News this Week

Science  26 Apr 2013:
Vol. 340, Issue 6131, pp. 412
  1. Around the World

    1 - Swansea, U.K.
    Measles Outbreak
    2 - Ya'an, China
    Longmenshan Fault Ruptures Again
    3 - Milan, Italy
    Protestors Steal Animals, Destroy Research
    4 - Vancouver, Canada
    Ocean Fertilization Experiment Still Making Waves

    Swansea, U.K.

    Measles Outbreak

    Public health officials in South Wales are sending vaccination teams from school to school in an effort to contain a measles outbreak that could become the largest in the United Kingdom since the combination MMR vaccine (which also protects against mumps and rubella) was introduced in 1988. According to Public Health Wales, more than 800 people have fallen ill and 80 have been treated in hospitals since the epidemic, centered in the city of Swansea, began late last year. The body of a young man who died in the city last week while suffering from measles is also being examined to determine whether the virus caused his death.

    Measles cases have increased in many European countries in recent years. In 2012, the Health Protection Agency counted 2016 measles cases in England and Wales, the highest number since 1994. The virus is highly contagious, and scientists estimate that 95% of people need to be vaccinated to protect against an outbreak. That coverage is rarely achieved in Europe, largely because many parents overestimate the risk of side effects of the vaccine and underestimate the risk that the disease poses.

    Ya'an, China

    Longmenshan Fault Ruptures Again

    Firefighters search for survivors on 21 April.

    CREDIT: CDSB - IMAGINECHINA/AP PHOTO

    The dragon woke again, and this time scientists weren't caught off guard. On 20 April, a magnitude-6.6 earthquake struck 13 kilometers below the surface of Ya'an, a city of 1.5 million in western China's Sichuan Province. As Science went to press, Chinese authorities were reporting that more than 200 people lost their lives in collapsed buildings and quake-induced landslides.

    The temblor struck about 130 kilometers southwest of the epicenter of the 2008 Wenchuan earthquake, a magnitude-8.0 event that killed more than 80,000 people. Five years ago, the northern segment of the Longmenshan fault ruptured; last weekend, it was the southern segment's turn. Before Wenchuan, few geophysicists paid attention to the fault, which "has a relatively low slip-rate" and hadn't uncorked a big earthquake for centuries, says Mian Liu, a geophysicist at the University of Missouri, Columbia. But in the past 5 years, he says, researchers have been studying the fault extensively, and they detected stress building up along the southern segment. Where the next big Sichuan earthquake will strike isn't clear—but, Liu says, odds are on the Xianshuihe fault, west of Longmenshan.

    Milan, Italy

    Protestors Steal Animals, Destroy Research

    Five people chained to the doors and valuable research mice wandering around free: That was the scene that greeted scientists with the University of Milan's Department of Medical Biotechnology and Translational Medicine on 20 April. During a national protest against vivisection that drew 400 demonstrators to the university, five members of the pro-animal movement Fermare Green Hill (Stop Green Hill) illegally entered the department's building, also home of the Institute of Neuroscience of the National Research Council (CNR).

    After hours of negotiations, the researchers were able to convince the intruders not to free most of the facility's animals, which are mainly used as models for neurodegenerative diseases. However, the intruders did take about a hundred transgenic mice and one rabbit and destroyed the identification cards on all the animal cages.

    The following day, a group of university scientists openly protested, for the first time in Italy, against pro-animal ideology, and the University of Milan sued Stop Green Hill. "Our animal models are treated according the European legislation. These people ruined years of research funded by national and European agencies" said Cecilia Gotti, a CNR researcher in Milan.

    Vancouver, Canada

    Ocean Fertilization Experiment Still Making Waves

    Questions are still spinning around the legality of a geoengineering experiment conducted last summer in international waters. Last week, a native Canadian tribe filed a legal motion in provincial court in British Columbia to challenge a search warrant of its offices that was executed by Environment Canada in March. The search was part of an ongoing government investigation into the Haida Salmon Restoration Corp.'s controversial experiment, which involved dumping 100 tons of iron dust into an eddy 321 kilometers west of the Haida Gwaii islands to encourage the growth of algae and thereby increase fish stocks (http://scim.ag/Haidafert).

    Environment Canada says that two international treaties on ocean dumping to which Canada is party prohibit the practice unless it can be deemed "legitimate scientific research." An attorney for Haida, which is affiliated with the Old Masset Village, a First Nation group in British Columbia, says that those treaties are nonbinding and that only domestic Canadian legislation can actually bar ocean fertilization. If the motion to challenge the search warrant is successful, the confiscated materials, including scientific records and files, will be returned. No arrests have been made or charges filed.

  2. Random Sample

    How Low Can They Go?

    CREDIT: MICHIGAN SEA GRANT

    The Great Lakes at the U.S.-Canadian border, with Asia's Lake Baikal and Africa's Lake Tanganyika, make up half the volume of the world's surface fresh water supply. This week, the National Oceanic and Atmospheric Administration (NOAA) reported that in January lakes Huron and Michigan dipped to their lowest point since monitoring began in 1860. The record continues almost 15 years of low water that began in 1998, a dry year with unusually warm water, extensive evaporation, and little precipitation and runoff flowing into the lakes. From 1998 through 2000, lake water levels dropped by about a meter, says NOAA hydrologist Andrew Gronewold, who is based in Ann Arbor, Michigan. Fish are cut off from the wetlands and rivers they need for reproduction, and giant commercial ships struggle to get through the channels that connect the lakes. NOAA and the U.S. Army Corps of Engineers predict lake levels will rise this summer, but not by much.

    ScienceLIVE

    Join us on Thursday, 2 May, at 3 p.m. EDT for a live chat on new exoplanet discoveries. How close are we to finding a mirror Earth? http://scim.ag/science-live

  3. Newsmakers

    Take Two: Research on Aspirin and Heart Disease Earns Prize

    FitzGerald

    Patrono

    CREDIT: SABINA LOUISE PIERCE; COURTESY OF CARLO PATRONO

    A pair of pharmacologists has won the prestigious Grand Prix Scientifique, given annually by the Institut de France for work in cardiovascular health. Garret FitzGerald of the University of Pennsylvania and Carlo Patrono of the Catholic University in Rome will share just over $650,000 (€500,000) for disentangling how low-dose aspirin staves off heart disease.

    "We competed, we collaborated, but we always remained friends," says FitzGerald of his relationship with Patrono.

    Their work, performed mostly in the 1980s and early 1990s, came after years of clinical trials mysteriously failed to show low-dose aspirin helping the heart. "People were saying, ‘We know in a test-tube aspirin inhibits platelet formation,’" reducing clots, FitzGerald says. "‘Why doesn't it in people?’"

    Often racing each other, Patrono and FitzGerald sought to bridge the gap between test tube and human being. They elucidated how aspirin acts on platelets and identified both the ideal drug dose and who would benefit most: people with unstable angina, who experience a proliferation of platelets, leading to blood clots and heart attacks.

    France Loses Molecular Biology Pioneer

    Jacob receiving his Nobel Prize.

    CREDIT: AP PHOTO

    French geneticist, World War II hero, and science writer François Jacob died on 19 April at the age of 92. Jacob was one of the fathers of molecular biology. Initially trained as a medical doctor and surgeon, he was severely wounded while serving as a medical officer for the Free French Forces. He began his research career in 1950 at the Institut Pasteur, when he began investigating how genes control enzyme synthesis. For his development of the "operon model," in which structural and regulatory genes coding for related proteins are arranged in units called operons, Jacob won the Nobel Prize in physiology or medicine in 1965, together with colleagues André Lwoff and Jacques Monod.

    The operon model "had a major impact on biology as a whole," because it pooled biochemistry and genetics, and also "answered a question that geneticists had been asking for more than thirty years," said biologist and science historian Michel Morange, a former student of François Jacob, in an obituary released by the Institut Pasteur. Jacob received the highest French military decoration for World War II and was a former Chancellor of the Order of the Liberation.

  4. Public Enemy Number One

    1. Richard Stone

    North Korea has one of the highest TB rates outside sub-Saharan Africa and a burgeoning drug-resistance problem. A remarkable unusual collaboration is hoping to turn the tide.

    Room for hope?

    Thanks to donations and preferential grain rations, conditions are improving at the Ryokpo rest home and other TB facilities.

    CREDIT: R. STONE/SCIENCE

    UNPA, NORTH KOREA—This village in rugged hills 2 hours south of Pyongyang has had it rough. Last summer, a typhoon wiped out most of its corn crop, and a second windstorm ripped stone tiles from roofs. Clinging to a slope facing the settlement, the Unpa tuberculosis (TB) rest home—a tidy gray concrete building with a red roof—took a battering. None of the staff members or 46 patients was harmed. But the hurricane-force gales shattered windows of a ward under construction that will house patients infected with multidrug-resistant (MDR) TB and sent its steel roof sailing down the valley. Surveying the damage, Heidi Linton, executive director of Christian Friends of Korea (CFK), a humanitarian organization based in Black Mountain, North Carolina, jots down a list of materials that CFK intends to purchase for the MDR wing. Occasional booms punctuate the stillness: Distant artillery fire as North Korea prepares for what it sees as an inevitable military conflict with the South.

    Rough decade.

    North Korea is struggling to rein in its TB epidemic.

    CREDIT: GLOBAL TUBERCULOSIS REPORT 2012, WHO/ ADAPTED FROM SHARON PERRY, DOCTORS WITHOUT BORDERS

    As war fever reached a frenzied pitch last month, Linton and six other Americans were in the countryside with North Korean scientists and physicians, joining forces against a common enemy: tuberculosis. TB has skyrocketed in the Democratic People's Republic of Korea (DPRK) in the past 20 years, according to the World Health Organization (WHO). Famines in the mid-1990s ignited the epidemic; chronic malnutrition ever since has added fuel to the fire. North Korea now has one of the highest TB incidences outside sub-Saharan Africa.

    That makes it unusual. Nearly all other countries with high TB case rates also have high HIV/AIDS rates. HIV suppresses the immune system, allowing TB to flourish. In North Korea, "essentially there is no HIV," says Gary Schoolnik, an infectious disease researcher and physician at Stanford University School of Medicine in Palo Alto, California. "That's why," he says, "the magnitude of the TB problem in North Korea is so surprising." It also means that among infectious diseases, TB is the biggest killer in North Korea; globally, the mycobacterium is number two, after HIV/AIDS.

    The TB menace unnerves North Korea's neighbors. China in recent weeks has tightened security along its border with DPRK, reportedly to stem a surge of refugees if conditions on the Korean Peninsula deteriorate. The potential burden is a real concern, says an official with China's health ministry in Beijing. "We're scared to death of its destabilizing effects," he says.

    Offering hope that North Korea can get control of the TB epidemic, DPRK's Ministry of Public Health, CFK, and Stanford in October 2010 opened a National Tuberculosis Reference Laboratory (NTRL) in Pyongyang. The effort is a rare example of scientific cooperation between North Korea and the United States and, at a time of heightened tensions, one of DPRK's few active links with the West. NTRL researchers can now diagnose TB cases that are resistant to first-line drug combinations, making it possible to spot patients who need more aggressive therapy. And the lab will soon add capacity to screen for extensively drug-resistant TB, known as XDR—the worst strains, some of which are close to impossible to treat. "This is a critical point in the development of their program, says Kathleen England, a Stanford microbiologist who is spending weeks at a time at North Korea's NTRL to help it win international accreditation, as early as 2015. Attaining that gold standard, says Schoolnik, who has been involved in the project since its inception, "would allow North Korea to join the global fight against TB."

    Slideshow

    Last month, I joined Linton's team on visits to four rural TB rest homes and two facilities in the capital: NTRL and the pediatric ward of the Pyongyang District #3 TB Prevention Hospital. (The DPRK government cleared my visit as a journalist.) The trip came at a delicate time, as South Korea and the United States were conducting annual military exercises that included stealth bomber flights over South Korea. Angered by a fresh round of U.N. sanctions imposed last month over its third nuclear test, North Korea's response to the drills was to sever hotlines, "scrap" the armistice ending the Korean War, suspend operations at the Kaesong industrial park—a joint venture with the South—and issue bellicose threats. Last month, state television aired interviews with North Koreans railing against U.S. imperialists and showed leader Kim Jong Un inspecting garrisons and planning military maneuvers. Buses and locomotives were festooned with camouflage netting, and a new propaganda mural in Pyongyang depicts a missile bearing down on Capitol Hill. "I've never seen things ratcheted up so high," says Linton, who has made more than 40 trips to DPRK since 1998 on missions to renovate hospitals and oversee distribution of donated food and materials, mostly in the southwest.

    North Korea may believe that its enemies are poised to strike. But TB, one of humanity's most enduring scourges, is already running rampant across the isolated nation.

    Empty bellies

    Along the highway leading south from Pyongyang, work brigades are out in force. One group of villagers is tilling paddies in preparation for transplanting rice shoots later in the spring. Lines of red flags on wooden poles flutter in the breeze, a DPRK way to promote camaraderie. A brigade of women is working on railroad tracks, using their hands to even out gravel between the ties, their bicycles lying haphazardly along the elevated bed. In a field down the road, a line of red signboards, each emblazoned with a white Korean letter, declares "Comrade Kim Jong Un, live 10,000 years!"

    At the Unpa TB rest home, Director Ko Gwang Sung invites us into a reception room. One wall shows a painted landscape of fractured granite peaks lapped by ocean waves: "Sea Kumgang," the coastal range of the Diamond Mountains in the southeast. Linton, who has been to Unpa nearly a dozen times, runs through a list of questions that she has prepared for each rest home. She takes the sanatorium's vital signs, quizzing Ko on how many doctors, patients, and beds the sanatorium has; the number of patients with infectious pulmonary TB; and whether drug stocks are sufficient.

    In much of the world, TB is in retreat. A 2012 WHO report notes that new TB cases have been falling for several years; since 1990, the mortality rate has decreased 41%. "[T]he world is on track to achieve the global target of a 50% reduction by 2015," WHO states. North Korea is bucking that trend. In 1994, it reported fewer than 50 cases per 100,000 people—a third of the rate of South Korea. By 2011, North Korea's TB incidence had climbed to 374 cases per 100,000 people—four times the rates in China and South Korea (see graph). Although there "certainly could have been significant underreporting" over the years, Schoolnik says, "I think the increase is real." WHO estimates that among North Korea's 24 million people, there are 91,200 active TB cases. That figure is a stab in the dark. "We are not able to get numbers from everywhere, so we assume the rate is higher," England says. Officials in Pyongyang keep data close to the vest. "Data are not being shared," England says.

    Ko, like other Korean TB workers, says that recently improved case detection could explain the stubbornly high incidence. In southwestern DPRK, at least, "cases are leveling off," says Ko, who witnessed how the epidemic began to unfold 2 decades ago. But by no means is there a consensus. "I'm not convinced it's slowing down. We may have a ways to go before we hit the top of that curve," Linton says.

    One point of agreement is that the roots of the present crisis lie in an epic famine that North Koreans call the Arduous March. Between 1994 and 1998, hundreds of thousands of Koreans starved to death; hunger-weakened survivors were vulnerable to infections. TB rates "climbed significantly," England says. The bug is everywhere: One out of every three people in the world has a latent TB infection that a healthy immune system usually keeps at bay. But in malnourished people, TB can break out of its cage and multiply in the lungs. A person with untreated pulmonary TB infects 10 to 20 people on average, Schoolnik says.

    Across North Korea, county governments oversee collective farms, gather up harvests, ship food to Pyongyang and to army outposts, and dole out what's left to the rest of the population. Linton's team has learned from its recent visits to rest homes that the government has set the grain ration for adult TB patients at 450 grams per day, handed out as corn or rice. The ration "is an improvement over previous years," Linton says. "It tells me that the DPRK government may finally recognize that TB patients should be prioritized in the distribution of food." But full rations are rarely met. Food consumption tends to tail off in spring, as stocks from the previous year dwindle. The lean months last until autumn, after the harvest. Meat is distributed only during holidays, such as last week's anniversary of the birth of Kim Il Sung, the nation's founder. To supplement diets, CFK distributes tons of donated canned meat to TB rest homes, accounting for 20% to 70% of patients' protein consumption. It also sends greenhouse kits, seeds, and soil inoculants.

    Another driver of the TB epidemic is an inconsistent drug supply, especially before WHO opened its country office in Pyongyang in 2001. North Korean firms produce at least two drugs used to treat TB—isoniazid and streptomycin—but quality is uncertain and administration is uncontrolled. Stanford researchers have bought both in hotel convenience stores. The health ministry has no funds to import TB medications, so its supply of reliable drugs now comes primarily from the Stop TB Partnership's Global Drug Facility, which operates out of WHO, and the Eugene Bell Foundation, a humanitarian organization based in Washington, D.C.

    A deep bond.

    Kim Ha's gift of pheasant eggs touched Heidi Linton.

    CREDITS: R. STONE/SCIENCE (2)

    Poor compliance with therapy has spurred TB rates higher. TB drugs must be taken daily for up to 2 years; abandoning a regimen in midstream breeds resistance and treatment failure. To ensure compliance, health departments around the world have implemented directly observed therapy, short-course, or DOTS, in which health workers watch patients take their medicine. North Korea began practicing DOTS routinely only about 10 years ago.

    Rampant resistance

    A watershed moment for Linton came in the spring of 2007, on a visit to the Hwangju TB Rest Home. The director, Kim Ha, presented her with several bluish-green pheasant eggs. "His hands were hot with fever," Linton recalls. "He was trying not to cough on us." Ill with TB, Kim had spent 4 days in the hills gathering the eggs—the most precious gift he could muster—to present to the CFK team. "He needed that protein. His staff, his patients needed that protein, way more than we did. I was in tears," she says. "Some people back in the States ask me why we do this, helping 'those ungrateful people,'" Linton says, voice breaking. She tells them about Kim's gesture. "If that's not gratitude, I don't know what is."

    Mounting toll.

    A health official logs sputum samples of suspected MDR patients in Unpa.

    CREDIT: R. STONE/SCIENCE

    Six years later, Kim, 58, is enduring his fifth bout of TB. This time it's MDR. "I was going to retire," he tells Linton, "but the food you sent us gave me the strength to work." After a stint in the army, Kim entered medical school and worked at Hwangju County TB Hospital before being assigned to the rest home. He vows to finish building an MDR ward here at the sanatorium before hanging up his stethoscope. MDR is a burgeoning problem in Hwangju, Kim says: "It's a big worry." He attributes the increase to frail health and poor nutrition, failure to adhere to drug regimens, and heavy alcohol consumption.

    Linton has a donation just for Kim: three pairs of handmade wool mittens. "The ladies didn't know how big your hands are, so they made these in different sizes," she says. "A lot of people are praying for you." Kim says thanks, and with a wan smile asks whether CFK can also donate a motorcycle.

    Each day before breakfast, Linton's CFK team gathers in their hotel for devotions. On Sunday mornings, they attend services at one of the three Christian churches in Pyongyang. CFK was founded after evangelist Billy Graham's visits to North Korea in 1992 and 1994 paved the way for Christian groups to come in. "It took a while for us to understand each other," says Schoolnik, who is not Christian. But Linton, he says, has been instrumental. "She has enormous on-the-ground experience and is extremely well-respected," he says. "I'm absolutely sure we could not have worked in North Korea without her."

    It will take more than prayer to tackle North Korea's MDR problem. DPRK's health ministry estimates that up to 15% of TB patients fail first-line treatment, which suggests that they are actively infected with drug-resistant strains. Based on those figures and drug resistance patterns elsewhere in Asia, North Korea could have as many as 15,000 people with drug-resistant TB, England says. Many, she says, are undiagnosed, untreated, or being treated inappropriately. Few MDR patients are isolated from others in TB wards or from healthy people. In the TB rest homes, "it's worrisome that a patient being treated for drugsusceptible TB could become infected with a drug-resistant strain by being exposed to another patient," says Edward Desmond, head of the mycobacteriology and mycology laboratory section at the California Department of Public Health in Richmond. "In the absence of data on the prevalence of drug resistance, it's impossible to calculate how serious this problem is," says Desmond, who has visited North Korea and worked on the TB project on his own time.

    Lending a hand.

    CFK has distributed greenhouses and water systems to TB rest homes.

    CREDIT: R. STONE/SCIENCE

    Paek Myong Hwa, director of the Suan TB rest home, says that in his region the number of suspected MDR cases is "stable," but that patient health "is getting worse." Scientists can only guess which strains are circulating. "We have no idea what the drug-resistance patterns are," England says. One of her main tasks these days is to help NTRL researchers implement drug-susceptibility tests, or DSTs. "As soon as they can independently do their DSTs, it will be a big step," she says.

    Even for top-notch public health systems, MDR is a heavy burden; therapy lasts 2 years and costs as much as 200 times that of the four-drug combo used to vanquish susceptible strains. Modern care cannot prevent one in five MDR or XDR patients from succumbing to the disease. Since 2008, the Eugene Bell Foundation has taken the lead on MDR in North Korea; it sends sputum samples from suspected MDR patients to Seoul for DST panels, and it tailors drug regimens to individuals. MDR patients are treated at district-level rest homes. But it can take days or weeks before they get appropriate MDR drugs, and there aren't nearly enough of these to go around. During that gap, some rest homes give suspected MDR patients traditional medicine, such as a tincture of wonchuri, or day lily.

    As North Korea's TB epidemic gained momentum, the need for a modern lab for diagnoses and uncovering drug-resistance grew more urgent. By 2008, North Korea was the only country with a high TB burden lacking a modern facility for culturing the bug and probing drug resistance. In January that year, the Stanford-led Bay Area TB Consortium hosted a delegation from DPRK's health ministry; later, the Nuclear Threat Initiative awarded the consortium a grant to purchase state-of-the art equipment to establish an NTRL at District #3 TB Prevention Hospital in Pyongyang (Science, 12 March 2010, p. 1312). Others that have pitched in to keep it going include the Richard Lounsbery Foundation, the Walter H. Shorenstein Asia-Pacific Research Center, and Zero TB World.

    Work on the lab never broke stride, even during acute political tensions that followed DPRK missile and nuclear tests, military drills, the sinking of South Korea's Cheonan naval vessel in March 2010, and the North's shelling of Yeonpyeong Island that November, which killed four South Koreans. "Our North Korean colleagues have overcome tremendous odds," Linton says.

    One step forward

    In a room with negative air pressure to prevent airborne microbes from escaping, a reed-thin technician, Kim Myong Hyok, reaches into a centrifuge and removes plastic Falcon tubes from a bucket one by one. In each tube is a sample of sputum that had been treated with n-acetyl cysteine to break up the mucus and sodium hydroxide to kill off microbial flora other than mycobacteria. Malachite green, added to inhibit fungal growth, gives the samples an alien look.

    After moving the centrifuge tubes to a biosafety cabinet, Kim takes one and decants off the supernatant, then dilutes the pellet in phosphate buffer. ("pH is important. Many little nuances are important," England says.) Kim pipettes some of the suspension onto the surface of a greenish gel in a test tube. Mycobacteria thrive on the Lowenstein-Jensen medium, a protein-rich goo made from antibiotic-free eggs. Another portion of the sample will later be smeared on a slide. "In the beginning here we used old-school, acid-fast staining," England says. They've since graduated to a fluorescent stain that lights up the bacterial rods bright yellow.

    Identifying gaps.

    "We have no idea what the drug-resistance patterns are," says Kathleen England, beside an NTRL sample incubator.

    CREDIT: R. STONE/SCIENCE

    The fact that this scene could be happening in any modern TB lab anywhere in the world is encouraging to England. She cut her teeth in the region in Zhengzhou, China, where from 2010 to 2011 she trained TB researchers involved in a U.S.-sponsored clinical trial. She next spent a year in Ulaanbaatar, where she designed labs for Doctors Without Borders and assisted Mongolia's National TB Reference Laboratory. The stint revealed to her the extent to which the disease blights impoverished communities in developing countries to this day. "Mongolia opened my eyes," she says.

    England's role in Pyongyang is broader still. Besides training NTRL's 14 staff members, she is assisting the lab in strengthening diagnostics, establishing quality assurance for lab activities, planning a drug resistance survey, developing regional labs with WHO, and preparing for accreditation. "The lab is a big help for our people," says Kim Hyon Chol, an NTRL microbiologist who is working with England on the resistance screening. "We're developing a cadre of talented, hard-working young people," Schoolnik says. "There is a true sense of trust on both sides."

    Last month, NTRL received a GeneXpert machine for rapid diagnosis of rifampicin resistance. MDR strains are defined as those resistant to isoniazid and rifampicin, the two most powerful drugs of the 6-month treatment for drug-sensitive TB. (The other two drugs are ethambutol and pyrazinamide.) Rifampicin resistance is used to diagnose MDR, because it almost invariably takes longer to develop than isoniazid resistance.

    "We're moving into molecular testing," England says. But bringing NTRL up to speed has been slow going, she says. "Progress continues at a snail's pace, which is okay as long as we keep moving forward."

    Before Stanford came on the scene, the only exposure to Western research practice that the TB specialists here had received was in southern India, from 2002 to 2004. With support from WHO, 19 Koreans each spent 15 days training at the National Institute for Research in Tuberculosis in Chennai. "It was difficult to judge how much they had understood and digested. They were not very communicative," says the institute's director, Soumya Swaminathan. A physician and a mycobacteriologist from Chennai paid visits to North Korea between 2004 and 2006. The doctor reported that patients "seemed severely malnourished," Swaminathan says, and the scientist "was frustrated" over the lack of a regular power supply that thwarted setting up TB cultures.

    Out into the light.

    Young TB patients get some fresh air at a pediatric ward in a northeast district of Pyongyang.

    CREDIT: R. STONE/SCIENCE

    Power woes continue to bedevil research facilities in Pyongyang, including NTRL. Last November, when power to the lab was cut, Schoolnik asked the Koreans why they hadn't switched on their backup generator. They explained that coupons used to purchase fuel at the local gas station were locked in the lab director's office, and he wasn't around. "I said, 'Let's go buy some diesel,'" Schoolnik says. Power outages can delay diagnoses and jeopardize patient care, England notes.

    Making inroads

    As TB case numbers rose in North Korea, villagers began to ostracize infected members of their communities. Here at Unpa, county officials planned to relocate the rest home in 2009. But "the new place found out it was a TB clinic and didn't want them to move in," Ko says. The idea was abandoned.

    That paid off for Unpa. In November 2010, CFK installed a water tank up the hill from the sanatorium. Unpa's residents, Ko says, were glad that the rest home had stayed put: The tank supplies fresh water to the nearby village. Next on Unpa's wish list is a wind turbine to generate electricity; power is so spotty that the rest home isn't even fitted with light bulbs.

    Back in Pyongyang, the CFK team drives past a diplomatic compound in Sadong District, in the northeast, and turns down a potholepocked lane packed with dilapidated dwellings. It's a poorer corner of the capital that few foreigners glimpse. Our van pulls up at a pink two-story building: the pediatric ward of the Pyongyang District #3 TB Prevention Hospital. It has a capacity of 100 patients, but today there are only 14 children, ages 6 to 15, and one infant. "As it gets warmer, we expect to have more," says the new director, Ri Sang Il. TB patients come out of the woodwork in spring, after being cooped up all winter huddling to stay warm, Linton says.

    In some ways, Ri says, children are easier to treat than adults. "They are eager to follow what the doctors recommend," he says. "But they can also be naughty," one of Ri's colleagues chirps up, before adding, somberly, that the kids spend about 4 months on average in the ward and get really homesick. About a third of the children have digestive problems from the harsh TB drugs.

    On this early spring morning, the pediatric ward is chilly. Nurses lead the children out into the sun for fresh air and warmth. The kids are wearing white pajamas with blue pinstripes over their clothes. "If people back home could spend 10 minutes here, driving through some of the areas we drive through, walking through patient wards, I think they'd get it," Linton says.

    She sees reason to hope. The scientists and administrators, she says, "long for something that's real. They long for truth." But Linton knows that it will take more than a modern lab to bring TB to heel. "We need to be infused with a passion to do whatever it takes to stop this disease, and reverse it," she says, "for the sake of their people and this region and the world."

  5. American Association of Physical Anthropologists | 9–13 April | Knoxville, Tennessee

    When Early Hominins Got a Grip

    1. Ann Gibbons

    Paleoanthropologists announced a modern feature in a rare, 1.4-million-year-old hand bone from Kenya, filling a 1-million-year gap in the fossil record and showing when key adaptations to toolmaking arose.

    Old hand.

    The point at the bottom tip of this bone suggests its owner could grip tools precisely.

    CREDIT: MATT TOCHERI AND CAROL WARD

    Human ancestors were handy, crafting stone tools as early as 2.7 million years ago. But back then their hands lacked the crucial adaptations for tool use seen in living people. About 1.7 million years ago, hominins found a way to make a better tool, and anthropologists have long suspected that they needed a different kind of hand to match. But the fragile bones of the hand are rarely preserved in the fossil record. At the meetings, paleoanthropologist Carol Ward of the University of Missouri, Columbia, announced a modern feature in a rare 1.4-million-year-old hand bone from Kenya, filling a 1-million-year gap in the fossil record and showing when key adaptations to toolmaking arose. "The changes in the hand seem to be occurring much earlier in time [than fossils showed before] and are associated with the evolution of Homo erectus," Ward said in her talk.

    About 1.7 million years ago, H. erectus began to make tear-shaped hand axes in the so-called Acheulean style, in which the blade is flaked symmetrically on both sides. This was a vast improvement over the simple choppers and flakes of the earlier Oldowan style and suggested that hominins were getting more dexterous with tools. But changes in the hand bones have been more obscure. No one has known just when our ancestors developed a complex of changes in the bones at the bases of the thumb, index, and third finger that allow a forceful precision grip. That grip, in which the fingertips and thumb press against an object in the grasp, such as a hand axe, is anatomically demanding: The hand has to curve to grip the tool, but it also has to stiffen at the base of the thumb and in the midhand, to stabilize the hand and dissipate force.

    Modern humans and Neandertals have this complex of traits, as does the 800,000-year-old H. antecessor from Atapuerca, Spain. But members of Australopithecus, which lived about 1.9 million to 4 million years ago, do not. Thus, this refined precision grip arose sometime between 1.9 million years ago and 800,000 years ago. But when? No one knew, because no fragile hand bones had been discovered during this time. "There's a huge gap of 1 million years in the fossil record for hands," Ward says.

    Then, in 2010, paleoanthropologist Fredrick Kyalo Manthi of the National Museums of Kenya in Nairobi found a bone at the newly discovered site of Kaitio on the edge of Lake Turkana in Kenya. The bone, the third metacarpal, sits in the middle in the hand, extending from the knuckle of the third finger to the wrist. Although it is just a single bone, it has a key feature—a bony point or styloid process—at the bottom. This point is "associated with making and using tools," Ward says, because it buttresses other bones to stabilize them and so allows a forceful precision grip.

    Ward's team can't say for sure which Homo species the bone represents, but they suspect that it was large-bodied H. erectus, our direct ancestor, who lived near Lake Turkana during this time and is thought to have left the Acheulean tools. The bone was larger than the same bone in the hand of co-author J. Michael Plavcan of the University of Arkansas, Fayetteville, "who has really big hands," Ward notes, implying a big individual.

    The fossil shows that by the time the Acheulean was well established, the precision grip was, too. "The discovery is significant because it corroborates evidence from other parts of the hand that the hominin hand may have become adapted to stone toolmaking with the appearance of the Acheulean," says paleoanthropologist Mary Marzke of Arizona State University, Tempe, who was not a co-author.

  6. Paleoanthropology Society | 2–3 April | Honolulu

    Following the Males' Trail, 1.5 Million Years Later

    1. Michael Balter

    A team described 1.5-million-year-old footprints of at least six individuals walking together across the sand at Ileret, Kenya. Coupled with experiments with living people, the researchers concluded that the size and direction of the prints suggest a party of males out hunting or on patrol, an example of male coalitionary behavior also seen in chimpanzees.

    HONOLULU—Fossils can say a lot about what human ancestors looked like, but their evidence is indirect when it comes to how hominins behaved. That's why rare finds of hominin footprints generate such excitement: They capture ancient human activity at a moment in time. But only a handful of such tracks are known.

    At the Paleoanthropology Society meeting here this month, a team described 1.5-million-year-old footprints of at least six individuals walking together across the sand at Ileret, Kenya. Coupled with experiments with living people, the researchers concluded that the size and direction of the prints suggest a party of males out hunting or on patrol, an example of male coalitionary behavior also seen in chimpanzees, says team leader Brian Richmond of George Washington University (GWU) in Washington, D.C.

    The team had earlier reported other footprints at Ileret, (Science, 27 February 2009, p. 1197), which showed that by 1.5 million years ago hominins had evolved a nearly modern foot. Richmond reported here on two new footprint trails: one headed east and the other west. The prints, made in mud near a river, were well preserved by later mud flows that quickly covered them and then hardened. The eastbound prints were made by six to eight individuals; the westbound prints were made by at least five. Some of the westbound prints were partly superimposed on the first set and could have been the same individuals coming back, Richmond said.

    Unlike TV detectives, who can tell exactly which shoe a culprit was wearing from their prints, the traces of barefoot hominins have to be interpreted cautiously, Richmond said. A footprint in sand is not a mirror image of the foot that made it, because it also reflects the type of sediment and how fast the maker was traveling.

    So in a companion talk, GWU Ph.D. student Kevin Hatala detailed experiments with the local Daasanach people, who traditionally walk shoeless. The researchers asked 20 Daasanach men and 20 women to walk and run barefoot across a strip of sand, moistened to various degrees, next to the Ileret site. The length of their footprints correlated well with the length of their feet, but print width was a poor predictor of actual foot width. The footprint dimensions were good predictors of height and reasonably good predictors of body weight, Hatala found.

    Footsteps on the sands of time.

    Comparing ancient and modern footprints at Ileret, Kenya (above), gives insights into early human behavior.

    CREDIT: BRIAN RICHMOND; KEVIN HATALA

    Three hominins lived near Ileret around that time: Homo erectus, H. habilis, and the australopithecine Paranthropus boisei. The prints were all too large to have been made by the smaller H. habilis or by females, the team concluded, and must have been made by males of either H. erectus or P. boisei.

    Such gatherings of males are seen "in humans that are hunting or tracking, or groups of male chimps out on patrol," Richmond says. "This male coalitionary behavior was probably represented in the common ancestor of humans and chimps."

    Others at the meeting expressed cautious enthusiasm. "Footprints are cool," says Ariane Burke, an anthropologist at the University of Montreal in Canada. But "interpreting social behavior based on footprints begs for extreme caution," says Zeray Alemseged, an anthropologist at the California Academy of Sciences in San Francisco. Anthropologist Susan Larson of the Stony Brook University School of Medicine in New York agrees, but adds that "at least this speculation has some basis in fact."

  7. Ardi's a Hominin—But How Did She Move?

    1. Ann Gibbons

    Researchers gave Ardi, the oldest and most complete skeleton of a potential human ancestor, new recognition as a hominin. They agreed with the discoverers that Ardi walked upright—albeit in a weird way—and that features in her teeth and skull make her a primitive member of the human family. But debate raged about whether she also climbed vertically in trees like an ape.

    Ardi, the oldest and most complete skeleton of a potential human ancestor, has been a leading lady of human evolution ever since she got top billing on the cover of Science in 2009. But while everyone praised the completeness of the partial skeleton, some researchers reserved judgment on whether Ardipithecus ramidus was actually a hominin, or upright member of the human family.

    At the meetings, a series of talks and posters gave Ardi new recognition as a hominin. Researchers who have had their first look at fossils or casts of the 4.4-million-year-old fossils agreed with the discoverers that Ardi walked upright—albeit in a weird way—and that features in her teeth and skull make her a primitive member of the human family. But debate raged about whether she also climbed vertically in trees like an ape.

    In 2009 (Science, 2 October 2009, p. 36), a team of 47 researchers co-led by Tim White of the University of California, Berkeley, showed that chimp-sized Ardi walked upright, planting her feet flat on the ground. Although she still clung to the safety of trees, the team suggested that she didn't climb vertically or swing through the branches like a chimp, but moved slowly on all fours when on top of branches, with an opposable big toe to grasp limbs. But other researchers continued to debate whether Ar. ramidus was part of the human lineage (Science, 29 January 2010, p. 532).

    Making headway.

    The bones at the base of Ardi's skull suggest that she had human traits.

    CREDIT: TIM D. WHITE

    In one talk, William Kimbel of the Institute of Human Origins at Arizona State University, Tempe, working with White's team, used the cranial base—the bones that form the base of the inside of the skull, around the opening for the spinal cord—to support Ardi's status as a hominin. Kimbel, an expert on Lucy's species, Australopithecus afarensis, noted resemblances between that species and Ardi, which is half a million years older but from the same region in Ethiopia. For example, both have a shorter and wider cranial base than an ape's. "What struck me was just how spread out the landmarks were around the center of the cranial base," Kimbel says. "In apes, they are crowded together in the middle." Hominins have a wider base than apes to accommodate a more forward position of the spinal cord.

    Others found Kimbel's talk convincing. "When I saw the cranial base, it struck me that it was reasonable as a hominin," says paleoanthropologist Eric Delson of the City University of New York. "Above the neck, I'm convinced."

    Below the neck, interpreting Ardi's anatomy is more complicated. The position of one key hand bone, the capitate in the center of the wrist, supports the idea that Ardi's wrist was flexible, allowing her to walk on flat hands and feet atop branches, reported anatomist Michael Selby of the Philadelphia College of Osteopathic Medicine, Georgia Campus, in Suwanee. But that view was challenged by paleoanthropologist Caley Orr of Midwestern University, Downers Grove, in Illinois. Using a 3D analysis of the wrist bones, he found that Ardi's wrist was too rigid to put her weight flat on her hands, suggesting that she moved through the trees in another manner, perhaps by vertical climbing as chimpanzees do.

    So while Ardi is on more secure footing as an upright walking hominin, the focus has shifted to what she did off the ground. "The big debate is how it was moving in the trees," says paleoanthropologist Will Harcourt-Smith of the American Museum of Natural History in New York City.

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