The headline generating paper published this week in a leading scientific journal, Kong, Augustine et al. 2013. “Rate of de novo mutations and the importance of father’s age to disease risk.” Nature 488(7412):471–475, has been promoted relentlessly in the mainstream media being featured, among other prominent venues, as the lead front page story in the New York Times. The Nature scientific paper purports to show data supporting a link between children born to older fathers and disease, specifically autism and schizophrenia.
The paper is based on the evaluation of the genetic makeup of 219 individuals, claiming significance for the finding that older fathers possessing a higher number of de novo genetic mutations than younger fathers produce more offspring with autism and schizophrenia. The purported association between older fathers and children with autism is being touted as a breakthrough finding that helps to explain the rise in the incidence of autism over the last two decades. The finding is claimed to support a genetic etiology for autism.
Putting aside issues of the limited number of subjects studied and the question of whether or not the statistical assumptions of the authors are accurate, a glaring issue in the study is that there exists no explanation how de novo mutations relate to autism, or whether they are causal absent other triggering factors. There exists no evidence that the existence of a greater number of de novo mutations in a father actually causes autism. There exists, in fact, no explanation in science as to how de novo mutations might cause autism – the mechanism that the authors theorize may exist is utterly unknown.
Significantly, the paper’s authors themselves state the following: "even through factors other than father's age do not seem to contribute substantially to the mutation rate diversity in our data, it does not mean that hazardous environmental conditions could not cause a meaningful increase in the mutation rate. Rather, the results indicate that, to estimate such an effect for a specific incident, it is crucial to take the father's age into account."
This statement is a profound acknowledgement that factors are at play other than the simplistic genetic etiology promoted in the media accounts of the paper. Putting aside the question of why the paper received extraordinary coverage in the media (all over 24 hour radio news last night - lead front page of NY Times today, etc. - we all know how that happens) the paper does not (1) offer any explanation of how or even if the high de novo mutation rate in older fathers is causal for autism or schizophrenia and (2) itself strongly suggests that the point here is susceptibility only. If anything, the paper’s findings strengthen the argument that environmental factors are the operative variable in autism etiology, and that children of older fathers may be more vulnerable to environmental injury than children of younger fathers.
Digging behind the headlines, then, what this paper may really show is that there exists a double role for environmental factors, as follows: (1) environmental factors cause de novo mutations, as reflected in the paper's data, and the mutations accumulate with age, (2) the de novo mutations create vulnerability in some children, and (3) environmental factors then trigger disease in the (environmentally-caused) genetically susceptible children.
Thus, rather than showing that autism or schizophrenia
may be primarily genetic, the paper supports the argument that the significant
operative variables are environmental.
Robert Krakow is an attorney in private practice in New York. Bob started his legal career with the New York Public Interest Research Group, a consumer advocacy organization. For nine years in the 1980s Bob was a prosecutor with the New York County (Manhattan) District Attorney’s office, serving as Bureau Chief of the special narcotics prosecution division. He founded his law firm in 1989, focusing on the trial of civil and criminal cases, and specializing in the representation of individuals injured by exposure to vaccines. Bob represents families of children with autism in a variety of venues, including insurance coverage disputes, vaccine exemption issues, IDEA education disputes with school districts, and claims of educational and medical neglect.