in plant and microbial biology. STEVE BODZIN is a graduate student in journalism.

such as the Department of Plant and Microbial Biology/Novartis agreement a few years ago, have received heated criticism. Do you have any personal perspectives on this trend?Yes I do. Strong ones, actually. First of all, if you look at the amount of research funding that comes from the private sector in universities, it is phenomenally small, so this [trend] has been greatly exaggerated. Number two, although people often don’t think of it this way, I view it at least in good part as a matter of academic freedom: if there is an investigator who wants to do a particular kind of research, and some private donor is willing to fund that research, then it is that person’s right to accept that money. [While others may] have a particular view of what a public university should be, I think that for them to try and prevent that person from doing that research violates that person’s academic freedom.

Congratulations on your appointment to the stem cell advisory board created as a result of Proposition 71. As a physicist, not a biologist, what is your role on the advisory committee?(laughing) Actually, there’s also a real estate person on the board. As you can imagine, anyone who’s ended up as a chancellor has a lot of experience with the organization of research. I have chaired Department of Energy panels that oversaw very large amounts of money—amounts of money comparable, actually, to the stem cell money. So I know a fair amount about the organization of research, and it’s really that part of it which our panel will be responsible for. Our panel will review reports by expert sub-panels from the outside; those are the people who will make technical judgments where you would have to be a biologist or a medical doctor or a life scientist of some sort.

Much of the debate surrounding Prop. 71 concerns ethical dilemmas posed by stem cell research. As an advisory board member, what role will you have in ethical guidance?I think overall that our board will be responsible for making sure that research is carried out ethically [and] that there are not egregious violations of ethical standards. We already know that a particular approach to ethics has resulted in the federal government extremely constraining this area of research. We’re fortunate to be in a state with a broader viewpoint, in which the issues of human health are balanced against particular viewpoints that some people have about the origins of human life. I think we’ve gotten the balance right in California with this initiative.

LTHOUGH malaria infects hundreds of millions of people each year and kills an estimated 1.5 million, most of whom are children, a majority of these cases could be cured by combination therapy involving the drug Artemisinin—a naturally

occurring compound extracted from the sweet wormwood plant. Unfortunately, sweet wormwood takes six months to grow to maturity, and the extraction of Artemisinin is a laborious process that itself takes several months. It seems incredibly frustrating that nature has provided the cure to this terrible disease but hidden it in such an expensive and out-of-the-way place. Why couldn’t the required chemical precursors be produced by a fast-growing lab bacterium like E. coli? That way the drug could be produced cheaply and quickly. Most of us might shrug our shoulders and go back to the hunt for sweet wormwood, but Jay Keasling, UC Berkeley professor of chemical engineering, and a whole community of like-minded researchers think differently. Rather than settle for the organisms nature provided, Keasling’s group created an organism to do exactly what they wanted. Starting with E. coli, they began adding the genes needed to make Artemisinin: first a pathway of genes

from S. cerevisiae (beer yeast) and then another critical enzyme, and just like that they had bacteria that produced the desired precursor. Seems like a good idea, doesn’t it? It seemed like a good idea to the Lawrence Berkeley National Lab as well: they created a whole department to encourage this kind of thinking.

The recent creation of the Synthetic Biology department at LBL, headed by Keasling, places Berkeley at the center of a new discipline at the interface between the life sciences and engineering. Synthetic biology holds incredible promise for the solution of problems in power generation and global health, but it also raises concerns that may make fears about genetically modified organisms (GMOs) seem paltry by comparison. As usual, Berkeley will be right in the thick of it.

Putting the pieces back togetherSYDNEY BRENNER, 2002 Nobel Laureate for Physiology or Medicine, has famously declared this era “the end of the beginning,” suggesting that molecular biology, which began in earnest with the discovery of DNA as the genetic material and the understanding of the structural properties that allow it to serve as such, has entered a second phase. Because of the enormous progress of the last 50 years, we now have a

Intelligent

by Alan Moses

D e s i g nPlaying with the building blocks

of biology

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“parts list” for the cell—we have some understanding of most of the basic molecular processes and sub-cellular structures found in most living organisms—as well as the ability to obtain complete descriptions of the genetic material for virtually any organism in the form of genome sequences. A middle period in molecular biology has arrived in which we must begin to understand how these parts interact to form the complex systems that are living organisms.

Analogous developments occurred in the 1960’s and 1970’s as physicists began to realize that knowledge on increasingly subatomic scales could not solve such seemingly simple and practically important problems as weather prediction. It became clear that they had to study the complex behaviors that arise as the simple building blocks of nature interact; subsequent breakthroughs in the field that became known as nonlinear dynamics and chaos theory began to offer a more complete picture of these complex phenomena. It

is widely believed that molecular biology must follow a similar trajectory—to begin to put the pieces back together, finally producing a picture of the whole organism. Synthetic biology sees itself as a fundamental step in this process.

What’s in a name?SO WHAT exactly is synthetic biology? Invariably, when a new discipline or department is created, it faces pressure to define itself. Otherwise, people might question why, in these days of tight university budgets, a department is being created to study something they’ve never heard of. Furthermore, synthetic biology must differentiate itself from new research institutes and departments that are already springing up under the auspices of “systems biology”, on the one hand, and more established departments such as bioengineering on the other.

Perhaps it is too early for us to define the scope of synthetic biology and to know whether ultimately it will carve itself a niche, but broadly speaking, we can say that synthetic biology aims to develop tools and methods to create biological molecules and cells for practical purposes. It takes what we’ve learned over the past fifty years about the constituents of life and attempts to use it to solve practical problems.

D e s i g nA Nobel laureate has famously declared this era as “the end of the beginning” in molecular biology.


Synthetic biology strives to combine (or synthesize) large amounts of disparate knowledge. As Keasling summarizes,

“Biology has done a great job of breaking things into pieces, but there has been less success in putting them back together.” Like advocates of systems biology, Keasling and Graham Fleming, director of the Physical Biosciences Division at LBL, under which the new department was created, use metaphors from electrical engineering. They liken cells to circuits, and suggest that we must shift our focus from defining basic biological “transistors” and “capacitors” to understanding the way they interact so we can understand the behavior of the whole computer.

Synthetic biology goes even further than other similarly holistic disciplines such as systems biology. Keasling emphasizes that in synthetic biology the focus is not just on understanding the way the parts interact, but on using that understanding to help molecular biology become what Keasling calls an “engineering discipline” that’s “focused on applications.” Keasling argues that synthetic biology is much more specific than systems biology, focused more at the cellular and genetic level, although he admits that some research that now falls under bioengineering might also be called synthetic biology.

Fleming suggests that “synthetic” is to be taken in all its meanings. Another, perhaps related, meaning is “synthetic” as in “synthetic chemistry”, where researchers literally synthesize more complicated compounds from their simpler, more available components. Thus, a goal of synthetic biology is to synthesize new organisms from a set of existing, well-understood components. Projects of this kind, such as the “BioBricks” project at MIT, are well underway. This project aims to characterize a number of biological building blocks—to understand their properties as completely as possible. Once this is done, these BioBricks will be available to be combined into larger and more complicated systems, and we can be confident we will understand their behavior. A future scientist will just choose the BioBricks and have the organism made to specification. These projects will form the fundamental tools that the synthetic biologist might use.

“As the name suggests, the bricks are to provide a foundation,” says Fleming. Just as a chemist might decide to create H2O by combining H2 with O2, a biologist might create a free-living

cell by combining a cell membrane BioBrick and a DNA sequence BioBrick with the BioBricks for transcription and translational machinery. This seemingly simple scenario is far beyond today’s capabilities. While the genetic material of some model organisms (like E. coli and S. cerevisiae) can be routinely altered, the creation of an entirely new living thing has never been accomplished.

This possibility raises perhaps the most exciting and con-troversial aspect of the name: the sense in which synthetic means artificial. Although not artificial in the way that syn-thetic fabrics mimic the properties of cotton or silk (these could be referred to as biomimetic, according to Keasling), synthetic biology has its sights set on synthesizing living sys-tems that are artificial in the sense that they have never ex-isted in nature. By combining the tricks that many different organisms have developed throughout the course of evolu-tion in a rational way, we will be able to generate organisms that perform functions not seen before. As with GMOs, the impact of synthetic organisms will be felt strongly in fields such as agriculture, where crops can be designed for pest or weather resistance. Synthetic organisms, however, can go much further. According to Fleming, one of the major reasons for the creation of the department at LBL was the incredibly exciting potential of synthetic biology “for im-proving human health and developing new ways to supply energy.” Projects of this scope attempt to develop bacteria that are redesigned to produce pharmaceuticals or swim to a tumor cell and destroy it, or synthetic viruses to be used

The creation of an entirely new living thing has never been accomplished.


as HIV therapy. Although such “made-to-order” organisms may seem far in the future, projects like these are already un-derway in labs such as Keasling’s at LBL and on the Berkeley campus.

Long-term goals for synthetic biology approach science

fiction: researchers supported by the Department of Energy at the Venter Institute (headed by Craig Venter, who led the private-sector effort to sequence the human genome) are trying to develop a synthetic organism to efficiently pro-duce hydrogen as a fuel source in a totally renewable way. Although an incredibly difficult challenge, according to Ke-asling, this type of project is the sort that synthetic biol-ogy should be aiming at—one that would revolutionize the way we think about harnessing the potential of living things. In addressing how long it will be before such advances can make an impact on daily life, Kristen Balder-Froid, the Divi-sion Deputy of Planning and Strategic Development for the Physical Biosciences Division at LBL, points out that what will ultimately determine the time before such organisms are commonly used is what sorts of regulatory bodies they must pass—and that is very difficult to tell at this point.

Regardless of how near in the future the applications of

synthetic biology might be, it is clear that the idea has been gaining momentum. To get a sense of how quickly synthetic biology has been developing, we can take a look at the short history of the discipline. Although the ideas and research projects connected with synthetic biology may have been around for some time, along with the creation of the first department (at LBL), the first-ever conference on synthetic biology was held at MIT this year. According to Fleming, the decision to create a new department at LBL came out of the realization that there were already a number of research labs doing synthetic biology on campus, though they may not have used the term. Creating the new department allows Berkeley to take advantage of the lead that it already has in the area as well as to recruit additional funding and faculty. It will also help focus efforts by creating a community in which the various groups can interact. Indeed, excitement in the area is still mounting, and although it’s not official yet, Fleming hints that another synthetic biology center or department affiliated with the Berkeley campus is already in the works. There have also already been several seminars on campus sponsored by the QB3 Institute, a California research initiative in quantitative biology, to help focus attention on exciting work in synthetic biology that is going on at Berkeley and elsewhere. Seminar speakers have ranged from UCSF’s Wendell Lim on reprogramming cellular switches to Harvard’s George Church on new methods for ultrafast DNA sequencing.

Escaping from the lab: fear and riskIN ADDITION to capitalizing on this growing momentum and excitement, the formation of the new department also allows researchers and funding agencies to coordinate their public information efforts. Technology that seems poised to alter the way we look at life itself raises many concerns both with respect to safety and also the social and political consequences of such advances. For example, Keasling points out that the synthetic biology department plans to work with the Goldman School of Public Policy and hopes to create programs to educate its scientists about public policy, to educate policymakers about science, and to educate the public about both. The importance of such a strategy cannot be overstated, particularly in the midst of public backlash against the use of GMOs in the agriculture industry. From the public’s perspective, when designing organisms, we must realize that we may be creating life forms that God and/or evolution never dared, or—worse—never dared again. Given public concerns about safety and ethics, strategy about the areas on which synthetic biology



should focus research will be crucial if the new discipline is to flourish.

One main area of concern is the potential environmental impact of newly-designed organisms. Could synthetic organisms escape and infiltrate the natural world? Keasling argues that completely synthetic organisms really don’t compete well in the wild—even the most successful experimental strains are usually pathetic compared to their natural counterparts. Synthetic organisms that are released either accidentally or for specific purposes would most likely die once out of the comforts of the laboratory. Keasling imagines synthetic organisms growing in controlled environments and used for specific tasks.

Although these answers may seem sufficient for now, if synthetic biology is successful and our ability to redesign organisms improves, our current ineptitude can’t be regarded as a very reliable safety feature. If we are eventually to use these organisms for clinical or industrial purposes, we must fully address questions about safety and risk. Otherwise, synthetic biology may be unable to avoid a backlash similar to the one that has left the public demanding the labeling of genetically modified (GM) products or the outright

banning of GM foods in Europe and general uncertainty about whether GM crops might represent environmental dangers. As UC Berkeley anthropology professor Paul Rabinow, who teaches a course called Genomics and Society and spoke at the first synthetic biology conference this year, puts it: “Most people think this stuff is dangerous.” Indeed, recent elections have led to bans on GMOs in two nearby counties and groups advocating similar measures in five other counties—including Berkeley’s own Alameda (see

“Strange Fruit” on page 19 of this issue). Fleming suggests that the ethical and social issues raised

by synthetic biology might be more relevant than the safety ones. He imagines that regulatory committees would oversee the creation and manipulation of living organisms. Rabinow emphasizes that the synthetic biology community must keep these issues in mind if their technology is to have the broad impact that seems possible. This is particularly important in what he calls today’s “risk-averse” environment, and given that “Americans are into values” right now.

In order to improve public perception, Rabinow suggests that focusing on world health issues such as low-cost HIV remedies might be a wiser strategy than trying to break into the agricultural world, which is already rife with consumer skepticism toward genetically modified foods. “Monsanto was spectacularly stupid and arrogant,” says Rabinow, referring to the manner in which they sold the first genetically engineered plants and the way they presented the technology to the public. Rather than focusing on the artificiality of genetically modified crops, they should have focused on the universality of the DNA language that makes such manipulations possible. He further suggests that companies should think critically about the markets they consider: developing recombinant growth hormones to improve milk production during the current surplus of milk is bound to be perceived as big corporate science hammering the last nail in the coffin of already struggling milk farmers. Instead, efforts should be aimed at areas where unsatisfied demand exists—such as development of cheap medicines to combat infectious diseases in countries where current technology is unavailable.

Critics label this type of suggestion as “experimenting on the third world”—trying experimental crops or medicines in poor countries where people are much more likely to accept untested food or medicine because they are suffering. In general acknowledgement of such safety concerns, Rabinow’s presentation at the first synthetic biology conference was entitled “Assembling Ethics in an Ecology of Ignorance.” Nevertheless, given the staggering numbers of people

Rather than simply tinkering with the organisms that nature has provided, we can begin to combine their parts in radically new ways.

suffering from diseases like AIDS and malaria, if progress is to be made, certain risks must be taken. He argues that we simply cannot foresee all the possible risks associated with a new discipline—especially one with the potential of synthetic biology. The attitude that all possible precautions must be taken, he claims, is untenable—we can’t possibly know all the ramifications of any given technology, and we just need to learn to accept that fact.

He also claims that the concerns about whether foods or medicines are natural will fade. Agricultural plants have always been manipulated and domesticated by humans—they haven’t been natural for thousands of years. Rather than thinking of synthetic biology as artificial, or unnatural, he likens it to the creations of chef Alice Waters of Chez Panisse, the Berkeley eatery credited with starting the culinary revolution now referred to as “California cuisine”. Ingredients native to environments from all over the world are taken out of their historical geographical context and grown organically, in a controlled way, in California and then combined in radical and delicious concoctions that were never previously imagined. Rather than focusing on the unforeseen consequences of combining the Laurus nobilis (native to the Mediterranean and Turkey) with a variety of Fortunella (originally East Asian), we can celebrate the triumph of human ingenuity and serendipity that brought both of these to California to create a bay leaf-scented panna cotta with candied kumquats.

What hath man wrought?CLEARLY synthetic biology raises all the same difficult safety and ethical issues GMOs do, and unfortunately it actually adds a new element of fear—human malice. If synthetic biology is indeed to be an engineering discipline, we need not only fear the unintended consequences of organisms modified slightly for benefit but also the whims of people or governments designing organisms with the intent to cause harm. Sensationalist fears in this direction have already been expressed. Following the same electrical engineering analogy to a perhaps inevitable conclusion, a news story on Slashdot.org, a technology news web site, suggested that once biological systems could be “programmed” we might see “biohackers” or maybe even “biospammers.” Synthetic bacteria could give us a cold and then spell out the name of a cough-syrup brand in green fluorescent protein.

The real risks of synthetic biology are probably much less exotic. For example, Keasling points out that in the past few years a milestone has been reached: technology now ex-ists for the rapid, cheap synthesis of long pieces of DNA.

While this may sound innocuous, according to Keasling “this means that it is easy to get copies of entire genes, or groups of genes, or even a virus.” Combined with the fact that molecular biology can be done relatively cheaply and without too much specialized equipment—“in a garage,” says Keasling—one could imagine the potential for danger if such technology falls into the wrong hands. Nevertheless, even with the availability of such technology, Keasling feels that the likelihood that it could be used for malicious pur-poses is very small: “it’s much easier for terrorists to get a truckload of fertilizer than to genetically engineer a bacteri-um.” Terrorists have shown that they can inflict damage and destruction with box-cutters and airline tickets—they don’t need to resort to advanced technology. Molecular biology is still too complicated and difficult to do without an enor-mous amount of technical skill and specialized knowledge. Nevertheless, individuals with the right combination of skill and intent are out there—one only needs to remember the envelopes of anthrax spores mailed to terrible effect in 2001. Rabinow reminds us that the potential exists for “one jerk…to spoil it for everyone,” and that scandal-mongering and malicious intentions are out there.

Rabinow suggests that synthetic biology follow the example of the self-regulation that was imposed by scientists during the first experiments with recombinant DNA. Nearly 30 years ago at the Asilomar conference center, just south of Monterey, scientists came together to discuss the safety and social issues surrounding their work on recombinant DNA, the first “genetic engineering.” Although the moratorium that was eventually imposed is now regarded as overly cautious, the attitude of self-regulation and caution is a valuable example to new disciplines. Kristin Balder-Froid

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points out that even if scientists can’t predict the potential risks of new discoveries, at least they can now use the example of how to communicate seriously and openly about the implications

of their work. Keasling adds that such self-policing policies are being put into eff ect already. For example, Blue Heron, one of the companies off ering synthesis of long DNA sequences up to 40 kilobases, long enough to synthesize a coronavirus like the one that causes SARS, checks all of the sequence synthesis orders they receive against all known pathogenic sequences. Presumably a red fl ag would be raised long before SARS was ever synthesized.

Despite the risks and fears, the promise of synthetic biology (or at least cheap antimalarial drugs) seems hard to resist. Th e Bill and Melinda Gates foundation also liked Keasling’s approach: they donated $42 million for the development of bacterially-produced Artemisinin with the goal of reducing the cost of malaria treatment around the world.

At the very least, synthetic biology represents a new way of thinking about the way we do biology. Rather

than simply tinkering with the organisms that nature has provided, we can begin to combine their parts in radically new ways. Th e creation of a department of synthetic biology at LBL puts Berkeley at the forefront of this new paradigm. Lest we forget, though, Berkeley is not only a center for groundbreaking research; it’s also home to social activism and liberal skepticism about the aims of big corporations and government. With that duality in mind, synthetic biology, unlike the biotech revolutions of the previous decades, seems to be proceeding with due deference to both the worst fears and the most noble dreams of the community. Perhaps as we ponder the magnitude of the act of synthesizing a completely new life form for the fi rst time, we might realize that we would not have it any other way.

ALAN MOSES is a graduate student in biophysics.

Want to know more?Visit the LBL Synthetic Biology Department online:www.lbl.gov/pbd/synthbio

The Keasling Lab website: www.cchem.berkeley.edu/jdkgrp

The BioBricks website: parts.mit.edu

It’s not easy to get high school students interested in science, especially in Cali-fornia, where student scores on standardized tests are among the lowest in the US. But imagine high school students spending their Sat-urday mornings using the laws of thermodynamics to design a machine that can crush a cupcake, or engi-neering buoyant shoes that can support a person walk-

If you would like to bring your knowledge and

enthusiasm to CalSci, please contact Steve

Andrews at sandrews.berkeley.edu

CalSCI...get involved!

ing on water. The CalSci Academy, part

of the Environmental Sci-ences Teaching Program (ESTP) at UC Berkeley, gives Bay Area high school stu-dents the chance to engage in hands-on projects that combine creativity with practical science. UC Berke-ley students work together to develop and apply an innovative curriculum to support and engage high-

schoolers in science. The program, run by Program Coordinator Steve Andrews and Professor William Berry from the department of Earth and Planetary Science, off ers undergraduate and graduate students the op-portunity to be both men-tors and teachers. —Pamela Han and Rachelle Callenback

of thePrisonerS

IVORYToweR

by Loren bentley

Serving Five to Life in Academia


“HOW much longer do you have?” It’s the question every graduate student dreads. Whether it’s parents, friends, or new students, nobody seems to realize how much that question hurts, or, for that matter, how hard it is for graduate students to pin down the answer. Real statistics are not well-advertised, so most students don’t know the average degree time, or even the percent of students who actually graduate. Besides this, the distribution seems so broad, it is hard to know if they will follow in the footsteps of the legendary tenth year, or replicate the feat of the whiz that finished in three-and-a-half years and already has a job.

Although many people have the vague idea that a PhD is a roughly five-year endeavor, the actual time required to complete a doctoral degree is almost always longer. In 2003, the median number of years between enrollment in graduate school and completion of the doctoral degree (elapsed time to degree, or ETD) in all fields in the US was 7.5 years.

The national median in the physical sciences (including mathematics and chemistry) was 6.8 years; in engineering it was 6.9 years, and in the life sciences it was 7.0 years. The typical time to degree for the humanities and social sciences is longer, and nationwide, the length of all graduate degrees increased steadily during the late twentieth century. The median registered time to degree (RTD or the time a student is registered in a graduate program) in the United States for students completing their degrees in 97 was 5.7 years, but by 99 it had climbed to 7.0 years.2,3

At Berkeley, the Graduate Division keeps track of each student in a database known as the “Monster” file, which goes back to the 960s. Berkeley’s average RTDs are shorter than the national averages, but still nowhere near five years. In 2004, the average RTD in life sciences was 6. ± 2.3 years; in physical sciences it was 5.7 ± 2.0 years; and in engineering it was 5.8 ± .8 years. Mary Ann Mason, the Dean of Berkeley’s Graduate Division, expresses the concern many feel about how long it takes to get a degree, noting, “It’s expensive in time and money for the student and for the University if the time line is too long.”

Of course, the story these statistics tell isn’t as clear as it appears at first glance. It is difficult to incorporate data about slow finishers and students who drop out. Many databases

only track students who complete their degrees, making it difficult to measure attrition from doctoral programs, which is itself a severe and complicated problem. Also, the length of graduate programs is often reported as the time between the awarding of the bachelor’s degree and the awarding of the doctoral degree (total time to degree, TTD)—roughly three years greater than RTD. Even after accounting for these factors, the statistics can be interpreted in different ways. The 988 Survey of Earned Doctorates conducted by the National Opinion Research Center (NORC) reported that TTD had increased by approximately 30% over the preceding twenty years. But a subsequent study found that the decreasing number of PhDs awarded over this time created a statistical bias and possibly more public concern than the issue may have warranted. Calculating time to degree based on entering, rather than graduating, class showed a more accurate—and still significant—increase of 0% over the same twenty year period.3

Happily for most, the trend has begun to level off, particularly for students in the sciences and engineering. According to the 2003 national survey, the median TTD was 0. years, or three months shorter than in 998.

How long should it take?SO HOW long should a PhD take? The Association of American Universities was formed in 900, and by 96 was already questioning the ideal duration for post-graduate study, proposing three years as an appropriate length. This number had not changed much by 964, when the Association of Graduate Schools and the Council of Graduate Schools issued a joint statement that a PhD program should take

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three, or at most four, years.3 This sounds great to today’s graduate students, who have had to come to terms with much longer degree times. This author’s informal survey of current Berkeley students in one graduate program showed that most think five years is the ideal RTD and six years is too much. Mason posed five years as the ideal time to degree in the sciences and engineering, and six years in the humanities and social sciences.

Many graduate students have heard that doctoral programs in other countries take years less than those in the United States. The US system was originally modeled after Germany’s, albeit with a more structured program and curriculum. The German degree is designed to take around three years, though time to degree has increased there, too.4 In England, the Doctor of Philosophy degree (DPhil) requires a minimum of three years of research. According to Oxford University’s web site, DPhil students must complete a thesis based on research, “of a kind which might reasonably be expected of a diligent and competent student after three or at most four years of full-time study.” This sounds attractive compared to the US system, but it is difficult to directly compare the systems since undergraduate education is so different; for example, German and British undergraduates focus on a specialty immediately.

But according to Dan Fletcher, assistant professor of bioengineering, who received a DPhil from Oxford as well as a PhD from Stanford University, there can be “more efficiency and less frustration in British versus US PhD programs.” He notes that the Oxford program was more structured, with a progress assessment after the first year involving both an oral exam and a plan for finishing thesis research in the remaining two years. In the US system, he says, it is possible to work on your degree until “every last ounce of interest in pursuing this field has been squeezed out of you.”

Winners and losersIF EVERYBODY thinks shorter is better, why does time to degree keep increasing? One reason is obvious: the longer you’re there, the more you learn, the more research you do, and the more productively you do it. Thus, adding a year

on the end of a graduate program can significantly increase students’ output in terms of research and publications, ben-efiting both them and their advisors. Of course, students also have reasons for wanting to get out quickly, but surpris-ingly, it is departments and institutions that may have the biggest interest in getting students out the door. Berkeley’s job is to produce graduates, particularly those who go on to notable careers. The faster they can do it, the more they can produce. Mason explains that time to degree is “often less important for the graduate student than it is for the institu-tion…there’s a good deal of expense and effort in training graduate students and the longer they stay, the tardier the payoff is in the sense that they are moving into the academic pipeline and continuing on with their careers.”

Without a doubt, long average TTD has broad repercussions. The recent summary of the Survey of Earned Doctorates by NORC noted its impact on “the faculties and administrations of the degree-granting institutions, as well as national public agencies and private organizations that support doctoral study.” This wasn’t news to the University of California. A feared shortage of PhDs in the 980s led the California State Senate to commission a study of the time

Suzanne Lee and Bosun Min, graduate students in MCB, are treated like

local wildlife.


to degree in the UC system by Maresi Nerad and Joseph Cerny, who was then Berkeley’s Vice Provost for Research. More recently, in 200 the UC convened a Commission on the Growth and Support of Graduate Education. Based on the anticipated undergraduate population and the needs of industry in California, the commission predicted a need for 40,000 new faculty by 200. Consequently, they set the goal of ,000 new graduate students in this decade. California is one of only five states in which graduate enrollment has declined—by 2% in the last decade—while nationwide enrollment has increased. Among the commission’s proposals to reach its goal was one to “expand current efforts to reduce the time graduate students take to complete their programs,” by monitoring progress closely, providing support services, and increasing student financial support.

Cerny, a professor of chemistry and former dean of graduate studies at Berkeley for fifteen years, feels that Berkeley’s current graduate program lengths in the sciences and engineering are reasonable for a top research institution, but are a factor in what he believes is the larger problem of the increasing time to the first job for scientists and engineers. Cerny was recently part of a committee to study education in his field, nuclear science. Their findings included the following:

“The median registered time from bachelor’s degree to

a PhD in nuclear physics or nuclear chemistry has been 7.0 years over the last five reporting periods (998–2002). Seventy percent of these PhDs then take one or more (almost mandatory) postdoctoral positions lasting an average of 3.3 years. Therefore, ten-plus years pass before the ‘typical’ nuclear science PhD has a first job. This is too long…We believe that the time to the PhD should be shortened to five and a half or six years.”5

Part of the problem, according to Cerny, lies in inadequate career advising: “Departments ought to be doing much more career advising as to what the typical jobs actually are.” Giving career guidance is not a high priority for many busy professors, nor are they often familiar with the many career paths their students could follow.

A 995 report entitled “Reshaping the Graduate Education of Scientists and Engineers” noted the 30% increase in time to degree in some fields and stated: “Spending time in doctoral or postdoctoral activities might not be the most effective way to use the talents of young scientists and engineers for most employment positions. Furthermore, because of the potential financial and opportunity costs, it might discourage highly talented people from going into or staying in science and engineering.”6

Mason also emphasizes the importance of decreasing the

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S O U R C E S : D I G E S T O F E D U C A T I O N S T A T I S T I C S 2 0 0 3 ( L E F T )U C B E R K E L E Y G R A D U A T E D I V I S I O N ( R I G H T )


time to first job. She noted that, more than graduate student time to degrees, “A bigger concern in this regard are the post-doc appointments, which tend to get longer and longer all the time. In the biological sciences it’s not uncommon to have a five year postdoc before your first job…That’s just elongating the experience for everyone, which can be very demoralizing, to be honest.”

Their fates in whose hands?THERE are a variety of opinions on who or what controls the time to degree. Asking a small sample of current PhD students at Berkeley whether the time they would take to complete their degree was within their control, responses varied from “it depends on my advisor” to “[it’s] managed by the individual.” The encouragement of their advisors and agreement on a research plan are both contributing factors. In general, students earlier in their programs felt they had less control, while students closer to graduation mentioned the effects of unexpected problems with experiments and difficulty maintaining focus. One student said, “There [were] way too many interesting projects that I wanted to do. A good portion of the projects aren’t thesis-related, but just too good not to investigate.”

When asked how students could influence their own completion times, Cerny advised that students “get into research as early as possible…figure out early what you want to do and start it.” He noted that in the Department of Chemistry, most students join a lab by the middle of their first semester. This has been true for the last half century, and, says Cerny, “Chemistry’s time to degree has been around 5.3 years for the past forty years.”

Good mentoring was described by Dean Mason as one of the most significant factors in graduate students’ academic experience. “For the graduate student, having a really good mentoring experience is probably the most important thing. And good mentors want to get them out…which means they’re really concerned about the welfare of that student as well.” A 996 study of former doctoral students supports

Mason’s belief, finding “that students’ aspirations to the doctorate are most affected by the relationship they have with their individual faculty research advisor.”7 For both men and women who left Berkeley before finishing their degrees, 54% cited a “lack of guidance from my advisor” as a factor in their decision to leave.7,8 In a multi-university study, interviews with faculty confirmed the lack of guidance, though the faculty view the problem from a very different perspective: their most common advising attitude was one of an open door without making any overtures.3

An important influence on time to degree is the unique set of mental and emotional challenges faced by graduate students. At Berkeley, 43% of the students seen at the Counseling and Psychiatric Services are graduate students, though they make up less than 30% of the student body.9 A survey by a Berkeley task force on Graduate Mental Health0 found that 45% reported emotional or stress-related problems within the past twelve months that had significantly affected their well-being or academic performance. 39% reported feeling frequently overwhelmed, while approximately 42% reported feeling exhausted “frequently” or “all of the time.”

Though personal or individual factors may determine where each student falls within the range of times to degree,

larger-scale institutional fac-tors—outside each student’s control—can have much greater influence on average times to degree. Funding policy is one of the primary institutional means of con-trolling time to degree. Other things being equal, students who receive fellowships or research assistantships have higher completion rates and shorter times to degree than students receiving teaching assistantships or fee waivers

or those who are totally selfsupporting.0 “It’s a matter of funding structure, and if you’re structured to finish in five and half years and then you’re cut off,” says Mason, “your professor is geared to giving you the appropriate project and to working more expeditiously with you.”

According to Mason, a good example of the influence of funding on graduation times occurred following her implementation of the Dean’s Normative Time Fellowship.

In the US system, it is possible to work

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found that in 993, PhD recipients whose programs ranked in the top quartile, “typically completed their studies more rapidly than graduates of lower ranked programs regardless of fi eld.”2 Another study found that, in general, better established programs of recognized quality and of smaller size had lower times to degree and higher completion rates. In an analysis of TTD in math and physics at three large (Berkeley, Chicago, Columbia) and four small (Cornell, Harvard, Princeton, and Stanford) universities, the larger programs averaged 6. years, while the smaller ones averaged 5.2 years (967-976 entering class). Th is study did not adjust for the fact that all the small schools cited were private institutions.3

Knowing is half the battleTHE CLARITY with which the guidelines for completing a PhD program are set out also infl uences time to degree.3 A lack of information is not just frustrating for the students—it actually increases the time to degree. One survey found that only 45% of the students responding said they had a very clear understanding of the criteria for determining when they would be ready to graduate. Similarly, only 3% said that they clearly understood the length of time they would be students.3

An informal survey of Berkeley graduate students in the

Th is fellowship is awarded in the Social Sciences and Humanities (where times to degree are longer, and funding less available) and provides dissertation funding for students who advance to candidacy within the time limit established for their program. Th e program has directly decreased time to advancement to candidacy for many students because they need to make quick progress to qualify for the fellowship.

Six institutional factors that infl uence time to degree were cited in the 99 study by Nerad and Cerny: degree requirements; teaching requirements and means of evaluating progress; faculty advising and departmental guidance; student fi nancial burden, fi nancial support and debt accumulation; campus facilities; and the availability of professional job opportunities and placement support. Not surprisingly, programs that require a dissertation prospectus and an early start on dissertation research have shorter times to degree. Further, programs that evaluate students’ progress annually and provide feedback have shorter times to degree. Teaching requirements also have an eff ect. At Berkeley, students teaching for more than three years average one year longer to graduate than students teaching less than three years.

Program quality is a factor that has consistently emerged as impacting time to degree. Th e 995 report, “Research Programs in the United States: Continuity and Change”

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The Usual SuspectSThere must be practical consequences when fewer than half of graduate students have a clear picture of when they’ll graduate. We wondered what they were, and set out to ask science graduate students at Berkeley one very simple question: “When are you going to graduate?” Here’s what they said.

Susan Parkinson (4th year PMB; top left): Next year. Steve Gross (4th year PMB; top right): I don’t know. Matt Prantil (2nd year Chemistry; bottom left): Um...I don’t know. So I got here in 2003...so like roughly Christmas 2008. Nathan Clack (4th year Biophysics; bottom right): Um...I think probably a year and a half.

Brad Prall (6th year Chemistry) May 2005 [cough attack]. Tomorrow? Dennis Wylie (3rd year Biophysics): Uh...I have no idea. Suzanne Lee (4th year

MCB): Hopefully in a year and a half, maybe? In theory? Emory Chan (5th year Chemistry): I don’t know. Probably, you know, a year or two. Why? Christine Stuart (3rd year Chemistry): Never. Rosalie Tran (2nd year Chemistry): I don’t know. Why? Dan Wandschneider (1st year Chemistry): What? From here? I don’t know. Philip Kukura (3rd year Chemistry): Are you recording this...so you can make fun of me when it doesn’t happen? Robert Blazej (5th year Bioengineering): Who wants to know? Nate Beyor (4th year Bioengineering): A long time. Why? Will Grover (6th year Chemistry): I’m not sure. I’m looking at December. Teris Liu (5th year Chemical Engineering): I don’t know. No idea. Nick Toriello (4th year Bioengineering): I don’t know. Later than you.


sciences found that most expected to graduate after a total of four to six years, or in other words, approximately the same amount of time they thought was ideal. Based on Berkeley’s statistics, a lot of them will take longer than that to graduate.

A little digging through departmental web sites at Berkeley usually yields one or two sentences about the duration of the program, often citing something like, “around five years.” Many programs list the “Normative Time” for their program, defined in Berkeley’s Handbook of Graduate Studies as the elapsed time students would need to complete all requirements for the doctorate, assuming that they are making adequate progress toward their degrees. But this is not necessarily the actual time required to finish doctoral studies, something only one program at Berkeley (Microbiology) states clearly on their web page for current and prospective students.

Molecular and Cell Biology is one of the few programs in which the expectation that students will complete their degrees in five years is clearly laid out in a schedule of thesis committee meetings and progress reports, but in other programs, expectations are communicated indirectly or more ambiguously. For example, the Biophysics Graduate Group implies the length of its program by stating that it guarantees only five and a half years of funding.

Where we go from hereTHOUGH many aren’t aware of it, the efforts of many institutions and national bodies are focused on improving graduate education, which includes decreasing the time to degree. But Mason points out that making these improvements is like shooting at a moving target: “Things do change so these questions can’t just be resolved once. Over the last ten years we have improved a little bit. It’s always a new set of faculty and a new set of students, so it’s a never-ending [situation].” For example, at this year’s first meeting, on January 9th, the UC Regents were presented with a detailed report on the importance of graduate education to California and the UC system—an effort to draw attention back to important issues that had been neglected since the work of the 200 Commission.

For the individual graduate student, whether taking courses, preparing for a qualifying exam, or planning the next experiment, it can be hard to see beyond the daily grind, but taking a step back and looking at the big picture can pay off. Studies show that awareness of graduation requirements,

actively seeking mentoring resources, writing a dissertation prospectus, and meeting with a dissertation committee can all help get the student out of the lab, into a cap and gown, and then onto the streets of the real world.

LOREN BENTLEY received her PhD in bioengineering from UC Berkeley. She took 6.5 years.

Want to know more? Check out the references, or see the book “On time to doctorate: A study of lengthening time to completion for doctorates in science and engineering,” available online at http://www.nap.edu/books/030904085X/html

How long will YOU be a graduate student?

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References

1. Hoffer, S., Welch, Williams, Hess, Friedman, Reyes, Webber, Guzman-Barron, Doctorate Recipients from United States Universities: Summary Report 2003. NORC at the University of Chicago, 2004.2. Summary Report 1996 Doctorate Recipients from United States Universities. National Academy of Sciences, 1998.3. Bowen, W.G. and N.L. Rudenstine, In Pursuit of the PhD. Princeton, NJ: Princeton University Press, 1992.4. Nerad, M., Preparing for the Next Generation of Professionals and Scholars: Recent Trends in Graduate Education in Germany and Japan. UC Berkeley, 1994.5. Education in Nuclear Science: A Status Report and Recommendations for the Beginning of the 21st Century. DOE/NSF Nuclear Science Advisory Committee Subcommittee on Education, 2004.6. Reshaping the Graduate Education of Scientists and Engineers. National Academy of Sciences, National Academy of Engineers, Institute of Medicine: Washington, DC, 1995.7. Humphreys, S. The Role of Women Graduate Students in EECS at UCB. in Bridging the Gap. Carnegie Mellon University, 1995.8. Kamas, L., Paxson, P., Wang. A, and Blau, R., PhD Student Attrition in the EECS Department at the University of California at Berkeley. Women in Computer Science and Engineering (WICSE), 1996.9. Prioritizing Mental Health, A campus Imperative: Proposal for a standing Academic Senate Subcommittee Addressing Student Mental Health. UC Berkeley, 2003.10. Ehrenberg, R.G. and P.G. Mavros, Do doctoral students’ financial support patterns affect their times- to- degree and completion probabilities? National Bureau of Economics Research: Cambridge, MA, 1992.11. Nerad, M., Doctoral Education at the University of California and Factors Affecting Time to Degree. University of California, Office of the President: Oakland, CA, 1991.12. Goldberger, M.L., B.A.Maher, and P.E. Flattau, eds. Research Doctorate Programs in the United States: Continuity and Change. Committee for the Study of Research Doctorate Programs in the United States, National Research Council (US), 1995.13. Golde, C.M. and T.M. Dore, “At Cross Purposes: What the experiences of doctoral students reveal about doctoral education.” The Pew Charitable Trusts: Philadelphia, PA, 2001.

LOW-CARB diets. Th e Da Vinci Code. Th at must-have Christmas toy that your little cousin just can’t live without.

If you doubt the power of fads, look no further.But how do fads start? And once they’ve started, how do they

propagate, infecting more and more people until they reach into every nook and cranny of society? In a November issue of the journal Physical Review Letters, a group of researchers working in California and France, including graduate student Th omas Gilbert of the Haas School of Business, describe how they teased apart the complex infl uence of word of mouth and advertising in the market.

Th e researchers investigated the sales trends of popular books on the online retailer Amazon.com. By looking at sale histories, they were able to trace how a book’s popularity spread through the “complex network” formed by the “social system of interacting buyers.”

Th ey found two very diff erent kinds of behaviors. Th e fi rst, termed an “exogenous shock,” starts when a book is given a large publicity kick from a newspaper article or from mention on a television talk show, for example. Th e sales histories of these kinds of books show a sharp spike followed by a longer decline in sales.

“Endogenous shocks,” on the other hand, result purely from word of mouth and a grassroots-up swelling. Th e sales histories of these books build up progressively until they reach a peak, and they then relax over a longer timescale than for exogenous shocks.

For both types of shocks, the scientists found that the data was best fi t by a model where each purchaser convinced, on average, one other person to buy the book.

Besides being of interest in marketing circles, the research may be important for those who study other types of complex networks such as the stock market or the chain of events that lead up to and follow earthquakes.

MICHELANGELO D’AGOSTINO is a graduate student in physics.

Read any good books lately?

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LETTER FROM

F rom where I’m writing, I can hear salsa music blaring from the street below me, it feels like the heat and

humidity are turned up to max, and somewhere in the distance roosters are crowing. Women braid each other’s hair on the balcony of the house across the street, and a canoe just pulled up to unload a shipment of chickens. It’s a typical day in Borbón, the town of about 5,000 people in northern coastal Ecuador that serves as the base of operations for my dissertation fi eldwork.

Th e Cayapas, Onzole, and Santiago rivers converge in Borbón, creating an urban center supported by forest logging. Sadly, the area is both a “biodiversity hotspot” and deforestation front; everywhere you look you see evidence of the booming logging industry. Huge logs fl oat down the rivers. Stacks of lumber ready for transport fl ank the roadsides. Men pile logs and planks of wood onto fl atbeds in town. Semis haul their loads back to Quito. Chainsaws hum. Borbón has the pulse of a frontier town—complete with prospectors, tradesmen, Indians, drugs, street justice, and missionaries. It’s not hard to imagine what the Wild West must have been like from this vantage point.

Before the recent construction of a road along the coast, the only way to reach the villages that dot these rivers was by boat. Th e umbrella research project that I am working with, funded by the National Institutes of Health and directed by Joe Eisenberg in UC Berkeley’s School of Public Health, is looking at the impact of road-building on the spread of infectious waterborne diseases in the region. I work with a team of researchers that includes 25 local health promoters from the study villages, three technicians from Borbón (the big city), an anthropologist and doctor and data entry staff from Esmeraldas (the really big city, a couple of hours south along the coast), a nurse and doctor and microbiologist from Quito (the huge capital city), and a gaggle of gringos who swoop in now and again to check on us and collect some data of their own. We spend our time traveling in dugout canoes to 2 communities scattered along the three rivers, asking the villagers lots of questions, and collecting their poop.

“Waterborne disease” is really just a euphemism for diarrhea. At dinner parties I usually use the former term

No need to worry. The local kids are keeping us safe with their karate skills.

to describe my work, since the latter either grosses people out or makes them giggle. Even though I work on these issues, I’m always shocked to know that diarrheal disease ranks as the third leading cause of death worldwide and is responsible for 9% of deaths in Ecuador.

Luckily, I don’t actually have to collect poop samples myself. Instead, for my dissertation project, I collect water samples and test for critters in the drinking water. My methods are actually quite simple—no two-photon microscopy or nanotechnology here, just old-fashioned water microbiology. I collect water samples and use various culture-based tests to determine the level of fecal contamination in the water. Given that these methods have been around for ages, it’s actually quite shocking that we still don’t know how to prevent the spread of waterborne disease.

From laboratory studies, we know a lot about the microorganisms that cause diarrhea and the biological mechanisms by which they cause disease. Th e trouble is that we don’t know much about how to control their transmission in fi eld-based settings. Th roughout the course of my research, I’ll be examining the quality of diff erent source waters, and comparing diff erent water storage and treatment techniques. My data on water quality will be combined with diarrheal disease outcome data from the larger study to explore how water quality aff ects people’s health. I’ll also compare how villagers perceive water quality at diff erent times of the year with what my petri dishes tell me about how safe the water is to drink.

Saludos Amigos,


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Th e most challenging part of my work is doing microbiology far away from any microbiology lab. Th e Fisher Scientifi c truck doesn’t deliver to Borbón, so I have to make sure I have everything I need before heading out to the fi eld and improvise whatever I forget. When I was fi rst testing out my techniques, a fellow graduate student and I set up a laboratorio clandestino in a hotel room, for lack of any other place to work in Borbón. (Somehow, I decided that locking myself up in a small room, sealing the windows, turning off the fan and turning on a fl ame when it’s 90 degrees with 90% humidity outside was a fun way to spend the summer.) We told the staff not to clean the room, but no doubt they peeked in to see the mattress propped up against the wall, the sheet duct-taped to the wall to cover the open windows, a table covered with fi lter fl ask, forceps, examination gloves, petri dishes, parafi lm, pipetters, etc. Gringos locos.

Now when I go out to villages along the rivers, I carry in the canoe with me a mobile lab to test for little critters growing in various water sources. Th e portable lab includes a “fi eld hood” to try and minimize contamination and my soon-to-be patented $0 incubator (they usually run around $3,000-5,000), made out of a bucket, a light bulb, a thermometer, and a dimmer switch. Who needs Fisher Scientifi c?

Th e other big challenge to overcome is knowing when people are giving you an honest answer versus telling you what you want to hear. One day I collected a water sample from a woman who told me that she treats her water with

chlorine AND boils it. When she off ered me a frozen coconut popsicle made from her water, I happily ate it, thinking it would be quite clean. 24 hours later whenE. coli bacterial colonies grew up on the plates of her water samples, I thought better of the decision.

But don’t worry, I’m staying safe and healthy and having a fun time. Especially with all the amazing salsa dancing at the Borbón discos.

See you soon, Karen

KAREN LEVY is a graduate student in environmental science, policy, and management.

Children often

help their parents

collect water and

bring it home (top).

I’ll be testing to see

what’s in that water

(right).

berkeley science review - spring 2005

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