The study, by Kari Stefansson and his team at Decode Genetics, in Iceland, used an elegant application of brute-force genetic sequencing to show that approximately ninety-seven per cent of the difference in the rate of de-novo mutations can be attributed to the age of the father. These new mutations arise during the production of eggs or sperm. Since females are born with a lifetime supply of eggs already in their ovaries, the number of de-novo (or novel) mutations a mother passes down is roughly fifteen, regardless of how old she is. Male sperm-producing cells, on the other hand, are constantly dividing, and as a result, the number of spontaneous mutations increases over time.
For sociological and environmental reasons, men are living longer and having children when they’re older. That, combined with the fact that we’re living in an era of diminished pressure from natural selection, means that Stefansson and his colleagues may have identified the single biggest factor in the ongoing development of the human genome: new mutations caused by old sperm. Mutations can be beneficial, but they are much more likely to be harmful—which means the changes will be overwhelmingly negative.
“This is really scary,” Alexey Kondrashov, an evolutionary biologist at the University of Michigan, said last Thursday from Moscow. In a Naturecommentary that accompanied the Decode study, Kondrashov raised the spectre of an inevitable “decline in the mean fitness of the population.” As it happens, it’s likely that this is already occurring. If you combine the findings of a 2009 PLOS ONE paper that examined the link between advanced paternal age and a decline in social and exploratory behaviors with Decode’s results, you get a scenario that is as alarming as it is plausible.
“Diagnoses of autism and schizophrenia is one thing, but [older fathers may have] a perfectly normal [child] in the sense that there may not be a diagnosis, but his IQ is 108 instead of 110,” Kondrashov says, noting that this hypothesis tracks with results from his own research on fruit flies. “This means this is a problem that will lead to very severe consequences for society over several generations.” Over the past several decades, these changes were likely masked by improvements in the environment—“getting rid of lead paint, fewer infections, less malnutrition, whatever”—but moving forward, Kondrashov says that he “strongly suspect our gene pool gets worse.”
As the implications of the study sink in, there may be a much needed discussion about some of the issues it raises. Should teen-agers be cold-storing semen for later use? Will totalitarian regimes try to impose what Kondrashov calls “some kind of soft and gentle eugenics” of the sort that Singapore attempted when it rewarded better-educated women for having more children? If they do, what is the ethical response? More prosaically, will older fathers start to worry every time their children seem less interested in playing with peers or exploring their surroundings? As Kondrashov notes, the world has dealt with concerns about genes, in the past, through the awful practice of eugenics; and the ability of men to live longer, and to procreate later, is a wonderful thing. But scientific knowledge is a blessing too, and the results of the Decode study should not be ignored.
At the moment, however, much of the public discussion has circled back to a perennial obsession when it comes to the etiology of autism: questions of guilt. One father I corresponded with on Twitter, who was almost forty when his autistic son was born, described last week’s news articles as “a kick.” He added, “I now feel very responsible for it.” Meanwhile, over at the Daily Beast, Hannah Brown, the author of a book about mothers raising children with autism, described it as a “small gift” to be able to think about the anxiety of divorced fathers of autistic children who left their wives and married younger women.
And, of course, there is the angry, vocal, and well-organized minority that insists, despite all evidence to the contrary, that vaccines are responsible for the rise in autism-spectrum disorder diagnoses. Stefansson, for one, finds this preoccupation “very strange.” “Autism is fairly heritable,” he says—which means that inherited mutations must make a “significant contribution.” Combine that knowledge with Decode’s data on de-novo mutations, and, Stefansson says, “we have the disease pretty well covered. So this is still another set of observations that indicate that this idea of toxic substances in the form of vaccines has no legs to stand on.”
Illustration by Floc’h.