For the first time, doctors in the U.S. have used the powerful gene-editing technique CRISPR to try to treat a patient with a genetic disorder.
"It is just amazing how far things have come," says Victoria Gray, 34, of Forest, Miss. "It is wonderful," she told NPR in an exclusive interview after undergoing the landmark treatment for sickle cell disease.
Gray is the first patient ever to be publicly identified as being involved in a study testing the use of CRISPR for a genetic disease.
"I always had hoped that something will come along," she says from a hospital bed at the Sarah Cannon Research Institute in Nashville, Tenn., where she received an infusion of billions of genetically modified cells. "It's a good time to get healed."
But it probably will take months, if not years, of careful monitoring of Gray and other patients before doctors know whether the treatment is safe and how well it might be helping patients.
Sickle cell affects millions of people around the world. About 100,000 are in the U.S., and most of them, like Gray, are African American. A genetic defect causes bone marrow to produce a defective protein that makes blood cells that are sickle-shaped, hard and sticky. The deformed cells get stuck inside blood vessels and don't carry oxygen normally, causing a host of debilitating and, often, eventually life-shortening complications.
"It's horrible," Gray says. "When you can't walk or lift up a spoon to feed yourself, it gets real hard."
For the study, doctors are using cells taken from patients' own bone marrow that have been genetically modified with CRISPR to make them produce a protein that is usually only made by fetuses and by babies for a short time following birth.
The hope is this protein will compensate for the defective protein that causes sickle cell disease and will enable patients to live normally for the rest of their lives.
"It's exciting to see that we might be on the cusp of a highly effective therapy for patients with sickle cell," says Dr. David Altshuler, executive vice president, global research and chief scientific officer at Vertex Pharmaceuticals in Boston. Vertex is conducting the study with CRISPR Therapeutics of Cambridge, Mass.
CRISPR Therapeutics announced the treatment of the first volunteer on Monday but did not name the patient. However, NPR got exclusive access to Gray.
"People with sickle cell disease have been waiting a long time for therapies that just let them live a normal life," Altshuler says.
"This is a very big deal," agrees Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at the institute where Gray volunteered. "This could benefit many patients."
Frangoul's center, Sarah Cannon, is conducting the study at HCA Healthcare's TriStar Centennial Medical Center in Nashville, which is one of eight sites recruiting patients for the research in the United States, Canada and Europe. Up to 45 patients ages 18 to 35 will eventually be enrolled.
Other doctors, scientists and bioethicists are also encouraged.
"This is an exciting moment in medicine. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases," says Laurie Zoloth, a bioethicist at the University of Chicago.
But Zoloth is also cautious. She worries that this and other studies starting up using CRISPR haven't gone through an extra layer of scrutiny by a panel of outside experts assembled by the National Institutes of Health.
"This a brand-new technology," Zoloth says. "It seems to work really well in animals and really well in culture dishes. It's completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker."
Frangoul acknowledges there are always risks with experimental treatments. But he says the research will go very slowly and carefully with close review by the Food and Drug Administration and other advisory panels.
"We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy," he says.
For her part, Gray says she understands there are risks. She also says that she knows the study is a first step and that other patients might only see benefits years from now.
"This gives me hope if it gives me nothing else," Gray says.
It will probably take several months before doctors detect the first signs of whether the genetically edited cells are producing helpful levels of the protein and even longer to know whether the cells are improving patients' health. And it will likely take many years to know whether the benefits last a lifetime, as hoped.
Gray, who is married and has four children, was diagnosed with sickle cell disease when she was an infant and started crying during a bath. One major symptom is agonizing, debilitating pain.
Like many sickle cell patients, her symptoms have prevented her from living a full life. She couldn't play like other children, was afraid to travel and had to give up her dreams of becoming a doctor or a nurse.
