Wrote Lisa Rein in an August 16 Washington Post Health section article, "Imagine a job that demands vigorous detective work seven days a week and most holidays but comes up empty three-quarters of the time. A job that's infinitely engaging but deals with people who are desperate and in chronic pain. Most will not get better."
"This is the world inhabited by William A. Gahl, clinical director of the Undiagnosed Diseases Program at the National Institutes of Health. For thousands of patients with mystery illnesses, Gahl's 10th-floor office in the NIH Clinical Center in Bethesda is the end of the line — if they are lucky enough to get there."
Excerpts from the Post story follow.
"We have a lot of incredibly sad cases," Gahl, 61, said in his small corner office, which is strewn with medical files of the program's 463 patients. Behind each of the many windows on his Macintosh screen is a case: A woman in her 30s whose face gets flushed so badly she needs to be cold for relief. A 34-year-old man with painful lesions all over his body who lost his right hand to gangrene. Two teenage brothers with paraplegia, poor balance and seizures whose parents are first cousins. One brother died of pneumonia before his NIH work-up, which uncovered a gene mutation. But a treatment for the other boy is far away.
"They see us as a sort of last ditch," Gahl said of his patients. "They’re appreciative of the fact that we're trying, even though we fail most of the time."
It's a day-to-day balance between saving lives and advancing science. About 6,600 human diseases have been identified, and most doctors are unlikely to run into more than a fraction of them. About 5,500 inquiries about the Undiagnosed Diseases Program have come in; 2,000 patients have competed for a spot, mostly through referrals from their doctors. About 80 percent are rejected.
"You're going to leave people on the battlefield, but if you think too much about that you're through," Gahl said.
The program is designed to go beyond the organ-centered focus of most medical specialties, to get a more holistic view. Gahl and his 30-member staff bring together scientists from all over the NIH, the country's top medical research institute. Every patient is seen for free, a luxury of the government that is rare in private research settings. Insurance and drug companies "don't have a focus that's uninfluenced by profit" when it comes to diseases that afflict just 200,000 patients a year, Gahl said.
There have been notable successes. Five siblings in a Kentucky family came to Bethesda barely able to walk, with calves as hard as rocks. Blood vessels in their legs, feet and hands had developed calcium deposits that prevented the flow of blood. Because every child in the family was affected — but the parents were not — Gahl and his team took a genetic approach, thinking the disease might be caused by a recessive gene.
They were right. Nine people from three families are now known to have the newly discovered disease, and Gahl is seeking Food and Drug Administration approval to treat them with an osteoporosis drug similar to Boniva that regulates calcium in the body.
Treatment is not a given when the scientists make a diagnosis. The FDA demands controlled trials and lengthy animal toxicity tests before it will approve a drug, and rare diseases, because they affect relatively few patients, do not rise to the top of the list. Earlier this year, Gahl's team identified an enzyme that could help a 5-year-old boy who cannot produce myelin recover from painful internal bleeding. He is the only known patient in North America with the genetic disorder.
The multiple studies required by the FDA will cost $1.5 million. Even if he could find funding, Gahl said, the boy will die before they are done. And he is angry.
During a recent lecture to students at Carnegie Mellon University in Pittsburgh, he waved the FDA's letter from the lectern as he explained the case. He choked up.
"We have potential treatments that make sense with very few side effects, and yet we're not allowed to use them," he said. "People in the rare disease community want to be protected, but they don't want to be protected to death."
