The Future of the “Selfish Gene” Metaphor

This past December, science writer David Dobbs published an essay (2013) in the online magazine Aeon (aeon.co/magazine/) that purports to explain why the ‘selfish gene’ concept is outmoded and should be retired.  It elicited a good deal of commentary, and in early March, Aeon published responses (Sapolsky et al., 2014) to the original article from four individuals (two scientists, a genetic counselor, and a philosopher) as well as additional comments by Dobbs.  For those who are interested in this controversy, responses to the original Dobbs article were also posted elsewhere by Richard Dawkins (2013) and Jerry Coyne (2013a, b).  Below, I provide a sense of the arguments of Dobbs, the tenor of the criticisms of Dobbs’s piece, and selected other critiques of the gene-centric approach to evolution. (more…)

Teaching the Relevance of Evolution to Understanding Immune Recognition

Last month, I completed teaching a graduate course for the tenth time.  After several years (in the early 1990’s) of thinking about launching a new alternate-year seminar course and then planning it, I began teaching PATH 480 in the fall of 1994.  The original name of the course, maintained through the first seven times I taught it, was: “Immunology, Evolution and Logic.”  Beginning in 2009, another faculty member, Derek Abbott, joined me in teaching the course, and the title was revised to: “Logical Dissection of Biomedical Investigations.”  In my portion of the course, I retained an emphasis on the relevance of logic and evolutionary principles to thinking about immune recognition and immune functioning more generally.  I focused class sessions on concepts and underlying assumptions critical to experimental investigations as well as on experimental design and data interpretation in articles reporting studies pertaining to immune recognition. Dr. Abbott has focused his portion of the course on the practical cognitive skills involved in reviewing papers and grant proposals pertaining primarily to innate immune signaling. (more…)

The Challenge of Breaking the Meta-Code: Context and the Meaning of the Genome

In lay publications, it is commonplace for writers to refer to the deoxynucleotide sequence of an individual’s nuclear genome as that individual’s “code” and to the determination of that sequence as “deciphering the code.”   Molecular biologists mean by the “genetic code,” not a DNA sequence but the relationships between RNA (or DNA) nucleotide triplets and particular amino acids.  For those interested in clinical genetics, the real code-deciphering challenge is much more daunting than determining nucleotide sequences; it is the mapping of genotypes to medically-relevant phenotypes, i.e. predicting diseases from the totality of sequences in a genome.

The somewhat cryptic paradox at the heart of genome-based personalized medicine at the present state of our understanding is easily put: (more…)

Levels of Selection, Logical Schemes, Selfish Genes, and Misleading Memes

Both Nature and Science are currently celebrating the 100th anniversary of the birth of an icon of logic, computer science, and mathematical biology: Alan Turing.  In reading Andrew Hodges’s spectacular biography of Turing (1983) many years ago I came to appreciate that the subject of the book was both a deeply creative and extraordinarily rigorous thinker.  Although Turing is known for seminal achievements in mathematical logic and computer science, his most directly practical and immediately consequential contribution was his facilitation of the Allied cause in World War II through his guidance of the effort to break the Nazi military code.  This effort called primarily on his prodigious talents for far-reaching inference and it was in reading about this effort that I was prompted to consider a concept that might be called “maximum deduction.”  Turing and his able colleagues needed to make every possible deductive inference (or at least very close to every possible inference) supported by the available data on German military communications in order to solve a problem of immense and immediate impact (the saving of Allied ships from devastating German submarine attacks). (more…)

Methodological Foundations for Evolution by Engineered Variation and Selection

As biomedical technology advances, the probability increases that evolution guided, constrained, or facilitated by scientists will be relevant to medicine.  Of particular interest in this context is the increasing ability of investigators to engineer microbes to produce gene products of benefit to individuals in need of specific treatments or for the general maintenance of health.  Applications of a more industrial nature are also readily conceivable.

There are different possible paths to the eventual goal of tailored microbial genomes.  One approach is the de novo synthesis of whole bacterial genomes followed by transplantation into selected cells previously rendered genome-free (Gibson et al. Science, 2010).  I have previously expressed doubt that this scheme is necessarily the most likely means to achieve the goal of engineering bacteria to express gene products and functions of our choosing (Greenspan, 2010).  The alternative approaches I had in mind were based on the reasonable supposition that it would ultimately be easier and more efficient for most researchers to employ enhanced versions of already well-developed technologies based on mutation and selection of existing microbial strains.

Church and colleagues (Isaacs et al. Science, 2011) have now obliged by demonstrating the potential for advances in microbial genome engineering based on enhancements in current methods applied to existing bacterial strains and their genomes.  More specifically, Isaacs et al. developed new strategies for introducing multiple mutations into the genomes of E. coli cells. (more…)