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This land was no good to anyone in 1859, when it was allocated to the Pima Indians. Today it has 13,000 Native American residents, living in squat cinder-block houses in scattered, dusty hamlets; three casinos that have boosted the tribal income to $100 million annually from $4 million; irrigated cotton, alfalfa, and citrus, for Pimas were always farmers; and a hospital and two kidney-dialysis clinics, with another medical clinic in the planning stage. Kidney failure is a deadly complication of diabetes, and Pimas, so far as scientists can tell, have the world’s highest rate of type 2 diabetes. The Pimas have grown to hate this superlative perhaps more than the disease itself.
Mary Thomas, the 60-year-old ex-governor of the tribe and presently its lieutenant governor, drove me around the community. A few miles south of Pecos Road, we came to the St. Johns Mission, a quiet, whitewashed church. There was once a Catholic boarding school for Indian children on the grounds. Thomas said that when she was 17 and in school here, she went for an eye test and was told she had diabetes.
“So you have type 1 diabetes?” I asked. In type 1 diabetes, the pancreas stops making insulin, the hormone that facilitates absorption of glucose from the blood into cells. Without sufficient insulin, glucose levels in the blood skyrocket, damaging organs, vessels, and nerves. Children with type 1 disease require insulin therapy for the rest of their lives.
“No,” Thomas said flatly. “I have type 2.” Forty years ago it was almost unheard of for teenagers to have this version of diabetes, in which high blood sugar occurs even when the person makes insulin. Doctors described that rather unusual condition as “mild” diabetes or “mature onset” diabetes. Today it is called type 2, or non-insulin-dependent, diabetes.
None of these terms do justice to today’s epidemic. In all population groups in America but especially among minorities, type 2 diabetes is spreading like a Sun Belt suburb. Unfortunately, Native Americans are ahead of the curve as the average age of diagnosis declines and the crippling consequences multiply. Roughly half of adult Pimas have diabetes, and other tribes are gaining on that rate.
Worldwide the disease is accelerating too. Health officials here and abroad expect up to half a billion cases by midcentury. Westernized diets and lifestyles are blamed—the fare paid by poor people for their fast passage to the modern world. So although the Pimas’ problem is small in the total number of cases, the impact on their community is huge.
Mary Thomas considers herself fortunate. Her health is not good, but by injecting insulin twice a day and taking a handful of oral medications, she has avoided the worst complications of diabetes: kidney disease, heart attack, stroke, blindness, and chronic infections that lead to foot amputation. Her mother, who was also a diabetic, died at age 68 of heart disease. “My diabetes is OK,” Thomas said, “but I can’t seem to get my weight off.” She carries 245 pounds on a big frame.
Because Indians’ risk of type 2 diabetes is at least twofold higher than it is for white Americans, and yet their lives are not so radically different, researchers think there must be a genetic element at work. But why indigenous Americans? Is diabetes a racial hallmark?
Race is a blind alley, geneticists believe. “No genetic markers are unique to this race,” said Leslie Baier, who studies the Pimas’ DNA for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). She means that no unique genetic variants, or alleles, have been found in Native American groups. Still, the demands of surviving in a difficult environment may have influenced their genes, making Indians innately susceptible to diabetes.
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Neel and those pondering diabetes after him came to realize that the thrifty gene or genes, if they existed, were not the critical part of the story. Type 1 disease is now thought to be an autoimmune condition in which inheritance plays a fairly minor role. As for type 2, “it is a complex disorder with strong environmental and genetic components,” said Robert Williams, an anthropological geneticist at Arizona State University. The catchall term “environment” stands for diet, lifestyle, and any other ingredient of health over which a person has at least some nominal control. The Indians’ diabetes epidemic, everyone agrees, was triggered by an unfavorable change in environment since the mid-20th century, that is, Neel’s “progress.”
Thomas well understands what took place. “Historically for the Pima, our DNA was steady all over the country,” she said. “Our diet was lean. We ate fish and game, beans and quail. Then, with the white man, a new diet came. They offered it to the Indians, and the Indians kind of became addicted to it. There was an onslaught of salts and sweets. And our DNA was forced to change.” Then she corrected herself, saying the DNA didn’t change—it couldn’t have, for genes evolve slowly within large populations, at the pace of millennia. She was referring rather to the physical transformation of people, an environmental effect that can happen rapidly. “You see a change in people. We’re evolving. People are getting taller, fatter. It’s not just the Pima,” she concluded, “but Americans.”
Scientists at the NIDDK laboratory in Phoenix have been studying type 2 diabetes on the reservation since the time when Mary Thomas was given a diagnosis. A whole floor of the Indian Health Service hospital in Phoenix is dedicated to Pima research subjects. Many studies have been prospective: The researchers took Pima volunteers who had “insulin resistance” or “impaired glucose tolerance,” the two precursors of diabetes, and monitored them as they developed the full-blown disease. A young Pima was most susceptible if both parents had contracted diabetes before age 45, less vulnerable if only one parent was diabetic, and least likely to become sick if both parents were healthy. The family studies of the Pima were the first in the world to demonstrate that type 2 diabetes was heritable. It was possible that habits fostering diabetes were being passed along too. In the last decade the work has moved from the physiology and pedigrees of diabetes into molecular biology. Although many valuable facts have been learned, including the discovery of a helpful class of drugs, no breakthroughs have been made, clinical or genetic, that might stop the disease.
about the series This is the last of three articles exploring the relationship between race, genes, and medicine in three far-flung populations. Although race is a socially powerful concept, most geneticists think it has no foundation in biology. Modern DNA studies show that the world’s population is too homogeneous to divide into races. But while dismantling the barriers of race, scientists have uncovered patterns of genetic mutation and adaptation in human populations. As archaic bands of Homo sapiens left Africa and spread over the world’s continents, their DNA evolved. Geography has left faint marks on everyone’s DNA. Although the differences are small, they show up in the diseases that different groups get and how these groups respond to drugs. To measure these differences is not to resurrect race by another name but to emphasize the role of history in shaping medical legacies. Researchers seeking genetic explanations for health have to explore the events written in the record of DNA. In the first article (www.discover.com/issues/mar-05/features/human-study-thyself/) about African Americans, geneticist Georgia Dunston points out that Africa contains the richest DNA diversity because it is the site of humanity’s oldest genes. Africans and their recent descendants in America may harbor clues to fighting diseases that other populations don’t possess. The second (www.discover.com/issues/apr-05/features/finlands-fascinating-genes) and third articles follow gene hunters into more isolated and homogeneous gatherings of people—the Finns at the top of the European continent and the Native Americans in Arizona and New Mexico. In the future, doctors will examine the genetic portraits of individuals, not populations. The path to understanding how individuals fit into genetically similar populations would run straighter if not for the old stigmas of race. Two of the three groups in Discover’s series, being minorities, are wary of genetic studies that may stereotype them further. In the past, science was not an innocent bystander when people were separated into races. |
