Fall 2008

end­­eavors Fall 2008

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

Stricken with lung cancer, Tomma Hargraves took a chance on a clinical trial.

Two years later, she’s glad she did. page 4

On page 12 of this issue, you will find a story about Professor Gary Bishop

Above: Volume I, Number 1, Winter 1984.

The third-generation Pixel Planes chip on the cover was built for drawing images on computer displays as fast as possible.

Today, specialized graphics chips are on virtually every personal computer. “But at the time of the Pixel Planes chip, hardly any PCs had specialized graphics processing units,” says Henry Fuchs (seated above right). “Our team, and the few others who were working in that area, would regularly get skeptical questions about why we were pursuing that line of research. Now the graphics processing units in PCs are often larger, more powerful, and more expensive than the CPUs next to them—a more powerful tail wagging the less-powerful dog.”

and his students, who are inventing technologies to help children with visual impairment learn to use their bodies as well as their minds. On page 4 of the Winter 1984 issue, you will find (if you never throw anything out) a photo of a gravely serious Gary Bishop, then a doctoral student in computer science, examining an electronic position sensor he’d helped to invent.

We didn’t plan this nice bit of symmetry, but it’s a fitting reminder that over the last twenty-five years thousands of young men and women have begun their careers on this campus, working with their faculty mentors, advancing their science and scholarship, until they were ready to guide their own protégés, here and around the world.

With this issue, Endeavors begins its twenty-fifth year. If you would like to send us something silver, fine, but we would be just as pleased to hear from anyone who recalls a favorite story from one of those twenty-five years’ worth of issues. The way we see it, good stories are better than silver; they’re gold.

A quarter of a century ago, G. Philip Manire, vice chancellor and dean of the graduate school, stern and imposing in his own black-and-white photo on the inside front cover, wrote in the inaugural issue that “the story of research and graduate education is not an easy one to tell” and that our scholars “are often better known in Berkeley or Oxford or Kyoto than they are in their own community.” We have been trying to change that. I hope we’ve made some headway.

Each time we plan the next edition, we remind ourselves that a magazine is only as good as its stories, and that our job is to tell as many good ones as we can. But the most reliable way to judge a magazine is by the quality of its readers, and we have some of the best. On this anniversary, that will be our one and only brag. Thank you for reading. And please stay with us for another twentyfive. We’re going for the gold.

—The Editor

end­­eavors Fall 2008 • Volume XXV, Number 1 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

Fall 2008

2 overview

32 Where will Conflict Strike Next?

cover story 4 Every Breath She Takes

34 megaChina

Radiation on the job, an Oscar for inventors, and school spending.

Behind every medical breakthrough, from Tylenol to Tarceva, stands a long line of volunteers. In a clinical trial, researchers put science to the test.

by Mark Derewicz

features 12 Fair Games

What good is a video game to a child who can’t see?

by Susan Hardy

15 Global Exposure

Some Carolina travelers take their best shot.

18 Return of the Fatal Cough

TB has been around for thousands of years. We thought we had it cornered; now it’s fighting back.

by Beth Mole and Margarite Nathe

24 Portrait in Jazz

Composer Stephen Anderson looks for the spark.

by Kelly Rae Chi

26 A Garden Speaks

Using science and math to predict the next trouble spot.

by Meagen Voss

Enormous gains and growing pains.

by Sheila Read

38 Slime and the City

Algae blooms choke China’s third largest lake.

by Mark Derewicz

40 Lingering Risks

What happens when women stop hormone therapy?

by Prashant Nair

42 The X-Philes

Taking philosophy to the streets.

by Mark Derewicz

47 in print

Beyond Baldwin’s fire, your sweetheart job, and asking why we suffer.

49 endview At a Congolese clinic.

Norris Brock Johnson hears a story quiet as stone.

by Margarite Nathe

Editor: Neil Caudle, Associate Vice Chancellor, Research and Economic Development Associate Editor: Jason Smith Writers: Kelly Rae Chi, Mark Derewicz, Susan Hardy, Beth Mole, Prashant Nair, Margarite Nathe, Sheila Read, and Meagen Voss

On the cover: UNC patient Tomma Hargraves volunteered for two clinical trials—one to beat cancer, and one to keep it from coming back.

Photo by Jason Smith.

Design: Neil Caudle and Jason Smith Print production and web site: Jason Smith

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

©2008 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 COURTESY OF THE U.S. DEPARTMENT OF ENERGY

Construction began at the Savannah River Site in July 1950. Before long a construction force numbering more than 38,000 was at work.

During the early 1950s SRS began to produce materials used in nuclear weapons. Workers with long-term exposure to radiation there had higher-than-expected rates of leukemia.

The risks of radiation

E

ach time you’re X-rayed or get a CT scan, you’re exposed to radiation. How does the government decide what level of radiation is safe? For many decades the United States has relied on data from the Japanese survivors of atomic bombs to set the safety standards for radiation exposure.

Steve Wing contends that a better source of information exists: the data on death rates and cancer incidence among workers at nuclear facilities. Wing says that his work and that of other researchers suggests that long-term exposure to low levels of radiation is more dangerous than we thought.

For twenty-five years UNC researchers have tracked the effects of radiation on nuclear workers. In a study of nearly 19,000 workers hired between 1950 and 1986, Wing and his coauthor David Richardson found that workers at South Carolina’s Savannah 2 endeavors

River Site had higher-than-expected rates of leukemia.

More importantly, they found an increase in the rate of deaths from leukemia as the radiation doses to which workers were exposed increased. On average, for every additional 130 millisieverts (mSv) of radiation exposure in their jobs, workers’ death rates from leukemia (other than chronic lymphocytic leukemia) doubled. Researchers knew the levels of radiation that workers had been exposed to because the workers’ employer required them to wear badge dosimeters that measured radiation.

By comparison, the typical patient undergoing a CT diagnostic study receives two to three CT scans, resulting in a radiation dose between 30 and 90 mSv, according to an article in the New England Journal of Medicine. A chest X-ray exposes a patient to

0.1 mSv of radiation, according to the U.S. Food and Drug Administration.

Despite the increase in leukemia deaths associated with increased exposure to radiation, the overall risk remains small.

The results are consistent with a growing body of evidence that studies of A-bomb survivors understate the risk of radiation, Wing says. He believes the U.S. government should consider lowering the maximum limit it has set for yearly exposure to radiation, based on the long-term effects on nuclear workers. ­—Sheila Read Sheila Read is a master’s student in journalism at Carolina.

Steve Wing is an associate professor of epidemiology in the School of Public Health. David Richardson is an assistant professor of epidemiology in the School of Public Health.

Y

ou can do all the innovating you want in the laboratory,” says Joseph DeSimone, “but if you can’t get it outside of the university walls you do no one any good.”

For eighteen years, ever since joining Carolina’s chemistry department as a twenty-five-year-old assistant professor, DeSimone’s driving goal has been to get his inventions in green manufacturing and medicine out of his lab and into the world.

He has more than 115 patents and 70 more pending. He founded two companies and licensed his innovations to leading manufacturers. For all this he was awarded the 2008 Lemelson-MIT prize, a $500,000 award that has been dubbed “the Oscar for inventors.”

The prize recognizes scientists who turn their ideas into inventions and innovations that change the world we live in and improve life for all of us.

DeSimone has a long list of innovations, from a polymer-based stent to a better way to make Teflon. But his newest invention might have the greatest impact of all.

The PRINT technology, or Particle Replication in Non-wetting Templates, can create nanoparticles that carry medicine to specific parts of the body. For instance, nanocarriers

Spending and tests

D

uring election season education policy is a hot topic for politicians. This year Gary Henry hopes a study he led will help voters assess whether candidates’ education plans are backed by hard evidence.

In a study commissioned by Governor Mike Easley, Henry and his colleagues examined the finances of 347 public high schools

NEIL CAUDLE

can be designed to take medicine directly to a tumor to attack cancer cells without harming healthy cells. The technology may lead to better treatments for cystic fibrosis, lung cancer, diabetes, and muscular sclerosis. It could also aid the development of vaccines.

“It just opens up all these different approaches for disease treatment because we can control the size, shape, and chemistry of these particles in a very effective and sort of systems-engineering manner,” DeSimone says.

Before PRINT, DeSimone’s most notable invention was an environmentally friendly manufacturing process that relies on supercritical carbon dioxide (CO2) instead of water and detergent to make high-performance plastics such as Teflon. The current detergent used to make Teflon in water is a persistent organic pollutant and has been banned by the United States Environmental Protection Agency.

Many plastics manufacturing processes use water, and it takes an immense amount of energy to dry the plastics. DeSimone’s manufacturing process uses 20 percent less energy than standard practice and reuses CO2 while creating the same Teflon and other fluoropolymers that are used in wire and cable jackets and insulation, flexible

in North Carolina. The study’s goal was to determine how spending affected student scores on statewide achievement tests and to investigate whether schools were using state funds effectively. Spending was divided into different categories, then correlated with student test scores from the past two years.

Among the main categories were regular instruction spending, supplemental instruction spending, and administrative spending.

Regular instruction covers expenses for typical classroom instruction while supplemental spending includes expenses for extra programs such as tutoring, summer school, and other student services.

According to Henry, the most important finding was that more money spent on regular classroom instruction resulted in better student performance. When the researchers controlled for factors such as the students’ race and socioeconomic status, there was still a positive connection between spending on regular instruction and test scores.

DAN SEARS

Beyond the walls

Joseph DeSimone with a roll of thin film based on his inventions.

tubing, and industrial films. DuPont licensed DeSimone’s breakthrough process and has built commercial plants based on the technology, leading to unique products and more environmentally sustainable manufacturing, says Nandan Rao, Global Technology Director of DuPont Fluoroproducts.

“His ideas,” Rao says, “are truly revolutionary and represent dramatic departures from what others have pursued.” ­—Mark Derewicz Joseph DeSimone is the Chancellor’s Eminent Professor of Chemistry at UNC and the William R. Kenan, Jr. Professor of Chemical Engineering at NC State.

Henry believes the primary reason for this finding is that teachers’ salaries are part of regular instruction spending. Higher spending helps “encourage experienced teachers to stay in the classroom and may motivate teachers to expend greater effort on instruction,” he says.

Henry hopes that his study will help change how North Carolina’s education funds are allocated. “This study provides strong justification for spending more on education and for targeting the funds for regular instruction,” he says. “Comparing campaign promises with the study findings can help voters decide which candidate will do more to raise educational achievement.”

—Meagen Voss Meagen Voss is a doctoral student in neuroscience in the School of Medicine.

Gary Henry is William Neil Reynolds Distinguished Visiting Professor in the School of Education. endeavors 3

Every breath she takes People have all kinds of reasons for joining clinical trials. Tomma Hargraves had just one: a hope for life.

by Mark Derewicz

T

omma Hargraves rubbed her sore neck and felt a hard knot. Her family doctor said

it was probably nothing serious, but to be safe he ordered a biopsy. The knot was a malignant lymph node.

Hargraves had lung cancer—stage 3b non-small cell carcinoma.

Her husband Bob searched the internet and found out that many stage 3b lung cancer patients who get standard care—chemotherapy, sometimes radionline told of even worse prognoses.

“My husband thought that I was as good as dead,” Hargraves says.

4 endeavors

COKE WHITWORTH

ation—die after one year. Some stories

Their son Josh, an emergency-room doctor, told his mom to get three opinions.

The first doctor said there was little he could do other than give her chemotherapy every three weeks.

“No radiation?” she asked. “No surgery?”

Not for someone in her situation.

The second doctor offered Hargraves a clinical trial that included chemotherapy and radiation.

For her third opinion, Hargraves went to Mark Socinski at UNC. His clinical trial was very different, an aggressive nine-month protocol that had never been tried before.

Hargraves started that trial in December 2006, two months after her diagnosis.

Socinski gave Hargraves one heavy dose of standard chemotherapy, then another three weeks later. Her hair fell out; she lost weight. But the tumors shrank, a sign Socinski knew had boded well for previous patients in his trial.

Hargraves rested for two weeks before starting a seven-week regimen of chemo every Monday and radiation every weekday.

The radiation doses were 12 percent higher than in standard care. At the same time, she took a new drug called Tarceva to keep microscopic cancer cells from spreading throughout her body.

In May 2007 the tumors were gone. Socinski found no cancer cells in Hargraves. But the trial wasn’t over. For the next eighteen weeks she took Tarceva and Avastin, another new drug designed to keep tumors from reforming.

Fourteen months later Hargraves was still cancer-free. She celebrated her sixtieth birthday in July.

“Doctors don’t like to use the word ‘cure’ when it comes to cancer,” she says, “so they say I’m acting like a cured patient. That’s good enough for me. I might be wrong, but I truly believe that had I not been in that trial I wouldn’t be here today.”

Stories such as Tomma Hargraves’ are why doctors do research—to help their patients live full lives for as long as possible while testing drugs and regimens that might help other people those patients will never meet.

But getting results takes more than hope and intellectual curiosity.

Just gaining approval to do a clinical trial is a tedious process. Research studies take time, sometimes the better part of a decade.

Late-stage trials that aim to change clinical

practices can be double-blind: patients don’t know if they’re receiving new treatment, standard care, or a placebo—and doctors don’t know either. Recruitment for these studies can be difficult because some patients don’t want to participate if they won’t know which treatment they’re getting.

Some people refuse to join research studies for fear of being guinea pigs. Others don’t live near hospitals that conduct clinical trials, which makes it difficult to participate in research and try the new therapies they may desperately need.

“I live very close to three very good hospitals,” Hargraves says. “I know there are a lot of people in rural areas who don’t want to make that trip.”

Why UNC? Hargraves is right; she’s fortunate to live in the Triangle. According to Shelly Earp, director of UNC’s Lineberger Comprehensive Cancer Center, about 3 percent of cancer patients in the United States are part of clinical trials. That number jumps to 18 percent at UNC and other academic centers that are trying to improve upon standard treatments that just aren’t good enough.

Not all patients fare as well as Hargraves— stage 3 lung cancer is extremely tough to beat, and some of Socinski’s trial patients died. But as Earp says, “We don’t do trials for diseases that are perfectly curable.”

Earp says that of all the issues involved in clinical trials, the one thing he wishes more people knew is that research participants receive special care. Several physician researchers and research nurses, in addition to regular clinical staff, look out for the patients. In fact, each patient is assigned a nurse coordinator who’s on call twenty-four hours a day, seven days a week.

While taking Avastin, Hargraves had a severe nosebleed that scared her so much that she contacted her nurse coordinator Maureen Tynan, who told Hargraves how to stop the bleeding and reassured her that a profuse nosebleed is a common side effect.

Tarceva can cause terrible skin irritations—dandruff of the body, as Hargraves calls it. Tynan put Hargraves in contact with a dermatologist who is familiar with Tarceva. Tynan was the one who set up all of Hargraves’s appointments, reminded her when her next consultations were, and made sure she reported every detail that the trial protocol demanded.

“The care that clinical trial patients receive is at least as good as, and often better than, the care regular patients get,” Earp says.

UNC sends information about available clinical trials to physicians around the state and encourages them to consider conducting trials at their clinics.

“We’re developing access to clinical trials for Rex patients and will soon have a joint program with East Carolina’s cancer center,” Earp says. “There are certain kinds of trials that you can only do under close monitoring at an academic center.”

Right now, even if doctors outside of a trial know about a promising new therapy, those doctors must follow the guidelines for standard of care. If they don’t, they could leave themselves open to malpractice lawsuits. And insurance companies often don’t pay for therapies outside the realm of standard care.

COKE WHITWORTH

“Doctors don’t like to use the word cure when it comes to cancer,” Hargraves says, “so they say I’m acting like a cured patient.

That’s good enough for me.” endeavors 5

COKE WHITWORTH

Don Yarborough insisted on being part of the liver-cancer trial. If the treatment didn’t help him, he said, maybe the research would help someone else.

6 endeavors

For the more aggressive trials, such as Socinski’s, an experienced staff should monitor all aspects of the protocol because toxic side effects have to be managed by people who have seen them before.

Don Yarborough weighed 250 pounds and stood 6-foot-5 when he came to UNC for a liver-cancer trial. His body rejected the first chemo treatment.

“I just broke out like a big fat strawberry,” says the sixty-two-year-old Vietnam War veteran. “I got humongous welts all over my body and I turned red in the face and ears.”

Bert O’Neil, Yarborough’s doctor at UNC, cut off the chemo immediately and didn’t think he’d restart it. But Yarborough insisted on being part of the trial. If the treatment didn’t help him, he said, maybe the research would help someone else.

“Well,” O’Neil told him, “it’s going to change your quality of life.”

“But it really hasn’t changed my quality of life,” Yarborough now says. “I’ve been so blessed.”

Yarborough has been part of O’Neil’s liver-cancer trial since September 2007, about four months after routine blood work revealed something wrong with his liver.

Duke oncologist Carlos Marroquin performed laparoscopic surgery, but the tumor had invaded the portal veins that feed blood to the liver. Marroquin told Yarborough that he probably had two months to live. But Marroquin also told him about Bert O’Neil’s clinical trial.

When Yarborough broke out with that rash but demanded to continue, O’Neil admitted him to UNC Hospitals so that nurses could slow-drip the chemo into his bloodstream overnight. It worked. Over the next few weeks Yarborough’s reaction diminished, thanks in part to an antihistamine. He now absorbs that same chemo in one hour, which makes his weekly trip from Wilmington, North Carolina that much easier.

Every Friday Yarborough’s brother Charlie picks up four dozen Krispy Kreme doughnuts for the clinic crowd before swinging by Don’s house at 4:30 a.m. to be at UNC by 7 o’clock. “Charlie and I, we’re both a couple of idiots,” Yarborough says. “We cut the fool all the time and we just keep ‘em rolling up there. But I’m going to tell you something: Doctor O’Neil’s group and those nurses are as fine a bunch of people as you will ever meet in your life.”

Yarborough takes three different kinds of chemo every third Friday and two kinds on the other Fridays. Two out of three weeks, he takes chemo pills every day. The therapy caused him no side effects for six months until, in April, he lost his appetite, started having digestive problems, and began feeling numbness in his fingertips and toes. Ten months after Yarborough started the trial, he had lost fifty pounds. If he loses any more weight, doctors might stop the treatments.

He can’t work his carpentry job because he can’t bend over without pain; fluid surrounds his stomach due to his damaged liver.

But each MRI has shown that his tumor has either shrunk or stayed the same.

No one knows how much time he has left.

No one knows if this clinical trial will give future liver-cancer patients another treatment option. But Yarborough has already lived eight months longer than anyone thought he would. And he says he still feels good.

“What I’m hoping for is that, with so much chemo, the tumor will say ‘enough is enough’ and start shrinking again,” Yarborough says, smiling. “This could go on for a while until it either kills me or heals me.”

The paper trail O’Neil’s clinical trial is one of thirteen his unit is now running on gastrointestinal malignancies. At Lineberger there are more than one hundred studies under way that range from basic biological research on tumor samples to aggressive, complex clinical trials, some of which involve researchers and patients from across the country.

O’Neil was under no illusion that his study would uncover some sort of cure; he hypothesized that combination therapy would prolong patients’ lives. It has taken O’Neil years to turn that idea into preliminary research data. The process hasn’t been easy. (For the steps in a typical study, see “The Life of a Clinical Trial,” page 11.)

“For those of us who are honest people interested in patients and don’t have any agenda other than wanting to advance science, the regulation for clinical trials is immense and immensely burdensome,” O’Neil says.

But the reasons for such strict guidelines, he says, are that around the world some researchers have overstepped the bounds of protocol, and some studies have gone terribly awry.

In 2006 a British pharmaceutical company was testing a new anti-inflammatory drug when several healthy participants suffered massive organ failure. The United Kingdom’s drug regulatory agency determined that researchers failed to follow protocol in several ways, but that such negligence did not lead to the unexpected biological reactions. BBC News, though, quoted experts who said the reactions should have been expected because the potential effects of the drug had been listed in scientific literature.

The study in Great Britain was a Phase I trial, meaning that the drug had been tested only on animals. UNC conducts Phase I as well as later-stage trials, but no matter the risk level, every trial must follow the same guidelines and procedures, starting with the search for funding.

Earp says that over the past decade the National Institutes of Health (NIH) has granted more money for clinical trials. The National Cancer Institute funds some of Lineberger’s trials through a core grant supporting the protocol office that processes every cancer trial at UNC. “However,” Earp says, “the largest single source of support comes from private donations to the center from donors who want to see scientific innovation turned into new therapies.”

A third major funding source is industry.

For example, a pharmaceutical company funds Socinski’s trial. As Earp says, the best place to test new therapies is an academic center that’s searching for good treatments and solid data.

But drafting the contract between UNC and a drug company can be a drawn-out process, says Barbara Longmire, director of UNC’s Office of Clinical Trials. And negotiations can add to the already lengthy approval process.

“We’re constantly trying to educate our faculty to know what a trial will cost because if they end up spending more time on the research than expected, somebody here is going to cover that cost,” she says. “That’s not to say that we can’t take a study that’s going to be a financial loss, but we need to know that going into it.”

After the funding agency approves a cancer-trial protocol, it’s sent to Lineberger’s protocol review committee, a group of two dozen experts who make sure each trial at Lineberger asks good scientific questions and uses sound scientific methods. From there the protocol might be sent to the General Clinical Research Center, a UNC group that assists faculty in many ways (though not all researchers at Carolina use the center).

He takes chemo pills every day for two weeks, then has a one-week break.

Each MRI has shown that his tumor has shrunk or stayed the same.

COKE WHITWORTH

endeavors 7

UNC’s Institutional Review Board has its say to ensure the rights and welfare of all participants. The protocol then goes back to the funding agency for re-approval.

All this can take longer than a year, which is why some drug companies and private research firms conduct their trials overseas, where researchers may have to follow FDA guidelines but can still save time and money.

“Depending on the research site, a researcher may not have the same level of bureaucracy and approvals that are required for trials stateside,” Longmire says. “Startup is often a lot faster at foreign sites. And depending on where researchers go, and the disease area being studied, there could be a much larger ready population that’s willing to participate in clinical trials.”

But Longmire says that university-based trials are still the gold standard because academic centers have “highly trained clinicians who know how to do research, and do it well, while supporting the university’s larger mission.”

The School of Public Health is trying to speed up the entire clinical trial process at Carolina with its Center for Innovative Clinical Trials, which brings together dozens of UNC researchers to figure out how to get trial approval more quickly and turn research

findings into clinical practice faster. And in June 2008, UNC received a $61-million grant to become part of NIH’s Clinical and Translational Science Award consortium.

Part of the grant will help researchers reduce the time it takes to turn their discoveries into treatments for patients.

Clinician versus researcher When O’Neil talked to Yarborough about his odds for survival on regular treatment, Yarborough asked to join the clinical trial.

Often the decision to volunteer is much tougher, and the doctor has to walk a fine line between the roles of clinician and researcher.

Joe Eron, who studies new HIV/AIDS therapies, sees hundreds of patients at UNC’s HIV clinic.

“When I talk to patients about a clinical trial,” Eron says, “the very first thing I tell them is, ‘No matter what I say in the next five minutes, and whatever you do or don’t want to do, I’m your doctor and I’ll be your doctor whether you want to do this trial or not. It doesn’t matter to me.’ I want them to feel free to say no because I’m in this powerful position and many patients have different levels of sophistication. And I really don’t want to hear, ‘Whatever you say, doc.’”

Eron says that some HIV/AIDS trials test a

combination of therapies that are considered the best drugs available. But right now Eron is running a trial to see if intensified therapy can drive the virus load below the point that doctors can measure. Standard tests can’t detect HIV below a certain amount of virus in the blood. But there’s an experimental test that can detect HIV down to one virus copy per milliliter of blood. Eron is using that test and a new drug called Raltegravir to see how low the virus load can be pushed.

“We would never offer this to a patient outside the clinical trial,” he says. “In this case, I have to really hear from patients that they completely understand that this experiment could have risk and no benefit. We enroll fewer patients in this kind of study.

We need fifty; we have forty-three. We’re getting close.”

He says that some patients, depending on their treatment histories, shouldn’t be enrolled in this kind of study even if they meet the trial’s general criteria. But patients often see ads for a trial and want to join, sometimes for the money. This, Eron says, gets tricky. The patient might really need that cash.

“I have to be careful,” he says. “They can’t do it solely for the money. I’ve been in situations where I’ve had to say, ‘The trial is not really good for you.’”

The Life of a Clinical Trial This timeline of calendar pages, covering four years of work days, represents the stages of a hypothetical clinical trial—in this case, a drug trial. Colors indicate different stages.

Original idea: 180 days

Researcher develops idea, consults colleagues, searches literature, talks to companies, seeks funding.

8 endeavors

Develop protocol: 95 days

Researcher writes a plan. What drug? Doses? Complications? The protocol covers everything that will happen in the study.

Legal, regulatory: 90 days

UNC negotiates contract with sponsor. Protocol Review Committee and Institutional Review Board review the protocol.

Enrollment: 260 days

Researchers recruit, enroll, and begin to treat patients in the study.

COKE WHITWORTH

Searching for answers Keith is in one trial that will continue until he dies, even if that’s of old age. Researchers will collect all the data from Keith’s many treatment regimens to see how he responded to various drugs during the course of his disease.

One of Eron’s more typical combination drug trials takes a few years to finish. Getting a novel drug through the three main phases of a trial—laboratory testing, animal testing, and human trials—and into clinical practice can take a decade or two.

Other kinds of research studies that don’t involve drug approval can take just as long, such as prospective studies that try to figure out causes and risk factors for diseases.

In the School of Dentistry, Bill Maixner heads up a seven-year Phase I study on temporomandibular joint disorder—TMJD—a chronic pain condition caused by inflammation where the upper jaw meets the lower jaw. Doctors aren’t sure what causes it.

Maixner’s $19-million grant includes three other universities—Florida, Maryland, and SUNY at Buffalo—all of which are recruiting eight hundred people each.

But the volunteers aren’t patients; they’re beginning the study as healthy controls.

Maixner predicts that about 3 percent will develop TMJD during the study, and the information gleaned from these people could help researchers figure out what causes the condition.

Maixner designed a battery of tests and questionnaires that measure pain sensitivity, anxiety, depression, and other potential risk factors. The tests take three hours. Then his team tracks participants for five years, asking them questions every three months about their mental and physical health. This information should give researchers enough data to pinpoint exactly what happens to those few who develop TMJD. Some participants are called back to the clinic for more testing. And each participant gives blood so researchers can look for genetic markers of risk factors.

ILLUSTRATION: NEIL CAUDLE

The flip side, Eron says, is when a research assistant knows that a patient is a prime candidate for a clinical trial, but the physician disagrees and doesn’t tell the patient about the trial. And that might be fine, Eron says, because the doctor might know the patient really well.

“Or it might be that the clinic is really busy and if a clinical trial coordinator is going to come in and talk to the patient for an hour, this will slow things down,” Eron says.

“I feel that the patient should participate in that decision, and I get worried that we sometimes assume we know what people want,” he says. “There’s a subset of patients who are extremely knowledgeable about HIV, and when you tell them there’s an opportunity to learn something that no one else knows about their disease, there’s a surprising amount of interest.”

Some patients actually do better during a clinical trial than they do afterward, even if the prescribed therapy is the same.

One patient we’ll call Keith was diagnosed with HIV in 1997. He’s been in ten drug trials at UNC and each time one ended he got worse.

“I’m much more diligent about taking my meds when I’m in drug studies,” Keith says.

“For one, someone’s buying the drugs for me so I feel obligated. Two, I don’t want to let them down. And three, they monitor me; I have accountability. When I’m not in a study, I’ll forget to take a pill here and there.”

Research study: 260 days Active research times vary, but often the study requires at least one year after the last patient is enrolled.

Follow-up

After the trial, researchers track the progress of patients, especially those with cancer or HIV/AIDS, sometimes for a year or longer.

endeavors 9

“If we can identify biological pathways that cause TMJD, then we can start to think of therapeutic targets,” Maixner says. “We can begin to think of new drugs or maybe even how to use drugs that are already on the shelf for other conditions.”

Researchers might also be able to find out why current TMJD treatments, such as behavioral therapy and antidepressant medication, help some people but not others.

Maixner’s team in Chapel Hill had no trouble finding volunteers for the study because the protocol is fairly benign, though volunteers are poked and prodded so that researchers can measure pain sensitivity.

Recruitment for other studies is much trickier. Clearly, not many healthy people are willing to volunteer to test the toxicity of a new drug, which is why such trials offer more compensation. But recruitment also isn’t easy for trials that test known drugs.

Researchers in Carolina’s psychiatry department are trying to figure out what happens in the brains of people with mental illnesses, especially when they take medications that have been on the market for years, such as lithium.

Recruiting is hard if patients think a drug is being “tested” on them.

Kelly Smedley is the program coordinator for several bipolar disorder studies. For one, her team needs to recruit ninety people with bipolar depression and another sixty for the control group. By July 2008, twentysix controls and sixteen bipolar depression patients had volunteered; seven others had dropped out.

“It’s very difficult getting people to do these medication studies,” Smedley says, “because many patients are concerned that it’s a study and that the medication is being tested on them.” Once enrolled, some patients couldn’t stick to the trial’s fairly rigorous protocol.

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Researchers use a standard three-hour psychological test to make sure all participants fit the research criteria. All bipolar patients who qualify get an MRI, which takes about two hours. Then they’re treated with lithium for four weeks before getting another brain scan. Those who respond to the lithium treatment continue to take it. Those who do not respond are given lithium and lamotrigine, which the FDA approved in 2003 for some bipolar depression patients. All patients get another MRI twelve weeks later, and all patients must go to ten 45-minute sessions at the clinic.

Beliza Powell, who has battled manic depression for years, didn’t mind the protocol despite having to drive to Chapel Hill from Sanford, North Carolina.

Last winter she fell into a deep depression.

She saw no hope and found no joy, not even in her grandkids. She says she contemplated suicide and knew that if she didn’t get help, she wouldn’t make it. Doctors in Sanford told her to go to UNC’s psychiatric emergency walk-in clinic, where she was told about the bipolar study. She agreed to join and started taking lithium.

“I began to feel better immediately,” says Powell, who finished the study but still takes lithium. “What I really liked about the program is that they educated me, talked to me through the whole thing. They helped me understand what the disorder is, why I was this way, and that I could live a normal life.

I’m still taking lithium and I feel normal.

I have my good days and bad days like everyone does. I have hopes and dreams.

I’m living.”

During the study, Powell experienced blurred vision, tiredness, heartburn, and hot flashes. Smedley says that some people dropped out of the trial due to side effects, especially lethargy, but Powell says her side effects subsided quickly.

One of her worst days was when she had a panic attack in the MRI machine.

“But I told myself I was being silly,” she says. “They gave me a movie to watch in there and then I was fine.”

Healthy controls also get MRIs at the beginning of the study. The first twenty people enrolled get a second MRI at week four and a third scan at week sixteen (see “My brain on magnets,” next page). The idea is to compare what’s going on in the brains of patients and controls because even though lithium and lamotrigine are common medi-

cations, scientists don’t really know how they work in the brain.

The trial is the first-ever controlled study to focus on the relevance of abnormalities in the frontal-limbic area of the brain and how that area responds to mood-stabilizing drugs over the course of several months.

From a recruitment standpoint, the protocol can be a tough sell—why not just take lithium and see what happens? Most bipolar depression patients who volunteer do not come from the psychiatry clinic.

“We have ads on TV and radio, in newspapers,” Smedley says. “We have flyers in libraries and grocery stores. We post on Craigslist, which has been successful and free. And we send e-mails to UNC staff and faculty. All of it approved through IRB.” Ready and willing Back at Lineberger, researchers get most of their trial volunteers from the clinic.

Tomma Hargraves was two months removed from her nine-month-long lung-cancer trial when Mark Socinski asked her if she’d consider joining a Phase III randomized clinical trial for Stimuvax, a new drug that doctors think may stimulate the immune system to prevent cancer from returning. The trial includes thirteen hundred patients from thirty countries. Hargraves didn’t hesitate to volunteer, even though it’s a double-blind study.

“I know the nurses are frustrated because patients don’t want to come to UNC for the trial unless they’re guaranteed to get the active treatment,” Hargraves says. “How else are we going to know if these things work or not unless somebody’s willing to be a guinea pig?” e Mark Socinski is a professor of medicine in the School of Medicine and an investigator in thoracic oncology. Shelton Earp is a distinguished professor of medicine and the director of the Lineberger Comprehensive Cancer Center. Bert O’Neil is an associate professor of medicine in the School of Medicine. Barbara Longmire is the director of UNC’s Office of Clinical Trials. Joe Eron is a professor of medicine and director of the Clinical Core of UNC’s Center for AIDS Research.

Bill Maixner is a professor of endodontics in the School of Dentistry. Kelly Smedley is the program coordinator for the Center for Research and Treatment of Bipolar Disorder.

For more information on how to volunteer for clinical trials, go to: http://ohre.unc.edu/ public.php.

My brain on magnets The MRI technician looks at my chart and says, “You worked at a woodshop for a few months; did you work with metal?”

“Um, I don’t think so,” I tell her.

“The reason I ask is because this MRI machine is really just a huge magnet,” she says. “If you have a tiny piece of metal in your eye that floated in from someone grinding metal, then the magnet could move it around”— she waves her hand wildly—“and cut your optic nerve.”

Now I’m scared. I don’t recall bits of metal floating into my eye socket, but I don’t remember a lot from my woodworking days.

I’m at UNC’s Magnetic Resonance Imaging Research Center because I thought I might like to write about being part of a research study, and I needed the $185.

This particular study is for bipolar depression. As far as I know, I’m part of the control group. I’ll have three neuropsych exams, and researchers will take pictures of my brain three times over the course of sixteen weeks.

I’ve never had an MRI, but the internet says it’s safe.

When I decide I have no metal in my head, the technician gives me earplugs and headphones, and she attaches a plastic cage around my head. The cage has a mirror, so I can look down the MRI tube and watch the U2 concert DVD I brought along.

She slides me in. There are three inches between my face and the top wall; I feel my hot breath tumbling back on me.

The machine pounds away like an electronic jackhammer, a wall of noise with some funky rhythm and muffled melodies. But I can see Bono clear as day, from his silly sunglasses down to his platform shoes.

A good hour in, an awful knocking sound jolts me and I feel like I’m riding an old washing machine. Not too long after, just as U2 strikes their last chord, the jackhammer stops. The crowd goes wild and I’m set free.

And I can still see.

For a clinical trial that compares normal brain activity with activity in people with bipolar depression, researchers used an MRI to image my brain. They let me watch a U2 concert DVD. In the first image, taken just before U2 started playing, the MRI shows my brain from the side. Then, as I breathe and oxygen gets pumped into my brain, the MRI picks up more detail. Lastly, the shot from above shows light penetrating my eye socket, proving that U2 did indeed enter my brain.

I ask the tech if some people can’t stay in that claustrophobic trap.

“Some try and can’t do it,” she says. “Some squirm around so much that the brain scans are blurry and useless.”

And if the photos are blurry, or people can’t stand the narrow tube, then their neuropsych exams are useless and researchers have to recruit more people.

Those MRIs and neuropsych tests help psychologists create a baseline for how a typical person’s brain works.

In one test I have to name as many animals as I can. In another, the research assistant rattles off fifteen words that I have to repeat. I long for the giant magnet, with or without U2.

I ask the assistant if some people circle true or false on the test without reading the questions.

“Yeah, that happens,” she tells me. “That’s why I’m sitting here with you. One guy fell asleep. Some people clearly don’t care. We have to weed them out so their results don’t screw up the study.”

I continue to answer—yes, I’ve been depressed; no, not for months at a time. I plod along for three hours, and I wonder: do I need the money this badly?

Maybe not, but the researchers seem to need me—so long as I don’t have metal in my head.

—Mark Derewicz endeavors 11

fair games For kids with visual impairment or other disabilities, video games can seem out of reach. But now computer scientists and their students are giving more kids a chance to play.

by Susan Hardy

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ILLUSTRATION: JASON SMITH

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normally quiet corner of Sitterson Hall, home to UNC’s computer science department, is full of chatter today as kids and adults wait in a knot. In the middle of the floor, a slender girl with bright blond hair hops onto a plastic mat divided into nine squares.

A tune starts to play, and the girl moves her feet, first tentatively, then with more confidence as she learns to stomp on the squares in time to the beat. The projector screen in front of her displays an equally blond animated character doing dance moves with her upper body, smiling when the player correctly hits a beat.

The game sounds a lot like the dance video games that have been popular in the United States for nearly a decade. But there’s one major difference: the girl standing on the dance pad is blind. She can’t see her dancing counterpart on the screen in front of her—and she doesn’t really need to. The game gives her audio feedback on her performance: a handclap when she steps in time to the beat, an occasional buzzer when she’s off rhythm.

Six-inch-wide pieces of carpet cover the centers of the squares on the pad, telling her feet where to step.

Like many of the other games on display nearby, Move to the Music includes visual effects to appeal to sighted players. But all the games were designed by student creators primarily for players who can’t see.

The students are getting lots of opportunities to test their work. Maze Day—named for a maze kids navigate by listening for the sounds of howling wolves and trumpeting elephants—has drawn seventy kids from around North Carolina, all of them visually impaired.

According to a November 2007 Associated Press- AOL Games report, 81 percent of children ages four to seventeen now play video or computer games at least occasionally. And the gaming sector is growing rapidly. Marketing research group NPD reported that Americans spent $17.9 billion on video games and consoles in 2007, up from $12.5 billion in 2006.

Players can get just about any kind of game they want, from sports to shooting games to online role-playing worlds with millions of characters. But the games all have something in common: you have to be able to see the screen in order to play.

It’s no mystery why so much more is available for sighted players than unsighted ones, says Gary Bishop, one of Maze Day’s organizers. “We’ve built this economy so that you can have whatever you want—as long as a million other people want it too.”

That’s why Bishop has led an effort to attract UNC students to projects that make technology accessible to people with visual impairment and other disabilities.

There’s one trend in the gaming industry that may be hopeful for blind people: the recent popularity of games incorporating a physical dimension. In 2001 Dance Dance Revolution (DDR) became the first popular dancing game to come to home consoles. Since 2005, Guitar Hero—a game that cues players to press buttons on a guitar-shaped controller to simulate playing rock music—has become popular with both kids and adults. And in 2006, Nintendo’s Wii console with a detached controller opened up the possibility for a variety of games in which players shake, wave, and swing the controller to direct on-screen action.

“There aren’t as many things you can do when you come home from school, if you’re a blind kid. You’re not running around outside as much, you’re not playing basketball or riding bikes.”

—Gary Bishop

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one of these popular technologies were marketed to visually impaired players. But with practice, a visually impaired kid can stomp on a pad, swing a controller, or strum a guitar as well as a sighted one can.

Moving around while playing a video game may be even more helpful for blind kids than it is for sighted ones. “There aren’t as many things you can do when you come home from school, if you’re a blind kid,” Bishop says. “You’re not running around outside as much, you’re not playing basketball or riding bikes.”

Exercise was an important motivation for the students who adapted DDR for people with visual impairment. In the original game, directional arrows moving on the screen cue a player to step on the up, down, left, and right arrows on a dance pad. “The game is being put in schools now as a way to get exercise, but obviously blind kids can’t use it,” says Jason Cisarano, who worked on Move to the Music. “We wanted to make something blind kids could play, but that would also be fun to do with their classmates or siblings who can see.”

Another group of students also used DDR pads to help kids exercise, but with a different twist. Rather than following along with music provided by the game, players press DDR pads with their hands and feet to make their own music.

The game, called TechNote, was a semester project by three first-year students—Christy Sink, Chase Jenkins, and Bethany Jasper—who took a seminar with Bishop called Enabling Technology. “It turned out a couple of us had been big band geeks in high school,” Sink laughs. All three group members had at least rudimentary skill on the piano, so they got together one day and composed several cheery clips of melodies a few seconds long.

They linked the sounds to a DDR pad on the wall. Another pad on the floor linked to percussion sounds. “Visually impaired kids tend to have more problems with motor skills,” Sink explains.

“With this game they’re moving their feet and pounding with their hands, so they get some upper body exercise as well.”

Other students used information readily available on the internet to write programs that can communicate with Nintendo’s Wii controller, called the Wii Remote or “Wiimote.” Given the task of making a sports game, one group picked a sport that would be familiar to their target audience: beep ball. The real-life game is based on baseball and played by many blind kids and adults, using a softball that beeps and bases that make buzzing sounds. endeavors 13

The game the students created combines verbal cues such as “Ready!” “Pitch!” and “Strike!” with simple figures that seem to zoom closer to the player as they run across a green field. The player swings the Wiimote to hit the ball, then shakes the controller back and forth to run toward a base.

Another group’s cowboy-themed game attaches the Wiimote to a strap worn around the chest. Seated on a rocking horse or exercise ball, the player hears mooing cows, clucking chickens, and so on, and “catches” the animals for points by leaning right or left and bouncing up and down.

“We had to think about a theme all young kids would understand,” says computer science major Chris Barefoot. “Kids love animals, and whether they can see them or not, they all know the sounds that different animals make.”

Above: Jordan places Sweet Tarts in holes on a board to create music. The Sweet Beat game uses a webcam to detect when a hole on the board is covered, and adds a new sound to the pattern of rhythms. Left: Animal sounds in Cymone’s headphones signal her to move her on-screen character by leaning left or right.

Photos by Kelli Gaskill.

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ost of the games at Maze Day are based on widely available technology with few modifications. “It reflects the focus I have now on commodity hardware,” Bishop says. “If I make custom hardware, nobody’s going to have a copy. But if I use stuff you can buy off the shelf, it’ll be relatively inexpensive and lots of people will be able to use it.” A lot of the games at Maze Day use microphones or webcams that can be bought for about $15. Even the DDR-style games are made up of inexpensive gear, and the only modification is gluing on some squares of scrap carpet.

There are a few more expensive or more technical exceptions, such as the Wiimotes, which currently sell for about $40. Maze Day this year also included a blind-accessible guitar-playing game, developed by two students in Bishop’s first-year seminar. As in

Guitar Hero, note cues on the screen appear to travel toward the player. The students’ innovation is in the guitar-shaped controller, which they modified to make buttons vibrate, first weakly, then more strongly to signal the player when to play a note.

Bishop’s goal, echoed by many of the students who worked on the accessible games, is to make most of their products freely available online, filling a niche that markets don’t.

Many of the games were written in popular computer languages such as Python that are backed by powerful libraries of open-source programming tools. This allows other programmers to easily improve or build on each other’s products.

All the groups of students said they may continue to work on improving their games outside of class. Carl Schissler, one of Wii Beep Ball’s authors, plans to put the game on the open-source web site SourceForge.

Kevin Coletta is working on a web site to advertise Move to the Music. He’s also trying to add an important feature: letting users import their own music files. The challenge is making a program that can reliably detect the beat of a tune, Coletta says.

For Bishop, who has organized Maze Day for four years, a major motivator is knowing that he and his students are in a relatively small pool of computer scientists working on such projects. This year their half-day event drew kids and teachers from as far away as Buncombe and New Hanover Counties.

“We even had one teacher who was from Alabama,” Bishop says. “People are willing to come from so far away—it tells you something about how little there is out there for these kids.” e Gary Bishop is a professor of computer science in the College of Arts and Sciences. Zachary Swartz, who graduated in May 2008 with a BS in computer science, and Trey Brumley, a senior majoring in computer science, worked on Move to the Music. Carl Schissler is a junior majoring in computer science. Jon Latane, a senior computer science major, and Mitchell Rao, a May 2008 BS graduate in computer science, worked on Wii Beep Ball. May 2008 BS graduates in computer science John Batchelor and Daniel Parker and senior computer science major Michael Zachary worked on Rocking Horse. Maggie Stafford and Rhiannon Little, sophomores in the College of Arts and Sciences, developed the accessible Guitar Hero game. Kevin Coletta is a senior majoring in computer science.

Global Exposures

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very year, hundreds of Carolina students, professors, and staff head abroad to study, conduct research, and run programs. Each November, UNC’s Center for Global Initiatives asks travelers to enter a photo competition. The next three pages feature entries and winners from 2007. For more information see http://gi.unc.edu/.

Jose Corbella, journalism “More than 70,000 people gathered in front of the Chilean military academy on September 11, 2006. Some went to say goodbye and some others to celebrate the death of the former Chilean dictator Augusto Pinochet. I never understood the love (and for some others, hate) that Chileans felt towards Pinochet until that night.

The atmosphere was sad and joyful at the same time—one of the strangest feelings I’ve ever felt.”

Nathaniel Nihart, international studies and African studies “I was climbing in the Dolomites when I came upon this shrine, one of the many Christian symbols that were so prevalent in the area.

It also served as a memorial for climbers who had died in the area or who were originally from the area.”

Sang Hee Jeong, Rotary peace scholar “I was travelling in Rajastan, India during a Christmas vacation from my work in Sri Lanka. My friend and I went into the desert on camels, walked by two local guides. They brought us dinner from the village, made a fire to keep us warm, made beds in the sand with sleeping bags, and guarded us through the whole night. The older man was a quiet person, but every motion he made seemed so meaningful.

When the morning came, he rose to the sun.”

endeavors 15

Ben Aiken, environmental studies “Three weeks of exploratory kayaking in the Himalaya mountains of Sikkim, India provided great adventure and an interaction with people who likely had never seen a kayak. This photograph was taken from a wobbly bridge upstream.”

Amanda Barbee, anthropology “After speaking to the students at a rural school in Kenya, I was walking to an intersection to catch a matatu (vans used for public transportation). On the way, I ran into a principal that I had met a couple of weeks before, who offered me a ride in his matatu. After driving for a few minutes, we stopped at his school and picked up the other passengers: thirty children. This was my own personal experience of the running joke in Kenya that in a matatu, there’s always room for one more.”

16 endeavors

Leah Gilbert, medicine and maternal and child health “I got this shot in the middle of a four-day hike through the remote Andes. We had reached one of the most breathtaking scenes of the hike...a full 360-degree view of snow-capped peaks and fertile valleys. I felt like I was truly in the middle of nowhere, but then four bright children came around the corner on the narrow trail snaking across the side of the mountain. One of them, seen in this photo, walked along the edge of precipitous cliff, admiring the view behind him. When I look at this picture, I’m reminded how hard it was for me to hike up these peaks, nearly 4,000 meters high, where the oxygen was thin and the air was frigid. Yet here were these four children, climbing through the Andes on their own, in sandals, not out of breath in the slightest. The Inca are an amazing and unique culture, surviving in isolation on top of the world.”

Shai Tamari, Rotary peace scholar “The sunset over the Wadi Rum desert has to be one of my most breathtaking experiences. While traveling in southern Jordan with five other UNC students, we stayed overnight in a Bedouin camp and witnessed this marvelous scenery­—a perfect ending for a perfect day.”

Julie Barrett, international studies “My friends and I, who had been studying in Argentina, took a trip through Peru and Bolivia at the end of our semester. We decided to get a better view of this crowded city from atop a lookout tower. Upon reaching the top, I was rather surprised to see these two women chatting happily to themselves, seemingly unaware of the tourists snapping pictures all around them. They were framed so perfectly with their city stretching out in front of them, and I found this image far more interesting than merely the landscape itself.”

endeavors 17

LIESBETH BERNAERTS

Tuberculosis patients wait to pick up their medications at a clinic in Kinshasa, Democratic Republic of Congo. They make the trip every day so that nurses can help them take their pills in the right combination.

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Return of the Fatal Cough Tuberculosis is on the rise.

Carolina researchers know why.

Now they’re battling the disease from every angle—treating patients, studying the biology, and trying to find a vaccine before drugresistant strains spread out of control.

by Beth Mole and Margarite Nathe In May of 2007 a sick man took a flight from Atlanta to Paris. He got married in Greece, and was touring Rome when he got a call from the Centers for Disease Control and Prevention (CDC). Stay where you are, they told him. We’ll send a private jet to pick you up. The U.S. government had placed a no-fly order on his passport because, according to CDC test results, he had an extremely drug-resistant form of tuberculosis— XDR-TB—which is infectious and often untreatable.

The media went berserk. CNN gave hourly updates on the man.

The CDC enacted its first federal quarantine in over forty years.

But the man panicked. He slipped onto another flight, and by the time officials finally quarantined him he’d left a trail of exposure all the way from Italy to Canada to New York.

In the end, it turned out the man had MDR-TB, a less dire drugresistant strain. He wasn’t as infectious as officials had feared, which was why he didn’t cause an outbreak over the course of his travels. But even so, says TB researcher Miriam Braunstein, “those kinds of events tell you that TB’s a real disease—a real threat.”

here are three things you should know right off the bat about tuberculosis and the bacteria that cause it: 1. A third of us on the planet—about two billion people—are infected with it.

2. Ninety percent of those who have it never show symptoms.

3. Most of the time, TB is curable.

Most people’s immune systems react to the threat of M. tuberculosis and keep the bacteria at bay. But a compromised immune system—which can come about through depression, HIV, or plain old age—can no longer fight off an infection.

At last count in 2006, there were 13,779 cases of TB reported in the United States.

We carry only a fraction of one percent of the world’s infected people (85 percent are in Africa). Beginning with the onset of the AIDS epidemic, the number of new cases began to grow; there are now nine million every year.

Number three on the list above may be the biggest reason we’re still living with tuberculosis today. Scientists in the 1950s developed antibiotic drugs that could cure TB patients completely, and after that, doctors were no longer trained to recognize the symptoms, prisons did away with quarantine facilities, and funding for TB research dried up. We still use the same treatment for TB today that we did in 1955. We use the same method of diagnosis—the tuberculin skin test—that we did a hundred years ago. And we’ve never had a dependable vaccine. As a result, scientists say, treatments for tuberculosis have seen less progress than those for any disease in the past fifty years.

After decades of inconsistent drug supplies, drug shortages, and poor drug quality, certain strains of TB have mutated and now hold strong against what drugs we do have.

The World Health Organization calls these strains “a grave public health threat.” As of February 2008, forty-six countries across the world had confirmed cases of XDR, including the United States.

Multidrug-resistant (MDR) TB is resistant to at least two first-line TB medications, and can take years to treat. Extremely drugresistant (XDR) TB is MDR that is also resistant to three or more of the six second-line drugs; it’s difficult both to diagnose and to treat, says epidemiologist Annelies Van Rie. Most people who contract XDR have no chance of recovery. endeavors 19

he disease’s greatest weapon is how easily it moves from body to body. All it takes is one cough to launch microscopic clumps of bacteria into the air. If the person sitting in the next seat on the bus inhales the clump— or even a single bacterium—M. tuberculosis can set up shop. The bacteria are soon detected by scavenging immune cells called macrophages, which immediately attack.

The macrophages ingest the bacteria in a process called phagocytosis, and then digest them much like a meal.

This attack usually spells the end of any invading germ, but M. tuberculosis has evolved methods to survive it. The bacteria do go through phagocytosis, but somehow they manage to halt the degradation process.

In those first few weeks of infection, M. tuberculosis survives and multiplies happily inside the macrophages. Eventually the bacteria reproduce so prodigiously that they burst free from the macrophage and infect other macrophages.

No one knows exactly how M. tuberculosis manages to thwart the macrophages, but microbiologist Miriam Braunstein and members of her lab at UNC are trying to find out. Studying the basic science of M. tuberculosis and how it causes disease, Braunstein says, could help us obliterate it.

By the time the bacteria are running rampant among the macrophages, the immune system of a healthy person realizes what’s going on and taps another line of defense: T cells. These immune cells can detect infected macrophages and release cytokines, which work like an emergency alert system to trigger intense immune responses. T cells trap infected macrophages and quarantine them into bundles of immune cells called granulomas. Inside the granuloma, T cells activate the infected macrophages using cytokines so they can finish the job of killing the bacteria.

The earliest unambiguous detection of the tuberculosis bacterium is in bison remains dated to 18,000 years ago.

This business of invasion and escape is usually silent in people who are healthy— at worst, they feel tired or have minor cold symptoms—because the reactivated macrophages kill the infection. But sometimes one or two bacteria can evade even the T-cell response and survive undetected in the granuloma (again, how M. tuberculosis manages this is unknown). They can lie dormant there for decades—up to eighty years—until age or infection weakens the immune system.

This is how TB in a sixty-year-old patient may have originated from an infection he got when he was twenty years old.

One third of us have TB bacteria in our bodies.

Worldwide, TB infects one new victim per second.

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n the hubbub surrounding the smallpox vaccine in the early twentieth century, the buzz among scientists was that a TB vaccine was not far off. But it turned out that the BCG vaccine, first tested on humans in 1921, wasn’t the cure scientists had hoped for.

BCG is made from a relative of TB called M. bovis, which lost its virulence after scientists grew it repeatedly on potato media.

While the BCG strain doesn’t cause disease in humans, the idea was that it would help human immune systems prepare for future TB infection by introducing something similar to the real thing.

But the main problem with BCG is that it doesn’t work for everyone; in some studies it has protected only sixty to eighty percent of people, and in other studies, it provided no protection at all. And since antibiotics to treat TB were discovered just over twenty

“In approaching the consumptive, one takes the disease because there is in the air something disease producing.”

—Aristotle

Ho Chi Minh

IAKOV FILIMONOV

Vivien Leigh A few notable Honoré de Balzac Frédéric Chopin victims of Louis Braille tuberculosis: King Tutankhamen W.C. Fields Elizabeth Barrett Browning

20 endeavors

Charles Bukowski John Keats

Edgar Allen Poe

Anton Chekhov Napoléon II of France George Orwell Stephen Crane Ralph Waldo Emerson

years after the BCG vaccine was developed, no one bothered to create a more effective vaccine. Today some countries require the BCG vaccination despite its shortcomings, but many scientists and doctors—including those in the United States—don’t even consider it to be a vaccine.

Braunstein studies how M. tuberculosis delivers proteins to cause the disease. “Most virulence factors of pathogens are secreted proteins,” she says, and so she began by looking at proteins secreted by the bacteria while they’re in the macrophage. Understanding this part of the bacteria’s process could help us develop a more effective vaccine, she says.

In 2003 Braunstein made a huge breakthrough: she found the specialized protein secretion system in M. tuberculosis called SecA2. Protein secretion systems are common in bacteria and work like mechanical ports that oversee what is allowed to leave the cell.

But scientists had never seen this system before, and no one had any idea what role it played in the disease. When Braunstein made a mutant strain of M. tuberculosis that lacked the SecA2 system, she found that it caused less disease in mice. “It also protected animals from TB infection better than BCG,” she says. The SecA2 mutant has now been licensed by a not-for-profit TB vaccine development company called Aeras that aims to use it in their efforts to make a more effective vaccine. If they’re successful, they’ll distribute it for the lowest possible cost.

“I like the fact that basic-science research can have very big implications in serious diseases,” Braunstein says. “I thought, ‘How did this protein get secreted?’ and now it may be a key to a new vaccine. When you’re not looking to cure the disease, you may come across something that will cure the disease.”

Hunchbacked figures that appear in Egyptian art tell us that tuberculosis has afflicted humans since at least 3,000 BC.

Robert Louis Stephenson Robert Heinlein Doc Holliday Andrew Jackson Simón Bolívar D.H. Lawrence

St. Francis of Assisi

Katherine Mansfield

Saint Thérèse de Lisieux Florence Nightingale Niccolò Paganini

Eleanor Roosevelt

Alexander Graham Bell Henry David Thoreau Thomas Wolfe All three Brontë sisters

LIESBETH BERNAERTS

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Eighty-five percent of the world’s TB cases are in Africa, where doctors don’t always have the benefit of climate-controlled hospitals and stockpiles of medicines. Here, a clinic nurse explains the disease and treatment to a tuberculosis patient in Kinshasa, Democratic Republic of Congo.

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raunstein and members of her lab continue to study SecA2, and the project is gaining momentum now that she’s working with professor of molecular pharmaceutics Tony Hickey. Hickey’s working to find the best way to get TB drugs (and eventually a vaccine) into the bodies of TB patients.

Pills haven’t been completely effective in the past, Hickey says. And with needles, there are the problems of storage, disposal, and making sure they’re not used more than once. So he started off by asking himself: if pulmonary TB attacks the lungs, and

transmission occurs through inhalation, wouldn’t it be more effective to deliver the medicine straight to the lungs? He’s been working to unravel this question for almost twenty years. And according to his studies, the answer is yes.

But it’s not just a simple matter of inhaling BCG. Scientists tried that back in the 1960s, and the results were inconclusive. The problem, Hickey says, was one of delivery. So he used a combination of chemistry, biology, and physics to try to make it work. “You have the chemistry, which is largely physical

• TB was once the leading cause of death in the United States.

• In the 1970s and early 1980s, the United States neglected the TB control efforts that it had begun in the 1940s. Between 1985 and 1992, the number of TB cases increased.

• In 2005, 1.6 million people worldwide—more than 4,300 per day—died from TB.

chemistry and particle-particle interactions,” he says. “And then the physics of taking the particle and putting it into an air stream and delivering that into the lungs, which is all based on aerodynamic behavior of small particles. And then the biology—whether or not you actually target the microorganism you’re trying to kill to treat the disease.”

So now Hickey is adapting technology from certain types of aerosol delivery devices, such as asthma inhalers. “But there are some subtleties to protein stabilization.

Most of the asthma compounds are very

“XDR-TB is very serious—we are potentially getting close to a bacteria that we have no tools, no weapons against .”

—Paul Sommerfeld, the Stop TB Partnership

SOURCES: WHO, CDC

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LIESBETH BERNAERTS

In sub-Saharan Africa medical staff are faced with an increasing workload and often-hazardous working conditions. Many of them leave the profession because of the risk of contracting HIV.

small molecules that are reasonably stable, so you don’t have to do much but make them into a particulate form.” With TB medications and vaccines, it’s tougher. Hickey wants to turn BCG into a powder (rather than a mist) that patients can inhale without having to use water. This will be especially useful in countries where clean water is scarce.

Right now Hickey and Braunstein are testing which TB antigens generate an immune response in guinea pigs. “Miriam and I are working on a protein-antigen aerosol for TB. There are all sorts of proteins and nucleic acids that the bug expresses that the body will generate an immune response to,” he says. “But there needs to be a lot more basic science to develop an effective new treatment.”

Because TB medications are meant to be taken all together, some patients have to swallow up to sixteen pills at a time.

A

lthough funding for TB research is flowing to scientists once again, they’re struggling to manage some new complications of the disease—namely HIV. TB is now the leading cause of death in people with HIV, and the two diseases have created what Annelies Van Rie calls a deadly symbiosis. Van Rie treats TB patients in South Africa, which accounts for 29 percent of the continent’s coinfections. “HIV drives the TB epidemic in sub-Saharan Africa,” Van Rie says. “So if you want to do something nowadays about TB there, you can’t neglect HIV.” One of the biggest roadblocks to containing the epidemic is that many African healthcare workers are only trained to treat one of the diseases. Nurses in the hardest-hit Afri-

TB is the leading killer of people who have HIV. Active TB will develop in 30 percent of people living with AIDS.

can countries have come under enormous pressure in recent years. Without access to continuous medical education (which doesn’t exist in their countries), their training is often haphazard, and many are never trained again during their careers. They also aren’t paid well and their working conditions are often terrible, Van Rie says; many die from HIV or move away to escape the risks. “The workload in sub-Saharan Africa has just increased,” she says, “but the nurses don’t increase.”

One of Van Rie’s latest research projects involved working with health-care workers at eleven clinics in the Democratic Republic of Congo. With all the new demands on the clinics, doctors and nurses were overwhelmed, and insisted they’d need additional staff and money to make ends meet. But after assessing how the clinic workers were using their time, Van Rie found that the TB nurses were only spending 20 percent of their work hours on TB-related duties; the rest was spent dealing with general medicine and administrative tasks. Van Rie showed her results to the clinic staff. The next time she checked in with them, they had managed to make ends meet with the staff they already had.

Van Rie’s research regularly takes her to Sizwe Hospital in South Africa, which is devoted exclusively to treating MDR and XDR patients. (See “A Prison for the Sick,” next page.) Public health officials all over the world are now facing the same problem: how to best treat people who are sick with drug-resistant strains.

In a January 2007 article in the Guardian, South African scientist Mary Edginton said, “You can look at it from two points of view.

From the patient’s point of view, you are expected to stay in some awful place, you can’t work and you can’t see your family. You

Tuberculosis is treatable and curable—even in people living with HIV.

Annelies Van Rie was one of the first scientists to identify superinfections in 1999. “That was tackling one of our main questions: once you’re infected with TB, can you be infected again? For example, with flu, we know you can be infected and then a couple of years later you can have flu again. For TB, the dogma was that that couldn’t happen.” But Van Rie showed that TB patients who have been fully cured of one TB strain could then be reinfected with another strain.

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will probably die there. From the community’s point of view such a person is infectious. If they go to the shops or wander around their friends they can spread it, potentially to a large group of people.”

MDR-TB is transmitted in hospitals much more often than other types of TB, Van Rie says, partly because overcrowding and poor ventilation often turn hospitals into breeding grounds for the disease. So while Braunstein, Hickey, and other scientists search for a vaccine, Van Rie and others are looking for the solution to treating dangerously contagious (and oftenterminally ill) patients with compassion and dignity.

“These patients feel whether you’re comfortable sitting with them or whether you’re scared of them,” Van Rie says.

“And if you’re scared of them, you’d better do some other job. If you’re scared of them, you can’t do good research. Your heart has to be in it.” e Miriam Braunstein is an associate professor of microbiology and immunology in the School of Medicine. Her work is funded by the Burroughs Wellcome Fund, the National Institutes of Health (NIH), and Aeras. Tony Hickey is a professor of molecular pharmaceutics in the School of Pharmacy. His work is funded by the Bill and Melinda Gates Foundation. Annelies Van Rie is an associate professor of epidemiology in the School of Public Health. Her work is funded

by NIH, the CDC, and the United States Agency for International Development. Myron Cohen, director of the Institute of Global Health and Infectious Diseases, provided background expertise for this story.

LIESBETH BERNAERTS

Clean water and basic supplies can be difficult to come by for some African clinics. Here, at a clinic where cups aren’t available, a woman washes down her TB pills with water from a plastic bag.

• People who have latent TB infection do not feel sick, have no symptoms, and cannot spread TB to others. About 10 percent of people with latent infection will develop TB disease. Some people develop active TB disease soon after infection, before their immune systems can fight the bacteria. Others get sick later when their immune systems weaken for another reason.

• If a person’s immune system can’t stop TB bacteria from multiplying, the bacteria attack, destroying tissue and causing active TB disease. TB bacteria can create holes in a person’s lungs.

SOURCES: WHO, CDC

A prison for the sick Johannesburg’s Sizwe Hospital is surrounded by razor wire and sealed behind a barricaded gate. Armed guards patrol the grounds.

Sizwe, like a few other South African hospitals, is dedicated solely to treating patients with highly contagious, drug-resistant strains of tuberculosis: MDR-TB and XDR-TB. South African law states that anyone diagnosed with MDR or XDR must be hospitalized for at least six months, or until they’re deemed noninfectious. But hospitalization means patients are completely isolated from their families, their jobs, and their communities. A few patients have been in Sizwe for years, and many never respond to treatment; their only chance of leaving is in a coffin.

“Almost every time I go there, there’s a riot,” says UNC epidemiologist Annelies Van Rie. “Or there was a riot the week before, or there will be a riot the week after. The patients are very, very unhappy there.”

The staff are unhappy, too: about 20 percent of the nursing posts remain vacant. “Hardly anybody wants to work there,” Van Rie says. “And everybody’s scared of XDR, so the doctors kind of zoom in and out. Many patients complain that they’re hospitalized but only see a doctor once a week. It’s a very difficult situation.”

Desperation sometimes drives patients to attack staff members or even take them hostage.

Many patients don’t even understand why they’re being detained, Van Rie says. “They just know they’re being held in a place with a lot of sick people and others who wear masks and give them a wide berth.”

Most escapes happen during the holidays. The police don infection-control gear, hunt down the escapees, and drag them back. They usually find the patients in their own homes, begging to stay with their families.

Right now TB test results take at least two months to produce, and patients must have two negative tests before they’re deemed noninfectious. Van Rie is working with colleagues to find a way to shorten patients’ time at Sizwe. “But we need data for that,” she says. “I think if we can develop very rapid methods to diagnose when somebody’s no longer highly infectious, then patients will understand when you say, ‘You’re ill, you might get sick from those drugs and we’re going to monitor that, we’re going to help you learn to swallow all these pills, tell you what the side effects are…’ I think that’s much better than what they say now, which is, ‘Six months at a minimum and it might be two years.’ I mean, how would you feel?” ­—Margarite Nathe Annelies Van Rie collaborates with South African doctors Ian Sanne, Martin Grobush, and Liesl Page-Shipp at Sizwe Hospital.

Patient: “We are held like prisoners, but we did not commit a crime.”

Chief medical officer: “XDR is like biological warfare. If you let it loose, you decimate a population.”

—New York Times, March 25, 2008 endeavors 23

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Portrait in Jazz

“There are hundreds of bands out there playing the same songs,” Fountain says. “I just felt like maybe the world didn’t need another one of those records, and he’s a great writer.”

Anderson released his newest album, Forget Not, in March of this year. The music is progressive, modern-style jazz that draws on classical techniques, reflecting Anderson’s training in both classical composition and jazz. “I’m trying to be innovative but still be aesthetically pleasing,” he says. So how did he do it?

He practiced and studied.

Stephen A nderson has one foot planted in jazz, one in classical composition, and an ear for the past. by

PAUL DAGYS

I

K elly R ae Chi

t’s a Thursday night in a crowded steak house in Raleigh, and over the sounds of people laughing and talking, Stephen Anderson is playing a solo on the house piano.

“It’s like, ‘Why do I do this?’” says Anderson, who paid his way through school by playing for audiences who seldom listened. “That guy’s on his cell phone, they’re speaking really loud over there, there’s ten other people getting drunk, and nobody’s listening.”

So during his college years Anderson stopped trying to compose the story lines of notes and chords he thought people wanted to hear. Instead he tried to strike a balance between familiar and innovative techniques by fusing styles and bending the rules.

That took a little encouragement. When he approached percussionist and friend Joel Fountain to record an album, Anderson at first wanted to play standards. But Fountain urged him to write his own songs.

Anderson developed his style during graduate school at the University of North Texas, where he studied the staples of classical and jazz, competed to play in the top bands, and composed some of the songs that would end up on Forget Not. The program at Texas formed a geographical bubble of jazz interest that contrasted sharply with the laid-back country tunes on the local radio stations. Competition was fierce, and students had a lot of fervor for the progressive jazz style, known then to be ahead of its time. The musicians would get fired up over colleagues’ mistakes in rehearsals and concerts. “It became almost violent on the bandstand if you made a mistake,” Anderson says. Some of the songs on the album reflect the zeal and the avant-garde style encouraged in the program, while others, such as “Antithesis,” are meant to contrast with it.

He pondered.

When Anderson is about to write a new piece of music, he says it’s impossible for him to ignore what’s already been written.

It’s a humbling process. “Who am I to say anything? There’s been so much said,” Anderson says. He studied every day for six months when he was about to take his qualifying exams in 2003. “I was living in the library and had all this music around me, just in awe of what’s been written,” he says. At times, it felt nearly impossible for him to find his own voice. “And then I felt kind of depressed for a few days, I picked myself up, dusted myself off, and thought, ‘Well, I’m going to draw on this. No one’s done George Crumb plus hip-hop. Then I could add my church background.’ And I run it all through my filter, and it comes out as something new.”

He wrote, played, and wrote.

If this sounds easy, it sometimes wasn’t.

The song “Forget Not” took Anderson months to figure out. He was listening to a piece by twentieth-century composer Béla Bartók, a Hungarian who borrowed rhythms from his recordings of peasants in the field. Anderson knew he wanted to emulate those rhythms on the album, and he knew he wanted a unique combination of notes in the chords.

“I’d change it and change it,” he remembers. “I was trying to find a way to make the chords match the groove.” Anderson has insomnia, but he puts it in a positive light. “If things are going well, I wake up and hear music in my head,” he says. “I’ll go and I’ll try to write it down.”

He had a little help.

Anderson e-mailed the music and recordings to Fountain and string bassist Jeff Eckels—Anderson had played with Eckels at Texas and on Joel Fountain’s latest album. “I didn’t say much after that.

I wanted to see what those guys could do,” he says. “Eckels creates all these melodies.

He hears the countermelodies and where to put things.”

Fountain says the trio worked well together for Anderson’s album because they were going for the same things musically. “I felt like we were all kind of looking for that spark and for the music to touch us deeply,” Fountain remembers. “That’s how we connected. Maybe we didn’t always get it, but we were always trying to look for something special.” e Kelly Rae Chi, a 2008 graduate with a master’s degree in journalism, is a freelance writer based in Garner, North Carolina.

Stephen Anderson is an assistant professor of jazz studies and composition in the College of Arts and Sciences. He received funding from UNC’s University Research Council and from the United Arts Council of Greater Greensboro Artist Hub. He has performed and recorded with the Lynn Seaton Trio and appears on two recordings with the trio for Nagel Heyer Records, Puttin’ On the Ritz (2005), and Ballads 2006 (compilation album). Anderson’s compositions have been performed by the West Point Military Academy Band, the North Carolina Jazz Repertory Orchestra, Lynn Seaton, and others. Forget Not was released in 2008 by Summit Records. endeavors 25

26 endeavors

a garden speaks After seven hundred years, Tenryu¯-ji tells its story. Norris Brock Johnson is listening.

by Margarite Nathe photos by Norris Brock Johnson

They had been sitting on the floor

for close to an hour in absolute silence, and Norris Brock Johnson was starting to get fidgety. Finally the priest gestured through the open wall in front of them, pointing past the immense stones in the pond to another outcrop that, for the past seven hundred years, has formed a waterless waterfall. “The only reason I have been drawn to the garden,” the priest confided, “is that I love the garden very much.

There are gardens in many other temples, as you know, but I love this garden in this temple.”

Johnson knew exactly he meant.

It was 1985 when Johnson first set foot in the Temple of the Heavenly Dragon (or Tenryu¯-ji, pronounced ten-ree-yoo-jee). He was an anthropologist with a Fulbright, teaching classes in Tokyo on American culture and traveling around the country on the weekends.

He was visiting Arashiyama—a mountain town west of Kyoto that’s famous for its cherry trees—when he saw the temple in front of him and the memories hit: his grandmother at the kitchen sink singing I come to the garden alone, while the dew is still on the roses…, his mother’s plot of flowers and vegetables, and the little Japanese black lacquer box she used to let him play with.

“I don’t know if I can explain it exactly,” he says. Put simply, he was immediately in love with the place.

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The priest looked pleasantly at Johnson for a long moment, then asked, “Why are you here?�

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T

enryu¯-ji is the ivy league of Buddhist allowed to speak with the other monks, who Garden. The story of the temple grounds monasteries, and people from all over were in strict training. “It’s the quietest place and their often brutal history includes what the world apply to go there to study Zen and I’ve ever been,” Johnson says. little is known about the garden’s builders, zazen (a form of practicing Zen that calls While he was there, he had drawn-out intimate descriptions of the temple’s private for long periods of cross-legged sitting). conversations with the priest about the interior, and translated bits of his conversaThe temple was first built more than six garden. Eventually, he was allowed to walk tions with the priest. And he says it’s been hundred years ago. It’s an incredibly peaceful alone through the restricted parts of the decades in the making. place, Johnson says, and you’d never guess grounds that the public never sees. He took Tenryu¯-ji began in 1339 when Emperor that over the centuries it’s been blown up, photographs, made sketches, and pored over Komyo gave Buddhists permission to build laid siege to, and battled over by emperors every inch of the pond garden. a temple on the site of an old villa. A priest and shoguns and warrior monks. It’s been “We don’t usually think of inanimate named Muso¯ Kokushi became the temple’s burned to the ground no fewer than eight things as beings,” Johnson says, “but some first abbot, and named it Tenryu¯-ji, or “Pretimes—the last was in 1864. But the original other cultures do. Beings have a quality of cious Zen Temple of the Celestial Dragon.” landscape garden has survived, and now it’s metabolism, of growth and change. If you People said a dragon slept in the pond there, one of the oldest in Japan. so the name seemed like a logical JASON SMITH Johnson went back to Tenryu¯ -ji choice. (In Japanese culture dragons again and again, lingering in the public are protective, divine beings that often areas long after the other visitors hibernate in lakes and rivers. They’re had left. He questioned caretakers associated with fecundity, growth, and and anyone else he could about the well-being, Johnson says.) grounds, but no one seemed to know Johnson and the priest continued much about its history. Johnson wasn’t their discussions. The priest told even sure why he was doing it, but Johnson the Buddhist names and finally, a little nervous and holding meanings of things in the garden, and out his business card, he approached he was curious to hear about Johnson’s a receptionist and asked to speak life as a university professor. Their with someone who knew about the exchanges had a glacial pace—they garden. took years. One of the things Johnson Eventually the local expert learned from the priest was that the appeared—a senior priest who was vegetation of the garden isn’t nearly the only one of some twenty resident as significant as its stones. priests who had any knowledge about the grounds’ history. He looked pleastones have a special place in Japaantly at Johnson for a long moment, nese culture—they even show up then asked, “Why are you here?” in the national anthem. Stories about Johnson didn’t expect that. He franthe earliest gardens in Japan include tically weighed his possible answers— stones that were inhabited by Shinto¯ to study your culture, to research the deities. temple, to find something—and in the Shortly after one of his chats with end discarded them. “I don’t know, the priest, Johnson reread the Epic exactly,” he said. of Gilgamesh—a poem from 3000 The priest nodded. “Come back BC—and found that it includes what again. Make an appointment to speak may be the first-ever written descripJohnson has studied many of Japan’s Zen Buddhist temple gardens over the past twenty years, but Tenryu ¯ -ji was the first. with me.” tion of a garden. The cuneiform poem “Living in that temple changed my life,” he says.

Johnson did go back. “For the first was carved on clay tablets in ancient six months, I visited constantly,” he Sumer (present-day Iraq). On Tablet says. “I kept staying late. They had XII, King Gilgamesh, the often-despito boot me out at closing time.” In the end, look at a garden over time, you’ll see that, cable antihero of the story, wandered into his persistence paid off. The priest extended like a person, it changes.” So on his evening the mountains in search of immortality. He a rare invitation: “You really should stay walks, he started to ask the garden questions: was stopped by man-dragon creatures who, weekends,” he said, “so the garden can begin Where are you from? Why are you here? “seeing his great intent and will,” allowed to speak to your heart.”

What was your childhood like? him to pass through the gates to the sun It took some time for Johnson to get To get answers, he spent years studying god’s garden. That garden, Johnson says, used to sleeping on the floor in unheated Japanese history and language, Buddhism, was made entirely of stones—there were rooms, to waking up at 4:00 a.m., to com- Zen, architecture, mineralogy, and geology. bushes made of pearls and agate, and trees munal bathing with the monks, and to using But those questions were Johnson’s first steps bore carnelian fruit, lapis lazuli leaves, and partition-less, unisex squat toilets. He wasn’t in writing Tenryu¯-ji: Life and Spirit of a Kyo¯to¯ hematite thorns.

S

endeavors 29

In this thirteenth-century Japanese scroll, the kawaramono sensui, or Riverbank Gardeners, build the Kitano Shrine in Kyoto. People from the upper classes thought these workers were half-animal, half-human, and charged them with doing much of Japanese society’s dirty work. The kawaramono built the gardens at Tenryu¯-ji. Illustrated Legends of the Kitano Tenjin Shrine (Kitano Tenjin Engi Emaki). Scroll e, Detail #5. Ink, color, and cut gold on paper. The Metropolitan Museum of Art, Fletcher Fund, 1925.

Photograph copyright The Metropolitan Museum of Art.

Suddenly Johnson had to re-examine the very idea of what a garden is. Now that virtually all human societies practice agriculture, he says, we tend to think of gardens as horticultural places to grow plants for food.

But before agriculture, humans’ survival depended upon stone tools, so it makes sense that the first idea of a fruitful plot of land would consist of stones.

Johnson took a year after that to study stones, and then went back to Tenryu¯-ji to continue his conversations.

“M

aybe it’s because I grew up on a farm helping my father, who was a carpenter,” Johnson says, “but I really wanted to know more about the people who actually built the garden.” Today, the priests at Tenryu¯-ji don’t maintain the grounds. If a stone tumbles over, no one can touch it until licensed state workers come and set it right. And when Johnson began to look into who the original workers were, he says, the details were shadowy.

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No one book on the subject exists, and it took a lot of digging before he’d pieced together enough information to understand why: the mysterious Riverbank Gardeners, as the builders were called, were barely human (or so people said) and no one at the time bothered to record much of anything about them. Their caste was so low that individuals didn’t have their own names— they were simply called by the name of the collective group: kawaramono sensui.

The kawaramono were relegated to living on the muddy, disease-ridden banks of the Kamo and Katsura rivers. Some Japanese paintings from the time depict them as hunched over, dark, and leering; other people in the scenes, especially the nobility, are relatively bright and tall. Rather than pay taxes, the kawaramono did manual labor, slaughtered horses and cows for leather armor, and worked as corpse-handlers for the samurai, who needed bodies on which to test their swords. The kawaramono also cleared away the human debris after battles

or disasters. But their intimate knowledge of gardening, stones, and the earth was famous, and people believed that in making gardens, the shaman-like gardeners actually brought the realm of the spirits into the realm of human beings. Johnson found that the kawaramono had built many of the gardens and temple landscapes in Japan, including the gardens at Tenryu¯-ji.

After the workers spent five years hauling boulders and moving earth, the garden was complete. The kawaramono were never allowed on the grounds again; they were too unclean for such a sacred space.

But how could the Buddhists—known as studious and spiritually enlightened— justify supporting such a system of labor?

“For many Buddhists at the time, it was incongruous,” Johnson says. Most Buddhists considered even the act of moving a stone lowly and spiritually polluting. But a few high-ranking Buddhists (namely Muso¯) were known as “stone-setting priests,” and they sacrificed their reputations by working

side-by-side with the kawaramono. “Muso¯ insisted that all work in the secular world revealed Buddha,” Johnson says. This was Muso¯’s personal practice of Buddhism.

T

he last chapter of Tenryu¯-ji answers some of Johnson’s most pressing questions. Why are we drawn to gardens in the first place? Why do some peoples, such as the Japanese, crave garden retreats so intensely that they invent miniature versions (think bonsai trees and rock gardens in trays) to enjoy in the middle of the city? And why do Buddhist temples have gardens at all?

One reason is historical, Johnson says.

The earliest Buddhist temples in Japan mimicked those in India, which generally had gardens with cistern-like ponds for water and utility within the compound. Not to mention that Siddhartha (or the Buddha) is said to have been born in a garden. The final reason, though, is pedagogical: the priests at Tenryu¯-ji point to the garden over and over again to illustrate lessons about Buddha and to train monks to look past the surface of the world’s people and things.

Johnson found this out when, one day, he and the priest sat together in silence, looking out at the stones in the water. Their reflections made the pond look bottomless, the priest pointed out, although it’s only three or four feet deep at any point.

“It is not good enough if the pond garden gives an impression of flatness,” the priest said. “It is important to give an impression of hidden meaning.”

For Johnson, that moment, and the notion of the garden as a mirror, has lasted.

“While Gilgamesh was in the Garden of the Sun, perhaps he saw his reflection in the carnelian leaves and what he saw was the slayer of his friend Enkidu and the destroyer of the mythic cedar forests,” Johnson says.

“At Tenryu¯-ji, I liked what I saw when the garden looked back at me.” e Norris Brock Johnson is a professor of anthropology in the College of Arts and Sciences. His book, Tenryu¯-ji: Life and Spirit of a Kyo¯to¯ Garden, will be published by Stone Bridge Press in early 2009. He received funding for his research from Dumbarton Oaks, the Institute for the Arts and Humanities, the University Research Council, the Japan Center, and from UNC-Chapel Hill. He held teaching positions in Japan at Waseda University and the University of Tokyo, Komaba.

“It is not good enough if the pond garden gives an impression of flatness,” the priest said. “It is important to give an impression of hidden meaning.”

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Using computer models to predict the next hot spot could help preserve the peace.

By Meagen Voss

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M

ore than a decade ago, political scientist Mark Crescenzi set out to foster peace by studying conflict. He wanted to use science and math to break down conflicts into their basic components.

Crescenzi learned that explaining how conflict happens is much easier than getting people to stop it. In spite of this rude awakening, he maintains that conflict research is valuable. “You have to understand the mechanisms of conflict before you know exactly where to apply pressure to stop it,” he says.

Traditional historians study conflict by examining the details of individual events. Political scientists such as Crescenzi take a broader approach: they compile events from several decades or centuries, identifying the patterns that lead to confrontation. Crescenzi’s strategy reveals trends that can easily be missed when events are studied one by one, he says. “We tend to get too focused on the unique aspects of historical events, which makes it harder to understand how history tends to repeat itself.”

Consider the Cold War. From the Korean War to the space race, it appeared outwardly that the United States and the Soviet Union were always at odds. There seemed to be no limit to what each country would do to undermine the other. But by looking at the countries’ relationship quantitatively, Crescenzi found that they got along better

ILLUSTRATION: NEIL CAUDLE

changes in countries’ affairs. “I was just a young grad student when I came up with the idea,” he says. Creating the model itself was relatively simple. Designing the research project was much harder. In order to get a complete picture of how countries connect, a good model would have to cover decades, if not centuries, of history.

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than expected. In fact, his calculations show that despite shocks such as the Cuban Missile Crisis, the relationship steadily improved over the course of the Cold War. Quantifying a relationship between two people is hard enough. So when studying the link between two countries for conflict research, political scientists use mathematical models to help characterize how countries interact. In a way, the models are like psychics, who use the answers to a few carefully selected questions to predict their clients’ futures. But a psychic who asks the wrong questions could misinterpret the past, leading to inaccurate predictions. So when researchers are developing a model, they want to ask the best questions they can.

Crescenzi says most of the models that have been used to define conflict potential between states were not accurate because they were static and only focused on a fixed period of history. Relationships between countries are never frozen in time, he says; they’re constantly evolving for better or for worse.

Crescenzi wanted to develop a dynamic conflict model that takes into account

he main challenge was what Crescenzi calls the “no lab” problem. Unlike scientists who generate their own data in laboratories, Crescenzi and his collaborator Andrew Enterline couldn’t directly observe the historical events they used in their research. They could only incorporate events found in public records.

Despite having to use incomplete data, they published their first version of the Interstate Interaction Model in 2001.

Crescenzi and Enterline were never quite happy with that first model. One problem, they realized, was that the model dealt only with militarized conflict. To predict conflict more accurately, the model would also have to take into account cooperative efforts or even periods of inactivity.

Crescenzi and Enterline had gathered data for the conflict portion of the model from a publicly available dataset of statistics on all violent interstate events that occurred worldwide between 1816 and 2001. It was tough to find a comparable source of data about cooperation. So Crescenzi and Enterline, along with a third collaborator, Stephen B. Long, settled on an imperfect but valuable measure: they decided to use membership in intergovernmental organizations such as the United Nations or NAFTA. Joining an intergovernmental body, they reasoned, is one of the strongest signs of international cooperation, and shows that a nation shares interests with the other members of the group. The size of a group also indicates cooperation intensity. For example, a country would be demonstrating more intense cooperation by joining the African Union than by joining a larger organization such as the United Nations.

The researchers also added a decay component to the model to better characterize the ebb and flow of interstate relations.

Countries typically go through periods where they interact little, making their relationship more neutral. This holds true even for the United States and Russia, who spent the latter half of the twentieth century

aiming nuclear missiles at each other. Within this tension there were periods of calm, such as the détente period of the 1970s. By incorporating cooperation and decay, Crescenzi’s model reflects a relationship that was more amicable than anticipated.

In the case of North Korea, on the other hand, there were no surprises. U.S. cooperation with the communist state has been consistently low for decades. Crescenzi’s calculations show that the relationship has been volatile since the Korean War and will likely remain that way for years to come. A similar situation exists with Iran. While there was some initial cooperation between the United States and Iran, those events have been overshadowed by an increasing tension.

Crescenzi’s model suggests that if a crisis were to occur with either North Korea or Iran, it would be nearly impossible to avoid militarized conflict. “As the environment becomes more hostile as a result of history, it becomes harder to negotiate your way out of a crisis,” he says.

To help predict future conflict, Crescenzi’s model gives interstate relationships a score between -1 and 1. A score of -1 indicates that two states are worst enemies; a 1 represents best friends. The lower the number, the more likely conflict will arise.

Crescenzi believes that his Interstate Interaction Model could be useful for improving the relations between countries.

Conflict models may not be able to solve crises directly, but they give officials a better understanding of how two countries relate.

Cues from the patterns generated by the model can help shape policy. Mathematical models similar to Crescenzi’s are often employed by the Pentagon and other government agencies to gauge how the United States should proceed in foreign policy matters. Will Crescenzi’s model make it to the Pentagon? It’s a long shot, he says. But he’s satisfied with the model’s accuracy. “Understanding the processes that generate events, both in the past and the present,” he says, “is what we do as social scientists.” e Meagen Voss is a doctoral student in neuroscience in the School of Medicine.

Mark Crescenzi is an associate professor of political science in the College of Arts and Sciences. His model was published in the September 3, 2008 issue of Conflict Management and Peace Science. endeavors 33

megaChina

The signature skyline of China’s urban revolution: Lujiazui district of Pudong, Shanghai, including the lower half of the Pearl of the East TV tower, Shanghai, 2007.

­The boom heard ’round the world Story by Sheila Read Photos by Thomas Campanella

34 endeavors

Imagine that a town the size of Chapel Hill grew to be larger than New York City in only thirty years. Impossible? Not in China.

The small fishing town of Shenzhen, situated across the border from Hong Kong, shot up from a population of 68,166 in 1978 to 8.27 million in 2006. Shenzhen became a leading manufacturing center in the 1980s after the Chinese government designated the area a special economic zone—in essence a testing ground for capitalism.

Americans best know China from the “Made in China” labels affixed to nearly every type of product available in our stores, from toys to clothing to furniture. We know that many well-paying manufacturing jobs have moved to China—including most of North Carolina’s textile and furniture industries—to take advantage of lower labor costs.

But behind the “Made in China” label is an unprecedented transformation of China’s cities and the consumer craze among the rapidly growing Chinese middle class. As newly prosperous Chinese consumers demand the same amenities Americans have long enjoyed—meat for dinner, cars, appliances, modern homes—pressure on the world’s finite resources of energy, raw materials, and food has increased dramatically.

Pancake development Thomas Campanella documents the urban transformation in China since the early 1990s in his new book, The Concrete Dragon: China’s Urban Revolution and What it Means for the World. “In terms of speed and scale and sheer audacity, China’s urban revolution is off the charts of Western or even global experience,” Campanella writes.

Today China has 102 cities with more than a million residents, compared to just 9 cities and only 50 metropolitan areas of that size in the United States. Many rural Chinese are moving into cities to find jobs; since the 1980s, an estimated 225 million people have migrated from the countryside into cities. Another 350 million—more than the population of the United States—will likely make the move by 2025.

In its race to modernity, China has been razing and rebuilding large parts of its cities, displacing millions of people. Beijing, with its growing perimeter of gated villa communities, housing estates, office parks, and shopping malls, is one of the most rapidly sprawling cities in the world.

Sprawl is such a common feature of the urban landscape that the Chinese call it tan da bing, or “making a big pancake,” Campanella says.

China is also building highways at record pace; the country had less than 200 miles of high-speed modern highways in the 1980s and 25,480 miles in 2006. By 2020, if China meets its projections for 53,000 miles of new highways, it will top the U.S. interstate system to become the largest highway system in the world. The Chinese are so proud of their new roads that there are tea-table style picture books featuring attractive aerial photos of the highways and interchanges.

Research zones inspired in part by North Carolina’s Research Triangle Park are wildly popular: in 2003 China’s cities had created nearly four thousand development zones in their suburban fringes. (Many of them failed to attract the hoped-for businesses.)

China is also building big; it has the world’s largest airport and shopping mall, many of the world’s tallest skyscrapers, the largest automobile showrooms, and the biggest gated community.

And China is building fast. In Shenzhen the Foreign Trade Center skyscraper rose at the rate of one floor every three days, which became known as “Shenzhen tempo.”

For those of us shocked at the massive scale and pace of building, Campanella reminds us of the nearest parallel: the building boom in major U.S. cities such as Chicago, home of the first skyscrapers, at the end of the nineteenth century.

“We were China once,” Campanella says. “We were a nation that did things in a big way.” Europeans touring the United States in the 1890s described the building boom in Chicago and Manhattan with the same mix of fear and admiration that strikes Western commentators who today describe Beijing or Shenzhen, Campanella says. Chinese cities are so willing to experiment that China has become the Holy Grail for architects and urban planners, he says.

Below: Xinghai Square, Dalian, 2006, currently the largest urban plaza in the world.

endeavors 35

Merging elevated highways, Nanjing, 2006. By 2025 China will have the most extensive national highway system on Earth.

Campanella explains that the feverish pace of modernization in China results from unleashed entrepreneurial zeal and yearning for a better quality of life. In 1949 the communist government led by Mao Zedong gained power after a twenty-three-year civil war against the ruling Nationalists. The new regime brought peace and order to the society, but also an increasing degree of control over economic and daily life. A passbook system known as hukou even dictated where people could live and work. During the Cultural Revolution, which lasted until Mao’s death in 1976, millions of students and intellectuals were sent to the countryside in an effort to erase class distinctions and eliminate the liberal bourgeoisie.

When Deng Xiaoping launched a bold program of economic reform in 1979, the population embraced the new opportunities to make money. “There was a pent-up longing to break out of decades of scarcity, poverty, and suffering,” Campanella says.

“The ambition—you can almost feel it in the air there.”

36 endeavors

The material desires of middle-class Chinese citizens, as Campanella describes them, are not unlike those of Americans.

They want safe housing in the suburbs with modern amenities and plenty of space.

They shop at IKEA and Wal-Mart, which at last count had 104 stores in China. They patronize drive-through McDonald’s and Kentucky Fried Chicken restaurants. Cars have become a status symbol. There are even Chinese McMansions.

Most suburban housing developments in China, though, are clusters of mid-rise and high-rise apartments on gated estates. These estates usually offer parking, landscaped parks, and services such as restaurants, clinics, convenience stores, and gyms.

Environment and health China’s rapid development, while improving standards of living for hundreds of millions, also has immense costs. One consequence—mentioned by almost anyone who has spent time in China—is air pollution. “You can’t go to China anymore and

An elderly woman awaits removal from her demolished neighborhood, Chongwen district, Beijing, 2004.

not be aware of how bad the air is,” says Gail Henderson, a UNC medical sociologist who has been doing research in China since the late 1970s.

Campanella, who spends part of each year at Nanjing University, said the air there is so polluted from chemical plants that when he returns to his apartment after a few days away, a thick coat of black soot covers every surface. He often develops a hacking cough during his time in Nanjing.

Air pollution, combined with the popularity of smoking among Chinese men, creates a “looming burden of disease,” Henderson says. An estimated 80 percent of Chinese men smoke; smoking is a ritual part of doing business in China.

Chinese people are also starting to develop the same kinds of weight-related health problems that burden the United States. “There’s been huge changes in the way people eat and move in China,” says Barry Popkin, who leads a university team that has done surveys on nutrition and health in 230 locations in China since 1989. When his team began doing surveys, there were almost no people who were overweight or obese. Now nearly one-third of adults are overweight or obese, Popkin says. Rates of diabetes and hypertension are increasing rapidly, as is mortality from cancer and heart disease.

The Chinese now consume three times the amount of cooking oil and meat that they did ten to fifteen years ago, Popkin says.

People are also more sedentary. Although millions still ride bicycles in China’s cities, the number has been plummeting in recent years. Those who can afford to drive prefer cars, and roads have become increasingly congested and dangerous for cyclists, Campanella explains.

Other consequences of China’s development include the exploitation of rural migrants who come to cities in search of work and end up in low-paying and often dangerous jobs in construction and industry. And China has destroyed much of its architectural heritage in constructing its modern cities, Campanella says. Virtually all of the historic hutong, or narrow-lane neighborhoods in Beijing, have been razed in recent years, often despite being listed as preservation zones.

China’s urban revolution also has broader consequences for the rest of the planet. One irony about China’s development, Cam-

panella says, is that it comes at a time that Western nations have finally become aware of the dangers of climate change. As humans burn more fossil fuels to power electricity, manufacturing, and transportation, climate scientists have been documenting rapid and unprecedented rises in the atmosphere’s carbon content.

Meanwhile, a new coal-fired power plant opens every ten days in China, according to Campanella. In 2007 China overtook the United States as the leading producer of greenhouse gases, according to the Netherlands Environmental Assessment Agency. In 2001 China’s total greenhouse gas emissions were 42 percent of the level of the United States.

China’s appetite for oil also places pressure on the world’s supply. China “is now the second largest consumer of oil in the world and burns through more fossil fuel than Russia and India combined,” Campanella writes. “If we continue our addiction to oil and China continues to demand oil, something’s got to give,” he says. China also buys large portions of the world’s coal, cement, copper, iron, and timber.

Campanella says that the United States has been wasteful in its use of oil and other natural resources for decades. “For China, reducing resource consumption is an even more urgent matter,” he writes. “The nation’s current course of fast growth and expanding resource use is utterly unsustainable.”

Sustainability movement awakens There is a small but growing movement toward sustainable development in China, says UNC’s Robin Visser, who studies Chinese art and culture. Visser says many recent Chinese films, novels, and art criticize the profiteering, corruption, waste, and shortsighted thinking that characterize much new development. “As people go through the transformation, they recognize there’s something missing,” Visser says.

In the last five years a new generation of architects and urban planners has become much more interested in sustainable building design, she says. Some are trying to recapture some of the lost values associated with traditional Chinese philosophies, which promote sustainability and simplicity. For example, Confucianism promotes moderation in all things, including consumption.

Confucianism also has a notion of harmony between people and nature. Taoism is also

“all about nature,” Visser says. It tries to help humans understand their dependence on nature, emphasizing minimalism. Likewise, Buddhism emphasizes harmony and respect for all living beings.

Visser senses a turning tide in thinking about sustainability among journalists, artists, and educators, but she says the average Chinese person is less knowledgeable about sustainability than is the average American.

And the vast majority of Chinese development remains unsustainable, Campanella says.

Still, there are some encouraging signs.

In 2005 the Chinese government passed a law promoting the use of renewable energy.

Dongguan Library: One of the world’s fastestgrowing cities, Dongguan aims for high culture.

Its sparkling new central library covers 125,000 square feet.

Solar water heaters glint from many rooftops (China has 60 percent of the world’s installed solar water heaters.) On June 1, 2008, Beijing began a ban on plastic bags.

Because China has shown itself willing to invest in ambitious urban development projects, Campanella says that China may show the rest of the world how to build a sustainable city. In coming decades China endeavors 37

plans to build a self-sufficient, sustainable city on an island in the middle of the Yangtze River near Shanghai. The city, called Dongtang, will get its power from wind farms and biofuels. Organic farms will provide food.

People will travel by solar-powered water taxi and buses powered by hydrogen fuel cells. Eco-tourism and high-tech industry will provide jobs.

There’s a lot at stake in whether China is willing and able to reinvent the city and promote sustainable living. “The continued growth of the Chinese economy—indeed the very viability of the People’s Republic— surely depends on it,” writes Campanella.

“And so do we all.” e Sheila Read is a master’s student in journalism at Carolina.

Thomas Campanella is an associate professor of urban planning at Carolina and a visiting professor at Harvard University. Gail Henderson is a professor of social medicine in Carolina’s School of Medicine. Barry Popkin is a professor of nutrition and director of the Nutrition Transition Research Program. Robin Visser is an assistant professor in the Department of Asian Studies.

Thomas Campanella (center, in sunglasses) with students and friends in China. The banner welcomes the UNC visitors.

WU WEI

38 endeavors

Water flowing from kitchen faucets looked like runny split-pea soup.

It smelled foul, and no one dared use it, not even to water plants.

I

t came from Taihu, China’s third largest lake. In June 2007 blue-green algae covered most of the 900-square-mile lake. The government shut down water supplies, including tap water for the four million people in Wuxi city. Chinese officials acted quickly, adding chemicals to try to kill the algae. They scooped out six thousand tons of slime, diverted water from the Yangtze River to flush the lake, and built a plastic barrier to prevent the algae from contaminating the water system again. They also extended the drinking-water intake farther into the lake.

Water color and smell returned to normal after a few weeks, but the blooms persisted until December. Many people refused to drink the tap water, which was understandable, says Carolina marine biologist Hans Paerl. Some blue-green algae, also known as cyanobacteria, produce toxins that can damage the liver, intestines, and nervous system. This hasn’t happened in China, but in 1996 one hundred people fell ill and fifty-five died when toxic blue-greens contaminated the water used at a dialysis clinic in Brazil.

Two weeks after the water crisis, Paerl was leaning over the side of a small motorboat to skim off some of Taihu’s scum for analysis. He discovered that China’s algae belong to the same genus as toxic algae found in North Carolina’s small ponds and stagnant estuaries, as well as in many larger bodies of water, such as Lake Erie, Lake Victoria, and the Baltic Sea. But nowhere are the blooms worse than on Lake Taihu, where habitats for eels, fish, and crabs are becoming endangered. Ten million people depend on a healthy Taihu for drinking water, fisheries, and tourism income.

China can try all kinds of things to kill or contain the algae, but the patient has been chronically ill for a while, Paerl says. Paerl is searching for the cure.

I

n 2007 Taihu’s massive algae blooms lasted from April to December. In each of the previous ten years, smaller blooms typically lasted from June until October, Paerl says. Before 1980, when the lake was known solely for its beauty, there weren’t any blooms. The lake was surrounded by fields of cotton, grain, tea, fruit, and grass.

Paerl says that Taihu’s problems began when China rapidly industrialized and embraced the market economy without limiting pollution of waterways.

Nutrient-rich sewage from wastewater plants and pollution from factories are the main culprits, Paerl says. Also, farmers can now afford fertilizers, which contain nitrogen and phosphorus that find their way into the lake. Blue-green algae thrive on these nutrients, and the result is a split-pea Taihu.

After last year’s water crisis, China’s premier Wen Jiabao called for cleaning up the lake and penalizing polluters. But China will have to do more.

“The first thing they need to do is treat all wastewater for nitrogen and phosphorous,” Paerl says. He estimates that city wastewater treatment plants are responsible for half the nitrogen and phosphorous in the lake. But dealing with the wastewater alone might not stop the bloom. And no one knows how many cutbacks will be needed from farmers and industries. So Paerl and scientists at the Nanjing Institute for Geography and Limnology of the Chinese Academy of Sciences are working together on recommendations based on bioassays of cyanobacteria samples they collected this summer.

New factories spring up each year in the densely populated Jiangsu Province.

Shanghai, sixty miles to the east, produces pollution that creates nitrogen-rich acid rain. Taihu is a very shallow lake, and it depends on rainwater for much of its replenishment. “This will be the biggest challenge because it will take a national effort to reduce nitrogen emissions to the air,” Paerl says.

China is promoting eco-friendly development but will soon pump more carbon dioxide into the atmosphere than any other country, warming the atmosphere and boosting blue-green algae growth.

SLIME AND THE CITY At China’s Lake Taihu, growth yields the wrong kind of green.

by Mark Derewicz

HANS PAERL

Above: Fed by pollution, algae invade Lake Taihu and are so persistent they’re “like cockroaches,” Hans Paerl says.

Last April, Paerl published an article in Science showing how algae blooms thrive in warm waters. Part of the warming problem has to do with stratification— when lakes form layers of water with different temperatures. With global warming, Paerl says, lakes are stratifying earlier in the spring and destratifying later in the fall. High temperatures help blue-green algae float to the surface where they absorb sunlight.

“They do very well under high ultraviolet light,” Paerl says. “They can move up and down the water column faster than any other organism because they can change their buoyancy. And they’re like cockroaches; they can survive on very little.”

Some cyanobacteria can fix nitrogen. That is, when they deplete the nitrogen in water, they can suck more nitrogen out of the atmosphere. The dominant bluegreens in Taihu can’t fix nitrogen, but the lake is home to other kinds that can.

If China limits nitrogen without limiting phosphorus, other kinds of blue-green algae could dominate, and these could be toxic. This is why Paerl and Chinese scientists are figuring out how much nitrogen and phosphorous should be limited.

“All this has been almost like a lesson in where not to build cities,” Paerl says. “Unfortunately, it’s too late to do anything about that. But it’s not too late for targeting reductions in nitrogen and phosphorous. This is not a doomsday scenario. Not yet.” e Hans Paerl is the William R. Kenan Distinguished Professor in the Institute for Marine Sciences. He received funding from the National Science Foundation.

Below: Pearl takes a sample of the slime from a small boat. He is working with Chinese scientists to recommend pollution controls that could help restore water quality in the lake.

LU ZHANG

endeavors 39

lingering risks Thousands of postmenopausal women stopped taking hormone replacement drugs after a federally sponsored study found that they were unsafe. But were the women safer after they stopped?

by Prashant Nair

40 endeavors

AMANDA ROHDE

M

illions of women in the United States have taken hormone replacement therapy, a treatment once heralded as a likely remedy for the health issues women face at menopause. A common form of the therapy—a cocktail of horse estrogens and synthetic progesterone—was approved by the Food and Drug Administration (FDA) to treat osteoporosis and the symptoms of menopause. The cocktail was also thought to keep heart disease at bay.

The evidence in favor of hormone therapy came from a series of observational studies. Randomized, controlled clinical trials of the drugs had not been conducted, but many doctors were convinced that the cocktail worked.

A l l t h at c h a nged i n 20 02 when scient ists conducted a randomized, double-blind, controlled trial as part of a large epidemiological study called the Women’s Health Initiative (WHI). The trial showed that combination hormone therapy using conjugated horse estrogen and synthetic progestin protected women from hip fractures but raised the risk of invasive breast cancer, heart attack, stroke, and blood clots.

In the trial, more than sixteen thousand postmenopausal women were randomly assigned to receive either the hormone cocktail or a placebo. The women were in the trial for an average of five and a half years before the health risks of the hormone combination became apparent and the trial was stopped. The FDA asked manufacturers to place new warning labels on the drugs and advised consumers to use the lowest effective dose or talk to their doctors about alternative therapies.

But Gerardo Heiss and other W HI researchers wanted to know more. “If a woman chooses to take the preparation,” Heiss asks, “what happens when she stops?”

From July 2002 to March 2005, Heiss and his colleagues followed up 15,730 women who had participated in the WHI trial. The women received annual breast exams and mammograms, and biopsies when needed. Heiss and his colleagues showed that some effects of combination hormone therapy were still present after two and a half years.

Women who had been tak ing the cocktail were 27 percent more likely than those who had been taking the placebo to

develop invasive breast cancer during the follow-up study. But the absolute risk of breast cancer in the hormone replacement therapy (HRT) group was lower in 2005 than it had been when the women stopped taking the drugs in 2002.

Heiss says the randomized assignment of participants to the two groups in the original trial canceled out the effects of differences in age, ethnicity, hypertension, smoking status, use of cholesterol-lowering drugs, and previous history of breast cancer and heart disease.

The researchers also examined the number of heart attacks, strokes, and blood clots during the follow-up study and found no signif icant difference between the HRT and placebo groups, indicating that the initial surge in the risk of cardiovascular events had ebbed after the HRT trial was stopped. The number of deaths due to all causes was not significantly different between the two groups. Heiss and his coworkers also found that the beneficial effects of the cocktail—decreased risk of hip fractures and colorectal cancer—disappeared once the therapy was stopped.

H

eiss says that women who appeared to benefit from the combination hormone therapy in studies prior to the WHI trial were better educated, had better access to health care, saw their physicians more often, and underwent cancer screening more regularly than the women in the WHI trial. “As a group, they showed a considerably more favorable health profile and survival than women who were not taking the preparation,” he says. Also, the observational nature of those early studies made it difficult to account for women who had stopped HRT due to side effects.

The lingering risk of breast cancer points to the need for continued screening, including breast exams and mammograms, for postmenopausal women who have stopped taking combination hormone therapy, Heiss says.

One limitation of the follow-up trial is that it took place over three years; the trial did not provide data about diseases that might develop over a longer period. Also, the women participating in the follow-up had been told at the end of the WHI trial whether they had been taking HRT or

findings Women in the HRT group were 27 percent more likely than those who had been taking the placebo to develop invasive breast cancer during the follow-up study.

The absolute risk of breast cancer in the HRT group was lower in 2005 than it had been when the women stopped taking the drugs in 2002.

The number of heart attacks, strokes, and blood clots during the follow-up study was not significantly different between the HRT and placebo groups.

The beneficial effects disappeared once the therapy was stopped.

a placebo. “Women possibly could have changed their behavior, once they realized the risks associated with tak ing the estrogen-plus-progestin combination. But we checked for their behavior, adjusted for it, and found it to be completely unrelated to the findings,” Heiss says.

The findings apply to combination hormone therapy that uses a specific mix of natural and synthetic hormones.

Some doctors prescribe bioidentical hormones, which have the same chemical structures as naturally occurring human hormones, but the drugs’ long-term health effects have not been studied in large clinical trials or observational studies.

Pharmaceutical companies are loath to conduct expensive, large-scale studies of bioidentical hormones because these compounds, having been invented by nature, cannot be patented. e Gerardo Heiss is a professor of epidemiology in the School of Public Health. His study, published in the March 2008 issue of the Journal of the American Medical Association, was funded by the National Cancer Institute, the National Heart Lung and Blood Institute, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, and the Office of Research on Women’s Health.

Wyeth-Ayerst Research, a pharmaceutical firm that manufactures the hormone cocktail and markets cancer-screening procedures, provided the medication and placebo for the WHI hormone study. The WHI trial was funded by the National Institutes of Health. endeavors 41

THE X-PHILES

42 endeavors

A rebel philosophical movement asks:

is the truth out there?

by Mark Derewicz

ILLUSTRATION: JASON SMITH

I

magine that a man wants to win the lottery, so he randomly picks five numbers and buys a lottery ticket. He wins. Did he do it intentionally? Most people say no; it was just luck.

Now imagine that a man wants to kill everyone in town, so he randomly picks five numbers and causes a nuclear meltdown.

Everyone dies. Did he do it intentionally? Most say yes.

That second scenario was luck, too, but the immoral act of killing people trumps luck, Joshua Knobe says. Knobe is one of the godfathers of experimental philosophy, a new movement at UNC and other schools that seeks to answer philosophical questions by asking actual people.

Knobe has asked hundreds of people about intentional action. And no matter the question, it seems that morality wreaks havoc with people’s perceptions of intention—even though most philosophers had thought for years that morality played no role in determining whether an act was intentional.

“You’d think that people would first try to figure out what’s going on in someone’s mind,” Knobe says, “and based on that people make a moral judgment, such as whether the person is to blame.”

The Knobe Effect, as it’s now known, occurs when we first figure out if something is morally right, wrong, or neutral, and then determine if a person did it intentionally.

Consider this: A manager tells his CEO that the firm’s new plan will earn a lot of money and help the environment. The CEO says, “I don’t care about the environment, I just want to make a profit.” The company goes ahead with the plan. It makes a profit and helps the environment. Did the CEO intentionally help the environment?

An overwhelming majority of people say no.

Now consider the opposite: a manager tells his CEO that the new plan will hurt the environment. The CEO says, “I don’t care about the environment, I just want to make a profit.” The company goes ahead with the plan and makes its money, but the environment is harmed. This time, the vast majority of people say the CEO intentionally harmed the environment. “In this case, we seem to decide that it’s morally wrong to harm the environment, and for that reason we end up concluding that the CEO intentionally harmed the environment,” Knobe says.

Other philosophers have asked different groups—psychopaths, four-year-old kids, people from other countries, people

with autism—the same or similar questions. The evidence is clear. Bad behavior—and even morally good behavior—seems to influence how we decide whether or not an action was done intentionally. And Knobe, too, is sometimes under the influence.

“The way I develop these experiments,” he says, “is to look inside myself and just think about what I’d say, and then I think, ‘Wait, I’d say all this weird stuff!’ Then I ask other people and they say the same things.”

But why would Knobe take to the streets to ask a bunch of ordinary people what they think? Isn’t philosophy the classic armchair endeavor? Not for Knobe and a group of mostly young philosophers who have embraced experimental philosophy—xphi for short—a new movement that’s getting mixed reactions within the larger discipline. Some philosophers think x-phi crosses the line into pop psychology, though many veteran thinkers don’t dismiss it outright.

Carolina philosopher Tom Hill, an expert on moral theory, says, “I think it can be valuable as long as good and sophisticated philosophers, such as Josh, are very careful about what conclusions they draw from their data. That’s the really controversial part—how and in what ways the empirical information is relevant.”

Geoffrey Sayre-McCord, who chairs Carolina’s philosophy department, agrees that experimental philosophers need to be careful about how they draw conclusions, but he also thinks x-philes are on to something good. He says that philosophers have always been dedicated to analyzing, articulating, and evaluating concepts such as free will and intentional action in the hope of finding definite answers. “But most philosophers do this depending solely on their own understanding of the concepts,” Sayre-McCord says. “A key feature of experimental philosophy is how it works to uncover the nature of the concepts.”

In the CEO experiment, Knobe found that 90 percent of people said that the CEO intentionally harmed the environment, but just 20 percent said the CEO intentionally helped the environment.

“Now, the temptation is to say, ‘Well, this just shows that people are no good with the concepts,’” Sayre-McCord says.

“But there’s a real bit of hubris in that dismissal. If you get robust results consistently, then there’s good reason to think, for instance, that our concept of intentional behavior has a moral eleendeavors 43

ment. I just don’t believe that philosophers have a lock on the concepts. So it’s relevant to try to figure them out.”

Although some other philosophers say x-phi turns traditional methods of critical thinking into the Gallup Poll, Knobe argues that x-phi actually is traditional philosophy.

“For almost all of history, philosophers were concerned about what human beings were really like,” Knobe says. “They wanted to know about human emotions, how human passion and reason interact, whether morality is innate or something we learn, and so forth.”

But in the twentieth century, many thinkers embraced analytic philosophy, which Knobe says can read something like this: Action (a) can be intentional if and only if the following six conditions are met: There exists some objective (o), such that the agent is seeking (o), and there exists— “It’s a very technical, quasi-mathematical discipline,” he says. “X-philes see themselves as sort of returning philosophy to the way it was traditionally—interested in a broader range of people.”

K

nobe didn’t invent man-on-the-street Q&As, but his fingerprints are all over x-phi’s genesis.

As a Stanford undergraduate in 1993, Knobe teamed up with a psychology grad student to conduct field experiments about the mind-set people need to have for a particular action to be considered intentional.

“We didn’t see this as philosophy,” he says.

“We published our work in a psychology journal.”

Knobe had no intention of becoming a philosopher. He feared becoming an academic; he wanted to work with people.

So he worked several jobs after college— teaching English in Mexico, working at a homeless shelter, helping people find affordable housing—but on weekends and after work he couldn’t help but write about philosophy, a hobby he had indulged since high school.

In 2000 Knobe finally took the plunge and starting doing doctoral work at Princeton.

He noticed that young philosophers at other universities were conducting interesting experiments. Then he read an article written by a Florida State University professor who 44 endeavors

deduced from Knobe’s psychology paper that morality had nothing to do with how humans view intentional action. “When I read his article, I thought, ‘Wait, that has got to be wrong,’” Knobe says. “So I started doing experiments to prove that this thing I wrote was wrong.”

That’s when he concocted the CEO experiment. Since then, he has come up with many more questions to uncover what humans are thinking when morality and intentionality collide. And a lot of young philosophers have embraced his way of doing philosophy.

Discussions of x-phi have heated up on blogs. Some thinkers question the method’s validity. Others love it. And some x-philes seem to revel in the controversy. Knobe isn’t really one of them, but his wife, musician Alina Simone, wrote an x-phi anthem that philosophy department staffer Jennie Dickson turned into a YouTube video in which the only image is an armchair on fire.

X-phi has now infiltrated many philosophy departments, including Carolina’s.

Doctoral student Felipe De Brigard has used experimental philosophy to challenge a long-standing theory about what humans value.

For centuries, many philosophers thought that everything humans do could be boiled down to the pursuit of pleasure. In the 1970s philosopher Robert Nozick devised a thought experiment to see if that was true. He thought that if given a choice between living in a virtual-reality machine (in which life would seem wonderful), and living a real life (no matter how terrible), people would choose the real life.

This, Nozick thought, meant that people don’t value pleasure above all else.

De Brigard, though, wasn’t sure Nozick’s idea told the whole story. He decided to ask people what they thought, adding a twist to Nozick’s experiment.

Imagine you’re already plugged into that virtual-reality machine and living a wonderful fake life, and then there’s some technical glitch that makes you aware of the situation. So the scientist in charge says you

can choose to stay in the machine or return to your real life.

De Brigard wanted to know what people would do if they found out that their real lives would be terrible, or wonderful, or a complete mystery. When told that their real lives would be terrible, 90 percent of people said they wanted to resume their wonderful virtual lives. When De Brigard gave people the other two options, 60 percent of the people still chose to stay in the machine.

“So people don’t seem to be seeking only pleasure,” De Brigard says. “Nozick is right.

But the experiment doesn’t suggest that people are valuing reality either. What I suggest is that people tend to value the status quo; they value the life they know, whether it’s real or not.”

“X-philes see themselves as sort of returning philosophy to the way it was traditionally— interested in a broader range of people.”

—Joshua Knobe

B

ut De Brigard doesn’t say that all people value the status quo. He says his experiment simply shows that philosophers should think twice before suggesting that all humans value one thing over another.

Another implication, he says, is that philosophers should be careful when using thought experiments—especially when the concept in question can be tested.

Consider one of Knobe’s favorite topics: intuition. Knobe says that some philosophers think about what a person’s ordinary intuition would be in a given situation and come up with a theory.

“But then experimental philosophers go out and check that ordinary intuition,” Knobe says, “and sometimes it’s the opposite of what the philosophers thought.”

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VINCIANE VERGUETHEN

He also says that experimental methods make it possible to do things that philosophers could never do in their own heads.

X-philes can concoct experiments to study how people of different cultures view intuition. They can study how young children feel about certain concepts. They can look at how quickly people answer different kinds of questions. They can make correlations

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between a person’s moral views and moral judgments.

“So, maybe there’s a certain distance you can go inside your own head,” Knobe says.

“But there’s an extra distance you can go when you take to the streets.” e Joshua Knobe is an assistant professor of philosophy in the College of Arts and Sciences. In

e humans like to think we know what’s going on inside our own heads. But philosopher Josh Knobe is proving that we often don’t know diddly. Consider his experiments about intentional action, morality, and what we value: Jake desperately wants to win a shooting contest. He knows that he will win the contest only if he hits the bull’s-eye. He raises the rifle, gets the bull’s-eye in the sights, and pulls the trigger. But Jake is not a very good rifleman. His hand slips, and the shot goes wild. Nonetheless, the bullet hits the center of the bull’s-eye. Jake wins the contest.

The majority of people Knobe asked say Jake did not hit the target intentionally. Whether or not most people are correct doesn’t matter to Knobe as much as what people think when morality enters the picture. Consider this: Jake desperately wants more money. He knows that he will inherit a lot of money when his aunt dies. One day, he sees her walking by the window. He raises his rifle, gets her in his sights, and pulls the trigger. But Jake isn’t a very good rifleman. His hand slips, and the shot goes wild. Nonetheless, the bullet hits his aunt in the center of her heart. She dies instantly.

In this case, the vast majority of people say Jake did hit the target—his aunt—intentionally. Why? Because people blame Jake and so they figure he must have intentionally shot her. Maybe he did. But logically—and according to many philosophers—people should also say that he hit the bull’s-eye intentionally in the first example. And most of us don’t say that.

Now consider an example where a behavior is morally good.

Klaus is a German soldier during World War II. His regiment has been sent on a mission that he believes to be deeply immoral.

Many innocent people will die unless he can somehow stop the mission. He decides that the best way to sabotage the mission is to shoot a bullet into his own regiment’s communication device. He knows that if he gets caught he may be imprisoned, tortured, or even killed. He could try to pretend that he simply made a mistake, but he is almost certain that no one will believe him. With that thought in mind, he raises his rifle, gets the device in his sights, and pulls the trigger. But Klaus isn’t a very good rifleman. His hand slips, and the shot goes wild. Nonetheless, the bullet hits the center of the 46 endeavors

summer 2008 he won the Hettleman Prize for Artistic and Scholarly Achievement by Young Faculty. Tom Hill is a Kenan Professor of Philosophy and Geoffrey Sayre-McCord is the Morehead Alumni Professor of Philosophy and chair of the Department of Philosophy. Felipe De Brigard is a doctoral candidate and Jennie Dickson is the program coordinator, both in the Department of Philosophy.

communication device. The mission is foiled, and many innocent lives are saved.

Here, most people say Klaus hit the communication device intentionally.

Knobe found that 23 percent of people say that Jake intentionally hit the bull’s-eye, 91 percent say Jake intentionally hit his aunt in the heart, and 92 percent say Klaus intentionally hit the center of the radio. Other philosophers have replicated this experiment several times. The results are always the same.

Here’s one of Knobe’s experiments about what humans value in light of morality: Suppose that Jim grows up in a culture where everyone is racist. He thinks the people around him are right, that he ought to do things to advance his own race, even at the expense of people of other races. But sometimes Jim feels that he might be wrong.

He finds himself feeling guilty, and as a result he winds up doing things to foster racial equality. But then he thinks that’s a mistake.

He thinks he ought to go back to doing racist things like everyone around him.

So, is it right to say that despite his conscious beliefs Jim actually values racial equality? Most people say yes, that despite the conclusion Jim comes to, he actually values racial equality.

Now imagine the scenario another way: Bob grows up in a culture where everyone believes in racial equality. He thinks the people around him are right, that he ought to be advancing the interests of all races equally. But sometimes Bob feels a pull in the opposite direction and he starts to feel guilty about doing things that harm his own race in order to advance the interests of other races. As a result he does things to foster racial discrimination. But then he thinks about it and realizes his mistake, and he goes back to work for racial equality.

So, is it right to say that despite his conscious beliefs Bob actually values racial discrimination? Most people say no. Bob values racial equality.

Joshua Knobe, an assistant professor of philosophy, conducted experiments on valuing with Erica Roedder, who joined Carolina’s philosophy faculty in fall 2008.

—Mark Derewicz

in print Beyond Baldwin’s fire For author Randall Kenan, today’s racial conflicts are more cultural than moral.

MARK DEREWICZ

The Fire This Time. By Randall Kenan. Melville House Publishing, 149 pages, $20.

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hen I read James Baldwin’s gritty 1963 memoir The Fire Next Time, I wondered if it was truly meant for someone like me, a middle-class kid from lily-white suburbia. It made me sweat.

Today as I read Randall Kenan’s memoir and essay The Fire This Time, I know his words are meant for eyes like mine. We now live in a country that might elect a black president. We live in Oprah Winfrey’s America. People get fired for slinging racial slurs. Universities, once segregated, now help poorer minority students attend college. But life along the color line is far from perfect.

The titles of both books refer to an ominous prophecy that a black slave wrote and sang—God gave Noah the rainbow sign. No more water; the fire next time!

Baldwin wrote honestly about what it meant to grow up black in Harlem, what it meant to be black in mid-twentieth-century white America. The struggles were many, but he saw hope and beauty in people black and white—even though he knew racism will die hard, if it ever will.

Kenan’s The Fire This Time takes a direct cue from Baldwin’s best-seller, telling stories of life in the United States and what race means here today. But Kenan’s book is different. It has to be, because no matter how much remains the same, so much has changed.

The Civil Rights Movement was a moral crusade, a fight for equality before the law.

Kenan says we revere Martin Luther King, Jr. and Rosa Parks because their cause was based on what was morally correct.

But today, race as an issue is more about culture than it is morality, Kenan says.

“Once the morality is removed,” he

writes, “we are left with a not-so-easily defined struggle. Race, as a rallying cry, as something over which to politically bond, at once loses its potency and is transformed into something unnecessary, even ugly; an excuse, something one should not be preoccupied with.”

From Hurricane Katrina to the violent, sexist music staking its claim to the rhythm and blues and hip-hop traditions, the fires along the racial divide come in varied forms this time.

Yet Kenan’s book is much more than a treatise on our problematic race relations; it weaves in history with culture and personal stories like Baldwin used to do. It didn’t make me sweat as much as it made me appreciate the depth of what it means—and could mean—to be an American.

—Mark Derewicz Randall Kenan is an associate professor of English in the College of Arts and Sciences. endeavors 47

The unanswered question Your sweetheart job Courting Your Career. By Shawn Graham. Jist Works Publishing, 194 pages, $12.95.

F

inding the perfect job is a lot like dating. In fact, the metaphor fits so well that readers might want to use Shawn Graham’s new book to find that someone special, too.

You’ve got to know your type, and to know your type you’ve got to first know yourself. Then you’ve got to get to know who’s out there; you don’t want to work for a firm just because it’s hot.

Yeah, flirting is okay. You can shadow an employee who has the kind of job you think you might like.

You can see people casually; it’s called interning. You can have several internships before getting serious.

Eventually you’ll have to narrow your search. Figure out what you don’t want, but be open. For instance, if there are no jobs available in Western Pennsylvania for a minor league hockey executive, try another state, or country, or sport.

Use your friends; they often know the people you need to meet. The folks at your school’s career services office, for example, know a lot of people.

Go clubbing. Job fairs are meat markets, yes, but if you know what you’re looking for, you might find it.

Always remember to dress appropriately. Those holey sneakers are not endearing, nor are they lucky.

Then comes the big day—the first date, I mean, first interview.

You can foul up here in all sorts of ways, and you might never get that call-back. But Graham has all kinds of sound advice to see you through.

And, he says, don’t worry; it only gets easier the more you do it.

—Mark Derewicz Shawn Graham is the associate director of the MBA Career Management Center at UNC’s Kenan-Flagler Business School.

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God’s Problem: How the Bible Fails to Answer Our Most Important Question—Why We Suffer. By Bart Ehrman.

HarperCollins, 294 pages, $25.95.

L

ast time we checked in with Bart Ehrman he had just published his best-selling book, Misquoting Jesus, in which he showed how scribes made many errors while copying the Bible and sometimes even added new material to the text. In his latest book, God’s Problem, Ehrman shows that the Bible is full of different and sometimes contradictory answers to the tough question of why humans suffer.

Ehrman says that Bible writers do give some good answers that we can relate to. Some people say they’ve suffered but then seen a purpose in it later. We’ve all done wrong, and sometimes people say they’ve experienced karmic justice.

COKE WHITWORTH

Bart Ehrman: the Bible is confusing on the topic of why people suffer.

But Ehrman says the Bible falls way short of explaining why the world is full of suffering.

After interpreting and deconstructing hundreds of Bible passages, Ehrman winds up agreeing with Ecclesiastes: why we suffer is a mystery. And that, Ehrman says, isn’t really an answer at all, if God is all-loving the way humans define all-loving. Ecclesiastes also says there’s no afterlife, so we might as well eat, drink, and be merry.

“My addendum to that,” Ehrman says, “is that it’s impossible to enjoy life fully if we know that other people are suffering. So part of embracing life should involve helping people who are suffering.”

—Mark Derewicz Bart Ehrman is the James A. Gray Distinguished Professor of Religious Studies in the College of Arts and Sciences.

God’s Problem is a New York Times best-seller. See the full transcript of the Endeavors interview with Bart Ehrman at http://research.unc.edu/endeavors/fall2008/.

LIESBETH BERNAERTS

LIESBETH BERNAERTS

endview Tuberculosis patients in many African countries must trek to the nearest clinic every day for what doctors call Directly Observed Treatment. Clinic staff watch patients take their medications to make sure the patients swallow the pills in the right combination and order. The World Health Organization says Directly Observed Treatment may help control the spread of TB and prevent drug resistance. Above: A man waits to see the nurse at a clinic in Kinshasa, Democratic Republic of Congo. Left: A baby with tuberculosis is weighed at the same clinic. Carolina tuberculosis researcher Annelies Van Rie says the percentage of TB patients who are children is relatively small, but many children who are infected with TB are also HIV-positive.

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endeavors

Page 26: Norris Brock Johnson first saw Japan’s

Page 34: When the Chinese say they are

Temple of the Heavenly Dragon as a tourist. But he knew right away that the garden had secrets to tell. Photo by Norris Brock Johnson

“making a big pancake,” they don’t mean they’re cooking. Take a look inside China’s building boom.

Photo by Thomas Campanella

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Page 15: Carolina’s Center for Global Initiatives holds an annual photo competition. Here, the sun illuminates the Basilica of St. Peter in Vatican City.

Photo by Elizabeth DeOrnellas