They had me at the phrase “genetic superheroes.”
The phrase isn’t in the Nature Biotechnology study itself, which has a long, journal-ish title involving “analysis of 589,306 genomes” and “severe Mendelian childhood diseases.”
But the accompanying commentary by Daniel MacArthur of Massachusetts General Hospital and Cambridge’s Broad Institute is headlined “Superheroes of disease resistance.” It describes “genetic superheroes, people who remain healthy even though they carry genetic variants known to cause severe Mendelian diseases,” such as cystic fibrosis or sickle-cell anemia.
Calling Marvel and Universal Studios: There’s a new breed in town. The journal paper describes an epic search among more than a half-million genomes that turned up a tiny population of 13 people whose genes dictated that they should have been very sick or dead — but weren’t.
I turned to Dr. Isaac Kohane, chair of Harvard Medical School’s Department of Biomedical Informatics, for insight. His thoughts are transcribed below:
What does it mean that [Dr. Rong] Chen and colleagues studied a half-million individuals and found that 13 of them appeared to be quite resistant to a set of mutations that, in the textbook, are said to be absolutely disease-causing? Is this the new fountain of youth? The new disease barrier? Who are these superheroes? And what does it tell us about our medicine, as practiced today, and about our biology?
One optimistic perspective is that, just like the 80-year-old morbidly obese individual, or the 110-year-old happy smoker, we can learn by looking at the genomes of these individuals — or perhaps their lifestyle — what’s protected them from what is commonly thought of as a disease-causing insult, whether genetic or otherwise?
And indeed, there are some examples where we have found natural accidents: mutations in individuals that, for example, seem to protect them from cardiovascular disease and are now resulting in possibly useful cholesterol-lowering drugs.
From this perspective, finding these individuals — and more like them — is the tip of the spear of the new genomic medicine.
Nonetheless, I would argue that there is a less black-and-white perspective on these superheroes. And that is that they constitute a few points on a continuum of what we call the penetrance of genetic variants. By that I mean, the likelihood that a genetic variant, a mutation, will cause disease based on everything else that maintains your health. Let me get concrete: Continue reading