The year is 1820 and a French orphan called Martin Fugate has just arrived in Troublesome Creek, a remote and sleepy settlement in eastern Kentucky. It is here he plans to start a family with his new wife, a red-haired woman called Elizabeth Smith, described as being as pale “as the mountain laurel that blooms every spring around the creek hollows”. The thing is Fugate isn't like any of the other men in the area. He has a rare genetic condition that has turned his skin a striking indigo blue. The couple went on to have seven children and four of them, like their father, had blue skin. Fast forward to the seventies and Benjamin Stacy has just been born. Stacy is the great-great-great-great-grandson of Martin Fugate and Elizabeth Smith – but by this point, the blue people of Kentucky are just a memory. Yet, to the surprise of his parents and the hospital's staff, Stacy inherits the family's distinctive blue coloring. This is because of a condition called methemoglobinemia, which causes methemoglobin levels in the red blood cells to rise above 1 percent. It turns the skin blue, the lips purple, and the blood a chocolate brown. Methemoglobinemia can be triggered by exposure to particular chemicals (benzocaine and xylocaine, for example), but in this case, it was inherited and the product of a faulty gene that most probably caused a deficiency in an enzyme called cytochrome-b5 methemoglobin reductase. Fortunately for the Fugates and their kin, there are no physical health problems associated with their blue skin. In fact, most survived well into their eighties and nineties. That isn't to say it wasn't a deep source of shame and psychological trauma. The family were embarrassed and discriminated against by their local community because of their skin color. This caused them to seek greater social isolation, which somewhat ironically, exacerbated the problem. This is because methemoglobinemia is, in almost all cases, a product of inbreeding. By some strange coincidence, Fugate had married a woman with the same rare genetic trait he had. It was not immediately obvious because, unlike Fugate, Smith had only one abnormal gene. As it is recessive, her skin was white, not blue. However, it did mean there was an extremely high chance the couple would pass the condition onto their children. Troublesome Creek was a small settlement with no roads or railways to connect it to the nearby towns. This meant the local girls and boys had an extremely limited supply of potential partners, a situation that unsurprisingly led to a lot of intermarrying. Fugate and Smith's son Zachariah, for example, ended up marrying his aunt. The extraordinarily tight community acted as the perfect incubator for the blue-skinned disorder to thrive in. Then Dr Madison Cawein arrived in the sixties. He had heard rumors of the blue people of Kentucky and recruited a nurse called Ruth Pendergrass to help him in his investigations. She had even been visited by a woman with dark blue skin herself when she was working at the county's health department. The woman wanted a blood test, she recalls. "Her face and her fingernails were almost indigo blue," she said in an interview with Cathy Trost. "It like to scared me to death! She looked like she was having a heart attack.” The pair began meeting members of the Fugate tribe, including a couple called Patrick and Rachel Ritchie, who Cawain described as "bluer'n hell". "They were really embarrassed about being blue," he added. "Patrick was all hunched down in the hall. Rachel was leaning against the wall. They wouldn't come into the waiting room. You could tell how much it bothered them to be blue." After a few medical tests to make sure it wasn't heart disease, the doctor and the nurse created a family tree. He suspected methemoglobinemia but couldn't be sure what was causing it. There were several suspects, including abnormal hemoglobin formation and excessive vitamin K consumption, but blood tests eventually revealed the true culprit: The blue Fugates lacked the enzyme diaphorase. Next, the cure. Cawain used a shot of methylene blue, a medication and dye, to turn Patrick and Rachel's blue skin pink. Methylene blue: the blue-colored dye that can transform skin from blue to pink. "They changed colors!" remembered Pendergrass. "It was really something exciting to see." The effect was only temporary because the methylene blue promptly exits the body via the urinary tract. Knowing that it worked, however, Cawain left them a healthy supply of methylene blue tablets to take daily. The Fugates were no longer blue. And what of the blue Fugates today? Better connections and a more integrated world have meant that while the recessive gene may live on, it is far less likely to cause methemoglobin. As for Benjamin Stacy back in the 1970s, experts suspect he only had the one faulty gene – he grew out of his blue skin. Source
