Researchers scour hundreds of thousands of human genomes to find people who seem resistant to diseases even though they have genetic inclinations toward them.
Since the human genome was first sequenced in the 1990s, medical journals have released a steady stream of papers linking specific genetic mutations to a host of diseases.
What about people whose genetics suggest they should have a disease, but they don’t?
Do the antidotes to common genetic diseases such as cystic fibrosis lurk alongside the disease-causing genes?
“We don’t normally look at healthy individuals. We look at people who have an illness and try to discover the cause of the illness,” Dr. Garry Cutting, a professor of medical genetics at Johns Hopkins University, told Healthline. “This study looks at healthy individuals and asks, ‘Why are they healthy if they carry changes in the genome that would predict that they should be sick?’”
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Researchers from the Icahn School of Medicine at Mt. Sinai and Sage Bionetworks used genome, and the more complete exome sequences, from nearly 600,000 people.
The study is part of The Resilience Project, a program launched in 2014 to search worldwide for people who seem to be immune to diseases they are genetically inclined to inherit.
They compared the genes to the participants’ medical records and found 13 people who were healthy despite having genes that would normally cause them to be sick, or in some cases, dead.
The researchers describe the people as “resilient, protected by undiscovered genetic or environmental factors,” and propose, “finding and studying these resilient individuals could pave the way to disease prevention and new treatments.”
Jason Bobe, MSc, an associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai and one of the study’s authors, said the idea comes out of the medical history of individuals like Stephen Crohn.
Crohn’s partner was among the first gay men to die of AIDS in the late 1970s, before the disease was named or scientifically understood.
After Crohn failed to test positive for HIV, researchers eventually found that he was immune to the virus due to a genetic mutation that produced white blood cells that lacked the latch that the HIV virus uses to penetrate and later hijack them.
Research on Crohn led to the development of the Pfizer drug Selzentry, approved in 2007.
“That story goes all the way through,” Bobe said. “That’s sort of what we want to repeat.”
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The Resilience project is still primarily a proof of concept.
The researchers weren’t able to rule out errors in the genetic sequencing in every case and they weren’t able to dive into the particulars of what made each of the 13 people resistant to disease.
“It really just points to the complexity that we still are unraveling, that in some way we’re really at the beginning,” Marcy Darnovsky, the executive director of the Center for Genetics and Society, told Healthline.
The authors weren’t able to follow up directly with study participants because the sequencing labs had not obtained consent that would allow for that.
“My takeaway is that, gosh, if you’ve got a great idea like this, let’s hope in the future we set this up with appropriate consent so that people know what they’re getting into when you get consent to re-contact them,” Cutting said.
The study’s authors are doing just that, asking for volunteers to participate in a second phase of the research that would plug the hole. They are developing a robust structure to get meaningful consent.
Consent for genetic testing is a complicated matter. Health issues identified through the testing can run the gamut from difficult weight loss, to increased risk of cancer, to a nearly certain death from Huntington’s disease.
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There’s also the matter of who owns discoveries made as a result of a patient’s genetic particulars.
Stephen Crohn is, in this respect, a cautionary tale. He received no compensation for the drug that was developed as a result of the research done on him.
Crohn questioned the fairness of that outcome, according to a Los Angeles Times obituary, though he took pride in the advances he’d helped make for science.
Bobe hopes that a robust consent process would tap into others’ altruism.
“I sort of consider myself a biomedical research producer, trying to create research experiences that people want to sign up for,” he said.
But nebulous questions swirl around the question of whether our genes are destiny, Darnovsky said.
While the researchers position their work as more evidence for precision medicine, which uses genetics to create unique treatments, whether for pain or cancer, Darnovsky argues that its conclusions show how imprecise our understanding of genetics remains.
“Assuming that they are correct that there are some people who have these protective or buffer genes, I think that shows us how complex and networked genetic effects really are with other genes and other biological effects,” she said.