THE BELL CURVE.

An interview with Atul Gawande

Every illness is a story, and Annie Page's began with the kinds of small, unexceptional details that mean nothing until seen in hindsight. Like the fact that, when she was a baby, her father sometimes called her Little Potato Chip, because her skin tasted salty when he kissed her. Or that Annie's mother noticed that her breathing was sometimes a little wheezy, though the pediatrician heard nothing through his stethoscope.

The detail that finally mattered was Annie's size. For a while, Annie's fine-boned petiteness seemed to be just a family trait. Her sister, Lauryn, four years older, had always been at the bottom end of the pediatrician's growth chart for girls her age. By the time Annie was three years old, however, she had fallen off the chart. She stood an acceptable thirty-four inches tall but weighed only twenty-three pounds--less than ninety-eight per cent of girls her age. She did not look malnourished, but she didn't look quite healthy, either.

"Failure to thrive" is what it's called, and there can be scores of explanations: pituitary disorders, hypothyroidism, genetic defects in metabolism, inflammatorybowel disease, lead poisoning, H.I.V., tapeworm infection. In textbooks, the complete list is at least a page long. Annie's doctor did a thorough workup. Then, at four o'clock on July 27, 1997--"I'll never forget that day," her mother, Honor, says--the pediatrician called the Pages at home with the results of a sweat test.

It's a strange little test. The skin on the inside surface of a child's forearm is cleaned and dried. Two small gauze pads are applied--one soaked with pilocarpine, a medicine that makes skin sweat, and the other with a salt solution. Electrodes are hooked up. Then a mild electric current is turned on for five minutes, driving the pilocarpine into the skin. A reddened, sweaty area about an inch in diameter appears on the skin, and a collection pad of dry filter paper is taped over it to absorb the sweat for half an hour. A technician then measures the concentration of chloride in the pad.

Over the phone, the doctor told Honor that her daughter's chloride level was far higher than normal. Honor is a hospital pharmacist, and she had come across children with abnormal results like this. "All I knew was that it meant she was going to die," she said quietly when I visited the Pages' home, in the Cincinnati suburb of Loveland. The test showed that Annie had cystic fibrosis.

Cystic fibrosis is a genetic disease. Only a thousand American children per year are diagnosed as having it. Some ten million people in the United States carry the defective gene, but the disorder is recessive: a child will develop the condition only if both parents are carriers and both pass on a copy. The gene--which was discovered, in 1989, sitting out on the long arm of chromosome No. 7--produces a mutant protein that interferes with cells' ability to manage chloride. This is what makes sweat from people with CF so salty. (Salt is sodium chloride, after all.) The chloride defect thickens secretions throughout the body, turning them dry and gluey. In the ducts of the pancreas, the flow of digestive enzymes becomes blocked, making a child less and less able to absorb food. This was why Annie had all but stopped growing. The effects on the lungs, however, are what make the disease lethal. Thickened mucus slowly fills the small airways and hardens, shrinking lung capacity. Over time, the disease leaves a child with the equivalent of just one functioning lung. Then half a lung. Then none at all.