BOSTON -- Sometimes it's hard to tell the hype from the hope.
For a decade now, gene therapy has been described as the Promised Land of modern medicine. When we get there, we'll be able to cure disease by changing our genetic makeup.
In his State of the Union address, the president talks about "miraculous improvements" and "precision therapies." In quarterly reports, biotech firms talk about their race for the cure. At conferences, scientists talk as if success were a tantalizing breakthrough away.
But to get from the promise to the land, we have to cross a vast territory of human experimentation. And today that territory looks more like the Wild West than the desert.
Last fall, Jesse Gelsinger, an 18-year-old with a genetic liver disorder, won a tragic distinction. He became the first human known to have died from experimental gene therapy. The prestigious program at the University of Pennsylvania where Gelsinger volunteered had so many lapses that the FDA shut it down.
Since then, the reports have escalated. It turns out that gene therapy researchers across the country had failed to file reports on nearly 700 serious "adverse events" when they occurred.
In Boston, we now know that three of the first six patients in one experiment died and a seventh fell seriously ill. In Philadelphia, a volunteer in the experiment that killed Gelsinger says she was never told her liver had suffered a bad reaction.
Questions to ask
The ethical questions raised by gene therapy are not really so different from other human experiments. Before we use people we are supposed to ask: Is this research ready and important enough for human trial? Can we make sure that the subjects know what they are getting into? When is consent truly informed?
But the hype and the hope behind gene therapy have added additional pressure.
At what point does the push for a cure overwhelm the need to protect patients? Do we need brakes?
At a Senate hearing last week, there were sounds of both urgency and caution. A young man with cystic fibrosis worried out loud about anything that would slow down the research. "My battle with C.F. is a race," he said, "Don't let me lose that race when the finish line might be just around the corner."
At the same time, a tearful father called his son Jesse's death, "an avoidable tragedy from which I will never recover."
Paul Gelsinger said he and Jesse were "misled" into volunteering. They consented, but consent isn't just a piece of paper; it's a process of informing someone so they know the degree of risk.
But many never get the whole story.
In real life, there is a dance of denial between researcher and subject. The researchers who are true believers stay in step with the subjects who are looking for hope. "You have a series of self-deceptions," says ethicist George Annas. "Subjects deceiving themselves, researchers deceiving themselves, the public looking the other way, hoping for help."
This is true when the research is done, as it often is, on terminally ill patients whose judgment may be clouded by desperation. And true when scientists spin the story, airbrushing candor in the interest of science.
The system, as it is, relies on the good faith of researchers.
But however faithful, there is almost inevitably some conflict of interest between researcher and patient.
We worry, and we should, when the conflict is financial. At the least, a patient should know if the researcher has a stake in the outcome. But the prize may be Nobel as well as financial. Indeed, altruism, ego and money all point equally to the need for an outside eye.
'Sobered us all'
At the hearing, Tennessee's Sen. Bill Frist said that Gelsinger's death had "sobered us all." There are always risks in research. But in our new sobriety we can enforce the current guidelines and pull together the bits and pieces of government regulation that are scattered from the FDA to the National Institutes of Health. We need to carefully monitor human experiments, to follow up and report.
Will this slow the race? There is a different price you pay for overdrive.
As Dartmouth's Ronald Green says, "Every cutting of ethical corners carries a price. It's a backlash against the research. Even when there are no risks or the risks are minimal, people may be unwilling to be involved."
For the past 10 years, gene therapy has had few successes. We still look for instant cures, from the lab to the medicine cabinet. But this is a long road, and we need safeguards on the way from the promise to the land.
Ellen Goodman is a syndicated columnist.