Genetic superheroes walk among us but they—maybe you?—don’t know it. Results from a study called the Resilience Project, released today, show 13 “resilient” people—out of over half a million genomes studied—who have genetic mutations that should have doomed them to serious, often deadly, childhood disease. But instead, they’ve apparently lived healthy lives into adulthood.
Wow, you are saying, so how do we get these people into a lab and study their DNA and find cures and get everyone to live happily ever after? Yeah, about that: The scientists have not been able to contact those people—not to tell them about their special genetic status nor to do any follow-up research. Research consent forms drawn up long before the Resilience Project even existed put the kibosh on the idea—yet another example of the tricky issue of consent for genetic studies.
The study, published today in Nature Biotechnology, is the first step for the Resilience Project—it’s proof that these resilient people really do exist. And for this first step, the scientists relied on genomic data originally collected for other studies. Most of the genomes, nearly 400,000 of them, came from people who sent their spit to the sequencing company 23andMe and checked the box on the accompanying form that said it was OK to use their DNA in research. “When you’re dealing with a retrospective study, you’re dealing with other people’s data,” says Jason Bobe, a geneticist at Mount Sinai involved with the Resilience Project. “It’s not answering all of your questions. It doesn’t have all the information you need.”
The Resilience Project scientists didn’t have names or contact information or complete medical records. The team had built a program to analyze genomic data to find people with mutations for 584 severe genetic disorders, like cystic fibrosis. They sent the program to their partners like 23andMe, the Children’s Hospital of Philadelphia, and the Beijing Genomics Institute, who ran it and returned the anonymized data of 303 candidates. Doing their best to verify using self-reported medical information from the people sequenced, the team winnowed down the candidates to 13 resilient people.
That’s where the buck stopped. For some of the data sources, participants had signed consent forms that did not allow them to be recontacted for any reason. “The last ‘generation’ of consents and corresponding sample collection for these kinds of large-scale studies were done with out recontact in mind,” says Jay Shendure, a genetics researcher at the University of Washington who was not involved in the study. The reasoning went that research labs are not held to the same standard as government-certified clinical labs. And for some people, unwanted genetic information can be a burden, too—for example, you might donate DNA for a liver study but does that mean you want to know if your DNA later turns up a gene for an unpreventable and incurable brain disease? Because of these limits, the Resilience Project was not able to verify medical records or, in most cases, resequence the DNA.
23andMe’s consent agreement doesn’t promise no recontact, but it doesn’t explicitly ask for consent to recontact either, leaving it in more of a limbo. Bobe says the Resilience Project has asked 23andMe to work out a process for recontacting the eight individuals1 identified in this study. “While we regularly recontact research participants,” 23andMe said in a statement to WIRED, “it can sometimes be a complex process, involving significant time and resources and that is the case in this instance.”
This recontact consent issue might not be a problem for ever. “Increasingly, research projects are building participant engagement into the structure of their research,” says Michelle Meyer, a bioethicist at Clarkson University and Mount Sinai. That could mean, for example, keeping patients in the loop when their DNA turns up an unexpected finding like genetic superpowers. Meyer has also consulted on the next phase of the Resilience Project, which will recruit an additional one million people who will expressly consent to recontact.
Bobe is in charge of this upcoming prospective study, and he’s taking participant engagement seriously. “I’ve worked on developing lots of new on ramps for people to experience biomedical research,” he says. “I consider myself a biomedical science producer, almost like movie producer.” (Though he declined to talk specifics before the prospective study’s launch.)
The Resilience Project has certainly its challenge set out. Just consider the typical patient who signs up for a study: It’s relatively easy to find and convince a cancer patient to join a study that could someday cure their disease, but the Resilience Projection will need to recruit healthy people—healthy people whose protection against faulty genes might only become known when they join the study. “We know we have to achieve very large numbers. We know it’s going to be rare,” says Bobe. But once the team identified those resilient people, they’ll finally be able to talk to them. Who knows, maybe they'll be talking to you on the near future?