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Killer in the Water

Tracing arsenic’s threats to health in the Badlands.

By Maryalice Yakutchik • Illustrations by Dung Hoang

Out here, life is sparse and unforgiving.

Neighbors include prairie dogs, porcupines and reclusive mountain lions. The residents, human and non, revel in remoteness. But this wide-openness can be daunting, especially for interlopers. It’s the kind of place where it’s easy to get lost; a missed turn can lead you astray a hundred miles. Signage isn’t a strong suit. Nor are safety nets. When a heifer wanders from its herd out onto a frozen river, it’ll stand, shaking, for a long time. Maybe forever.

When it’s 14 degrees below zero in November and a pipe breaks, or 114 in the July shade and a well suddenly stops, bottled water and plumbing supplies are not always handy or affordable.

Here, where South Dakota’s prairies unfurl into badlands, Ana Navas-Acien and colleagues are investigating bad water—specifically well water tainted by arsenic—and how it affects health.

Everyone is clear about the fact that too much of the colorless, odorless metalloid is not good for a person. Depending on the amount, it can cause death in minutes, or illness over decades. Arsenic in drinking water is considered one of the prominent environmental causes of cancer death in the world. Both the EPA and WHO currently agree on a threshold of 10 parts per billion (ppb) of arsenic in drinking water. Mounting evidence from places plagued by naturally occurring arsenic that contaminates groundwater—like Bangladesh, Taiwan and Chile, for instance—shows that chronic exposures to high levels (greater than 100 ppb) contribute not only to cancer but also diabetes, cognitive deficits, cardiovascular disease... The list of maladies related to high arsenic exposure is long, and growing.

But what nobody knows for sure—and what Navas-Acien, MD, PhD ’05, is committed to figuring out—is whether even low exposures to arsenic are harmful over the long haul. And: Can genetic and environmental factors make seemingly insignificant chronic exposures especially bad for certain people?

The environmental epidemiologist has focused the attention of an international interdisciplinary team on an area where generations have been exposed to low-to-moderate levels of arsenic in drinking water. By querying data from a long-running population-based cohort study of Native Americans known as the Strong Heart Study (SHS) and by conducting genetic and epigenetic analyses on blood and urine samples supplied by the SHS, the researchers are discovering precisely where and how arsenic does its damage. They’re finding out how genetic makeup and diet cause some to suffer more from a public health burden that’s long been under the radar in the U.S.

More than 100 million people around the world are exposed to arsenic levels in drinking water above the 10 ppb standard. In Bangladesh, for instance, cases of groundwater-caused arsenic toxicity are common. In the U.S., surveys of drinking water indicate that about 80 percent of water supplies have less than 2 ppb of arsenic, but 2 percent exceed 20 ppb of arsenic, according to the Agency for Toxic Substances and Disease Registry. A U.S. Geological Survey study revealed that slightly less than half of 30,000 arsenic analyses of groundwater in the U.S. were at 1 ppb or lower, and about 10 percent exceeded 10 ppb. Investigations of groundwater in South Dakota, New England, Michigan, Minnesota, Oklahoma and Wisconsin suggest that arsenic concentrations exceeding 10 ppb are more widespread and common than previously recognized, according to a National Water-Quality Assessment Program report.

Illustration by Dung Hoang.

The maximum contaminant level for arsenic in drinking water was reset in 2001 by the EPA, which cut it in one fell swoop from 50 ppb (established in 1942) to the current standard. Some argue that 10 ppb is needlessly strict. But arsenic experts like Navas-Acien and colleagues are not convinced that the existing standard for arsenic in drinking water is low enough. Even if the current standard was halved to 5 ppb, that likely wouldn’t translate to “healthy,” the physician-scientist contends, as in: not contributing in a discernible way to chronic disease. The set point of this most recent 10 ppb threshold, she suspects, has more to do with feasibility and risk assessment than lifelong wellness.

“Because of what we know from studies in humans and animals, I would only drink water that’s below 1 ppb,” Navas-Acien says.

EPA standards don’t govern private wells, and rural and often impoverished populations disproportionately rely on wells contaminated with arsenic. In the Dakotas, the geology is such that arsenic leeches down into groundwater and contaminates wells. It’s not unusual for private well water in this region to hover in the low-to-moderate contamination range, between 10 and 100 ppb.

Nor is it unusual for American Indians to die from heart disease. Cardiovascular disease is the No. 1 cause of death in the U.S., and rates among American Indians exceed those of the general population.

Navas-Acien is passionate about lots of environmental factors that play roles in human disease. Tobacco, for instance, holds a special place in her heart. “And cadmium and lead, they are very interesting metals!” she enthuses.

“But arsenic is especially intriguing. Let me show you.”

The 42-year-old associate professor in Environmental Health Sciences produces a laminated periodic table from a shelf in her Bloomberg School office. It is written in Flemish and French. It’s personalized with a red ink line that she drew decades ago to separate the metals from non. It’s, well ... loved.

“This is from high school,” she explains, digressing from revealing arsenic’s personality to share a bit of her own. In 1983, when she was 11, her parents declared the family was moving from Granada, Spain, to Brussels, Belgium. They shoe-horned their three daughters into a tiny, white Simca 1200 stuffed with suitcases. But what really made the 2,000-kilometer road trip excruciating, Navas-Acien recalls, was that her dad smoked as he drove.

“We would complain, ‘Stop smoking!’ We hated it. My younger sisters and I would hide his cigarette packs and not tell him where they were.”

The girls’ haranguing eventually hit home.

“One day, about a year or so after the move, he announced, ‘It’s going to be very hard for me, but I am going to do it.’ He told us that if we ever in our lives smoked, we may never do so in front of him.”

Navas-Acien’s first environmental health intervention was a resounding success: Her dad kicked the habit. And neither she nor her sisters ever smoked.

In the Northern Plains of the U.S., pocked gravel roads connect places like Buzzard Butte and Yellow Bear Canyon. Lots of lonely miles separate the blue-sided bungalows, battered trailers and ranch houses that rely on private wells.

Here, Navas-Acien has plans to co-direct a new project with Christine Marie George, PhD, an assistant professor in International Health and expert on water interventional research. Their three-site study involves assessing the acceptance of filtration devices by American Indian households relying on wells contaminated by more than 10 ppb arsenic as well as those devices’ long-term effects on arsenic exposure and, ultimately, health.

The team expects its proposed intervention trial will be tough, and not only for logistical reasons. Navas-Acien’s dad was a pushover compared to, say, a resourceful guy named Bud May whose cattle ranch sits squarely in the middle of the southernmost study site, a locale targeted for the most intensive intervention program—one where the distribution of filters will happen in the context of strategic community outreach efforts and an educational campaign.

None of the hundreds of miles of service pipelines maintained by Mni Wiconi, the tribally owned and operated community water supplier for this region,reach May’s property.

He’s more than fine with that.

“There’d be houses popping up if the pipe did come out here,” he says. “And well water here is better than anything you can find in a store, as far as quality and taste.

“Is there some arsenic in a well around here? It wouldn’t surprise me. Are there going to be some long-term problems? More than likely. But if it’s not eatin’ holes in my gut as I drink it, I’m not going toworry about it.”

The 29-year-old smiles broadly if sheepishly, having caught himself sounding like a “backwoodsy redneck,” though it’s clear he’s not one. A former college football player whose father was Lakota and mother is Scandinavian/German, May has a bachelor’s degree in kinesiology and a master’s in athletic administration. He also has just a touch of paranoia with regard to his well, he admits. If it got tested, maybe somebody might deem it contaminated, giving the government cause to shut it down, he worries.

“I don’t want it condemned,” he says. “This is my only source of water out here. The cattle are healthy. The horses are healthy. I’m healthy. To be honest with you, I don’t want it tested. Ignorance is bliss.”

As he heads over to the corral to check on his horses’ water situation, he recalls how bleak and rundown this property was before he purchased it and put in “a whole lot of man hours.” He plans to raise his family here, he says, pointing out that on a really clear day, you can see the outline of the Black Hills on the western horizon.

The Lakota once were nomadic. They depended on the tatanka (buffalo) as well as mighty rivers that bordered what formerly constituted the Great Sioux Nation. Dispossessed of their hunting grounds and flooded out of the fertile bottomlands of the dammed Missouri River, they now depend on the government. Tribes are confined to a hodgepodge of depleted remnants of sovereign lands, nations within a nation. A bitterness about broken treaties and hostility over water rights sometimes surfaces. But deep down, there is resiliency and overwhelming graciousness.

Navas-Acien met wary skepticism when she first visited the tribes to propose her studies, two of which are ongoing (epidemiology and genetics) and two in the planning stages (an epigenetic investigation and the intervention trial). But her patience and sensitivity won the people’s trust and earned endorsement of her investigations, from not only the Strong Heart Study steering committee and Indian Health Service but also public health specialists and elected officials from tribes of the Great Plains region.

"This community has had everything thrown at them, from infectious disease to the U.S. military. And yet they’ve still survived."

Lyle Best, MD, the SHS principal investigator in the Dakotas, says it’s apparent that Navas-Acien is not about one-off research projects for self-serving purposes. A born-and-bred North Dakotan, Best appreciates her genuine commitment to the Native people with whom he has worked for 30 years, as much as her expertise about a contaminant impacting a resource considered sacred here.

“Water is life,” says Reno Red Cloud, an Oglala Sioux tribal water administrator who is consulting with Navas-Acien and George on the proposed intervention. He suggested it be named “Strong Heart Water Study for Private Wells.” This sixth-generation grandson of Chief Red Cloud—a battle-hardened leader who, in the mid-1800s, was both feared and respected by the U.S. government—lends all-important local support to the study’s implementation.

So does Cheyenne River Nation Councilman Ryman LeBeau, chair of the Environment and Natural Resource Committee for his tribe. With a long, black braid and degree in environmental science, LeBeau treads a line between the traditional and the modern, embodying the spiritual and visceral ties his people have to the land and water: “The way we think is connected to this place,” he says.

The fact that Navas-Acien’s studies are ancillary to the long-running Strong Heart Study assuages the doubts that some can’t help but have about the motives of researchers who come here wanting American Indians’ blood, urine and genetic information. The worry is that sensitive, personal data can get misused and reused without consent or authority. Native people have been burned by scientific studies in the past, the results of which have embarrassed and further stigmatized tribes.

“The SHS has been here a long time,” LeBeau observes. “That relationship is established. I think that’s the way it should be. It fits well within the community.”

Among the stubborn stereotypes swirling around American Indians is that they won’t participate in or comply with scientific studies—a notion the SHS has been disproving for a quarter century.

“Understanding requires data,” LeBeau reasons. “Without that, you can’t change things. Maybe this won’t help me, but [it might help] my kids, my grandkids.”

LeBeau, 35, is a father of four kids, ages 7 months to 11 years. He’s the kind of dad who, when his wife isn’t feeling well in the morning, takes time to braid the hair of his squirming 4-year-old son Ryze (even though it’ll make him late for a meeting). He’s the kind of councilman who tells it straight about why he’s late: “It looks easy when my wife braids his hair, but it took me a lot longer. I was tempted to say the heck with the braid.”

LeBeau is woven into his community. Entwined with his people’s past. Unwilling to say the heck with the future.

“Our culture is here, our language, our elders, our ceremonies,” he says, alluding to men whose prayers emanate from sweat lodges, women who piece together star quilts and children whose elders are buried at Wounded Knee. “It’s happening here.”

Also happening here, more often than in other places, is stuff that makes people sick, and causes them to be guarded.

“This community has had everything thrown at them, from infectious disease to the U.S. military,” says SHS project coordinator Marcia O’Leary, BSN, a lifelong South Dakotan and founder of Missouri Breaks Industries Research Inc., a small but determined Indian-owned research firm in Eagle Butte, South Dakota. “And yet they’ve still survived.”

The community’s desire is for more than mere survival, however. “People here want good health just like everybody else,” she says. Standing in their way, O’Leary adds, is “tremendous poverty.”

The counties served by Missouri Breaks include at least a handful—Perkins, Shannon, Ziebach, Bennett and Dewey—that rank among the nation’s top-15 poorest. Rates of suicide, addiction and unemployment are miserably high here.

“The arsenic is one cog on the wheel,” observes Randolph Runs After, MPH, an environmental health specialist based in Eagle Butte. As tribal sanitarian, his daily concerns range from bed bugs and rodents to fracking and the Keystone XL Pipeline, which is proposed to run under the Moreau and Cheyenne rivers on tribal lands.

Navas-Acien’s focus on arsenic contamination isn’t meant to distract attention or divert resources from these myriad in-your-face issues plaguing American Indian communities, she says. Rather, her collaboration with these communities aims to bring scientific evidence to the fore, empowering them in the overarching battle against poverty and its toxic trappings.

Harmful as arsenic is for everyone, it’s worse for some. Navas-Acien’s group has found that people who have both diabetes and arsenic exposure seem to have a higher risk of cardiovascular disease than people with diabetes alone, or arsenic exposure alone.

“Clearly, there is some heterogeneity in the way that people respond to arsenic,” Navas-Acien observes.

Arsenic metabolism happens mainly in the liver. The process depends on an enzyme called arsenic methyl transferase (arsenic 3MT) that transfers a simple structural unit of organic compounds called a methyl group from so-called methyl donors—folate, for instance—to arsenic. The conventional thinking is that arsenic gets “methylated” for the purpose of detoxification; that methylated compounds are easier to excrete and are less toxic. Navas-Acien’s team is demonstrating a new level of complexity related to this process, showing that intermediary metabolites can be quite toxic and likely are linked to cardiovascular disease and diabetes.

In studying methylation patterns of arsenic, her colleagues found high levels of hereditability, indicating strong familial connections in the way that individuals metabolize arsenic. They even pinpointed a region of the genome that seems to be responsible for this.

Methylation of arsenic depends on more than genetic factors, however. Smoking plays a role. Death rates accelerated among smokers exposed to arsenic, others have found, indicating arsenic’s apparent amplification of the damaging effects of smoking.

Diet plays a role. Folate, a methyl donor commonly known as vitamin B9, is found in foods like spinach and broccoli. High folate levels correspond with different forms of methylation. One form appears advantageous for the heart but may be disadvantageous for diabetes; another appears advantageous for diabetes but may be disadvantageous for the heart, revealed Navas-Acien’s former student Chin-Chi Kuo, MD, PhD ’14, MPH ’11. It’s hardly cut-and-dried.

Illustrations by Dung Hoang.

“Human metabolism is so complex,” Navas-Acien says. “We are looking at just the metabolism of arsenic and we see these very intricate connections with disease.”

She and colleagues reported an association between long-term exposure to low-to-moderate arsenic levels and cardiovascular disease incidence and mortality in November 2013 in the Annals of Internal Medicine. Rates of cardiovascular illness were often doubled for those with chronic exposure to arsenic, according to Bloomberg School PhD student Katherine Moon, MPH ’12, the study’s first author.

The obvious next question was why? And: How and where does arsenic wreak havoc on heart health?

By tracking methylated species of arsenic traveling from the liver through the bloodstream, the team sees evidence that the innermost layers of the wall of the carotid artery are thicker in people chronically exposed to low-to-moderate arsenic than in those who aren’t—an indication of the presence of atherosclerotic disease.

“We measure in the carotid artery, but probably this thickening is happening everywhere, in all the arteries,” Navas-Acien contends.

The really tricky thing about chronic disease is the multiple interdependent risk factors at play. Navas-Acien is exposing and tugging on one colorless, odorless string hiding deep in the complicated tangle that constitutes cardiovascular disease.

A folate-poor diet of processed foods is not uncommon on reservations and could exacerbate health effects from arsenic exposure just as surely as smoking. The rate of smoking on one South Dakota reservation where Navas-Acien’s team is studying arsenic exposure still exceeds 50 percent—higher than the U.S. smoking rate ever was.

Illustrations by Dung Hoang.

If Navas-Acien could convince the Lakota nation to stop smoking—as she convinced her dad—cardiovascular health here would improve measurably. But individual behavior change is painstaking and incremental. She prefers to come at population health from the environmental side: Tweak the exposure to arsenic or secondhand smoke, and hopefully impact some biggies like cardiovascular disease and diabetes—central drivers of heart disease in Indian country.

That’s been her goal since she first began investigating arsenic as a graduate student. Back then, she thought there’d come a point when all her arsenic-related questions would be answered. The naïveté of her younger self makes her smile.

“I feel like the more I know about arsenic, the more there is to know.”

Illustrations by Dung Hoang.