Embracing a Fuller History of the Application of Evolution to Medicine

In a recent blog post (http://evmed.asu.edu/blog/evolutionary-medicine-top-ten-questions), Randy Nesse suggests that the presentations and discussions at the second annual conference of the International Society for Evolution, Medicine, and Public Health (ISEMPH) were

“… instigated 25 years ago as George Williams and I discussed and grappled with how evolution could be useful for medicine, and what to call the enterprise.”

In her chapter (Bentley, 2016) introducing the just published book, “Evolutionary Thinking in Medicine: from Research to Policy and Practice,” the author acknowledges activity that can be considered evolutionary medicine in the years prior to 1991 but confines it to before roughly 1940.  Following the end of World War II, Professor Bentley finds little to no evidence of significant work in the field until the 1990s.  Unfortunately, these claims disregard substantial numbers of evolution-related studies that either influenced fundamental understanding of human health and disease or affected medical practice. (more…)

Aminoacyl tRNA Synthetases: Exemplars of the Fluidity of Protein Structure and Function through Phylogenetic History

Earlier this year I was afforded the opportunity to hear Paul Schimmel, of the Scripps Research Institute, lecture on aminoacyl transfer RNA (tRNA) synthetases (aaRSs), a topic on which he is a leading authority.  These enzymes attach particular amino acids to specific tRNA molecules for incorporating those amino acids into growing polypeptide chains by ribosomes.  The basic features of these enzymes that contribute to the fundamental function of translating messenger RNAs (mRNAs) are conserved from humans through the most evolutionarily primitive single-celled organisms.  Thus these enzymes might be presumed to correspond to prototypical vegetative gene products, i.e., gene products necessary for essential cellular functions that have little to do with more recently evolved functions beyond protein synthesis.  So, it was extremely interesting to learn that in organisms that arose later in evolution there are other functions, unrelated to aminoacylation of tRNAs, associated with many of the aaRSs.  These functions of aaRSs are summarized by Guo and Schimmel (Nature Chem. Biol., 2013).

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Malaria-Specific Antibody Diversification via Interchromosomal Insertion of a Non-Immunoglobulin Gene Sequence

Identifying broadly neutralizing antibodies against infectious agents such as influenza A viruses, HIV, and Plasmodium falciparum that display impressive degrees of antigenic variation is a major focus of investigators developing therapeutics and vaccines for pathogens of importance in public health (Corti and Lanzavecchia, 2013).  In a previous post, I discussed one study (Klein et al., 2013) illustrating the sorts of unanticipated types of mutations found for broadly neutralizing antibodies against HIV.  Lanzavecchia and colleagues have now identified antibodies reactive with antigens encoded by different isolates of Plasmodium falciparum and expressed on infected erythrocytes (Nature, 2015).  They find an unexpected source for the heavy chain variable domain amino acid sequences that confer the broad anti-malarial reactivity against proteins in the RIFIN family. (more…)

Tissue-Specific Stem Cell Mutation, Selection, and Evolution as a Cause of Aging

There is a mature literature on evolution and aging intended to explain how, despite selection for the morphological, metabolic, physiological, and behavioral prerequisites for survival and procreation, with the passage of time bodies deteriorate ultimately resulting in death. The focus of such explanations is typically on concepts such as age-related variation in the potency of selection and the related notion of antagonistic pleiotropy (Fabian and Flatt, 2011), by which suggests that genes able to promote survival and reproductive success in youth may increase loss of function with age. These concepts address selection on intact organisms. In contrast, a recent article in Science (Goodell and Rando, 2015) contains an article addressing the role of selection directly on somatic cells and in particular tissue-specific stem cells. (more…)

Towards Xenografts in Clinical Transplantation: Multiplexed Negative Selection of Porcine Endogenous Retroviruses with CRISPR-Cas9

Clinical organ transplantation is now a large medical enterprise, with more than 29,000 organ transplants performed in 2014 in the United States alone (https://www.unos.org/data/transplant-trends/#transplants_by_organ_type+year+2014). Nevertheless, the number of organ donors is insufficient to meet the demand for new organs. For example, in the U.S. during 2014, there were 17,104 kidney transplants but 101,035 individuals on the waiting list for such transplants. Therefore, a recent study in Science (Yang et al., 2015) offers an important proof of principle for a necessary but not necessarily sufficient step on the path to safely using pig organs to substitute for failing human organs. (more…)