Professional Documents
Culture Documents
science
review
Spring 2009 Issue 16
Lab on a chip
Artificial leaves
Green chemistry
%JHHJOHVQUIFQBTUt4QBNt)).*JOWFTUJHBUPSTtBorn to Be Goodt#FOEJOHMJHIUt#SBJONBHOFUT
BERKELEY DEAR READERS,
science Spring has arrived in Berkeley: the grass is growing, seasonal allergies are blooming, and a new
review Editor-in-Chief
issue of the Berkeley Science Review is here. This springtime weather has me thinking green (along
with the rest of the country), and thus I’m happy to unofficially dub this issue of the BSR “The
Green Edition.” Politicians are focusing on new plans for carbon taxes and caps, but here at Berke-
ley researchers are thinking about green in more creative ways. Photosynthesis, the original green
Rachel Bernstein technology, produces a tremendous amount of energy, and Tracy Powell explores how researchers are
investigating its mechanisms and applying those lessons to a new generation of solar energy panels
Art Director
(p. 16). Other groups are working to create power from more unlikely sources. One project is turn-
Tim De Chant ing up the efficiency for converting heat energy into electricity, as Jasmine McCammon describes on
Assistant Art Director page 6, and Susan Young’s brief, “Poo Power,” will tell you all about how microbial fuel cells can turn
organic waste into electricity (p. 13). With Berkeley’s own Steven Chu as President Obama’s Secre-
Victoria Wojcik
tary of Energy, it probably comes as no surprise that Berkeley researchers are working on alternate
Copy Editor energy sources, but going green also means decreasing the footprint of toxic chemicals we leave on
Katie Peek the planet. On page 27 Lee Bishop and Mitch Anstey write about a new green chemistry movement
taking shape on Berkeley’s campus. Even Hanadie Yousef’s archaeology feature uncovers sustainable
Editors farming techniques from Hawaii (p. 41).
Greg Alushin Does it sound like we’ve got green on the brain? Well, there are researchers looking into how
Dan Gillick our minds work, too. Colin Brown writes about a controversial technique that can induce temporary
Hania Köver brain lesions for both research and patient treatment (p. 23), and if you’ve ever wondered how all
those video games affect your intelligence, it turns out that some games can actually train your brain
Frankie Myers
and improve your IQ—Katie Hart has the full story on page 12. Finally, on our back page Louis-
Robin Padilla
Benoit Desroches debunks the myth that we only use 10% of our brain. And, although this may be
Anna Wiedmann the green edition, you can also read about materials that bend light backwards (p. 8), the deluge of
Layout Editors spam that shows up in your email inbox (p. 49), and what a canyon in Idaho might tell us about
water on Mars (p. 7).
Merredith Carpenter
Speaking of green, we have an almost entirely new editorial staff for this issue. While it was sad
Jacqueline Chretien
to see so many of our seasoned veterans leave us for greener pastures (or, in some cases, to focus more
Marek Jakubowski on their research) and daunting to think about training a new editorial board, it has been exciting to
Robin Padilla have so many fresh faces and new ideas. I’d like to thank the entire editorial staff for their enthusiasm
Orapim Tulyathan and willingness to commit precious hours to this magazine, and also the former members of the staff
Terry Yen who have provided so much support during this transition. Finally, without our dedicated layout edi-
tors and our wonderful Art Director, Tim De Chant, the magazine would never have come together
Photographer so beautifully. If you’re interested in getting involved, or if you loved—or hated—one of our articles,
Niranjana Nagarajan we’d love to hear from you at sciencereview@gmail.com.
Web Editor
Enjoy the issue,
Jesse Dill
Printer
Sundance Press
Rachel Bernstein
© 2009 Berkeley Science Review. No part of this publication may be reproduced, stored, or transmitted in any form without the express permission of
the publishers. Financial assistance for the 2008-2009 academic year was generously provided by the Office of the Vice Chancellor of Research, the Office
of University Relations, the UC Berkeley Graduate Assembly (GA), the Associated Students of the University of California (ASUC), and the Eran Karmon
Memorial Fund. Berkeley Science Review is not an official publication of the University of California, Berkeley, the ASUC, or the GA. The views expressed
herein are the views of the writers and not necessarily the views of the aforementioned organizations. All events sponsored by the BSR are wheelchair
accessible. For more information email sciencereview@gmail.com. Letters to the editor and story proposals are encouraged and should be
emailed to sciencereview@gmail.com or posted to the Berkeley Science Review, 10 Eshleman Hall #4500, Berkeley, CA 94720. Advertisers: contact
sciencereview@gmail.com or visit sciencereview.berkeley.edu.
COVER: Chemists, engineers, physicists, and other experts are cracking the secrets of photosynthesis to harvest the sun’s power to meet our increasing de-
mands for energy. Painting by Micheal Hagleberg.
3
[Entered at the Post Office of Berkeley, C.A. as Second Class Matter.]
A BIANNUAL JOURNAL OF PRACTICAL INFORMATION, ART, SCIENCE, MECHANICS, CHEMISTRY, AND MANUFACTURES
Berkeley, April No.
Features page
Photosythesis ...............................................................16
Illuminating alternatives for solar energy research by Tracy Powell
Zap! .............................................................................22
Magnets trip up brain function by Colin Brown
Green Chemistry..........................................................27
Chemists clean up their act by Lee Bishop and Mitch Anstey
4
Current Briefs page
Fishy Physics ..................................................................8
Metamaterials bend light backward by Aaron Lee
Reaching Out...............................................................14
Building relationships between science and society by Melanie Prasol
Departments
Labscopes .......................................................................6
Sticky fingers by Jessie Dill
Looking for bosons by Laura Erickson
Hotwired by Jasmine McCammon
Mars in your backyard by Sharmistha Majumdar
Look both ways by Chat Hill
5
labscopes
Sticky fingers
T hanks to recent work from UC Berkeley engineers, the makers of Scotch Tape may have to rethink their prod-
uct line. Taking a cue from geckos—which can climb nearly any surface with their sticky but self-cleaning
feet—Jongho Lee, a postdoc in Ronald Fearing’s lab, has developed a material that can stick to both dry and wet
surfaces, and even gets stickier with repeated cycles of adhesion and release. This sticky surface, made out of
LABSCOPES
T he Large Hadron Collider (LHC), powered up for the first time last fall by the European
Organization for Nuclear Research (CERN), is the largest and most complex machine ever
built. Its primary purpose is to smash beams of particles together, traveling in opposite direc-
tions inside a 17 mile underground tunnel at tremendous velocities. The much-hyped ATLAS Hotwired
experiment aims to support or disprove a quantum theory involving the Higgs boson, which
would help explain how mass-
less particles can have mass.
As part of a huge international
F ossil fuel combustion produces about
90% of the world’s power, but in the
process, 60 to 70% of the energy stored in
collaboration, scientists at the the fuel is lost as heat. Devices to scavenge
Lawrence Berkeley National this heat and turn it into electricity, called
Laboratory (LBL) designed thermoelectrics, have been around for de-
and partially fabricated the cades—providing power for the deep space
distribution feed box (DFBX), probes Voyager I and II, for example—but
connecting the LHC’s cryo- their efficiency is generally too low to com-
genic, electrical, and vacuum pete with conventional elec-
systems to the different col- tricity, making them imprac-
liders and to the CERN con- tical for most applications.
trol center. The DFBX plays a Thermoelectrics produce
role in all four major collider electricity from a tempera-
experiments: ALICE (A Large ture difference, so the ideal
Ion Collider Experiment), ATLAS material for such a device
(A Toroidal LHC ApparatuS), LHCb (Large Hadron conducts electricity well
Collider beauty), and CMS (Compact Muon Solenoid). Growing an- but can also maintain a
ticipation was put on hold, however, as a faulty connection led to a helium leak that temperature gradient.
will delay a restart until September 2009. Unfortunately, good
— L AUR A E RICK SON electrical conductors
also tend to conduct
heat well. To solve this
6
Mars in your backyard
M ost canyons result from gradual geological processes over millions of years, but
short, massive deluges of water can also scoop out a chasm. For example, geo-
morphologist Michael Lamb and his colleagues from the UC Berkeley BioMARS proj-
ect believe that a sudden megaflood carved the amphitheater-headed Box Canyon
LABSCOPES
in southern Idaho. Amphiteater-headed canyons, so named because they end in
round, steep walls, are usually found in soft, sandy conditions and are thought to
result from groundwater emerging as springs to erode the canyon walls, but Box
Canyon is carved into much harder basalt, which made Lamb and his coworkers
give it a second look. The canyon currently has no surface water flow, but Lamb
believes that the many depressions, or “plunge pools,” at the canyon’s base were
formed by ancient waterfalls. Its head also has telltale scour marks likely left
by surface water. And the team’s calculations indicate that only vast amounts of
very fast-flowing water could have moved the massive boulders downstream to
their current resting places. They estimate that the canyon, up to 70 meters deep
in some places, was formed by a flood lasting only 35 to 160 days. Of particular
interest are the similarites between Box Canyon and amphitheater-headed canyons on
Mars, also carved into basalt. If the Martian canyons evolved in the same way, through
flooding rather than groundwater erosion, this could shed light on unanswered questions
about water’s role in the Red Planet’s past.
Image courtesy of Austin Roorda
—S HARMISTHA M A JUMDAR
N ot satisfied with your 20/20 vision? How about 20/8? Austin Roorda can give it to you,
as long as you’re looking into his machine. Roorda, chair of the UC Berkeley Vision Sci-
ence Graduate Group, has developed the Adaptive Optics Scanning Laser Ophthalmoscope,
or AOSLO, a machine that allows him to see your retina—and you to see images—with un-
problem, Professors Peidong Yang and Arun precedented clarity. Adaptive optics was originally developed by astronomers to eliminate
Majumdar turned to silicon nanowires that de- distortions in their images by measuring and correcting for fluctuations in the atmosphere
couple electrical and thermal conductivity. The between the stars and their telescopes. For Roorda’s
nanowires are so tiny (about 100 nanometers application, he says, “adaptive optics is a way to re-
in diameter, or one-thousandth the diameter of move the blur caused by imperfections in the eye’s
a human hair) that they cannot sustain the vi- optics,” including the lens, cornea, vitreous humor,
brations that would result in heat transfer, and and even the film of tears that covers the eye, all of
etching the nanowires to roughen their surface which are constantly changing. AOSLO uses a laser
restricts the vibrations even further. While the to detect aberrations in the eye and then corrects
heat conductivity is greatly restricted, the elec- the image—or adapts—in real time. The correc-
trical conductivity remains relatively robust, tion works both ways: Roorda sees clearer images
leading to an efficient ther- of patients’ retinas, and patients see extremely crisp
moelectric device. While images projected by the laser directly onto their
these devices are not yet retinas. Roorda’s first goal is to screen patients for
ready for large-scale use, eye diseases by examining the retina on a cellular
they may bring us one step level. He also aims to test the limits of human vi-
closer to the thermoelectric sion. Theoretically the retina limits our visual acu-
dream. As graduate student ity to roughly 20/8, and one subject, with the help
Michael Moore says, “You’re of the AOSLO, has achieved this limit. Whether
basically getting something it’s peering into the furthest skies or depths of eyes,
from nothing.” adaptive optics provide great insight.
7
c u rrent brief s
f i s hy phy sic s page 8 bat t le of t he bu g s page 10 t r a i n you r
b r a i n p a g e 12 p o o p o w e r p a g e 13 s c i e n c e r e a c h e s o u t p a g e 14
8
BRIEFS Metamaterials
Image courtesy of Luis Argerich
Refraction, the redirection of light by a surface or material, is getting put to new use bending light after it reflects off specially designed metamaterials.
rial composed of nanosized ‘meta-atoms’ that magnetic wave propagating in another direc- allowing them to propagate far enough to
we can engineer to control the path of light,” tion. The incoming magnetic field is unaware be resolved. Zhang’s group demonstrated a
says Jie Yao, a graduate student in Zhang’s lab of the wires and follows the new electric field, working “superlens” in 2005 (“The Sharpest
and coauthor on the Science paper. resulting in a new electromagnetic wave. Image,” BSR Fall 2005), being able to resolve
Fabricating negative index materials for Since the magnetic field is not absorbed in two lines separated by one-tenth the wave-
visible light has been a challenge due to its the process, less energy is lost as the wave length of red light. Superlenses could lead to
short wavelengths. Previous metamaterials moves through the material. inexpensive optical microscopes that would
have achieved negative indices only at micro- An alternative optical metamaterial was be able to resolve structures as small as liv-
wave and infrared wavelengths, which are at devised by stacking alternating layers of silver ing viruses. “The idea is simple enough that
least one and a half times that of red light. and insulating magnesium cut into a nano- it could one day be used even in high school
These metamaterials have also been relatively scale fishnet pattern. As described in their biology classrooms,” explains Leo Zeng,
thin, consisting of a single to a few meta- August 2008 Nature paper, these layers form postdoctoral researcher and lab manager of
atomic layers. Increasing the thickness of the small circuits that induce an electromagnetic Zhang’s group.
material resulted in considerable energy loss wave moving in the opposite direction as the In fact, overcoming the diffraction limit
due to absorption in the material. Zhang has original. “This new design has incredible flex- is just one of several applications achiev-
also overcome this limitation and achieved ibility and it is simple,” says Jason Valentine, able by mastering the manipulation of light.
effective three-dimensional metamaterials graduate student and coauthor of the article. These materials may one day play a role in
measuring tens of meta-atomic layers thick. “You want the simplest design possible when high speed optical computing, cavities that
Previous metamaterials were construct- dealing with fabrication.” This design also can trap light in a way that mimics the envi-
ed so electrons in the metamaterial would demonstrated better energy efficiency com- ronment around a black hole, and cloaking
oscillate at the frequency of the incoming pared to previous metamaterials. devices. Zhang’s remarkable achievement of
wave (see “Metamaterials World,” BSR Fall Such metamaterials can enable research- bending red light the “wrong” way has laid
2006). This allowed the wave to be absorbed ers to overcome the diffraction limit and re- the necessary groundwork for the develop-
and re-emitted in another direction. Zhang’s solve details smaller than the wavelength of ment of practical application of metamateri-
metamaterial takes a new approach by rely- the incident light. When light waves impact als. “The results demonstrated in these two
ing on silver’s conductive properties. Light a material, a pattern of waves is formed near papers seemed impossible in 2003, but we
is an electromagnetic wave, consisting of an the material’s surface. Details smaller than did it,” says Zeng. “We are limited only by
oscillating electric field with a perpendicular the wavelength of light are in these waves, our imaginations of what is possible.”
magnetic field. The incoming electric field, yet they decay and vanish almost instantly.
when aligned with the silver wires, induces a Negative index materials placed close to the
current in the wires that emits a new electro- object can amplify these evanescent waves, Aaron Lee is a graduate student in astronomy.
9
1. Injection
During infection, viral DNA is 2. Incorporation into
injected into the bacterial cell. Bacterial DNA
Short pieces of the viral DNA are
BRIEFS Bacterial immunity
4. Detection and
Response
The next time the bacterium
or its progeny encounter that 3.Transcription
virus, they use the previously- The bacterium makes RNA from
acquired information to target the DNA in the CRISPR region
the virus and evade infection. that can interfere with the DNA
of another invading virus through
base-pair interactions.
Illustration by Tony Le
Battle of the Bugs ruses that infect them. Scientists have long Molecular and Cellular Biology. “That’s what
known that bacteria can be infected by virus- evolution is. The bug responds and then the
The evolution of bacterial es called bacteriophage (from the Greek for virus responds in kind, as a consequence of
immunity “bacteria-eaters”). There can be no quarter in that selective pressure.”
the conflict between these foes, as the phage Scientists had believed that bacteria
It is war. Every two weeks, half of the popu- cannot reproduce without infecting the bac- evade viral pathogens primarily by systemati-
lation is destroyed. The survivors adapt to teria, while the bacteria will not survive to cally eliminating any foreign DNA that they
outsmart the enemy, but the enemy quickly propagate if the phage infection is success- find inside of themselves, which is often in-
evolves its strategy and will continue to kill. ful. “It really is a tug-of-war,” explains Blake jected by viruses. Recent findings over the
This is the largest arms race on the planet: Wiedenheft, a postdoctoral fellow in Jennifer past four years, however, suggest that bacte-
the epic battle between bacteria and the vi- Doudna’s laboratory in the Department of ria are capable of much more complex ap-
10
BRIEFS Bacterial immunity
proaches to warding off viral invaders. “What While the mechanism of CRISPR-based im- terized the microbial community,” says Sun,
we’re beginning to realize,” says Wiedenheft, munity still remains hazy, what is clear is that “and now we’re looking at how viruses and
“is that bacteria have an immune system that the next time the bacterium encounters that microbes co-evolve.”
adapts to viruses. It will recognize those vi- virus, “it uses the information it just acquired The Banfield lab is excited about the
ruses, and it will be prepared to defend it- from the parasite to target that parasite to kill CRISPR system because it provides a “his-
self against them.” This notion of adaptive it,” explains Wiedenheft. Essentially, it’s a flu torical” genetic record of which viruses have
immunity is conceptually very similar to shot for bacteria. infected which bacteria. This information is
the way the human immune system works. The realization that microorganisms enabling microbial ecologists to study the
Once we’ve been exposed to a particular show such sophistication in their defense interplay between these populations in their
pathogen, either by a vaccination or by prior against viral parasites has sparked significant native environment, eliminating the need for
infection, we are much less likely to be in- scientific interest, and multiple laboratories cultured samples in the laboratory. By se-
fected a second time. Our bodies remember at Cal have begun to explore the CRISPR- quencing samples taken from the ecosystem
the infectious agents that have previously based immune system. Jennifer Doudna’s at different times, the group’s research has
been encountered and maintain an arsenal of lab is trying to sort out the mechanisms of uncovered that both the viruses and bacteria
countermeasures against them, like antibod- the CRISPR immune system by deducing have been evolving at an incredibly rapid rate.
ies, proteins that bind to these invaders and the structure and function of its constituent Once bacteria have targeted a viral sequence
target them for destruction. proteins. Her lab has recently determined in their CRISPR region, the selective pressure
Despite this similarity to human adap- the three dimensional structure of the only to survive drives the viruses to change the se-
tive immunity, the newly discovered bacterial protein common to all eight versions of the quences of their genome to avoid destruction
immune system has a completely different immune system discovered in different spe- by the bacterial immune system. Thus, the
mechanism. It is based on nucleic acids and cies of bacteria. This protein has the ability CRISPR system is actively influencing the di-
is centered around a region of the bacterial to degrade DNA in a test tube, supporting versity of the microbial population and driv-
chromosome that goes by the descriptive ac- the group’s hypothesis that it is involved in ing the evolution of the ecosystem.
ronym CRISPR: clusters of regularly inter- early stages of CRISPR-based immunity, such How could the revelation that bacteria
spaced short palindromic repeats. These re- as viral DNA recognition and processing into use adaptive immune systems to ward off
petitive sequences were noticed in the DNA the CRISPR region. Studying this mechanism viral pathogens impact higher organisms,
of many bacteria when their genomes began sheds light on the tactics employed by bacte- like people? “We’re studying this CRISPR-
to be sequenced twenty years ago, but no- ria in their ongoing battle with viruses, but virus interaction in acid mine drainage, but
body was sure of their purpose. It was only understanding the full extent of the war re- it could be applied to any system in which
four years ago that researchers recognized quires studying the entire microscopic eco- you have microbial communities,” says Sun.
with excitement that the “spacer” sequences system in action. Bacterial communities involved in commer-
in between the repetitive elements actually Jill Banfield’s lab, in the Departments of cial processes such as yogurt production and
match sequences from the genomes of viruses Earth and Planetary Science and Environ- biofuel generation are of particular interest.
that infect the bacteria. mental Science, Policy, and Management, “That’s going to require that they’re grown in
It appears that when bacteria recognize is addressing this question by studying the high density and confined situations,” says
the DNA of an invading virus, they cut it up interdependent population dynamics be- Wiedenheft. “And what happens in those
and incorporate a short piece of the virus’ tween bacteria and viruses in the environ- situations, just like in human populations, is
genetic material into their CRISPR region ment. Christine Sun, a graduate student in that a virus can really spread and wipe out
between the repetitive sequences. Exactly the Banfield lab, explains their interest in a an entire population. It can shut down your
how this leads to immunity is still a subject particular model ecosystem known as “acid whole operation. If we can immunize bacte-
of active research. Recent reports suggest mine drainage,” the result of erosion from ria against the viruses that infect those bugs
some similarity to the mechanism of RNA metal or coal mines. “It’s a really acid rich en- that we’re exploiting, then that has obvious
interference (RNAi) in higher organisms. It vironment, where the pH can go down below economic consequence and benefit.” Thus, as
seems that bacteria make RNA from the DNA 1, and so very few organisms can thrive in we gather new intelligence about the CRISPR
of the CRISPR region, which is then diced these areas.” Because this niche ecosystem is immune system, humans stand to become
into small pieces that are hypothesized to in- so inhospitable, the lab can sequence samples beneficiaries in the ongoing war between
terfere with either the DNA genome or the of DNA from the environment, determine ex- bacteria and phage.
messenger RNA of an invading virus through actly which microorganisms were present,
the same sort of base-pairing interactions and even reconstruct complete genomes for
that stitch together the double helix of DNA. many of them. “Over the years Jill has charac- Katie Berry is a graduate student in chemistry.
11
Train Your Brain
How video games can be good The unpublished study used two types ing specific skills can lead to an overall in-
of training on kids in an Oakland elementary crease in IQ. “We think of both reasoning and
for you
school. One group played reasoning games processing speed as being really important
such as Towers, a game in which players components that subserve cognition,” Bunge
We largely accept that we can manipulate must strategically plan several moves ahead says. “Your mind has to be quick enough to
our bodies by changing our exercise and eat- to transfer rings from one post to another. be able to think through problems, otherwise
ing routines—but what about our brains? The other group played games intended to you’re going to lose the thread and you won’t
Because the brain is traditionally viewed as increase processing speed, like Blink, a card be able to, for instance, do a mathematical
the locus of our true “self,” too often we treat game based on matching shapes and colors calculation. So, processing speed is really im-
it as immutable. But just as our bodies grow as quickly as possible. The games themselves portant. And on the other side, being able to
and change, so do our brains. Mounting evi- were not exceptional: Blink and Towers are plan out, strategize, and tackle a novel prob-
BRIEFS IQ
dence from the field of neuroscience suggests both commercially available. But the results lem, as in the reasoning, is also important.”
that our environment molds our brains, and were intriguing. “Keep in mind it’s a fairly Bunge’s study highlights the significance
that we can exploit this plasticity through di- small group of kids so far, and we’re going of growing up in a cognitively enriched en-
rected training, perhaps vironment, where chil-
even to increase our in- dren play games and
telligence. interact with adults,
“Intelligence is for performance on
perceived as a unitary tests that measure
phenomenon, but a lot intelligence. Unfor-
of this can be attributed tunately for less privi-
to culture,” says Mark leged children, other
Kishiyama, a post- research suggests that
doctoral fellow in Pro- the converse is also
fessor Robert Knight’s true: Kishiyama and
lab in the Helen Wills Knight published a
Neuroscience Insti- study earlier this year
tute. “Americans tend which suggests that
to attribute intelligence kids from lower socio-
12
Poo Power
for the next step in terms of intervention.” Harnessing the energy of organic food sources and transfer them ex-
Both Bunge’s and Kishiyama’s studies ternally to the anode of the fuel cell, thereby
waste
are preliminary, with limited sample sizes creating the electric flow.
that temper the strength of their conclu- All organisms must get rid of the elec-
sions. What these studies truly represent is a Like spinning straw into gold, microbial fuel trons generated by metabolism, but not every
jumping-off point: they offer a set of testablecells (MFCs) can create electricity from seem- organism does it the same way. “We breathe
responsibility in light of modern understand- ficient enough to suit crobes in soil from
ing of the human brain. “There are all kinds most energy needs. your own back yard,
of things that we’re thinking about in terms In MFCs, bacteria act as did Coates’ son
of frontal lobe immaturity potentially being a as living catalysts to for a science fair
mitigating factor for sentencing,” says Bunge. drive energy produc- project. The bacteria
Research with adolescent brains, for instance, tion, but despite this, in MFCs often come
suggests that prefrontal cortex, and thus some most efforts toward from sewage treat-
higher cognition, is still developing into the improving the effi- ment “sludge,” so
early twenties. Why then, Bunge wonders, ciency of MFCs have most MFCs are pow-
are children under the age of 18 locked away not focused on the ered by a complicat-
for life, especially given that brain function biological details of A microbial fuel cell. Electrons flow between the anode ed mix of unidenti-
is trainable? Bunge says she is hopeful that the waste to wattage chamber (right side), where bacteria grow, to the cathode fied bacterial species.
her work and that of her colleagues will help conversion. A recent chamaber (left side). “We wanted to make
bring reform to the legal system. “The judges report from Professor [the bacterial com-
that I have been speaking to find it hearten- John Coates’ group in munity] as simple as
ing to know that there’s at least some evidencethe Department of Plant and Microbial Biol- possible so we’d have the best chance of iso-
that your brain function can change.” ogy, however, demonstrates that focusing on lating those key players responsible for the
the bacteria that power MFCs can not only electron transfer on the electrode,” says Kelly
bring to light the biological mechanisms be- Wrighton, a graduate student in the Coates
Katie Hart is a graduate student in chemistry. hind MFC energy production lab and lead author in this study.
but can also lead to the dis- To cultivate a simplified community,
covery and isolation of bac- Wrighton and coworkers set up a restrictive
teria that are especially profi- growing environment within their MFCs.
Eran Karmon cient at energy production.
Fuel cells are devices that
First, they maintained their fuel cells at
130˚ F, a higher temperature than most, which
E d i t o r ’s Aw a r d convert chemical energy into
electrical energy. In a conven-
favored thermophilic (heat-loving) life while
preventing the growth of bacteria that pre-
tional hydrogen fuel cell, a fer more moderate temperatures. Second,
negatively charged electrode, they established an oxygen-free environment
the anode, is the site of a within the MFC to select for microbes ca-
chemical reaction that splits pable of “iron-breathing” respiration. Finally,
hydrogen into hydrogen ions a non-fermentable carbon source facilitated
and electrons. The released external electron transfer to the anode by
electrons flow through an ex- the microbes. After 100 days of monitoring
ternal circuit that lies between the current produced by the MFCs, Wrigh-
the anode and the positively ton and coworkers removed the anode to see
charged electrode, the cath- who was growing on its surface.
ode, creating an electric cur- With the help of recent innovations in
In memory of Eran Karmon, co-founder and
first Editor-in-Chief of the Berkeley Science rent. In MFCs, on the other DNA-based “fingerprinting” of bacteria, they
Review. This award is given annually to hand, bacterial metabolism found the reactors that produced electricity
the Editor-in-Chief of the BSR thanks to a acts as the electron source: contained a different collection of bacteria
generous donation from the Karmon family. bacteria release electrons from than the control reactors that did not. Over-
13
all, the absolute numbers of bacteria cells in
current-producing systems had decreased as
compared to the more dense starting culture;
however, certain members of the starting
community had actually grown in number—
and their identities were surprising.
The cellular proteins we know to be ca-
pable of transporting electrons are found in
cell membranes. Before this study, all bacte-
BRIEFS Scientific dialog
chemy, but perhaps even more adept. tions in the UC Berkeley community that analyze that problem, and propose a solution.
seek to address this problem. Participants develop communication skills
One approach is to better educate scien- not commonly practiced in academic science
Susan Young is a graduate student in molecular tists in the policy process and to teach them to and learn how to approach a technical prob-
and cell biology. communicate effectively with non-scientists. lem from a different vantage point. Topics
The Science, Technology, and Engineering in 2008 included privacy issues in personal
Policy Group (STEP) is a student-run organi- genomics, constraints on pharmaceutical
zation that brings together students from var- research, and utilization of alternate energy
ious backgrounds to discuss a wide range of sources. For students who plan to pursue a
science and technology issues. Unlike more career in science, these skills will hopefully
14
prove useful in com- are being asked to make decisions about stem performance art, political discourse, and sci-
municating effectively cell policy? Laurel Barchas, a former under- entific research, as well as the ideas of other
with the public and in graduate and current laboratory technician at scholars to develop theories on how society
considering broader is- UC Berkeley, believes that public understand- and science influence each other. Rafferty de-
sues when conducting ing is critical. Together with Professors Charis scribes her work as examining “what it means
research. “I think STEP Thompson and Irina Conboy from the gen- to have a body.” Modern technology allows
is important because der and women’s studies and bioengineering people to dramatically alter their bodies in a
we need people with an departments, respectively, Barchas received variety of ways, from organ transplantation
interdisciplinary skill a $25,000 grant from the Edmond D. Roth- and prosthetic limbs to cosmetic surgery.
man embryonic stem cells. Yet there are wide able culture and should
misconceptions about stem cell research. A not be eliminated.”
pilot survey by the UC Berkeley Stem Cell Politicians, scien-
Initiative found that about 20% of surveyed tists, and the public are
people incorrectly thought umbilical cord inextricably intertwined.
blood was a source of embryonic stem cells. The public votes for
This belief has been used as a justification government officials and
that cord blood, not human embryos, should who will soon be voters and help them un- those officials act based on the ideals of their
be used as a source of stem cells. Cord blood, derstand the science and policy of stem cell constituents. From debates about global
however, is a source of a more mature cell research, as well as possibly spark an interest warming and privacy concerns in personal
type that does not afford the same therapeu- in science. An important component of the genomics to discussions about stem cells,
tic potential as embryonic stem cells. Equally program is to acknowledge the ethical debate many modern issues have strong scientific
concerning is a misapprehension that stem concerning human embryonic research. As and technological components. How much
cells will help cure a variety of diseases over- Laurel explains, “The point of these presenta- government officials and the public know
night. The first, and only current, clinical tions is to give the students information on about the underlying science, as well as the
trial of a human embryonic stem cell therapy this very interesting and complex topic and effectiveness of the scientific community’s
was just approved on January 23, 2009, and let them choose for themselves. We try for communication with both groups can have
many more years will likely pass before any an unbiased approach and to tell the whole large ramifications on legislation and policy.
such therapies become available to the pub- spectrum.” She is currently trying to expand Programs like STEP and the Stem Cell Edu-
lic. To ensure continued support for bills like the program statewide. cation Outreach Program, as well as the indi-
Proposition 71, it is critical to communicate Another important aspect of the in- vidual efforts of scholars like Kelly Rafferty,
the pace of science and to instill realistic ex- terface between science and society is how are facilitating that much-needed discourse.
pectations that can be met by researchers. well the scientific community understands
The recent deliberations over the stem the public’s interests. Kelly Rafferty is a doc-
cell bill in California illustrate an important toral candidate in performance studies and Melanie Prasol is a graduate student in
question at the intersection of science and so- also a predoctoral fellow with the Berkeley molecular and cell biology.
ciety: should the general public have a good Stem Cell Center. In her studies, she draws
understanding of stem cell research when they on information from multiple fields, such as
15
Photosynthesis
by Tracy Powell
16
Illuminating alternatives for
solar energy research
plants can actually outperform solar cells, vented them from realizing their cost-saving
transporting absorbed energy with near-per- potential.
fect efficiency. Scientists are therefore probing Foremost among their faults, novel PV
photosynthetic mechanisms of energy trans- materials are not durable. Customers would
port, with the goal of using their discoveries likely object to the hassle of replacing their
to improve the overall efficiency of photovol- PV panels (even cheap ones!) on a daily or
taic materials. monthly basis, and continual replacement
In addition to their energy transport ef- fees offset any savings gained from using in-
ficiency, plants also excel at doing their job expensive materials. Researchers must there-
on the cheap. They are made out of water, fore find ways to extend the lifetime of these
carbon, and a few minerals—all inexpensive, novel PV materials. Additionally, even the
plentiful materials—and they essentially as- most promising solar technologies will re-
semble themselves. In contrast, commercial quire innovations in large-scale manufactur-
solar panels are constructed of exquisitely ing techniques to minimize production and
pure silicon crystals, whose manufacture is assembly costs.
both energy-intensive and expensive. Poly- It is here, in the design and assembly
silicon, the bulk material from which PVs of cutting-edge solar cells, that understand-
are produced, currently costs around $150 ing the biology of photosynthesis becomes
per kilogram. At that price, manufacturers relevant. How do biological systems use free,
are happy to incorporate silicon slivers into nonpolluting ingredients to produce effec-
consumer electronics; tiling the nation’s roofs tive photochemical devices? How do they
with the stuff, however, is less feasible. To assemble complex light-harvesting systems
make solar power competitive, it is widely under everyday conditions, without elabo-
believed that the retail price of photovoltaic rate manufacturing techniques? How do they
units must drop by 70%. maintain and repair these systems for indefi-
Many next-generation PV technologies nite periods of time? Researchers are seeking
are therefore aimed at reducing manufactur- to answer these questions, and hope to one
ing costs. These advances range from devel- day apply lessons learned from Nature to the
oping cheaper ways to manipulate silicon to rational design of solar energy tools.
replacing it with other inorganic compounds,
such as copper or even iron pyrite (fool’s Some (self-)assembly required
gold). Other strategies include using organic Cost of manufacture is a major hurdle to
dyes, exploring the PV properties of novel commercializing any photovoltaic technolo-
Converting photons into electrons is a nanomaterials, or replacing inorganic solar gy. It’s generally safe to assume that if a manu-
multi-step process, the first stage of which is materials with organic compounds. (Here, facturing process demands 99.999999999%
to absorb as many photons as possible from organic refers not to your local farmer’s mar- pure reagents, ultra-high vacuum chambers,
sunlight. Plants are generally confined to ab- ket, but to materials made mostly of carbon and temperatures of 1500˚ C, it’s probably
sorbing light from the red and blue portions and hydrogen atoms.) not cost-effective (these, incidentally, are
of the spectrum, while photovoltaic materials Though these new PV materials may some of the traditional requirements for mak-
absorb energy from a wider range of visible succeed in dropping manufacturing costs, ing silicon wafers). On the other hand, if a PV
wavelengths. (This is why plants look green, they have so far been less efficient at convert- material can put itself together in a simple,
while solar cells appear black.) PV materials ing photons into electrons than traditional, water-based buffer, even die-hard penny-
can therefore reap a bumper crop of photons silicon-based devices—organic solar cell re- pinchers are likely to give it a big thumbs-up.
from each unit of available sunlight, while searchers, for example, recently trumpeted Such is the logic behind Rebekah Miller’s re-
plants trap a much smaller fraction of avail- an all-time conversion efficiency high of just search, which investigates how to exploit the
able energy. This difference accounts for much over 6%. Such reduced efficiency might be an self-assembling properties of biological mol-
of plants’ photon conversion inefficiency. acceptable tradeoff for a significantly cheaper ecules to build inexpensive light-harvesting
Once photons have been trapped, the technology, so long as the overall cost of gen- structures.
absorbed energy must travel to sites where erating electricity was lower. Unfortunately, As a doctoral student in Professor Mat-
electrons are actually generated and export- organic and other next-generation PV materi- thew Francis’s lab in the Department of
ed. In these later steps of energy conversion, als suffer from other problems that have pre- Chemistry (she recently graduated and is
17
now at MIT), Miller began her research with
tobacco mosaic virus coat protein (TMVP), a
simple biological unit that can aggregate into
organized structures. Using basic, benchtop
reactions, she chemically attached light-
absorbing dye molecules to each protein.
Once placed in the proper solutions, these
modified TMVP molecules assembled them-
FEATURE Photosynthesis
e -
wavelengths that penetrate the depths. Each
species’ pigment content has been optimized Illustration by Tony Le, Tracy Powell, and Tim De Chant
to absorb wavelengths of light available in
their environment. Similarly, to cope with
changing light quality on a shorter timescale,
many plants can adjust the ratio of different Electrons eventually power a
chemical process called the Calvin
forms of chlorophyll present in their leaves,
Cycle, which consumes carbon
maximizing efficient light use. dioxide to build sugar molecules.
This flexible approach to light absorp-
tion appeals to engineers. Just as photosyn- A Quantum of Sol
thetic organisms rely upon a variety of bio- Photons are absorbed by chlorophyll molecules in an
logical pigments, researchers have developed antenna protein. The absorbed light energy is efficiently
shuttled along a path of acceptor molecules to the
many synthetic pigments, each of which ab-
reaction center, where it triggers release of an electron.
sorbs a unique spectrum of light. By mixing
18
and matching the pigments shackled to her
TMVP structures, Miller’s assemblies could
one day be optimized to expand the range
of wavelengths from which they can harvest
light, greatly enhancing their flexibility and
efficiency.
Currently, researchers in the Francis lab
are working to combine TMVP light harvest-
FEATURE Photosynthesis
ing antennae with small molecules that can
conduct electricity, with the goal of designing
functional electronics that operate like bio-
logical systems. On a more basic level, study-
ing the behavior of these assemblies could
help improve our understanding of how light
energy is transmitted on the small spatial
scales relevant to PV design.
However, despite the potential advan-
tages in cost, tunability, and manufacturing
simplicity, directly incorporating biological
components into photovoltaics would also
bring special challenges. Primarily, biologi-
cal molecules tend to degrade quickly, par-
ticularly under high-intensity light. Accord-
ing to Miller, preliminary evidence suggests
that the three-dimensional structure of the
TMVP scaffold may help to stabilize it, pro-
tecting the assembly against light-induced
decay. Nonetheless, the overall vulnerability
of organic PV components has led scientists
to search for better mechanisms to protect
PHOTOVOLTAICS them—a search that has led to closer exami-
nation of how biological systems maintain
themselves under challenging environmental
conditions.
Do-it-yourself fixer-upper
It doesn’t matter whether you’re a plant
or a PV engineer—if you lavish time, effort,
and precious resources on constructing a
light-harvesting system, you want it to last.
Unfortunately, components in both natural
and manufactured photosystems degrade
over time. Organic solar cells, for instance,
rarely last more than a single day. The chemi-
e -
cal reactions that lead to this decay are not
always well understood, but oxidation (the
same oxygen-dependent process that rusts
your car and browns your apples) is a likely
culprit. Simply by isolating it from oxygen,
Electrons in this current an organic PV’s lifespan can be extended from
are harnessed to provide
days to weeks.
electrical power.
Similarly, in plants, key photosynthetic
proteins can be damaged or destroyed by
How PV Panels Work oxidation within minutes of activity. At noon
Photons are absorbed by the negatively charged surface on a sunny day, for instance, plants are bom-
of a solar cell. The absorbed light energy jostles electrons barded with high-energy photons. This light
loose; these are siphoned off into an electric circuit. The
energy is temporarily absorbed by chloro-
electrons travel toward the positively charged surface of
the solar cell, forming a current. phyll molecules, rendering them chemically
19
volatile until they have passed the energy ior in the plant cell itself.) Ahn then used tion is a distant prospect. However, he sug-
off to other acceptor molecules. Under low- a technique called ultrafast pump-probe gests that solar energy researchers might one
intensity light, this handoff is rapid: energy is spectroscopy to identify which of the puri- day mimic plants’ protective mechanisms
immediately siphoned away and expended in fied protein candidates facilitate zeaxanthin’s by seeding PV materials with molecules that
controlled, downstream chemical reactions. protective quenching. In keeping with its prevent degradative chemical reactions (like
But when light is intense, the plant’s photo- impressive name, this method offers the ul- zeaxanthin).
synthetic machinery can be overwhelmed. A timate in laser-light machismo: fast, power- In a more general sense, a better under-
backlog of absorbed energy builds, and excit- ful, exquisitely controlled lasers bombard a standing of how photosynthetic energy con-
FEATURE Photosynthesis
ed chlorophylls have nowhere to expel their sample with light. An initial “pump” pulse of version can be controlled at such small scales
excess energy. These dangerously reactive laser light triggers a chemical reaction in the could also improve PV design. Fleming, for
chlorophylls can then spawn destructive oxi- sample—in this case, exciting a chlorophyll instance, has likened zeaxanthin’s quench-
dative reactions that cripple proteins, damage molecule bound to a sample protein. Subse- ing activity to a protective dimmer switch.
membrane components, and generally wreak quent laser pulses (the “probes”) are deliv- By clarifying how this molecule regulates the
havoc in the cell. ered a few trillionths of a second later, and al- flow of energy through the photosynthetic
Fortunately, plants have evolved an array low researchers to collect information about protein complex, his group hopes to improve
of clever mechanisms to shield themselves how the sample has changed as a result of the scientists’ control over the behavior of energy
from the oxidative dangers of photosynthe- initial pump stimulus. Because data can be generated by PV devices. Indeed, to better
sis. To learn more about these protective collected over minute increments of time and understand energy fluxes in plants, research-
strategies and whether they might be adapted space, researchers can actually track physical ers in the Fleming lab have looked beyond
for solar cell design, chemists and biologists and chemical reactions as they occur. Ahn’s purely protective mechanisms and applied
are collaborating to understand fundamental spectroscopy experiments therefore allowed their advanced spectroscopic techniques to
protective mechanisms. Of particular interest him to watch photosynthetic proteins absorb other important steps of photosynthesis.
is a pigment called zeaxanthin (pronounced light energy, then measure whether or not ze-
zee-uh-ZANTH-un). axanthin could stabilize the excited chloro- A quantum of sol
Zeaxanthin has long been known to phylls in a quenching reaction. One question to which Fleming and his
stifle (or “quench”) chlorophyll’s hazardous Using this method, Ahn first narrowed collaborators have applied their expertise is
chemical reactions under high-intensity light. down which of several protein clusters par- understanding what happens to solar energy
However, “the exact mechanism for this kind ticipated in quenching. He showed that the once it has been absorbed by the plant. Based
of quenching was not well studied,” explains major light-harvesting antenna (one impor- purely on photon absorption efficiency,
Tae Ahn, a postdoctoral fellow in Profes- tant complex of photosynthetic proteins) did plants do a relatively shabby job of harvest-
sor Graham Fleming’s chemistry laboratory. not undergo quenching after laser excitation, ing the photons available in sunlight. How-
Frustrated by the fragility of organic photo- indicating the proteins that compose this ever, once a photon is absorbed, its energy is
voltaics in his graduate research, Ahn became complex did not participate in zeaxanthin’s transferred to electrons with remarkable effi-
interested in zeaxanthin as a potential model protective efforts. However, after an initial ciency—approximately 97%. By comparison,
for protective energy quenching in next-gen- zap with the laser, three proteins from a sec- PV materials typically only achieve 20–90%
eration PV materials. ond cluster, called the minor light-harvesting energy transport efficiency once light energy
To better understand how zeaxanthin antenna, did facilitate quenching. From a is absorbed. Understanding how biologi-
protects the plant, Ahn first wanted to iden- daunting lineup of potential candidates, Ahn cal systems manage such energy thrift could
tify exactly where its quenching activity oc- had identified three proteins responsible for therefore inspire efficiency breakthroughs in
curs. This was no trivial task. Textbook dia- quenching: CP26, CP29, and CP43. artificial photosynthetic systems.
grams may reduce photosynthesis to a parade Working from this preliminary identi- Plants have evolved a specific architec-
of comfortably spaced cartoon blobs, but in fication, Ahn collaborated with Tom Aven- ture to support efficient energy transfer, pack-
reality this process transpires in dense, dy- son, then a postdoc in Krishna Niyogi’s lab ing light-absorbing chlorophyll pigments into
namic rafts of proteins, swaddled in mem- in the Department of Plant and Microbial protein clusters called antennae. Photons of
brane and cloistered in the deepest recesses Biology, to further pinpoint the mechanism light are absorbed in the antennae, and the
of the chloroplast. Zeaxanthin could be in- of quenching. Focusing on CP29 as a case resulting energy hopscotches from one chlo-
teracting with any of hundreds of these mol- study, Ahn determined that in order for rophyll molecule to the next until it reaches
ecules. Furthermore, its quenching reaction quenching to occur, the protein must be able another protein complex called the reaction
lasts mere trillionths of a second. Pinpointing to bind two chlorophyll molecules very near center. Here, the energy finally escapes in
the exact site of this ephemeral process re- to zeaxanthin. This suggests that, in periods the form of an electron, and is used to power
quired some serious sleuthing. of high-intensity light, physical proximity al- downstream chemical processes like making
To narrow the hunt, Ahn collaborated lows zeaxanthin to donate an electron to this sugar.
with Roberto Bassi, a biochemist at the Uni- nearby pair of over-excited chlorophylls—a To make solar energy conversion as effi-
versity of Verona, Italy, who had purified chemical mechanism that could stabilize its cient as possible, absorbed energy must seek
several photosynthetic proteins suspected chemically volatile neighbors. the shortest, speediest escape route from the
of interacting with zeaxanthin. (This in vitro When asked about immediate applica- antenna to the reaction center. Until recently,
approach removed much of the biological tions of this knowledge to PV design, Ahn researchers usually depicted this escape as
bric-a-brac that obscures quenching behav- acknowledges that practical implementa- you would any normal biochemical phenom-
20
An artist’s rendering improvements to solar technology. Today, for
of the “quantum beat” example, solar cells rely on simple diffusion
phenomenon seen by
of charged particles to transport absorbed
Engel.
solar energy to a conductive surface. Future
PVs might instead mimic plants’ separation
It is as if the most of light-harvesting and electron-donating
efficient path is functions—improving performance by ef-
calculated ret- ficiently shuttling light energy from antenna
FEATURE Photosynthesis
roactively. Engel structures to a synthetic reaction center.
sought to discern This sort of advance could redefine the
Image courtesy of Tae Ahn
21
MAGNETS TR
FUNC
22
RIP UP BRAIN
CTION
by Colin Brown
that region. If the area targeted by the pulse common and powerful technique is repete- obscure its effects. According to Miller, “with
is involved in a particular cognitive task, this tive TMS, or rTMS, where a train of pulses lesions you have no control over the location
disruption will manifest itself through subtle is applied over several minutes. This leads to or the extent of the damage. TMS gives you
behavioral effects, such as an increased error more extended “offline” disruptions that can that very focal control over the region of dis-
rate when reading letters from a screen. By last as long as half an hour after the treatment. ruption. You can take someone who is oth-
pairing behavioral measures with carefully Depending on where the pulse is applied, erwise totally normal, and very transiently
timed TMS pulses, researchers can establish a the effects of rTMS treatments can mimic disrupt the region you’re interested in.”
causal role for a region in a particular task. those seen in so-called “lesion” patients who
“Essentially, you’re introducing transient have experienced damage to the region from Virtual lesions
Illustration by Terry Yen; Image public domain
noise to a region, and if that region is criti- stroke or other brain injuries. Since the effects Miller’s work used this rTMS lesion-
cally involved at that time, it’s not going to of rTMS are controllable and fade after a few ing approach to study a brain process called
perform that function as efficiently”, said minutes, researchers can create temporary “refreshing”, which allows the brain to pick
TMS researcher Brian Miller, a recent gradu- “virtual lesions” to disable almost any brain out interesting bits of information from the
ate from Mark D’Esposito’s lab at Berkeley. region at will. Examining real lesion patients swamp of sensory data that passes through
The disruption of a region after a single can yield profound insights into the function its visual and auditory systems. When Miller
TMS pulse lasts for a very short time, usually of healthy brains, but the size and severity of and his colleagues used fMRI, which maps re-
just a fraction of a second after the pulse is the damage can vary widely among individu- gions of neural activation, to scan the brains
applied. While even these short pulses can als, and the reorganization that takes place as of people during a task that involved refresh-
be useful for some applications, a far more the brain heals itself following an injury can ing, they ran into a problem—they found two
23
generally hard-wired, the regions of the mo-
tor cortex that connect to a particular muscle
can change in both size and “excitability”—
24
Professor Rich Ivry from the UC Berkeley Psychology
department shows off a TMS coil used by his lab.
FEATURE Zap!
make these left-versus-right choices. By creat-
Image courtesy of Colin Brown
25
TMS in the clinic unclear. Since TMS is relatively easy to apply and more efficient means of guiding plastic-
The ability of rTMS to noninvasively alter and has few side effects, researchers have tried ity and shaping behavior.” The UC Berkeley
brain function with few apparent side effects using it to treat all types of disease, including researchers consulted for this story agreed
makes it particularly appealing as a treatment mania, obsessive-compulsive disorder, post- that studies of neuroenhancement should be
for psychiatric disorders. By far the most suc- traumatic stress disorder, and schizophre- pursued, if for no other reason than to allow
cessful example of this strategy is for depres- nia. Results from most of these trials have these techniques to be applied safely. “We
sion, especially in patients who don’t respond been mixed, however, and it is likely that a shouldn’t close the door out of hand,” says
well to antidepressant drugs. TMS may even deeper understanding of both the neural ba- Ivry. “If these things do turn out to have some
be able to take the place of electroconvul- sis of these disorders and the physiological truth to them, people are going to use them.
sive treatments (commonly known as “shock mechanisms of TMS will be needed before it Science’s best guide here is to make sure that
therapy”) for some. Most of these treatments is widely used to treat these conditions. they’re properly evaluated.”
FEATURE Zap!
26
F rom 1961 to 1971, over 20 million gal-
lons of the powerful defoliant Agent Or-
ange were sprayed across the jungles of South
fornia, and the automotive repair industry ad-
opted a mixture of the chemicals hexane and
acetone as a substitute. Tragically, auto me-
health. And it doesn’t just apply to people
in labcoats: the plastics in water bottles and
kids’ toys are also potential risks that need to
Vietnam. The herbicidal active ingredients chanics began experiencing numbness of their be assessed. The diverse ways that chemicals
destroyed millions of acres of forests, but per- hands and feet, and some were even rendered affect individuals and the environment means
haps even more tragically, the contamination wheelchair-bound. It was eventually deter- the success of the green chemistry movement
of Agent Orange with the carcinogen dioxin mined that hexane was being metabolized into will require chemists working together with
caused hundreds of thousands of deaths and a potent neurotoxin in the mechanics’ bodies, an array of other professionals to ensure that
continues to affect the people of southern causing nerve damage. This so-called “regret- chemicals are created, tested, treated, and dis-
Vietnam to this day. Dioxin is now infamous table substitution” illustrates the difficulties posed of properly.
as one of the world’s most potent cancer- inherent in designing and regulating chemi- The green chemistry movement is be-
causing chemicals. cal tools, weighing their benefits against often ginning to take hold at UC Berkeley. An im-
27
Most consumer product manufacturers things are costly, especially in the chemical
The Carbon Connection are not required to assess the safety of chemi- arena. The problem is the costs are not as-
The linkage between two carbon at- cals in their products, so this vast responsibil- signed in the right place.”
oms is one of the most common bonds ity is left to government agencies. With the As waste disposal prices and regulations
in nature, seen in everything from petro-
current costs of a full toxicological screen ap- have grown, this “cost assignment” has begun
leum to perfume to proteins, and organic
proaching five million dollars, the government to shift, and corporations are becoming keen-
chemists often want to create bonds be-
tween carbons on different molecules to does not have the resources to screen each new ly aware that green chemistry can be a huge
chemical as it comes to market. This means benefit for the bottom line. “Companies don’t
FEATURE Green chemistry
28
from something that’s being dealt with in the
public arena because then it feels like they have
to take sides or be an advocate just because
there are advocates in the process.”
In some cases, chemists shy away from the
concept of green chemistry because they don’t
understand what it means. “I think from a lot
of academic chemists’ perspectives, the situa-
29
Modeling Molecules
Testing chemicals for safety is often a long and expensive process. tial effects, uncovering another layer of the toxicological profile that
But what if we could predict, without any actual tests, the dangers has previously been very difficult to address. The predictive models
of a certain chemical? Professor Dale Johnson of the Department Johnson uses have been shown to be 60 to 75% accurate, and the
of Nutritional Science and Toxicology employs an approach called primary factor limiting this approach is the lack of experimental data
quantitative structure-activity relationship (QSAR) that uses com- on how chemicals affect human health and the environment, an ob-
puter software to do just that. This method is based on the phe- stacle that Wilson and Schwarzman highlighted in their report on
FEATURE Green chemistry
nomenon that chemicals with similar structures generally have simi- challenges to California’s successful regulation of chemicals. “The
lar biological effects and impacts on the environment. Using existing thing that is really missing,” Johnson describes, “is enough data to be
data on the properties of known chemicals, QSAR is able to predict able to create the right kind of model that is not overly generalized.”
the toxicity, bioaccumulation, and environmental persistence for new If this primary toxicological data is generated, QSAR has the poten-
chemical structures. These models can even go so far as to predict tial to be a rapid, low-cost solution for assessing a chemical’s safety
the products of metabolic degradation pathways and their poten- before it is even created.
of the chemicals they work with, they gener- groups and so on, such that they all have an kind of careful, integrated thinking involved
ally do not possess the requisite knowledge. understanding of chemistry, chemical princi- in evaluating the sustainability of a chemical
To address these issues, Mulvihill and some ples, sustainability, and toxicology.” He feels or a reaction.
graduate student colleagues started the Green that students educated in this way “can im-
Chemistry and Sustainable Design seminar prove the processes in chemical companies, Where do we go from here?
series, offered for the first time this past fall. improve the way chemicals are handled, and The challenges posed by the principles of
The series covers toxicology, as well as green improve the legislation that is put forward.” green chemistry cannot be addressed through
chemistry in academia, industry, and public Toward this end, as part of the college’s legislation, business practices, or research
policy. Experts in these fields were invited effort to revamp the undergraduate labora- alone. Our society and economy depend on
from within the university and across the tory courses, Mathies plans to make sustain- chemicals that often pose hazards to ourselves
country, and in demonstration of support for ability an integral part of the undergraduate and our environment. “Our world is becom-
the seminar, many speakers even offered to chemical education. He feels that broad pro- ing a chemical world, and it affects not only
pay for their own travel expenses. Mulvihill motion of sustainability concepts has been the environment but every person and natural
was pleased by the response to the seminar hampered by the lack of a common language resource we have,” says Johnson. If no green
series; according to surveys, student interest alternative to a given hazardous chemical or
in green chemistry and sustainability dramat- process exists, then one has to be created,
ically increased after participating. “Students “Our world is becoming a which requires focused research with sustain-
are more and more interested in pursuing re- chemical world, and it affects ability as an explicit goal. Creating a society
search that relates to issues of importance in every natural resource we that fosters that kind of research and its trans-
our society,” Mulvihill says. lation into economically viable products will
This seminar series was the first sig- have.” require a population that is educated in the
nificant effort to introduce elements of green principles of green chemistry and other as-
chemistry into the chemistry department’s and understanding to allow communication pects of sustainability. Appreciation of this is
curriculum. Tony Kingsbury, executive-in- between groups with diverse interests. Citing beginning to take hold at UC Berkeley, lead-
residence of the Sustainable Products and the fact that 54% of the students that pass ing to dramatic changes in the way students
Solutions Program, a collaboration between through this university will take at least one are educated and research is carried out. On
the Dow Chemical Company Foundation, course in chemistry, Mathies feels that the col- the potential impact of these changes, Mathies
the Haas School of Business, and the College lege can provide that “common language and says, “If we train the students properly, then
of Chemistry that provides the primary fund- common understanding that allows people to they will go out into the world and we will see
ing for the green chemistry seminar series, communicate better and achieve solutions.” a transformation.”
remarks that he is seeing increased interest in Furthermore, laboratory spaces are being
sustainable chemistry all the way up to Dean renovated to operate in a more environmen-
Mathies. “What this college should be doing,” tally friendly fashion and experiments are Lee Bishop and Mitch Anstey are graduate
says Mathies, “is providing the knowledge being updated to use greener chemicals. Ma- students in chemistry.
and information and education necessary thies hopes to incorporate the 12 principles
to put people out there who can work for of green chemistry, as outlined by Anastas
chemical companies, who can work for the and Warner, into the laboratory curriculum
government, who can work with advocacy in an effort to illustrate to the students the
30
Funding
the Future
The Howard Hughes Medical Institute contributes millions to
Berkeley research
by Meredith Carpenter
nal Revenue Service, understandably dissatis- Since the early 1990s, the HHMI has
fied with this arrangement, soon challenged held periodic national competitions to
the organization’s non-profit status. So, in search for new investigators. Prior to 2006,
the late 1950s, the Howard Hughes Medical they would invite about 200 research insti-
Institute began funding 47 medical investiga- tutions—universities and academic health
tors at nine different institutions. centers—to nominate two to four researchers
As of 2008, the HHMI’s endowment had “in the ascending phase of their career” for
grown to a whopping $17.5 billion that funds each competition. Starting in 2006, however,
Robert Tjian, Professor of Molecular and Cell Biology at
354 investigators at 71 host institutions, as UC Berkeley and HHMI Investigator for 20 years, is the the competitions have been “open,” mean-
well as a myriad of grants that support teach- new president of the HHMI. continued on page 35
31
Cal’s Newest HHMI Investigators
Christopher Chang
Assistant Professor of Chemistry and Faculty Scientist in LBL’s Chemical Sciences Division
To Christopher Chang, copper isn’t Domaille plans to use these sensors to study the distribution
are required for proper function- metal pools moving around,” says Chang, “things you wouldn’t
ing of the human nervous system, normally think that copper would do, so it must have its own chan-
though the reasons for this are still nels, transporters, and targets.” Misregulation of copper pools in
poorly understood. “It’s interesting the brain has also been linked to diseases such as Alzheimer’s and
to us because brain tissue actually Lou Gehrig’s, so work in the lab may aid in the understanding of
contains more of these metals than any other part of your body,” those disorders.
says Chang. The Chang lab uses chemistry to study neurobiology, The Chang lab is also looking into the role of reactive oxygen
with the goal of better understanding how the brain works on the species, and particularly hydrogen peroxide, in normal brain func-
molecular level. tion. Reactive oxygen species are molecules that can produce free
To study the role of copper in the brain, the lab is working radicals, which can damage DNA and other cellular components.
on ways to visualize the metal in living cells, particularly under However, “we’ve been interested in this idea that in certain places,
conditions of neural activity, neural stem cell development, in- generated at certain times and at certain levels, hydrogen peroxide
jury, and disease. “We’re approaching it from a chemical point of has a role in neurotransmission and stem cell growth and develop-
view, where we develop a fluorescent probe ment in the brain,” says Chang.
that will selectively detect copper, and use “Because it’s so complex, it To study the role of hydrogen peroxide,
that new tool to do experiments that were makes sense that it would members of the lab are taking a similar ap-
previously inaccessible due to experimental
limitations,” says Dylan Domaille, a gradu-
need different chemistry proach to how they study copper—designing
fluorescent sensors that can report on the
ate student in the Chang lab. “It’s been ob- than you would find presence of the molecule. “We have a small
served that copper is released during syn- anywhere else.” molecule that fluoresces in the presence of
aptic activity, and recent evidence suggests hydrogen peroxide, so it’s a way of asking if
some sort of neuroprotective effect,” he explains. “That’s probably there’s any hydrogen peroxide in what you’re looking at,” explains
one of the predominant hypotheses now in terms of what’s hap- Evan Miller, another graduate student in the lab. “We’re particularly
pening in the brain, but we want to know what’s happening on interested in living systems because hydrogen peroxide is part of
the molecular level at a higher resolution.” how cells talk to each other.” In fact, Miller has already used one of
One complicating factor is that copper can actually exist in these molecules to map molecular pathways of hydrogen peroxide
two forms depending on its number of electrons—while it mainly production in living brain cells.
takes the form of copper(II) in nature and outside the cell, it is Ultimately, these studies have implications for understanding
changed into copper(I) at the cell membrane, and this is the pre- aging and neurodegeneration, in addition to illuminating how the
dominant form inside the cell. “We’ve got a few copper(I) de- brain works on a basic level. To Chang, the existence of signaling
tectors, but copper(II) is more difficult,” Domaille explains. “It’s pathways unique to the brain is not surprising. “You have some-
easy to make a molecule that fluoresces and then turns off when thing that’s really unique in terms of controlling senses like sight,
it binds copper(II). But practically, that’s difficult to use because hearing, thought, memory, and motor skills,” he says. “So because
you’re looking for a dark spot in a bright background, and you’d it’s so complex, it makes sense that it would need different chemis-
rather look for a bright spot on a dark background. We’re still try than you would find anywhere else.”
working on that.”
32
Cal’s Newest HHMI Investigators
Abby Dernburg
Associate Professor of Molecular and Cell Biology and Faculty Scientist in LBL’s Life Sciences Division
Photo by Noah Berger/AP, ©HHMI; Image courtesy of Abby Dernburg
Abby Dernburg studies a type of cell division called meiosis, which produces gametes (eggs and sperm) in
sexually reproducing organisms. Gametes contain half the genetic material of the parent—in humans, one set
of 23 chromosomes. That way, when two gametes are combined at fertilization, the complete complement of
genetic material (in humans, two sets of 23 chromosomes, one from each parent) is restored, resulting in new
genetic diversity. A key step in meiosis is the exquisitely controlled pairing of the two sets of chromosomes,
FEATURE HHMI
each with its so-called “homolog.” This step ensures that when the
chromosomes are distributed to the gametes, each gamete gets one
copy of every chromosome. Errors in this process, which result in
missing or extra chromosomes in the offspring, can cause problems
ranging from Down syndrome to miscarriage.
Using the nematode worm Caenorhabditis elegans as a model organism, members of the
lab study the mechanisms underlying the pairing of homologous chromosomes. Worms are
especially useful for these studies because they are transparent, giving researchers a con-
venient window for watching the stages of meiosis in the live organism. The Dernburg lab
has already discovered that, in worms, specific sequences of DNA on each chromosome are
required for the pairing of homologs during meiosis (see BSR Spring 2007). Without these
sequences, the chromosomes are unable to find each other and are segregated incorrectly. In
addition, Dernburg has identified proteins that bind to the sequences and help bring the two Gamete precursors undergoing meiosis in
homologs together. Now, members of the lab are investigating the steps of the pas de deux that a nematode worm, stained to highlight the
chromosomes (blue) and one of the specific
culminates in the physical pairing of each set of chromosomes. In addition, they are studying sequences that helps homologous chromosomes
how the cell checks whether chromosomes have paired before allowing meiosis to continue. pair (orange).
Photo by Noah Berger/AP, ©HHMI; Image From Mossman et al., Science 310, 1191-3 (2005). Reprinted with permission from AAAS
Jay Groves
Associate Professor of Chemistry and Faculty Scientist in LBL's Physical Biosciences Division
Jay Groves’s research defies placement in a single department. A biophysicist by training, he is a professor
in the chemistry department who studies cell membranes. Groves is interested in how large-scale col-
lective interactions, such as the association of individual lipid molecules and proteins that make up the
cell membrane, affect the overall properties of the system without changing its chemical makeup. For
example, signaling across the cell membrane (i.e., relaying a signal originating from outside of the cell to
the inside) occurs through specific proteins embedded in the membrane. However, in some cases, it is
not simply the action of a single signaling protein that matters, but also the clustering of those proteins
into patterns.
One example of this phenomenon, and a focus of research in the Groves lab, is the T cell receptor
(see BSR Spring 2006). When a cell is infected by, for example, a virus, it takes pieces of proteins from that virus and displays them on
receptors on its surface—a signal that helps to draw the attention of immune cells. One of these immune cells is the T cell, which uses
its T cell receptor to bind to the receptors on the infected target cell. During this interaction, the
bound receptors cluster into a bull’s-eye configuration, and the T cell is activated to kill infected
cells or help mobilize other immune system cells.
It would be difficult to study this interaction and clustering using traditional molecular biology
methods, so Groves takes a very different approach. He uses live T cells, but the interacting cell is
replaced by an artificial cell membrane, complete with receptor proteins, on a nanostructured sur-
face that allows Groves to guide the movements of the interacting proteins. He then constrains the (left) A T cell bound to the artificial cell
movement of the bound receptors in certain ways, creating “spatial mutations” in otherwise chemi- membrane. (right) The same cell, with its T
cally equivalent cells, and watches how these changes affect T cell activation. Using these tools, cell receptor fluorescently labeled in green
and the receptors on the artificial mem-
Groves and his former student Kaspar Mossman found that the radial positioning of the receptors is
brane labeled in red. Note the disruption
required for proper signaling activity. Currently, in addition to continuing his studies of the T cell re- of the bull’s-eye pattern by the grid on the
ceptor, Groves is using his hybrid cell system to investigate mechanisms of cell signaling in cancer. artificial membrane.
33
Cal’s Newest HHMI Investigators
Yang Dan
Professor of Molecular and Cell Biology
Few UC Berkeley professors can claim to have a YouTube video of their research findings. But Yang Dan’s
video is understandably popular—it shows the viewer what it’s like to see through the eyes of a cat. Dan
studies the neurobiology of vision, specifically how visual information is encoded and processed in the brain
and how neural circuits are shaped by visual experience. “We think about coding—how do you take visual
input to turn it into electrical signal?” explains Dan. “And then you can also go backwards and ask how you
FEATURE HHMI
decode information. So if you observe the neural response, can you guess what stimuli were out there?” She
studies these questions on multiple levels, using mathematical models and measurements of neural activity
in both individual neurons and live brains to develop models for different aspects of vision.
Dan made the video now on YouTube by recording the electrical activity of 177 neurons in the cat’s thalamus, a region of the brain
that receives signals from the eyes. With knowledge of how these neurons responded to light and dark, she and her collaborators then
used sophisticated computer programs to translate the cells’ firing into a two-dimensional recapitulation of the animal’s field of vision.
Michael Eisen
Associate Professor of Molecular and Cell Biology and Faculty Scientist in LBL's Genomics Division
34
ing researchers from 121 top institutions can This group creates lists of the top applicants; allowed me to buy instruments and get into
apply directly, although institutions can still however, the final decisions are made by the a kind of science I couldn’t do otherwise. It
nominate researchers who do not nominate President and one or two of the Vice Presi- kicked me up a couple of notches, and I think
themselves. “I think it’s a much more demo- dents of Scientific Research. most people’s experiences are like that.”
cratic way of doing it, because you don’t have Tjian also emphasizes that the HHMI
this middle layer of people making decisions Kicking it up a notch hopes the funding will not benefit the recipi-
about who should be nominated and who For those lucky few who are selected, ent lab alone. “It allows you to hire the right
shouldn’t,” says Tjian. “I was very happy to how does the money actually change their re- people, get the right kind of equipment, and
see that happen.” search? “The really big difference the Hughes then make the equipment available to your
Competitions usually take place every can make is that if you have one or two NIH colleagues. The whole idea is that within any
three years, but they are sometimes held grants, and they’re limited to $250,000 each, given department, only a small percentage
FEATURE HHMI
more frequently, with each one focused on you’re at half a million and you’re pretty are Hughes investigators, but we hope that
a particular research area or investigator ca- much tapped out,” Tjian explains. “Well, our the Hughes funds get used in a more equi-
reer stage. A recently completed investigator research might really need $1.5 to $2 mil- table way.” For example, several years ago
competition, held in 2007, resulted in the ap- lion, if you run a really aggressive research Tjian used his HHMI funds to start a mass
pointment of 56 new investigators—includ- operation. The Hughes was that lifeline that spectrometry facility, which consists of a set
ing five from Cal. “I think it’s fantastic that of instruments used to determine the ex-
Berkeley got five new investigators. MIT Down On the Farm act mass or sequence of amino acids in a
is the only other university that got five, protein (among other tasks); this facility is
A new crop of scientists is being cultivated at
and everybody else got three or less, which now open to the university community.
Janelia Farm, the HHMI’s “freestanding laboratory”
is a real statement for Berkeley’s quality,” located in Ashburn, Virginia. The farm–named for In his new role as HHMI President,
Tjian says. “Another thing I like about the Jane and Cornelia Pickens, whose parents origi- Tjian is contemplating his goals for the or-
Berkeley group is they’re very diverse in nally owned the property–is modeled after AT&T’s ganization, especially in light of the recent
their fields—they cover not just molecu- Bell Labs, which was famous for its basic research economic downturn. “A lot of it is trying to
lar biology, but also bioengineering and programs that produced such innovations as radio figure out where we can make the most dif-
chemistry.” astronomy, the transistor, the UNIX operating sys- ference—what fields and which scientists
The 2007 competition specified that tem, and UC Berkeley Professor/Secretary of Ener- should we be supporting that we’re not
applicants be between years four and ten of gy Steven Chu’s work on laser cooling that earned supporting today, and how much should
tenure-track faculty appointments. In con- him the Nobel Prize in Physics in 1997. we be doing outside of the borders of the
trast, the recent 2009 competition focused According to the HHMI’s website, the objective United States in the international scene,”
on early career scientists who have been of Janelia Farm is to allow scientists to “pursue fun- he explains. “There’s no doubt that there’s
faculty for only two to six years. And unlike damental problems in basic biomedical research tremendous talent all over the world that
in previous competitions, applicants for that are difficult to approach in academia or indus- the Hughes has not supported, and how
try because they require expertise from disparate
the 2009 competition were not required to much should we be viewed as an interna-
areas, they are too long-term for standard funding
already be receiving one or more active na- tional organization rather than a national
mechanisms, or they are outside the current pri-
tional research grants. The goal, according orities of other funding agencies.” However, rather one? That’s something I’m going to be
to the competition announcement, was “to than hosting researchers working on many unre- thinking about hard.”
identify the nation’s best biomedical scien- lated topics, the Janelia Farm senior staff chose to Clearly, the HHMI has been a major
tists at a critical early stage of their faculty concentrate on two main areas: the identification force in biomedical science, particularly in
careers, and to provide them with flexible of general principles that govern how information the last few decades. The idea of awarding
funding to develop scientific programs of is processed by neuronal circuits, and the develop- grants to people instead of specific proj-
exceptional merit.” The award recipients, ment of imaging technologies and computational ects is still unique in the realm of research
announced in late March, included Associ- methods for image analysis. funding. Regardless, the strategy seems to
ate Professor of Molecular and Cell Biology The labs at the research center are fully funded be working—12 of the current HHMI in-
Kristin Scott, who studies the biology of by the HHMI and are supervised by group lead- vestigators are Nobel laureates. “We don’t
taste perception. ers, who, because they are not required to perform know where the discoveries are going to
For all investigator competitions, ap- administrative duties or submit grant applications, happen,” says Tjian. “So you just have to
are expected to play an active role in research in
plicants must submit a curriculum vitae, find people who are really passionate about
the lab. Postdoctoral fellows and graduate students
a summary of their research plans, and what they’re doing. They don’t really see it
can also undertake research at Janelia Farm, though
five publications reflecting their most im- the latter must first attend either the University of as work—they see it as their life, and all
portant scientific contributions. The se- Chicago or Cambridge University for a year before they need are the resources.”
lection process takes about a year. “If you completing their PhDs at the Farm. “The junior fac-
start at 1,000 and you need to choose 50, ulty at Janelia Farm have groups of three people
you can imagine it’s a really rigorous re- only, and the senior faculty have groups of eight, so Meredith Carpenter is a graduate student
view process,” says Tjian. Once the list is they’re very small,” says Robert Tjian, HHMI Presi- in molecular and cell biology.
narrowed to a few hundred, it is sent to dent. “The idea is that you have no other distrac-
the HHMI Scientific Review Board, which tions–no teaching, no writing grants. Just do your
consists primarily of non-HHMI scientists. research and train your people properly.”
35
Lab on a Chip
36
ranging from large wells designed to collect control nanoliters of fluid (one billionth of a cause PCR requires successive heating, cool-
clusters of cells to microscopic traps that cap- liter), allowing for more efficient fluid con- ing, and mixing cycles, the chip can automate
ture single cells. trol and thus more sensitivity for on-chip this process and the reaction time is reduced
In addition to the maze of capture wells, measurements. As a result, chips can con- to less than 30 minutes, compared to the two
the lab has developed an on-chip procedure tain capillaries where, as Mathies describes, or more hours needed for the standard, lab-
to break trapped cells apart using a targeted “one microliter of fluid [one millionth of a scale procedure.
electrical current, releasing the cells’ inter- liter or close to the smallest visibly discern- In more advanced experiments, the lab
nal contents for further analysis. Under an able drop of liquid] would now be nearly two has expanded technology developed for the
alternative scheme, an electric pulse briefly meters long on-chip.” With this kind of accu- Human Genome Project to form rapid se-
compresses the cells’ outer membranes to racy and control, standard manipulations are quencing and genotyping chips that read
allow external genetic material to enter the transformed into entirely new dimensions of each “letter” of the genomic material within
cell and become incorporated into the host distance, time, and efficiency. a minute biological sample. In collabora-
genome. This on-chip genetic trick can be One traditional laboratory process that tion with Matthew Francis and Carolyn Ber-
combined with on-chip cell culture in which has benefitted tremendously from the re- tozzi, also in the Department of Chemistry,
a temperature-controlled chamber is used as duced scale and integrated fluid management the Mathies group developed a single chip
an incubator to proliferate single cells after is the polymerase chain reaction (PCR), a that combines single cell capture, PCR am-
applying the genetic modifications. Lee’s lab process that uses repetitive synthetic reac- plification of unicellular DNA or RNA, and
is now using these basic cell manipulations
to create chips that test and validate current
models of cancer cell adhesion, tumor forma-
tion, and nerve cell function.
37
An example of a cell culture
device developed in the Lee lab
(left). Cells are loaded into the
circular chambers on the right
and can grow for a period of
days or weeks. Nutrients diffuse
genotyping experiments are seen as a neces- dents are primarily interested in harnessing size. Additional membrane-like elements that
sary tool for stem cell biologists, tumor and the advantages of the reduced-scale chips to filter or concentrate proteins from a micro-
cancer researchers and geneticists alike. arrive at new and more effective protein ma- fluidic solution also add separation power.
nipulations with the hope of improving both These complementary elements are used in
Prototyping protein chips laboratory and clinically relevant measure- concert through a combination of fluid flow
Efforts such as the Human Genome ments. As a first step in this direction, they and electric current to move and enrich pro-
Project and large-scale genetic screening for have introduced protein separation, labeling, teins in a prescribed way.
heritable diseases have provided compel- and detection systems into their glass-etched This technology is only useful if the
ling reasons to pursue DNA-based micro- chips. proteins can be visualized, which is usually
chip analysis, but Herr and other research- On-chip protein separation gels are one done by some sort of labeling procedure. In
ers are keenly aware that protein analyses are of the many customizable tools in Herr’s the lab and on-chip, researchers use purified
equally powerful for disease diagnostics. It is on-chip arsenal. These homogenous poly- antibodies that have light-emitting molecules
proteins that really do the work of keeping mer gels start as a liquid that is introduced attached to them to bind to and visualize
cells healthy and fighting off disease. Accu- into an empty chip and solidified into place proteins that they are interested in following.
rate and real-time measures of such processes with the aid of laser light. Once the gel is in While long available on the lab scale, the re-
through protein profiling affords great power place, an electrical field is applied to the chip duced scale environment of the chip allows
for improving treatment regimes and individ- to drive charged proteins through the gel in Herr to concentrate and then label proteins
ualized drug development. Herr and her stu- accordance with their molecular charge and to measure samples of very low abundance.
There are all kinds of different cells, and often the number and type The potential medical applications of these pores were the driving
of cells in a sample can provide a lot of information about the health force in their creation. Professor Lucy Godley of University of Chi-
of a patient or the success of an experiment. Wouldn’t it be great if cago, a coauthor on the Lab on a Chip paper, is interested in develop-
there were a quick and easy way to count and characterize cells? Me- ing a means to quickly diagnose acute promyelocytic leukemia (APL),
chanical engineering professor Lydia Sohn’s lab designs microscopic a blood cancer that usually afflicts adults and can cause fever, fatigue,
pores, hardly wider than a single cell, to do just that. weight loss, and other unpleasant symptoms. APL is readily curable,
The pores are millimeter-long channels, through which liquid flows but treatment must be administered quickly, often within 24 hours of
and conducts a current. Foreign objects (including cells) entering the admittance, and is dangerous when given to non-APL patients. APL
pore block the flow and thus cause a drop in conductivity. To actually patients admitted on nights and weekends are sometimes not di-
characterize specific cells that pass through, the pores are lined with agnosed quickly and may die as a result. Godley believes a device
antibodies that interact with markers on the cell surface, slowing based on the pore system could provide a quick and simple method
cells with the marker of interest. By measuring the duration of the of detecting APL-associated cell types, allowing a faster response
conductivity drop, it is possible to distinguish between cells with the and hopefully saving lives. The portability and low cost of the system
marker (long drop) and those without (short drop). Sohn published a should make its incorporation into the medical field relatively easy.
paper in the August 2008 issue of Lab on a Chip demonstrating proof- The devices themselves cost less than a penny each, and the handheld
of-principle for this system. box to monitor pore conductivity costs only $1000.
38
These measures are then used to distinguish iated Joint BioEnergy Institute (JBEI) and the ly sensitive blood serum measurements to see
normal and disease-associated protein pro- University of Michigan School of Dentistry if leakage from the central nervous system to
files in just a single drop of liquid, such as published a paper showing that on-chip mi- the plasma can be detected, and whether this
from a tear, a drop of saliva or spinal fluid ex- crofluidics can be used to accurately test saliva correlates with the degree of trauma.
tractions, creating “a cleaner format through for proteins that have clinical importance for The diagnostic power of biochips is cer-
which standard clinical measurements can be oral health. This so-called point-of-care diag- tainly not limited to diseases of the Western
done in an automated or hands-free way,” as nostic study shows that fluorescence-based and developed world. Herr is just beginning
Herr says. measurements of a saliva protein known to to become involved in infectious disease diag-
be associated with progressing gum disease nosis through affiliations with organizations
Direct cell characterization can be useful for a number of clini- out in the field making diagnoses within a few years.
cal and research applications, but Swomitra Mohanty, a postdoc in In addition to directly saving lives, the pores can aid researchers
the Sohn lab, is interested in a different use for the pores: antibody working to better understand diseases. Bioengineering professor
detection. The body’s immune system creates specific antibodies in Irina Conboy studies stem cell aging, a process strongly tied to con-
response to different infections, so identifying antibodies can be a ditions such as Parkinson’s and Alzheimer’s. She needs to separate
means for diagnosis. The assay uses glass beads that only bind a given specific stem cells from mixed populations but finds existing sort-
antibody of interest. The beads are exposed to a patient’s blood ing techniques such as fluorescent-activated cell sorting (FACS) to
serum and then passed though the pores. If the antibodies of inter- be too difficult and destructive. FACS requires special preparation
est are in the serum, they will coat the beads, effectively increasing to label the cells before use, and during this time, cell function can
their size and leading to a greater drop in conductivity when travel- be affected. By contrast, cells can be put through the pores without
ing through the pore. Mohanty hopes to use this system to study any modification. In addition, while FACS requires many thousands of
neglected diseases, especially because the pores’ portability and low cells, the pores are effective with just a few hundred. Conboy is find-
price make them ideal for use in the developing world. Currently, he ing the pores to be a useful addition to her toolkit, and many more
is investigating the capability of the pores to distinguish between lep- researchers could similarly benefit from this new technology.
tospirosis and dengue fever, two tropical diseases with similar symp-
toms but very different treatments. With any luck, the pores will be ––Michael J. Brown
39
FEATURE Lab on a chip
(less than $1 each), thanks to economies of the levels and compositions of molecules nology that is routinely used as evidence in
scale brought about by the consumer elec- that can provide strong evidence as to the criminal court, but the Mathies lab has devel-
tronics industry and the use of older (but still past or current existence of life on Mars. The oped a chip that can analyze blood samples
very reliable) chip technology, he has long group took great pains to demonstrate that at the site of the crime in only a few hours by
envisioned modifying the chips to measure a the instrumentation was sufficiently sensitive a single technician. With the advent of this
whole host of disease antigens to assess infec- to make accurate measurements from a vari- chip, the multiple days of work by several
tion rates among isolated, at-risk populations. ety of samples found on the planet’s surface. forensic scientists are reduced to a chip, a
This type of on-the-ground rapid testing also “We really feel that we developed the most chip-reading instrument, a laptop, and a few
interests international health organizations sensitive measure of its kind that is currently man-hours of work.
who wish to track disease epidemics as they available, all because of the technological ad- Positioned on the brink of upward ex-
spread by making population-wide compari- vances that can be housed within our chips,” pansion, the lab-on-a-chip researchers at UC
sons of strain variation and environmental Mathies says. Berkeley all envision powerful ways that bio-
response to the propagating epidemic. Mathies and his group have also been logical microchips can expand opportunity
shaking up detection system development both inside and outside the lab. If chip tech-
Taking chips far and wide with more earthbound innovations by com- nologies successfully reach the marketplace,
It is easy to recognize how biochips are bining their DNA analysis technology with they will be able to provide up-to-date infor-
immediately applicable to health care and their chip manufacturing expertise. A group mation to help individuals and organizations
disease diagnostics, yet this is a narrow sub- of his scientists recently designed, tested, and to monitor and improve personal and public
set of the practical applications for micro- validated a fully self-contained human DNA health, food and drug safety, and environ-
chip technology. Lab-on-a-chip groups like forensics chip. The chip intakes a miniscule mental metrics. In what has commonly been
Mathies’s have repeatedly shown that chip- amount of human blood from a crime scene called our current “age of information,” these
based chemical detection systems that mea- and outputs a signature DNA profile that biological microchips are poised to be a key
sure a plethora of compounds have immense can be compared to a national databank of instrument for furthering our comprehen-
commercial and industrial utility for analysis previously characterized genomes. Within sion of the biological information that will
and discovery projects. Although the launch the chip, the extracted blood-borne DNA is be ubiquitously desired for its diagnostic and
timeline has recently been delayed to 2016, subjected to a PCR reaction to copy certain instructive power in the coming century.
his lab has already manufactured a chip and regions of human chromosomes that are so
reader that will travel aboard the next Mars highly variable from person to person that
Rover to look for biochemical traces of life on they are considered a unique DNA finger- Paul Hauser is a graduate student in nutrition
the Red Planet. This chip uses small samples print for every individual, even members of science.
collected from the planet’s surface to measure an immediate family. This is the same tech-
40
Peering
How archaeolog y
into the Past by Hanadie Yousef
and lavish parties. But for UC Berkeley archaeologists, these places are
rich with artifacts waiting to be excavated and analyzed. Archaeology, however, is not
limited to ancient bits of pottery. In actuality it covers a range of disciplines and hundreds of thousands of years of history.
While in some cases archeologists study the evolution of ancient civili- ancient ruins. Archaeologists have been uncovering ancient artifacts in
zations, archeology is also used to better understand more recent societ- Greece for over 100 years, and in some ways the history of the country
ies. Whether it is the study of ancient Greece or Hawaiian agriculture, seems completely exposed. But when UC Berkeley’s Classics Depart-
Berkeley archaeologists are traveling the globe to dig up the mysteries ment started its own archeological excavation in 1973, there was still
of our predecessors. an important question to be resolved. Written records suggested that
athletic competitions similar to today’s Olympics were held in Ancient
Unearthing history Nemea, located near Athens but there was no known physical evidence,
In a single day in modern Athens, an ambitious tourist can see the and the historical events surrounding these games were also obscure.
Acropolis, the Parthenon, the Temple of Zeus, and a number of other The search for evidence of the Nemean Games, carried out by
41
Professor of Classical Archaeology Stephen bump-raising thrill was the discovery of the asked him about it, he all but dismissed the
Miller and his team of archaeologists, re- entrance tunnel to the stadium,” says Miller. question. “At some point in the third week
quired a number of phases. First, they had to “We proved that the Greeks, at least by the age or so, a student put up her hand and said,
study the surface debris of stone or ceramics of Alexander the Great, knew how to build ‘Professor Miller, you have told us all about
at various sites to choose an interesting place the arch and the vault, a discovery that actu- the athletic competitions and various ath-
to begin their search. Next, they began exca- ally made it into the Encyclopedia Britannica letic facilities and athletic practices, but you
vating the site, digging deeper and deeper to Yearbook.” The arch and the vault are a fun- haven’t mentioned any locker rooms.’ ‘Well,’
move backwards through time. Each layer of damental construction system used to create I responded, ‘you have learned that the an-
soil was searched for broken pieces of pot- roofs or ceilings and span the space between cient Greeks competed in the nude so you
FEATURE Archaeolgoy
tery, coins, and other artifacts to deter- should understand they didn’t need
mine the time period of that soil deposit. locker rooms to put on their uniforms.’
All the materials were collected, labeled, Her hand shot back up. ‘But Professor
and taken to the site’s museum for clean- “The single biggest, chilling, goose Miller, where did they leave the clothes
ing, conservation, and cataloguing. bump-raising thrill was the discovery they took off?’ No scholar, to the best
Bits of pottery can provide valuable of my knowledge, had ever asked that
information through chemical analysis of
of the entrance tunnel to the question, and it came back to me 15
their composition and residue found on stadium.” years later when the Nemea locker room
their surfaces, but piecing together an en- began to emerge from the earth.”
tire vessel provides a much fuller view of Besides discovering the physical
its purpose and implications for the so- remnants of the ancient Greek athletics,
cieties that used it. “This process is much like walls and other supports. It had been previ- Miller and his graduate students also uncov-
putting together a jigsaw puzzle,” says gradu- ously assumed the Greeks used a simpler sys- ered key events that shaped the history of
ate student John Lanier, who has worked in tem that only supported flat roofs. the Nemean Games. They found evidence
Nemea studying ancient Greek pottery un- Miller also discovered an ancient locker that Nemea, which began to function as an
der the guidance of Kim Shelton, Assistant room where the Greeks could undress be- athletic center in 573 BCE, was destroyed in
Professor in the Department of Classics and fore competing in the nude—the first ever 415 BCE and that the destruction was accom-
director of the Nemea Center for Classical identified locker room from Ancient Greece. panied by fire, bronze arrowheads, and iron
Archaeology, founded in 2004 upon Miller’s When Miller began his excavation, locker spear points. “In other words, a battle was
retirement. “These same techniques gener- rooms were the furthest thing from his mind. fought in this neutral, apolitical sanctuary, al-
ally have been used in archaeology since the In fact, when a student in an undergraduate most certainly with the Spartans,” says Miller.
early 20th century,” says Shelton. “But work course he was teaching in 1975 “The excavations have also
was conducted more quickly, less care- shown that the games did
fully and by more work- not take place at Nemea
ers. Less was also known for a couple of generations
about the historical and thereafter, even though we
chronological context of know from written sources
the finds than we know that they were held during
now.” this period.”
42
tel, and a bathing house. Despite slain by a serpent.
this vast construction, within two Apart from a shrine
generations (by 271 BCE), the for Opheltes that
games had left again for Argos was excavated by
and never returned. In the end, Miller’s group and
according to Miller, the Nemean probably built many
Games were held in Nemea for hundreds of years
only about 25% of their history. after Opheltes lived,
One of Miller’s proudest there is no evidence
FEATURE Archaeolgoy
achievements thus far in the that Opheltes was ever
study of Ancient Nemea has in Nemea. The history
been the resurrection of the that has been passed
Nemean Games, beginning in through the ages by
1996. Today’s Nemean Games word of mouth, poetry,
are organized and run by a and folk tales indicates
local group, The Society for that the events the
the Revival of the Nemean myths are based on took
Games, in collaboration with place in the Bronze Age,
UC Berkeley. “Although the Nemean Games Berkeley archeologists sift at which point Nemea
were known previous to Berkeley’s arrival at through soil to uncover ancient artifacts at Nemea. was a kingdom. By the
the site, it was Professor Miller who found the time the Nemean Games were held, Nemea
location and excavated the stadium, and who was not a town with inhabitants, but just a
was instrumental in creating the society for plans to take research in a new direction. In sanctuary for Zeus and a site for the games.
the revival of the games,” says Shelton. particular, she is interested in why Ancient Shelton is making plans for new excava-
Nemea was chosen as a site to honor Zeus in tions, beginning in 2010, to find evidence of
Digging deeper into time the first place. According to myth, the Nem- human settlement in Ancient Nemea before
As the current director of the Nemea ean Games were founded after Opheltes, the the founding of the games. She wants to know
Center for Classical Archaeology, Shelton baby son of a Nemean king, was tragically who was in Ancient Nemea during the time of
43
the myths and what their lives were like. She archaeologists are studying civilizations that Kirch, director of the OAL and professor in
also wants to learn more about the religious existed more recently. On a different set of the Departments of Anthropology and Inte-
history of the site. During the times of the islands, these in the Pacific Ocean, Berkeley grative Biology, is heading the project on the
Nemean Games, Nemea contained not only a archaeologists are actively studying native Berkeley end, while his principle collabora-
stadium for the games, but also held temples, Hawaiian society and its relationship to agri- tor from Stanford is biology professor Peter
gardens, and cyrpus groves that made up an culture. The Oceanic Archaeology Laboratory Vitousek.
entire sanctuary to Zeus. Was there also a (OAL), established by UC Berkeley in 1989, Kirch’s team is trying to understand how
sanctuary in the time of the myths, during carries out research into the archaeology, pre- the agricultural systems of pre-European Ha-
the Bronze Age? In other words, do religious history, and historical anthropology of the waiians related to the environmental aspects
FEATURE Archaeolgoy
practices such as sacrifices and rituals go Pacific Islands and their indigenous peoples of the landscape, such as soil nutrient distri-
back to prehistoric times? Shelton’s exper- and cultures in the hope of applying what bution and the long term effects on soil prop-
tise is in ceramics and pottery, and she hopes they learn to modern agriculture. erties, and its sustainability. “We are looking
to study these types of artifacts, along with Since 2001, archaeologists, ecologists, at the linkages between agriculture, soils, and
small metal fragments and any architectural demographers and soil scientists from sev- human population, through the perspective
evidence, to separate myth from fact. eral universities, including UC Berkeley, of archaeology. We are linking natural science
have been collaborating on archaeology proj- with social science to determine the real long
Ancient sustainability in Hawaii ects in Hawaii. They are using Hawaii as a term processes associated with changing so-
Shelton’s and Miller’s work fits the tra- model system to understand the link between cieties,” said Kirch.
ditional view of archeologists as researchers changing social and political structures of Kirch and his colleagues have studied
uncovering the history of civilizations that human civilizations and their non-industrial- the effect of long term agriculture and the
existed thousands of years ago, but some ized agricultural production systems. Patrick impact of several hundred years of cultiva-
Pre-European Hawaiians tended scenic fields like this one in the Kahikinui agricultural zone for several hundred years.
44
tion on soil nutrients on the Hawaiian island
of Maui by combining a geochemical method
of dating with an archaeological approach.
Kirch’s team mapped out the landscape of
the Kahikinui agricultural zone, locating all
temples that operated as centers for control-
ling overproduction. Based on this analysis,
they chose to study layers of soil in various
locations once used by native Hawaiians for
FEATURE Archaeolgoy
cultivation, as well as the layers of soil from
uncultivated areas as a comparison. They
then measured physical characteristics of the
soil such as pH, density, color, texture, and
the amount of key chemical nutrients. “We
were able to get quantitative measurements
of key nutrient loss in soil over 300 years of
intensive cultivation,” said Kirch. The team
has found that the soil used by Hawaiian
farmers for growing crops has significantly
lost its nutrient value, which affects crop
yields. In a research project published in Sci-
ence, they showed that centuries of cultiva-
tion resulted in significant loss (28 to 75%)
of calcium, magnesium, sodium, potassium,
and phosphorous content.
Kirch and collaborators are also studying
the relationship between climate, soil fertility
and the kinds of agricultural systems devel-
oped on the Hawaiian archipelago by the na-
tive Hawaiians before European contact. In
another Science paper, Kirch and collabora-
tors analyzed climate and soil fertility on the
young and old islands in the Hawaiian archi-
pelago to determine the methods of farming
used by native Hawaiians in the past. They
distinguished between two kinds of agricul-
ture, one suitable for drylands that depends
on rainfall to feed crops, and an agricultural
system based on wetland irrigation. They re-
ported that irrigated wetland agricultural sys-
tems are found primarily on the older islands
due to their well-developed natural drainage
networks. In contrast, archeological evidence
has shown that dryland agricultural systems Alex Bare and students lay out an excavation grid in Kaupo, Maui.
are constrained to younger islands.
To determine the factors that confined
large dryland agricultural systems to the are more predictable and controllable. that this may explain why aggressive and ex-
younger islands, Kirch’s team studied the The differences between rain-fed dry- pansive chiefdoms developed on the younger
rainfall and soil fertility in the Kohala Moun- land and irrigated wetland agricultural sys- islands, while societies on the older islands
tain area. They found that on the younger is- tems on the younger and older islands of the were more peaceful.
lands, the amount of rainfall and soil fertility Hawaiian archipelago give insight into the so-
fell in the boundaries necessary to allow high cial and political structures of the native Ha- The timing of societal evolution
crop yield from intensive dryland agriculture, waiian societies that developed on these is- Berkeley researchers in Hawaii are also
while on the older islands, greater rainfall re- lands. Dryland agricultural systems are more studying the sociopolitical and religious
sulted in less fertile soil, as measured by the labor-intensive, have lower crop yields and changes that took place in Hawaii before Eu-
amount of phosphorous and base nutrients are more vulnerable to climate perturbations ropean contact. In particular, they are looking
therein. Nevertheless, wetland irrigation agri- in comparison to wetland irrigation systems. at the types of rituals conducted to honor the
cultural systems allow greater crop yield and Therefore, Kirch and his colleagues inferred god of agriculture at the temples construct-
45
ed at agricultural sites. Coral branches were
thought to be sacred to the god and were
taken out of the sea and placed on temples to
honor him. Based on a precise dating meth- Leprosy Settlements in Hawaii
od that measures the decay of the element
uranium to the element thorium, known as
thorium-230 dating, Kirch’s group and his James Flexner, one of Kirch’s graduate To accomplish his goals, Flexner has
colleagues dated the coral offerings and de- students, is conducting an archaeologi- conducted surface mapping and exca-
termined the exact construction period of cal study of the inmates of the leprosy vations at different kinds of house sites
FEATURE Archaeolgoy
temples to honor the gods of agriculture at settlement at Kalawao, which was active from the Kalawao settlement. He’s also
the Kahikinui district on the island of Maui. from 1866-1900. Leprosy is caused by been analyzing numerous artifacts he has
The usual method used to date archaeo- the bacteria Mycobacterium leprae, which collected from the old inmates of the
logical remains, radiocarbon dating, mea- stimulate a severe inflammatory reaction leprosy settlement and is also looking
by the body that damages the peripheral into numerous archives, researching the
sures the relative amounts of two isotopes of
nerves and upper respiratory tract. The relevant 19th century documents to try
carbon, one common and one relatively rare,
primary external symptoms of leprosy to understand what people in the past
and assigns a date to the objects based on are skin lesions that, when left untreated, thought about leprosy.
those amounts. While the use of thorium-230 eventually lead to permanent damage “What’s really interesting is the fact
to date objects has been available for some of the skin, nerves, limbs and eyes. His- that many of the people exiled to Ka-
time, this was the first time it was applied to torically, patients around the world have lawao really worked hard to create a
archaeological research. “This technique isn’t been quarantined, or forced to live in working community, even though many of
new,” Kirch says, “but its application to dat- leper colonies. Kalawao in Hawaii is one them were torn away from their homes
ing cultural remains is new. The really neat such place. and families,” said Flexner.“The landscape,
thing about this is typically when you use ra- Flexner is studying the historical ar- and the things they left behind, help tell
diocarbon dating, you get a high error rate, chaeology of the leprosy settlement at that story in a way that the written docu-
like plus or minus 50 years. With this coral Kalawao. “The goal of my project is to ments typically don’t. Leprosy is a pow-
dating technique, you get plus or minus three explore the ways that spatial organiza- erful symbol for stigma and isolation, and
to four years! It has really aided in being able tion and material culture structure the it’s fascinating to see how people coped
to resolve the chronology of these sites.” day-to-day practices of social life in situ- with the disease, which causes a number
ations of lifelong incarceration, as medi- of physical complications in day-to-day
A more accurate prediction of the time
ated through the stigma attached to lep- life, and with being exiled from the sup-
period in which the temples in Maui were
rosy in this case,” explained Flexner. port of their families and communities.”
built was needed to make inferences about
the sociopolitical and religious changes that
occurred in pre-contact Hawaii. They used
this dating information to determine when
the temples were constructed and when the a Hawaiian archaeologist, but to be effective sometimes the influence is even more tan-
rituals associated with them—such as the in that pursuit you need to gain a substantial gible, like when ancient races to praise Zeus
collection of surplus food and goods as trib- understanding of biology, botany, geology, are brought into the modern world.
ute and the imposition of ritualized controls and even astronomy. All of these disciplines
of production—occurred. They are discover- answer different questions and ultimately al-
ing that the temples in Maui were construct- low us to better understand how past people, Hanadie Yousef is a graduate student in
ed within a very narrow time span of about Hawaiians in this case, lived and thought molecular and cell biology.
60 years, from 1580 to 1640 CE. The tim- about their world.”
ing of intensive temple construction reflects “This research is significant because it
a fundamental change in the sociopolitical is relevant not only to Hawaii but anywhere Want to do more
structure of the inhabitants of the Kahikinui in the world with non-industrialized agricul- with science?
district. Kirch concluded that Hawaiian ag- ture, such as Africa and Southeast Asia,” says
ricultural societies were transformed rapidly Kirch.
from small chiefdoms to larger states that
used a religious ideology based on a temple Archaeology and the modern world
ritual system to control agricultural societies. Whether they are studying sports from
Studying the agricultural societies of Ha- ancient Greece or the more modern native
waii and how they relate to the ecology of the Hawaiian agriculture, archaeologists are
archipelago, as well as studying the sociopo- unearthing the evolution of human civiliza-
litical and religious aspects of these societies, tion and culture, from the era of hunters and The Berkeley Science Review is always
required the integration of many fields. Alex gatherers to advanced societies with complex looking for new writers, editors, artists,
Baer, a graduate student working on the proj- architectural and cultural foundations. Not and layout editors.
ects in Hawaii, explains the significance of only do discoveries about past societies have
s c i e n c e r e v i e w. b e r k e l e y. e d u
this interdisciplinary research. “I’m trained as implications for our current way of life, but
46
Back Address Inbox
Today
Spam
Calendar Grows Up
Contacts The increasing threat of internet abuse
by Dan Gillick
Tasks
47
and running it themselves. Once installed, were never delivered (blacklists block all $10 spent, assuming they keep all the profit
the software broadcasts its availability to the email from a list of addresses that are known from the purchases. And yet, the spam keeps
Storm network. A master server organizes to be operated by spammers, for example), coming.
tasks and “proxy” bots distribute specific and 99% of what remained was probably
instructions to “worker” bots, which return blocked by inbox spam filters. In the end, 10 Abuse arrives
status reports and request more work. Some thousand users visited the pharmacy page, The world’s first email spam (the term it-
estimate that Storm, at its peak in late 2007, and just 28 tried to make purchases, aver- self derives from a Monty Python skit involv-
controlled over 1 million com- ing singing Vikings at a spam-
puters. heavy restaurant—repetition ad
Kreibich and his colleagues In 2003, Slammer infected 75,000 nauseum) was sent on May 3,
intentionally installed the soft- computers in under ten minutes. 1978 by Gary Thuerk, an aggres-
FEATURE Spam
48
Worker bots ATMs failed. Paxson estimated that a well-
Gateway
written worm could cause upwards of $100
1
billion of damage in a day.
Traffic Archive
Master The invisible hand
servers While worms continue to plague the
4 2 Internet—Conficker infected nearly 15 mil-
Proxy bot 1
3 lion Windows-based personal computers in
January—the worm era, characterized by an
C&C Storm Proxy bot 2 intrepid anarchist playfulness, gave way to
C&C something with real staying power: markets.
FEATURE Spam
Rewriter “A sophisticated underground economy has
emerged to profit from Internet subversion,”
Proxy bot 8 Paxson explains. Bots are herded together
into botnets, computational armies with
Injected Injected Target Pharmacy/
Spam Webmail regular Mail Infection WWW enormous collective bandwidth, and “dirt-
cheap access to bots fuels monetization via
relentless torrents of spam.”
Image courtesy of Christian Kreibich
49
in gradually, perhaps a few thousand email ents, appear to be acts of “hacktivism,” but fer overflow.” By studying a piece of software,
addresses at a time, to email regarding Viagra, the monetary incentive—demanding ransom an attacker can often find a specialized input
knock-off watches, stolen software, awesome from companies unprepared to parry such that causes the program to crash, and in the
postcards. Modern spam filters are clever, attacks—is feeding a post-cause generation. process, return control to the attacker rather
Kreibich explains, so “no two emails that Unfortunately, spam and DDoS are just than the user. While it is good programming
Storm sends are exactly the same.” The bots the tip of a formidable iceberg. Identity theft, practice to include checks for buffer over-
are instructed to create random permutations by logging keystrokes on compromised com- flows, Saxena says “missing a few is all but in-
of the essential words and letters, specifically puters or by coordinated password guessing, evitable.” Programmers, after all, are human.
designed to slip past the defenses of Gmail, for example, appears to be on the rise, though Microsoft’s updates or “patches” often add an
Hotmail, and Spamassassin. it seems that this is not yet the focus of most overflow check for some buffer buried deep
botnet operators. More generally, any kind of in the Windows operating system. Unfortu-
FEATURE Spam
What are we up against? private information with value, from internal nately, according to Saxena less than 5% of
While a few extra emails about sexual business statistics to government secrets, cre- users update in a timely fashion. In addition,
enhancement products are mostly an annoy- ates incentives for theft. Song’s group has shown that exploits can be
ance, the possibilities for an attacker who generated automatically by using a Microsoft
controls hundreds of thousands of computers Bitblazing patch to find flawed code—a serious concern
are alarming. Shortly before the 2008 South Opportunities for attackers create re- given how quickly worms can spread.
Ossetia war, a Distributed Denial of Service search projects for graduate students like More generally, the group is interested
(DDoS) attack took down the web sites of those working with Dawn Song, a computer in program analysis, a subfield of computer
Georgian President Mikhail Saakashvili and science professor at UC Berkeley. A deep un- science concerned with inferring the behav-
the National Bank of Georgia. This was the derstanding of what makes software exploit- ior of a program from its source code. This is
work of a botnet, its bots instructed to con- able and the ability to infer the logical struc- important for security because it is “a step up
nect to these sites simultaneously, overloading ture of a program before running it are the from antivirus signatures,” Saxena explains
the servers that process incoming requests for keys to buttressing the user side against even (traditional antivirus software looks for dis-
data (it remains unclear whether this was co- the most novel attacks. Broadly speaking, tinctive sequences of characters in files—like
ordinated by the Russian government). these are Song’s research goals in her group’s a fingerprint), “which fails because malware
DDoS attacks, described in a Wired article BitBlaze project, which aims to screen soft- encodes itself.”
as “the digital equivalent of filling a fishtank ware for potential danger and defend against Consider the problem Kreibich and
with a firehose,” have recently targeted the malicious code—exploits that cede control to his colleagues faced in reverse engineering
BBC, CNN, AlertPay (online payment), and an attacker. Storm. Following an AwesomePostcards link
GoDaddy (domain name registration), for ex- Prateek Saxena, a graduate student intentionally, they downloaded a 140 kilo-
ample. Some of these, like a current attack on working with Song, outlines the most com- byte executable file. That’s around 300 pages
KidsInMind.com, a movie rating site for par- mon exploit around, involving a “stack buf- filled with 0s and 1s. From this binary novel,
they sought first to distill the command and
control structure of Storm, and second, to
create a subtly modified version of the file for
their research purposes. Song’s group would
like to scan such binary files automatically,
looking for suspicious instructions.
Their approach is two-pronged. The first,
static analysis, is more theoretically appealing
and more challenging. Each computer pro-
gram, at heart, enacts some underlying flow
chart. A student in an introductory computer
50
spammer commission
paid
generic
email pharmacy pills
target Affiliate site
Viagra! page -
advertismen redirects
program non-US
t
Image courtesy of Stuart Brown
with supply
pharma other
FEATURE Spam
link recipients
clicks
email on link
recipient
ship to customer
sale made
The general structure of an economically mature Viagra spam campaign. The spammer provides addresses and a means to distribute email via a botnet
while the pharmacy procures and ships cheap pills. Then, any entrepreneuring individual can rent the spammer’s services, making a profit by sending traffic
to the pharmacy.
approach to understanding a mysterious market economy. “The fundamental insight the fullest,” says Chuang.
binary file. Saxena calls this strategy “taint is that there is a misalignment of incentives If the basic problem is a misalignment,
tracking.” The researchers create a “virtual at work.” While the botnet operators profit, then the solution may involve re-aligning.
machine,” an operating system running in- the perceived cost to each user is effectively Chuang and his students are just beginning to
side the normal operating system, and run zero. Individuals almost never know if they explore what this might involve. The “stick”
programs in this controlled environment, are infected and don’t care. Even if the result scenario makes users economically liable for
collecting information. What data is read is some kind of identity theft, the connection security breaches originating at their comput-
from memory and written to memory? What between a dodgy website visited six months ers; the “carrot” option—”typically more suc-
files are accessed? Is any connection estab- ago and some mysterious credit card charges cessful,” says Chuang—rewards users who
lished with remote computers? What kind? is tenuous at best, and practically, the credit invest in security. Good behavior—keeping
By assembling such statistics for known safe card companies and banks almost always as- antivirus software up to date, installing op-
programs and known malware, they can sume the financial burden in such cases. erating system patches, avoiding suspicious
compute the probability that some unknown Chuang likens
program may be dangerous based on its be- the botnet phenom- The Russian Business Network
havior. enon to a kind of
One goal of the BitBlaze project is to rev- “reverse free-riding.” The notorious Russian Business Network (RBN), referred to as
olutionize antivirus software by combining Whereas file sharing “the baddest of the bad” in a report written by security company
elements of both static and dynamic analysis. or public television VeriSign, is “a for-hire service catering to large-scale criminal opera-
By testing unknown software in a controlled benefit everyone re- tions.” Originally organized by computer science graduate students
analysis environment, Song hopes to dramat- as a legal Internet service provider, illegal activity proved financially
gardless of their sup-
irresistible. Little is known about the network, but rumors abound:
ically improve protection for Internet users. port, botnets are “a
it has been blamed as the perpetrator of the Georgia cyber-attacks;
“People download random programs all the peer-to-peer network its leader, known as “Flyman,” is supposedly related to a powerful
time, like curious children will chew on just contributing to net- Russian politician; it is the alleged operator of Storm.
about anything,” Song says. Internet users work insecurity—a
Many Internet providers host illegal material—online gambling
need something like watchful parents to keep public bad as op-
sites, for example—but according to VeriSign, “the difference is that
them out of trouble. posed to a public RBN is solely criminal.” They also seem emboldened by immunity
good.” To free-ride from Western law enforcement. When, in late 2006, the Nation-
Carrots and sticks the Internet is to con- al Bank of Australia tried to fight the “Rock Phish” scheme that
Professor John Chuang, at Berkeley’s tribute to a public tricked users into revealing account numbers and passwords, the
School of Information, shares Song’s feelings bad. “Botnet opera- RBN took down their website for three days.
about required supervision, but takes more tors have stumbled “RBN feel they are strongly politically protected.They pay a huge
of an economist’s perspective. “How did bot- upon or engineered amount of people. They know they are being watched. They cover
nets come about?” he asks rhetorically, refer- technology based on their tracks,” says VeriSign. According to the report, only strong
ring not just to the technical achievement but this misalignment political pressure on Russia will keep the RBN in check.
to their centrality in the developing black- and exploited it to
51
Geographic locations of spam
“conversions”: 541 users (yel-
low flags) clicked on emulated
greeting cards and 28 users (red
flags) tried to pay for products
at the mock pharmacy site.
websites and downloads—could result in a just a side-project, an experiment much less nity to “make money from home”—receiving
rebate from an Internet service provider like fruitful than their primary activities. and re-shipping packages or transferring
Comcast or Verizon. Otherwise, Chuang sug- Kreibich admits he knows little about funds to international bank accounts. What
gests, they could raise premiums, like car in- economics, but his sense is that the market is differentiates these mule requests from typi-
surance rates increase after an accident. far from mature. To study this question, the cal spam is that there is often a person at the
The car insurance analogy is not per- group, which recently hired a new postdoc other end. “We responded to one of these
fect, but it reveals something about how new with an economics background, is trying to emails,” says Kreibich, “and sure enough,
and unregulated the Internet industry is. measure diversification. Spam emails have we were able to see from the reply—this guy
“I’ve heard this line about how we call it the links, and each link is associated with a do- in Moscow was using a Macbook, running a
‘Information Superhighway’,” says Chuang, main, which somebody had to register. Un- particular version of Microsoft Outlook.” By
“and yet there’s no license to drive or driver’s fortunately, databases with this information automatically generating responses, spam-
education.” A reckless driver is dangerous for are neither centralized nor standardized, so ming the spammers, the researchers could
everyone on the road, so it’s good for society automating these lookups is difficult. Worse, try to assemble a map of mule requests. Such
to insist on training drivers and penalizing data would be invaluable, Kreibich suggests,
them when they go too fast. Perhaps Internet In 2008, a botnet took because “the economy may be bottlenecking
users should be treated similarly. on mule supply”—a crucial method for dis-
down the web sites tributing the money-laundering task.
Missing data of Georgian President As with each project, “we have no idea
Back at the International Computer Sci- what we’ll find,” Kreibich says, since so much
ence Institute, Dr. Paxson produces a few
Saakashvili and the National about the market and its operators is still un-
photocopied pages from a precarious stack. Bank of Georgia. known. In November, two Internet service
They are transcripts of legal proceedings— providers decided to stop routing traffic from
a credit card fraud case. He flips through registrars offer “domain testing,” allowing a McColo, a web host suspected of housing
and points to a table indicating the stolen potential client to see what kind of traffic a computers involved in criminal activity. In
amounts, a few million dollars in total. “This new domain name receives before finalizing one day, worldwide spam dropped by over
guy’s not a punk,” he says, “but he’s prob- their purchase. Spammers capitalize on this 60%. The demise of Intercage, another host
ably not a kingpin either.” Such fragmented service, using a temporary domain for a few known to have operated a number of Storm’s
evidence is Paxson’s response to a question days and then moving on. control servers, led to a similar but less dra-
about the size of the industry. “I wouldn’t feel Another way to study diversification is matic reduction in September. Both McColo
comfortable quoting a number. Not even an through the appearance of the destination and Intercage are based in California. “We
order of magnitude,” he says. sites. While spam emails show impressive always suspected Storm was operated out of
To understand the discrepancy between variety, the pharmacy sites they link to, for another country, likely Russia,” Kreibich says,
the retail price of spam (how much a botnet example, are quite consistent, allowing the “and here it turns out that some of their most
operator charges to send junk email) and the researchers to make some inference about crucial infrastructure was located just down
conversion rate observed in the Spamalytics the major players in the field. At this point, the street.”
study requires much more information about Kreibich says they have a reasonable idea of
the industry. The statistics suggest that Storm “which botnets are sending which spam.”
is not particularly decentralized—perhaps a One interesting proposal, Paxson’s idea, Dan Gillick is a graduate student in computer
few disgruntled expert programmers making which has not yet developed into a research science.
a good living selling Viagra. Or maybe the project, involves studying the unusual “mule”
one campaign the researchers tracked was market. Some spam emails offer the opportu-
52
53
book review
Born to Be Good instead engage in reconciliation. When we
see embarassment, after all, our first impulse
by Dacher Keltner is to playfully downplay the significance of
WW Norton & Co. the slip-up and join in laughing it off.
352 Pages, $25.95 In addition to jen emotions, there are jen
BOOK REVIEW
54
who k new?
So Smart After All
T his issue’s “Who Knew?” will be my
last for the Berkeley Science Review, so I
not surprising that the rats could run through
a maze, even remembering their trajectories
over the course of multiple trials.
vasive neuroimaging. Oxygenated and de-
oxygenated blood respond differently in the
WHO KNEW?
thought I would end my run with a bang. I presence of a magnetic field; this allows neu-
will make all of you 10 times smarter by the Another remarkable feature of the brain roscientists to track blood flow changes in the
end of this article. It’s a bold statement, but that could help to propagate this myth is its brain, which are then interpreted as neural
trust me. You see, you’ve been consistently powerful compensatory ability. The left and responses accompanying cognitive activity.
lied to for many years, especially in popular right hemispheres can adjust for deficien- By comparing images of a human performing
entertainment and advertising, forging an im- cies in the other half, and many specialized certain tasks with a baseline image, research-
pressively resilient myth. The culprit? The regions are bilateral, meaning copies are ers are able to locate where neural activity
belief that we use only 10% of our occurs for such functions as high-level
brains. reasoning, processing of auditory and
The origins of this myth are visual stimuli, memory recall, language
somewhat hazy. Some argue that recognition, and so on. For instance,
it began in the 1700–1800s with if you are asked a series of easy math
the development of phrenology, problems (2+2=?), this establishes your
a pseudo-science that associates baseline image for basic reasoning. A
certain behavioral traits with the complex follow-up math question will
size, shape, and details of the activate the neurons responsible for
skull. Others attribute the origins higher-level quantitative reasoning,
to a misunderstood or misinter- and the difference in the images high-
preted quote from Einstein. The lights this region. The important result
modern, quasi-scientific version from fMRI studies is that every region
of the myth likely has its roots in of the brain has an associated function.
a particular experiment conduct- These images are by far the most de-
ed in the 1930s by Karl Spencer finitive proof that we use 100% of our
Lashley, an influential American brain—the catch is that we do not use
psychologist and behaviorist. He all of it at a single given moment.
removed portions of rats’ brains This specificity for a given con-
and found that they performed scious task may be another reason why
Image courtesy of Gaetan Lee
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