An Unlikely Crusader
At first glance, High seems an unlikely person to bear the hopes of patients and researchers for a hemophilia cure. She’s a small, tidily dressed woman whose disarming friendliness and pleasant North Carolina diction make her easy to underestimate. There’s not a trace of condescension in her voice-something rare in a doctor of her stature. But she’s a woman of force who has made her share of enemies among colleagues and competitors. “She’s straight, she says what she believes, and people don’t want to hear the truth,” says Lou Aledort.
High has relentlessly pursued gene therapy for hemophilia for more than a decade. In the late 1980s, when she was a junior faculty member at the University of North Carolina, her lab cloned the canine factor IX gene. After she left UNC, High continued experiments with the university’s colony of hemophilic dogs. Her team’s successful treatment of the dogs is one reason researchers think hemophilia gene therapy might well work in humans.
Another reason is that the new clotting factor gene would only have to find its way into a relatively small number of cells to make a difference for patients. Just 1.5 percent of the normal level of factor should greatly shorten bleeding episodes, and 5 percent should effectively cure. What’s more, the protein only has to make it into the bloodstream, not a particular organ or tissue, to do its job.
Finally, knowing if the treatment is working-or not-won’t be hard. Just take a blood sample, separate plasma from red cells, and run a simple clotting test. A big problem with other diseases that researchers have tried to treat with gene therapy, such as cystic fibrosis, is that it’s almost impossible to measure accurately levels of normal protein, and improvements in symptoms might not be obvious for years. In this respect, hemophilia is easy, says High: “All we’ve got to do is draw blood.”
Still, such a clear “readout” means failure will be obvious right along with success. And that’s just one of the things that keeps High up at night. She frets, for example, over premature data leaks, and worries that reporters will get their facts wrong. She also wonders whether she should be spending more time with her three children. But as she watched a surgeon inject the first dose of her vector into a patient’s thigh last June, her anxiety gave way (at least temporarily) to relief: Nothing bad happened.