Twenty-six-year-old Richard Cash arrived in what was then called East Pakistan straight out of his internship at Bellevue Hospital in New York City. The year was 1967, and Cash had been assigned to the U.S. Public Health Service as an alternative to military service under the Vietnam War draft. Here he was, a young man with little experience outside of his hometown of Milwaukee, witnessing life and death in one of the most impoverished and densely populated places in the world. In the rainy season it was even worse, with epidemics of cholera--a disease barely mentioned in Cashs medical school textbooks--devastating both the cities and countryside. Cash says he found himself for the first time in his medical career "really treating people who would die if I wasnt there--people who were really sick."
Cash is now in his 20th year on the faculty of the Schools Department of Population and International Health and in his 22nd year with the Harvard Institute for International Development. He says he hadnt really planned a career in international health--though with a self-effacing laugh, he admits that in his mental autobiography at that time, he may have projected "this sort of Albert SchweitzerTom Dooley image of going out into the middle of the jungle." As things turned out, Cash would be a coauthor of a different, though no less compelling, story: a stunning public health tale in which deft intervention saves millions of lives at a cost of a few pennies each.
Cash was a key figure in the effort that showed that low-cost, easy-to-use oral rehydration therapy would work to treat cholera and other diarrheal diseases. In 1968 Cash and David Nalin, now director of vaccine scientific affairs at Merck & Co., administered the first clinical trial proving that oral treatment for diarrheal dehydration was practical and effective. Mushtaque Chowdhury, director of research of the Bangladesh Rural Advancement Committee (BRAC)--a large nongovernmental organization that pioneered teaching home preparation and administration of oral rehydration therapy across Bangladesh--calls Nalin and Cashs work a "landmark contribution" to public health around the world. Adds Chowdhury: "I still dont understand why this did not attract the attention of the Nobel committee."
Diarrhea Is Deadly
Oral rehydration is the use of a saltwater-glucose solution (called oral rehydration solution, or ORS) along with regular feeding to replenish the bodily fluids lost during diarrhea. ORS was first tested in adults with cholera, but all the leading health organizations now recommend the therapy as the standard treatment for acute diarrhea in children who are not in shock. Throughout the world diarrhea is a common yet serious threat to childhood health. The World Health Organization estimates that children under the age of five collectively suffer 1.5 billion episodes of diarrhea each year. Before the advent of oral rehydration, an estimated five million children died each year from diarrhea because they lost so much fluid they became severely dehydrated. That number has fallen to an estimated four million deaths a year, although Nalin disputes the figure, saying, "ORS has certainly had a more profound effect than only a million a year."
Oral rehydration has been especially effective in reducing the case-fatality rates in cholera outbreaks, which can hit 50 percent. The therapy was first widely used during the 1971 civil war that resulted in East Pakistans independence from Pakistan and the establishment of the separate country of Bangladesh. Six million people fled over the border into India; cholera swept through the refugee camps during the summer monsoon months, and the case-fatality rate reached 30 percent. When a research team from Johns Hopkins treated nearly 4,000 cholera victims with oral rehydration and maintenance therapy--preceded, in the most extreme cases, by administering enough of the very limited supplies of intravenous fluids to correct shock--the case-fatality rate plummeted to between 3.6 and 1 percent. Twenty years later, during the 1991 outbreak of cholera in Peru, more than a quarter of a million Peruvians suffered from acute diarrhea. Three million packets of oral rehydration solution were distributed and administered, resulting in an amazing survival rate of over 99 percent. According to Mushtaque Chowdhury, the small number of deaths from diarrheal illnesses reported in the wake of catastrophic floods in Bangladesh last August and September is evidence that oral rehydration therapy saves lives.
Cash doesnt sit still for long in his office. He gets up to rummage through a drawer of old photographs (photos in which he sports an earlier, mink-brown version of the salt-and-pepper beard that now covers half his face), or to look for a videotape of Hugh Downs singing the praises of oral rehydration on 20/20. He leans back in his chair, answers the phone, leaves the room entirely to talk to a student or tease a colleague, displays a New York Times article about dehydrated waterfowl. A man of enthusiasms, Cash loves to travel, loves to collect art from the places he visits, loves meeting new people, loves teaching.
This winter he spent six weeks outside the U.S. teaching in the southern Indian state of Kerala, working with BRAC in the Bangladeshi capital of Dhaka; and attending both an International Clinical Epidemiology Network meeting in Bangkok and a conference outside Geneva on ethical issues in field research. Cash sees his time on the road and in the field as essential to his teaching. "The only way you can transmit new ideas or messages to your students," he says, "is to go out and experience them yourself and try to take as many lessons as you can."
Cash learned his own first lesson, which led to many others, in Bangladesh. When he first traveled to the country 32 years ago, Cash was assigned to the Cholera Research Laboratory run by the National Institute of Allergy and Infectious Diseases. Scientists at the lab had been experimenting with oral solutions as a substitute for intravenous therapy for some time, but until Cash paired up with another young CRL research fellow, David Nalin, no one had run a successful trial of the by-the-mouth alternative.
Though not the most common, cholera is the most severe of all watery diarrheas. Caused by a bacterium, cholera kills by inducing massive diarrhea and loss of water and salt--the physiologic equivalent of a severe drought. The patient becomes eerily calm, and his or her skin loses elasticity. A person can die in a matter of hours. Cholera is passed through contact with contaminated stool, usually via unclean food or water. War, floods, and other natural disasters are associated with the disease because sanitation falls apart under these circumstances; people drink dirty water when their only other choice is not drinking at all.
Before oral therapy, the standard treatment for diarrheal dehydration from cholera and other diseases was the administration of intravenous fluids and fasting. But intravenous treatment was expensive, hard to transport to rural areas, and difficult to use outside a clinic. And fasting, especially for already malnourished patients, actually prolonged the recovery period. So a cheaper, more convenient method of treatment had to be found.
A key discovery came in the 1950s, when physiologists showed that the addition of glucose to saltwater made sodium move more efficiently across a semipermeable membrane, such as the wall of the small intestine. That was a breakthrough for rehydration therapy because membrane-crossing sodium "pulls" water with it. And without the glucose, the water in salt solution would move in precisely the wrong direction--out of the body instead of in. The patient would become even more dehydrated than before, possibly dying from hypernatremia (excess sodium in the blood). Lab discoveries are one thing, putting them into practice is another; some of the initial experimentation with glucose-spiked saltwater solutions was, in fact, disastrous. In a 1962 clinical trial in the Philippines, five out of 30 patients died.
Magic in This Method
East Pakistan, Fall 1967. That season--"no one knows why," says Nalin--there was no cholera in Dhaka. So Cash and Nalin were sent to the Christian Memorial Hospital in Chittagong, near the border with Burma, to assist in a cholera outbreak. They were each assigned to head one of two projects carried over from the year before. Nalin followed a rehydration protocol that called for giving the solution intragastrically, or directly into the stomach by tube. It was, he recalls in an ironic tone, "one in a long series of ORS trials that failed."
The protocol failed, explains Nalin, chiefly because it called for each patient to receive the same amount of formula per hour, regardless of how much fluid was being lost in the stools and urine. Despite the setback, Nalin says he became convinced that oral rehydration solution would work if the proper studies were done comparing what was being put into the patients with what was coming out. Cash credits Nalin with recognizing that "we have to have a methodology, a clinical way of doing things. What people lose, we replace, and we do it over four-hour periods, and we look at urine output and so on." Although intravenous treatment relied on the measurement of fluid input and output, no one before Nalin and Cash had argued that such measurements were just as critical to the study of an oral treatment. "Everybody thought it was a magic bullet, and it would work by magic," says Nalin, explaining that because it was seen as a field treatment for use in rural areas, the attitude was that oral rehydration was low-tech, the quick-and-dirty solution that would have to work without setting precise specifications.
Returning to Dhaka, Cash, Nalin, and local investigators performed the trial that would establish the efficacy of an oral solution. The solution they used contained glucose plus sodium, potassium, bicarbonate, and chloride in concentrations approximating the levels at which they were found in cholera stool. The men took turns sleeping on a cot next door to where nurses treated three groups of patients according to three different methods: intravenously, intragastrically, and orally. The intragastric and oral methods reduced by 80 percent the amount of intravenous fluid needed to rehydrate a patient. The results were published in the Lancet in August 1968. Later, Cash and Nalin also demonstrated that the therapy worked for other kinds of diarrheal diseases.
Then in 1971 the Johns Hopkins team used oral rehydration with great success in the Bangladeshi refugee camps. These camps exemplified what Cash had come to realize by the time he came back to the U.S. in 1970: disease alone did not cause the sickness he saw. Structural problems got in the way of both effective disease prevention and treatment. "When youre in the midst of it," Cash says, "you see why kids are getting diarrhea-polluted water. Why are kids coming in with tetanus? Why are children coming in with treatable conditions and dying of those conditions? Why are women dying from childbirth? Why is there so much malnutrition? And you begin to not only look at the health interventions, but then you begin to look at social interventions."
Cash Gets Credit
Oral rehydration, powerful as it is, can only save lives if patients suffering from acute diarrhea get the therapy. "When we started out," says Cash, "we thought, Well, look at this; this is great. Everybodys gonna use this now, right? There it is. But everybody wasnt using it." To popularize the therapy, BRAC began a ten-year campaign in 1980 to educate Bangladeshis on the use of oral rehydration therapy; Cash served as a scientific adviser. "So now we went from the hospital to the clinic...treating hundreds of thousands of people," Cash explains. "And then BRAC and others took it even further. Right into the very"--Cash gives a cluck and thrusts his hand forward to emphasize his last word, the key word--"community." The campaign was not just about treating illness, Cash says; it was about empowering Bangladeshi women and families.
BRAC workers went directly to villages and taught rural women to concoct the rehydration solution in their own homes using common ingredients and easily learned measurements. Then the homemade solutions were tested in field laboratories that Cash helped set up. Across Bangladesh, in 15 million households, BRAC popularized the phrase, "A pinch of salt, a fistful of gur." (Gur is an unrefined sugar common in Bangladesh.) Sadia Afroze Chowdhury, MPH91, headed the health and population division of BRAC from 1991 until this year, when she became senior public health specialist at the World Bank. Of Cashs contribution to BRACs work, she says, "Hes extremely practical, and he has helped us go down to the root of a problem."
To Cash, this part of the story is no less a breakthrough than his work with Nalin: "Its sophisticated science that starts it, but then its all of that adaptation, which requires just as much creative energy, creative thought. But what it means is that you have to be there, to see how these things are playing out. You cant sit in this office and do it. Because how can you anticipate all these things? Who would think that, Well, maybe people dont have a teaspoon in the house?" In the end, he says, "The development of ORS was not just to reduce the amount of IV that you needed, although thats how it started out. It then became more and more, How do you take the treatment to where people are?"
Thats why Cash travels. He takes with him hope and a strong belief in human generosity, tempered by a distinctively Cash-style pragmatism. "Health has a lot to be proud of," he states, referring to the advances that have been made in public health over the course of his lifetime. "On the other hand, we have horrible inequities." And then, "Yeah, I think a lot of things are better. But certainly no, no, no grounds for complacency."
-- Eman Quotah