DANVILLE, PENNSYLVANIA—Dana Atkinson begins to cry as she recalls the January phone call that cast a pall over her future and that of her children. “I’m just still processing. It’s a lot. Especially when your kids are involved,” says the 38-year-old nurse, who works at the Geisinger Medical Center here near the banks of the Susquehanna River. (She asked that Science not use her real name.)
Months earlier, during a routine medical checkup, a lab technician had drawn a vial of Atkinson’s blood. With her consent, some of the sample went off to Regeneron Pharmaceuticals, a biotech company in Tarrytown, New York, where the stretches of her DNA that encode proteins were sequenced. Atkinson forgot about her donation until the phone rang at home this winter. The caller, a research coordinator at Geisinger, told the mother of three that she carried a rare mutation linked to Long QT syndrome—a heart rhythm disorder that can cause the organ’s electrical activity to suddenly go haywire, triggering fainting, seizures, and even death.
The caller provided few details, but advised Atkinson to come in soon for a consultation. “Though I have a medical background, I barely understood what I was positive for,” she recalls. But the nurse understood enough to worry about her own health and that of her children, who might have inherited the mutation. And she also wondered about her mother’s death 38 years before. She had died in her sleep, just 6 weeks after giving birth to her only child. An autopsy revealed nothing—but Long QT is a syndrome that leaves no obvious clues.
During Atkinson’s follow-up at a medical center in Forty Fort, Pennsylvania, a genetic counselor told her that although she carried the disease-linked gene variant, she didn’t necessarily have the syndrome. And if she did, her doctor could help her reduce her risk of developing problems. The counselor then had Atkinson diagram her family tree, to pinpoint other relatives who might also carry the dangerous variant. Atkinson’s children have had their DNA screened, but their mother has not yet shared her news or their results with her extended family. She’s still not ready.
Ready or not, more than 400 other Pennsylvanians have received similar calls, letters, or electronic messages over the past 2 years as part of the world’s largest clinical genome sequencing effort, the first available to average Americans as part of standard primary medical care. Known broadly as the MyCode Community Health Initiative and run by the Danville-based Geisinger Health System, the effort has so far sequenced the protein-coding DNA, or exomes, of more than 92,400 people. More than 166,000 have enrolled in the study, and the goal is to ultimately enlist half a million of the nonprofit’s 3.3 million patients. Geisinger asks each participant whether they are willing to be contacted if the sequencing reveals a DNA variant that puts them at risk for disease—and roughly 85% have agreed to be part of the experimental program called GenomeFIRST Return of Results.
In addition to using the sequencing results to prevent and treat diseases, Geisinger hopes to answer myriad questions, from how primary care physicians with little genetics knowledge cope with advising patients informed of disease mutations, to the challenges of “cascade testing”—the follow-up with relatives who could also be at risk. The project will inform ongoing debates, including how much people should be told about what their genomes reveal. “This is the future of health care,” predicts Michael Snyder, director of Stanford Medicine’s Center for Genomics and Personalized Medicine in Palo Alto, California. “Incorporating a person’s genome sequence information into disease risk assessment is a no-brainer.”
Beyond the ethical, medical, and scientific issues being explored by Geisinger is the crucial question of whether widespread genomic screening as a preventive medical measure is cost-effective. Regeneron is paying for each patient’s initial DNA sequencing, in return for access to those data and Geisinger’s health records, but that isn’t likely to be practical nationwide.
The cost of widespread genomic testing in the United States would fall mainly to insurance companies—and they will want to be sure that testing does not open the door to unsustainable health care costs, says David Veenstra of the University of Washington in Seattle, who studies the implications of using genomic information in health care. Veenstra, who is working with Geisinger researchers to assess GenomeFIRST’s cost effectiveness, adds: “In about 5 years I think we are going to have a very serious discussion about whether this is something that should be implemented in almost a public health sense.”
