There is reason to believe that among the key traits that distinguish humans from the primates that are phylogenetically closest to us are cognitive and social abilities as exemplified by language and diverse aspects of social interaction and cultural expression. It is reasonable to speculate that these characteristic human phenotypes are based on differences from closely related species in neural development, which in turn ought to reflect differences in the nucleotide sequences of the genes that encode proteins or RNA molecules involved in this process. A study (1) published in Cell in October of this year by Christopher A. Walsh of Harvard Medical School, his associates, and collaborators from numerous institutions focuses on so-called human accelerated regions (HARs), portions of the human genome that have diverged more rapidly than other regions from the genomes of the species most closely related to humans. Doan et al. sought to identify mutations in HARs that are associated with abnormal cognition and social behavior of the sort that can be found in autism. (more…)
Recently, I heard the latter portions of the radio version of a play, “Lucy” by Damien Atkins, relating to autism and produced by L.A. Theatre Works. “Lucy” was originally performed and reviewed as long ago as November of 2007, but I was not aware of it until I encountered the production for radio about one week ago. The plot revolves around a couple (Vivian and Gavin) with a daughter (Lucy) who is 13 years old and has a severe form of autism. Of particular interest for the EMR readership is how Lucy’s mother, Vivian, views the relationship between the direction of human evolution and the prevalence of autism and the need for individuals with autism to receive therapy. (more…)
A minimal requirement for evolution via natural selection is heritable phenotypic variation that affects reproductive success, or more generally, genetic success. The concept of heritability is often used somewhat loosely in casual non-technical conversation, but there is also a precise technical definition – actually there are two widely-employed technical definitions, each of which is characterized below.
Consideration of the meaning and usefulness of heritability is prompted by the publication of a new study (Hallmayer et al., 2011) addressing the relative contributions of genetic and environmental variation in the origins of autism. (more…)
We usually consider medicine as a predictive scientific endeavor, as methodical in application as noble in purpose. But for some diseases, such as schizophrenia, the first treatments showing any effectiveness, including lithium, chlorpromazine, and even electroconvulsive therapy, were discovered entirely by accident. After the discovery of the first antipsychotic treatments, a period of allegedly rational schizophrenia drug development ensued, focusing on drugs that block the brain dopamine receptor DRD2 that was considered, based on very limited evidence, as the critical lock for chemical antipsychotic keys. Some of the drugs worked – more or less, with serious side effects. Truly rational drug development, however, required understanding of the causal basis of disease, which for brain diseases like schizophrenia requires, to a considerable extent, understanding the dark inner workings of the brain itself.
But the causal basis of one relatively-simple brain disease, Fragile X syndrome, has, in the past few months, been deciphered – a true milestone in the touted medical march from brain to computer, lab bench to bedside. Afflicting about 1 in 3000 children, Fragile X is the most-common known cause of both intellectual disability and autism. A series of studies, led by researchers including Gul Dölen and Mark Bear at MIT (Dölen and Bear 2008) and Randi Hagerman at UC Davis (Hagerman et al. 2009), has identified the core neuronal defect caused by mutation of the fragile X gene, and shown they can fix it – literally cure it (Figure 1) – in mice. The fix involves (more…)