Oral Rehydration Solution (ORS) saved 10 millions from death ....

A pinch of salt, a fistful of sugar, a jug of clean water. The simple elixir known as oral rehydration solution (ORS)--recently ranked No. 2 in a British Medical Journal survey of greatest health advances of the last 150 years--has saved tens of millions of people from death by infectious diarrheal diseases since the early 1970s. At the cost of a few cents, almost anyone alert enough to swallow can survive cholera, which can kill a man in four hours by draining him dry.

In a landmark paper published in the Lancet in 1968, the Harvard School of Public Health's Richard Cash and his chief collaborator, David Nalin, reported the results of clinical trials in Bangladesh, then East Pakistan. In rigorous tests, they showed that this simple solution worked as well as sterile intravenous fluids, a scarce and costly option in the Third World. Though researchers at Harvard and elsewhere had worked out the principles behind oral rehydration in the 1950s, the pair, then U.S. Public Health Service physicians in their 20s, were the first to administer ORS clinically in a reliably effective way.

BRINGING SCIENCE TO THE PEOPLE HSPH’s Richard Cash, a pioneer of lifesaving oral rehydration therapy, now trains researchers throughout the developing world. In January of 2007, Cash will receive the annual Prince Mahidol Award in public health from the King and Queen of Thailand, in Bangkok, sharing the honor with researchers David Nalin and Dilip Mahalanabis.

"Those were heady times," remembers Cash, a senior lecturer in the Department of Population and International Health at HSPH, sitting in his cluttered office next to a three-foot-high statue of Shitala, the Indian goddess of smallpox. "We thought, 'This is great! Everybody's going to use this, right? We can all go home now.' But everybody didn't use it."

To get ORS to the masses, he says, researchers faced huge obstacles: A medical culture that clung to IV therapy as superior to what they perceived as a primitive oral form; a very high prevalence of illiteracy, especially among women; and no way to distribute ORS packets to remote, roadless areas.

In a presentation to a group of India's health leaders last spring, Cash chronicled a 10-year effort to surmount those daunting hurdles, using ORS to drive home a point as relevant today as it was years ago. What low-income nations need most is not "parachute research" handed down from rich, industrialized countries, but assistance in building their capacity to do research at home, where the problems are.

"You can't sit here in the U.S., do your research, and expect your ideas to work a thousand miles away," Cash tells his students. "The questions you ask come from the environment you're in. You're much less likely to ask the right questions if you're not there."

With one foot in Boston, the other in South Asia, Cash practices what he preaches. Since 2000, he's been spending the Winter session with HSPH students in Kerala, India, home to a public health school where he has taught for nine years. Today, in tiny Bangladesh, he's helping to launch another such school--one he hopes will, like Harvard, become a training ground and research hub for students from all over the world.

40 Million rescued since 1978
In a cover story on October 16, 2006, the European edition of Time reported that oral rehydration therapy has rescued at least 40 million people from the grip of water- and sewage-born pathogens since its adoption by the World Health Organization (WHO) in 1978. Since then, WHO estimates, annual deaths worldwide among acute diarrhea's chief victims--children under age 5--have plummeted from 5 million to 1.9 million.

Why, then, does the illness still kill so many in developing countries worldwide every year?

The answer, Cash says, is anything but simple. One billion people lack clean water; more than 2.4 billion lack a basic toilet. Oral rehydration therapy is not a cure, only a means to hydrate tissues while the immune system battles bacteria or viruses. And promoting ORT presents unique challenges in every country--issues research can help address, Cash notes.

In Bangladesh, in 1971, 10 million people fled to neighboring India to escape civil war. Crowded into camps, they seemed doomed to perish from hunger and a massive cholera outbreak. But in a desperate, grand-scale test of ORT organized by Johns Hopkins researchers based in Calcutta, 95 percent of the refugees survived.

Here was dramatic proof that ORT worked in the field. Still, it took a 10-year campaign by the International Centre for Diarrhoeal Disease Research in Bangladesh (ICDDR,B) and the nongovernmental organization now known as BRAC to turn a scientific discovery into a home remedy. Beginning in 1980, BRAC sent an army of 10,000 female health workers into the Bengali countryside, where they taught ORT to 13 million illiterate mothers. Children, too, learned the ORS recipe through one-room schools set up by BRAC that today number 37,000. In time, this simple solution became part of the national lore. At least 75 percent of families use ORS to treat diarrhea, according to government surveys.

The lesson, Cash says, is that no matter the problem--diarrheal infections, HIV, malaria--answers must be tailored to cultural norms, values, and practices. By way of example, he points to tuberculosis. Because treatment for the disease takes at least six months, helping patients complete their therapy is a major challenge. To ensure compliance, villages in Bangladesh enlist volunteers to serve as coaches. Moreover, patients (or, if they are too poor, their communities) must pay a modest bond up front, which they get back only upon completing treatment. At that point, their coach also earns a small sum.

"You must peg the payment at a level people can afford, but make it high enough that they'll miss it if they fail to follow through," explains Cash. In the United States, he says, a strategy that relied on community support to ensure patients' compliance "would never fly, given our emphasis on privacy and personal freedoms. But in a culture where the community is important to one's survival and the need to control infectious diseases is extremely urgent, this strategy can work."

'Rock star' in Dhaka
"Taking science to the people," as Cash puts it, is the operative word at BRAC University, in Dhaka, the Bangladeshi capital. In addition to collaborating with ICDDR,B researchers for 35 years, Cash has been an architect of the university's James P. Grant School of Public Health, one of only two in the country. Named in honor of the late UNICEF director, the new school saw its first 26 MPH students graduate in January of 2006. By design, many were admitted from developing countries--Tanzania, Uganda, Afghanistan, the Philippines, India, and Pakistan. Half were Bengali. Half were women.

Cash was the "obvious choice" to help lead the feasibility study for the school, says its international director, Demisse Habte. According to Habte, a former director of the ICDDR,B, Cash is "like a rock star" in the world of public health, adding, "To much of Asia, he is Harvard University."

REAL-WORLD LESSONS at the new James P. Grant School of Public Health in Bangladesh, students are immersed in field research. In this slum in the capital city, Dhaka, they interview women regarding health-seeking behaviors and other health practices.

To map out a curriculum, Cash sat down with BRAC's founder and president, Fazle Hasan Abed, and colleagues from Columbia University's Mailman School of Public Health, the London School of Tropical Diseases, and the University of Amsterdam. A priority, they agreed, was to teach problem-solving through field research. Instead of taking five classes a semester in nine months, Grant students tackle courses one by one, in three- or four-week modules over 11 months. This intensive format is "the only cost-effective way to do it," says the School's dean, Mustaque Chowdhury, a former BRAC research director and Bell Fellow at the Harvard Center for Population and Development Studies who has known Cash for more than 30 years. The fledgling school now borrows six of its eight faculty members from universities in England, Sweden, the Netherlands, and the United States. Cash teaches introduction to public health and infectious disease epidemiology at the Grant School during HSPH's Winter term and the summer.

"Richard's an awesome teacher," says one of only two Americans in the Grant School's class of 2007, Noah Levinson, speaking over an Internet connection from Dhaka. Having founded a small NGO, Calcutta Kids, in a sprawling city slum in West Bengal, India, Levinson says he "wanted to study public health in a setting like the one I'm working in. I couldn't do that in the U.S."

"Richard has a deep passion for Bangladesh--knows the culture, knows the people," Levinson adds. "He is highly respected there. When he talks, people listen."

With close ties to the ICDDR,B, the Grant School has the potential to become a research magnet. But the school must recruit a permanent, high-caliber faculty--a challenge, Cash says, since "to attract good people, you must create an exciting learning environment and pay them well." To recruit first-rate students, full scholarships are being offered to students in the first five years, thanks to support from BRAC, ICDDR,B, UNICEF, the James P. Grant Trust, and the Bill & Melinda Gates Foundation.

'We want to train leaders'
It took a deadly cyclone, massive flooding, and a concert organized by the late Beatle George Harrison, in 1971, to bring Bangladesh to the West's attention. As refugees returned home from India following the end of the War of Liberation, newscasts portrayed their newborn country as the epicenter of human misery. That image persists despite substantial progress in this struggling democracy toward the Millennium Development Goals, ambitious benchmarks that hold governments accountable for health and economic growth (see http://www.mdgbangla.org/index_en.html).

"I'm from India, and even I had the false impression, growing up, that Bangladesh was a miserable place," says HSPH master's degree candidate Hirshini Patel. But on a Winter-term trip planned last year by Cash, with stops at BRAC, ICDDR, B, and the Grant School, Patel says, "I was amazed at what I saw. The natural beauty was stunning, and the people were gracious and welcoming." And resourceful, she adds. There was vibrancy, optimism, and determination, despite the widespread poverty.
"In one very small village we all crowded around one man with TB. He showed us his skin lesions and answered our questions, which were pretty personal," Patel says. "But he was very open, genuinely interested in helping us learn."

Today one in four Bengalis live on less than $1 a day, on the margins of survival. Yet, according to a 2005 U.N. report, the country is making meaningful progress toward its Millennium targets. BRAC, founded in 1972, has played a pivotal role by economically empowering families, especially women. A major contribution of this NGO, one of the world's largest, is its support of primary education for girls. This, along with ORT and other investments in public health, have prompted declines in infant-mortality and fertility rates (now 56 infant deaths per 1,000 and 3.3 live births per woman, respectively).

As celebrated in October, when the Nobel Committee awarded its Peace Prize to the Grameen Bank and its founder, Muhammad Yunus, the country is the birthplace of microlending, through which loans as small as $10 enable even beggars to operate vegetable stands, sell crafts, and start other small businesses. According to the World Bank, Bangladesh has seen a rise in gross domestic product per capita in the last three years of 4.3 percent.

But big challenges remain. Diarrheal diseases persist for lack of clean water and sanitation. "Our maternal death rate is one of the highest in the world," laments Chowdhury. Arsenic poisons well water in thousands of villages, he says. And pneumonia is a major killer of children, owing to what he calls "our number one problem: a lack of trained professionals."

That's where Cash, and Harvard, can help--"by training some of our faculty, and sending more faculty here," Chowdhury says. "We want to train leaders."

Reciprocal discoveries
Research assistance, too, is what Harvard can offer. Cash's own studies focus on ethical issues in research in developing countries. Last summer, Cash led ethics workshops in Beijing, New Dehli, and Karachi. A book he'll soon publish presents dozens of real-life dilemmas. How do you get informed consent in a society in which individuals cede decision-making to village elders? Should studies relax stringent U.S. protocols where researchers in other countries deem them irrelevant? What happens when researchers in South Asia don't define plagiarism in the same way their American collaborators do? Is it reasonable, in a study of prostitutes' attitudes toward condom use in a country rife with HIV, to hire men to pose as clients?
The answers, Cash notes, again depend on local policies and cultural norms. For example, "the Terri Schiavo [right-to-life] case would never have happened in China," he points out. "There, patient welfare is a family matter, and the government has no role."

On both ethical and pragmatic grounds, Cash objects to Western nations that lead studies overseas, yet fail to adopt the results themselves. Ironically, he notes, ORT has never been widely used in the United States. For children there is Pedialyte, costing $6 a bottle. Adults are hospitalized and treated intravenously. Even now, several hundred elderly Americans die of dehydration each year, in part because people's awareness of thirst declines in old age. One U.S. company is refining ready-made ORS for the country's aging population.

Bringing health to the world's most vulnerable people is an uphill climb, but Cash draws inspiration from small victories and his curious, ambitious students. Let others retire. For his next project, he hopes to help plan curricula for new public health schools to be created, with an assist from Harvard, by the Public Health Foundation of India, an innovative partnership between India's private sector and the central government. As for teaching, Cash says, "I'll be doing that forever."

For a detailed account of the development of oral rehydration therapy by Richard Cash and others, see www.hsph.harvard.edu/review/summer_solution.shtml. To learn more about HSPH's research collaborations in the developing world, see https://webapps.sph.harvard.edu/cfdocs/worldmap/map.cfm.