by Cathy Trost 
 
 ©Science 82, November, 1982 
 
 Six generations after a French orphan named Martin Fugate settled on the banks of eastern Kentucky 's Troublesome Creek with his redheaded American bride, his great-great-great great grandson was born in a modern hospital not far from where the creek still runs. Trost writes that he eventually lost the blue tint to his skin, but as a child his lips and fingernails still got blue when he was angry or cold. As a transfusion was being readied, the baby's grandmother suggested to doctors that he looked like the "blue Fugates of Troublesome Creek." Most lived to their 80s and 90s without serious illness associated with the skin discoloration. For some, though, there was a pain not seen in lab tests. "That was the pain of being blue in a world that is mostly shades of white to black." Most of what scientists know about the family was discovered by Cawein, the grandson of Kentucky's poet laureate, who had done pioneering research on L-dopa as a treatment for Parkinson's disease. Cawein would drive back and forth between Lexington and Hazard an eight-hour ordeal before the tollway was built and scour the hills looking for the blue people he'd heard rumors about. At an American Heart Association clinic in the town of Hazard, Cawein found a nurse, Ruth Pendergrass, and she was willing to assist. Her name was Ruth Pendergrass, and she had been trying to stir up medical interest in the blue people ever since a dark blue woman walked into the county health department one bitterly cold afternoon and asked for a blood test. "Her face and her fingernails were almost indigo blue," she told Trost. It like to scared me to death! She looked like she was having a heart attack. I just knew that patient was going to die right there in the health department, but she wasn't a'tall alarmed. She told me that her family was the blue Combses who lived up on Ball Creek. She was a sister to one of the Fugate women." One look at Luke was enough to "get those doctors down here in a hurry," says Pendergrass, who joined Cawein to look for more blue people. More families were found -- Luke Combs, and Patrick and Rachel Ritchie, who were "bluer'n hell" and embarrassed by their skin color. Cawein and Pendergrass began to ask questions -- "Do you have any relatives who are blue?" "They were really embarrassed about being blue," he said. After ruling out heart and lung diseases, the doctor suspected methemoglobinemia, a rare hereditary blood disorder that results from excess levels of methemoglobin in the blood. Methemoglobinemia is a blood disorder in which an abnormal amount of methemoglobin -- a form of hemoglobin -- is produced, according to the National Institutes for Health. He found references to methemoglobinemia dating to the turn of the century, but it wasn't until he came across E. M. Scott's 1960 report in the Journal of Clinical Investigation (vol. Scott was a Public Health Service doctor at the Arctic Health Research Center in Anchorage who had discovered hereditary methemoglobinemia among Alaskan Eskimos and Indians. It was caused, Scott speculated, by an absence of the enzyme diaphorase from their red blood cells. Normally, people have less than about 1 percent of methemoglobin, a type of hemoglobin that is altered by being oxidized so is useless in carrying oxygen in the blood. In other words, to get the disorder, a person would have to inherit two genes for it, one from each parent. "If I carry a bad recessive gene with a rare abnormality and married, the child probably wouldn't be sick, because it's very rare to meet another person with the [same] bad gene and the most frequent cause therefore is in-breeding," Tefferi said. All of the blue Fugates he tested had the enzyme deficiency, just like the Alaskans Scott had observed. They took the doctor to see their uncle, who was blue, too. Just like the Alaskans, their blood had accumulated so much of the blue molecule that it over- whelmed the red of normal hcmoglobin that shows through as pink in the skin of most Caucasians. The odds against it were incalculable, but Martin Fugate managed to find and marry a woman who carried the same recessive gene. Of their seven children, four were reported to be blue. One of Martin and Elizabeth Fugate's blue boys, Zachariah, married his mother's sister. The Fugates married other Fugate cousins and families who lived nearby, with names like Combs, Smith, Ritchie and Stacy. "If you'll notice," he observes, tracing lines on his family's chart, which lists his mother's and his father's great grandfather as Henley Fugate, "I'm kin to myself." Relatives described the boy's great-grandmother Luna Fugate as "blue all over," and "the bluest woman I ever saw." One of their sons, Levy, married a Ritchie girl and had eight children, one of them Luna. That suggested an inbred line that had been passed from generation to generation. The genetic form of methemoglobinemia is caused by one of several genetic defects, according to Tefferi. The only thing Stacy can't or won't remember is that his wife Luna was blue. The bluest of the bunch was Luna, and she lived a healthy life, bearing 13 children before she died at the age of 84. As coal mining and the railroads brought progress to Kentucky , the blue Fugates started moving out of their communities and marrying other people. Modern Fugates Still in Kentucky 
 
 ABCNews.com was unable to determine if Benjamin Stacy is still alive -- he would be 37 today. Doctors say Benjy likely carried only one gene for methemoglobinemia, because he eventually had normal skin tones, and the likelihood of him marrying a woman with the same recessive gene would have been small. By the time reports appeared in the media on the disorder, the Stacy family was upset with insinuations about in-breeding that fed into stereotypes of backwoods Appalachia. "Everyone around here knows about the blue Fugates," says Hilda Stacy who, at 26, looks more like a sister than a mother to her children. Note: In this instance the reason for cyanosis was not methemoglobinemia but Rh incompatibility. The Fugates probably had a deficiency in the enzyme called cytochrome-b5 methemoglobin reductase, which is responsible for recessive congenital methemoglobinemia. But the Fugates' story still offers a window into a medical mystery that was solved through modern genetics and the sleuth-like energy of Dr. Madison Cawein III, a hematologist at the University of Kentucky's Lexington Medical Clinic.
– America is home to people of all colors: White, black, and… blue? Strange but true: ABC News this week unearthed a story from 1982 about a family of blue-skinned people that once lived deep in Kentucky. The blue people first came to the fore when a baby named Benjamin Stacy was rushed to the hospital in 1975 with skin described as "as blue as Lake Louise." But the boy's grandmother was unconcerned about the disease, saying the boy looked like the "blue Fugates of Troublesome Creek." That fascinated hematologist Madison Cawein III, who, in his words, went "tromping around the hills looking for blue people." Sure enough, he found some who were "bluer'n hell," and concluded that they had a rare, hereditary disease called methemoglobinemia, which makes it difficult for hemoglobin to carry oxygen to the skin. It's a recessive trait and rare, so it's unlikely to occur often—unless there's inbreeding involved, as was the case with the Fugates. Benjamin Stacy's father once showed a reporter his family tree, remarking: "If you'll notice, I'm kin to myself."