# News this Week

Science  03 Aug 2012:
Vol. 337, Issue 6094, pp. 506
1. # Around the World

1 - Ratchaburi Province, Thailand
Dengue Vaccine Shows Promise
2 - Washington, D.C.
U.S. Court Says Stem Cells Are Drugs
3 - Washington, D.C.
Fracking Report Under Scrutiny
4 - Halle, Germany
Poor Review for Biofuels
5 - Washington, D.C.
Ape Research Ban Moves Forward in Senate

## Ratchaburi Province, Thailand

### Dengue Vaccine Shows Promise

A vaccine against dengue—a debilitating and sometimes fatal viral disease that's widespread in the world's tropical regions—has shown promise in its first phase III trial, although it hasn't entirely fulfilled the hopes of its producer, French vaccine manufacturer Sanofi. In a trial among 4002 children aged 4 to 11 years in Ratchaburi Province in Thailand, the vaccine proved safe and effective against three of the four circulating dengue strains, the company said in a press release on 25 July. The vaccine was designed to protect against all four strains, which dengue experts say is the ideal.

Sanofi declined to issue details of the study; they will be submitted for publication soon, a spokesperson says. A vaccine that protects against only three strains “might slow down licensure a bit,” says Duane Gubler, a dengue expert at the Duke University–National University of Singapore Graduate Medical School Singapore, but would still “be very important from a public health point of view.” Because of cross-protection from the other strains, vaccinated people would be unlikely to develop the most severe—and often fatal form—of the disease, called dengue hemorrhagic fever, Gubler says. At least five other dengue vaccines are in clinical trials.

## Washington, D.C.

### U.S. Court Says Stem Cells Are Drugs

A U.S. federal court has found that a stem cell therapy offered by a Colorado clinic is a regulated drug. The ruling could spur a U.S. Food and Drug Administration (FDA) crackdown on other clinics offering untested adult stem cell treatments.

Regenerative Sciences Inc. in Broomfield, Colorado, uses stem cells extracted from a patient's own bone marrow to treat bone and joint injuries. The company calls its treatment a medical procedure. But in a 2010 suit, FDA argued that because the stem cells are more than “minimally manipulated” and the procedure uses reagents that cross state lines, the cells are an FDA-regulated biological drug. On 23 July, the U.S. District Court for the District of Columbia in Washington, D.C., granted FDA an injunction, agreeing that “the cultured cell product is a drug” according to federal law.

University of Minnesota bioethicist Leigh Turner says the ruling “is particularly important given … the proliferation of [U.S.] clinics marketing stem cell procedures,” many of which “appear to be pushing stem cell quackery.” Regenerative Sciences plans to appeal.

## Washington, D.C.

### Fracking Report Under Scrutiny

A controversial study of hydraulic fracking released in February will be reviewed by an independent panel of experts. The study was criticized last week when an advocacy group highlighted the financial ties of geologist Charles “Chip” Groat, the lead author of the study, to an energy company.

The report analyzed the risks and benefits of hydraulic fracturing, or fracking, a type of drilling used to extract natural gas from shale. It found that fracking hasn't contaminated ground water.

But Groat, former head of the U.S. Geological Survey and now associate director of the Energy Institute at the University of Texas, Austin, didn't disclose a potential conflict of interest: He serves on the board of Plains Exploration & Production Co., which conducts fracking in the United States.

Groat says he thought his board membership wasn't relevant to the project and he didn't have an actual conflict of interest. In a statement released on 24 July, Steven Leslie, provost and executive vice president of the University of Texas, Austin, said he hoped to have the independent review of the study completed in a few weeks. http://scim.ag/Groatfrack

## Halle, Germany

### Poor Review for Biofuels

Germany's National Academy of Sciences Leopoldina has come down firmly against the use of crops for energy. In a report issued on 26 July from a panel of more than 20 experts who have been working together since 2010, the academy concludes that biofuels should play only a small part in the move toward sustainable sources of energy.

Biofuels use more land area, generate more greenhouse gas emissions, and have a greater impact on the environment than other alternative energy sources such as photovoltaic solar energy, solar thermal energy, or wind power. Biofuel crops may also find themselves competing with food crops for valuable land.

## Washington, D.C.

### Ape Research Ban Moves Forward in Senate

A Senate panel last week approved a bill that would ban invasive research on great apes in the United States. The Great Ape Protection and Cost Savings Act of 2011, sponsored by Senator Maria Cantwell (D–WA), would ban research that may kill, injure, or cause fear, pain, distress, or trauma to a great ape—defined as a chimpanzee, bonobo, gorilla, orangutan, or gibbon. It would also require that the more than 900 chimpanzees now being used in invasive research in the United States be retired. An amendment adopted during markup by the Senate Committee on Environment and Public Works would set up a federal task force to approve exemptions after consulting with the public.

Research advocacy groups say the bill conflicts with a 2011 Institute of Medicine report recommending that chimp research continue under specific circumstances. The Federation of American Societies for Experimental Biology protested that the bill would make it difficult to start a research program quickly to study an emerging disease. A House of Representatives version of the bill is awaiting action by the House Energy and Commerce Committee health subcommittee; some onlookers say a final bill is unlikely to be approved by the full House and Senate this year.

2. # Random Sample

## First Light for HESS II

The world's largest telescope to observe the highest energy photons from space saw its first light in Namibia last week. Paradoxically, the HESS II telescope—with a dish the size of two tennis courts—does not direct its gaze out into space, but inside Earth's atmosphere.

High-energy gamma rays are immune to conventional optics and don't penetrate the atmosphere. So HESS II looks out for flashes of blue light, known as Cherenkov radiation, emitted by the cascade of particles that ensue when a gamma ray hits the upper atmosphere. Its ultrafast snapshots can tell astronomers the incoming particle's energy and direction. HESS II “resolves the cascade images at unprecedented detail, with four times more pixels per sky area compared to the smaller telescopes,” says Pascal Vincent of France's National Institute for Nuclear and Particle Physics.

Astrophysicists think the gamma rays come from cosmic particle accelerators such as supermassive black holes, supernovae, and pulsars. HESS II, an addition to the four smaller dishes of HESS I that have operated at the site since 2004 (Science, 3 September 2004, p. 1393), will give them unrivaled information about such objects.

## Raindrops Keep Falling on My …

Birds do it. Bees do it. Even raindrops do it—pollinate flowers, that is. In China, researchers were puzzled by the high reproductive rates of an orchid called Acampe rigida. As flowers go, A. rigida doesn't have much going for it: It has an attractive odor but offers no nectar reward to would-be pollinators, and such “deceptive” species tend to produce few fruits. Furthermore, it flowers during the rainy season, when visits by insects tend be rare. Nor do its flowers seem designed for self-pollination. So plant reproductive biologist Jiang-Yun Gao from the Chinese Academy of Sciences Xishuangbanna Tropical Botanical Garden and his colleagues spent 4 years studying this orchid in the wild and in the lab.

The researchers filmed the flowers during a rain shower (as well as under an actual showerhead), and discovered a curious effect: When rain splashes on the orchid's male sexual organs, it flicks a tethered, pollen-laden bundle upward. As the bundle bounces back on the tether, it lands exactly where it needs to be to pollinate the flower. Plants shielded from rain, on the other hand, produce no fruit, Gao's team reports this week in Annals of Botany.

A few other plants can be pollinated in the rain, but A. rigida seems to be the first discovered that really depends on rain to do this job. “I think it is likely to make plant reproductive biologists appreciate that rain is not always detrimental for flowers, causing damage, but in some cases can actually aid in promoting reproductive success,” says co-author Spencer Barrett, a botanist at the University of Toronto, St. George, in Canada.

## By the Numbers

15.4 Percentage of men who have sex with men in the United States who are infected with HIV, according to a study published online 20 July in The Lancet.

53 Number of low-income countries that are projected to move to middle-income status by 2020, according to Bernhard Schwartländer, director for evidence, strategy, and results at UNAIDS.

104 Kilometers per hour that a cheetah can run, or a duck can fly—still almost twice as fast as even the fastest Olympic athlete can run, notes a study published 28 July in Veterinary Record.

## ScienceLIVE

ScienceLIVE is on hiatus. We will return at 3 p.m. EDT on Thursday, 6 September, with a chat on head trauma in soldiers.

3. # Newsmakers

## Three Q's

Paleobotanist Kirk Johnson was named the new director of the Smithsonian Institution National Museum of Natural History last week. Chief curator at the Denver Museum of Nature & Science, Johnson, 51, will start on 29 October, replacing Cristián Samper, who on 1 August took over the Wildlife Conservation Society in New York City.

Q:How do you want to influence the community?

The museum is the urban touchpoint to the natural world. You have all these scientists making all these discoveries one wall away from 7.4 million visitors. I will be exploring ways to use social media, innovative exhibitry, and the Internet to make what happens at the museum more accessible.

Q:What challenges does the Smithsonian natural history museum face?

There's a tremendous amount of confusion in this country about what science is and how science accrues knowledge for the betterment of the community. Connecting the content and the joy of science to the public is something that can be done better here than any place else in the country.

Q:Do you have any innovative ideas for the renovation of the dinosaur hall?

When people go to a museum, they see dusty dinosaurs; they don't realize that new dinosaurs are being discovered at an incredible rate every year. My thought is: How do you make this exhibit something that demonstrates the vitality of paleontology? It's also a science that has tremendous information about how the planet has changed through time. To realize that the polar regions have been forested for most of our history, not just covered by ice … is a very amazing thing [about which] most people in the street have no idea. But that's paleontology 101.

4. Polio Campaign

# The Polio Emergency

1. Leslie Roberts

Can a tough new taskmaster and ramped-up program finally push the global eradication initiative over the finish line?

“We are convinced that polio can—and must—be eradicated. We are equally convinced that it will not be eradicated on the current trajectory.” So declared the Independent Monitoring Board (IMB), an oversight body recently constituted to ride herd on the Global Polio Eradication Initiative (GPEI), in a pivotal October 2011 report with blunt language that broke the mold of bland bureaucratic white papers. Using words such as “dysfunctional” and “diseased,” the report said that GPEI—the biggest, most expensive, and longest running public health program in history—may never eradicate polio without fundamental changes in a culture and management style the board generally characterized as insular, stuck in old habits, averse to criticism, and resistant to innovation.

The eight-member IMB did have some kind words, noting the program's early success in knocking down cases by 99%, its increasing agility in stamping out new outbreaks, and its decisive progress in India—that country, long considered the hardest of the hardest places, would soon go 1 year without a case, erasing any lingering doubts that polio eradication was feasible. Overall, the board said, the program is good and its staff members dedicated. But “good” was not enough to pull off what has been done only once before in human history—the eradication of a human disease, smallpox, in 1979. For that, GPEI had to be “great,” and the initiative was falling considerably short, IMB said. As it starkly warned in its next report: “[GPEI] will succeed spectacularly, or fail monumentally.”

The report jolted a program that for 2 decades has struggled to rid the world of the crippling poliovirus—a task that proved far more difficult than anyone ever anticipated but was now tantalizingly close. GPEI had weathered plenty of criticism, but no one had challenged program leadership like this and questioned its fundamental ethos (Science, 12 May 2006, p. 832).

Some in the global program—a partnership of the World Health Organization (WHO), Rotary International, the U.N. Children's Fund (UNICEF), the U.S. Centers for Disease Control and Prevention (CDC), and most recently, the Bill & Melinda Gates Foundation—embraced the report, calling it refreshingly frank. Others say it felt like a punch in the gut, sapping the morale of some and offending others. It was especially tough for the staff members on the front lines, who had been working for years in the roughest spots on earth, such as Afghanistan, Somalia, and the Democratic Republic of the Congo, to be told their efforts weren't up to snuff, says Chris Maher, an Australian epidemiologist who oversees all the troops on the ground and easily matches IMB in bluntness. However valid IMB's criticisms, he says, “My guys are pretty damn good.”

But most agree that the report was instrumental in reinvigorating a program that was years behind schedule and billions of dollars over budget—and bone-tired from chasing the poliovirus across the globe for the past 24 years. “Do I like it? When you get medicine that tastes bad, do you like it?,” says WHO's Bruce Aylward, a Canadian epidemiologist and physician and longtime leader of GPEI who was recently promoted to assistant director-general for polio, emergencies, and country collaboration at WHO. “But do you need it? … I wouldn't have turned around the whole program if I didn't think it needed it.”

And turn it around they did, with a raft of changes, an infusion of new resources, and a new sense of urgency, all of which seem to be producing results. In June 2012, with polio cases at an all-time low, GPEI earned rare words of praise from IMB: “In recent months, the Programme has broken free of its decade-long stagnation.” But, the board warned, these gains were fragile, and failure was still a very real possibility.

## Stalemate

When the program started in 1988, 125 countries were infected with poliovirus and an estimated 350,000 children were paralyzed each year. By 2006, there were just four countries where the disease was endemic—India, Nigeria, Afghanistan, and Pakistan—where poliovirus transmission had never been interrupted. Globally, cases of polio had dropped by 99%, thanks to massive campaigns conducted multiple times a year in infected and at-risk countries to immunize every child under age 5 with two drops of oral polio vaccine. Then the program got stuck, unable to vaccinate all children and eliminate the last 1% of cases. Since 2000, cases have fluctuated between 500 and 2000 a year, concentrated in the poorest, most marginalized children in the world (Science, 26 March 2004, p. 1960).

## Thirty-five million times six

Messy and complicated, Pakistan is the perfect case study for why it is so hard to eradicate poliovirus from its last few strongholds—and what it might take to pull it off. Wiping a human disease off the face of the earth, which has only been done once before, for smallpox, requires synchronized vaccination campaigns executed with near-military precision multiple times a year to reach all the children under age 5 with two drops of oral polio vaccine. In Pakistan, that means immunizing some 35 million kids about six times a year. But in Pakistan, nothing much works as it should, and certainly not with precision.

For a while, Pakistan seemed to be on track. Sure, it was always a trouble spot—one of the few countries where transmission of the poliovirus has never been stopped. But since the program began in earnest there in 1994, cases dropped more or less steadily, reaching an all-time low of 28 in 2005.

Even when cases began to climb in 2008, there wasn't much alarm; GPEI was focused on India and Nigeria, then considered the biggest threats to success. In Pakistan, the mantra was, once vaccinators could get into the tribal areas along the troubled border with Afghanistan, polio would disappear. And if Pakistan went, Afghanistan would follow.

“After Pakistan cases [dropped] in 2005, it looked extremely good. The focus and pressure changed before the job was done,” says Dennis King, who heads UNICEF's polio eradication program in Pakistan and is coordinating that agency's influx of new workers. “When cases were going down, it looked like what we were doing was working, and it largely was,” says Chris Maher, WHO's top operations man, who for the past 20 years has combated polio in the toughest spots in the world and now splits his time roughly between Pakistan, Afghanistan, and Nigeria, the last three endemic countries.

Then in 2011, cases shot up “in a very scary way,” Maher says, in sharp contrast with India, which soon went a year without a case and has now been removed from the list of endemic countries. Pakistan's case count topped out at 198 by the end of 2011. That may not sound like a lot, but for every child paralyzed, 100 or 200 others are infected asymptomatically and are silently spreading the virus.

What's more, cases were not just clustered in the tribal areas but had spread to previously polio-free places across the country, such as Punjab, where there were no apparent obstacles to reaching the children. And in 2011 for the first time, poliovirus from Pakistan jumped the border into China, sparking a large outbreak.

## A perfect storm

Maher and others attribute the explosion of cases last year to a perfect storm of all the problems that are Pakistan: poverty and illiteracy; a health system in tatters; ethnic and sectarian violence; a government struggling to deal with corruption and dysfunction; huge population movements; and, especially since 9/11, rising extremism and anti-Western views—not to mention the natural attrition that accompanies any program that has dragged on for so long. Equally important, he says, is the nature of the beast that they are fighting—the poliovirus—which, after all these years, still manages to surprise. “I think there are some years when conditions are more favorable” for widespread polio transmission, Maher says. “To some extent it is cyclical as with any infectious disease—something we don't give enough weight to especially as far as polio is concerned.”

What's clear, Maher says, is that “if you knock the virus down to fairly low levels, it is not going to stay there. That is not the nature of the disease. Unless you can take it one step further from knocking down the virus to knocking it out, you will be punished.” And that's what happened in Pakistan.

Sometime in the mid-2000s, it became apparent that poliovirus circulated in three distinct transmission zones in Pakistan, each with its own unique genetic signature: the Federally Administered Tribal Areas (FATA) and adjoining Khyber Pakhtunkhwa (KP), formerly known as the Northwest Frontier Province, in the northwest along the border with Afghanistan; Balochistan, which is south of FATA and also shares a porous border with Afghanistan; and Karachi at the southern tip of the country on the Arabian Sea, with 14 million people, the only megacity in the world to have polio. And within these zones, polio is concentrated in 33 high-risk districts where, for various reasons, it has been impossible to vaccinate all the children. Not coincidentally, these holdouts tend to be the most badly broken of all the broken places in Pakistan, Maher says.

In 2011, 73% of all cases were genetically linked to these three areas. “They drive the agenda,” Maher says. “You can do a brilliant job in 80% of the country, but it makes no difference if you do a lousy job in the rest.” FATA and KP are home base to the Taliban and al-Qaeda and a training ground for jihadists. There, myriad tribes and clans are at war with each other, the federal government, and the West. Female literacy is a mere 3%. The area has been pounded by U.S. drone strikes, which have killed an estimated 1900 to 2900 people since 2004, according to the New America Foundation. Abbottabad, where U.S. Navy SEALs killed Osama bin Laden in May 2011, is in KP, and the CIA's fake vaccination campaign there to try to identify his family has only inflamed animosity to and suspicion about polio vaccination, which is rumored to be a Western plot to sterilize or otherwise harm Muslim children. In parts of the tribal areas, no polio campaigns have been conducted in the last 3 years; in January 2011, 38% of the children in Khyber Agency, FATA, were inaccessible, according to WHO data. (That number, which fluctuates, dropped to 20% in January 2012.)

Balochistan borders Kandahar and Helmand in Afghanistan, where poliovirus circulation is unchecked and people and the virus move freely across the border. It's a dangerous place, where kidnappings and other crimes are rampant, and a climate of fear keeps vaccinators out. Recently, the Taliban has extended its reach in Balochistan. Like FATA and KP, the province is a hotbed of religious extremism and anti-American views. In the first few months of 2012 in Quetta Block, the hottest polio hot spot in Balochistan, the proportion of parents who refused to let their children be vaccinated increased dramatically. Of all the missed children there, about 50% were “active refusals,” according to UNICEF (see graphic).

And then there is Karachi, “which has all the problems in the world,” says WHO's Tariq Masood, who is an area coordinator in Karachi. That city has a large minority and migrant population that settles in the squalid periurban slums that stretch for miles. With so many people traveling in and out of the city, Karachi serves as the hub and amplifier of the virus—it was virus from Karachi that sparked the outbreak in China. Most of the migrants are Pashtun, the dominant ethnic group in Afghanistan and tribal areas but an unwelcome minority in Karachi. In 2011, 77% of all polio cases in Pakistan occurred in Pashto-speaking people, although they account for just 8% of the population. Across the country, huge numbers of people are on the move, often between the three transmission zones, fleeing the violence of the tribal areas, in search of seasonal jobs, or displaced by the historic floods of the past 2 years. And when they travel, the poliovirus often goes with them.

In all three transmission zones, the federal government has little control; instead, power is concentrated at the local levels, where corruption and nepotism are rife. Over the years, Durry says, polio eradication became something of a full-employment act. Polio money lined the pockets of corrupt officials, who dispensed jobs as favors, turning over vaccination posts to their brother or their cousin, who might in turn pass it on to their kids, who would work for nothing but did nothing, either. “We created a monster,” Durry concedes.

In many places, unmotivated and unpaid vaccinators showed up late and stopped early. Sometimes the campaigns didn't take place at all: ghost campaigns, Durry calls them. All too often teams didn't inspire trust—say, if they were children, or they didn't speak Pashto, or if the only vaccinators were men. The battle is won or lost “in those 30 seconds when the mother opens the door and decides,” Durry says. And at the end of the day, data were falsified.

In its October 2011 report, with cases soaring, IMB labeled Pakistan's program “deeply dysfunctional,” citing its “diseased core” and calling the government on the carpet and urging it to “fundamentally re-think” its program.

## The surge

Even before then, alarmed at the rise in cases, GPEI began to intensify its operations in Pakistan. In May 2011, WHO brought in Durry, an Ethiopian-born epidemiologist who had delivered some of the toughest countries on time, such as Somalia and South Sudan. If anyone could turn around Pakistan, the reasoning went, he could. “They do this to me all the time,” he says somewhat ruefully.

By December, the Pakistani government, with help from WHO and the other GPEI partners, had crafted its “augmented” emergency action plan for polio eradication in 2012. The new plan declares polio eradication a national emergency and puts in place strict new measures to ensure what officials call “accountability” at all levels. To see that this plan actually did something this time, the government appointed Shahnaz Wazir Ali to a new position as the country's “focal person” for polio eradication. Smart, driven, exacting, and with the ear of the prime minister, Wazir Ali has made a huge difference, program leaders say. In May, she led a delegation to India to learn from the experts firsthand.

Borrowing a leaf or two from India's playbook, the ramped-up efforts are concentrating on the country's 33 high-risk districts—and within those, specific towns or subdistricts like Pishin in Balochistan's Quetta Block and Gadap in Karachi—where large numbers of children are missed in each campaign. Those 33 districts are where all the “surge” personnel have been deployed—some 1000 from UNICEF and 350 from WHO. The WHO teams assist with technical issues such as training, surveillance, and monitoring; UNICEF works with the community to try to increase acceptance of, and generate demand for, the polio vaccine. Data from a January 2012 survey show the magnitude of what the organization is up against.

One of the biggest changes is at the grassroots level, where the old network of ineffectual supervisors has been booted out, replaced by the higher-level district commissioners, who are like mayors in the United States. The plan spells out exactly who must do what, including the composition of the vaccination team, the number of meetings to hold, and who must attend to prepare for each campaign. If a union council, or town, is not prepared, the round is canceled; workers' salaries are docked, or they are put on probation, or sometimes fired.

In the high-risk districts, efforts are focused on the highest-risk populations, mainly the Pashtun, migrants, and nomadic populations. Mobile populations will be the Achilles' heel in Pakistan, Durry says, because so many travel in and out of the tribal areas where virus circulation is unchecked. The key, he says, is to anticipate their movements and make special arrangements to vaccinate them wherever they are.

In the past few months, the program has set up tens of permanent transit posts that offer polio drops 24/7 at common entry and exit points from FATA/KP, Balochistan, and Karachi. At one toll booth alone in Karachi, 13,688 children were vaccinated between 23 April and 9 May, according to WHO. Efforts are also under way to negotiate access to the tribal areas. In the meantime, Durry's team is trying to figure out how best to take advantage of any opportunity to get in and out of conflict zones quickly. One strategy is to deliver multiple doses of vaccine at very short intervals—a few days apart instead of the usual 4 to 6 weeks. No empirical studies have proved that this strategy works, but it seemed to help quickly boost immunity in Somalia, where Durry first introduced it, and it's worth a try, he says.

## Off the critical list

In June 2012, with cases down significantly from the previous year (so far to date there have been 23 cases compared with 60 this time last year), IMB took Pakistan off the critical list, commending the government for significantly improving its game—while still warning that tough challenges remain.

What's most encouraging to Durry is that environmental sampling, the testing of sewage water for poliovirus, is clearing up in some places—most surprisingly in Gadap town in Karachi, where samples have been positive for years (see sidebar, p. 520). But just as Gadap improved, positive samples have cropped up in Lahore, Punjab, where everyone assumed the program was working fine. That means redoubling efforts on that front, Durry says: “We have to put more resources into central Pakistan without losing our focus on places like Karachi.”

There are plenty of other caveats. Pakistan has yet to bear the full brunt of the high season when cases rise along with the rains. There's been little progress in Pishin, where Durry says “we are still trying to make things happen without intimidation and sometimes sabotage” and where, as in much of Balochistan, vaccination is still done by children as young as 8. Parts of FATA remain inaccessible, and a June letter from a Taliban leader in North Waziristan saying the Taliban will block vaccination until U.S. drone strikes stop certainly didn't help, although it is unclear how much it hurt, says Aziz Memon, the national chair of Rotary's PolioPlus program in Pakistan, noting that in many places, “We didn't have access anyway.”

Even so, Durry says, “Pakistan is in the best position ever to finish the job,” and he thinks the country can—if the program can sustain momentum and somehow get access to the children in FATA. “If we had denied that there is corruption and a problem in management and just tried to go around it, we never would have reached anywhere,” Durry says. “But once you know the problems, the solutions are not that tough.”

6. Polio Campaign

1. Leslie Roberts

On 17 July in the town of Gadap in Karachi, Pakistan, two gunmen shot at two men who were participating in a national polio vaccination campaign—sadly, a not uncommon occurrence.

On the morning of 17 July in the town of Gadap in Karachi, Pakistan, two gunmen pulled alongside a white Nissan pickup truck belonging to the World Health Organization (WHO) and opened fire, shooting a Ghanaian doctor in the abdomen; his Pakistani driver suffered a grazing wound on his shoulder. Both men, who were participating in a national polio vaccination campaign, are recovering. As investigations began, WHO suspended its activities in Gadap. Three days later, on 20 July, another WHO polio worker, Muhammad Ishaq, was shot and killed outside a Gadap clinic.

The attacks, sadly, are not uncommon. Polio workers in Pakistan have received death threats. Two doctors on WHO duty and their driver were killed in a roadside bombing in Afghanistan in September 2008. And just last year 23 people, including five WHO and two UNICEF staff members, were killed when the jihadist terrorist organization Boko Haram bombed U.N. House in Abuja, Nigeria. The attack in Gadap came just as the town was, for the first time, showing signs of progress in its fight against polio.

Gadap is a squalid, festering slum that many have long feared would be the undoing of the country's, and the world's, fight to eradicate polio. It is one of just 10 so-called sanctuaries for the poliovirus worldwide—places where the virus has been impossible to dislodge.

Gadap, and especially one area known as Union Council 4, has everything working against it, says Chris Maher, who runs country operations from WHO headquarters in Geneva. It is a receiving ground for migrants from across the country, especially those fleeing the violence in the tribal areas and Balochistan. Many are Pashtun, an underserved minority in this part of the country. In Pakistan overall, 8% of the population is Pashto-speaking; in Union Council 4, that number climbs to 73%.

The migrants crowd into multifamily dwellings where they have no basic services such as clean water or sanitation, much less routine childhood immunizations or other medical care. Literacy rates are low. Many Pashtun don't know what polio is or that a vaccine can prevent it. Suspicions run high. The population is understandably skeptical of a government that provides them with nothing and then comes around repeatedly offering drops of polio vaccine, says Tariq Masood of WHO's Karachi office. “In their minds, often the government and the U.S. are bombing their children in [the tribal areas], so why is there so much concern for our kids here?” he says.

Polio-vaccination campaigns in Gadap have been consistently lousy. The often unpaid vaccinators, whose job is to go house to house and give drops of oral polio vaccine to every child under age 5, have little incentive to work. In March, for instance, the campaign was delayed for 2 days because the vaccinators, unpaid for the past 9 months, went on strike. Some 80% of the teams don't speak Pashto, and child vaccinators are common. It's not surprising that mothers turn away vaccinators who come to their doors, saying their children are asleep, or refuse outright because they have been told that the vaccine is made of monkey kidneys and other nonhalal materials and will make their children weak and sterile. Since 2006, 80% of the polio cases in Gadap have been from Union Council 4. Samples of sewage water in Gadap have consistently tested positive for the virus, indicating rampant circulation.

After another disappointing performance during the March vaccination rounds, Elias Durry, who runs the Pakistan program for WHO, and his colleague Salah Tumsah, who runs the Sindh province operation, decided to shake things up. Instead of bringing in vaccinators for a few days during each campaign, the program has hired women from the community to work full-time since April, providing not just polio drops but also other services such as newborn follow-up. “It has made a huge, huge difference,” Durry says.

Rotary International and the U.N. Children's Fund have also been focusing their efforts there. In April, the two organizations, in collaboration with Coca-Cola, conducted a massive cleanup of Union Council 4, carting out an estimated 160 tons of garbage. It is one of the ways Rotary is trying to “give the message that we are there not just for polio but for everything else,” says Aziz Memon, national chair for Rotary's PolioPlus program in Pakistan.

Rotary conducted a major survey in Gadap in June. Of 7000 children they checked for the finger marking that indicates they were vaccinated, only four hadn't been—and they were quickly vaccinated, too, Memon says.

Most encouraging of all, Durry says, is that for more than 4 months, the environmental samples from Gadap have tested negative, suggesting the virus is in retreat.

WHO's Bruce Aylward, who leads the Global Polio Eradication Initiative from Geneva, says it is unclear whether the two shootings were related and whether they specifically targeted polio workers. Until they get more evidence, he says, “Our operating assumption is that [the shootings] may be related, and that affects how we approach security.” WHO insists the attacks will not distract from the job of wiping out polio in Pakistan. But the shootings make uncomfortably clear just how much is out of the program's control.