Blue people inhabited Kentucky in 1950s
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. Methemoglobin which is blue, is a nonfunctional form of the red hemoglobin that carries oxygen. It is the color of oxygen-depleted blood seen in the blue veins just below the skin.
If the blue people did have methemoglobinemia, the next step was to find out the cause. It can be brought on by several things: abnormal hemoglobin formation, an enzyme deficiency, and taking too much of certain drugs, including vitamin K, which is essential for blood clotting and is abundant in pork liver and vegetable oil.
Cawein drew "lots of blood" from the Ritchies and hurried back to his lab. He tested first for abnormal hemoglobin, but the results were negative.
Stumped, the doctor turned to the medical literature for a clue. 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. 39, 1960) that the answer began to emerge.
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. In normal people hemoglobin is converted to methemoglobin at a very slow rate. If this conversion continued, all the body's hemoglobin would eventually be rendered useless. Normally diaphorase converts methemoglobin back to hemoglobin. Scott also concluded that the condition was inherited as a simple recessive trait. In other words, to get the disorder, a person would have to inherit two genes for it, one from each parent. Somebody with only one gene would not have the condition but could pass the gene to a child.
Scott's Alaskans seemed to match Cawein's blue people. If the condition were inherited as a recessive trait, it would appear most often in an inbred line.
Cawein needed fresh blood to do an enzyme assay. He had to drive eight hours back to Hazard to search out the Ritchies, who lived in a tapped-out mining town called Hardburly. They took the doctor to see their uncle, who was blue, too. While in the hills, Cawein drove over to see Zach (Big Man) Fugate, the 76-year-old patriarch of the clan on Troublesome Creek. His car gave out on the dirt road to Zach's house, and the doctor had to borrow a Jeep from a filling station.
Zach took the doctor even farther up Copperhead Hollow to see his Aunt Bessie Fugate, who was blue. Bessie had an iron pot of clothes boiling in her front yard, but she graciously allowed the doctor to draw some of her blood.
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.
Once he had the enzyme deficiency isolated, methyleneblue sprang to Cawein's mind as the "perfectly obvious" antidote. Some of the blue people thought the doctor was slightly addled for suggesting that a blue dye could turn them pink. But Cawein knew from earlier studies that the body has an alternative method of converting methemoglobin back to normal. Activating it requires adding to the blood a substance that acts as an "electron donor." Many substances do this, but Cawein chose methylene blue because it had been used successfully and safely in other cases and because it acts quickly.
Cawein packed his black bag and rounded up Nurse Pendergrass for the big event. They went over to Patrick and Rachel Ritchie's house and injected each of them with 100 milligrams of methylene blue.
''Within a few minutes. the blue color was gone from their skin," the doctor said. "For the first time in their lives, they were pink. They were delighted."
"They changed colors!" remembered Pendergrass. "It was really something exciting to see."
The doctor gave each blue family a supply of methylene blue tablets to take as a daily pill. The drug's effects are temporary, as methylene blue is normally excreted in the urine. One day, one of the older mountain men cornered the doctor. "I can see that old blue running out of my skin," he confided.
Before Cawein ended his study of the blue people, he returned to the mountains to patch together the long and twisted journey of Martin Fugate's recessive gene. From a history of Perry County and some Fugate family Bibles listing ancestors, Cawein has constructed a fairly complete story.
Martin Fugate was a French orphan who emigrated to Kentucky in 1820 to claim a land grant on the wilderness banks of Troublesome Creek. No mention of his skin color is made in the early histories of the area, but family lore has it that Martin himself was blue.
The odds against it were incalculable, but Martin Fugate managed tofind and marry a woman who carried the same recessive gene. Elizabeth Smith, apparently, was as pale-skinned as the mountain laurel that blooms every spring around the creek hollows.
