Wrong with Geschwind?: Dubious Ideas About Autism and Human Evolution


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 Possible Evolutionary Explanation for the Frequency of CCR5Δ32

In 1996, Dean et al. (Science), demonstrated that a loss-of-function allele (CCR5Δ32) encoding a version of the chemokine receptor, CCR5, confers very substantial resistance to infection with HIV-1 in the homozygous state and slows progression in the heterozygous state.  Given the relatively recent origin of HIV-1, this finding raised the question of what source of selection could account for the frequency, approximately 0.08 among Caucasians according to Dean et al., of this allele.  A recent paper (Alonzo et al., 2013) offers new information on a relationship between CCR5 and a different pathogen that might offer insight into the evolutionary trajectory of CCR5Δ32.

The new study presents compelling evidence that leukotoxin ED (LukED), one of a family of bi-component exotoxins produced by Staphylococcus aureus, can bind to CCR5 and thereby cause cell death.  LukED consistently produces substantially more cytotoxicity for CCR5+ than CCR5 cell lines of several types.  Ligands for CCR5, including the drug, maraviroc, which is approved for clinical treatment of HIV-1 infection, significantly inhibit both the binding of LukED to cells and the magnitude of associated cytotoxicity.  LukED also binds to and kills CCR5+ primarycells, such as human memory T cells, macrophages, and dendritic cells. (more…)

Potential Influence of Winner-Take-All Markets on Human Evolution and Medicine

In the book, The Winner-Take-All Society (1995), Robet H. Frank and Philip J. Cook discuss a hypothetical scenario in which a new genetic technique allows babies to be engineered so that they have a 99% chance of performing 15% better on the standardized tests used in American college admissions, such as the Scholastic Aptitude Test (SAT) without actually being smarter in other contexts.  In 1% of babies so engineered, a severe emotional disability will result.  Frank and Cook speculate that many parents would be willing to risk the odds that an enginnered child would not be among the 1% of offspring who suffer the ontogenetic costs of the procedure.  They further argue that as more people exploit this genetic modification, the emotional pressure on the hold-outs would increase.  (more…)

A Personal Perspective on Prospects for Personalized Medicine

A common consequence of the evolutionary process in many species is extensive genetic diversity.  As has become apparent in recent studies (Tennessen et al., Science 2012; Nelson et al., Science 2012), the growth of the human population coupled with what is believed to be reduced selective pressure, presumably in part due to the life-promoting and life-saving effects of modern medical interventions, has facilitated a truly impressive range of rare variants in human genomes.  Some of these rare variants are expected to be associated with predispositions to various diseases and medical conditions.  Hence, as a consequence of human evolution the need for personalized medicine arises.

It is in this context that a recent study (Chen et al. Cell 2012) by Michael Snyder, the chairman of the Stanford Genetics Department, and his colleagues is of special interest.  It is a technological tour de force and tour de self applied to blood samples from Snyder himself and in which Snyder and his associates combine multiple systematic high-throughput types of analysis (genomics, transcriptomics, proteomics, metabolomics, and more) i.e., as the authors’ preferred jargon would have it, a multi-dimensional integrated personal omics profile (iPOP).  This analysis revealed a genetic variant predisposing to type 2 diabetes mellitus that led Snyder to screen for type 2 diabetes which subsequently developed.  The authors claim that therefore this approach is a guide to the personalized medicine of the future.  In what follows, I evaluate these claims, informed in part by my personal experience with an infrequently-recognized form of personalized medicine that has been in operation for no less than 15 or so years and possibly much longer depending on how precisely the concept is defined.  I emphasize at the start that I support a role for personalized medical care in several senses not limited to the purely genetic but note that this approach, the substantial hype notwithstanding, nevertheless faces challenges and limitations. (more…)

From Ethereal to Material: Abstract Origins of Practical Genomic Analysis

Since the announcement, approximately ten years ago in June of 2000, that a first draft of the (almost) complete nucleotide sequence of a human genome had been assembled, much interest has been directed to the ways in which genomic information can facilitate investigation into the evolutionary origins of humans and their diseases as well as to the ways in which this new knowledge can be put to practical use in medicine and other fields of endeavor.  For example, just a few months ago, James Lupski and colleagues published an article (2010) in The New England Journal of Medicine that illustrated the potential of whole-genome sequence determination of a proband and more focused genotyping of family members to identify the genotype responsible for a disease phenotype (for the curious, Charcot-Marie-Tooth disease, (more…)