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Between 1980 and 2000, ORT treatment decreased the number of children under five dying of diarrhea from 4.6 million worldwide to 1.8 million—a 60 percent reduction. Last year, the accomplishment garnered four of ORT’s developers, all of whom have been affiliated with the School of Public Health, the prestigious Pollin Prize for Pediatric Research (see sidebar). But the development of ORT, from its inception to its use in the refugee camps in India in 1971, was neither seamless nor direct.
But the development of ORT, from its inception to its use in the refugee camps in India in 1971, was neither seamless nor direct.
As early as 1830, a saline injection was used with success on a cholera patient, yet the practice did not catch on. Common, and often lethal, 19th-century remedies for cholera instead included blood letting—precisely the wrong thing to do for someone dying of dehydration—and, in one doctor’s office, intravenous injections of cow’s milk. “Starving” patients to give the gut a rest, also a wrong-headed and deleterious approach, was common into the 1950s. The physiological mechanisms of acute diarrhea were not yet understood.
“Almost every culture has a grandmother cure, like chicken soup,” that may be useful but lacks the optimal mix of sugars and salts that ORT has, explains William Greenough, MD, a professor of International Health at the School who was a physician at the Dhaka lab starting in 1962. But if the patient doesn’t ingest enough of the chicken soup to replace what he’s losing, it won’t work. In the 1950s, somewhat effective therapies, like carrot soup, were tried clinically. These were hit-or-miss concoctions, however, rather than a scientifically formulated replacement for the exact substances being lost in acute diarrhea.
Throughout the 1940s, ’50s, and ’60s, scientists made advances in determining exactly what happened when a person was inflicted with acute diarrhea: what is lost with the diarrhea and the mechanisms through which, using a specific combination of glucose and sodium, fluids and nutrients could be replaced. These physiological discoveries would make it possible to develop effective intravenous treatments and, later, an effective oral rehydration solution.
A second integral part of the ORT story is the unusual degree of cooperation and healthy competition that developed between two laboratories, both of which were launched in the early 1960s and both of which drew researchers from the School of Public Health. The Johns Hopkins International Center for Medical Research opened in Calcutta, while, just 150 miles away, the Dhaka Center (officially known as the Pakistan-SEATO Cholera Research Laboratory and later the International Centre for Diarrhoeal Disease Research, Bangladesh) was established under NIH’s direction. These two centers, often in tandem, played pivotal roles in finding a treatment for cholera in adults, and then acute diarrhea in children.
The first step was to perfect IV therapy. This, according to Greenough, was accomplished fairly quickly. The mortality rate dropped from 30 to 40 percent for untreated villagers to less than 1 percent with IV treatment. “They were like resurrections,” he recalls. “Families would bring a dying relative in, and we would take them off the rickshaw, lay them down on the sidewalk, and hydrate them there. Everyone in the family watched what would happen—they’d come back to life.”
But in the developing world, resources for IV treatment were scarce. The treatments required prohibitively expensive supplies, from needles to sterilization equipment, as well as trained workers. “In the 1962–63 period there were very large outbreaks in several refugee situations. With no IV solution, they were just dragging the sick out to die,” says Greenough. “It was clear there was no way to get IVs” to the victims. A simpler technique was needed.
By 1962, NIH researchers learned of the work of Robert A. Phillips, a Navy doctor who had treated cholera patients in the Philippines with an oral fluid. NIH saw the potential, but Phillips’ experiment had been based on an incorrect physiological hypothesis, and the resulting mixture resulted in the death of five patients. These deaths “weighed heavily” on Phillips, writes Joshua Nalibow Ruxin in his book, Magic Bullet: The History of Oral Rehydration Therapy. When Phillips took over the Dhaka Lab in the mid-1960s, he brought with him a deep-seated bias against oral rehydration.
In spite of the authoritarian Phillips’ resistance, some ORT research continued, in part because of the persistence of Norbert Hirschhorn, MD, who worked under Phillips at the Dhaka lab (and would later join the faculties of the Hopkins Schools of Public Health and Medicine in the early 1970s).
Phillips, says Hirschhorn, only trusted the researcher who was also his personal physician. “He appointed me to be his physician—he had high blood pressure—so he trusted me.” Hirsch-horn is now a poet and consultant for the Yale/World Health Organization Collaborating Center on Health Promotion Policy and Research at Yale’s School of Medicine.
When Hirschhorn proposed re-opening investigation into oral rehydration, Phillips initially said, “We can’t ever do that again.” Hirschhorn replied: “Let me see your data.” Phillips relented. “He brought me into his office and locked the door. He said, ‘Here’s my safe, with all the data. I’m going to leave you alone for an hour.’ Then he left, locking the door,” recalls Hirschhorn. Hirschhorn read the data and saw where Phillips’ formula had gone wrong—too much salt—and convinced Phillips to let him try again, with an adjusted formula. Phillips agreed on the condition that Hirschhorn sleep next to the patients to make sure they didn’t die.