The Evolution & Medicine Review

Heredity is particulate, but development is unitary.  Everything in the organism is the result of the interactions of all genes, subject to the environment to which they are exposed.

T. Dobzhansky 1961, p. 111

The chief analytical ultimacy in the new life sciences enterprise is represented by the capability of shifting scientific reduction to the smallest relevant molecular level for understanding life.

R. D. Alexander, 2008

I have no doubt that in reality the future will be vastly more surprising than anything I can imagine. Now my own suspicion is that the universe is not only queerer than we suppose, but queerer than we can suppose.

J. B. S. Haldane, 1927, p. 286

Kenneth Weiss, in his deeply-scholarly review of recent progress in the genetics of diseases mediated by effects from many genes, suggests that researchers are stalking ever-smaller, more elusive genetic prey - variants slightly increasing risk of disease - with ever-more powerful technological and analytic weapons.  He reminds us that population-genetic theory from nearly a century ago predicted just such a multitude of infinitesimal, variable effects as we are now observing, and that more research efforts might be better deployed other places than genome scans with more genetic markers, cases and controls.

I agree, and suggest that we try spending more money and research effort on true evolutionary disease genetics.   True, in that we must draw tightly together, for the first time, two disparate fields: (1) the study of the molecular and phenotypic selective pressures that have given rise to modern humans, (2) the study of the genetic and environmental underpinnings of polygenic disease. Disease risk, like our other traits, has evolved, but you would hardly know it from reading the pages of American Journal of Medical Genetics, Molecular Psychiatry, or other disease-genetic journals whose authors either ignore evolutionary principles or view them with deep suspicion as untestable speculation. Positive selection, antagonistic pleiotropy, and intragenomic conflicts are all expected to generate pervasive effects on disease risk but are virtually unexplored - as are, we must admit, the workings of the genome itself.  The genome’s machinations will surely turn out to be queerer than we can now imagine, but we must still try to reduce their vast complexities, by attacking with not just more nucleotide data at the bottom, but also with evolutionary concepts and methods across all levels from DNA to development, physiology, morphology and cognition.  A Darwin’s Dulcinea can be seen to embody love of this evolutionary venture, to understand our evolved selves, and our malaises, from single nucleotide polymorphism to brain.  Is this quest hopeless? If so, ultimately, nothing will make sense.

Alexander, R. D.  (2008) On ultimacy in the life sciences.  Unpublished Essay.

Dobzhansky, T. (1961) In: J. S. Kennedy (Ed.). Insect Polymorphism. London: Royal Entomological Society.

Haldane, J. B. S. (1927) Possible Worlds and Other Papers.

Chatto and Windus: London, 1932, reprint.

The Dawn of Evolutionary Epidemiology:
Applying Evolutionary Theory in an Epidemiologic Context
September 14-16, 2008

Early Bird Rates until Sept 9th, register online!

The meeting is at The Westin LaPaloma Resort & Spa
3800 East Sunrise Drive, Tucson, AZ 85718

Full meeting info is at:
http://www.acepidemiology2.org/meetings/2008Tuscon/08Tusconamprogram.html
Continue Reading »

Commentary on: M. Ackermann, B. Stecher, N. E. Freed, P. Songhet, W.-D. Hardt, and M. Doebeli (2008) Self-destructive cooperation mediated by phenotype noise. Nature 454:987-9

One of the most exciting developments in microbial population biology over the past few years is the recognition that high levels of phenotypic noise - in which genetically identical microbes express different genes and manifest different phenotypes despite a common environment - is widespread in bacterial populations and that this noise plays an important role in bacterial evolutionary ecology (e.g. Elowitz et al. 2002, Balaban et al. 2004, Rosenfeld et al. 2005, Acar et al. 2008, Veening et al. 2008). I have always thought that the best explanations for this phenomenon involve bet hedging in uncertain environments (Seger and Brockmann 1987), and indeed this bet-hedging perspective has been well supported by mathematical modeling (e.g. Thattai and van Oudenaarden 2004, Kussell et al. 2005).

But in this week’s issue of Nature, Martin Ackermann and colleagues propose an alternative explanation Continue Reading »

Tags: bet hedging, co-evolution, cooperation, infection, inflammation, phenotypic noise, Salmonella, self-destructive cooperation, virulence

Eye color phenotypes (from Eiburg et al. 2008)

Perhaps the main lesson we eventually learn in school is how little we actually know. In elementary genetics, we were taught that there are two alleles for eye color, blue and brown, with brown dominant, allowing simple assessment of whether we were more likely fathered by dad or the mailman. In these simple Mendelian days, eye color was not considered to be a focus for natural selection, except perhaps in the context of an associated trait, pale skin, being favored to help accrue vitamin D in the high, dark latitudes of northern Europe. Only over the past few months has a series of publications begun to reveal the true complexities of human eye-color genetics, genomics, selection and evolution. In the context of tantalizing data linking eye color to social behavior, rather than just skin and hair color, these studies show that the metaphor of eyes as windows to souls may be more than poetic. Continue Reading »

Tags: behavior, eye color, pleiotropy

Autism is traditionally considered as a severe disorder involving some combination of repetitive behavior and restricted interests, deficits in social reciprocity and language, and mental retardation. But there is a long tradition of counterpoint to such disabilities, in so-called savant skills in fields that range from mathematical calculation and memory to art and music (Heaton and Wallace 2004). In each case, autistic savant skills represent rare yet astounding enhancements of human ability, beyond imagining for most of us. Understanding the cognitive and neurodevelopmental bases of such skills holds the promise of better understanding the causes of autism and enhancing human mental abilities to beyond the norm, if not at least helping us remember where we left the keys. Continue Reading »

A recent article by Hood and Jenkins provides an overview of a May 2007 Meeting on Evolutionary Medicine organized by Diddahally Govindaraju, Peter Byers and Stephen Stearns and hosted by the National Evolutionary Synthesis Center.   Continue Reading »

In 2005 Sarkis Mazmanian and colleagues showed that a single polysaccharide from an intestinal commensal, Bacteroides fragilis, could largely correct the subnormal and functionally distorted development of the immune system that occurs in germ-free mice (Mazmanian et al. 2005). More recently they have shown, using three different models of intestinal inflammation, that the same polysaccharide, given by mouth, can turn on crucial immunoregulatory pathways (Mazmanian et al. 2008). In the discussion of the latter paper they state:- Continue Reading »

Tags: Hygiene Hypothesis, immunoregulation, microbiota, Old Friends Hypothesis

The placenta is the unique organ of therian mammals, key to their evolution and viability. The chorion is the outermost of the extra-embryonic membranes, and in birds and reptiles it is a simple membrane in contact with the shell allowing gas exchange. But in eutherian mammals the chorion is highly vascularised by the allantois to form the placenta. While the placenta serves the common role in all eutherian mammals of supporting fetal nutrition and oxygenation, serving as the route to excretion and providing an immune barrier between the mother and fetus, there are enormous species differences in the structure of the placenta. Continue Reading »

Tags: conflict, fetus, imprinting, placenta

Do worms protect us against autoimmune diseases? The epidemiological evidence is strongly suggestive. Ethiopian, Brazilian, Venezuelan, and Gambian adults have less asthma when infected with nematodes; Gabonese schoolchildren with schistosomiasis have fewer allergic reactions to dust mites than do those who are not so infected, and children living on farms in Germany have fewer allergies than children living in cities (Wilson & Maizels 2004). One of the most debilitating autoimmune diseases, multiple sclerosis, is virtually absent in Roma, Inuit, and Bantu, is rare in the indigenous peoples of the Americas and Asia, and is rare in the tropics generally. And in the developed world, Continue Reading »

Tags: Helminth therapy, Hygiene Hypothesis

Death is one of the most mysterious and inexorable problems in biology. How does life end? What is the true nature of death? Is it absolute—a fundamental state? Or is it relative and a matter of degree? Can it be defined as part of some basic reality, a detail of an unknown whole rather than merely an illusion? Although any living creature anytime can lose its life, no creature can lose its death. This is why death is safe and secure in all living things. As bioethicist Ronald Dworkin (1993) noted, death, as it were, is part of life’s dominion. Continue Reading »

Tags: Aging, Death, Ethics