Spring 2009 by Endeavors

endeavors SPRING 2009

Research and Creative Activity • The University of North Carolina at Chapel Hill

THE PLANT THAT LAUNCHED A THOUSAND SEEKERS page 5

NEIL CAUDLE

Early this spring,

on the two hundredth anniversary of Charles Darwin’s birth, I flipped a kayak in the cold, choppy waters of Academy Bay, one of Darwin’s ports of call in his year-long exploration of the Galapagos Islands. My excuse? The boss dared me to take a fast but tippy boat. Not very evolved of me, you might say. And you would be right. After an hour or so battling the wind and whitecaps off Angermeyer Point, we finally regained the harbor and came ashore near an enormous mural depicting the great man himself, a finch perched on his finger. At that moment, it occurred to me that our landing was very much like the weary, waterlogged arrival of almost every other form of life that ever gained a foothold on this prickly slab of rock. But as they came ashore, those other living things got busy evolving. We humans would do well to follow their example. We were in the Galapagos to plan a research program that will, with our partners in Ecuador, attempt to figure out what Homo sapiens, an especially aggressive invasive species, is doing

to the most famous ecosystem in the world. In several parts of the islands, tourists and settlers have polluted the groundwater, imported all manner of alien pests, and plundered sea cucumbers and other species almost to the point of extinction. In this year for celebrating Darwin, we are hoping that science can help turn that trend around. Perhaps the most obvious way to honor Darwin in this magazine would be to write about research on the topic of evolution. But when Darwin went to the Galapagos as a young man, evolution wasn’t on his mind. Having studied medicine and divinity, and dabbled in geology, Darwin hitched a ride with Captain FitzRoy aboard the HMS Beagle for the pure adventure of exploring new lands. By our great fortune, Darwin turned out to be a gifted observer, and his elegant prose is an inspiration to anyone who studies the natural world. And so in this issue, we honor Darwin with several stories about scientists who are doing as he did, exploring life in its amazing abundance, wherever it might lead. —The Editor

endeavors

Spring 2009 • Volume XXV, Number 3 Endeavors engages its readers in the intellectual life of the University of North Carolina at Chapel Hill by conveying the excitement of creativity, discovery, and the rigors and risks of the quest for new knowledge. Endeavors (ISSN 1933-4338) is published three times a year by the Office of the Vice Chancellor for Research and Economic Development at the University of North Carolina at Chapel Hill.

Send comments, requests for permission to reprint material, and requests for extra copies to: Endeavors Office of Information and Communications CB 4106, 307 Bynum Hall University of North Carolina at Chapel Hill Chapel Hill, NC 27599-4106 phone: (919) 962-6136 e-mail: endeavors@unc.edu

Holden Thorp, Chancellor Bernadette Gray-Little, Provost and Executive Vice Chancellor Tony Waldrop, Vice Chancellor, Research and Economic Development

contents Spring 2009

2 overview

28 Zena’s Arctic Adventure

cover story: life unlimited 5 Every Living Thing

34 A Good, Swift Kick

Baric’s bat virus, a new cancer classifier, low-dose x-rays, and chemo by the body clock.

In the Smokies, the woods are full of biologists these days. But no one’s found the twinflower yet. by Mark Derewicz

features: life unlimited 14 Fly Club

Why does the fruit fly have so many fans? by Susan Hardy

16 Tardi-whats?

An undergrad in the land of the midnight sun. by Zena Cardman

Paul Cuadros and his soccer heroes help unite a poultry town. by Mark Derewicz

37 What’s Stopping Bird Flu’s Big Step?

The H5N1 virus hasn’t flown the coop—yet. by Beth Mole

40 Targeting Tumors

Are tiny water bears biology’s next big stars? by Jason Smith

Carolina is part of a national network to unravel the genetics of cancer. by Prashant Nair

19 Frogsong

43 How will Turkey turn?

A froggy went a-courtin’. by Meagen Voss

A daughter sees her country’s fearful history through her mother’s eyes. by Mark Derewicz

21 No place like it

Magnetic memory leads turtles home. by Johanna Yueh

features 22 Life by the Andaman Sea

Carolina J-schoolers document fighters, farmers, and mahouts in Thailand. by UNC photojournalism students

46 in print

The costly War on Drugs, and Hemingway, line by line.

49 endview

Drosophila drawings.

Editor: Neil Caudle, Associate Vice Chancellor, Research and Economic Development Associate Editor: Jason Smith Writers: Zena Cardman, Mark Derewicz, Susan Hardy, Beth Mole, Prashant Nair, Margarite Nathe, Kate Pedone, Jason Smith, Meagen Voss, and Johanna Yueh

On the cover: Twinflower (Linnaea borealis) grows in the Royal Society for the Protection of Birds nature reserve of Abernethy in the central highlands of Scotland. Photo by Laurie Campbell.

Design: Neil Caudle and Jason Smith Print production and website: Jason Smith

http://research.unc.edu/endeavors/

©2009 by the University of North Carolina at Chapel Hill in the United States. All rights reserved. No part of this publication may be reproduced without the consent of the University of North Carolina at Chapel Hill. Use of trade names implies no endorsement by UNC-Chapel Hill.

overview SARS, before its big leap Ralph Baric built a bat virus to learn how to improve the SARS vaccine. Right: Coronaviruses are named for the halo of club-like protein structures that surrounds each virion. Image by Russell Kightley.

ver since the SARS outbreak of 2002, scientists have been trying to trace the history of the SARS-causing virus. Now virologist Ralph Baric has built a bat virus that simulates what the strain probably looked like just before it made the leap to infect humans. Baric has been studying coronaviruses for twenty-five years. In 2003, when scientists identified a coronavirus, SARS-CoV, as the cause of severe acute respiratory syndrome (SARS) , his lab built the first working molecular clone of the virus. (See Endeavors, Fall 2003, “Stalking SARS.”) It’s been five years since the last recorded case of SARS, but that hasn’t stopped Baric from continuing to study the virus and its relatives. He knows that SARS-CoV, or something very like it, could—and probably will—come back. “Precedent suggests that it’s inevitable,” he says. Ebola went silent for about ten years between outbreaks. Chikungunya, a mosquito-borne virus native to Asia, disappeared for twenty years before reemerging in the late 1990s. Ebola and chikungunya can tell us something about SARS-CoV because all three are zoonotic viruses, meaning that they can jump from nonhuman animals to humans or vice versa. So even when they’re not infecting humans, the viruses—or their close 2 endeavors

relatives—are still getting passed around in animal populations. SARS-like viruses have infected several species, including horseshoe bats, civet cats, and humans—in that order, according to a widely accepted model. Baric agrees that the virus moved between civet cats and humans, but he thinks it might first have jumped from bats straight to humans. “When you compare their DNA sequences, the bat strains appear to be closer to the human side than the cat side,” he says. Baric and his collaborators think that SARS-CoV came about when bat coronaviruses recombined with each other, forming a new strain that infected humans. If this is true, then SARS-CoV might still be hanging out in bats, and human reinfection could occur at any time. Whether or not that hypothesis is correct, bats are still a reservoir of SARS-like coronaviruses that could mutate to jump species again. That’s why Baric’s been studying everything he can about the bat virus strains. His team used genome sequence data from a National Institutes of Health database to make the synthetic bat virus. There’s a small region of the virus called the receptor binding domain (RBD)—the part that determines what kind of host the virus can latch on to. The team gave the synthetic virus the right

genes to allow its RBDs to bind to human cells. “This simulates the recombination that might have occurred in a mixed infection,” Baric says. As soon as he had the bat virus with the SARS-like RBD, Baric started experimenting with it in mice, which are susceptible to the same RBD as humans. Baric will soon publish data on a vaccine platform that prevents some SARS-like viruses from infecting mice, including elderly mice, who, like elderly humans, are the population most likely to die of SARS. That’s not enough for Baric, who is studying more bat coronaviruses to try to improve the vaccine’s range. His team wants to build a vaccine platform that offers the flexibility of modern flu vaccines, which are genetically altered each year to fight current virus strains. “We want to be able to respond quickly next time any of these viruses reemerge,” he says. —Susan Hardy The bat coronavirus reconstruction project, presented in December 2008 in the Proceedings of the National Academy of Sciences, was colead by Mark Denison, a professor of pediatrics at Vanderbilt University. Baric received funding from the National Institute of Allergy and Infectious Diseases and the Gillings Innovation Fund.

Predicting a breast cancer’s aggression

omen diagnosed in any stage of breast cancer will soon be able to get a more comprehensive test that will help doctors plan their treatment. Developed by Charles Perou and colleagues, the test predicts the aggressiveness of breast tumors and anticipates how cancer will respond to chemotherapy. The test uses fifty genes to classify a tumor as one of four subtypes that vary in prognosis and drug susceptibility, and require different courses of treatment. For example, the test can identify estrogen-receptive tumors, helping some patients who might traditionally have been given chemotherapy avoid it in favor of hormone-blocking drugs. Other tumors of the aggressive Luminal B subtype

don’t respond well to chemotherapy or to hormone-blocking drugs, making them good targets for cutting-edge therapies. Although the new test looks for a complex set of traits, it uses technology that’s already in many pathology clinics. “Instead of sticking with the microarray platform that we used to discover the genes, we chose a platform called quantitative RT-PCR,” Perou says. “Some labs may already have much of the equipment needed to run the assay.” A study of about seven hundred patients published in February 2009 confirmed the test’s ability to predict how tumors will respond to chemotherapy. Larger clinical trials are under way. The patent-pending test is being marketed by University Genomics

and ARUP Laboratories as the Breast Bioclassifer, and will be available commercially in summer 2009. —Susan Hardy Charles Perou is an associate professor of genetics and pathology in the School of Medicine and a member of the Lineberger Comprehensive Cancer Center. The diagnostic test was developed by a collaboration of researchers at Carolina, the University of Utah, and Washington University in St. Louis, Missouri. The Office of Technology Development (OTD) is the only UNC-Chapel Hill office authorized to execute license agreements with companies. For more information, contact OTD at (919) 966-3929 or visit http:// research.unc.edu/otd/.

Better x-rays at lower doses

team led by Etta Pisano has developed a new x-ray machine that captures higher-quality images and emits less radiation. Conventional x-rays create shadow pictures, Pisano says. An x-ray machine beams tiny particles called photons at a patient. Most of the photons bounce off, but some are absorbed and travel through the patient to create an image. Pisano’s machine uses the photons that bounce off instead of the ones that are absorbed. “If you don’t need to absorb photons, you can make an image at a much lower dose of radiation,” she says. Low-radiation technology has been around for decades, but the machines that used it were far too large and expensive for hospitals. Pisano’s innovation was to pack the same technology into a smaller machine. Her team, which includes researchers at the Brookhaven National Laboratory, first tested their machine on breast cancer in tissue from cadavers. They soon found that the machine was capable of producing high-quality images of any part of the body. Pisano’s next step is to have a team of engineers build another machine that can be sold to hospitals. Right now she is raising capital to fund the project, and she anticipates that they will produce an FDA-approved machine in two years. “Once we get this product out on the market,” she says, “it will replace conventional x-ray imaging.” —Meagen Voss Meagen Voss is a doctoral student in neurobiology.

Etta Pisano is vice dean of the School of Medicine, director of the Biomedical Research Imaging Center, and a professor of radiology and biomedical engineering at UNC. Funding for this project came from the National Institutes of Health. The Office of Technology Development (OTD) is the only UNC-Chapel Hill office authorized to execute license agreements with companies. For more information, contact OTD at (919) 966-3929 or visit http://research.unc.edu/otd/.

High-res, lower risk. Pisano’s new technology captured this image of a live rabbit using only one-tenth the radiation dose typically used to obtain a neonatal chest radiograph. Image by Etta Pisano, Dean Connor, Zhong Zhong, and F. Avraham Dilmanian.

endeavors 3

Beating the clock on cancer

hen it comes to treating cancer, timing is everything—early detection, precise dosing schedules. But time of day? Aziz Sancar thinks that the susceptibility of tumors to anticancer therapy depends in part on the biological clock, the body’s daily timekeeping mechanism. In an oscillating pattern called circadian rhythm, cells throughout the body adjust their functions over a twenty-four-hour period in sync with the cycle of the sun. The rhythm is controlled by a light-sensitive master clock in the brain and coordinates vital physiological processes such as body temperature, blood pressure, and the sleepwake cycle. Clinical observations have suggested that time of day affects cancer patients’ responses to chemotherapy. But doctors haven’t understood the physiology of this phenomenon, so chemotherapy regimens don’t include time-of-day criteria.

Sancar’s team found that DNA repair activity in a mouse brain is ten times higher in the late afternoon than in the early morning. He has experiments under way to measure circadian regulation of DNA repair in other mouse and human tissues. His goal is to identify the time of day when chemotherapy-induced DNA damage has the greatest advantage over the body’s natural DNA repair activity. Scientists know that general interference with the biological clock can affect vulnerability to cancer. Epidemiological studies have shown that female populations including night-shift nurses and other nighttime workers have a higher incidence of breast cancer than those who work traditional hours. “Disrupting the clock predisposes animals to cancer—this was the dogma,” Sancar explains. But the dogma lacked a biological explanation.

Sancar hypothesized that the underlying link between circadian rhythm and chemotherapy effectiveness is the DNA damage response—the natural process by which cells restore damaged DNA. Sancar points out that many anticancer drugs work by lethally damaging the DNA of tumor cells. “So we then considered DNA repair as a factor, because whether the damage is repaired will determine whether the cancer cell dies,” he says.

ancar’s genetic approach to answering this question yielded surprising results: eliminating one of the four key components of the biological clock machinery, a protein called cryptochrome, actually delayed cancer formation in mice susceptible to tumors. The lab found that cancer cells that lack cryptochrome die more readily than other cancer cells by a process known as apoptosis. It is this increase in apoptosis that essentially protects the animal from tumor growth. Sancar is confident his findings will spur exciting work on the circadian regulation of cancer. “These findings tell us there is this connection. To translate this to clinical medicine will be a big challenge, and we will have to fine-tune it,” he says. —Kate Pedone Kate Pedone is a postdoc in the Lineberger Comprehensive Cancer Center. Aziz Sancar is the Sarah Graham Kenan Professor of Biochemistry and Biophysics in the School of Medicine and a member of the Lineberger Comprehensive Cancer Center. His findings were published in two papers in the February 24, 2009 issue of the Proceedings of the National Academy of Sciences.

Five stories about the blooming, flying, buzzing, wiggling

4 endeavors

DNA CLOCK: RUSSELL TATE

world.

MARK DEREWICZ

every living thing LAURIE CAMPBELL

Linnaea borealis

Peter Whiteâ&#x20AC;&#x2122;s quest for twinflower has led to a whole lot more. By Mark Derewicz endeavors 5

Peter White tells the story this way: On a warm, sunny day in August 1892, an amateur botanist named Albert Ruth trudged up a narrow mountain trail, surveying the forest floor. Out of the corner of his eye he noticed a stretch of small green plants. He made his way off the path to get a closer look and saw two pink flowers rising from a thin stem surrounded by round, green leaves. He got down on his knees, snipped off a sample to put in his tin box, and continued up the mountain. “Everything around Ruth would’ve been exciting because his exploration was at the dawn of the age of understanding which species occur in the Smokies,” White says. “He wouldn’t have had to go very far off-trail to find interesting things.” Back in Knoxville, Ruth mounted his finding on herbarium paper and wrote above it, “Sevier County, in mountain woods.” 6 endeavors

Known as Linnaea borealis, or twinflower, the species had been named for Carolus Linnaeus, the father of taxonomy, who sometimes wore the flower pinned to his lapel. Twinflower is common to northern climes such as Scandinavia and Nova Scotia. It also grows in the Appalachian Mountains of New York and Pennsylvania and has been seen rarely in West Virginia. No one has ever found it in Virginia or North Carolina. Albert Ruth, who collected about fifty thousand different plants, is the only person to have found twinflower in Tennessee. Or did he? In 1981, White traced Ruth’s footsteps through the mountain woods of Sevier County, now part of the Great Smoky Mountains National Park. At the time, White was a young ecologist working for the Upland Fields Research Laboratory in Tennessee. But White found no twinflower. Over the next two decades, still searching for one rare plant, White turned up two

ZEBRA SWALLOWTAIL BY MIKE THOMAS

JEFF DAVIS

spans eight hundred square miles along the Tennessee-North Carolina border. Within it are drastic elevation changes—from eight hundred to six thousand feet above sea level. The Smokies—part of the Appalachian Mountains—are very old, much older than the Rockies or Himalayas. And during the last ice age, the Smokies were not glaciated. Because of all this, the park is teeming with incredibly diverse life forms, perfect for an all-taxa inventory. Trying to document every single species is kind of like White’s search for Linnaea— noble, fun, but extremely difficult. Would scientists look under every rock and inside every cave throughout such a big chunk of land, much of which is tough to traverse? Could they find every species of fungi or bacteria, or the rarest of moths? Could White finally find Linnaea borealis?

Left: The scene of the quest. Is it possible to find every species in the most biologically diverse national park in the United States? Scientists and volunteers from around the country have been scouring the Great Smoky Mountains National Park to find out.

hundred other plants never known to grow in the park. All of them are now part of the All Taxa Biodiversity Inventory (ATBI), an ongoing project that involves thousands of scientists and volunteers dedicated to preserving the park’s ecosystem. White chaired the ATBI from 2003 to 2007 and codirects the project’s science committee. So far, ATBI scientists have found more than six thousand species that no one knew existed in the park, and nearly nine hundred more that are new to science. All told, scientists have documented nearly seventeen thousand species in the park. Nobody knows how many more are waiting to be discovered—possibly tens of thousands, White says. The ATBI is one of the largest, most ambitious science projects in the world. No one has ever documented every living thing in such a large area, White says. The Great Smoky Mountains National Park, which turned seventy-five years old this year,

Left: Portrait of Carolus Linnaeus with a twinflower pinned to his lapel. Above: Albert Ruth’s notation, which inspired the search.

endeavors 7

he idea of finding every single species in a conservancy or national park had been floated before—in Costa Rica, for instance, where it never got off the ground. Keith Langdon, a biologist with the Great Smoky Mountains National Park, heard about the Costa Rican plan and thought that his park should do an all-taxa inventory. After all, the park has a congressional mandate to preserve everything within its borders. How can you protect and preserve what you don’t know is there? Langdon had already been helping hundreds of scientists each year organize research trips to the park. He thought he could coordinate them for an all-taxa inventory. Langdon called White, who had published the most recent checklist of wildflowers in the park. (See Endeavors, Fall 1998, “Wild as the Hills.”)

“I had set up permanent vegetationmonitoring plots where you take a chunk of forest and map every tree and go back every five years to see how much the forest is changing,” White says. “So Keith and I were buddies already.” Langdon invited 120 scientists, all of whom showed up for a meeting in Gatlinburg, Tennessee. “This showed the incredible enthusiasm that was out there for doing something grand, something Don Quixotelike,” White says. To their astonishment, the ATBI attracted more than one thousand scientists and college students from across the country, as well as eight hundred educators, students, and interested citizens. Hundreds of other scientists from twenty countries also participated, some volunteering time to compare newly found species in the park to

specimens in museums around the world. But even with thousands of volunteers it would take centuries to look for every bit of life in every square foot of the park. So White, in charge of creating the ATBI science plan, separated the search for species into two major categories—structured sampling and traditional, unstructured observation. The latter is what happens when scientists and volunteers wander through the landscape looking for new species. They use intuition and instinct to determine if a particular habitat is worth their time and effort. If they find nothing new, they walk faster, White says. If they find something interesting, they walk slower. This takes a lot of patience and time, especially when trying to find elusive creatures such as spiders, salamanders, or sluggish caterpillars and their adult forms, butterflies and moths.

Upper Left Woodland Stonecrop Sedum ternatum The woodland stonecrop belongs to the genus Sedum. Sedums grow to be many different sizes, from shrubs to tiny ground covers such as this one, which grows to be four inches tall. Upper Right Glowworm Phengodes laticollis These beetles are called glowworms because larviform females and larvae have bioluminescent organs. Lower Left Green Specklebelly Pseudocyphellaria aurata This lichen lives in trees at low elevations. In June 2008, 563 species of lichen have been discovered in the Great Smoky Mountains National Park. Lower Right Yellow Fringed Orchid Platanthera ciliaris This orchid can reach 40 inches in height and has flowers that are yellow or orange. It lives in fields, meadows, and open woods and is found only occasionally.

IMAGES COURTESY OF DISCOVER LIFE IN AMERICA

8 endeavors

COURTESY OF DISCOVER LIFE IN AMERICA

ack in his day, Russian novelist Vladimir Nabokov spent years in pursuit of butterflies. He’d spot an interesting one floating through a meadow, wait for it to settle on a flower, and then swoop it up in a net. The butterfly might’ve looked similar to another one he had already caught. But there might have been, say, red dots on both wings, possibly signifying a new species. Nabokov would take it back to his house, check the literature on butterflies with red dots, compare his specimen with others from museum collections, and—if he was really serious—submit his discovery to peer-reviewed journals. Unstructured sampling is the most efficient way to quickly inventory a habitat, and with a little training just about anyone can do it. But the method isn’t sufficient for an alltaxa inventory. You miss too much when you sweep through an interesting landscape in a single pass. So White’s science plan includes structured, year-round sampling. Twenty scientists were assigned to lead taxonomic working groups, or TWIGS, in their fields of expertise. There’s the slimemolds TWIG, the reptiles TWIG, the fungi TWIG, the plants TWIG, and so on. The plan also includes special teams, such as the tree climbers from Central Missouri University, charged with finding fungi, snails, and whatever else lives atop the tallest, oldest trees in the Smokies. TWIG leaders set twenty plots that vary by elevation, vegetation, topography, geology, human activity, and other environmental and biological factors. Sometimes researchers set up standardized traps for various lengths of time to catch different species of bugs or bees, for instance. Over time, different species accumulate in the traps, allowing scientists to estimate how many species are in a particular area. Or scientists simply go to these plots throughout the year to see what they can find. Because the twenty plots are representative of the whole park, scientists can estimate how many species might exist across the entire eight-hundred-square-mile span. But there’s a lot of stuff you can’t find with traps and observation, and enormous reaches of the park remain unsampled. White estimates

Scientists named the Lamar Alexander springtail after the Tennessee senator in appreciation of his support for research funding.

that forty thousand to two hundred thousand species inhabit the park. Had Nabokov still been around to take part in the ATBI’s structured sampling, he would’ve been assigned to the lepidoptera TWIG led by Dave Wagner, an ecologist at the University of Connecticut. Wagner’s quest for life falls somewhere between traditional observation and structured sampling. “We descended onto the park en masse, hit it as hard as we could, and then got out of town,” Wagner says. “It was like a paramilitary operation, and we ran it like one.” Over the course of one weekend, Wagner worked with eighteen of the top taxonomic authorities in the world, twelve graduate students, and twenty or so volunteers. They searched for butterflies and set forty traps at different elevations and in every kind of habitat they could think of. “We sent a team up a mountain with llamas that carried our traps and batteries so that we could sample the grassy balds at higher elevations,” he says. “At night we used lights to attract moths to white sheets. We looked under leaves for tiny moths. We set baits— brown sugar and beer, the more fermented the better. That stuff can attract moths from

hundreds of yards away.” Wagner led these bioblitzes four times between 2000 and 2006. Each time, his group processed about forty thousand specimens. Often they targeted habitats where they thought particular moths might live. This is how they found a moth that an expert from the Smithsonian Institution recognized in the field as a species new to science. “It’s black and white and perches on the upper side of leaves,” Wagner says. “Essentially, it mimics a splat of bird poop. That’s its gimmick.” During these blitzes, Wagner’s team held sorting and identification workshops so that all the species could be tallied and cataloged. Before the ATBI, there were 891 butterfly and moth species known to flutter through the park. Wagner’s group found 944 species new to the park and 36 species new to science. Only one other TWIG outdid Wagner’s group—the beetles TWIG. Prior to the inventory, scientists had documented 887 beetle species in the Smokies. During the inventory, they found 1,448 species new to the park and 42 new to science. And then there’s the really tiny stuff, such endeavors 9

as tardigrades and bacteria. Tardigrades are microscopic creatures also known as water bears because they live in moist areas and resemble pudgy bears. Before the ATBI, scientists knew there were three species of tardigrades in the park. During the inventory, they found fifty-six species new to the park and eighteen new to science. (See “Tardi-whats?,” page 16.) As for bacteria, no one had ever documented which species were in the park before ATBI scientists found 479 (270 of which are new to science). Finding new bacteria might not seem as interesting as watching a weird-looking caterpillar turn into a previously unknown species of butterfly, but the results could be more important, White says. In the hot springs of Yellowstone National Park, scientists found a bacterium now used in DNA testing and other molecular applications. They also found a bacterium that might help improve the production of biofuels. There aren’t any hot springs in the Great Smoky Mountains National Park, but the hundreds of previously unrecorded bacteria found during the ATBI no doubt have some purpose in the park’s ecosystem. ATBI scientists also found sixteen different

The Cucullia convexipennis caterpillar, found during a bioblitz, has not been found any farther south than the Great Smoky Mountains. Photo by Mike Thomas.

viruses, eleven of which are new to science and five—including West Nile virus—that are new to the park. Scientists are now studying the rare virus’s distribution in the park. Some species found during the ATBI, such as the Chinese jumping worm, are invasive. Ecologists were surprised to find the worm, which devours the upper layers of earth that are necessary for soil to recycle nutrients and retain moisture. “Fishermen probably bought the worms at local bait shops and then released them,” White says. Luckily, ATBI scientists found the worm before the species became widespread.

White also says that the ATBI could find helpful species. In the early twentieth century, uncontrolled logging in the Southern Appalachians led to severe soil erosion. White says that the Smokies might be home to organisms that could help replenish the eroded landscapes. “Some of the smallest critters are the lungs and power plants or the digestive system of the ecosystem,” White says. But we don’t really know how all the species interact as part of this scheme. The inventory also has an educational benefit. Teachers have taken hundreds of students to the Smokies to help find species. In 2004 high school students from Cherokee, North Carolina, searched for soil invertebrates for the ATBI. They found a bunch of tiny, wingless soil insects called springtails and sent fifty specimens to University of Tennessee professor Ernie Bernard, head of the nematode TWIG. He noted that the tiny creatures had a purple tint and white rings around their antennae. He suspected that the students might have found a new species, but when he and graduate student Kelly Felderhoff went back to the Smokies to verify the finding, they found no springCOURTESY OF DISCOVER LIFE IN AMERICA

The Chinese praying mantis, Tenodera aridifolia sinensis, has invaded the park.

10 endeavors

tails. Several times over the course of three years, Felderhoff returned to the original site with no luck. In February 2008 Susan Sachs of the Appalachian Highlands Science Learning Center took another class of students from Cherokee back to the Smokies. After digging in the dirt for an hour, the students came up with a few possible matches. Back at her lab, peering through a microscope, Felderhoff determined that the students had unearthed a springtail species called Pogonognathellus nigritus. In 1951 a researcher had discovered this species in New York. But it was never found again, so the species name had been invalidated. Thanks to the students, the ATBI has verified the existence of Pogonognathellus nigritus, which has a much wider range than anyone had thought.

hile planning for his trip to the Smokies in 2006, White pored over old U.S. Geological Survey maps at UNC’s Wilson Library. He found one from 1893 that showed the only three trails that Albert Ruth could have used to penetrate the higher elevations of Sevier County at Newfound Gap, Indian Gap, and along Porter’s Creek. White took notes and headed to the Smokies with grad student Julie Tuttle and seven others. They parked at the visitor’s center, hiked four miles into the wild, and set up camp. The twinflower search was on. “We kind of zigzagged back and forth on the slope, hoping to run into it,” White says. “Sometimes I thought we were searching for a needle in the haystack and we’d never find it, and sometimes I thought it was right around the next bend.” On day one the group hiked up the steep north-facing slopes that are between four thousand and five thousand feet above sea level. White told his volunteers to call him on his cell phone if they saw clumps of green leafy plants scattered along the forest floor. A few hours later, they came across a patch of plants with fuzzy flowers. To the nonexpert, it looked like twinflower—small, pretty and pink, surrounded by delicate green leaves. White looked it over and knew it was not Linnaea. It was Oxalis montana. They took a

sample for the ATBI. As the search continued, White told everyone to look for paper birches. Discovered in the park in the 1970s, just a few dozen of the trees grow there. White knew that Linnaea likes to cozy up to paper birches. Carefully hiking down the steep mountainside, White’s crew came upon a long, narrow clearing strewn with rocks, rubble, and downed trees. Some time ago, an avalanche there crushed everything in a path twenty meters wide. “There are a huge number of landslides in this area,” White says. “The only population of Linnaea could’ve been taken out, for all we know.” Later on they spotted Clintonia borealis, which grows in the same cold, moist evergreen forests as Linnaea. They documented nineteen species of plants and one animal species—a snail that quickly retreated inside its shell and started spinning on its side when picked up. The next day they found ten more plant species, but not Linnaea. They marked their locations on maps using GPS so White could keep track of where his search had taken him. In 2008 White used those maps for another search with three more volunteers.

On July 19 White’s group left the Appalachian Trail and headed down a rugged north-facing slope. Three hundred meters off-trail, they spotted a cluster of eight paper birches. They scrambled to the base of each tree and searched the surrounding area. Again, no Linnaea. But those trees wound up being the most southern population of paper birches in North America, another ATBI discovery. White’s maps are now speckled with red and purple dots that represent where he’s searched for Linnaea as part of the ATBI’s vascular plant TWIG. His search is mostly traditional observation but is getting more structured thanks to maps that his former graduate student Todd Jobe produced. For his dissertation, Jobe wanted to figure out how easy or difficult it would be to walk to different parts of the park. He thought this would help TWIG leaders plan more efficient sampling trips. He researched human physiology and energy expenditure to calculate how accessible any part of the park is from any trailhead. He used published models of humans walking on treadmills and added into his equations various simulations of people hiking through vegetation, across COURTESY OF DAVE WAGNER

Above: This moth, Ligdia wagneri, a species new to science, was discovered in the park. It was named for Dave Wagner. It perches on the upper side of leaves and mimics a splat of bird poop to conceal itself from predators. Right: Dave Wagner (center, in cap) catches moths by flashlight. Wagner’s group has found 944 species new to the park and 36 species new to science. Wagner is an ecologist at the University of Connecticut and head of the lepidoptera taxonomic working group.

endeavors 11

streams, and up and down steep slopes. The maps show vast areas of the park that are tough to get to, and give researchers a good idea of how long it would take to explore these areas and how physically taxing such trips would be. Jobe and fellow grad student Jason Fridley also made models showing the bias of unstructured specimen sampling. They collected data on where flora sampling had been done in the park between 1974 and 2003. As they suspected, most scientists had sampled near easily accessible trails. Could sampling near paths capture the true diversity of the park? “In general, the sampling had captured the major vegetative communities, such as spruce-fir forests,” Jobe says. “But within a spruce-fir zone there are big patches that were not sampled. We might be missing things about some of those communities.” Spruces grow high up mountain slopes, and a lot of that land is not easily accessible. Jobe used his maps to pinpoint the most inaccessible places in the park, and then hiked to them. In one case, he looked for a particular outcrop of igneous rock, figuring that this landscape might reveal something different from areas with no outcrops. He

found the spot. The view was unbelievable. But he says, “We saw nothing different there.” Smiling, he adds, “No Linnaea.”

n his Chapel Hill office, White wheels his chair around to his computer to show me one of Jobe’s maps of the Great Smoky Mountains National Park. “These brown areas are where we’ve been searching for Linnaea,” he says. “But there’s a mountain that’s even more remote than where we’ve been. And if we don’t find it in these valleys, then I want to go there, to Mount Guyot, because that’s really hard to get to. Very few biologists have been to the top of that mountain for any length of time.” In the summer of 2009, White will drive to the Smokies, park at the visitor’s center, and spend the night at a shelter in the woods of North Carolina. Then he’ll hike to Newfound Gap and search a few northfacing slopes and the valleys where Porter’s creek is nestled. He’ll look for pretty pink twinflower. He doubts he’ll find any; he knows the odds are against him. But he can’t stay away. Chances

are he’ll find something no one knew was there. Still, White is somewhat vexed that he hasn’t been able to find what Albert Ruth stumbled upon. It’s made him wonder if Ruth actually found twinflower in the first place. It doesn’t help that Ruth misidentified the plant as Mitchella repens. When Ruth retired to Texas he took his personal collection with him but left thousands of specimens at the University of Tennessee herbarium. In 1934 the herbarium burned to the ground, forcing botanists back into the field to refind tens of thousands of plants. They wrote letters to universities across the country—including UNC, which has the largest herbarium in the South—asking for help in replenishing the university’s collection. A thirty-year-old botanist named Jack Sharp wrote to Albert Ruth’s daughter Gertrude to see if she was willing to send her father’s collection to Knoxville. She was. And Sharp pored over thousands of pressed plants until he came across a curious label that read, “Mitchella repens, Sevier County, in mountain woods.”

Todd Jobe, a postdoctoral fellow in UNC’s geography department, produced this map to show where scientists had conducted sampling in the park. Many of the highest and least accessible elevations (in yellow and orange) have not yet been sampled.

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But Sharp noticed that the plant was clearly Linnaea. So he relabeled it. White has seen the original specimen. It’s Linnaea borealis. In Ruth’s own writing, the label reads, “Sevier County.” He could’ve forgotten that he had traded plants with a botanist from the north, White says. Or maybe Ruth got confused and labeled the specimen incorrectly years after he thought he had found it in the Smokies. But White says it’s more likely that Ruth compared his specimen to the literature and saw that Mitchella repens, which does strike a close resemblance to Linnaea, is common in the eastern United States. “I think Ruth found Linnaea,” White says. “But it could just not be growing there anymore. I happen to think it’s still there and I have a checklist of places I’d like to go and look. Now, maybe it’s like the paper birch. Maybe we’ll find a different population than the one Ruth found.” The ATBI still considers Linnaea a species of the park, but with one qualification: “Linnaea borealis: not seen in over one hundred years; go forth and hunt for it.” e Peter White, cochair of the ATBI science committee, is a professor of biology in the College of Arts and Sciences and is the director of the North Carolina Botanical Garden, which oversees seven hundred acres of university-owned protected areas, as well as the Coker Arboretum, Battle Park, the Mason Farm Biological Reserve, and the UNC Herbarium’s seven hundred thousand plant specimens. Todd Jobe is a postdoctoral fellow in the geography department in the College of Arts and Sciences. Dave Wagner is a professor of ecology and evolutionary biology at the University of Connecticut. To raise money for the ATBI, the core organizers created Discover Life in America, a nonprofit with a board of directors that White has cochaired. The National Parks Service is using the Great Smoky Mountains National Park ATBI as a model to conduct all-taxa inventories at other national parks. Anyone interested in learning more about the species found during the ATBI can go to www.dlia.org, where each species has its own web page.

MARK DEREWICZ

The new Education Center at the North Carolina Botanical Garden is a “green” building.

Growing Green

hen Peter White became director of the North Carolina Botanical Garden in 1986, his staff was already outgrowing the Totten Center off Fordham Boulevard in Chapel Hill. In 1999 the garden received a gift of $2.6 million, and by 2007 White’s fundraising team had come up with enough additional money to start construction of a new building. Scheduled to open in summer 2009, the N.C. Botanical Garden Education Center is designed to meet the platinum standard in the LEED rating system of environmentally friendly construction. White says it was only natural to strive for platinum. “This garden has always carved out a niche in biodiversity, conservation, and environmental issues, unlike many other gardens that are purely about beauty or horticulture,” he says. The center is made up of three two-story wooden buildings connected by covered breezeways. Porous paved parking lots allow rain to filter through to the ground and water the garden. Underground water-storage units and seven giant cisterns also aid irrigation. Solar panels will provide at least 15 percent of the center’s energy needs. The buildings’ wood siding was made from Atlantic White Cedar trees blown over near the North Carolina coast during hurricanes. The roofs are metal, which will reduce heating and cooling costs, as will a geothermal heat-exchange system. Clerestory windows let in light and heat in winter, but are shaded in summer. Trees on the site were made into trim for the insides of the buildings. Oak flooring came from trees felled during demolition projects in the Triangle. The center’s elevators have energy-efficient motors and use no hydraulic fluid. At first, the project was called the Visitor Education Center. But White dropped the ‘visitor’ part. “We’re calling it the Education Center because the word visitor has a connotation of coming and going and just visiting,” White says. “And we want to convey a message of participation. We want people coming to classes, lectures, and summer camps. We want them to do field hikes. It’s not like a visitor’s center off I-40.” —Mark Derewicz LEED—Leadership in Energy and Environmental Design—is a voluntary rating system overseen by the U.S. Green Building Council. The garden’s new education center was funded in part by a gift from the estate of Kay Bradley Mouzon. endeavors 13

Left: A common fruit fly. Photo by Jan Polabinski. > SCIENTIFIC NAME: DROSOPHILA MELANOGASTER (GREEK FOR “DARK-BELLIED DEW LOVER”) > SIZE: 2–4 MILLIMETERS ( ) > ALSO CALLED: POMACE, VINEGAR, OR WINE FLIES > EATS: FRUITS, VEGETABLES, FERMENTING LIQUIDS > PREDATORS: ANTS, BEETLES, YELLOW JACKETS, OTHER FLIES

fly club This little bug is a workhorse of science. by Susan Hardy

n 1908, when the word genetics was just three years old, a biologist began studying trait inheritance in a fruit fly called Drosophila melanogaster. His students grew the flies in milk bottles stolen from the cafeteria and inspected the insects using hand lenses. Today, labs still have rooms full of bottles of fruit flies. Interest in Drosophila hasn’t waned since the early twentieth century; if anything, it’s gotten stronger. Why? When scientists want to understand the genetics behind human biology—from how our cells get energy to what causes autism— they can’t learn it all by studying humans. They can turn genes in our DNA on and off in a Petri dish, but they can’t see what effect those changes would have in a fully grown person. Scientists need an animal they can study from birth to death. It should have a simpler genome than ours, one that’s easier to manipulate, but with genes that build the same proteins as ours and perform similar functions. And its generation time should be measured in days, not years, so that scientists 14 endeavors

won’t have to wait long to see the product of an experimental genome. Enter Drosophila. Inside its two-to-fourmillimeter body is a surprisingly familiar anatomy, from a bilobed brain organized like ours to cells that grow, move, and divide the same way human ones do. A hundred years after scientists began studying this little insect, it’s still giving us clues about how our own bodies work. Ask any Carolina researcher who works with fruit flies what makes Drosophila special, and the first part of the answer is always the same. “It’s this amazing history,” says biologist Corbin Jones. Fruit fly research began in Thomas Hunt Morgan’s lab (the one with the stolen milk bottles). “He picked Drosophila because it was easy to take care of and he could breed it rapidly,” Jones says. Morgan’s lab screened thousands of fruit flies for mutations. Eventually they found one that had white eyes. When they bred the fly, only male offspring inherited the strange eye color. That led Morgan and his students

to prove that chromosomes determine sex and that genes are on chromosomes. Some fly researchers today still do pretty much what Morgan did a century ago. It’s now called discovery biology, says Jay Brenman, who started out looking for neurodegeneration in flies. His lab fed thousands of flies a chemical known to create mutations, then screened them for evidence of neuron dysfunction. “It’s like opening up the hood of your car and hitting something with a hammer, and then trying to figure out what the piece you broke was for,” he says. Brenman enjoys working backwards from a mutant fly to its genetics because he never knows where the genes he finds will take him. The neurodegenerative flies in his lab had a mutation in an enzyme, AMP-activated protein kinase (AMPK). Other researchers had discovered that AMPK regulates how cells use glucose. Some think that it could be a target for type 2 diabetes treatment. Brenman isn’t working directly on diabetes. He’s still doing what he likes best— breaking stuff under the hood of the car. But

life unlimited now his lab is wielding the hammer a little more selectively, studying parts of AMPK and the other proteins it interacts with, trying to discover how they work together. AMPK is in just about every living thing you see, animal and vegetable alike. It’s one of the countless structures we all inherited from a common ancestor hundreds of millions of years ago. On the level where Brenman operates—studying the basic machinery of cells—many of the differences between humans and fruit flies disappear. Steve Rogers works on that same level. In fact, his lab rarely works on whole organisms—only on cells. The group studies how cells divide and how they crawl. Flexible cytoskeletons that make our cells move in an uneven crawling gait are another thing humans and flies inherited from our common ancestor. “Most people actually die of cell motility disorders,” Rogers says. “For example, cancer metastasis: the bad prognosis usually comes when cells break off and form secondary tumors. And there’s heart disease, atherosclerosis. It occurs when macrophages that normally guard the body crawl to a site of blood vessel damage and metabolize cholesterol improperly. So the idea is, if we can understand how cells crawl, we can come up with therapeutic strategies to prevent harmful movement.” Rogers can, and has, studied human cell movement. But even though he can alter the genome of a human cell culture however he likes, he still needs his fruit fly cells. For Rogers and other scientists, the problem with human genomes—all mammalian genomes—isn’t just that they’re big. It’s that they’re redundant. By current estimates, humans have twenty to twenty-five thousand protein-coding genes, compared to thirteen thousand found in Drosophila. Yet about 70 percent of human genes that cause genetic diseases have orthologs in fruit flies, many fly researchers say. That means those human genes and fly genes can be traced to a common ancestor. It also means that fly genes do a lot of the same things ours do; the flies just have fewer genes involved in each function. This is one of the reasons why a lot of genetics research begins with flies instead of mice, a common animal model that’s more closely related to humans. “With mice, there would be less of a chance we’d get a gene that has an observable effect,” Rogers says.

Scientists can explain the redundancy. In the distant past, some time after our ancestors diverged from insects’ ancestors, one or more whole-genome duplications occurred, so that a mutant ancestor had a genome twice as large as its parents’. “We think of a genome as this stable thing that gets passed from generation to generation,” says geneticist Jeff Sekelsky. “But all sorts of things happen to it—gene duplications, chromosomal rearrangements.” Sekelsky studies genes involved in DNA repair pathways in Drosophila. These are the mechanisms that maintain genome stability. Without them, our bodies wouldn’t be able to repair cell damage. “The theory is that in an early step in cancer, cells lose the mechanisms for preserving stability,” Sekelsky says. The genes his lab studies have orthologs in humans. People with mutations on those genes can’t repair cell damage well and tend to get cancer when they’re young. The lab focused on two of the many DNA-repair mechanisms in fruit flies. If one mechanism gets knocked out by a mutation, the other one compensates. But when both fail, the flies die. “If tumor cells lack one repair pathway, as we think they do, we might be able to knock out a second pathway,” Sekelsky says. Radiation and other treatments could then target the weakened tumor cells without doing as much damage to healthy cells. “If we have a direct impact on treatment, I think it’s going to be there,” Sekelsky says.

hen we’re looking at AMPK, cytoskeletons, or the behavior of DNA, it’s pretty clear how studying fruit flies helps us understand other animals. But researchers also use Drosophila to study the genetics of things that don’t translate quite so simply between species. Take our sense of smell. You might not think it’s at all like how Drosophila detects its food—after all, fruit flies don’t have noses. “Their antennae are their noses,” Corbin Jones explains. “The human nose has olfactory sensilla, tissue that has all these chemical receptors. Flies have them too, but on little hairs coming off the antennae.” Flies and vertebrates also share a system for processing odor information. “If you had one receptor for every odorant, you’d need hundreds of thousands,” Jones says. Using the receptors in combination gives us a more subtle ability to perceive scents.

Jones is studying the genetics of scent perception in a species of Drosophila that’s particularly finicky in its food preferences. His lab is pinpointing the genes connected to Drosophila sechellia’s food choice behavior. Once he’s found the right genes, Jones will try to find out whether they’re also involved in behavioral responses to odors in other fruit fly species. And since the scent machinery is fundamentally similar to ours, he may be on the way to identifying genes that are involved in food choice in vertebrates. Other researchers use Drosophila to make an even bolder connection, studying the flies to learn about conditions that are unique to humans. Manzoor Bhat’s lab genetically altered flies to not produce neurexin, a protein that’s thought to be abnormal in the neurons of people with autism. Neurexin is controlled by several genes in mice and other vertebrates, and no one else had been able to produce an animal model lacking the protein. Bhat found that his neurexin-knockout flies had defective synapses—the channels through which neurons signal to each other. Bhat thinks that similar synaptic changes in humans probably contribute to autism. Working in an area of fruit fly research explicitly linked to human health, Bhat is used to explaining how his work on a tiny insect can relate to the much more complicated human brain. “It’s not that our flies have autism,” he says. “It’s that the same protein mutations that are thought to cause autism can be seen in the fly.” By explaining the protein’s function in a simpler system, he hopes to give researchers clues about how neurexin works in other animals. “Obviously, the fly is not a human,” Bhat says. “But there are many things that are the same between the systems. This protein just happens to be one of them.” e Corbin Jones and Steve Rogers are assistant professors of biology and Jeff Sekelsky is an associate professor of biology, all in the College of Arts and Sciences. Jones receives funding from the National Science Foundation, Rogers from the National Institutes of Health (NIH) and the American Heart Association, and Sekelsky from the American Cancer Society. Jay Brenman is an associate professor of cell and developmental biology and Manzoor Bhat is a professor of cell and molecular physiology, both in the School of Medicine. Brenman’s research and Bhat’s neurexin study were funded in part by the NIH. Steve Crews and Mark Peifer also provided information for this article. endeavors 15

tardi-whats? This pudgy little microbe may teach us a lesson in evolution. by Jason Smith

Left: Scanning electron micrograph of an adult tardigrade (Hypsibius dujardini). Image by Willow Gabriel. > ADULT BODY SIZE: 0.1mm to 1.5mm ( ) > NUMBER OF LEGS: 8 > FIRST DISCOVERED: 1773 > ESTIMATED HISTORY ON EARTH: 600 MILLION YEARS > EASILY FOUND IN: LICHENS, MOSSES, DUNES, BEACHES, PONDS > SHRUGS OFF EXTREMES OF: RADIATION, PRESSURE, TEMPERATURE...

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life unlimited

“One of the most spectacular pageants on Earth involves a complex creature developing from a single fertilized egg. Anyone who’s a parent is still amazed that it works…What makes a snake different from a lizard, what makes a zebra different from a giraffe, are changes within that developmental process.”

—Evolutionary biologist Sean Carroll in Discover magazine, March 2009

ince she first learned about them in day care, my five-year-old has been mesmerized by microbes. She swats them out of the air, she stomps her feet to crush them; she is ruthless. And one day, when she told me that she wanted to see some microbes, I knew just the man to call. A week later we found ourselves in Bob Goldstein’s biology lab, peering through his microscope at a curious little critter that looked like an overstuffed couch with eight legs, tiny claw-like toes, a little round head, and two beady eyespots. It was bumbling through the water, munching on specks of something too small to see. Until that morning, it had been living in Goldstein’s back yard on a bit of moss. It’s a tardigrade, Goldstein explained. Tardi-what? They’re also called water bears, he added. I was hooked. Tardigrades—the name comes from the Latin for “slow walker”—are harmless to humans. But they just might be the most oddball animals on the planet. They can live almost anywhere, from the highest mountains to the deepest seas, at the poles or the equator. They like moisture, but when they don’t have enough they can enter a kind of dry hibernation called the tun state. Once in that state, they are impressively hard to

kill. They can survive doses of x-ray radiation hundreds of times stronger than you or I could live through. They can withstand extreme temperatures—scientists have heated them to 300 degrees Fahrenheit and cooled them to within a degree or two of absolute zero, the temperature at which all molecular motion stops. Pressure extremes don’t faze them, either. They have survived both the vacuum and the solar radiation of open space, something no other animal can do. In fact, it doesn’t much matter what you try to do to them: “Just put them back into some water,” Goldstein says, “and they walk away to tell about it.” No one fully understands how tardigrades pull this off. But what are they, I wondered? Are they like plankton? Some kind of microscopic insect? No, Goldstein explained. They’re tardigrades. On the tree of life, they have their own phylum. We humans share a phylum with sea squirts, crocodiles, and about a hundred thousand other animals. Tardigrades hoe their own row. There are around one thousand known species of the little guys. “But there are probably several thousand species out there,” Goldstein says. “Most tardigrades you’d find are new species.” (See “Every Living Thing,” page 5).

Goldstein is a developmental biologist who’s also interested in evolution, in how all the different organisms on Earth got here. The journey from fertilized egg to fully formed animal is complicated and not well understood. “We know a bit about how development works in specific organisms,” Goldstein says. Fiddle with the right fruit fly genes, for example, and you can end up with flies that have unusual eye coloring or longer wings. Broadly, that’s how evolution works: small changes in DNA, over time, form new species. But how? Two organisms that outwardly seem nothing alike can have a lot of genetic overlap. Your limbs and a fruit fly’s legs are built by the same genes. Sean Carroll, a leading evolutionary biologist, compares development to choreography. “You’ve got the same dancers,” he told Discover magazine, “but the ballet is based on different cues.” Goldstein says that if you look at images of bat embryos taken at different developmental stages, “the embryos look like a mouse, look like a mouse, look like a mouse…and all of a sudden you see that these giant wings have developed where there would have been mouse legs otherwise.” How did we get from mouse to bat? Goldstein’s work, he says, is about understanding the trajectories evolution can and can’t take.

hen he came to Carolina in 1999, Goldstein was looking for an organism he could use to study evolutionary development. He settled on tardigrades. They don’t have too many genes. He can grow them in the lab. They develop reasonably quickly. Their embryos are small and clear, so he can see what’s going on inside. And their branch on the tree of life happens to be right next to the branches of two of science’s most-studied organisms: the nematode C. elegans and the fruit fly Drosophila (see “Fly Club,” page 14). “The fact that tardigrades are closely related to these other organisms means they probably have roughly the same genomes,” Goldstein says. “And that means we can make one-to-one comparisons more often than we could with a distant relative.” Those comparisons may help scientists figure out how very similar genomes can produce very different animals. endeavors 17

“In the 1960s,” Goldstein says, “tardigrades were briefly in line to be groomed as biology’s next big stars: when Sydney Brenner was looking for a new model organism for applying genetics to study development and neurobiology, he stopped at tardigrades, but decided they had too many neurons.” Brenner eventually chose the roundworm C. elegans, which is now the model organism for studying developmental biology.

oldstein and his lab are pretty much the only scientists anywhere who study evolutionary development in tardigrades. He wants to find a way to mess with a tardigrade gene to see what happens when it’s not working properly. Jenny Tenlen, a postdoc in Goldstein’s lab, is using RNA interference to do that, and Goldstein says it seems to be working. “This was one of the big hurdles: if we couldn’t find any method to disrupt gene function, then we weren’t going very far at all. I went into this project thinking I’d only continue for as long as it gave us green lights,” he says, “and it’s just given us one green light after another.”

Six developmental stages of a tardigrade embryo, from the four-cell stage (top left) to the sixty-cell stage (bottom right). During these stages, cells may be competing to become the immortal germ cells. Image by Willow Gabriel.

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Goldstein is a gadget guy—he has three or four Roomba robotic vacuum cleaners, one of which cleans his lab. He created the Animal Detector, a motion-sensitive webcam that films critters that wander into Goldstein’s suburban back yard to eat the food that he and his young son Duncan leave out for them at night (tally so far: raccoon, squirrel, opossum, rabbit, cat, robin, sparrow, wren, cardinal, gray fox, earthworm, human). He has biology-lab gadgets, as well: two fancy microscopes that can record multiple optical planes over time. Goldstein uses these microscopes to create videos of tardigrade embryos developing. “You can play back these films and see cells dividing on one side of the embryo and cells dividing on the other side,” he says. “And from that, you can reconstruct cell lineages: you can watch from the one-cell stage as it divides to two cells, and then four, and so on. And you can figure out the relationships between the cells, which can be important for just broadly understanding how development works.” Goldstein and Tenlen are looking closely at germ cells in tardigrade embryos. Germ cells, which are made by all sexually reproducing animals, are sex cells: as an embryo develops, it sets aside one cell to become

This female tardigrade carries three large oocytes, or immature egg cells, inside her body. Image by Willow Gabriel.

a germ cell, and this cell will eventually become either an egg or a sperm. In a sense, Goldstein says, the germ cell carries the organism’s immortality: it’s the germ cell’s DNA that is passed on when an organism reproduces. But we don’t really know a lot about how organisms single out a specific embryonic cell to become the germ cell. Goldstein and Tenlen think that in the tardigrade, two embryonic cells may compete for the honor. If that turns out to be true, and if Goldstein and Tenlen can figure out exactly how and why it happens, they may have taken a step toward figuring out how development influences evolution. “Evolution is the topic that unites all of biology,” Goldstein says. “In my mind, development is the part of evolution that we’ve been missing for a long time.” e Bob Goldstein is an associate professor of biology in the College of Arts and Sciences. The National Science Foundation funds Goldstein’s tardigrade work. See Goldstein’s videos and images of tardigrades at http://tardigrades.bio. unc.edu/. Goldstein’s Animal Detector appeared in the March 2009 issue of Make magazine. In October, a Russian spacecraft will take tardigrades to Phobos, one of the moons of Mars, to see if they can survive a three-year space journey.

life unlimited JASON SMITH

frogsong Can warty mating calls help us learn how communication evolves? by Meagen Voss Above: An adult male túngara frog (Physalaemus pustulosus) calls for a mate in Gamboa, Panama. Photo ©Ryan Taylor. > ADULT BODY SIZE: 25‑35mm ( ) > FEEDS ON: INSECTS > PREDATORS: FRINGE-LIPPED BATS, SNAKES, OPOSSUMS > FOUND IN: BELIZE, COLOMBIA, COSTA RICA, EL SALVADOR, GUATEMALA, GUYANA, HONDURAS, MEXICO, NICARAGUA, PANAMA, TRINIDAD AND TOBAGO, AND VENEZUELA

chorus of túngara frogs sounds like a Star Wars movie in the rainforest. The male frogs produce two calls: a sharp zing like laser fire and a monotone, robotic staccato. Sabrina Burmeister believes that the frogs, despite their futuristic sounds, will help shed light on the evolution of communication. Social communication between humans is complex. Simply talking on the phone requires coordination of intricate pathways in the brain. How these pathways came to exist is unknown. “There are a lot of mysteries underlying how complex nervous systems have arisen,” Burmeister says. It’s hard to study the evolution of the brain because brain tissue rarely fossilizes. The best method for recreating the brain of an ancient animal is to make a mold of the inside of its skull. This mold, called an endocast, can be used for making broad comparisons of brain structure, but not much else. To study the more elaborate features of the brain, scientists have to rely on living animals. Frogs are good models for communication because their simple brains make it easier to study complex communication circuits. And frogs have predictable communication behavior: they only produce calls when they’re breeding. endeavors 19

SABRINA BURMEISTER

A mating pair of túngara frogs.

o study the túngara frog’s breeding behavior in its natural habitat, Burmeister and her students travel to field stations in Central and South America. When Burmeister bought a map for a trip to Guyana, she was surprised to find only one major highway in the entire country. Guyana is connected by a network of small rivers, so the best way to get around is by boat. Burmeister travels so far because the túngara frog has a special breeding strategy: female choice. In colder climates, frogs have shorter breeding periods, so strategies such as scramble breeding— where many males attempt to breed with a single female—are more common. Because it lives in a tropical climate, the túngara frog is able to breed almost year-round. The male frogs gather along the edge of a mud puddle and call out to the females in the middle. A female selects her mate by swimming over and touching him. When working with wild animals, Burmeister admits, there’s a lot of variability. The team created standardized conditions by testing all of the frogs in acoustic chambers at the field station laboratory. They put female frogs into the chambers and then played recorded mating calls from the male túngara frog and other species. The female frogs were more active when they heard the túngara calls. Burmeister and her students were interested in the brain activity stimulated by the calls. They analyzed the females’ brain tissue for genes that indicate neural activity. Lisa Mangmiele, a grad student in Burmeister’s lab, examined a collection of genes called immediate early genes. When part of the brain is stimulated

Neuroethology? Sabrina Burmeister is part of a growing field of science called neuroethology, a combination of neurobiology and ethology. Neurobiology is the study of any part of the nervous system. Ethology is the study of animals’ behavior in their natural habitat. Ethologists are interested in documenting animal behavior in the wild. Neuroethologists are interested not only in the behavior but in how the nervous system makes behavior happen. Most neuroethologists focus their studies on the control center of the nervous system: the brain. 20 endeavors

by a sound, sight, smell, or some other sensation, neural activity is triggered like a row of falling dominoes. This activity turns on the immediate early genes. By tracing the activation pattern of the genes, Mukta Chakraborty, another grad student, was able to see where the dominoes fell. She found that the genes were activated in auditory regions of the brain. Also, the genes were more active when the túngara call was played than when the call of another species was played. Chakraborty suspected that hormones play a role in response to mating calls. She injected nonmating female frogs with different hormones to see whether they would cause the females to approach a speaker playing the male mating call. She found that estrogen, or estradiol, was all that was needed to get them to approach. Burmeister thinks that the estradiol could be interacting with receptors in the brain that affect how the females interpret the mating call. While hormones explain why females approach the mating call, they do not explain why females choose one male over another. Burmeister says females overwhelmingly prefer males that produce the staccato tone, also known as the complex call. Eighty percent of the time, females will choose the complex call over the laser fire tone (the simple call). But why? Túngara frogs’ reproduction depends on the calls. So the auditory circuits of their brains are connected to regions associated with mating. Burmeister and her students examined the gene activity of each region wired to the auditory circuit. But so far their data don’t show an activity pattern that reflects a preference for the complex call. One possibility is that their tests are not sensitive enough to detect the pattern. Another possibility is that the pattern exists in a part of the brain, such as the olfactory region, that’s separate from the auditory circuit. If that turned out to be true, Burmeister says, “it would be a major shift in our thinking of how the frog brain accomplishes these tasks.” If the complex call is better at attracting females, why have the simple call at all? Because the complex call can be very dangerous. “It attracts frog-eating bats,” Burmeister says. But she also suspects that testosterone, or other hormones or brain chemicals, may affect the frogs’ ability to produce the calls. For now, Burmeister plans to keep her main focus on the females. Her next step is to pinpoint the brain region that selects the complex call over the simple call. Her students are examining regions outside of the auditory circuit that are active during sexual behavior. Burmeister also wants to make real-time recordings of the frogs’ brain activity with a technique called electrophysiology. She’s planning to go back to South America to study communication in more frog species, especially relatives of the túngara frog. By comparing species, Burmeister hopes to learn more about how their common ancestors communicated. “If we can get a handle on what those ancestral brain structures might have been like, then we can hypothesize about how the brain has changed through evolution,” she says. e Meagen Voss is a doctoral student in neurobiology. Sabrina Burmeister is an assistant professor of biology in the College of Arts and Sciences. Lisa Mangmiele and Mukta Chakraborty are doctoral students in biology. Burmeister received funding from the National Science Foundation and from UNC’s Department of Biology.

life unlimited

no place like it How do sea turtles and other migratory marine animals find home again? by Johanna Yueh Above: A nesting green turtle (Chelonia mydas) in Hawaii. Photo by Courtney Endres. > ADULT SIZE: UP TO FIVE FEET LONG > AVERAGE WEIGHT: 440 POUNDS > FEEDS ON: SEA GRASS > LIFE SPAN: UP TO EIGHTY YEARS > STATUS: ENDANGERED

arine animals such as sea turtles and salmon routinely migrate back to their birthplaces from hundreds or even thousands of miles away. Kenneth Lohmann and his colleagues have a new theory about how they do it. Every oceanic region on Earth has a slightly different magnetic signature. At birth, an animal may read and store the unique magnetic field of its home. Later, the animal may remember that magnetic address as it travels back to the place it was born. Lohmann’s theory will be difficult to test because only about one out of every four thousand sea turtles survives long enough to breed. Baby fish face similarly long odds. But Lohmann thinks that his theory could lead to new ways to protect marine animals. “Ideally, it might be possible to steer turtles to protected areas where we would like them to nest,” he says. “It might also be possible to use magnetic imprinting to help re-establish salmon populations in rivers where the original population has been wiped out.”

In 2001 Lohmann and his team showed that baby turtles use magnetic information as a guide on their first trip across the Atlantic. And in 2004 they discovered that mature sea turtles use a more sophisticated magnetic map as they search for food. But why go to so much trouble to return home? Scientists think this homing instinct evolved because animals that returned home produced more offspring than those that did not. “For animals that require highly specific environmental conditions to reproduce, assessing the suitability of an unfamiliar area can be difficult and risky,” Lohmann says. “In effect, these animals seem to have hit on a strategy that if a natal site was good enough for them, it will be good enough for their offspring.” e Johanna Yueh is a senior majoring in journalism. Kenneth Lohmann is a professor of biology in the College of Arts and Sciences. endeavors 21

Life by the Andaman Sea In 2008, three and a half years after the tsunami that battered Southeast Asia, Carolina journalism students set out to document the lives and culture of the people of southern Thailand. Here are five of the stories they found. Hear and see more at: www.andamanrising.org

Sakbantoon Sutiprapa stretches after winning a Muay Thai fight the night before. He is thirty-four years old and must constantly work to compete with younger fighters.

ZACH HOFFMAN

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ZACH HOFFMAN (ALL)

Even at the age of eight, Muay Thai fighters are considered professional boxers. Sutiprapa trains children as young as seven in the traditional art of Muay Thai.

“It’s the kind of fighting

that shakes your heart,” Sakbantoon Sutiprapa told Zach Hoffman, a senior majoring in journalism. Sutiprapa teaches the martial art of Muay Thai, which is the national sport of Thailand. “Muay Thai is a gentlemanly sport,” Sutiprapa says. “We might be fighting in the ring, but outside the ring we are friends. “It’s about taking care of your body. I take care of my body very well. I’m going to box until my body fails me.” Hoffman’s story is titled Striking Heritage.

Sutiprapa rests in the corner of the ring between rounds.

Sutiprapa delivers a powerful kick. Because there are several ways to strike, Muay Thai is sometimes called “The Art of the Eight Limbs.”

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KATE NAPIER (ALL)

“We work together to develop our community,” Wahala said. “We know each other; we know almost everyone, and there is a feeling of togetherness.”

“I get everything I need,

whether it’s a little or a lot,” Habbideen Wahala told Kate Napier, a senior majoring in journalism. Wahala fishes, raises shellfish, and grows hydroponic vegetables. Napier’s story is titled The Sabai Life. Napier says “sabai” is a Thai word with no simple English translation. It describes happy, comfortable living. “There are times when it’s exhausting and hard,” Wahala says. “But I’m not the kind of person to stress or think too much about this way of life.”

Wahala rebuilt some of his shellfish and fish farms after the tsunami, but now he spends more time farming and less time fishing.

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A young Muslim student. Wahala teaches Arabic to children in his village. “If you are born a Muslim,” he said, “it is a crucial part of your everyday life.”

SELKET GUZMAN (ALL)

Surin Jaitrong bathes his elephant Plai Gaew every day.

“This is what I have to do,” Jaitrong said. “You let everything go. Your mind becomes clear. No adjusting is needed.”

“It remembers you by your smell and by your tone

of voice,” Surin Jaitrong told Selket Guzman, who graduated from Carolina in 2007 with a degree in journalism. Jaitrong says his elephant “will know instantly if a foreigner is a good person.” Guzman’s story is titled My Elephant, My Brother. “Elephants stand out, look regal and intelligent,” Jaitrong said. “They are enchanted creatures. They are our family and we must protect our family always.”

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PHIL DAQUILA (ALL)

A man rests in his home on stilts a few feet above the water of Phang-nga Bay on the island of Ko Panyee, southern Thailand.

“I tried to live on the mainland, but I couldn’t,” a man from a fishing village on the tiny island of Ko Panyee told Phil Daquila, a master’s student in the School of Journalism. “Though our roofs are practically attached to each other, we are free to do whatever we want.” There are around three hundred homes on Ko Panyee, and about twenty-six hundred residents. Daquila’s project is titled Anchored in Faith.

Ko Panyee’s tsunami evacuation route goes straight up a limestone karst.

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In a heavily Buddhist nation, almost all of Ko Panyee’s inhabitants are Muslim.

NACHO CORBELLA (ALL)

“Being a monk is like being a book,” Wongpet said. “If anyone cares to open it and read, they would benefit so much from what they read and learn.”

“I’m doing it to wash away the sins that have accumulated from my relatives and family, so that when they die they can go to heaven,” Juttipong Wongpet told Nacho Corbella, a master’s student in the School of Journalism. Wongpet became a Buddhist monk for fifteen days. Corbella says that Buddhist men in Thailand can choose to be ordained for any amount of time, from a few weeks to a lifetime. Corbella’s story is titled Robed in Merit. e

“My name was Juttipong Wongpet. Now, after the ordination, I am known as Pharakamon. It means ‘one who has great perserverance.’”

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Above: The runway for the Twin Otter planes that land at the McGill Arctic Research Station. Wolf Peak is in the background and Colour Lake is in the foreground. Below left: Zena Cardman’s watch at five minutes to midnight. Below right: The Twin Otter that carried Cardman and the rest of the crew to and from their field camp on the island. Facing page, top: Axel Heiberg’s toilet. Once full, it’s emptied into one of the other two barrels, where the solid waste is burned. “You’re actually not allowed to pee in the can,” Cardman says, “because urine is really nasty when it burns.” Facing page, bottom: Thompson and White Glaciers reflected in Cardman’s shades.

Above: Axel Heiberg Island, part of Nunavut Territory, Canada, is uninhabited except for a small seasonal research station.

JASON SMITH

> COORDINATES: 79° 26 ’ 0” N, 90° 46’ 0” W > AREA: 16,671 SQUARE MILES > HIGHEST POINT: OUTLOOK PEAK (7,300 FEET) > LANDMARKS: FOSSIL FOREST, THOMPSON GLACIER, WHITE GLACIER, McGILL ARCTIC RESEARCH STATION, PERENNIAL SPRINGS

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Zena’s Arctic Adventure

an undergrad looks for life in unlikely places story and photos by Zena Cardman

The toilet on Axel Heiberg Island

is an old, rusting fuel barrel with a plastic seat stuck on top. You think your toilet seat at home is chilly sometimes? Try sitting

on the can in the Arctic. I

’d arrived at this foreboding toilet on Axel Heiberg just a few moments earlier, after flying in from Resolute Bay. Resolute is the northernmost place in this hemisphere to which you can take a commercial flight, and it’s the take-off point for many Arctic expeditions. The bay is home to a small Inuit community (population 229) and an airport. When I say “airport,” though, don’t think tarmac and terminals. The runways are gravel. The buildings are very small, and so are the planes. After a sleepless night, we crowded into the belly of our tiny Twin Otter with all of our cargo and took off for Axel Heiberg Island. The view from Axel’s sole toilet is a striking panorama of tundra, where two colossal glaciers are slowly making their way into the valley between iron-colored mountains. Situated in the Canadian High Arctic barely ten degrees of latitude from the North Pole, Axel Heiberg is truly otherworldly. endeavors 29

summer here and summer there

CARDMAN VISITED AXEL HEIBERG BETWEEN JULY 20 AND AUGUST 4, 2008. GRAPHIC: JASON SMITH. SOURCES: CANADA’S NATIONAL CLIMATE DATA & INFORMATION ARCHIVE AND WEATHERUNDERGROUND.COM.

t was exactly this resemblance to another planet that lured me to Axel in the first place. Our team was led by Chris McKay, a planetary scientist with NASA and coinvestigator for the Phoenix Lander. We set up base camp at the McGill Arctic Research Station (its acronym, appropriately enough, is MARS). With MARS as our home base, we set out to collect samples for astrobiological research.

Above: Chris McKay, a NASA planetary scientist and the leader of this Arctic expedition, looking for carbonates on the side of a cliff that overlooks Thompson Glacier. Left: Some of Axel’s springs gush out of the ground and flow downhill like streams. Here, the white coloring is gypsum. The gray is a film of sulfur-reducing bacteria.

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I usually get funny looks when I say the word astrobiology. After all, how can we expect to study the origins and distribution of life throughout the universe when we don’t even know whether life exists outside of this planet? Astrobiologists start by asking basic questions about the conditions surrounding life. What are the telltale signs that an environment once supported life? What would life need in order to begin and then survive in the harsh environments on planets such as Mars? Finding these answers begins right here on our home planet. Astrobiologists study the unlikely life surviving in Earth’s most extreme environments—places so cold, so dry, or so bizarre that scientists once considered them uninhabitable. These environments are great analogues for extraterrestrial terrains. Temperatures on Axel Heiberg get as low as –40 °F, several degrees colder than Mars’s warm weather. On a warm day, Martian temperatures can reach a balmy –30 °F. Mars was probably warmer at some point in its history, when the tilt of the planet was shifted so that the polar regions got more sunlight. This overlap of temperatures makes Axel Heiberg a good place to learn about potential sources of water in Mars’s subzero environment. Water is an important piece in the puzzle of extraterrestrial life, since most life on Earth needs water in some form in order to survive. To ast robiologists, A xel Heiberg’s perennial springs are some of the most interesting features on the islands. The springs come right out of the ground, about half an hour’s hike from the McGill Arctic Research Station. Some look like

little streams flowing down the side of the hill, others look like seeps oozing up from below, and still others look like bubbling ponds. Don’t let the Jacuzzi effect fool you, though—the springs are actually quite cold. Fascinatingly, they stay liquid year-round, despite an average annual air temperature of 5 ° F. We found that each spring is unique—water temperatures and flow rates vary between individual springs. Ma ny springs in cold climates on Earth derive heat from volcanic activity underground. But on Axel Heiberg, a lack of observed magmatic activity makes it necessary to develop a new model. Our accumulating research indicates that the springs probably originate nearly half a mile underground. Scientists who have been studying these springs since the 1980s suggest that the geothermal gradient alone is enough to raise the temperature of the water. Hydrostatic pressure from a nearby lake then forces the springs to flow upward through the permafrost, making their way to the surface through tube-like structures of gypsum, a salt composed of calcium sulfate. By the time the springs reach the air, they have picked up so much salt that they have three times the salinity of saltwater. The salt acts like an antifreeze, allowing the springs to stay liquid even when the weather is well below the normal freezing temperature of water.

Above: Two Inuit schoolteachers wrote out the names of the research team in Innuktitut. Below: Arctic cotton, a member of the sedge family. Wolf Peak is in the background.

Above: Lepus arcticus, an Arctic hare. In winter the hare’s coat is white. In summer months, the coat eventually turns brown for better camouflage around mud and rock. The Arctic hare’s ears are shorter than those of other hare species.

ources of liquid water may be the obvious places to look for life, but organisms can flourish even where water is perpetually frozen. I spent much of my time in the Arctic digging holes in the permafrost, collecting soil samples in a search for life. Axel Heiberg may be harsh for most large life forms, save the occasional caribou or well-insulated Arctic hare. Look on a smaller scale, though, and you’ll find bacteria thriving in permafrost nearly a meter underground. Permafrost occurs on Mars, too, opening the doors for more analog studies. On Earth, permafrost is characteristic of polar regions. It thaws during the summer, creating an “active layer” of soil. Dig through the layer of soft soil and you will eventually hit the solid, perfectly flat table of ice-cemented ground that exists in the Arctic and Antarctic. Analysis of our soil endeavors 31

TAMMY MORGAN

samples in laboratories back in the United States revealed the presence of metalreducing and sulfur-reducing bacteria much like those found at the other end of the earth in Antarctic permafrost. Frozen soil isn’t the only place on Axel Heiberg to find bacteria. Axel’s springs are another logical place to look for life—and indeed, the springs are surrounded by slimy layers of sulfur-reducing bacteria. Microorganisms even form colonies called endoliths inside giant chunks of rock or gypsum salt. It seems as though life can find a niche no matter how unbelievable the environment. To me, a community of bacteria living where nothing else can is one of the most compelling scientific beauties I can imagine on Earth. I’d pick a barren, frozen desert over a teeming jungle any day, and Mars is the most enticing desert I know. e Zena Cardman is an undergraduate biology student at UNC. She received funding from the UNC Burch Fellows Program and the North Carolina Space Grant to conduct research in British Columbia and the Canadian Arctic during the summer of 2008. In the Arctic, she also filmed high-definition footage for the PBS television series NOVA . You can see more pictures, videos, and read Cardman’s travel updates at www. zenacardman.com. For more information about the Burch Fellows program, visit www. burchfellows.unc.edu. 32 endeavors

Above left: Cardman on Axel Heiberg. Above right: Cardman says the station’s potted-meat collection has been accumulating for more than twenty years, and is kept mostly as a joke: “I don’t think anyone has ever had to resort to eating a can of vintage Klik.” Right: The view from the foot of White Glacier. Below: Margarita Marinova, Cardman, and Rob Palassou. “We were studying microorganisms that live about a meter underground,” Cardman says. “I spent a lot of time with my head and arm down in holes, scooping out permafrost samples with a spoon. One day, I’m minding my own business when all of a sudden my feet are in the air and my head and shoulders have been shoved so far into the hole that I get stuck. I had to get dug out. Awesome.” TAMMY MORGAN

the mystery mounds B

y most measures, Pavilion Lake is completely normal. A picturesque body of fresh water in British Columbia, carved out by a glacier some eleven thousand years ago, it has an ordinary pH, temperature, and mineral content. Yet the lake hosts a collection of bizarre structures that may someday help us detect past or current life on other planets. In the mid-1990s, scientists discovered microbialites at the bottom of the lake, luring researchers from NASA, the Canadian Space Agency, and a number of universities. Microbialites are intricate carbonate formations that can be created by diverse microbial organisms. They look like coral, but without the tropical color schemes. In fact, microbialites are modern analogues for Precambrian reefs, which were some of the earliest indicators of life on Earth. Such structures were once common on the surface of Earth, but these days they are typically found only in extremely salty water. So what were microbialites doing in Pavilion Lake? I came face to face with them while SCUBA diving alongside other scientists with the Pavilion Lake Research Project. In shallow waters, microbialites are small and resemble cauliflower. Up close, you can see individual sand-like grains. Some crumble like dirt between your fingers. As you dive deeper, the microbialites become larger and harder, and resemble giant artichokes. Since 2004, scientists have been diving extensively in the lake. Yet SCUBA diving has its limitations. And so this year, for the first time, the Pavilion Lake Research Project brought in a pair of Nuytco DeepWorker submersibles to explore the lake. Simply deploying the subs was a bold undertaking. Usually DeepWorkers are launched from enormous ships with the help of cranes. But with nothing but highway access to the lake, ships and cranes were not an option. Instead, we built a miniature barge, like a floating swing set. We lowered the subs by hand on chains, and divers guided them out from under the barge. Twice each day pilots flew the submersibles over predetermined contours of the lake, taking high-definition video of the lake bottom. Using the ninety hours of video recorded, our goal is to create a high-resolution map of microbialite morphologies throughout the lake. Combined with ongoing biochemical experiments in the lake, our new knowledge of microbialite distribution will eventually help us see the big picture. We hope to piece together how these microbialites are formed, and why their structures are so varied. —Zena Cardman

Above: Darlene Lim, a researcher at NASA Ames and principal investigator for the Pavilion Lake Research Project, saws through a microbialite sample. “We’re interested in the center of microbialites, as well as the most recently formed outer layer, and a handsaw happens to be a convenient way to slice them open,” Zena Cardman says. “This was one of the ‘artichoke’ microbialites from deep down in the lake, so it was particularly dense.” Below left: Astrobiologist Dale Andersen, diving next to one of the deep microbialite mounds in Pavilion Lake. Below right: Pavilion Lake in Marble Canyon, British Columbia, Canada is one of the few places on Earth where microbialites can be found. > COORDINATES: 50° 52’ 0.37 N, 121° 44’ 30.88” W > MAXIMUM LENGTH: 3.6 MILES > MAXIMUM WIDTH: 0.5 MILES > SURFACE ELEVATION: 2,690 FEET > LANDMARKS: CLIFFS OF MARBLE CANYON, CHIMNEY ROCK, THE TOWNS OF LILLOOET AND CACHE CREEK

JASON SMITH

DONNIE REID

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Paulâ&#x20AC;&#x2122;s team gave bigotry

a good, swift kick.

by Mark Derewicz JASON SMITH

As part of the 2009 Carolina Summer Reading Program, thousands of first-year students are reading A Home on the Field by Paul Cuadros. It is the first book the selection committee has chosen that was written by a UNC faculty member. Itâ&#x20AC;&#x2122;s also a true story that the committee thinks will spark discussion about immigration in North Carolina. 34 endeavors

hen Paul Cuadros was a young boy, he felt most at home playing soccer with his dad and brothers in an empty Michigan Stadium. They spoke only Spanish. In school, Cuadros felt out of place. He could barely speak English and he looked different—Peruvian brown in a sea of white. “I spent my days in school educating myself, navigating the system on my own terms without my parents,” he says. Cuadros never did feel entirely comfortable, but he became fluent in English, captained his high-school soccer team, and graduated from the University of Michigan. Twenty years later, Cuadros was spending his days in another football stadium, this time as soccer coach for Jordan-Matthews High School in Siler City, North Carolina. Most of his players were Hispanic, and several could barely speak English. Some longtime residents were angry about the influx of Hispanics; they wanted to kick these kids out of the country. Cuadros thought his players could make something of themselves. But he had no idea that they would help ease the town’s racial tensions. ••• Cuadros, the son of immigrants, was raised in a tiny basement apartment in the church where his father Alberto was a janitor. At night, Alberto washed dishes at a candy store. His family was able to move into a house after a university researcher, himself the son of an immigrant, gave Alberto a job caring for lab animals. Alberto hated the job, but it came with health benefits and pushed the Cuadros family into the middle class. Cuadros never forgot his roots, and he became an investigative reporter specializing in race and poverty. In 1998 he found a story he says he’ll be reporting on for the rest of his life. He was working for the Center for Public Integrity in Washington, D.C., when his research found that Hispanic populations were skyrocketing in towns with meatpacking or poultry plants. He wondered how these towns would be affected and how whites would respond. He decided to find out, moving to Pittsboro and focusing on Siler City, a town of eight thousand people with two poultry-processing plants. In 1990, just 4 percent of Siler City was Hispanic. Ten years later 39 percent was Hispanic, nearly equal to the percentage of whites. Schools became overcrowded, and many teachers wound up spending a lot of

time helping Hispanic students who had limited English skills. This angered a lot of white and black parents, Cuadros says. The town’s health-care system was straining under pressure from so many new residents, many of whom were uninsured and undocumented. Rural slums rose up. Still, the town’s economy was surging, thanks in part to the influx of Hispanic consumers. In February of 2000 anti-immigration sentiment morphed into blatant racist rhetoric when a few citizens organized a rally featuring David Duke, a former Ku Klux Klan Grand Wizard. Hundreds of people attended. One man told Cuadros: “I’m mad because there ain’t no Greyhound buses here to load them up and send them back where they come from.” Cuadros says, “What people don’t understand is that these poultry companies recruited workers from Mexico. This migration was planned.” During the 1970s, slaughterhouses moved from cities to rural areas in order to break up unions, Cuadros says. These factories would

companies paid Mexicans to travel north and sometimes provided them with housing. But chopping chicken all day is hard, dangerous work. After a year or two, many workers moved on to better jobs in construction or restaurants, for instance. “Chicken processing is a gateway industry,” Cuadros says. When workers quit, factory owners dipped back into the Mexican labor pool. A former human-relations director at a poultry company told Cuadros, “We had something called a buddy bonus that if you brought a new employee and they stayed X amount of time, you got X amount of dollars and a coupon. We did a lot of innovative things to have people spread the word.” Eventually, Cuadros says, word of mouth in Mexico sufficed. Back at Town Hall, Cuadros asked David Duke why the rally wasn’t held outside a chicken factory. Duke responded, “Maybe we’ll go there next.” But Duke didn’t go there; he went to Golden Corral, where Cuadros, hoping to get an interview, watched Duke down a plate of fried chicken. JEFF DAVIS

Cuadros the coach recruited Hispanic kids and white kids for the same team. It worked.

ship whole chickens and sides of beef to local butchers, who would prepare various cuts of meat for consumers. Processing plants took over meat preparation in the late 70s and early 80s, creating disassembly lines to debone chicken and produce the prepackaged meat now available at any supermarket. At the same time, Americans began preferring chicken to red meat, and the poultry industry boomed. To maximize profits, companies hired workers—often blacks—at low wages, until they found an even cheaper labor force south of the border. In many cases, Cuadros says, chicken

n the summer of 2000 Cuadros conducted a race relations experiment: he started a soccer team with white players from Pittsboro and Hispanic kids from Siler City. The players responded well to each other, and the team had a great year traveling throughout North Carolina. But some opposing players and spectators shouted ethnic slurs at the Hispanic players. “That was freaking amazing,” Cuadros says, still in disbelief. When the season ended, a few players told Cuadros that their older brothers had tried to start a soccer program at Jordanendeavors 35

Matthews, but the principal had turned them down three years running. “I thought that was strange,” Cuadros says. “I mean, how hard is it to start a soccer program? So I decided to do something that reporters don’t typically do. I got involved.” By then, Cuadros had been hired as a stringer for TIME magazine; his beat was North and South Carolina, and since immigration was becoming a hot story, some ideas for a book began percolating in his mind. Cuadros met with school officials but was rebuffed whenever he broached the subject of creating a soccer team. The main problem, he realized, was cultural. “The dominant culture of any small-town community has its institutions—football, basketball, baseball,” he says. Frustrated with his lack of progress, Cuadros enlisted the help of county commissioner Gary Phillips, who had some clout in Chatham County and agreed with Cuadros that creating a soccer team should not be a big deal. And just like that, Cuadros got his team. Despite making a few enemies and causing quite a stir along the way, Cuadros did not retreat back to Pittsboro; he volunteered as the assistant soccer coach. The next year, in 2003, he became head coach. The team was made up of kids from different backgrounds. Some had just arrived from Mexico. Some were born in North Carolina. A few players had come to Siler City from large cities because their parents had feared

gang wars in Los Angeles or Chicago. Four players were white. The team gelled and became an immediate contender, thanks in part to Cuadros breaking the players’ street-ball habits. But during the first few seasons, spectators again slung ethnic slurs, and opposing players took a few too many cheap shots on the field. After one game, fans threatened the team. “Just wait ‘til y’all get up here,” said one man, who knew that the team had to walk through the grandstand to get to the bus. Cuadros kept his players on the field until the entire stadium was empty. Cuadros became more than a coach, helping some kids manage their troubled family lives, encouraging them to go to class and graduate, and making sure they understood the consequences of their decisions. He translated for a mother when her son injured his knee during a game and needed surgery. He made sure to help the kids however he could because he knew the custom they faced at home—when you turn sixteen, you’re on your own. “That worked in Mexico, but it can have disastrous results here,” he says.

uadros figured he had the makings of a good book, a story about what those Hispanic kids went through—where they came from, who they are, and why playing high school soccer meant so much to them. His five years of immigration reporting would add context. He found a literary agent, who pitched the idea to editors.

JEFF DAVIS

Cuadros after the state championship: The ‘problem people’ turned out to be winners.

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Then Jordan-Matthews won the 2004 conference title, earning home-field advantage throughout the playoffs. The team beat rivals who had been its nemeses in 2002 and 2003. And in the final game of the season Jordan-Matthews dominated Lejeune High School, a highly touted team from Jacksonville, to win the state championship. The players were overjoyed and carried Cuadros off the field, state trophy in hand. Back in Siler City, many people—white, black, and Hispanic—hailed the players as heroes. The book Cuadros had pitched—A Home on the Field—turned into a modern-day Hoosiers. Three publishing houses bid for the rights, and Cuadros settled on Rayo, an imprint of HarperCollins. “For a lot of longtime residents, the boys stopped being those ‘problem people’ and became winners,” Cuadros says. “That season gave people a reason to cheer and support the Hispanic community and to see themselves as part of that community. That’s a big thing. Bigger than I thought it would be.” Things have changed a lot since Cuadros moved to Chatham County. His players don’t hear slurs anymore. Siler City went through an economic boom, and many residents recognize that it was largely because of Hispanics who paid taxes, shopped, ate out, and bought houses there. A lot of longtime residents are still furious about illegal immigration and resent crowded schools. Blacks, whites, and Hispanics are still often cloistered in their own neighborhoods. But they’re rubbing elbows a little more, Cuadros says, and most Hispanics want to assimilate and are learning how. Cuadros’s former players, for instance, all speak English, work jobs, pay taxes, raise kids, and want to improve their lives. And, Cuadros says, there’s a sort of generational trust that’s slowly building between Hispanics and non-Hispanics in Siler City. “Over time, everyone has to deal with each other,” he says. “When you get to know people a little bit, you see their humanity.” e Paul Cuadros is an assistant professor in the School of Journalism and Mass Communication. In 1999 he won a fellowship from the Alicia Patterson Foundation to report on immigration issues in the South. A Home on the Field was published in 2006. Cuadros is the head coach for the boys’ and girls’ varsity soccer teams at Jordan-Matthews High School in Siler City.

NEIL CAUDLE

What’s stopping bird flu’s big step? by Beth Mole Bird flu is a danger wherever people mingle with birds and fowl, especially in crowded, unsanitary conditions. For years, the H5N1 bird flu has been considered an imminent threat to public health because it can jump from birds to humans. Ray Pickles is trying to learn what could prevent H5N1 from taking the next step—jumping from human to human—and becoming the next pandemic.

Infected cells of the human windpipe (shown in green in this micrograph from Ray Pickles’ lab) are a breeding ground for the flu virus.

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BETH MOLE

ust kind of stare at one spot,” Meg Scull said as she adjusted the focus. I peered through the lenses and saw yellow cells assembled in a cobblestone pattern. It took a moment, but then I could see it—the cells were twitching in unison, making the liquid on top of them swirl like a whirlpool. I was watching the lining of a windpipe—human airway epithelium (HAE)—living and growing in a plastic dish. “Sometimes when I need a break, I’ll just come in here and watch them,” Scull said with a laugh. Scull, a microbiology and immunology grad student working with Ray Pickles, is using the HAE model to figure out why bird flu isn’t spreading among humans. The HAE model twitches because the top layer of cells is ciliated. The hair-like structures sway together rapidly, carrying foreign particles up and out of the lung like crowd surfers at a rock concert. But because the model HAE grows in a dish, the cilia just move things in a circle, creating the whirlpool. The ciliated epithelium cells of the HAE are where an inhaled flu virus replicates if an infection is successful. If bird flu infects someone’s HAE, it could spread from person to person around the globe. Bird flu migration The H5N1 strain of bird flu has been running rampant in wild fowl and devastating poultry populations in Asia for years, and has slipped in and out of media attention in the process. In 2004, Time Asia Magazine speculated that H5N1 could be the next human pandemic. “H5N1 is making big news again because they’ve had three deaths so far in 2009 in China,” Pickles says. Since 2004, H5N1 has spread to avian populations in Europe and Africa. There have been relatively few cases of H5N1 infection in humans, but when the virus does infect a person it tends to be deadly.

“All influenza viruses have originally come out of avian species,” Pickles says. “H5N1 is just one example of an avian flu that can get into the population with the possibility of a pandemic.” Waterfowl carry influenza viruses in their GI tracts with few or no symptoms and constantly shed viruses. So places such as ponds where waterfowl often congregate are swarming with bird flu viruses, Pickles says. 38 endeavors

Meg Scull, a microbiology and immunology grad student, keeps watch over infected cells.

“Why aren’t we just picking these viruses up willy-nilly?” When influenza H5N1 reaches chickens, they do get infected—and something strange happens. There’s an actual change in the virus, allowing it to infect all kinds of cells, not just those found in the bird’s GI tract. “In chickens, no organ is spared and the virus becomes rampant,” Pickles says. This is why poultry workers have made up the majority of cases of H5N1 in humans. “Because of the sheer amount of virus that’s being produced, you have the susceptibility of the poultry workers to get inoculated with high doses,” Pickles says. Poultry workers handling infected chickens would be exposed to infected tissues, blood, and aerosols, all containing extremely high levels of flu virus. “That’s a very different exposure than you see with somebody sneezing on a table and you picking it up two days later,” he adds. Scientists and public-health experts studying the flu have accepted the idea that an unusually high level of H5N1 is necessary for it to make the jump from birds to humans. But are we closer to understanding the risk to public health? “The big question now is the whole transmission thing,” Pickles says. If the virus

could be transmitted, it could move from the few infected poultry workers to people around the world. Enter the flu Once a flu virus enters the human airway, it needs to usurp a cell’s machinery and replicate. The ciliated cells of the airway’s epithelium are easy targets. To avoid being carried away by the swaying cilia, the flu virus uses surface proteins to attach and drag itself into the cell. These proteins, called hemagglutinin and neuraminidase, are found all over the surface of the viral particle. Hemagglutinin and neuraminidase have been shown to be crucial for flu infection. In fact, the designation for flu viruses refers to the type of hemagglutinin and neuraminidase the virus carries: H5N1 carries the fifth defined type of hemagglutinin and the first defined type of neuraminidase. Most vaccines against human flu target hemagglutinin. The reason we get vaccinated each year is because hemagglutinin continually mutates. Hemagglutinin binds to a sugar called sialic acid on the ciliated airway epithelial cells. Once the binding occurs, the other viral surface protein, neuraminidase, cuts the

two apart. In essence, the viral particle claws its way to the cell by continually binding and releasing sialic acid with hemagglutinin and neuraminidase, like a retractable grappling hook. “These two sort of evolved together to match the activity of the other,” Scull says. When the virus makes it to the cell, it enters and starts the infection process. “The virus ends up replicating in the nucleus and then gets transported back out and assembled,” Scull explains. When the new viral particles are assembled and ready to leave the cell, the hemagglutinin and neuraminidase allow the virus to pull its way up and out so that it can infect the next cell. The transmission thing “When we get a circulating flu virus, we’re coughing and sneezing, depositing stuff everywhere; people are picking it up,” Pickles says. If you’re infected, the expanding viral population and the subsequent immune response damage your airway epithelium, which causes coughing and sneezing as your body tries to clear the debris. “But with the documented cases of H5N1, it seems to be a different story,” Pickles says. “It seems that there are very few common cold symptoms. There’s no sneezing and most of the infection seems to be taking place in the lower airways and the lungs, so it’s more like pneumonia.” If you don’t sneeze and cough, it’s much harder to transmit the virus. Scull and Pickles think there are at least two reasons why H5N1 doesn’t transmit well in humans. The first is that the hemagglutinin and neuraminidase of H5N1 have adapted to function best at the temperature of the avian GI tract, which is much warmer than our upper airways. The other reason has to do with the type of sialic acid the hemagglutinin binds to. The temperature of the avian GI tract is around 104 degrees Fahrenheit, while the human upper airway epithelium, where human flu viruses infect, is around 89 degrees. Scull and Pickles’ data show that the bird flu hemagglutinin and neuraminidase are most efficient at 104 degrees. They took an attenuated human flu virus and engineered it to carry hemagglutinin and neuraminidase from avian flu. Then they infected their model HAE with this avianized human flu. By measuring the level of virus in the HAE, they found the avianized human

flu was much worse at infecting when the HAE was at 89 degrees—the temperature of the upper airways. “It’s not a huge molecular structure that people spend years studying,” Pickles says. “It’s related to the simple fact that we have a different temperature in our airways. It’s an innate defense.” But our lower airway epithelium is 98 degrees, closer to the temperature of the avian GI tract. If a person were exposed to high levels of H5N1—such as the exposure levels poultry workers face—infection might occur in the lower lung. “And if I were to guess, I would say that once the virus gets into that lower lung, it’s really, really hard to control,” Pickles says. Our immune system controls viral infections with inflammation. “Sending inflammatory cells into the lower lungs has a much greater consequence than sending them into our big airways where we can clear things.” Not only is the avian hemagglutinin adapted to function at higher temperatures, it also preferentially binds to different sialic acids. Sialic acid is a generic sugar that can attach to other sugars in at least two ways: 2,3 and 2,6 linkages. The hemagglutinin of avian flu viruses preferentially binds to sialic acids that are in a 2,3 linkage, meaning that the second carbon on sialic acid attaches to the third carbon of another sugar. Hemagglutinin of human flu viruses, on the other hand, tends to bind to sialic acids that are attached to other sugars in a 2,6 linkage. “In influenza pandemics, all of those viruses bound to 2,6 linked sialic acid,” Pickles says. “So it seems to be that if you’re

a flu virus and you want to go from person to person, you need to bind to 2,6 linked sialic acid. We don’t really know what advantage that confers to allow for transmission between people.” The lab’s data suggest that if you have a virus that prefers 2,6 linked sialic acid, it does better at the temperature of the upper airway epithelium. “So it could be that mutating to prefer 2,6 linked sialic acid enables you to replicate at a lower temperature,” Scull says. If H5N1 were to mutate to infect the upper airway epithelium like seasonal human flu viruses do, would it be less likely to enter the lower lung and cause life-threatening disease? Or would it just be a transmissible virus that our immune systems won’t recognize? “Flu is a virus that’s so common because it has this incredible ability to mutate. And although small mutations are actually okay for us, because antibodies give us some protection, big mutations—such as when you introduce a new hemagglutinin into the population—have the potential to be devastating,” Pickles says. “When we first got into influenza I thought, ‘What is there to do in influenza research?’ because this has been studied for years. It’s really amazing what we still don’t know.” e Beth Mole is a doctoral student in the Department of Microbiology and Immunology in the School of Medicine. Ray Pickles is an associate professor in the Department of Microbiology and Immunology. Funding for his bird flu research comes from the National Institutes of Health.

BETH MOLE

Ray Pickles at his microscope: “All influenza viruses have originally come out of avian species,” he says. “H5N1 is just one example of an avian flu that can get into the population with the possibility of a pandemic.”

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targeting tumors by Prashant Nair

40 endeavors

s part of the Cancer Genome Atlas network, oncologists Neil Hayes and Charles Perou study changes in gene activity that could spur cancer. Last September, Hayes and a team of scientists found that the activity of a handful of genes was unusual in the brain cells of patients suffering from a kind of brain tumor called glioblastoma. Scientists now think of cancer as a constellation of diseases in which the body loses its ability to put the brakes on cell growth and movement. The changes that cause the brakes to fail may be situated anywhere in the genome. Personalized medicine, which tailors therapy to the individual’s genetic makeup, could revolutionize how doctors treat cancer. But to truly personalize treatment, oncologists need to understand all the genetic abnormalities that could trigger the disease. Mining the genetic information hidden in cancer cells is no mean feat. There’s a whopping number of nucleotide bases to parse; the human genome contains about twentyfive thousand protein-coding genes, according to the National Human Genome Research Institute. And that doesn’t include the more than 98 percent of our genome that’s made up of noncoding DNA, most of whose functions scientists have yet to plumb. To confront the challenge, the network brought together eighteen institutions that are trying to improve doctors’ ability to diagnose, treat, and prevent cancer. The scientists are documenting changes in the composition and behavior of DNA from tumor tissue removed during treatment. The tissues are cataloged and stored without any identifying information in a central repository in Phoenix, Arizona. Researchers at one or more of eight participating institutions analyze samples of each cancer tissue. They then make the documented genomic changes available in public databases, which scientists everywhere can mine to figure out which of those changes might have triggered the cancer. Last September, the network published in the journal Nature the first results of its comprehensive study of glioblastoma, a recurrent, malignant brain tumor that the National Cancer Institute (NCI) estimates killed thirteen thousand people in the United States last year. Most glioblastoma patients die within fourteen months of diagnosis. The scientists analyzed the genomes of about two hundred glioblastoma patients whose tumor samples had been stored at the repository in Arizona. They then compared the patients’ “cancer genomes” with their normal genomes—prepared from the patients’ unaffected blood cells. Hayes says the team chose glioblastoma for their first study because it presented the fewest technical challenges. “Scientists at NCI felt that glioblastoma was less complex and easier to profile for mutations and gene expression changes than other cancers,” he says. Unlike other cancers, glioblastoma tumors show little morphological variation among patients, making glioblastoma a relatively easy subject for a pilot study. “That, of course, doesn’t mean it’s easy to treat,” Hayes says.

Treating certain kinds of lifethreatening cancer is like shooting in the dark. That’s because oncologists don’t know all the genetic abnormalities that underpin the disease. UNC scientists are now part of a nationwide effort to understand all the genetic changes that occur in certain types of cancer. Their assignment: brain tumors.

Left: Brain cross-section showing a glioblastoma tumor (dark area, far left). Image: S. Brandner. > MEDICAL NAME: GLIOBLASTOMA MULTIFORME > WHAT IS IT? THE MOST COMMON AND MOST MALIGNANT FORM OF BRAIN TUMOR > MORTALITY/MORBIDITY: WITHOUT THERAPY, ALMOST ALL GLIOBLASTOMA PATIENTS DIE WITHIN THREE MONTHS. PATIENTS TREATED WITH OPTIMAL THERAPY HAVE A MEDIAN SURVIVAL OF ABOUT TWELVE MONTHS. > GENERAL SYMPTOMS: HEADACHES, NAUSEA, VOMITING, CHANGES IN PERSONALITY OR MOOD > CAUSES: UNKNOWN IN MOST CASES

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Despite some year-to-year declines and increases, incidence rates and mortality rates for brain cancer and other nervous system cancers in the United States have remained about the same over the past twenty years. (Data for Hispanics and Asians/Pacific Islanders not available before 1992.) Source: National Cancer Institute. Graphic: Jason Smith.

One of the challenges is to identify the exact points where the problem begins. “If you knew those points, you could target your anticancer therapy downstream to those points,” Hayes says. “If you don’t know, you can hit the tumor cell all day long upstream of those points and see no effect.”

Hayes says it’s hard to find tumor samples of suitable quality for analysis. “We need at least 200 milligrams of brain tissue from each patient to extract the DNA and the RNA for analysis,” he says. But the scientists had access to sufficient numbers of glioblastoma tumors, which was another reason they chose to study that type of cancer. The team found several genetic changes in the tumors. At the time the study went to press, the team had complete sequence information for about half of the two hundred samples, and in all of those sequences eight genes were significantly mutated. In addition, an array of genes involved in cell division and in intracellular growth signaling showed altered copy number—the number 42 endeavors

of copies of a gene present on the chromosome. Some genes had too many copies; others had too few. There was also abnormal activity in the genes involved in growth regulation, powering some biochemical pathways that lead to cancer-cell proliferation while short-circuiting others that lead to cancer-cell death.

ayes says the experiment is the most comprehensive analysis of glioblastoma tumors to date. Perhaps the team’s most significant contribution, he says, was to present a network view of brain tumors by turning the spotlight onto a mix of players from interconnected as well as far-flung cellular pathways. That illumination is crucial for tailoring therapy and forming prognoses. One of the biggest challenges facing the team is to identify the exact points where the problem begins in the pathways of cancer cells. “If you knew those points, you could target your anticancer therapy downstream to those points. If you don’t know, you can hit the tumor cell all day long upstream of those points and see no effect,” he says. Such a pathway-driven approach to treatment has become the cancer community’s M.O. The trend in cancer therapy has steered away from treating tumors based on where they are in the body, and toward targeting them based on their genetic signatures. “That allows us to think about therapies in a rational way,” Hayes says. In a nod to this approach, the team also

uncovered a novel mechanism of resistance to the frontline brain-tumor drug temozolomide. Oncologists prescribe the drug to patients regardless of their genetic makeup—largely for lack of an alternative therapy—but have long known that patients whose tumor cells have a modification in one gene respond better to the drug. The gene, MGMT, repairs damaged DNA. Its modified form, which involves the addition of a methyl group to the gene, makes patients responsive to temozolomide. That’s because the drug kills tumor cells by damaging their DNA. Tumor cells with a methyl group attached to MGMT are unable to repair DNA damage; methyl groups muffle the genes they’re attached to, producing an effect scientists call gene silencing. The link between MGMT methylation and response to temozolomide is old news, but the team found that the methylation of the MGMT genes in some glioblastoma patients could also make normal brain cells prone to mutations because of impaired DNA repair. They observed more mutations, and different kinds of mutations, in the brain cells of patients whose MGMT genes were methylated. This information could help oncologists evaluate the best treatment option for such patients should alternatives become available in the future. “I think we’ve shed a little light on the important targets and their prevalence in glioblastoma tumors,” Hayes says. To oncologists used to shooting in the dark, that little light represents a whole new way of looking at brain tumors. e Prashant Nair is a master’s student in medical journalism at Carolina. Coauthors of the study were Neil Hayes, an assistant professor of hematology and oncology, Charles Perou, an associate professor of genetics and pathology, and Michael Topal, a professor of pathology, all in the School of Medicine. The National Institutes of Health, which created the Cancer Genome Atlas network, funded the study. The Lineberger Comprehensive Cancer Center is one of eight Cancer Genome Characterization Centers in the network; other members include MIT’s Broad Institute, Harvard Medical School, Memorial Sloan-Kettering Cancer Center, Lawrence Berkeley National Laboratory, the Sidney Kimmel Cancer Center at Johns Hopkins University, HudsonAlpha Institute for Biotechnology, and the University of Southern California’s Epigenome Center.

GETTY IMAGES

Violence escalated through the 1970s until the military seized power in September 1980. The coup was Turkey’s third in twenty years.

How will

Turkey turn?

A Burch scholar learns how Turkey’s tempestuous past will shape its future. by Mark Derewicz

ON THE NIGHT OF SEPTEMBER 14, 1980, Cangüzel Güner was at home in Ankara, Turkey when she heard a pounding at the door. Three men had come to arrest her father. His crime: being a member of the Turkish parliament during a military coup. “It was pitch black and here were these soldiers taking my father into the darkness,” Cangüzel says. The family heard no word of his whereabouts for two months. Twenty-eight years later, Cangüzel’s daughter Yekta was in Turkey with nine other Carolina students for a seven-week Burch Field Seminar with UNC history professor Sarah Shields. The students spoke to Turks of all stripes from large cities and tiny hamlets, trying to learn what makes Turkey tick. Is the country of the East or of the West, and in which direction will it turn now? They also spent hours in discussions with Shields, an expert on Turkish and Ottoman history. The students had incredible experiences, but while they were in Turkey rumors swirled of another military coup. Yekta, for one, was particularly troubled. She started researching the 1980 coup and its origins. When she returned to Chapel Hill, she sat down with her mother, who is the associate director of the Carolina Center for the Study of the Middle East and Muslim Civilizations. The two of them talked for hours about how and why Cangüzel’s father was arrested and what this had meant for his family. This oral history, combined with Yekta’s formal research, helped her write a unique research paper about why coups occur in Turkey and how they damage the lives of innocent people. endeavors 43

After traveling to her native Turkey, Yekta Zülfikar (right) was inspired to research her family history, including the story her mother, Cangüzel Zülfikar (left), told her about the 1980 coup. Photo by Mark Derewicz.

Turkey is unusual. It’s not really Middle Eastern, despite its location. But it’s not wholly part of Europe, despite the government’s desire to join the European Union. The country is 99 percent Muslim, and outranks every Middle Eastern nation except Yemen in prevalence of Islam. But until now, Turkey’s government has been vehemently

secular. Today’s ruling party has an Islamist past and is trying to change decades of antireligious legislation, including laws that controlled all religious institutions and banned women from wearing headscarves in certain places such as 44 endeavors

government offices and universities. And Turkey is a democracy with a president and

a parliamentary system, but it has weathered several coups, one of which came right after Cangüzel’s father joined the parliament.

n 1977, when Cangüzel was thirteen, her father, Agâh Oktay Güner, told his family that he wanted to get into politics. “We were strongly against the idea, but I kept my feelings inside,” Cangüzel told me. “Then I hugged him and closed my eyes. There I saw three gallows. And I knew; three politicians had been executed after the 1960

coup. I opened my eyes. I was crying and I said, ‘I wish you would not do this, but I’ll support you.’ I knew what he was thinking. Since he was four years old, when his sister died in his mother’s arms, my father wanted to become a politician to help the poor.” When he got older and people came to him for help, Cangüzel says he found that only politicians had the power to help them. But Yekta says that her grandfather, who represented the city of Konya, became part of a deadlocked parliament in which none of the parties could unite to form a majority government. They were helpless to quell the street violence between political factions, much to Güner’s chagrin; he had been pleading for nonviolent solutions. The military allowed the violence to escalate, and in some cases even instigated it. In her research, Yekta found that Turkey’s parliamentary system had a major flaw that allowed the coup to take hold: politicians, not the people, elected the president back then. When President Korutürk’s term ended in the summer of 1980, the parliament failed to elect a successor even after one hundred rounds of voting. Some citizens begged the army to intervene, Yekta says. And then it did. Yekta says that her grandfather was one of 122,600 people the army swept up. “Many were journalists, teachers, businessmen, lawyers, and politicians,” she says. “It didn’t matter which political party they belonged to.” Güner was in jail for two months before his family was allowed to visit. Back home in Chapel Hill, Yekta documented her mother’s experience, scribbling down notes while in the car or at dinner. “Not knowing what would happen really took a toll on us,” Cangüzel says. “I became melancholic. My younger sister became even quieter and gave herself completely to her studies. My youngest sister Sâmiha, who was eight, could not comprehend everything. Her hair started falling out, leaving spots the size of quarters.” When they were finally allowed to see their father, Sâmiha latched on to him and would not let go. He had to peel her off at the end of the fifteen-minute visit, leaving as his family wept. Weeks after her father was arrested, Cangüzel was walking past a storefront when she heard a radio broadcasting the names of people who could be executed for “crimes against Turkey.” Her father was on the list.

he men who carried out the 1980 coup claimed to be preserving the legacy of Mustafa Kemal Atatürk, the founder of the republic and Turkey’s first president. Images and statues of Atatürk are ubiquitous throughout Turkey. Carolina students snapped photos of Atatürk posters plastered on café walls. Huge pictures of him hang high above airport check-in counters. And his mausoleum in Ankara looms large on the landscape. Many Turks hold Atatürk in extremely high regard, Yekta says. And his ideology, Kemalism—rooted in strong Turkish nationalism—is something of a dogma among his most devout followers. But as with all ideologies, she says, Kemalism can be interpreted in different ways. An extreme, even inhumane version fueled the 1980 coup. Yekta and Cangüzel agree that Atatürk was a great thinker and strategist who gave women the right to vote and focused on industrialization and education. But some Turks have used his name to stoke political division instead of to encourage unity. The 1970s were incredibly divisive times, Cangüzel told her daughter. Anyone could be dubbed an enemy not only for what they said or wrote, but for their appearance. “For men, a mustache kept a certain way determined whether you leaned right or left,” Cangüzel says. “For women, there were ways of wearing parkas in winter. Sometimes the colors you wore, the way you combed your hair, what newspapers you read—such things divided people and families terribly.” After the coup, 650,000 people were arrested and nearly 1.7 million were put under investigation. Thousands lost their jobs and their citizenship. Fifty people were executed, and hundreds more were tortured to death. Some of these people desired violent revolution. The vast majority, Yekta found, did not. Her grandfather, for instance, was a moderate who one week prior to his arrest had brought together twenty European nations to take a joint stance against international terrorism. In a speech just before the coup, he said: “This republic was established on a multiethnic, multicultural, multireligious, and multilingual society. And no matter how hard we try to establish a nation-state of a single group, this

plurality is our heritage and our richness. Turk, Kurd, Laz, Greek, Armenian, Sunni, Alevi—we all come from the same heritage. Violence is no solution to our problems.” How was such a man a threat to the state? Yekta says that General Kenan Evren, who led the 1980 coup, thought that Turkey’s problems arose from the lack of a single ideology that everyone believed in. But Evren’s interpretation of Kemalism, Yekta argues, was not like the version borne of Atatürk’s rule. “In the 1930s, Kemalism was more open to freedom of speech and thought than it is now,” she says. When her grandfather spoke of Turkish unity and pluralism, the army thought he was a threat to the one true ideology. Güner’s case, along with thousands of others, went to trial. Cangüzel told Yekta that her grandmother and two family friends took her grandfather’s speeches and contrasted them—line by line—with what the prosecutor accused him of. His lawyer used these facts for the defense. Güner was found not guilty of treason and released from prison on November 26, 1981. But he was not the same man, Cangüzel says. And the family never recovered. Her parents divorced, and Cangüzel cannot speak of the coup’s aftermath without great sadness. When Yekta was in Ankara in 2008, news

broke that Turkey’s moderate government had uncovered a plot to overthrow the state. According to seized documents, a shadowy nationalist group called Ergenekon planned to create a groundswell of popular protest through rallies, followed by bombings and assassinations, culminating in an economic crisis and armed coup. Then, a right-wing secular dictatorship would be installed. All this because the new president wants Turkey to join the European Union and his party lifted the ban on headscarves, which some people consider too Islamic. Two years ago, Turkey changed a law so that the people—not Parliament—vote directly for presidential candidates. This, Cangüzel and Yekta think, should help stop coup attempts. “Hopefully nothing like the 1980 coup will happen again,” Yekta says, “and democracy will truly be respected from now on.” e Yekta Zülfikar, a sophomore majoring in international studies, received an Undergraduate International Studies Fellowship from the Sonja Haynes Stone Center to take part in the Burch Field Seminar in Turkey. Her research has inspired her to pursue a profession in diplomacy. Cangüzel Zülfikar, an expert in Turkish and Ottoman history, is the associate director for the Carolina Center for the Study of the Middle East and Muslim Civilizations. She also teaches Turkish at UNC as part of the Languages Across the Curriculum program in the Center for European Studies.

The mausoleum for Mustafa Kemal Atatürk in Ankara. The name Atatürk means father of the Turks, and his influence has not diminished since his death in 1938. This photo was taken by David Gilmore, who spent seven weeks in Turkey as part of a UNC Burch Field Seminar.

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in print

Art Benavie has been a macroeconomic theorist for thirty-five years. What he’s learned about the economics of the drug war, he says, blows him away. Photo by Jason Smith.

The War on Drugs: a losing proposition? Drugs: America’s Holy War. By Arthur Benavie. Routledge, 178 pages, $29.95. IN 1992, A YOUNG MAN NAMED FLACO was running a small operation on the corner of 110th Street and Lexington in East Harlem that was bringing in six million dollars a year. Flaco ran his business—selling heroin—like a military machine. Several layers of captains, lieutenants, sergeants, and street-level pushers separated him from his product and cushioned him from the police. But then narcotics agents pounced on one of Flaco’s sergeants. Desperate to avoid jail, the man spilled every name and address he could think of. After another six months of heavy surveillance, undercover buys, the full attention of twenty narcotics agents, and the cooperation 46 endeavors

of two federal agencies, the police finally had a case against Flaco’s army. They arrested fourteen members, including Flaco, and charged them all with federal conspiracy. Many will spend the rest of their lives in prison. It was the most successful operation that the narcotics unit had ever conducted. Almost immediately, though, the heroin started flowing again and a turf war broke out over the vacancy on the corner. The police had already blown their budget; there was little they could do but watch. What’s more, the investigation hadn’t come close to nabbing the real kingpin of 110th Street, a middle-aged Puerto Rican man named Macho. Police failed to stop the drug flow, says economist Art Benavie, but they succeeded in bringing about a wave of violence.

Benavie’s been a macroeconomic theorist for thirty-five years, and spent the last four researching the war on drugs. After combing through research and reading everything he could about illicit drugs, he says that besides being a huge fiscal drain, the drug war is also a major cause of homicides, property crimes, HIV transmission, drug poisonings, and overdoses. “What I learned blew me away,” he says. That intersection in New York City is a microcosm of America’s drug war, Benavie says. And it’s a losing battle “because of the straight economics of it. You’re running up against the law of supply and demand, which even the most powerful government on the planet cannot repeal.”

hen there’s a consumer demand for any product whose legal market has shut down, the black market throws open its doors. “And the motivation to sell on the black market is enormous,” Benavie says, “because the profit margin is enormous.” For example, a kilogram of heroin in Afghanistan or Pakistan—where the opium poppies that are made into morphine and heroin grow— can go for $300; by the time it arrives on U.S. streets, it’s worth $300,000. “That’s a tax-free mark-up,” he says. “How can any law enforcement stand up to that?” The goal of drug-law enforcement is to reduce the amount of illicit drugs on the street, thereby inflating the prices enough to make them unaffordable for consumers. But even after we’ve spent about forty-four billion dollars a year on the war, drug supply and use in the United States haven’t gone down. And the street prices of cocaine and heroin have been dropping since 1980. “But if the prices do go up, it’s very dangerous,” Benavie says. “Because then property crimes and murder rates go up, because people have to commit crimes to get these drugs. And here’s the worst part of it: if the price really goes up, it’ll motivate labs to make synthetic drugs such as fentanyl, which can be a hundred times more powerful. If it went up too far, we could have a lethal drug out there that’s much worse even than contaminated heroin.” The numbers really add up in Benavie’s book, Drugs: America’s Holy War. His statistics, anecdotes, and hard facts are almost overwhelming. The same push-down-pop-up model of supply and demand makes it especially dif-

ficult for police to weed out a specific drug, Benavie says. If one substance becomes scarce, users substitute another—usually more potent—drug. In the 1990s, when the government cracked down on imported marijuana in southern Florida, the price of marijuana rose and drug lords switched their stock to cocaine and heroin, which are far easier to smuggle; the harder drugs were suddenly cheaper and more abundant, and sales skyrocketed. (This crackdown also boosted domestic marijuana-growing, and the United States is now one of the world’s leading producers.) The same thing happened during Prohibition, when alcohol was made illegal—beer and wine virtually disappeared while whisky and gin became ubiquitous. And studies have shown that when Prohibition ended, the rates of alcohol consumption stayed close to the same. Violent-crime rates, though, plummeted, and the likes of Al Capone and his cronies were out of a job. The only way to really win the war on drugs, Benavie says, is for the U.S. government to wrest control of the trade from the black market, just as it did with alcohol in the 1930s. Benavie doesn’t advocate drug use. But the war on drugs, he says, amounts to a very expensive crusade. Warehousing half

tion by black market suppliers and diseases spread by infected needles. More than a third of AIDS patients in the United States contracted the disease by using infected needles to inject drugs, and many drug offenders contract and spread diseases once they’re in prison, where drugs and unprotected sex are the norm. Because there’s no FDA approval for black-market products, there’s no way to tell how potent a drug is or with what it’s been mixed. Heroin manufacturers stretch their supplies by mixing in anything from lactose to baby laxatives to strychnine. And any black-market drug, including marijuana, can be contaminated with toxic byproducts, bacteria, or viruses that could transmit hepatitis, tetanus, and malaria. Many Americans fear that legalization would lead to an out-of-control increase in the use of hard drugs. It’s possible, Benavie says. But studies in other countries have shown that legalizing drugs doesn’t usually increase drug use, he says, and even when there is an increase, it is brief and temporary. If the United States could tax illicit drugs at the same rate it taxes for alcohol and tobacco, Benavie says, the government could save that $44 billion a year in fighting the war and it could generate an additional $33

Even after we’ve spent about $44 billion a year, drug supply and use in the United States have not gone down.

a million drug offenders who have mandatory minimum sentences puts a real strain on prisons. The average sentence for a nonviolent drug felony is seventy-five months; the average for a violent felony is fifty-six months. Because drug offenders must serve mandatory minimum sentences, wardens routinely grant early releases to violent offenders in order to make room for droves of drug offenders, most of whom are nonviolent. The war against drugs should actually be a war for public health, Benavie says. Most drug-related deaths are due to contamina-

billion a year. “Take the $77 billion—think what we could do with that money,” he says. “For example, we spend $37 billion a year on food stamps; it would cover that. We’ve been spending $29 billion on the National Institutes of Health, $6 billion on the National Science Foundation. Add those together, and we still have a few billion dollars left over. That’s what that money could mean.” —Margarite Nathe Arthur Benavie is a professor emeritus of economics in the College of Arts and Sciences and continues to teach at Carolina. endeavors 47

Papa, with and without women Reading Hemingway’s Men Without Women: Glossary and Commentary. By Joseph M. Flora. The Kent State University Press, 189 pages, $24.95.

en Without Women.” What a quintessentially Hemingway title. What’s next, “Fighting Bulls and Fishing at the Muscle Man Lodge”? But if you love reading short stories, then you can really only ignore the man for so long. I was once a member of what Joe Flora says is the Dumb Ox school of thought—the idea that Hemingway was just a big galoot who was too macho for his own good, and a ham-handed writer to boot. But reading Men Without Women, Hemingway’s second major collection of short stories, changed that. “Hemingway never went to college, and he was a very young man when he wrote these stories,” Flora says. “But he knew a heck of a lot—so much more than he had any right to know.” How to treat a hand shriveled on the front lines of a war, for instance; the precise grip you should maintain on your lance to hold off an angry bull and keep it from skewering your horse; the distinct sound of silkworms chewing. But he also wrote about what matters to all of us—disease, war, death, love.

Ernest Hemingway and one of his cats at Finca Vigía (“Lookout Farm”), his home in Cuba for twenty years. Photographer unknown. Courtesy of the John F. Kennedy Library and Museum, Boston.

lora—a smiling, genteel, scholarly man, over whose desk hangs the biggest deer skull I’ve ever seen—read his first Hemingway story in college. Since then, he’s slowly tracked the man and his legend across the world, starting with Lake Walloon in Michigan’s wild Great North, and from there to Key West, where the descendents of Hemingway’s six-toed cats still slink around his old house by the dozen. Eventually, Flora went all the way to Paris. He and his wife rented a car there, drove the route from The Sun Also Rises to Pamplona and Madrid, and, of course, bought tickets to a bullfight. “You see what Hemingway can do to you?” he says. Five years ago Flora began working on Reading Hemingway’s Men Without Women: Glossary and Commentary. This is the best kind of guide for the obsessed reader—it stalks every line of every story, details the real-life history of each scene and event, and goes deep into the symbolism that Hemingway couldn’t resist (what did those silkworms mean, anyway?). I’ve taken to keeping Flora’s book next to me when I open my copy of Men Without Women. When I ask Flora about the book’s title, he shakes his head. “Hemingway never was one,” he says. “He never divorced a wife until the next one was lined up. He grew up surrounded by women. And then we get a book called Men Without Women. This is a man who couldn’t do without women!” —Margarite Nathe Joseph Flora is interim director of Carolina’s Center for the Study of the American South and a professor of English in the College of Arts and Sciences. Left: Ernest Hemingway in Paris, March 1928, a year after he’d published Men Without Women. “Hemingway people tend to be very passionate,” Joe Flora says— and he fits right in. “I study him because his stories get me. When you read these stories, you are there.” Photograph by Helen Pierce Breaker. Courtesy of the John F. Kennedy Library and Museum, Boston.

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endview I

n 1921, the fruit fly Drosophila melanogaster was becoming the lab animal of choice for scientists studying heredity. Geneticist Alfred Sturtevant decided to write a comprehensive review of North American species of Drosophila. He included just about everything a scientist from that era could observe about the little flies. Descriptions of the mating rituals of nineteen different species. The relative lengths of the joints of their legs. What he had successfully fed Drosophila immigrans (banana, pineapple, apple, tomato, sour boiled potato, bran mash, and graham-flour paste). These drawings by Edith M. Wallace were some of the earliest detailed color images of Drosophila to circulate among scientists. For scientists hunting mutations that could help them map a chromosome or discover how genes influence each other, the tiniest variations in a flyâ&#x20AC;&#x2122;s appearance could be important scientific clues. This image is from The North American Species of Drosophila by Alfred H. Sturtevant, with drawings by Edith M. Wallace. It was published in 1921 by the Carnegie Institution of Washington (now the Carnegie Institution for Science). A copy of the book can be found in UNC-Chapel Hillâ&#x20AC;&#x2122;s Biology/Chemistry Library.

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endeavors

Page 22: Three and a half years after the Asian

Page 14: Fruit flies like this one may hover

Page 28: Carolina undergrad Zena Cardman,

Tsunami, Carolina photojournalism students visited Thailand to document the lives and culture of the people there. Photo by Selket Guzman.

around your overripe bananas and drive you crazy, but in the lab theyâ&#x20AC;&#x2122;re indispensable. Photo by Jan Polabinski.

an aspiring astrobiologist, traveled to the Arctic to help figure out how life originated in our solar system. Photo by Zena Cardman.

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