Over the past three years, researchers examined the genomes of almost 600,000 healthy adults, finding 13 lucky individuals who had the genes for fatal or severe childhood diseases, but who somehow managed not to develop the illnesses. It seems like the start of a huge medical breakthrough, but there’s one big catch—because the genome databases are protected by privacy agreements, the researchers are unable to identify or follow up with the patients.
“You can imagine the level of frustration,” Stephen Friend, genomics professor at the Icahn School of Medicine and lead author of the study tells Gina Kolata at The New York Times. “It is almost as if you got to take the wrapping off the box but you couldn’t open the box.”
Even so, the study, published in Nature Biotechnology, is a proof of concept of sorts for Friend. For years, he’d worked in the public and private sector investigating ways to fix the genetic defects that lead to disease. Frustrated by the lack of progress, he began thinking: What if instead of trying to fix broken genes, we try and find genes that cancel out or prevent the genes from expressing themselves, otherwise known as “compensating mutations?”
That’s why Friend and his team spent three year combing genetic databases from 11 large studies and the genetic testing firm 23andMe, eventually narrowing their search down to 13 individuals over the age of 30 with verifiable mutations for eight deadly childhood diseases, including cystic fibrosis and autoimmune polyendocrinopathy syndrome. Learning what other genes those individuals might have that prevented the expression of the diseases encoded in their DNA could lead to new therapies.
There may be flaws in the research since Friend and his colleagues were not able to double check the genetic data or examine the subjects. Garry Cutting from Johns Hopkins points out to Jocelyn Kaiser at Science that some of the findings are odd, like finding three individuals each with two copies of an extremely rare cystic fibrosis gene. Still, he thinks the idea of combing genetic data to find compensating mutations is exciting.
Following up on the project will be difficult. Daniel MacArthur, a geneticist at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, points out in his commentary on the paper that it will take the genomes of tens of millions of people willing to participate in the study to find compensating mutations.
Still, Friend is not daunted and is recruiting 100,000 people to have their genomes sequenced for the next stage of the research.