research penn state 2009/2010

2009–10

Mammoth AchievementNext-generation DNA sequencing shines new light on evolution—and extinction.

Volcano Anatomy • Engineering the Brain • Reefs on the Brink

Research | Penn StateV o l u m e • 3 0

N u m b e r • 1

Cover Story

Departments

34

Mammoth Achievement

Forget Jurassic Park. By success-

fully sequencing the DNA of a

long-extinct species, Stephan

Schuster and Webb Miller have

helped push back the boundaries

of molecular biology.

4 Profile: Stellar Detective

6 Encyclopedia: Targeting Melanoma

Follow the Glow

Stopping Malaria’s Spread

History on Ice

Splitting Water 2.0

Selenium and AIDS

War: Not the answer?

Advanced Search

40 Worth Reading: A Sporting Chance

Standing Stone

No Leaf Unturned

Origins of Species

Typecasting Labor

Master Detective

42 On the Web: Look, Listen, Learn

43 Endpaper: Visualizing the Distant Past

On the cover:

Artist’s rendering of a woolly mammoth, long-dead cousin of the elephant. Decoding the genome of this ancient species may tell us why it vanished. See “Mammoth Achievement” on page 34.

Cover photo credit: © 2009 Mark Newman/AlaskaStock.com

Research/Penn State is published by the Office of the Vice President for Research at The Pennsylvania State University. The magazine samples the diversity and drama of Penn State’s $765-million-a-year research program as a public service to inform, entertain, and inspire the University community. Opinions expressed do not reflect the official views of the University. Use of trade names implies no endorsement by Penn State. ©2009 The Pennsylvania State University. For permission to reprint text from Research/Penn State (U.Ed. RES 10-13) contact the editor: phone 814-865-3478; fax 814-863-5368; e-mail [email protected]. Visit www.rps.psu.edu to learn more.

Publisher: Eva J. Pell Editor: David Pacchioli Associate Editor: Melissa Beattie-MossAssistant Editor: Sara BrennenProduction Manager: Joan ScholtonDesigner: Bryan BennerContributors: Amitabh Avasthi, Adam Eshleman, Charles Fergus, Scott Johnson, Sara LaJeunesse, Gigi Marino, A’ndrea Elyse Messer, Jenna Spinelle, Fred Weber

This publication is available in alternate media on request. The Pennsylvania State University is committed to the policy that all persons shall have equal access to programs, facilities, admission, and employment without regard to personal characteristics not related to ability, performance, or qualifications as determined by University policy or by state or federal authorities. It is the policy of the University to maintain an academic and work environment free of discrimination, including harassment. The Pennsylvania State University prohibits discrimination and harassment against any person becauseof age, ancestry, color, disability or handicap, national origin, race, religious creed, sex, sexual orientation, gender identity, or veteran status. Discrim- ination or harassment against faculty, staff, or students will not be tolerated at The Pennsylvania State University. Direct all inquiries regarding the nondiscrimination policy to the Affirmative Action Director, The Pennsylvania State University, 201 Willard Building, University Park, PA 16802-2801; Tel 814-865-4700/V, 814-863-1150/TTY.

2 0 0 9 – 1 0

Features

S e e O u R w e e k l y f e a t u R e S O n t h e w e b a t : w w w . R P S . P S u . e d u

14

The Anatomy of a Volcano

With remote sensing and an international army of

geologists, SEA-CALIPSO takes the measure of an

angry mountain.

20

Brain Storms

Researchers at the Center for Neural Engineering

believe their work on the physics of seizures will yield

an electrifying new treatment for epilepsy. Patients

like Jessica Gordon hope they’re right.

26

Behind the Mask

Penn State researchers look below the surface of

terrorism to understand what compels and repels

individual involvement.

30

Trouble in Paradise A better understanding of coral–algal symbiosis

may help predict the survival of endangered reefs

around the world.

Stellar Detective: A Profile of Mercedes Richards

By Adam Eshleman

Printed on the pages of Mercedes Richards’ high school yearbook, a friend’s parting sentiment reads:

“Mad Mercy! Her ambition is to obtain a Ph.D. in Astronomy!”

Like only a few of her classmates back in Kingston, Jamaica, Richards, now profes-sor of astronomy and astrophysics at Penn State, loved looking up at the skies. “I made a decision ’round about sixth grade or so that I wanted to be an astronomer,” she declares. Having set her sights on the stars at such a young age, Richards has since become one. After academic stops at the University of Virginia and the Institute for Advanced Study in Princeton, she joined the Penn State faculty in 2001. In 2008, in recognition of her record of international accomplishment, she was awarded Jamaica’s highest academic honor, the Musgrave Gold Medal. “Mad Mercy” has come a long way, but it hasn’t always been easy. “The road I have traveled has not been smooth,” she says. “There have been some obstacles.”

A Star is Born“The stars in Jamaica are really, really beautiful,” Richards remembers. “My father and I would just sit outside and talk about life and philosophy under the canopy of the skies. More than anything else I wanted to understand what was going on. Why do stars shine?”

Richards credits her father—a police detective—for bestowing on her the skills of observation and deduction, and she is grateful to her mother—an accountant—for instilling in her the importance of precision in her work. While raising her in a suburb of Kingston, her father often took her to a nearby botanical garden shortly after dawn. In the early morning quiet, father and daughter sat in awe of the nature around them (“It was like

being in a place of worship”), and her father taught her to identify the nuanced varieties of plant species.

Today, Richards uses that same set of skills to examine the stars. “What I do is definitely detective work,” she explains. “Astronomers want to know what hap-pened. We look for evidence. We have to piece it all together like forensic scientists of the sky.”

Richards’ research specialty is binary stars, systems of two stars orbiting around a common center. Binaries are important to astronomers because their orbital patterns, determined by the gravity that binds them, provide a direct method for calculating a star’s mass. But binary stars are more than cosmic dance partners; they often behave somewhat like sibling rivals, interacting in ways that can lead to cataclysmic tantrums. “Most of the exciting things that happen in the sky occur in binaries,” says Richards.

If a young star like our sun, for instance, pairs with a white dwarf—a small, super-dense star that has burned most of its fuel—the white dwarf’s superior gravity strips gaseous matter from the surface of its partner, she explains. “The gas flows around the white dwarf and piles up like a traffic jam.” Called an accretion disk, this growing pile-up becomes increasingly pressurized, eventually triggering a thermonuclear reaction. These fantastic explosions, known as novae and supernovae, can emit more energy than our sun will generate throughout its entire life span.

Finding FlowBecause vast distance prevents astrono-mers from actually seeing the build-ups to these calamities, they use a process called spectral analysis to learn what’s happen-ing. As a prism separates sunlight into its rainbow of component parts, or spectra, a spectrometer splits the accretion disk’s electromagnetic radiation into characteris-tic patterns. Richards studies these patterns like fingerprints, determining a star’s elemental composition and its motion relative to Earth. It’s a task, she says, that reminds her of her childhood, and being dazzled by the colors cast by crystal chandeliers.

To test the gas-flow model she created for her doctoral thesis, Richards borrowed a technique from the medical field. “Astrotomography is very much like taking a CAT scan of the stars,” she explains. “We

get many spectral observations from all around our patient—the binary system—as it moves in relation to the Earth. Then we add all those observations together. The resulting composite image shows us how the gas moves between the stars.” Using this method, she not only con-firmed her model’s accuracy, but also showed that the force of gravity operates between binary stars just as predicted by the laws of physics. While compiling tomographs of several binary pairs she saw “a beautiful image of gas flowing along the predicted path,” she remembers.

Richards has continued to model gas flows between binaries to the present day, currently in collaboration with a team of Russian scientists. (“It’s interesting because we communicate by e-mail and we’ve never actually met in person,” she says.) Her dream is to one day create a full-blown three-dimensional model of these flows. “It’s going to take a while,” she laughs. “But I’m like a dog with a bone. I’m not letting go.”

Planetary PoliticsWhile planets aren’t her specialty, Richards was involved in one of the more high-profile astronomical decisions of recent years as a voting member at the 2006 meeting of the International Astronomical Union (IAU) in Prague. There, to the dismay of schoolchildren and skywatchers around the world, Pluto was stripped of its status as a full-fledged planet.

Given recent discoveries of more and more planet-like objects at the edge of our solar system and beyond, she says, “It was obvious that Pluto didn’t belong with the larger planets.” Though she acknowledges that behind-the-scenes politics made the decision controversial, in the end she cast her vote to change the definition of a planet and re-categorize Pluto as a dwarf.

Last fall, when she received the e-mail explaining that she had won the Musgrave Gold Medal, Richards at first thought it was a joke. Vaguely recognizing the e-mail’s author, she telephoned her mother in Jamaica before deleting it, and found that indeed the Institute of Jamaica had chosen to recognize her with its most prestigious honor, reserved for Jamaicans who have made “a significant international impact” through academic accomplishment. Only fourteen other scientists have received the gold medal in the award’s 111-year history.

P R O f i l e :

4 Research/Penn State 2009–10

In her acceptance speech in Kingston, Richards urged the government of Jamaica to have a higher regard for science. “In Jamaica the cultural stuff—Bob Marley, dance, history—is perceived to be closer to people’s lives than science,” she explains. “Science is thought of as something that weird people do. I’m hoping kids will learn to see that science is something natural and positive.”

“I disagree when people say that what astronomers do is useless,” she adds. “Astronomy has an influence on every aspect of our lives. The time on your watch is set by astronomers,” she says, tapping her wrist.

Debts RepaidThe high school that Richards attended in Kingston, St. Hugh’s, was segregated by gender; her classmates, as well as her teachers, were all female. “Having those female teachers gave me a boost,” she recalls. “As a young woman I could say, ‘Hey, I can be like them.’” Thus inspired,

she was able to soldier on through graduate school at the University of Toronto at a time when she says an all-male faculty tended to be tough on female students. The early encourage-ment also helped in her first academic position in a department where she was the only female faculty member.

Today, as a tenured full professor at Penn State, Richards loves inspiring her students (“infecting” them, as she puts it) with a passion for science. “I think I would lose something very important if I were locked away just doing research and not teaching,” she says. Named a Harlow Shapley Visiting Lecturer in astronomy by the American Astronomical Society in 2004, she visits college campus-es throughout the United States, Canada, and Mexico.

Back home, she teaches Astro 001, an introductory course in which hundreds of non-science majors enroll each semester. “I feel I’m on a mission,” she says. “It’s very important for us to pass on an

understanding and an appreciation of science because these students are going to be running the government and our universities. I want them to say ten years from now, ‘Wow, I enjoyed that class. Science is fun.’”

Her busy academic schedule allows her little free time. Even leisure reading— detective novels are among her favorites—is a luxury, she says. “I don’t really have enough time for friends,” she admits. But for “Mad Mercy” Richards, “That’s part of the price you pay if you want to be successful in any field.”

“I love the feeling that I have when I discover something new,” she says. “And I try to pass on the excitement of astronomy to as many people as possible.”

Mercedes Richards, Ph.D., is professor of astronomy and astrophysics in the Eberly College of Science; [email protected].

M. S

cott

Joh

nson

Mercedes Richards and a pair of binary stars.

www.rps.psu.edu 5

encyclopediatargeting Melanoma

Gavin Robertson is not a man who uses the word “hate” lightly, but he makes no secret of his desire to slay the dragon that is malignant melanoma. “This is the deadliest form of skin cancer,” he says. “There’s an approximately 4 percent increase per year in new cases and no effective treatment available for metastatic disease. The worst thing is getting calls from patients and their families who are desperate for a cure, for some

good news. It’s so hard telling them we’re not there yet.”

Robertson—associate professor of pharmacology, pathology, dermatology, and surgery at the Penn State College of Medicine—has new reason to believe that hopeful treatment news is ahead.

Tests in mice suggest that the new drug he and col-leagues have developed is both safer and more potent than conventional therapies in targeting melanoma tumors. Based on the anti-cancer compounds in cruciferous

vegetables, the new drug called isoselenocyanate “got a 60 to 70 percent response rate in mice,” says Robertson. “That’s significant.”

For Robertson and his research team, including professor of pharmacology Shantu Amin, the goal has been to unravel the signaling pathways involved in tumor development and identify drugs to target them.

In all life forms—from single-celled bacterium to multicellular humans—cells communicate with each other through chemicals, such as

hormones and neurotransmit-ters. Protein molecules on the surfaces of cells, called receptors, recognize these incoming chemical messages, and—when all goes right—they react by initiating the requested change in some aspect of cell behavior, from activating the immune system to fight infection to turning a fertilized egg into a fully formed baby.

But things don’t always go right. Sometimes when complex sequences of proteins are activated, a new “abnor-

mally active signaling pathway” is created—and researchers believe that communication glitches in these pathways can give rise to cell changes, and ultimately to cancer.

“We set out to target the proteins that trigger mela-noma,” Robertson explains. “Ninety percent of normal skin moles contain a mutant protein called B-Raf, but don’t proceed to become melano-mas. We wanted to know why some do and how to turn off that mechanism.”

Robertson and colleagues discovered that in about 70 percent of melanoma tumors another protein is at work alongside B-Raf called Akt3, which is ten times more active in malignant cells than in normal ones.

For cancer to start, the activity in the B-Raf pathway has to be in a particular, narrow range, says Robertson. “When this pathway is too active, it actually inhibits cancer and a mole develops that does not become cancerous. But when the A protein, Akt3, holds hands with the B protein, the B-Raf, and transfers information to it, it adds a phosphate to the mix and the pathway activity then drops into just the right range, and melanoma develops.”

Knowing that you’d have to eat “impractical amounts” of cruciferous vegetables such as cabbage and kale to obtain a therapeutic level of their cancer-fighting nutrients, sulforaphane and selenium, Robertson and colleagues sought to develop a drug using these nutrients that could deactivate the Akt3 pathway.

“We modified the chemical structure, increased the carbon chain length to make it more soluble, then popped

out the sulfur and replaced it with selenium,” explains Robertson. “We knew from studies that selenium deficien-cy is common in cancer patients, and selenium has also been shown to destabilize Akt proteins in prostate cancer,” he adds.

The result? “When we tried the sulfur version, it had no effect on the melanoma tumors in mice,” Robertson notes. “But when we used the selenium version of the drug, up to 70 percent of the mice showed tumor regression.” The selenium-enhanced compounds “significantly reduced the production of Akt3 protein and shut down its signaling network,” Robertson adds with a grin.

Though still years away from human trials, Robertson envisions a drug that could be used intravenously by melanoma patients, as well as preventively in sunscreen by the general public. (Some of the research on topical applications was done by Hershey High School senior Natalie Nguyen, an intern in Robertson’s lab. Nguyen’s project took third place in the 2009 Intel International Science and Engineering Fair.)

“I think we’re finally figuring out how to treat cancer,” Robertson says. “Where today’s cancer drug ‘cocktails’ sometimes poison nonspecifically, I think tomorrow’s treatments will target several specific proteins.

“This is where I see us going, long term,” he says. “The patient will come into the clinic with metastatic melanoma and we’ll take a blood sample to profile what the ‘bad genes’ are for that particular person. Then we’ll be able to choose from an arsenal of drugs to

Eat your veggies: New drug is based on anti-cancer compounds in cabbage and broccoli.

Sar

a B

renn

en


encyclopediagive them a personalized treatment based on their own cancer. We’ll see better efficacy and lower toxicity.”

“It’s my belief,” Robertson adds, “that our new drug will be in that arsenal.”

–Melissa Beattie-Moss

Gavin P. Robertson, Ph.D., is associate professor of pharmacology, pathology, dermatology, and surgery at the Penn State College of Medicine; [email protected].

follow the Glow

Think back to high school biology and you may recall some basics about cellular respiration: how organelles called mitochondria function like little power stations, converting nutrients from food into a high-powered cell fuel called adenosine triphos-phate, or ATP.

ATP powers the activity of every cell—and every living thing—on Earth. Yet without a key coenzyme called nicotin-amide adenine dinucleotide (NADH), ATP could not be made.

NADH is aglow with good press these days for its potential use in helping cancer specialists differentiate between healthy and cancerous cells, especially in early disease stages.

Penn State Associate Professor of Bioengineering Ahmed Heikal and graduate student Qianru Yu have made two intriguing discoveries about this enzyme: They pioneered a method for measuring NADH levels in living cells, and then deter-mined that NADH mol-

NADH, a coenzyme found in all living cells, could serve as a biomarker for diag- nosing cancer. Here, a new microscopy technique converts the compound’s natural fluorescence into an accurate measure of its concentration within a single live cell.

Ahm

ed H

eika

l

ecules—which are naturally fluorescent—are twice as prevalent in breast cancer cells as they are in normal breast cells, a trait that could serve as an indicator of easily missed early-stage malignancies.

Using a combination of microscopy and state-of-the-art spectroscopy, Heikal and Yu have found a way to convert NADH’s fluores-cence into an accurate measure of its concentra-tion in live cells, as a means of analyzing whether a cell’s metabolic and respiratory processes are healthy or damaged.

Normal cells are aerobic, explains Heikal. Inside healthy mitochondria, both oxygen and NADH are essential to convert energy from nutrients into ATP. But some cancer cells (those in tumors, for example) are anaerobic. Their mitochondria are disabled, causing the voracious, rapidly dividing malignant cells to use a faster form of metabolism—glycolysis—to turn sugar into energy without using oxygen. During this process, Heikal notes, “The concentration of NADH inside these diseased cells increases.”

The method of testing intracellular NADH levels used by Heikal and Yu offers several advantages over existing approaches. “Conven-tional techniques require cell destruction,” says Heikal. “Studying living cells, noninva-sively and under physiological conditions, is important because it allows us to understand how they function under diseased conditions.” What’s more, he notes, “We can measure real-time dynamic changes with high spatial

resolution as the cells respond to external stimulation from drugs, mechanical stress, or virus infection.”

One challenge that remains to be overcome, Heikal and Yu say, is that their technique uses ultrashort infrared laser, which penetrates only a fraction of a millimeter into biological tissues. “This inherently limits our ability to monitor mito-chondrial activities and NADH concentration deep in human tissues or organs,” Heikal says. He predicts that new nonlin-ear, fiber-based imaging techniques currently being developed in research laboratories around the world will provide the solution.

If and when they do, the potential of this diagnostic

tool “is limitless in both basic and applied research as well as in clinical setting,” Heikal says. “Our quantitative and noninvasive approach would be ideal in helping to diag-nose a wide range of diseases,” including neurodegenerative conditions such as Alzheimer’s and Parkinson’s, as well as cancer, and even aging. The same approach he says, could be applied to study other fundamental questions in cell and molecular biology.

--Melissa Beattie-Moss

Ahmed Heikal, Ph.D., is associate professor of bioengineering in the College of Engineering; [email protected]. Qianru Yu is a graduate student in the same department.

www.rps.psu.edu 7

Stopping Malaria’s Spread

Every year, malaria—spread through mosquito bites—kills about a million people around the globe. The deadly insects are widely combated with insecticides, but many of these chemicals eventually become ineffective, as repeated exposure breeds resistance.

“Insecticides sprayed on house walls or bed nets are some of the most successful ways of controlling malaria,” says Andrew Read, professor of biology and entomology at Penn State. “But they work by killing the insects or denying them the human blood they turn into eggs. This imposes an enormous selection in favor of insecticide-resistant mosquitoes.”

Read and his colleagues Matthew Thomas, professor of entomology at Penn State, and Penelope Lynch, a doctoral student at Open University in the United Kingdom, argue that insecticides that kill only older mosquitoes are a more sustainable way to fight the deadly disease.

Female Anopheles mosqui-toes spread malaria by biting infected humans and ingest-ing the malaria parasites along with the blood they need to reproduce other mosquitoes, the researchers explain. The parasites are then implanted in the mosquito’s gut wall, where they mature and eventually migrate to the mosquito’s salivary glands. The next time the mosquito bites a human, the disease is transmitted.

All told, this process takes at least ten to fourteen days. Fortunately for humans, most

mosquitoes are dead by the end of that time—their normal lifespan is only two to three weeks. It’s the outliers, mosquitoes that live up to eight weeks, that are the problem. “It is one of the great ironies of malaria,” says Read. “Most mosquitoes do not live long enough to transmit the disease. To stop malaria, we only need to kill the old mosquitoes.”

He and Thomas are working on a new fungal pesticide that will do just that. “We could spray it onto walls or onto treated materials such as bed nets, from where the mosquito would get infected by the fungal spores,” says Thomas. The fungi then take ten to twelve days to do their work.

To study the impact of such late-acting insecticides, the researchers constructed a mathematical model of malaria transmission. Using data from disease hotspots in

Africa and Papua, New Guinea, they showed that insecticides that kill only older mosquitoes reduce the number of infectious bites by about 95 percent.

Critically, the researchers also found that resistance to late-acting insecticides spreads much more slowly than resistance to conventional insecticides, and that in many cases, it never spreads at all.

Because most mosquitoes die before they become dangerous, late-acting insecticides do not have much impact on breeding, so there is much less pressure for the mosquitoes to evolve resistance, explains Read. “This means that late-life insecticides will be useful for much, much longer than conventional insecticides—maybe forever,” he adds.

—Amitabh Avasthi

Andrew Read, Ph.D., is professor of biology and entomology and Matthew Thomas, Ph.D. is professor of entomology in the Eberly College of Science. Both are affiliated with the Penn State Center for Infectious Disease Dynamics. Their e-mail addresses are [email protected] and [email protected]. Penelope Lynch is a doctoral student at Open University in the United King-dom. The findings reported above appeared in the April 7, 2009, issue of PLoS Biology.

CD

C P

ublic

Hea

lth L

ibra

ry (P

HIL

)

Anopheles mosquito


tures near the continent. “The ocean’s warming and melting the bottom of the floating ice shelves has been the dominant control on West Antarctic ice variations,” he says.

Pollard and DeConto have compared their model with the early results of ANtarctic geological DRILLing, or ANDRILL, a multinational collaboration to drill through the ice to ocean floor sedi-ment—in effect, going back in time to recover a history of paleoenvironmental changes.

“The ice sheets in our model changed in ways that agree well with the data collected by the ANDRILL project,” Pollard says. Further, “Our modeling extends the reach of the drilling data to justify that the data represent the entire West Antarctic area and not just the spot where they drilled.”

history on ice

One major threat of planetary warming is the melting of the great polar ice sheets and the resulting rise in global sea level. Particularly worrisome to researchers is the fragility of the West Antarctic Ice Sheet, or WAIS, whose bed lies well below sea level, accelerating the natural flow between the grounded ice sheet itself and the floating ice shelves that make up its boundary.

When these floating shelves melt sufficiently, Penn State senior research scientist David Pollard explains, they no longer buttress the grounded ice upstream, which then flows faster and rapidly drains the massive interior ice. The grounding line—the junction between the floating ice shelf and upstream ice resting on bedrock—retreats, converting more grounded ice to floating ice. Eventually, nearly all of the ice sheet on the Pacific side of Antarctica can disappear.

Indeed it has done so, as past climates have waxed and waned—but little was actually known about this history. Recently, however, Pollard and Robert M. DeConto, professor of climatology at the University of Massachusetts, created a computer model of WAIS’s last 5 million years. To specify past variations in snowfall, sno.wmelt, and ocean melting, they relied on records of deep-sea oxygen isotope ratios that indicate temperature changes in the oceans.

“We found that the West Antarctic ice sheet varied a lot, collapsed and re-grew multiple times over that period,” reports Pollard. These changes have been rapid and strongly influenced by ocean tempera-

Along with the rapid appearance and disappear-ance of ice, the researchers note that both the ANDRILL record and their model show that, early in the 5 million-year history, the periodicity of glaciation and melting was about 40,000 years, which matches the pattern in the Northern Hemisphere. According to Pollard, this pattern is probably attribut-able to the tilt of the Earth’s axis, which varies with the same period. Nearer to the present, cycle time increases to about 100,000 years, in alignment with the Northern Hemisphere’s ice ages.

During past warm periods, the model also shows, major collapses took a few thousand years—the expected time scale of future collapse of the West Antarctic ice sheet if ocean temperatures warm sufficiently.

The researchers note that when atmospheric carbon dioxide levels have been at about 400 parts per million, “as in the early part of the ANDRILL record, West Antarctic ice sheet collapses were much more frequent. “We are a little below 400 parts per million now and heading higher,” says Pollard. “One of the next steps is to determine if human activity will make it warm enough to start the collapse.”

—A’ndrea Elyse Messer

David Pollard, Ph.D., is senior research scientist in Penn State’s College of Earth and Mineral Sciences’ Earth and Environmental Systems Institute; [email protected]. Pollard and Robert M. DeConto, professor of climatology at the University of Massachu-setts, reported their findings in the March 19, 2009, issue of Nature. The National Science Foundation supported this work.

Modeled Antarctic ice sheet at particular times through the warm Marine Isotope Stage 31 event, around 1.07 million years ago. A similar drastic collapse of West Antarctic ice may happen in the next few thousand years due to greenhouse gas warming. Ice sheet elevations and floating ice shelf thicknesses shown by two different color scales; “yr BP” is years before present.

Dav

id P

olla

rd

www.rps.psu.edu 9

Splitting water 2.0

Hydrogen’s promise as a fuel has researchers around the world focused on cheaper, cleaner ways to produce it. One time-honored approach, splitting water into its constitu-ent elements, typically requires either electricity or heat.

Now, scientists at Penn State and Virginia Commonwealth University have found a way to generate hydrogen at room temperature, by exposing selected clusters of aluminum atoms to water. The key, they say, is in the geometries of these clusters, which play a previously unknown role in determining whether they will react with water molecules.

“Our previous research sug-gested that electronic proper-ties govern everything about these aluminum clusters,” explains A. Welford Castleman Jr., Eberly Family Distinguished Chair in Science and Evan Pugh Professor of chemistry and physics at Penn State. “But this new study shows that it is the arrangement of atoms within the clusters that allows them to split water.”

The research team, which includes Penn State graduate students Patrick Roach and Hunter Woodward as well as Virginia Commonwealth Professor of Physics Shiv Khanna and postdoctoral as-sociate Arthur Reber, created individual aluminum clusters by vaporizing aluminum with a laser, then allowing the vapor to cool. They then exposed the clusters to water in a custom-designed flow-reactor,

and found that they reacted differently depending on their sizes and their unique geomet-ric structures. Three of the clusters produced hydrogen from water at room tempera-ture, they found.

“Traditional techniques generally require a lot of en-ergy at the time the hydrogen is generated,” Khanna notes. “But our method allows us to produce hydrogen without supplying heat, connecting to a battery, or adding electric-ity.” He hopes to look next at the possibilities of recycling clusters for repeated use and controlling how they release the hydrogen they produce.

“Generally, this knowledge might allow us to design new nanoscale catalysts by chang-

Computer rendering of aluminum clusters reacting with water to produce hydrogen.

ing the arrangements of atoms in a cluster,” says Castleman. “The results could open up a new area of research, not only related to splitting water, but also to breaking the bonds of other molecules.”

—Sara LaJeunesse

A. Welford Castleman Jr., Ph.D., is Eberly Family Distinguished Chair in Science and Evan Pugh Professor of Chemistry and Physics at Penn State; [email protected]. Shiv N. Khanna, Ph.D., is professor of physics at Virginia Common-wealth University; [email protected]. The team’s findings ap-peared in the January 23, 2009, issue of the journal Science. Their research was supported by the Air Force Office of Scientific Research.

A.C

. Reb

er, V

CU

/PS

U


Selenium and aidS

The micronutrient selenium, touted in some studies for cancer-fighting properties, may also slow the progress of the AIDS virus, says K. Sand-eep Prabhu, assistant professor of immunology and molecular toxicology at Penn State.

In lab tests he and his colleagues conducted with human blood cells, Prabhu says, “We have found that increasing the expression of proteins that contain selenium negatively affects the replica-tion of HIV. Our results suggest a reduction [of] at least tenfold.”

Humans and animals need selenium to maintain normal metabolism. In the body, selenium becomes incorpo-rated into so-called selenopro-teins, which are known to be especially important in reducing the stress caused by infection, thereby slowing its spread.

When a virus infects a person, it quickly acts to degrade these selenoproteins so that it can replicate unhindered. “Since HIV targets the selenoproteins,” Prabhu explains, “we thought that the logical way to deal with the virus is to increase the expression of such proteins in the body.”

He and his team first isolated blood cells from healthy human volunteers who did not have HIV, and infected those cells with the virus. Next, they added tiny amounts of a selenium compound—sodium selenite—into the cell culture to see the effect on viral replication.

Their results indicate that the addition of selenium inhibits the replication of HIV at least tenfold, compared to cell cultures in which no selenium is added. In contrast, when the researchers selectively reduced production of the selenopro-tein TR1, they observed a three-and-a-half-fold increase in viral replication.

Prabhu believes that TR1 works by upsetting the chemical structure of Tat, a protein that helps the virus replicate. “Once we fully understand the function of these selenium proteins,” he says, “it will give us a handle to come up with more effective drugs.”

—Amitabh Avasthi

K. Sandeep Prabhu, Ph.D., is assistant professor of immunology and molecular toxicology in the College of Agricultural Sciences; [email protected]. His work is funded partly by the National Institutes of Health. The findings described above were published in the Journal of Biological Chemistry, November 28, 2008. Co-authors of the paper include postdoctoral scholar Parisa Kalantari; visiting faculty member Kambadur Muralidhar; and graduate students Vivek Narayan, Ujjawal H. Gandhi, and Hema Vunta, all of Penn State; Satish K. Natarajan of the University of Nebraska; and Andrew J. Henderson of Boston University.

Selenium crystals

www.rps.psu.edu 11

war: not the answer?

Among some isolated South American indigenous groups, aggressive, vengeful behavior was seen as the way for men to gain status and family. Now, an international team of anthro-pologists says the macho guy does not always get the girl.

“In 1988, Napoleon Chagnon published evidence that among the famously warlike Yanomamo of Venezu-ela, men who had participated in a homicide had significantly

more wives and children than their less warlike brethren,” says Stephen Beckerman, associate professor of anthro-pology at Penn State. Working among the Waorani of Ecuador, however, Beckerman and colleagues have found the opposite to be true.

The Waorani forage and grow manioc in the lush rainforest of the Amazon basin. At their first peaceful contact with the outside world in 1958, they numbered about 500 people, and were known to be even more bellicose than the Yanomamo. Warfare and murder were common, and they practiced their violence on each other as well as on outsiders. Over a period of fourteen years, missionaries pacified the entire population, to the point where aggressive warfare and raiding are now almost gone.

For the Waorani Life History Project, Beckerman and his colleagues interviewed ninety-five men in twenty-three settlements, including any man old enough to have experienced warfare before the pacification. They collected genealogies, reproductive history, warfare history, and individual life stories. Their findings? More aggressive men did not acquire more wives than milder men. They did not have more children, and their wives and children did not survive longer. In fact, warlike men had fewer children who survived to reproductive age.

Why did aggression and warlike behavior work for Yanomamo men, but not for the Waorani? One cultural difference suggests a clue. While both the Yanomamo and the Waorani used violence

for revenge, the researchers say, the Yanomamo’s warfare cycles had peaceful interludes during which warriors could reap the benefits of battle, and accrue wives and children. The Waorani men, in contrast, did not incorporate these lulls. Waorani were even known to initiate fresh mayhem based on something that had occurred in their grandpar-ents’ generation.

No doubt as a result, another difference between the Yanomamo and the Waorani is that even with chronic warfare, the Yano-mamo population had grown over the two centuries before Chagnon’s investigation. In contrast, “The Waorani, as far as we could tell, were well along in the process of killing themselves off at the time of peaceful contact,” Beckerman says.

—A’ndrea Elyse Messer

Stephen Beckerman, Ph.D., is associate professor of anthropology at Penn State; [email protected]. Other researchers involved in the Waorani Life History Project are Pamela I. Erickson of the University of Connecticut; James Yost; Jhanira Regalado of the Museo de Historia Natural, Escuela Politécnica Nacional, Ecuador; Lilia Jaramillo of the Carretera Panamericana, Cotopaxi, Ecuador; Corey Sparks of the University of Texas, San Antonio; Moises Iromenga of the Organización de la Nacionalidad Huaorani de la Amazonia Ecuatoriana, Ecuador; and Kathryn Long of Wheaton College. The National Science Foundation supported this work, which was reported in the Proceedings of the National Academy of Science on May 19, 2009.

Waorani informant at rest.

Cou

rtes

y S

teph

en B

ecke

rman


advanced Search

No matter how good a search engine is, sometimes it’s neces-sary to change your search term to get the information you need. But what if you didn’t have to change terms yourself? What if the search engine could do it for you?

Jim Jansen, associate professor of information sciences and technology at Penn State, analyzed nearly 1 million Web searches in order to detect patterns in the way people reformulate their queries, and to create models capable of predicting those patterns.

Jansen and co-authors Amanda Spink and Danielle Booth found that in 22 percent of queries, search terms were reformulated or changed to more precisely convey the information the user was seeking. “Users typically moved to narrow their query at the start of the session, moving to reformula-tion [i.e., trying different terms] in the mid- and latter portions of the sessions,” Jansen says.

The researchers also found that users rarely ask for system assistance in helping to find the desired information—perhaps because they are too focused on using their own search

Is search engine behavior predictable?

terms. “It appears that assistance to narrow the query and [suggest] alternate query terms would be most beneficial immediately after the initial query submission,” says Jansen, when the user is making a cognitive shift [and is more] open to system intervention.

“The key point is that we are moving from descriptive aspects to predictive models in Web searching,” he adds. This advance, he says, is a critical step in helping to design more advanced search engines. The ability to accurately predict query patterns, Jansen suggests, will lead to better automated assistance.

—Jenna Spinelle

Jim Jansen, Ph.D., is associate professor in the College of Infor- mation Sciences and Technology; [email protected]. Danielle Booth is an alumna of the College of Information Sciences and Tech- nology at Penn State. Amanda Spink, Ph.D., is professor of information science at Queensland University of Technology, Australia. “Patterns of Query Reformulation during Web Searching,” was published in the online edition of the Journal of the American Society for Information Science and Technology in July 2009. The Air Force Office of Scientific Research and the National Science Foundation funded this research.

www.rps.psu.edu 13

Soufriere Hills volcano, Montserrat

Bar

ry V

oigh

t

Barry Voight first went to Montserrat, an island in the British West Indies, in March 1996. The veteran volcan-

ologist had been invited by the island’s government and by staff at the Montserrat Volcano Observatory (MVO), who were monitoring a lava dome that had been growing for four months atop the previously dormant Soufriere Hills volcano. The steep, cone-shaped volcano occupied the southern end of the 40-square-mile island, towering 3,000 feet above the capital city of Plymouth, population 7,000.

The government officials and MVO scientists wanted Voight’s opinion on the potential danger from a crater-wall collapse on the volcano’s western flank, which directly faced Plymouth. More than twenty-five years earlier, Voight had accurately predicted that a massive avalanche on Mount St. Helens, in the Cascade Range in Washington, could trigger a destructive lateral blast, which took place on May 18, 1980. Since then, as a member of the U.S. Geological Survey’s Volcano Hazards Response Team, Voight frequently had inspected ready-to-blow

Volcano

The Anatomy

of a

With remote sensing and an international army of geologists, SEA-CALIPSO takes the measure of an angry mountain.

By Charles Fergus

volcanoes around the world. At times, he and his fellow volcanologists gave advice leading to evacuations that saved hun-dreds, if not thousands, of lives.

“The Soufriere Hills volcano looked very different in 1996 than it does now,” Voight recalls. “The slopes and even the crater were forested, apart from the new lava dome and some localized spots downwind where sulfur and chlorine gases had killed the vegetation. In Plymouth, ash dusted the interiors of the shops, and you noticed the gas—it affected your vision and breathing when you caught a whiff of bad air. Folks were sitting on the curbs, covering their noses with handker-chiefs and wiping their tearing eyes.”

The day after he arrived, Voight caught a helicopter flight to the volcano’s rim. He clambered down a notch in the crater wall and inspected the swelling lava dome and the surrounding crater walls. From his field notebook: “Yellow block and ash flows and tuff beds with altered, weath-ered matrix. Took block and bag samples at various elevations.” Another entry: “Simon [Simon Young, a British volcanolo-

gist attached to the MVO] said he was concerned whether an old guy like me would be OK on the mountain. Someone asked him how it worked out, and Simon replied, ‘I stopped worrying when I saw him bouncing down into Gages like a mountain goat.’”

Predicting DisasterVoight felt that the crater wall on the western side of the volcano was stable. However, he judged Plymouth to be at serious risk from a pyroclastic flow, a scorching storm of fragmented lava, ash, and gas that could be released by an explosive collapse of the lava dome. The flow could surge out of the crater, race down the mountain, and overrun the town in as few as three minutes. Voight also judged that a small village on the eastern slope was at extremely high risk of destruc-tion if an explosive eruption took place.

“The person heading the MVO at the time had little volcano crisis experience, but tightly controlled the information flow concerning the situation,” Voight says. “His communications to the public

www.rps.psu.edu 15

officials in charge of evacuating Plymouth were way too optimistic.

“In the report I made to the governor, the chief minister, and other officials, I made sure they got my unvarnished opinion about the risk the population was facing. I had investigated a volcano disaster in Java a few months earlier, where there had been a hundred casual-ties from pyroclastic currents—ash hurricanes. I thought the same threat existed on Montserrat, and I used photos I’d taken of burn victims in Java to illustrate my point.

“Within a few weeks, evacuations were carried out. A few months later, the village on the eastern slope was subjected to a blitz of incandescent ballistic blocks as large as a meter in diameter, and numer-ous fires were set. There were no casual-ties, because the place had been evacu-ated. Over the next three years, a series of pyroclastic flows destroyed and buried Plymouth bit by bit.”

During and after those eruptions, 8,000 of Montserrat’s 13,000 inhabitants fled the island, half of which was turned into an

ash-and-lava wasteland. The authorities built a new capital and airport at the island’s north end.

Voight became a charter member of the Risk Assessment Panel, formed in 1997 to advise the United Kingdom and Montser-rat governments, and later was named to its successor group, the Scientific Advisory Committee, on which he currently sits. The committee gives detailed assessments of the volcano at least twice a year, and these appraisals help guide decision making by local and UK officials and the MVO. Over the same period, Voight has carried out a series of research investiga-tions on the island.

In 2002, Voight also helped organize a team of scientists to form the Caribbean Andesite Lava Island Precision Seismo-geodetic Observatory, or CALIPSO. “The acronym came into being after a very fine margarita imbibed in Washington, D.C.,” Voight notes, adding: “The name fits in all respects.” Seven years later, the Soufriere Hills volcano remains one of the world’s most closely studied stratovolcanoes.

Sulfur HillsMontserrat lies southeast of Puerto Rico in the Leeward Islands chain. George Martin, the Beatles’ former producer, has a home there (“He very kindly gave us permission to located a key borehole site on his prop- erty,” Voight says), as do many retired Canadians and Americans, who mingle with a native population of Caribbean, African, Irish, and English descent. Montserrat is a place of steam vents, sulfur deposits, bubbling mud pots, and tropical verdure, with the volcano frowning over all.

Stratovolcanoes are explosive and dangerous. They are among the most common volcanoes in the world. Many of them, including the one on Montserrat, produce magma that forms the igneous rock andesite. The word comes from the Andes mountain range on the western rim of the South American tectonic plate. Montserrat and other Caribbean islands sit above the northern rim of the South American plate, where it is subducting, or sliding, beneath the Caribbean plate. Above this zone, volcanoes erupt. A similar

“The internal plumbing of an active volcano is a huge puzzle for earth scientists,” Voight says. “It’s almost impossible to get direct measurements.”

Bar

ry V

oigh

t

Aerial view of the east coast of Montserrat after the gigantic lava dome collapse in 2003 left an open scar on the volcano. Inset: Barry Voight.


situation exists from Chile to California to Alaska, and from the Kurile Trench off Kamchatka to Japan, the Philippines, and Indonesia—all places where Voight has worked. This great arc of volcanism is called the Pacific Ring of Fire.

Three volcanic centers—Voight calls them “a series of dome clusters”—have developed on Montserrat. Silver Hills, at the island’s north end, is 2.6 to 1.2 million years old. The centrally located Centre Hills are 950,000 to 550,000 years old. (The Silver Hills and Centre Hills are currently inactive.) The Soufriere Hills (soufriere is French for sulfur) are younger than 200,000 years.

From the time the island was settled in the early 1600s until recently, there were no eruptions (although the geological record shows that one took place between when Christopher Columbus discovered and named Montserrat, in 1493, and its settlement by Europeans). Earthquakes caused by pulses of rising magma shook the island in the 1890s, the 1930s, and the 1960s; however, the magma lacked the energy to break through the ground surface. In the early 1990s the Soufriere

Hills volcano began acting up again, with lava breaking out in November 1995. (Voight explains: “It’s magma when underground, lava when it gets out.”)

“With CALIPSO, we’re looking at the subduction process on a very basic level,” Voight says. “The movement of one tectonic plate beneath another causes the mantle to melt, and the molten rock, or magma, accumulates under the earth’s crust. We’re studying how the magma evolves and makes its way through the crust to the earth’s surface.”

Ears to the GroundThe CALIPSO system is the first borehole monitoring array of its type to be deployed at an andesite volcano. It includes four holes, 600 feet deep and 4.5 inches in diameter. At the bottom of each are a strainmeter and a seismometer. A micro-barometer and a high-precision global positioning system (GPS) sit at the surface. “The ground is a hundred times quieter 600 feet down,” Voight explains. “We can record smaller events and deeper events—such as earthquakes caused by magma moving—than would be possible

at the noisier ground-surface level. And we can record earth strain to an extremely high level of precision.”

Voight and his colleagues combine data from the boreholes with information collected from GPS and seismic instru-ments at surface sites around Montserrat, gas detectors on the volcano and auto-mated camera systems facing the cone, and ongoing visual observations.

The GPS and strain devices can measure both the up-and-down and sideways movements of numerous points on the island. “During periods when magma is building up inside the volcano,” says Voight, “the ground surface inflates like a balloon. When magma erupts from the volcano, the ground surface deflates. This happens all over the island—the ground can fall several inches while magma is being released.”

The instruments recorded a tremen-dous eruption in July 2003, when a newly built dome collapsed, releasing more than 200 million cubic meters of lava. Accord-ing to a journal paper Voight co-authored: “This appears to be the largest lava dome collapse in the worldwide historic record for any volcano.”

During and after the 1996 eruptions, 8,000 of Montserrat’s 13,000 inhabitants fled the island, half of which was turned into an ash-and-lava wasteland.

Voight examines Plymouth, the destroyed former capital of Montserrat.

Cou

rtes

y B

arry

Voi

ght

www.rps.psu.edu 17

Measurements taken during this and other eruptive phases show the volume of lava released by the volcano to be much greater than what would be expected from the amount of ground subsidence taking place. To resolve this apparent contradiction, Voight and his colleagues decided to look inside the volcano. “The internal plumb-ing of an active volcano is a huge puzzle for earth scientists,” Voight says. “It’s almost impossible to get direct measure-ments. We needed to use remote sensing.”

Voight and fellow researcher Steven Sparks, a geoscientist at the University of Bristol in England, launched a research effort called SEA-CALIPSO: They would use seismic waves produced by explosions at sea to examine the volcano and the island on which it perches.

Sounding it OutSeismic tomography, developed in the 1970s, relies on seismic waves caused by earthquakes and explosions. “You measure the velocity of the waves to compose a picture of the hidden structure,” says Voight. “Tomography literally means ‘slice-pictures,’ in which a series of high-resolu-tion two-dimensional slices are pushed together to yield a 3-D image.” He likens the technique to a hospital CT scan (CT stands for “computerized tomography”) that employs X-rays to build a picture of organs inside the human body. In both the medical and the geological applica-tions, advanced programs run by powerful

computers solve hundreds of thousands of equations to identify subsurface details.

In preparing for SEA-CALIPSO, the researchers deployed more than 240 seismic recorders and geophones on Montserrat. Some were installed along roads, or had already been placed in monitoring stations. Others had to be carried on trails cut into the rugged rainforest interior, or landed from boats along the coast and then hauled to strategic points inland. The team also sank ten ocean-bottom seismometers deep into the sea around the island.

In December 2008, the British research vessel James Cook circled Montserrat, towing an array of air guns that fired off explosions at sixty-second intervals. “Think of a hospital CT scan, with the X-ray emitter slowly circling the patient,” Voight says. More than four thousand omnidirectional explosions were set off over three days. The land-based and ocean-bottom sensors recorded the arrival times of the seismic waves produced by the detonations.

The 89.5-meter research ship also trailed a streamer of hydrophones to pick up underwater sound impulses that came bouncing back. Data from those impulses would help the researchers characterize faults on land that extended out into the sea, and different kinds of formations and volcanic deposits on the sea floor. During the experiment, Voight remained on Montserrat to guide the operation and to

help deploy and monitor the instruments, along with Eylon Shalev of Aukland University (NZ); the co-leader, Sparks, was onboard the ship, with oceanographer Tim Minshull advising from Southampton (UK).

The explosions produced 115,158 rays: paths traveled by seismic waves though geological materials whose physical properties caused the impulses to proceed at differing speeds. “Tomography yields a map of rock velocities at different locations,” Voight says. “We can convert these velocities into characteristics like stiffness, porosity, elasticity, and probable rock type.” The researchers also evaluated seismic information that CALIPSO had recorded following local and regional earthquakes. The immense quantity of data took months to crunch, to get the first look. “And we are still crunching,” says Voight. “There is plenty left to do.”

“We found that we could see down to five or six kilometers below sea level,” says Voight. “We had hoped for more depth, but most of the seismic rays were curved, and bottomed out sooner than expected. This had to do with characteristics of the local crustal rock.” The researchers detected a high-velocity crystalline core under the Soufriere Hills and the Centre Hills. They saw the glimmer of a slow-velocity region under the volcano, “possibly related to shallow magma storage,” says Voight.

Hot and HeavyBelow five kilometers, the imaging became less precise—“like a photo that’s slightly out of focus,” Voight says. SEA-CALIPSO was able to map the seismic energy bouncing off key reflecting layers farther down. Analyses guided by Penn State geoscientist Chuck Ammon located the crust-mantle boundary at a depth of about 30 kilometers, and a deeper region of slow velocity under the south part of the island.

Things are hot and heavy down there, where the plates grind beneath Montser-rat. Says Voight, “Rocks involved in the subduction slab begin to dehydrate, to lose water. The released water-rich fluid acts as a catalyst that promotes a partial melting of the mantle. Only a fraction of the mantle melts—roughly 10 percent—and this molten material, of basaltic composition, begins to migrate upward.

“The melt collects together, and when it reaches a certain size and density, it rises more rapidly, a lightweight magma balloon propelled by its buoyancy through the soft, heavy mantle rock that surrounds

“The Soufriere Hills volcano looked very different in 1996 than it does now,” Voight recalls.

J.J.

Ham

mon

d

Air gun shooting from the RSS James Cook, toward Montserrat in the distance.


it. The basaltic magma ponds at the base of the crust. At this point it can, in some instances, drive a fracture—called a dike—all the way through the crust to the earth’s surface, causing an eruption.

“Under Montserrat, things are happen-ing a bit differently. The basaltic magma begins to crystallize, creating a liquid that’s stickier and richer in silica: andesite. The andesite then rises in pulses to shallower levels, where it collects in chambers. Repeated injections of hotter basalt energize the magma, making it more mobile.”

The magma flows upward into the Soufriere Hills volcano fairly continuously and at a relatively constant rate of two cubic meters per second—“about the volume of a large refrigerator,” says Voight. “During periods between erup-tions, the magma fills a series of chambers that may be stacked on top of each other.

We think there’s some sort of semicon-tinuous transfer of magma between the chambers, and at times that transfer becomes rapid.”

Andesite magma is rich in water, carbon dioxide, and sulfur dioxide gases. Some gas is dissolved in the magma, and some sits there in bubbles. As new magma enters the system from below, it makes room for itself by compressing the resident bubbly magma. The magma also pushes against the chamber walls, which causes the surface of Montserrat to elevate.

“The chamber system acts as a huge magma sponge,” says Voight. “On top, a dome of sticky, mostly solidified lava caps the system. Pressure can build up gradu-ally beneath the dome, and the eruption can restart.

“During an eruption, the magma that’s been squeezed inside the volcano’s res- ervoir is decompressed. That explains

why the volume of lava produced by an eruption can be much greater than one would estimate, based simply on the amount of surface subsidence.”

The Fire Next Time SEA-CALIPSO revealed a prominent fault trending northwest into the Caribbean on the western side of Montserrat. “This fault line has been active in the recent geologi-cal past,” says Voight. “We think it influenced the location of the different areas of volcanic domes on the island, as well as the magma chambers inside the Soufriere Hills volcano.

“One of the great things about the erup-tion at Montserrat—mind you, this is strictly from the scientist’s perspective, and not the viewpoint of somebody living on the island—is that the activity hasn’t stopped. The eruption didn’t build to a climax, go on for a week, then end. The volcano’s relatively slow development meant we could put up instruments when and where we wanted them. So we’re still learning. We’ve made many discoveries, and we will make others.”

According to Voight, the research at the Soufriere Hills volcano is a benchmark study that will help earth scientists understand other subduction-type stratovolcanoes. “The more we know about the system on Montserrat,” he says, “the better we can forecast eruptions and anticipate other dangerous events, both here and at other andesite volcanoes around the world.”

Barry Voight, Ph.D., is professor emeritus of geology and geological engineering in the College of Earth and Mineral Science; [email protected]. Current Penn Staters participating in the research on Montserrat include Professors Charles Ammon and Derek Elsworth; postdoc-toral researchers Dannie Hidayat and Christina Widiwijayanti; Ph.D. candidates Vicki Miller, Roozbeh Faroozan, Winchelle Sevilla, and Josh Taron; and many undergraduate students. CALIPSO AND SEA-CALIPSO have drawn together scientists from Penn State, the University of Arkansas, Carnegie Institution of Washing-ton, Cornell, Duke, Arizona State, New Mexico Tech, Bristol University (UK), Durham University (UK), University of Auckland (NZ), National Oceanographic Centre (UK), Montserrat Volcano Observatory, British Geological Survey, and Seismic Research Center (Trinidad). The PASSCAL (IRIS) Consortium and Scripps Institute of Oceanography aided SEA-CALIPSO. The National Science Foundation, Natural Environmental Research Council (UK), British Geological Survey, and Discovery Channel have helped to fund the research.

Clockwise from top left: on deck with Montserrat in the distance; superstructure of the RSS James Cook under a tropical sky; crew stowing cable; air gun array and frame.

Cou

rtes

y B

arry

Voi

ght

www.rps.psu.edu 19

Researchers at the Center for Neural Engineering

believe their work on the physics of seizures will yield

an electrifying new treatment for epilepsy.

Patients like Jessica Gordon hope they’re right.

By Melissa Beattie-Moss

BrainStorms


of 2 million Americans with epilepsy. She

believes the head injury she sustained in

a serious car accident in 1996 is respon-

sible for her condition.

It’s possible, say her neurologists, but

they’re quick to point out that this is a

disorder with dozens of contributing

causes ranging from genetics, brain

tumors, and viral infections to overmedi-

cation, Alzheimer’s disease, and birth

trauma. Pinpointing the exact cause is

often difficult and sometimes impossible.

Getting a solid diagnosis can also prove

tricky. The disease’s most common

symptom—loss or impairment of con-

sciousness—can be caused by so many

other factors that physicians often take a

watch-and-wait approach.

With more than forty different types of

epilepsy in the medical literature, this

disease is more accurately understood as a

group of syndromes with distinct symp-

you are at a conference, out to

dinner with colleagues in the

hotel dining room. Mid-conversa-

tion, you freeze with the fork

halfway to your mouth. Your hands are

shaking and you can’t hold your head up.

The next thing you remember seeing is a

paramedic standing over you asking,

“What is your name? Do you know where

you are?” Your head is full of thoughts but

the few words you get out are garbled

beyond recognition.

The next morning, you are still weak

and foggy-brained, remembering only bits

and pieces of what happened.

What happened, explains Jessica Gordon,

was an epileptic seizure—her first major

episode and the one that led to her being

diagnosed in 2008 with a partial complex

seizure disorder.

Gordon, a 32-year-old Penn State

alumna and registered dietitian, is one

toms, all involving episodes of abnormal

electrical activity in the brain. How do you

outsmart a foe you can barely define?

With tremendous determination,

patience, and the collaboration of many

people, says Steven J. Schiff.

Schiff—director of the two-year-old

Penn State Center for Neural Engineer-

ing; Brush Chair Professor of Engineer-

ing; and professor of neurosurgery,

physics, and engineering science and

mechanics—trained as a pediatric

neurosurgeon and still scrubs in to the

operating room once a week at Penn State

Milton S. Hershey Medical Center. He has

spent decades researching the physics of

nervous system disorders, particularly

epilepsy, the spasticity of cerebral palsy,

and Parkinson’s disease.

His challenge since being recruited by

Penn State in 2006 is nothing less than

assembling and leading one of the most

www.rps.psu.edu 21

interdisciplinary bioengineering collabo-rations in the nation, with the common goal of contributing significantly to the next generation of brain–computer interface technologies.

Risk versus Benefit The need for new solutions almost always arises from frustrations with today’s limits. In the case of epilepsy, only one-third of patients’ seizures can be “well controlled” using anticonvulsant drugs, explains Schiff; in another third, the epilepsy can be “reasonably controlled.” (Even in these cases, such drugs are “far from ideal,” he notes, “because they influence every cell in the brain and have a tendency to affect cognition and produce a host of side effects.”)

A full third of all patients have what is termed “pharmacologically intractable epilepsy.” For this last group, the primary treatment offered is surgical resection (removal) of the damaged lesions within the brain, usually within the hippocampus, an area associated with learning and memory.

“There is always the potential hazard that the part of the brain you’re cutting into is not going to function well again,” says Schiff. “There is almost no part of the brain that is not serving some useful function. For example, when the temporal lobes are resected, there is some decre-ment in verbal memory if the left side is operated on, and in spatial memory if the right side is operated on.”

Jessica Gordon echoes the concerns of many patients when she says, “Given the chance that undergoing brain surgery would not be effective, combined with the potential complications, I’m not choosing a surgical resection route.”

More Rational TherapiesThe future of seizure treatment—and perhaps the treatment of brain and behavioral disorders in general—belongs to electrical-stimulation therapies, Schiff believes.

“We’re about five years away from a new epilepsy implant

and we’re working on one for Parkinson’s as well.”

Bruce Gluckman (left) and Steven Schiff

Fred

eric

Web

er


This stimulation is delivered by means of a thumbnail-sized computer chip—akin to a pacemaker for the brain—that sends tiny jolts of electrical current applied to specific neural targets. The goal: to block abnormal electrical patterns and stop the symptoms of disease—seizures, spasticity, tremors—before they happen.

The procedure, called deep brain stimu-lation or DBS, involves surgically implant-ing electrodes into targeted areas of the patient’s brain, along with a small battery. To date, almost 40,000 Parkinson’s patients have undergone DBS surgery, with mixed results. While many patients experience a welcome reduction of their tremors and rigidity, some have side effects, including involuntary movements, insomnia, anxiety, and depression. There’s still too much trial and error in choosing and calibrating the pattern and amplitude of the implants’ electrical signals, says Schiff, and that ultimately limits the treatment’s success in reducing a broader range of the disease’s symptoms.

“What we’re striving for,” he emphasizes, “is the development of more rational ways of interacting with the brain electrically.”

A Productive PartnershipBruce Gluckman emphatically agrees. Gluckman, associate professor of engi-neering science and mechanics and of neurosurgery, has been Schiff’s primary research partner for more than fifteen years.

Together, these two scientists—each with different and complementary strengths—are intent on the same goals: to find more sensitive, precise, and individualized strategies to monitor brain activity and suppress seizures before they strike, and to shape the center into a pioneering player in the growing field of neural engineering.

Casual and outgoing, Gluckman is essentially a physicist and self-described experimentalist. His primary expertise is in “the group dynamics of individual systems,” with an emphasis on the interaction between theoretical ideas and experimental results, and how to apply

what is learned directly to models of neural systems.

“My role in the center is more in day-today operations in the lab, where I’m focused on instrument development,” he adds.

The instrument in question is the center’s main (though by no means only) focus: a prototype of the next generation of human brain implant device, based on neurological research on the brains of rats.

“I think we’re about five years away from a new epilepsy implant and we’re working on one for Parkinson’s as well,” Gluckman says with obvious excitement. “We just have to make sure we can get the bugs worked out first.”

Schiff, soft-spoken and intense, is clinically oriented in his research ap-proach, says Gluckman of his partner’s drive to address health-related questions. But, he adds, Schiff is excellent at building interdisciplinary bridges between the center and a diverse network of scientists around the world, as well as within the center itself.

“By combining our skills, I think we’ve been able to do some very unique things,” Schiff says, “with the emphasis always coming back to finding better solutions for people suffering with brain disorders.”

How do you outsmart a foe you can barely define?

With tremendous determination, patience, and collaboration.

The Body Electric “The simplest way I can explain how I feel during a seizure,” says Jessica Gordon, “is that I am stuck in a moment in time that I cannot get out of. I feel like a machine on pause, and I just want someone to hit the ‘play’ button.”

An important aspect of the center’s research, says Gluckman, is the quest to understand the neural firing patterns inherent in a healthy brain. This will help researchers piece together what makes that complicated organ (“a three-pound wet computer”) malfunction, and determine how to hit the correct “‘play’ button” for patients like Jessica.

The brain, for all its complexity and mystery, is essentially an electric circuit, Gluckman explains. More than 100 billion brain cells (neurons) communicate with one another through “wires” called dendrites and axons, at connecting junctions called synapses. With an estimated 1 quadrillion synapses within the human brain, the normal functioning brain provides a constant flow of data to its own neural circuitry, enabling it to make adjustments in its electrical firing through a continuous process of reevalua-tion and readjustment.

“In healthy brains, there are a host of mechanisms for keeping the network stable,” he notes. “They involve combina-tions of excitatory and inhibitory neurons. When input comes in to a layer, there’s a balance between the neurons that want to fire off and the ones that tell the others not to fire too often.”

“One could say that temporal lobe epilepsy arises from malformations or miswiring in the hippocampus,” he adds. “That’s why this part of the brain is a major target for surgical resection. Our objective is to create a prosthetic—a control system—that will sense the instability in the hippocampus that precedes a seizure and reroute the network before the patient experiences cognitive deficits.”

Would such an advance replace surgical resection as the treatment of choice for

Advanced circuitry for improving the accuracy of devices that stimulate the brain and record its electrical activity.

Fred

eric

Web

er

www.rps.psu.edu 23

intractable patients? “That’s the objec-tive,” Gluckman says, nodding. “It’s as if there’s an electrical chain reaction that gets set off in the hippocampus and we’re trying to interrupt it before it gets started.”

“Broadly speaking,” adds Schiff, “we are asking the question: How do you sense that a nervous system is not functioning properly, that its rhythms are wrong, and readjust those rhythms by stimulation?”

Loops and FrequenciesThe Center for Neural Engineering is currently composed of three connected laboratories on the third floor of the Earth–Engineering Sciences Building on the west end of the University Park campus. In one of those labs, Schiff, Gluckman and colleagues are building and fine-tuning small implantable electronic chips that record the firings of single neurons under low-frequency electrical stimulation.

“Low frequency” may be key in taking the guesswork out of choosing the best electrical pattern and amplitude for implanted devices, Schiff and Gluckman believe. Unlike the high-frequency current (defined as above 100 Hz, or 100 cycles per second) most often used in neural stimulation, they are working with cycles under 100 Hz—”what we call polarizing low-frequency electrical fields, or PLEF,” Gluckman clarifies. After years of research with hippocampal brain slices and implanted animals, they’ve determined that very low-frequency current, which creates a constant field lasting longer than the firing of a single neuron, allows them to shift the normal “set point” of brain cells. In turn, this modulates the way cells respond to input.

In short, adds Schiff, “we can make neurons less responsive to the electrical bombardment of a seizure.”

Of equal importance, the two research-ers have discovered they can simultane-ously record electrical activity within the brain during treatment as they adjust response. In effect, a closed-loop system is created, allowing them to create “continu-ous feedback control devices” that interact with the seizures and automatically refine the level of stimulation as needed.

This, explains Gluckman, is a big step toward the more rational implantable device they seek—a device that could someday evolve into an even more sophisticated brain–computer interface, in which signals passing back and forth from the brain to the computer would, in effect, train both.

Says Schiff, with evident hopefulness, “We’re pushing the envelope in develop-ing what should be the next generation of closed-loop systems.”

Control and Chaos If you talk to neural engineers for more than a few minutes, you can expect two words to pop up repeatedly: control and chaos. These are the shorthand names of two principles of physics and engineering used to create models of brain behavior.

The electrical behavior of the brain’s neurons, explains Schiff, is a physical system governed by the same laws of “nonlinear dynamics” that apply to planetary systems, meteorology, and even dripping faucets.

Better known as chaos theory, the idea is that small—even almost impercep-tible—changes in a system’s conditions can lead to radically differing outcomes. This “sensitive dependence” is sometimes referred to as “the butterfly effect,” based on the notion that the beating of a butterfly’s wings on one side of the world could cause a tornado on the other side.

Chaotic systems—whether the brain’s neural firings or the drips from a leaky faucet—appear to be random and intrinsically unpredictable, a researcher’s worst nightmare. Yet advancements in mathematical modeling reveal something startling: Underlying the apparently chaotic behavior in nonlinear systems, there are predictable organizational patterns.

“The behavior of tens of thousands of neurons in a brain slice is really complex,” Gluckman says with a grin. “But when we analyze their activity with computational modeling, it looks much simpler than what you might expect.”

Can successful neural engineering devices be built based on data from computational models?

“Control-engineering principles, such as those used in modern aerospace engineer-ing, can be applied to neuroscience,” Schiff maintains. “I think the Boeing 777 was the first airplane almost entirely developed from physical and mathemati-cal models on computers. They didn’t have to test-fly different versions of the airframe; they could do it in computation. And when they finally built it, it flew—and it flew well.

“Of course, all of biology—and my aerospace friends may roll their eyes at this—but all of biology is much, much, much more complicated than something as simple as an airplane,” says Schiff. “We don’t know nearly as much about brains to make use of our engineering knowledge. Nevertheless, we are beginning to take that engineering knowledge over to a variety of diseases of the brain.”

Bridging the DisciplinesCorina Drapaca, assistant professor of engineering science and mechanics, is the newest member of the center. A specialist in computational mechanics and medical image analysis, she has a Ph.D. in math-

“We have one of the best materials research programs

in the world, and we want to exploit that knowledge.”

A custom electrode interface for an implant that can read the brain’s electrical activity.

Fred

eric

Web

er


ematics and is particularly interested in mechanical brain diseases such as hydrocephalus and Chiari malformations. Says Schiff, “She embodies the core disciplinary expertise of engineering science and mechanics and translates this to a better understanding of brain disease and improving treatment.”

Looking ahead, Schiff, Gluckman, and their Penn State colleagues—including Drapaca, Jian Xu, Andrew Webb, Fran-cesco Costanzo, and Sulin Zhang, among others—will have plenty of opportunities to build bridges between neuroscience and other disciplines such as engineering, materials science, and nanotechnology, just for starters.

In 2011, the Center for Neural Engi-neering will relocate to a custom-designed 22,000-square-foot facility in the new Materials/Life Sciences complex, under the governance of the Huck Institutes of the Life Sciences. The new location will have room for about fifteen faculty members, some of whom will be drawn from within the University. “We’re also vigorously recruiting people who will be new to Penn State,” Schiff adds.

One goal: better assistive devices for patients who can’t use their bodies well anymore. “Hershey has a very, very impressive ALS (amyotrophic lateral sclerosis, or Lou Gehrig’s disease) clinic,” notes Schiff. “We’re working well in our current temporary laboratories, but we look forward to having even more sophisticated facilities for optical imaging, high-energy laser research, whole animal research, and behavioral testing and monitoring.”

Space for a brain–machine interface teaching lab is already reserved in the building plans. “In the future,” says Schiff, “we are going to have a course where our students play neural ping-pong as one of the laboratory exercises. We want to guide students into projects that lead into the unknown.”

The center will be located near both the Materials Research Institute and the Center for Infectious Disease Research, a proximity Schiff calls “crucial to what we’ll be able to do here that’s unique at Penn State. We have, arguably, one of the best materials research programs in the world, and we want to exploit that knowledge. The neural devices we’re creating have to survive in the brain for decades. We need to devise materials that, very gently, can pass electricity into the biological organ without generating toxic chemicals or passing too much current, which can burn a hole in the brain. We need batteries that can last a lifetime, recharged perhaps by the body’s own activity. These things are hard to do, but we feel it is extremely important to develop effective and safe neural prosthetic devices. We will make sure the devices developed at Penn State are known for extensive research and development into safety.”

Better neural devices will eventually mean the surgical process of implanting them will become much less invasive, says Schiff, adding that they could be placed on the brain’s surface rather than deep within it. That would be welcome news for patients like Jessica Gordon.

“Nanotechnology and neural implants are fascinating,” she says, “but I like to

hope that some day there will be options other than invasive surgery.”

For Jessica, things are looking better lately. After a medication adjustment, she has gone without a single seizure for eleven weeks. A recent EEG showed improvement and she looks forward to resuming her career as a nutritionist.

“I have been able to start running again,” she says, “and I hope to be able to run in a marathon within one year of my diagnosis. Life is one present moment after another; some are wonderful and others are painful. ‘This too shall pass’ is a phrase I’ve learned to repeat quite frequently,” she says.

Decreasing those painful times for patients with neurological disorders is what drives Schiff and Gluckman.

“I went into neuroscience because it’s the last frontier,” says Schiff. Lightly touch-ing his fingers to his head, he adds, “The brain is the one thing we really don’t understand. In years to come, I want to look back at what we’ve accomplished at the Center for Neural Engineering and be able to say we didn’t rush things, we didn’t focus on making a splash in the media or making money from new inventions. We did it carefully—and most important, we did it right.”

Steven J. Schiff, M.D., Ph.D., is Brush Chair Professor of Engineering and director of the Penn State Center for Neural Engineering. He can be reached at [email protected]. Bruce J. Gluckman, Ph.D., associate professor of engineering science and mechanics and of neurosurgery, is associate director of the Penn State Center for Neural Engineering. He can be reached at [email protected]. Corina Drapaca, Ph.D., assistant professor of engineering science and mechanics, can be reached at [email protected]. In October 2009, the Center for Neural Engineering received a $1 million challenge grant from the National Institutes of Health as a Biomedical Core Research Center.

www.rps.psu.edu 25

Behind the MaskPenn State researchers look below the surface of terrorism to understand what compels and repels individual involvement. By Gigi Marino

B y the age of 18, Indonesian-born Mohammad Nasir bin Abbas was studying the strategy of terrorism and refining his weapons skills at the so-called “Mujahidin Military Academy” in Afghanistan. By his early twenties, bin Abbas had been

recruited by the newly formed Jemmah Islamiyah (JI), a radical Islamic organization operating from Southeast Asia. Achieving a key leadership role, he was placed in charge of a training unit that included territories in Malaysia, Indonesia, and the Philippines.

Bin Abbas holds strong opinions and values. He believes in Sharia, the strict Islamic law that advocates dismemberment for theft and stoning for adultery. He trained the JI militants responsible for the Bali bombings that killed more than 200 people in 2002. And yet, he himself did not participate in those bombings, having already become disil-lusioned with JI because of its willingness to strike at civilian targets.

In fact, since then, Nasir bin Abbas has become an outspoken critic of Jemmah Islami-yah’s fanatical militantism. He is a member of an informal and iconoclastic community of ex-terrorists—once violent individuals who no longer participate in extremist activities. His story and the stories of others like him, says John Horgan, provide valuable lessons for the study of terrorism.

Photo by Frederic Weber


www.rps.psu.edu 27

“People who have disengaged from terrorism

aren’t necessarily deradicalized.”

“Only in the last couple of years have we actually

started to look at how and why terrorists quit.”

Horgan is director of Penn State’s Inter-national Center for the Study of Terrorism (ICST). His latest book, Walking Away from Terrorism: Accounts of Disengagement from Radical and Extremist Movements, published by Routledge Press in May, examines case studies from several former terrorists as a framework for understanding the complex connective tissue that binds people to ter-rorist organizations and the circumstances that inspire them to leave.

“Only in the last couple of years have we actually started to look at how and why terrorists quit. It puzzles me why we have ignored it so long. One assumption is that once terrorist movements come to an end they are no longer relevant,” Horgan says. “From my perspective as a researcher, this is the best time to go in and speak to these people about their involvement. It’s safe for them to talk, and it’s safe for us to question them.”

Horgan, who has been interviewing former terrorists since 1996, when he was a Ph.D. student at University College Cork in Ireland, talked to bin Abbas in Jakarta, Indonesia, in 2007. “While he had no moral qualms about targeting the military or other symbols of the state, he drew the line at deliberately targeting civilians,” says

Horgan. “He said he was shocked at how far the movement was willing to go. For him, that was his point of departure.”

Horgan is quick to point out that disen-gagement neither predicts nor predicates deradicalization. “The assumption is that we can somehow turn terrorists, change their beliefs,” says Horgan. “One of the

really striking findings from the new book is that people who have disengaged from terrorism aren’t necessarily deradical-ized. They may have left the movement, but they still hold the same attitudes and beliefs that they acquired inside it—views about the legitimacy of terrorism or the killing of innocents.”

It Takes a Team Penn State’s ICST began in 2006 under the leadership of President Graham Spanier and Professor of Psychology Kevin Murphy, the center’s first director, in cooperation with the Worldwide Universi-ties Network, a group of sixteen universi-ties from the United States, the United Kingdom, Europe, and China. Murphy, who is world renowned for his research on the efficacy of the polygraph test, said at the time, “Drawing on the talent and resources of an international consortium of universities, we follow a cross-cultural, cross-disciplinary model that aims to bring the best researchers together to further our understanding of terrorism, and use that knowledge to help reduce the threat of terrorism.”

Horgan embraces that interdisciplin-ary approach. He says, “On a typical day

around our table, we have two psycholo-gists, an entomologist, a political scientist, a history and religious studies scholar, and a scholar from communications arts and sciences.”

At first glance, the entomologist may seem like the odd person out, but Horgan says that curiosity about how terrorists

mask their identities led him to the insect world. He wanted to learn about mimicry and camouflage. “As it turns out,” he says, “entomologists know all about these issues.”

Professor of entomology Mike Saunders is working on a taxonomy of mimicry and deception to be used specifically for studying terrorist behavior. For example,

in Batesian mimicry (named, as are other types, for the biologist who first described it), a harmless insect looks fierce to thwart predation. In Mullerian mimicry, the mimic and the prey share warning patterns and colors, and are both toxic to predators, who learn to avoid them. In Wasmannian mimicry, mimics look like their predators and get lost in the shuffle. In Peckhamian mimicry, the predator mimics its prey in order to pounce upon it. “I haven’t looked at insect behavior in this light before,” says Saunders. “We’re in the initial stages of developing our model, and we don’t know if it will hold up yet, but if it does, it could be quite useful.”

Another upcoming project for the center involves the transfer of technol-ogy among different terrorist groups. Last year, Horgan presented a paper with suicide-terrorism expert Mia Bloom on the IRA’s 1990 proxy-bomb campaign. “This is a little-known event in northern Irish history where the IRA kidnapped in-dividuals they deemed to be collaborators and forced them to drive trucks laden with explosives into British Army checkpoints,” says Horgan. “Such was the negative reac-tion, even within the IRA community, that after the first bombing the IRA decided to stop the campaign.” However, Horgan notes that in the wake of the short-lived campaign, similar proxy bombings have turned up in Afghanistan, Iraq, and Co-lombia. He says, “We strongly suspect that these movements have learned from the IRA’s use of the tactic.”

Bloom, who has since joined the Penn State faculty as an associate professor of women’s studies, also studies ethnic conflict, child soldiers, wartime rape, and the phenomenon of female terrorists. Her book, Bombshell: Women and Terror, will be published next year by Penguin Press. Other center fellows include political science professor Philip Schrodt from the University of Kansas, whose research focuses on predicting political change

Fred

eric

Web

er

John Horgan


“There is a real hunger out there for reliable,

empirically validated information.”

using statistics and pattern recognition; political science and sociology professor Ricardo René Larémont from SUNY at Binghamton, an expert in Islamic law, politics, and religion; and Penn State Harrisburg’s Michael Kenney, associate professor of political science and public policy, who studies terror networks. Kevin Murphy, an organizational psychologist who now directs special projects, has authored ten books and has thirty years of experience working with military and security sectors.

“There are very few centers like ours, that engage in truly multidisciplinary work,” says Horgan. “Our signature area is the psychology of terrorism. There is a real hunger out there for reliable, empiri-cally validated information.”

Everyday PeopleHorgan, Irish by birth, didn’t meet an Irish militant until he started working on his dissertation. He is not driven by an unsettled conflict with his homeland’s fractured history. He does not even admit partisanship and is meticulous about keep-ing politics on a solidly academic level. He is not attracted by the intrigue and deceit,

but rather by the sheer banality that often is companion to utterly hideous behavior

Studies like Stanley Milgram’s famous 1961 experiment showed that ordinary people would inflict pain on others in the name of following orders. In 1971, Philip Zimbardo had to cease his Stanford Prison Experiment because the participants acting in the roles of guards were becom-ing too sadistic. As a psychology student, Horgan says, “I was always captivated by the idea that in certain situations, extreme behavior can be elicited from people who are not necessarily distinctive or unusual in any way.

Horgan met his future mentor and collaborator Max Taylor, a leading expert in the psychology of terrorism, early in his student days at University College, Cork. “He would come to lectures and talk about these ideas,” he says. “I was hooked from day one.”

Together, Horgan and Taylor have developed a rigorous process for eliciting both qualitative and quantitative material

from interviews with former terrorists. Horgan feels that much of what is written is opinion rather than scientific fact, and that discussion about terrorism submits too readily to cliché. “It’s very easy to over-state or understate the dangers associated with terrorism,” he says. “We ought to be able to objectively analyze terrorism with the tools we have at our disposal.”

Key to the center’s mission is dispelling misconceptions about terroristic behavior. At the top of that list is the assumption that terrorists can be profiled. “People become involved in terrorism in many different kinds of ways. We also tend to ne-glect the fact that people change because of being involved with a terrorist group,” says Horgan. “Forty years of research in terrorism hasn’t revealed any meaningful terrorist profile. I suspect there probably never will be one.”

Another assumption the center seeks to unseat is that there is a single root cause of terrorism. Although it may appear plausible that societal forces like poverty or discrimination are the driving forces, Horgan counters that this notion has proved to be deeply problematic. “There are multiple ways of explaining terrorism,”

he says. “There are many people who are radicalized but who don’t participate in it. The terrorism studies community is mov-ing away from single theories.”

Horgan’s own work looks at three phases: how and why people become involved in terrorism, what sustains their involvement, and what, if anything, causes them to dis-engage from active terroristic activities.

“It’s only recently that we’ve come to uncover the complexity associated with how and why people become involved,” says Horgan. “That complexity is disheart-ening to people. But unless we acknowl-edge and appreciate it, any initiative aimed at preventing terrorism is doomed to failure.”

Consider the case of Omar Bakri Mu-hammad, former leader of Al Muhajiroun, an extremist movement in the UK. He is currently being tried by the Lebanese gov-ernment for training al Qaeda terrorists.

Omar Bakri defies simple categoriza-tion. He does not directly participate in terrorist activities, but holds extremist beliefs. Horgan, who interviewed him in

Lebanon for Walking Away from Terrorism, says Omar Bakri still has a lot of anger and blames the West for threatening the security of the Muslim world. “He told me, ‘Radicalization is not something that is bad. I believe radicalization is an essential part of life. … I do not see anything wrong with it, especially as we see the direction the whole world is going.’ ”

Horgan reflects, “One of the lessons from the book is that while in some cases people liter-ally do walk away, in other cases, walking away from one kind of involvement in terrorism means walking toward another kind of involvement. A person might move away from actively seeking to bomb people to a role in the political front. Or they might move from running a terrorist Web site to escalating their involvement. Disengagement is a more complex process than we think.”

In more than a decade of interviewing for-mer terrorists, Horgan says he is surprised how much they are willing to reveal. “You just have to ask the right questions.” An-other surprise, he says, has been that in all those interviews, only one person felt that he had no other choice but to become an active terrorist. Contrary to the popular belief that terrorists are brainwashed, Horgan concludes, the fact is that the vast majority of people involved in terrorist acts have freely chosen to participate.

What does hearten Horgan and his col-leagues is the attention and respect they have received from U.S. legislators. “We have the ear of policy makers,” he says, “and we have been warmly welcomed by individuals whose role it is to formulate new strategies for countering terrorism.”

Horgan thinks again about his role as an applied psychologist. “The whole point of academic research is for it to have an impact and be relevant in the community at large.”

Not a moment too soon.

John Horgan, Ph.D., is associate professor of psychology in the College of the Liberal Arts and director of Penn State’s International Center for the Study of Terrorism (ICST); [email protected]. His latest book, Walking Away from Terrorism: Accounts of Disengagement from Radical and Extremist Movements, was published by Routledge Press in May.

www.rps.psu.edu 29

Trouble in ParadiseTrouble in ParadiseBy Sara LaJeunesseBy Sara LaJeunesse

Acropora secale, Great Barrier Reef, Australia. Inset: Todd LaJeunesse swims past a colony of Acropora corals in the central Great Barrier Reef.30 Research/Penn State 2009–10

A better understanding of coral–algal symbiosis may help predict the survival of endangered reefs around the world.


A dozen rusty fishing boats rock gently on the surface of the shimmering, aquamarine water.

Their wood has splintered and their paint has peeled from years of exposure. I scan the horizon, looking for the research vessel that will carry us out to the reef, but I see nothing that seems suitable for an expedition.

Just as I conclude that our boat has not arrived, two men with dark tans and round bellies approach across the white sand, mutter something in Portuguese to our Brazilian colleague, and set about gathering up our things. I watch, appre-hensively, as they hoist crates of expensive scientific equipment onto their heads and wade out into the ocean. They head for a rickety vessel adorned with a sun-faded painting of Saint Peter, the patron saint of fisherman.

I am on the beach in João Pessoa, the capital city of Paraiba state in northeast Brazil, in the company of Todd LaJeu-nesse, an assistant professor of biology at Penn State, and Bill Fitt, a professor of biology at the University of Georgia. We’re here not for sun and fun, like most of the pale-skinned tourists lounging nearby, but to investigate the ecology and evolution of corals and the symbiotic algae, known as Symbiodinium, that inhabit their cells. The two Americans and their Brazilian colleague, Cristiane Francisca da Costa, are part of an international, World Bank-funded team that is studying the impacts of environmental stresses on coral reefs around the world.

Coral reefs are diverse ecosystems paralleled only by tropical rainforests in the number of species they support. A healthy reef can harbor millions of organisms, from hair-like strands of cyanobacteria woven into soft mats to barrel-shaped sponges—little smokestacks that purify rather than pollute. Reefs are home to parrotfish that pluck algae with curved beaks and violet-tinged lobsters that scavenge dead animals from the ocean floor. They are visited by giant sea turtles that glide gracefully among coral heads and sleek reef sharks that feast on colorful fish. The hub for all this diversity is the corals and their Symbiodinium, which

together provide residents and visitors alike with habitat and food.

Thriving reefs are important to human economies as well. They support fisheries, control coastline erosion, provide tourism opportunities, and serve as a potential source for medically important com-pounds we don’t even know about yet. In fact, the United Nations estimates the annual value of just one square kilometer of coral reef at some $600,000.

Barrage of threatsThese underwater sanctuaries have long suffered from a barrage of threats, including pollution, disease, and overfishing. Their most devastating environmental stressor, however, may turn out to be global warming. Corals rely on their photo-synthetic partners to convert sunlight into food, but when temperatures rise, the colorful algae die, leaving coral to starve. Known as bleaching, this phenomenon can lead to the collapse of entire underwa-ter ecosystems. Slight increases in ocean temperature, as little as 2 to 3 degrees Fahrenheit, can kill vast swathes of reef.

LaJeunesse and Fitt are investigating the possibility that certain coral–algal partner-ships can withstand the effects of global warming. So far, their search has taken them to reefs off the coasts of Mexico, Thailand, Zanzibar, Australia, Hawaii, and Barbados, among other exotic places. “Our data show that different geographic regions are home to unique combinations of host and symbiont,” says LaJeunesse. “Each of these combinations may respond

differently to stresses.” In the eastern Pacific, for example, he has found that a coral in the genus Pocillopora teamed with a particular Symbiodinium can withstand higher temperatures than the same Pocillopora when it associates with another species of algae. Here in João Pessoa, the team will investigate coral–algal symbioses in a region that so far has been relatively unaffected by global warming. Regional ocean currents have prevented the local waters from heating up, LaJeunesse explains. “This site will serve as an important benchmark we can compare to other sites that have been affected.”

Brazil’s reefs are special for another reason, too: They contain several species of coral, including a rare bluish-green branching coral called Mussismilia hartti, not found anywhere else in the world. “The reason Brazil has so many endemic species,” says Fitt, “is that the outflow of the Amazon River has prevented the exchange of genes between corals here in the southwestern Atlantic and those in the Caribbean. The Isthmus of Panama further isolates the Atlantic reefs from the Pacific.”

Brazil’s unique corals may in turn harbor unique species of algae. “There are two basic types of Symbiodinium,” explains LaJeunesse. “The ones we call specialists associate only with certain species of coral host. Generalists are less picky. Some of Brazil’s endemic corals may contain algal specialists that are unknown to science.”

Out to seaI wade out to our modest-looking research vessel and begin to climb up a thin-railed ladder when a calloused hand reaches down, grabs my arm and gently pulls me out of the water. The hand belongs to Iran, the boat’s owner. A local fisherman, he has been hired for the day to take us to two reefs where we will collect samples of as many species of coral as we can find.

From the boat, the reef looks like a colossal creature

crouched at the bottom of the sea.

Echinopora mammiformis

www.rps.psu.edu 31

Iran yanks the throttle and the boat’s engine sputters to a start. Instead of a steering wheel, he uses a long, smooth tree branch to guide the rudder. As we head out to sea, the high-rise hotels and condominiums that line João Pessoa’s beaches become smaller and smaller in the distance.

Located at the easternmost tip of the Americas, João Pessoa is one of Brazil’s oldest cities, founded by the Portuguese in 1585. Although it is larger than Pitts-burgh, with about 672,000 residents, its numerous parks and nature preserves earned it a designation as “the second-greenest city in the world” by the United Nations in 1992. Even with all the green space, however, local residents have noticed dramatic changes in recent years. “When I was a boy, there were only two tall buildings in João Pessoa,” says Iran. “Now there are dozens.”

I am pleased to find that he speaks English, since my repertoire of Portuguese words is limited to olà (“hello”) and obrigada (“thank you”). Before we get far, I ask him about Internet stories I have read claiming the waters off this point are known for shark attacks. Iran dramatically points to a large scar on his left elbow.

Barbara, under the supervision of renowned marine biologist Bob Trench. Although Fitt is twenty years LaJeunesse’s senior, the two crossed paths during Fitt’s return visits to his alma mater while LaJeunesse was a student. Cristiane Francisca da Costa, in turn, studied with one of Fitt’s former colleagues. Now a professor of biology at the Universidade Federal de Campina Grande, she is a well-known expert on Brazil’s corals. Her knowledge of local species is a valuable complement to the Americans’ expertise in coral–algal interactions.

A rare find“The first site we are going to has a relatively high diversity of corals,” Francisca da Costa informs us. The spiral curls of her coffee-brown hair whip around as the boat cuts through the wind. “We should be able to find at least eight species there, four of which are endemic to Brazil.”

When we arrive at the site, the water is gray and murky. Heedless of the sharks that may be lurking, the scientists squeeze themselves into tight-fitting wetsuits, strap on flippers and air tanks, and step out, one by one, over the edge of the boat. From the rail, I hand them sacks of gear: hammers and tiny chisels for breaking samples, plastic collection bags, and underwater cameras. Then they disappear beneath the surface.

In a few minutes, I decide to check things out for myself—not diving but snorkeling. Even through the mask, the turbidity prevents me from seeing anything at a distance, but up close I make out some chestnut-colored coral heads—masses of genetically identical polyps—and a small school of butterfly fish, white with golden stripes. I also find a sea hare, a slug-like, fluorescent-yellow animal with stubby antennae.

Eventually, I return to the boat, and shortly thereafter I see big bubbles breaking on the water’s surface as the biologists ascend. Floating a few feet from the boat, they gently hand me their sacks of tools. Then they toss dozens of clear plastic bags onto the boat’s slippery deck, each bag containing two-inch fragments of pink and brown corals.

“I found Mussismilia hartti!” exclaims Francisca da Costa as she climbs onto the boat. She reaches for a towel. “No one has

looked at its Symbiodinium,” she continues excitedly. We all gather round to peek at the specimen in her palm. Its lovely blue-green shade makes it look like a small bouquet of flowers. From its base sprout several stalks of calcium carbonate, the hard, non-living substance that corals secrete as they grow. At the end of each stalk sits a plump coral polyp, its tiny tentacles radiating outward like the petals on a flower.

Underwater colossusWe soon push on to our next site, a few miles to the southeast. The water here is much clearer. We’re farther from the mouth of the Paraiba River, Francisca da Costa explains, and as a result there is much less sediment. The plan this time is to sample corals around the edge of the reef, about twelve feet below the surface, and then to swim over the top of the reef, which lies just a few feet underwater. Small changes in depth can significantly influence the composition of a coral community, LaJeunesse explains.

From the boat, the reef looks like a colossal creature crouched at the bottom of the sea. And it is a colossal creature, in a way. Most corals reproduce by cloning themselves until they have formed sizable colonies, or heads. In healthy ecosystems, these colonies become enmeshed with those of other species, eventually forming dense reef patches, some of which are so large they can be seen from space.

The view from below the water, however, is entirely different—a sunny underwater paradise. Tiny black fish with purple faces dart in and out of the reef’s crevices; electric-blue tangs skirt the reef’s edge; and goby fish with their protruding eyes attempt to blend in with the sand and rocks.

Coral reefs are diverse ecosystems paralleled only by

tropical rainforests in the number of species they support.

“There are many dangerous sharks in these waters,” he says gravely, but he can’t suppress a following giggle. I think he is pulling my leg.

As we make our way to the reef, about half a mile offshore, the three biologists discuss their plan for collecting small samples from individual coral colonies. LaJeunesse and Fitt have been working together since Todd signed on as a postdoctoral researcher in Bill’s lab at the University of Georgia back in 2000. However, the two have known each other for even longer. Both did their graduate work at the University of California, Santa

Todd LaJeunesse preparing to dive

Acropora nasuta


As I snorkel, I see bits of colorful coral here and there, but most of the reef is smothered by lush, green leaves with long, feathery tips. Fitt, swimming nearby, pauses to tell me that this is a green algae. “Its presence here indicates nutrients, maybe from the sugar cane fields along the Paraiba,” he says, treading water. “These algae are a problem—they tend to suffocate the corals underneath. They prevent the Symbiodinium from getting the sunlight they need to make food.”

Returning to the boat, I wait for the biologists to finish their work, and Iran begins to regale me with tales of his life on the sea. Soon enough the divers return, and I can see from LaJeunesse’s face that he’s disappointed. “We didn’t find anything new,” he says simply, as he climbs over the side. Fitt, behind him, is more sanguine. “We did get replicate samples,” he says. “The lack of new species might mean we’ve thoroughly sampled all the host species in this immediate area.”

Food for ThoughtLater that evening, we stop for dinner at a traditional restaurant near the beach in João Pessoa. Waiters dressed in brightly colored costumes bring out carafes of pineapple juice and fish-ball appetizers. Next come platters of sizzling goat meat and beef steaks garnished with grilled onions. There are bowls of rice, mashed potatoes, fried bananas, and pinto beans mixed with celery, onion and ground manioc, a Brazilian staple. For dessert, we are presented with a traditional cake, bolo de rolo, made up of alternating layers of soft dough and guava jelly.

Full and happy, we head to the univer-sity to process the day’s samples. They must be handled quickly, LaJeunesse explains, before the DNA degrades and becomes useless. When we enter Francisca da Costa’s lab, five of her undergraduate and graduate students are there to greet us. The hour is late, but they are eager to learn some new techniques.

With a hammer and chisel, Todd breaks the coral fragments into tiny pieces and places them into finger-sized plastic vials, each containing a liquid salt preservative that will protect the organisms until he is ready to analyze them. Back in his lab at University Park, he explains, he will extract DNA from the Symbiodinium samples and then use a ribosomal fingerprinting technique to rapidly identify their species. The assay separates fragments of DNA based on their sizes, and the resulting pattern is unique to particular species.

Although this technique has been used for many years to identify certain mi-crobes, LaJeunesse was the first to expand its application to Symbiodinium. As a graduate student, he explains, he studied a type of sea anemone that associates with Symbiodinium, but was unable to identify algal species with the available techniques. A friend who had been using ribosomal fingerprinting to identify bacteria suggested he try it. After many months of adjustments, LaJeunesse was able to tailor the method to his needs. Now the application is widely used by coral biologists.

Once he has identified the species of Symbiodinium he has collected, LaJeunesse tells the students, he will use commercial software to construct a phylogenetic tree that depicts the evolutionary relationships between the different species of both coral and algae. “This will help us predict how specific symbioses will respond to climate change,” he says.

Using a different set of samples, Fitt then shows the group how to dry and weigh the coral fragments so as to accurately determine their biomasses, the amount of living tissue they contain. “The thicker the corals’ living tissue is, the more Symbiodinium they contain, and the healthier they are,” he says. Fitt is particu-larly interested in measuring biomasses in Brazil because he has observed loss of biomass among certain Caribbean species, a condition he attributes to heat stress. “The corals here are not known to have experienced bleaching, but I want to be sure,” he explains.

New cluesTwo weeks later, back in University Park, LaJeunesse’s carefully packaged samples arrive in the mail. He calls me as soon as he’s finished analyzing the first subset, and sounds so eager to share that I immediately head for the lab.

“I’ve discovered some really interesting things,” he says excitedly, as I look for a place to hang my coat. “Remember how we expected Mussismilia harttii to harbor a new symbiont? What I found is that it contains a species indistinguishable from one that lives in the Caribbean! This means there may be some gene flow across the Amazon River boundary.” He describes how he will employ population genetic markers—tools that look for variation among genes in populations—to test this new hypothesis. If he finds that the Mussismilia’s genes are similar to those of the Caribbean species, then he can be sure that gene flow is occurring. But if the

genes differ significantly, then the two organisms likely have been separated for thousands of years and have evolved into different species.

Another coral species, Siderasterea stellata, he reports, is capable of harboring any of three different symbionts, a previously unseen variability that may be advanta-geous in terms of natural selection. It will take several months to analyze the rest of his samples, LaJeunesse acknowledges. Still, he’s already eager to return to Brazil to investigate some of the country’s other reefs, especially those farther from land. One of these, the Abrolhos Bank, is consid- ered to be among the world’s most unique.

“Our ultimate goal is to continue to collaborate with Francisca da Costa on a nationwide survey,” he says. Such a survey will help LaJeunesse and his colleagues understand the specifity of host–symbiont relationships—how geography and environment influence it and how it changes over time. The data will also serve as an important baseline for tracking host–symbiont communities.

“Corals have experienced major alterations in climate in the past, but they have never faced the rapid changes that are occurring today,” says LaJeunesse. “Understanding the basic biology will help us predict the extent to which these sensitive creatures will respond to unprecedented change.”

Todd LaJeunesse, Ph.D., is assistant professor of biology in the Eberly College of Science, [email protected]. William Fitt, Ph.D., is professor of biology at the University of Georgia. Cristiane Francisca da Costa, Ph.D., is professor of biology at the Universidade Federal de Campina Grande in Campina Grande, Paraiba, Brazil. The work described above is funded by the World Bank.

Acropora humilis

www.rps.psu.edu 33

Webb Miller (left) and Stephan Schuster

Fred

eric

Web

er


Stephan Schuster was never all that interested in ancient DNA. As a

young genomicist at the Max Planck Institute for Developmental Biology in his native Germany, his forte had always been bacteria. By deciphering and comparing the genomes—the genetic blueprints—of various microbial species, he sought to unlock the secrets of these ubiquitous creatures: how they evolve and interact with the organisms that host them.

Schuster’s early work had attracted considerable attention. In particular, a study done with colleagues in Germany and England in 2004 laid bare the fascinating life cycle of Bdellovibrio, a predatory microbe whose efficient dispatching of its rivals suggests the promise of a “living antibiotic.” But when Schuster accepted an offer to join Penn State’s Center for Comparative Genomics and Bioinformatics in 2005, he knew he had a decision to make. “I had to rebuild my lab,” he remembers. “And I had already learned that there was a big change in technology about to happen.” This change was the emergence of a next-generation DNA-sequencing

Forget Jurassic Park. By successfully sequencing the DNA of a long-extinct

species, Stephan Schuster and Webb Miller have helped

push back the boundaries of molecular biology.

By David Pacchioli

MaMMoth achieveMent

machine, brainchild of a biotech start-up in Connecticut named 454 Life Sciences.

The automated “reading” of DNA sequences—the paired strands of nucleotides, or bases, that make up our genetic alphabet—had long depended on a chemical process developed by the British biochemist Frederick Sanger back in 1977. The so-called Sanger method had transformed biology, birthing the field of genomics and culminating in the successful decoding of the entire human genome, completed in 2003. But the sheer costliness of Sanger sequencing had placed strict limits on its use.

The emergent 454 machine, employing a new technology called sequencing by synthesis [See sidebar, page 39], allowed for “massively parallel” sequencing of DNA fragments—which meant a vast increase in speed, and a correspond-ing drop-off in cost. Its developers envisioned that this approach would open up whole new frontiers of basic and biomedical research.

For all its promise, however, initial reaction to the new machine was “surprisingly reserved,” Schuster

remembers. The first 454 did seem to have some drawbacks. It was capable of reading only about 100 bases at a time, compared with 800 or so for the latest Sanger sequenc-ers, and this shorter read length would make it harder to reassemble fragments of DNA into a complete genome. There were also questions about its accuracy. Established researchers, and funding agencies, moreover, were heavily invested in the existing technology.

For Schuster personally, the moment was an important one. DNA sequencers are costly equip-ment, and a successful enterprise would certainly require multiple machines. The path he chose would be defining. But as he crossed the Atlantic to embark on the next stage of an already flourishing career, that choice became clear. His goal, after all, was to “explore the limits” of DNA sequencing, Schuster told himself. “I decided I would rather risk my start-up money on the new technology than continue to work with the established one,” he recalls.

www.rps.psu.edu 35

The 454 GS20 sequencer he requested for his brand-new lab at University Park was only the fourth one off the production line—the first purchased by a university. And it was the 454 that led Schuster to the woolly mammoth.

Faded Genes The study of ancient DNA, which began

in the mid-1980s, has always been bedeviled by two realities. First, the genetic trail erodes over time. Over hundreds and thousands of years, the DNA molecules of a defunct organism inevitably disintegrate, leaving only a welter of fragments. These faded traces, in turn, are mashed up with sundry other bits and pieces, the equally degraded DNA of the plants, animals, and microbes that, over millennia, happened to die on top of or near—or inside—the body in question. This many-layered presence of competing information is excruciatingly hard to interpret: Lifting the original fingerprints from a recently unearthed Roman coin might actually be easier.

To minimize their handicap, research-ers in ancient DNA must seek out the most pristine of specimens, remains either mummified or frozen (preferably both) of the most enduring of biomaterials: bones and teeth. “Hydroxyapatite—that’s a mineral contained in bone—binds the DNA and stabilizes it,” Schuster explains. “But bone is also a highly porous material, and in the process of putrefaction, bacteria grow deeper and deeper into it, using the

last remaining organic materials, amino acids, as a body decomposes. In the end, these bacteria also die, and they deposit their own DNA on top of the animal’s or person’s DNA.”

Even the best specimens, therefore, have yielded little in the way of useful information. Using traditional Sanger sequencing, Schuster says, only a tiny fraction—at most 2 percent—of the DNA picked up from a sample of ancient bone would be likely to be the DNA of the creature to whom the bone actually belonged. “And that was not enough to sustain a large-scale project.”

To Schuster, however, in the blue-sky excitement of trying out a new technology, the notoriously poor quality of ancient DNA smelled like opportunity. To the extent that it can be recovered at all, he knew, the stuff turns up as alphabet soup, snippets only dozens of base pairs long. You don’t get long strands of intact code. “I thought that might be a good match for the 454’s short read lengths,” Schuster says simply. What others had seen as a flaw

might turn out to be an asset. Acting on this hunch, Schuster set about lining up as many samples of ancient DNA as he could. “We systematically explored all kinds of animals that went extinct within the last 100,000 years,” he recalls. “One of these samples happened to be from a mam-moth, and it worked for us immediately.”

Joining Forces“I first saw sequence data from a woolly mammoth on November 18, 2005, at about 3:30 in the afternoon,” Webb Miller recalls with a wry smile. “Stephan walked into my office and said, ‘Hey, I’ve got something here that I think you’re going to find really interesting.’ And that was it.”

The two had been looking for a way to collaborate since Schuster’s arrival at Penn State some months earlier. Miller, eighteen years Schuster’s senior, had been a pioneer in the now-exploding field of bioinformatics. (His trailblazing efforts were recently recognized with a career award from the International Society for Computational Biology.) After starting as a computer scientist in the late 1960s, he became intrigued by early reports of the Human Genome Project, and, looking for a new challenge, decided to take the plunge into biology.

One of Miller’s early successes, the Basic Local Alignment Search Tool, or BLAST, for which he and two colleagues devel-oped the computer algorithms, is still one of the most widely used programs for searching databases of genetic sequences. In the years since, Miller, now professor of biology and of computer science and engineering at Penn State, has made a specialty of developing and applying methods to compare longer and longer sequences of DNA, most recently com-plete vertebrate genomes. “Webb has played an essential role in nearly every vertebrate genome sequence project,” says colleague David Haussler of the University of California at Santa Cruz. He was, in short, the perfect match for Schuster and the woolly mammoth.

“Coming from the microbial world, I found mammalian genomes very intimi-

the study of ancient Dna, which began in the mid-1980s, has always been bedeviled by two realities.

Hair of the mammoth: Encased in keratin, ancient DNA remains viable.

S.C

. Sch

uste

r


dating,” Schuster explains. “Mammalian genomes contain a lot of repeat elements— less than 2 percent of the genome is coding, where the actual information is stored. This compares to 90 to 95 percent in a bacterial genome. You could say that almost nothing is coding in a mammalian genome, and almost everything is coding in a bacterial genome. You need very different computational tools to be able to assess them.”

Their first paper together was published in the journal Science in December 2005. Working with Hendrik Poinar of McMaster University, a leading expert in ancient DNA, Schuster and Miller presented sequence data retrieved from a 28,000-year-old mammoth jawbone that had been frozen in the permafrost of northern Siberia. Using the present-day African elephant for comparison, they were able to identify 13 million DNA base pairs—a tiny fraction of the beast’s genome, but by far the largest piece that had ever been sequenced. More impor-tant, they were able to show that fully 50 percent of what they had gleaned was actual mammoth DNA, and not that of an environmental contaminant. No prior study involving an extinct mammal, Schuster says, had ever yielded more than a few percent.

A Whole New FieldSome months later, Schuster was in Europe visiting with another leader in ancient DNA research, Tom Gilbert of the University of Copenhagen, when the lunchtime talk got around to specimens. Gilbert, having tired of the contamination issues he encountered working with fossil bones, had begun experimenting with hair as a source material. Although it is routinely analyzed for evidence in present-day crime labs, hair had been pretty much ignored by the ancient DNA crowd. “When people thought of sequenc-ing DNA from hair, the usual assumption was that the material must come from the hair root,” or follicle, “because the hair shaft appears to be dead,” Miller explains. Skin cells attached to the follicle make juicy tidbits for crime scene investigators, but they degrade rapidly.

Gilbert’s trials, however, had revealed that the hair shaft itself contains DNA. Even better, this DNA is encased in keratin, the tough fibrous protein that Miller calls “a kind of biological plastic.” Thus protected, it should remain viable much longer than DNA from even bone. And unlike bone, Schuster says, it could be easily decontaminated—“by shampoo-

ing and then soaking in ordinary house-hold bleach.”

In September 2007, the three research-ers, working with a large international consortium, published in Science the complete mitochondrial DNA for ten woolly mammoths taken entirely from tufts of hair, some of them 50,000 years old. It was significant that these samples had been stored away in institutions, not frozen in ice. One of them, in fact, came from the famous Adams mammoth, which had been kept at room temperature in a Russian museum for over 200 years. That such material could yield such rich genetic information suggested that their sequencing method might be applied to specimens of other extinct and non-ex-tinct species held in collections around the world. This broad new application for DNA analysis even inspired them, only half in jest, to coin a term for this new field of study: museomics.

Going NuclearMitochondrial DNA, or mtDNA, the strange scrap of genetic information found outside the cell nucleus, is valued by researchers for a number of reasons. Hundreds of copies of this information are present in every cell, which makes it that much easier to recover. And mtDNA evolves much faster than its nuclear counterpart, which makes it useful for spotting differences within a population. But mtDNA makes up only a tiny fragment of an individual’s genetic blueprint (in the mammoth, only 13 of some 20,000 genes). To get the bigger picture requires unraveling the entire genome.

No one had ever attempted this feat for an extinct animal. Sample quality aside, with traditional Sanger sequencing the task was simply too expensive. With the next-generation machine, however, it was suddenly feasible to sequence the same stretches of DNA over and over (and over, up to twenty times), which is critical for spotting mistakes and getting a true read. In the case of the mammoth, there was the added advantage of having a close relative available as a reference. “We had a pretty good sequence of the African elephant to map onto,” Miller says. “That greatly simplifies the job of analyzing these little fragments.”

In November of last year, after months of effort, Miller and Schuster published in the journal Nature a paper that riveted the scientific world: Using hair taken from two mummified specimens, they had success-fully sequenced more than 4 billion bases

of DNA, roughly 140 bases at a time. By comparing against their elephant guide, they could confirm that 3.3 billion of these bases were mammoth DNA. In all, they estimated they had accounted for 50 to 70 percent of the entire mammoth genome, with the rest waiting only for additional funding. Whatever the exact percentage, this was a dataset “100 times more extensive” than any yet seen for an extinct species, Schuster said. “This really is the first time that we have been able to study an extinct animal in the same detail as the ones living in our own time.”

These results, combined with those of the earlier mtDNA study, yielded several new insights into mammoth—and elephant—evolution. Woolly mammoths apparently separated into two groups around 2 million years ago, and these groups eventually became genetically distinct sub-populations, Schuster says. One of these groups died out approxi-mately 45,000 years ago, while the other lived on until the last Ice Age, about 10,000 years ago. The data also show a closer relationship between mammoths and modern-day elephants than was previously suspected: “Their genomes are over 99 percent overlapping.” In that remain-ing fraction of a percent, he and Miller have begun to look for the genetic causes of some of the mammoth’s unique traits, including its adaptation to extreme cold.

Ice Age 2?These revelations met with keen interest throughout the ancient-DNA community, but it was something else Schuster said, quoted at the tail end of a Penn State press release, that caught the attention of the wider world. “By deciphering this genome,” he allowed, “we could, in theory, generate data that one day may help other researchers to bring the woolly mammoth back to life.”

“Ice Age Mammal May Walk Again,” boomed one of the resulting headlines. “Jurassic Park-style breakthrough,” blared another. The story was picked up and trumpeted by dozens of news outlets around the world, and Schuster was interviewed on Fox News and Good Morning America, following video clips from Mammoths to Manhattan and Ice Age 2. Although raising a mammoth was not the object of the study, he said, blinking a little under the studio lights, “most experts would agree” that, in the wake of the new data, “for the first time it is not entirely impossible to think about” doing so. His careful qualifications seemed lost on his TV hosts.

www.rps.psu.edu 37

Miller, for his part, was even more dismissive. “At first I thought it was a stupid idea,” he admits. “But I’m starting to get more interested. I’d like to see more research being done in reproductive technology, for the possibility of human benefit down the road, and this might be a relatively safe way to do that.” He muses. “It would be sort of like a moon shot.”

Schuster’s current argument is that, given the theoretical possibility, rapid advances in the practice of genetic engineering over the last five years make it inevitable that scientists will one day have at least the capability of cloning a mam-moth. “Just look at the amount of manipulation that is already being done in farm animals,” he says.

The easiest way to proceed would be to alter the genome of a modern-day elephant by introducing mutations—in-serting mammoth DNA at the approxi-mately 400,000 sites (out of 4.5 billion) where elephants and mammoths differ. This hybrid genome would then be

injected into an elephant embryo and carried to term in an elephant mother. (“You would get what we call a mammoth-ified elephant,” Schuster says. “We have no idea what it would look like.”) A more radical approach would be to use a completely reassembled mammoth genome to synthesize a set of actual mammoth chromosomes. As far fetched as that may sound, Schuster points out, genomics pioneer Craig Venter has already succeeded in synthesizing the chromosome of a bacterium.

“This field of synthetic biology is unfolding as we speak,” Schuster says. “We will be able to design entire organisms, and as a side product we will one day be able to synthesize the chromosomes of extinct animals. However—and here is my word of caution—at the moment when we are actually capable of doing this, the technology will have such profound impacts on human society that I don’t think we will have much interest in a folly like resurrecting a mammoth.”

Extinction BiologyIn April of this year, Schuster and Miller were named to Time magazine’s list of “Top 100 Most Influential People”—along with Michelle Obama, Energy Secretary Steven Chu, and the Twitter guys. Craig Venter, who wrote their citation, discount-ed the possibility of bringing a mammoth back to life. The real accomplishment, he wrote, was in “pushing the limits of DNA analysis, both to explore our past and perhaps predict our future.”

Boutique science aside, the real benefits of the mammoth genome project, Schuster and Miller agree, will likely come in the here-and-now realm of extinction biology. One of their immediate goals is getting a better handle on just what forces killed off this mighty creature. “There are many hypotheses,” Schuster says, “but all of them are hard to substantiate when you look closely.” Their sequencing data already rule out humans as culprits, he says, at least for that first big wave of extinction 45,000 years ago. “There were no human hunters in Siberia at that time.”

The mtDNA data have also revealed a surprisingly low level of genetic diversity across mammoth populations, which may have made the species especially suscep-tible to environmental threats. “We’re actually thinking about three separate extinction events,” Miller says: “the one at 45,000 years ago, the famous one at 10- to 12,000 years ago, and then there were actually some woolly mammoths that survived on isolated islands up until about 3,700 years ago. It could well be that they’re not due to the same causes.”

Their techniques, they believe, can yield important answers for other long-lost mammals too, and even, says Schuster, for reptiles and amphibians, “particularly if we can get parts similar to hair that contain keratin—like scales, horns, and claws. This is a very robust and widely usable approach.”

Already, he and Miller have turned their attention to more recent cases of extinc-tion, like the Tasmanian tiger, a wolf-like marsupial also known as the thylacine. “One of the things we want to see is what does a population look like ten years before it goes extinct, or twenty, or thirty years,” explains Miller. “We can’t do that with the woolly mammoth, not at that resolution. But with the Tasmanian tiger, we know exactly when it went extinct: September 7, 1936. There are something like 700 known specimens of this animal. We can sequence all of them, and know when they were collected. We can really watch the endgame of a species.”

Understanding the genetic underpinnings of past extinction events may be crucial for protecting other potentially threatened species—including, perhaps, our own.

Skilled hands manipulate fractions of small droplets containing mammoth DNA.

S.C

. Sch

uste

r


Clues to the FutureSuch data provide valuable points of comparison for present-day endangered species, the researchers say, such as the Tasmanian tiger’s legendary relative, the Tasmanian Devil. Currently teetering on the edge of extinction, the Devil is being wiped out by an infectious facial cancer whose spread is facilitated by inbreeding—a lack of genetic diversity so acute that it knocks out immune response. By sequencing animals that have the cancer and compar-ing those sequences against those of animals that have resisted the disease, and careful outbreeding based on the results, they suggest, wildlife biologists might create a new starter population that could be held in captivity with the hope that someday the cancer will have run its course. “We hope the Tasmanian Devil becomes the first instance where genome technol-ogy has been put to work in order to try to save an endangered species,” says Schuster.

Understanding the genetic underpin-nings of past extinction events, he and Miller argue, may be crucial for protecting other potentially threatened species, including, perhaps, even our own. “What makes us so sure that we cannot go extinct?” Schuster asks. “We are so happily messing around, even actively contributing to a change in our environment, believing that we are untouchable. By reconstruct-ing the biological history of the last 10,000 years—the big change that has happened since the last Ice Age—we may find a message stored in the fossil record that is very important for our future.

“This is my fascination with genomics, these final answers,” he says. “You can sequence genomes down to the very last base pair. And by then making compari-sons you have an excellent way of really understanding the biology that is going on—in evolution, in function, in disease. This is why I’m convinced that next-gener-ation sequencing is the biggest thing that has happened in biology in a long time.”

Stephan C. Schuster, Ph.D., is professor of bio- chemistry and molecular biology in the Eberly College of Science; [email protected]. Webb C. Miller, Ph.D., is professor of biology and computer science and engineering in the Eberly College of Science; [email protected]. Both are associated with Penn State’s Center for Comparative Genomics and Bioinformatics. The mammoth research reported above was funded by Penn State, Roche Applied Sciences, a private sponsor, the National Human Genome Research Institute, and the Pennsylvania Department of Health.

DNA Sequencing:The Next Generation

The “sequencing-by-synthesis” approach first marketed by biotech start-up 454 Life Sciences (now a division of Roche Diagnostics) allows for “massively paral-lel” DNA decoding—it can handle over a million sequencing reactions at the same time, compared with the old method’s 96. Even in its first incarnation, Stephan Schuster says, the 454 machine could easily outproduce more than fifty of the old-style Sanger-based sequencers at about one-sixth the cost.

At the core of the new machine is a glass slide no bigger than a credit card, its surface pocked with 1.6 million tiny wells. As Schuster explains, single molecules of DNA are chopped into fragments, and each fragment is stripped down to a single strand. These strands are then attached to tiny sugar beads, and each bead in turn is encased in a lipid bubble. Inside this microreactor, the single-strand frag-ments are amplified by polymerase chain reaction (PCR) to make 10 million copies. Then the bubbles are burst, and one bead, with its attached copies of DNA, is placed in each of those tiny wells (B). There, the strands are exposed to a wash of known nucleotides (As, Ts, Gs, and Cs) that hook up with their complementing bases (A) to build new double-strands—this is the synthesis part.

Each time a new base latches onto a strand it gives off a compound called a pyrophosphate, which is chemically converted into the enzyme luciferase, the same glowing stuff that’s present in a firefly’s tail. The resulting flash of light is de-tected by a digital sensor, in effect reading off the sequence of bases in the grow-ing chain (C). Then powerful computers look for matching sequences to begin the daunting job of knitting the fragments back together.

“As a result of this process,” Schuster says, “we are doing with a small group of people and a cluster of rooms what used to take hundreds of people and whole buildings full of machines. We are one of the world’s smallest genome centers.”

–DP

Pho

to c

red

it: 4

54 S

eque

ncin

g ©

200

9 R

oche

Dia

gnos

tics

www.rps.psu.edu 39

A Sporting Chance Standing Stone No Leaf Unturned

Fans of the World Unite! A (Capitalist) Manifesto for Sports Consumers by Stephen F. Ross and Stefan Szymanski (Stanford University Press)

You say you want a revolution? In Fans of the World Unite! Stephen F. Ross and Stefan Szymanski offer just that: a comprehensive plan to reorganize U.S. professional sports, which they maintain are badly served by monopolies of self-interested team owners.

Ross, a professor of law and founder of the Institute for Sports Law, Research, and Policy at Penn State, and Szymanski, an economics professor at London’s City University, have long shared an interest in how organizational structures impact sports practice around the world. In the United States in particular, they argue, the current system, with its high ticket prices, TV blackouts, and closed leagues, not only oppresses fans and holds cities hostage to increasing demands for multimillion-dollar tax subsidies, but damages the sports it promotes.

Beginning with “A Sports Fans’ Mani-festo” (which self-mockingly echoes the U.S. Declaration of Independence) and citing along the way Alan Greenspan and Yoko Ono as well as Karl Marx and Adam Smith, they lay out a playful but serious case for reform based on two simple but radical ideas: league governance indepen-dent of team ownership and a European-soccer-style relegation system that pro-motes winning teams and demotes losers. Could be a game changer.

–DP

Obelisk: A History by Brian A. Curran, Anthony Grafton, Pamela O. Long, and Benjamin Weiss (M.I.T. Press Burndy Library Publications)

From its ancient origins as an element in sun worship to its appearance in today’s New Age healing spas, the obelisk has long been an object of fascination. Defined as a four-sided tapering monument that ends in a pyramid-like shape at the top, the classic obelisk—made famous by ancient Egyptian culture—is constructed out of a single massive stone. By quarrying a stone weighing hundreds of tons and setting it upright at a temple entrance, a leader displayed his might and created a timeless memorial to his rule.

Despite their massiveness, many Egyptian obelisks were shipped to ancient Rome and Constantinople, and in the eighteenth and nineteenth centuries were installed in world capitals including Paris, London, and New York. The origins, travels, and enduring appeal of the obelisk are presented in a comprehensive new survey by historians Brian A. Curran, Anthony Grafton, Pamela O. Long, and Benjamin Weiss. The authors—including Curran, associate professor of art history at Penn State—combine impressive scholar-ship with a lively, readable tone and many fine illustrations, as they explore everything from the engineering challenges of constructing and moving the obelisk to its symbolism in the realms of politics, nationalism, and religion.

–MBM

Manual of Leaf Architecture by Beth Ellis, Douglas C. Daly, Leo J. Hickey, John D. Mitchell, Kirk R. Johnson, Peter Wilf, and Scott L. Wing (Cornell University Press)

Whether one is a backyard botanist or tropical ecologist, this manual—illustrated with more than 300 photographs of prepared stained leaves and dozens of line drawings—comprehensively describes, compares, and classifies the leaves of flowering plants, including leaf traits such as organization, shape, venation, and margins.

The ability to describe and identify plants based on their leaves rather than their flowers is especially useful for those who work with fossil leaves (typically found without flowers) or whose interest is tropical plants with irregular and brief flowering cycles.

The authors (including Peter Wilf, Penn State associate professor of geosciences) combined rigorous scholarship and a detailed examination of thousands of living and fossil leaves to create this book.

Colleagues have called it “a major contribution,” “indispensable,” and “eminently practical,” and plant biologist Lawren Sack of UCLA remarked that “for those of us who study leaves, this guide is analogous to the first manual on human anatomy.” Clearly, the Manual of Leaf Architecture—published in association with The New York Botanical Garden—looks like an instant classic in its field.

–MBM


w O R t h R e a d i n G :

Origins of Species Typecasting Labor Master Detective

The Timetree of Life by S. Blair Hedges and Sudhir Kumar (Oxford University Press)

When we think of evolutionary history, we think of phylogeny—the relationships among species represented by the all-em-bracing family tree of life. Equally impor-tant to scientific understanding, however, are timescales—knowing just when all those individual branches diverged.

Long after Darwin, establishing timescales was still dependent on the fossil record, and results were necessarily approximate. More recently, advances in DNA sequenc-ing have allowed molecular clocks that can pinpoint divergences, and many research-ers have devoted themselves to establishing accurate “timetrees” for individual species. Now, Blair Hedges at Penn State and Sudhir Kumar at Arizona State University are leading an initiative to synthesize these efforts into a unified whole.

As a first fruit, Oxford University Press has published The Timetree of Life, a comprehensive resource edited by Hedges and Kumar that includes timetrees and evolutionary histories for all of the major groups of organisms. A companion online database (www.timetree.org) allows researchers and students to retrieve and update the data as new studies are completed.

“The ultimate goal,” says Hedges, “is to chart the timescale of life—to discover when each species and all of its ancestors originated, all the way back to the origin of life some 4 billion years ago.”

–DP

Shadow of the Racketeer: Scandal in Organized Labor by David Witwer (University of Illinois Press)

In the late 1930s, as organized crime muscled in on a newly legitimized labor movement, crusading columnist Westbrook Pegler uncovered a union corruption scandal involving payments by Hollywood movie studios to the Chicago mob. Pegler’s relentless exposé spurred the conviction of two prominent union leaders and won him a Pulitzer Prize.

It was a shining example of the power of muckraking journalism, writes David Witwer, associate professor of history and humanities at Penn State Harrisburg, in Shadow of the Racketeer. But it was something else, too. Using FBI and court records, Witwer demonstrates how Pegler, backed by the prominent publisher Roy W. Howard, carefully framed the scandal, ignoring the active role of business leaders and their own close ties to organized crime while tarring the entire union movement as corrupt and dangerous.

This shaping of the news, Witwer shows, strengthened conservative attacks on New Deal policies and spawned antilabor legislation culminating in the Taft–Hartley Act of 1947. Instead of effecting real reform, Witwer argues, Pegler successfully used the scandal to push a broader antilabor agenda at a crucial juncture in U.S. history.

Pegler’s legacy, he writes, “was a language of suspicion for organized labor … a menacing depiction of organized labor’s power that antiunion forces evoked throughout the postwar era.”

–DP

Edgar Allan Poe and the Dupin Mysteries by Richard Kopley (Palgrave Macmillan)

Richard Kopley, professor of English at Penn State DuBois, first became intrigued with Edgar Allan Poe in the late 1970s when he read The Narrative of Arthur Gordon Pym in a graduate course. “I was amazed by the mysterious vision at the end of the novel,” Kopley says, “and I was convinced there was a solution to be found.”

Sleuthing for solutions to the mysteries in Poe’s writings and life is the focus of Kopley’s most recent book, Edgar Allan Poe and the Dupin Mysteries. Although Poe is most widely known as a master of the macabre, Kopley’s book underscores Poe’s often-overlooked role as the inventor of the modern American detective story. Through diligent primary source research and secondary criticism, Kopley closely ana-lyzes three Poe stories (“The Murders in the Rue Morgue,” “The Mystery of Marie Rogêt,” and “The Purloined Letter”) and presents fresh and surprising insights about Poe’s intense genius, dark themes, and tragic life.

–MBM

w O R t h R e a d i n G :

www.rps.psu.edu 41

The Web is evolving—and so is Research Penn State magazine. Each week, we make research come alive on our Web site through exciting multimedia stories. Explore our videos, slide shows, audio inter-views, and interactive graphics at www.rps.psu.edu. From YouTube, Facebook, Twitter, and Flickr, to Research Unplugged podcasts, iTunes U, and our RSS feed, there are so many ways to connect to the best in Penn State research.

itunes u: Search for Pennsylvania State university to find dozens of offerings!

LEARN: Listen in as we call Uganda and Tanzania to discuss Penn State’s AfricaAr-ray initiative with two geoscience graduate students working there: www.rps.psu.edu/inconversation/africa.html

LOOK: What’s the buzz about native bees? See them up close in this slide show on Pennsylvania Native Bee study: www.rps.psu.edu/pennsylvania/nativebees

LISTEN: Acclaimed cellist Kim Cook gives a living room performance—and music history lesson—in a series of video interviews: www.rps.psu.edu/profiles/cook.html

youtube: www.youtube.com/user/ResearchPennState

facebook: www.facebook.com/pennstateresearch

twitter: twitter.com/psuresearch

O n t h e w e b :


Visualizing the Distant PastBy Melissa Beattie-Moss

On the left, a hadrosaur browses in a Cretaceous stream. On the right is a view of the devastation after the K/T asteroid impact. In the middle is a moth on a leaf of the Cretaceous plant Erlingdorfia montana. Non-avian dinosaurs went extinct at the K/T, while plants and their insect predators suffered losses of diversity.

W hen you’re a paleobotanist trying to visualize prehistoric ecosystems, it helps to be

married to a paleo artist who can bring that bygone world to life in drawings. Such is Peter Wilf’s good fortune. His wife, illustrator Rebecca Horwitt, frequently finds artistic inspiration in her husband’s research findings, and her images (created with pen, colored pencil, and ink on paper) have been published alongside his articles in numerous research journals, including Science and the Geological Society of America’s magazine GSA Today. (Horwitt also illustrated the newly published Manual of Leaf Architecture, reviewed here on page 40.)

Wilf, associate professor of geosciences at Penn State, is particularly interested in the time period 65 million years ago when an extraterrestrial object impacted the Earth near the Yucatán in Mexico, stopping photosynthesis worldwide and dooming the dinosaurs to extinction. The time of the impact—called the K-T boundary—marked the end of the Cretaceous period and the beginning of the Tertiary period. Dinosaurs were far from the only life forms to go extinct, Wilf reminds us: “Eighty to ninety percent of the Cretaceous plant species, including all the dominant species, disappeared.”

Horwitt, a self-trained artist with a background in biology and geology, has worked for the Evolution of Terrestrial Ecosystems Program at the National Museum of Natural History, creating a database of fossil localities from Plio- Pleistocene Africa.

“Working with a scientist to illustrate his or her research findings is always both a challenge and a fascinating treat,” she says. “The process begins with in-depth discussions about what the illustration needs to show. Time, place, scale, flora, and fauna are all important elements.”

Through their combined efforts, Horwitt and Wilf provide a rare glimpse back in time.

e n d P a P e R :

www.rps.psu.edu 43

Research/Penn Statethe Pennsylvania State university320 kern buildinguniversity Park, Pa 16802-3303

Nonprofit Org.U.S. Postage

P A I DState College, PA

Permit No.1

www.rps.psu.edu

A SPECIAL RESEARCH UNPLUGGED CONVERSATION

The Art and Science of

GlassA special Research Unplugged conversation with Dr. Carlo G. Pantano, Distinguished Professor of Materials Science and Engineering, and Director of the Materials Research Institute at Penn State

Friday, March 26, 2010Noon to 1:00 p.m.Penn Stater Conference Center Hotel

This special event is open to the public and is sponsored by the Graduate School Alumni Society and University Relations. Lunch will be provided and reservations are required. Lunch prices are: $8 per person for members of the Penn State Alumni Association, $12 per person for nonmembers. To make your reservation or for more information, contact the Graduate School at 814-865-9452 or e-mail, [email protected]

research penn state 2009/2010

Documents

pennsylvania state university

university policy

university park

university community

comresearchpenn state

featuress e e o u r

pell editor

nondiscrimination policy