Wednesday, 18 January 2012

Iodine Deficiency Disorder (IDD)- Water Under the Bridge Article from Harvard Medicine (2004)- Points to BioLargo Opportunity




Water Under the Bridge
A neurologist turns to hydrology, agronomy, and veterinary medicine to tackle the world’s most preventable cause of mental retardation.
by GORDON WORLEY

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As a young boy growing up in Indiana, G. Robert DeLong ’61 would toss sticks into creeks to gauge the speed of the water. Little could he have known how useful his childhood game would prove decades later, when he set out to eradicate a disease that for centuries had been devastating children in a remote corner of China.

DeLong traces his fascination with iodine deficiency disorders (IDD) to nearly 25 years ago, when his mentor, John Stanbury ’39, suggested that he join a medical trip to Ecuador. “I thought the reports would turn out to be exaggerated,” DeLong recalls. “But in a single month in an Andean mountain village I saw 120 cases of a disease that, until then, I’d only read about in textbooks. These were people in whom prenatal iodine deficiency—and the resulting fetal hypothyroidism—had caused cretinism, characterized by blighted physical and mental development, spastic-rigidity, and deaf-mutism. The disease just debilitated the entire community.”

DeLong remembers in particular one young woman whose limbs were so twisted that she had to use her elbows to drag her body across the floor of her family hut, with all the painful laboriousness of a beached mermaid. Her family members would often prop her up outside, then carry her in when it began to rain.

When this same young woman became pregnant, she might have given birth to a baby as impaired by iodine deficiency as she had been. But as part of the local IDD control project, she received an intramuscular injection of iodine-in-oil during the second trimester of her pregnancy. The daughter she delivered is now a college graduate who speaks three languages.

In the decades since his first encounters with IDD, DeLong, a professor of pediatric neurology at Duke University, has witnessed many other instances of the transformative power of even tiny doses of iodine in preventing the disorder. So when he encountered unusually high rates of the disease in Xinjiang, a province in northwestern China, he became determined to find a solution.


THE SALT OF THE EARTH

Symptoms of iodine deficiency have plagued humankind for millennia. A second-century frieze of Buddha and his disciples, for example, shows a figure with goiter. Drawings from the thirteenth century depict people with goiter and cretinism, and Renaissance painters from Dürer to Rubens captured on canvas many subjects with goitrous necks.

Today, iodine deficiency still condemns many thousands of children to cretinism, tens of millions to varying degrees of mental retardation, and hundreds of millions to milder degrees of mental and physical impairments. An estimated 1.6 billion people are at risk for IDD, now recognized as the most common preventable cause of mental retardation worldwide.

Nearly one-third of the globe’s inhabitants live in areas of natural iodine deficiency. The regions most affected are mountainous ones, where glaciation, snow, and rainfall leach the mineral from the soil; flood plains such as that of the Ganges; and inland continental expanses far from the world’s oceans, which are the primary sources of iodine.

Countries around the world have responded to the problem, adding iodine to tea in Tibet, bread in Australia, and fish paste in Thailand. Yet fortifying ordinary table salt with iodine, the most common method, is also considered the best. IDD was endemic in the Appalachian, Great Lakes, and mountainous western regions of the United States, for example, until the 1920s, when iodized salt consumption became widespread.

Iodized salt does not offer a solution for people living in many remote areas of the world, though. Some communities find it too expensive or difficult to obtain; others reject it as less flavorful than locally available salt. Efforts to provide oral or injected iodine-in-oil to people living in areas with endemic IDD often fail because of issues of cost, distribution, or sustainability. Cultural traditions and superstitions may create obstacles as well.


TESTING THE WATERS

The problem of iodine deficiency is hardly new to Xinjiang: while traveling through the region during the thirteenth century, Marco Polo recorded observations of people with diminished intelligence, deafness, spasticity, and enlarged throats. Throughout the intervening centuries, the tragic consequences of iodine deficiency have continued to plague Xinjiang, whose water and soil contain some of the planet’s lowest levels of naturally occurring iodine.

A constellation of factors had contributed to the failure of efforts to provide the people of Xinjiang with iodine. Some of the barriers were cultural. Forty percent of the region’s inhabitants are Uighurs, a Turkic people who comprise the largest of China’s minority groups. The Uighurs—most of whom live in villages dotting the perimeter of the Taklimakan Desert—find iodized salt not only less affordable, but also less savory than the rock salt so abundant in the desert.

“The Uighurs have a tradition of picking rock salt off the desert floor, dissolving it in big clay pots, and then using the brine for cooking,” DeLong says. “The desert salt has a ‘brighter’ flavor—likely from its magnesium content—but unfortunately it contains little iodine.”

Exacerbating the problem was the centuries-long contentious relationship between the Uighurs and the majority Han, who dominate the country’s central government. And so the Chinese authorities’ attempt to offer iodine pills failed, among other reasons, because the Uighur women suspected officials of trying to slip them contraceptives.

Efforts to introduce iodine intramuscularly had fallen short as well. Injections such as those used in Ecuador required medical expertise and supplies not widely available in Xinjiang. And local public health authorities were skittish about injections for another reason: in 1988, the area had suffered a hepatitis epidemic that had left 500 dead, and they wanted to avoid the risks of shared needles.

When DeLong first visited Xinjiang in 1989, he found one in ten children suffering from severe IDD and one in three exhibiting symptoms of iodine deficiency. “We were examining literally hundreds of children,” he says. “Some showed extreme mental retardation and could not walk, stand, or even sit. Even the ones without severe signs were slack and dull-eyed. They simply lacked the natural vivacity of children.”

During repeated trips to Xinjiang, as DeLong pursued his initial goal of studying the impact of iodine deficiency on fetal brain development, he pondered ways to prevent the calamity from occurring in the first place. By then he had grown close to two Chinese colleagues, Ma Tai, a leading expert on IDD in China, and Cao Xue-yi, the head of Xinjiang’s Health and Anti-Epidemic Station. Together they explored—and rejected as impractical—possible solutions to the seemingly intractable problem.

Then, one day after working in the clinic, the collaborators happened to drive to the countryside to see the main irrigation dam, 20 miles upstream. “We looked out over the Hotien River with its complex system of irrigation canals, the basis of all human life there,” DeLong says. “It was fascinating, but I didn’t give it much thought. Back in the capital the next day, I chatted with a local water chemist about the concentrations of various minerals, such as iron and copper, in the water. But the penny still didn’t drop.”

That evening, DeLong says, “We were driving to a Uighur comedic performance when suddenly it hit me. I practically shouted, ‘We can drip potassium iodate into the irrigation water!’ Dr. Ma threw up his hands and cried, ‘We’ll all go to jail!’ But by the next day, he was thinking about it seriously. It quickly became clear that the idea could work.”

DeLong had realized that iodinating the irrigation water could protect entire villages. The plants would absorb the iodine that had leached from the treated water into the soil. The animals, in turn, would ingest the iodine-rich plants. At the top of the food chain, people would finally consume sufficient levels of iodine.

Obtaining approval for his proposal from suspicious local communities would be tricky, DeLong knew. But an incident that had taken place the previous year had helped convince the wider Uighur community of the physician’s good intentions.

Late one afternoon DeLong, Ma, and their team were working in a small clinic in the village of Tusala when a sandstorm swept in from the desert. DeLong’s wife, Nancy, who has shared his IDD work at every stage, recalls that day.

“About three o’clock the room suddenly became almost as dark as night, with an eerie yellow light,” she says. “A gale force wind was blowing the trees sideways and sending dust swirls skyward. The patients covered their mouths and noses with their headscarves and huddled along an inside corridor. The lights flickered and went out.”

Just as the medical team had begun examining patients again, a great commotion of people burst into the room; they were bringing in a young boy who had picked up a live cable blown down by the storm. For several long minutes DeLong desperately tried mouth-to-mouth resuscitation and chest compressions but could get no response. Then someone mentioned that the boy’s father had transported him to the clinic in a donkey cart for six kilometers.

“I shined a light into the boy’s eyes,” Nancy DeLong says. “He was dead. Bob straightened up, told the father he was sorry, and stood helplessly in tears, as the father, fighting for control, gently lifted his child, wrapped a sheet—now a shroud—around him, and carried him from the room, clasped tightly to his breast.”

“Tragically, our sustained efforts couldn’t revive the boy,” Ma later recounted. “Yet his family bent down to express their heartfelt gratefulness. And the story about the American doctor spread, even to the capital.”

The reservoir of good will that DeLong generated that day may have helped his cause when, a year later, he and his team explained the proposal to iodinate the irrigation water to villagers in the chosen site of Long Ru township. Each phrase was painstakingly translated into Mandarin, then into Uighur. To the team members’ relief, they found a receptive audience. The villagers discussed the dilemma, then took a vote.

“When we met with the village leaders in Long Ru, the temperature was hovering near zero,” remembers Nancy DeLong. “They were all sitting around in their thin coats and wool hats. Their breaths sent tiny clouds into the air and their wonderful weathered faces looked like stone. Then suddenly everyone erupted: ‘Yes, we approve!’ ”


THE BOTTOM OF THE BARREL

One of the first tasks facing DeLong’s team was calculating the flow rate of the canal. Impatient for the arrival of outside help, DeLong drew on his youthful penchants. In the eighth grade he had taken an interest inventory test that recommended he become a county agricultural agent. So it was with a sense of familiarity that he tackled the challenge.

“We stripped to our undershorts, waded into the canal to measure its cross-section, then threw sticks in the water and recorded how fast they floated by,” DeLong says. “I felt like I was back on my uncle’s farm in Indiana, tossing twigs into the creek. Much later, we learned that our estimate was within 10 percent of the official measurement.”

The team next devised a primitive delivery system: a 55-gallon oil drum coated with epoxy paint to prevent oxidation and rigged with a spigot that could be turned on and off. The spigot was not precise enough in regulating the output, though, so they used intravenous tubing and two clamps to cobble together a simple valve to provide a steady flow. They tested their contraption overnight in a hotel parking lot—and found that it worked.

Next they perched the oil drum on a wooden bridge spanning the irrigation canal. For two weeks during the spring of 1992, the team dripped a 5 percent solution of potassium iodate into the canal, which supplied four villages in Long Ru township with water. They hired a local villager to protect the drum from theft, refill the tank, and monitor the flow rate. At night, the man would unfurl his rolled-up blanket and sleep right on the rough-hewn bridge.

Soon more men were needed to safeguard more barrels. Decisions about the placement of the drums and the timing of the dripping were made with the input of local officials, particularly the kuai-ji, or water accountants, who oversaw all aspects of irrigation for the region. During the spring planting, as many as 20 tankfuls of potassium iodate solution were dripped into a canal from a single site.


THE TASTE OF SUCCESS

Measurements from samples sent to a laboratory in Ürümqi, the capital, revealed that iodine concentration in treated areas had increased four-fold in the soil within weeks and three-fold in the crops and animals within months. Within one year, nearly all local women of childbearing age had iodine levels well out of the danger zone. The results were most dramatic in children conceived after the program began. Within three years of the first dripping, the infant mortality rate fell by half. Later assessments showed that the average height of five-year-olds had increased by four inches. And the intelligence quotients of children born after the dripping averaged 16 points higher than those of children born before the dripping.

“When we first arrived in Xinjiang, I thought the children were withdrawn because they were afraid of us,” says Nancy DeLong. “But as time passed, and the treated water took effect, I realized that the children were growing livelier.”

Local livestock thrived too. Within a year, sheep production had increased by 40 percent. And as a result, the average annual family income rose 5 percent.

From their initial study, published in 1994, DeLong and his colleagues concluded that treating irrigation water was an effective and relatively inexpensive method of supplying iodine to people in irrigated areas where IDD is endemic. With the support of the Thrasher Foundation, the Joseph P. Kennedy, Jr. Foundation, Kiwanis International, and UNICEF, the team undertook a major expansion of its program in 1997. Iodine dripping now protects 2.6 million people from IDD in the 16 most severely deficient areas of Xinjiang. Thirteen and one-half tons of potassium iodate have already been dripped, at a cost of less than six cents per person.

Iodine concentrations in soil, crops, meat, and human urine, monitored since the one-time dripping, indicate that a single dripping can provide iodine for at least six years. Iodination of irrigation water has now been undertaken in Inner Mongolia and is planned for Kyrgyzstan.


THE SALINE SOLUTION

But what about iodine-deficient areas of the world where widespread irrigation doesn’t exist? In the heart of Siberia, at the geographic center of Asia, lies Tuva, the poorest republic in Russia. Home to a Mongolian people, Tuva is renowned for its rich folklore, skilled artisans, andkhoomei, a form of throat singing whose haunting notes are said to mimic the wind sweeping across the steppes. The area is also known for its elevated rates of IDD.

There infant mortality runs high, and in some areas nearly half of the newborns have hypothyroidism caused by iodine deficiency. The lasting economic disruption that followed the collapse of the Soviet Union has made iodized salt an impractical solution. And, unlike the people of Xinjiang, the Tuvans do not rely on irrigation water. They depend instead on animal herding for their livelihood, raising sheep, cattle, horses, goats, and even camels on the elevated steppes of their ancestral homeland.

When DeLong reflected on the high rates of severe IDD in Tuva, he reasoned that the most efficient way to distribute iodine would be by adding potassium iodate to salt licks for the animals on whose products—mutton, beef, milk, cheese, and yogurt—the people relied. “We knew,” he says, “that iodinating salt licks had been successful in the Netherlands and England, where the iodine levels in cows rose dramatically.”

The plan required machinery for crushing rock salt, adding iodate, and making salt blocks. The Tuvan government approved the plan and promised to supply the potassium iodate and workers to operate the plant. Local authorities agreed to distribute free iodinated salt blocks to all herders in the region.

But the machinery still needed to be financed, manufactured in India, and transported by ship, the Trans-Siberian railway, and truck to Tuva. And all this had to be arranged from half a world away. DeLong secured financial support from friends and members of Kiwanis International. By the fall of 2002 the machinery had arrived. So DeLong returned to Tuva with his Kiwanian friends.

“One of them was a high school mechanical shop teacher,” DeLong says, “and he had that machine up and running in two days.” By the time the Kiwanians staged a repeat visit the following spring, local workers were turning out iodinated salt blocks and distributing them to Tuva’s mountain communities.

“Their sheep had been producing poor quality wool because of the lack of iodine,” DeLong says. “If we’re lucky, the salt licks should improve not only human health, but also the health of the local wool industry.”

DeLong and his team hope that, as knowledge of the health benefits, affordability, safety, and economic advantages of iodinating irrigation water and salt licks spreads to affected areas of the world, so will the adoption of their practical methods. “With all the medical technologies we have to work with today,” DeLong says, “it’s easy to forget the incredible difference an ancient trace mineral can make to a single life, to a community—even to the world.”

Gordon Worley ’73 is an associate clinical professor at the Duke University School of Medicine.

This article appeared in the Spring 2004 issue of the Harvard Medical Alumni Bulletin.

Photo caption: Gordon Worley’s idea to introduce an iodine solution into the water systems of a remote part of China helped reduce the incidence of iodine deficiency disorders among residents.

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