Errors in our code of life – our DNA – can cause disease.
Large numbers of studies have tried to understand these mutations by looking at people who become ill.
But the international team of researchers tried the opposite approach – searching for people harbouring damaging mutations but who remain healthy.
“Millions of years of evolution have produced far more protective mechanisms than we currently understand,” said Dr Eric Schadt from the Icahn School of Medicine at Mount Sinai Hospital in New York.
He added: “Most genomic studies focus on finding the cause of a disease, but we see tremendous opportunity in figuring out what keeps people healthy.”
The researchers scoured DNA databases containing information on 589,306 people.
They found 13 healthy people who should have developed one of eight genetic diseases: cystic fibrosis, Smith-Lemli-Opitz syndrome, familial dysautonomia, epidermolysis bullosa simplex, Pfeiffer syndrome, autoimmune polyendocrinopathy syndrome, acampomelic campomelic dysplasia and atelosteogenesis.
The report said the diseases were so severe that it was “highly unlikely that such an individual would have manifested the disease without it being clearly annotated in their health records”.
Prof Stephen Friend, from the Icahn School of Medicine, said: “Finding these individuals is a starting point to searching for the other changes, eg in the genome, that might give us clues to develop therapies.
“Study the healthy, don’t just study the sick.”
However, this is where the tantalising story ends. The scientists were unable to go out and find the lucky 13 because of the consent rules signed when their DNA sample was taken.
It means they do not know what is protecting them against disease.
It also leaves the team unable to prove that errors in testing, bad record keeping or mosaicism – in which the genetic defect affects only some cells in the body – are not behind their findings.
“Because of the inability to confirm the source or validity of the variants and the inability to recontact the individuals, this paper does not constitute a proof of principle,” Dr Ada Hamosh, from Johns Hopkins University, argued.
And while Dr Scott Hebbring, from the University of Wisconsin, described the study as “fascinating” he also cautioned that diseases can present very differently even between patients that have same mutations.
Some may have few symptoms at all.
The research group is aiming to do a new study from scratch where patients can be traced. It also argues that other forms of protection – from infections to dementia – could be detected through this approach.
Dr Daniel MacArthur, from the Massachusetts General Hospital, said: “Finding genetic superheroes will require other kinds of heroism – a willingness of participants to donate their genomic and clinical data and a commitment by researchers and regulators to overcome the daunting obstacles to data sharing on a global scale.”
Dr Matthew Hurles, from the Wellcome Trust Sanger Institute, said the study “exemplifies the often unforeseen benefits that can be achieved from responsible sharing of anonymised genetic and clinical data”.
However, he added: “The full benefits of such altruistic data sharing is only fully realised when it becomes possible to go back to the resilient individual to try to understand how their resilience is achieved.
“This poses research and ethical questions. Personally, if I were that individual, I’d happily share my genome if it could help someone else who had been dealt a less favourable genetic hand.”