Laying Siege to A Deadly Gene

Brianna Oas has never drawn an easy breath. When she was a baby, her tiny chest convulsed at the slightest irritation. Instead of laughing, she would cough; instead of crying, gag. She succumbed to an endless string of , respiratory infections -- pneumonia, a cold, bronchitis, pneumonia again -- that ordinary antibiotics seemed powerless to curb. Diagnosed with a "failure to thrive," Brianna weighed less at one year than she did at six months. Finally, last August, just after the child's third birthday, her anxious parents took her to the University of Washington pulmonary clinic in Seattle. Chest X rays revealed that a thick, bluish mucus had started to accumulate in her airways. "She already had some permanent scarring to the lungs," recalls Dr. Bonnie Ramsey, Brianna's physician and an expert in lung disease. "She was a very sick little girl."

Brianna was suffering from cystic fibrosis, the most common inherited disorder among whites and a disease that afflicts 25,000 Americans, killing more than 500 every year. Just 10 years ago, the prospects for a girl her age were as bleak as they were inevitable. As the combination of chronic infections, clogged airways and digestive problems took their toll, she could not have expected to outlive her teens. But now, says Ramsey, "Brianna has an excellent chance of living into adulthood." In fact, although Ramsey and other clinicians are reluctant to raise false hopes, Brianna and thousands of other babies born with CF in the past few years may even live to see a cure. Says Ramsey: "In the next decade, we are going to see a revolution in treatment for this disease. We can really, truly think about a cure."

In the past two years alone, researchers have reported preliminary success with two separate therapies that for the first time treat the underlying cellular disorder as opposed to just the symptoms of the disease. More promising still, doctors are closing in on a technique for replacing the defective CF gene, which was discovered in 1989. The discovery has spawned an unprecedented proposal to screen tens of millions of Americans for the defect, so that couples can avoid having an affected child. After decades of relative quiet on the CF front, scientists have their eyes on the prize. "This is a wonderful place to be right now," says Michael Knowles, a CF researcher at the University of North Carolina. "Just a decade ago, these therapies were abstractions."

For half a century, doctors have been treating cystic fibrosis symptom by symptom, doing their best to stem the rising tide of mucus triggered by the disease. As this abnormally thick fluid builds up in the lungs, pancreas, liver and other organs, it not only serves as fertile ground for damaging infections but also blocks the passage of vital digestive enzymes to the intestine and stops up sperm in the testes. As a result, patients have difficulty breathing, digesting food and even reproducing. "This is a disease that simply wears you down," says Ramsey.