Jonathan Latham and Allison Wilson
Just before his appointment as head of the US National Institutes of Health (NIH), Francis Collins, the most prominent medical geneticist of our time, had his own genome scanned for disease susceptibility genes. He had decided, so he said, that the technology of personalised genomics was finally mature enough to yield meaningful results. Indeed, the outcome of his scan inspired The Language of Life, his recent book which urges every individual to do the same and secure their place on the personalised genomics bandwagon.
So, what knowledge did Collins’s scan produce? His results can be summarised very briefly. For North American males the probability of developing type 2 diabetes is 23%. Collins’s own risk was estimated at 29% and he highlighted this as the outstanding finding. For all other common diseases, however, including stroke, cancer, heart disease, and dementia, Collins’s likelihood of contracting them was average.
Predicting disease probability to within a percentage point might seem like a major scientific achievement. From the perspective of a professional geneticist, however, there is an obvious problem with these results. The hoped-for outcome is to detect genes that cause personal risk to deviate from the average. Otherwise, a genetic scan or even a whole genome sequence is showing nothing that wasn’t already known. The real story, therefore, of Collins’s personal genome scan is not its success, but rather its failure to reveal meaningful information about his long-term medical prospects. Moreover, Collins’s genome is unlikely to be an aberration. Contrary to expectations, the latest genetic research indicates that almost everyone’s genome will be similarly unrevealing.
We must assume that, as a geneticist as well as head of NIH, Francis Collins is more aware of this than anyone, but if so, he wrote The Language of Life not out of raw enthusiasm but because the genetics revolution (and not just personalised genomics) is in big trouble. He knows it is going to need all the boosters it can get.
What has changed scientifically in the last three years is the accumulating inability of a new whole-genome scanning technique (called Genome-Wide Association studies; GWAs) to find important genes for disease in human populations. In study after study, applying GWAs to every common (non-infectious) physical disease and mental disorder, the results have been remarkably consistent: only genes with very minor effects have been uncovered. In other words, the genetic variation confidently expected by medical geneticists to explain common diseases, cannot be found.