Parents of children with fatal diseases must decide whether to enroll them in experimental clinical trials.
Sometime in the next few weeks, a surgeon in Portland , Ore., will drill a series of small holes in a young child's brain and inject neural stem cells. The child has a rare brain disease that is usually fatal before puberty. The hope is that the cells will halt the progression of the disease.
But the treatment itself could kill the child, which raises a difficult ethical question: When is it appropriate to test unproven treatments on children?
The young child has Batten Disease. If you've never heard of Batten Disease, count yourself lucky.
"I had a daughter that had juvenile Batten Disease," says Lance Johnson, director of the Batten Disease Support and Research Association. "[The disease] started when she was five."
Batten Disease is an inherited disease that affects the nervous system. Patients lack an enzyme essential for breaking down certain fat and protein compounds. Over time, the compounds build up inside nerve cells and eventually, the cells stop working.
The first sign of trouble is usually vision problems, which was the case with Johnston's daughter. But that was just the beginning.
"She had her first seizure at age 9," he says. "She was totally blind at age 13. She started having mobility problems at that time. She [then] started having severe dementia. Cognitive functioning problems, behavioral problems when she was 15. She couldn't walk any longer at 17. She had a feeding tube put in at 19. She was totally bedridden at 20, and she died at 22 [in 1993]."
Johnston says if his daughter were diagnosed today, the outcome would be the same. There is no cure for Batten Disease. And because the disease is rare, there's not a lot of pressure to find a cure.
A company called Stem Cells Inc. thinks it might have a solution. Studies in mice suggest that neural stem cells produce the missing enzyme. They think these stem cells might produce enough of the enzyme to stop nerve cell damage.
"Out of the darkness of desperation, there's a glimmer of light," says Johnston. "It's something that you can reach out and grasp and hold on to and pray that it will, will work and save your child's life."
Scientists have no idea how many stem cells will be needed to halt the damage to the brain and they don't know the correct amount to give patients. Too many could be harmful, so they plan to start cautiously and establish that the procedure is safe.
Stem-cell researcher Robert Steiner said he takes great pains to explain to families that the first patients are joining a safety study, not a study designed to help their illness.
"It's really to see if putting these stem cells into the brains of these children is safe and doesn't cause side effects," says Steiner. "We hope that there may be some benefits, but the families have to understand going into this we're not promising, by any means, any benefit."
The real challenge," says bioethicist Alan Fleischman, "is not only to inform the families, but to be sure the families don't have exaggerated expectations as to what's possible."
Fleischman, who works at the New York Academy of Medicine, says you have to go beyond simply laying out the facts to the families, especially when you're talking about a potential cure for an incurable disease, and especially when you're talking about children.
"Research projects like these require what some of us have called special scrutiny." he says.
In other words, researchers must take a second and third and fourth look at a study to come up with the best estimate of the likelihood that someday the procedure will keep sick children alive. Then they must weigh that against the risks -- the risk any invasive procedure involves -- and the unknown risk of injecting stem cells into the brain.
Fleischman says it may even be worthwhile to bring in an independent advocate to make sure parents are being realistic about the risk they're exposing their children to and to make sure that they aren't acting out of desperation.
Lance Johnston says the parents of children with Batten Disease know the score.
"Parents who are going to have their children treated have done their background work," he says. "They've made informed decisions about this. They understand the risks that are being taken. And in spite of the risks that are inherent to any type of invasive procedure like this, they're willing to take these risks in the hope that the procedure, the treatment will save their child's life."
Not everyone says yes to an experimental therapy. Johnston says, however, that those who do know what they're doing. Even if the procedure doesn't help their child, some parents will participate because it might help others in the future.
Eric Kodish, a bioethicist at the Cleveland Clinic Foundation, says that, if anything, children are being overprotected when it comes to medical research.
"[It has] resulted in [a] lack of information about medicine for kids," he says. "Pediatricians don't know the right dose to use all the time. We don't get new cancer drugs, we don't get new drugs for neurological diseases, we don't get drug development, or device development, for that matter, for kids the way we have it for adults. And that's an ethical problem."
For the parents of children with Batten Disease, the ethical problem is a terrible one. The choice is to do nothing or enroll your child in an experimental research study at the very earliest stage. Lance Johnston says parents are at the frontier of medical science.
"We don't really know for sure what will happen once the stem cells are injected into the brain," he says. "Because once they're injected, you can't take them back. So the children and the families who are going to have this done are, in fact, pioneers."
The scientists carrying out this research are reluctant to talk about it. They won't give interviews and they're encouraging the families who are participating not to talk about it either. They have promised to publish the results of the research, whether they are good or bad.