A quarter of a billion dollars. That's the price tag pharmaceutical companies pin on the bassinet of every new drug. For big drug companies with shareholders to please, it takes a lot to justify that kind of expense—like a projected annual return of $250 million. It's the law of supply and demand. It's capitalism.

But what if you've just found out that your ten-year-old daughter has a fatal disease, so unusual it's taken six months of doctors' visits and tests to diagnose, and so rare no drug company can afford to research a cure. What if you soon discover that two more of your children have also inherited that disease?

If you're David and Lynn Frohnmayer of Eugene, Oregon, you get to work. You create a community of other families with children similarly affected. You start a newsletter, you start a yearly retreat. And you contact scientists at universities and research institutes who don't have to answer to shareholders, who just might be able to help your children.

One of those universities is Carolina. One of those researchers is Christopher Walsh.

This spring, Walsh, assistant professor of medicine, will launch the clinical trial of a treatment he believes may cure Fanconi anemia (FA). The most common form of inherited bone marrow failure, FA affects between 2,000 to 3,000 people in the U.S. and Europe. Right now the only cure is a bone marrow transplant, and that option is available for just one-third of FA patients—those who are lucky enough to have compatible bone marrow donors. The remaining two-thirds of patients live on borrowed time, taking drugs to keep their blood counts high, trying to avoid the infections that trigger bone marrow failure. A child with FA has an average lifespan of 22 years.

Being the parent of a child with a rare disease is tough. Most family practitioners will have never heard of it, let alone diagnosed a similar patient. And if your doctor isn't familiar with a disorder, imagine having to educate yourself on the subject—plowing through medical abstracts, using a diction-ary to translate nearly every word.

But despite its rarity, there's a surprising amount of information available about FA. Much of it can be found online. Families have set up web sites to keep friends updated on their children's progress, to encourage fund-raising support. The Fanconi Anemia Research Fund (FARF) has a site that includes a handbook for nonmedical readers and two newsletters, the first covering medical research news, the second, family news.

Walsh credits the Frohnmayer family with creating this community spirit. David Frohnmayer, president of the University of Oregon, father of five children, three with Fanconi anemia, and founder of FARF, has spent the last 15 years of his life campaigning to raise money and awareness for FA.

"We knew we needed to do something to help speed the research. So we started sponsoring scientific conferences, bringing together researchers to talk about their latest findings, their therapeutic efforts," Frohn-mayer says. The first conference, in 1989, attracted 18 people. To find that group, Frohnmayer and his wife, Lynn, combed FA literature, looking for researchers with even a slight interest in the disease. This year is the 10th anniversary of that first conference, and Frohnmayer expects more than 100 scientists to show up.

Campaigns of this sort are crucial—one of the most frightening aspects of a rare disease is just how limited treatment options can be, nearly as rare as the disease. Since private companies can't afford to invest much time and money in an unusual disorder, research and treatment development is largely left to publicly funded researchers.

Besides funding yearly conferences, FARF also supplies grants to individual research projects. Frohnmayer says, "With our seed money, scientists have been able to get several million more in research funds from public institutes like the National Institute of Health (NIH)."

But it's not the money that draws scientists to FA research. "Scientifically, it's very important," Frohnmayer says. "It deals with so many issues at the biological level—stem cells, DNA repair, birth defects, bone marrow failure."

Walsh agrees. "Bone marrow and stem cells are the bread and butter of hematology," he says. "FA is just intrinsically interesting for a hematologist."

Most anemias are characterized by a slowdown in red blood-cell production. But with FA, the production of every blood cell—red, white, and platelet—slows down. Without enough red blood cells to transport oxygen, white blood cells to fight infections, and platelets to clot hem-morrhages, an FA patient becomes vulnerable to infection and internal bleeding. This condition is called "aplastic anemia," and it is a surefire sign of bone marrow failure.

Walsh started out working in a lab that studied aplastic anemia in one group and gene transfer experiments in another. "Putting the two concepts together wasn't difficult. Actually, it was a snap," Walsh says.

It took a moment to pair Fanconi anemia and gene transfer, but it has taken four years for Walsh to get that couple into a clinical trial. He spent the first few of those years at the NIH before moving to Carolina in 1996, where he has a small lab up on the seventh floor of the Thurston Bowles Building—the gene transfer wing.

FA is an ideal candidate for gene transfer because, while there are eight forms of FA, each patient has only one malfunctioning gene. Three of those variations, FA-A, FA-C and FA-G, have been isolated. While other research labs are working on isolating the remaining five, Walsh has focused his research efforts on FA-A, the gene that affects more than 70 percent of FA patients.

In April, Walsh and 10 FA patients will start their trial—testing the therapeutic effects of transplanting a corrected gene back into patients' bone marrow. He'll treat both adults and children, and it doesn't matter how poorly or how well they are doing. Walsh says, "As long as they have FA-A, they can participate."

The key to this trial is its gentleness. Traditional bone marrow transplants, currently the only way to "cure" FA, are life-threatening. A patient undergoes a course of drugs and radiation to kill every bit of marrow, then the transplant and another course of drugs to prevent infection. Recovery can take more than a year, if a patient survives. Because people with FA are extremely sensitive to radiation and often develop tumors and leukemia as a result of treatment, transplants are often viewed as last resort therapy.

This transplant protocol is different. Patients skip the radiation and drugs, giving their immune systems a huge break. All they have to donate is a bit of bone marrow, leaving the tricky part up to Walsh and his team.

To make the fix, the research team plans to track down a few stem cells from each patient's marrow by extracting blood and then spinning it through a centrifuge. To those stem cells, they'll introduce a retrovirus—carefully engineered to transport the repaired genetic material back into the cells.

Once the vector inserts itself and its payload into the stem cells, it should swap out the old gene with the new—establishing the correctly functioning gene into the stem cells. These cells will leave their lab life and get transplanted back into each patient. The next step—wait and see.

Theoretically, stem cells are perfect cells to receive gene therapy, because, once repaired, they have the ability to create legions of each blood cell type free of the faulty gene. And although it's impossible to repair every stem cell, Walsh has found that corrected stem cells outperform defective stem cells. By using certain drugs that the faulty FA genes are "exquisitely sensitive to," the researchers can even accelerate the decline in the number of unrepaired stem cells.

Those drugs were the last holdup before the trial's start. Walsh and Carolina's Office of Technology Development (OTD) spent nine months negotiating with three pharmaceutical companies on the West Coast to persuade each to give Walsh permission to use its drug. In late March, the companies gave the go-ahead.

Companies are typically delighted to grant that permission, but at a price—money, or exclusive licensing. Because Walsh needed to use drugs from all three companies, but couldn't afford the costs, he and OTD had to spend a lot of time on the phone to California. That's where Frohnmayer came in again. He played a part in persuading the companies.

He says, "I'm speaking from a bully pulpit—speaking as a parent and as an officer of FARF. I remind the licensing guys that lives are hanging in the balance."

Meanwhile, the FA community eagerly waits for the trial to begin. The Frohnmayers are holding out hope that someday soon their youngest daughter Amy—their only surviving child with FA—won't have to worry about her white blood cell counts or her platelet levels, that she'll be able to focus on being a teenager, growing up.