The Evolution & Medicine Review

Two recent papers published online at scienceexpress.org describe studies of antibodies claimed to interfere with infection of host cells by a wide range of HIV-1 strains.  These studies strongly suggest that the evolutionary potential of the humoral immune response may be necessary to combat the diversity of HIV-1 antigens that results from the extraordinary pace of HIV-1 evolution. Continue Reading »

Tags: affinity maturation, antibody evolution, CD4-binding site, gp120, HIV-1, somatic hypermutation, virus neutralization

Disease as a byproduct of adaptation

An article chock full of content on antagonistic pleiotropy and balancing selection  by Razib Khan on the  Discover Magazine web page.

The deep reach of the pharmaceutical industry into academic and clinical medicine sets up ample opportunity for conflicts of interest on the part of biomedical researchers. To minimize the risks that such conflicts could introduce bias into the scientific literature, most publications impose reporting regulations that make transparent any financial stake that an individual researcher may have in the subject of his or her publications. Similarly, most institutions regulate the nature and scope of such financial agreements.

However, there appears to be significantly less oversight when it comes to an individual researcher’s ability sign away freedom of inquiry and publication. In a commentary in this week’s Chronicle of Higher Education, Harvard School of Public Health professor Marc Lipsitch points out that few universities have explicit regulations to prohibit researchers from signing consultation agreements that severely curtail their freedom to express their opinions or choose the direction of their research. And in the absence of such regulations, Big Pharma are starting to ask for precisely these types of contractual restrictions. Lipsitch reports his own experience: Continue Reading »

In previous posts, I discussed, respectively, the use of selection to generate an antibody of potential value in treating influenza A virus infections (1) and the relevance of protein dynamics to the evolution of protein function (2).   A recent paper in Science (3) offers evidence suggesting that internal protein dynamics play a crucial role in shaping the evolution and spread of resistance to the influenza neuraminidase inhibitor, oseltamivir (Tamiflu®). Continue Reading »

Tags: drug resistance, evolvability, fitness, influenza neuraminidase, mutation, oseltamivir, phylogenetics, protein folding, protein stability, viral evolution

I recently completed reading one of the most stimulating books (1) on the conceptual aspects of evolution that I have read in many years.  The author, Peter Godfrey-Smith is a philosopher of biology at Harvard.  He has written widely on topics in the philosophy of science and is the author previously of an exceptionally thoughtful introduction (2) to that field.

The new book is intended both to clarify philosophical thinking about concepts central to evolutionary theory and to advance biological understanding of the processes of evolution.  Godfrey-Smith also proposes as an objective of the book, if I can do his precise wording justice in abbreviated form, the implications of evolutionary science for broader questions of interest to philosophers, scientists, and perhaps others. Continue Reading »

Tags: agential perspective on evolution, cultural evolution, levels of selection, minimal requirements for natural selection, population attributes, population thinking, reproduction, “gene’s eye view” of evolution

Soscia, et al.   in  PLoS One. 2010; 5(3): e9505 (open access)          doi: 10.1371/journal.pone.0009505.

The Alzheimer’s Disease-Associated Amyloid  beta Protein Is an Antimicrobial Peptide

Evolutionary epidemiology 20 years on: Challenges and prospects

A couple of months ago, my institution hosted a one-day symposium on phylogenetics. One of the speakers was John Avise, a member of the National Academy of Sciences and the individual generally credited with originating the field of phylogeography. His talk and those of two other speakers were focused on subjects most typically regarded as part of biology, not medicine. However, the fourth lecturer on the program applied some of the same methods and patterns of thought to the interactions between HIV and its human hosts, thereby illustrating the potential relevance of phylogenetic analysis to matters of clinical significance. A recent paper in Science (Harris et al., 2010) provides another such example.

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of major significance in many countries. According to Maryn McKenna (2010), author of a recent book on this pathogen, there are almost 19,000 deaths and almost 370,000 hospitalizations annually attributable to MRSA infections in the United States. The yearly total costs for these infections are estimated to be in the billions of dollars. Continue Reading »

Tags: accessory genome, antibiotic resistance, convergent evolution, core genome, genotyping, indels, mobile genetic elements, mutation rate, next-generation DNA sequencing, SNPs, virulence

Physicians who care for patients with malaria or who study malaria pathogenesis have been most concerned with merozoites, the asexual form of the parasite that infects red blood cells and that is responsible for the pathological manifestations of the disease. From evolutionary and public health perspectives, however, we need to pay more attention to gametocytes, the sexual forms that are transmitted to mosquitoes. Malaria parasites have evolved life history strategies that maximize their transmission to mosquitoes and then on to new hosts, and this has presumably involved optimizing the production and transmissibility of gametocytes over the course of an infection. Continue Reading »

The complete course on evolutionary biology taught by Stephan Stearns at Yale is now available on the web.  It free, wonderful, and accessible from anywhere.

POSTDOCTORAL FELLOWSHIPS IN EVOLUTIONARY BIOLOGY AND RELATED FIELDS Continue Reading »

The Final Report from the Symposium on Evolution and Diseases of Modern Civilization at the Berlin Charité provides an overview and reports from all five workshops in a single pdf.

For a copy, click here.

Medicine, evolution and natural selection: An historical overview

By Fabio Zampieri

Quarterly Review of Biology 84 (4) 2009, p 333-355.

Investigation of model organisms can sometimes be misleading about the biology of humans, but this is often because expectations about similarities between different species, especially when studied in substantially different contexts, are unrealistic (Casanova and Abel, 2004). Viewed as entities of roughly comparable complexity, model organisms can be of value more as approximate guides to what complexities and intricacies might be encountered than as templates permitting precise one-to-one extrapolations among comparable genes, gene products, or networks of interactions.

It is in the spirit endorsed in the preceding paragraph that a paper (2009) by Ralph Greenspan (no known familial connection) on the genetics of behavior in Drosophila is of particular interest. Greenspan reviews studies of selection (of fruit flies) for several different behavioral phenotypes (e.g., aggression, mating speed, and locomotor activity), in which gene expression changes in fly heads (i.e., primarily brain tissue) are assessed. Continue Reading »

Tags: gene expression profiling, gene networks, large-effect mutants

POST-CONFERENCE UPDATE, 24th March 2010

• A report on the conference is here (pdf); thanks to Gillian Pepper
• Photos from the conference are here; thanks to Nick Pound
• The programme with abstracts is here (pdf)
• The list of registered attendees is here (pdf)

The glycoproteins and glycolipids in other great ape species contain N-glycolyl-neuraminic acid (Neu5Gc) as their primary sialic acid. Sometime after the divergence of the lineage leading to Homo, a deletion mutation inactivated the gene CMP-Neu5Ac hydroxylase (CMAH), which codes for the enzyme that catalyzes the synthesis of Neu5Gc from N-acetyl-neuraminic acid (Neu5Ac); because we lack this enzyme, our glycoproteins and glycolipids contain Neu5Ac rather than Neu5Gc. Several years ago, Ajit Varki, Pascal Gagneux, and their colleagues proposed that the loss of CMAH may have gone to fixation in the human population because it conferred resistance to malaria, and that P. falciparum became an important human pathogen after it gained the ability to recognize Neu5Ac (Martin et al. 2005). A recent report by Stephen Rich and his colleagues provides strong support for this hypothesis (Rich et al. 2009). Continue Reading »

Tags: host-pathogen coevolution, malaria

In an 1858 humorous poem The Deacon’s Masterpiece, or the Wondeful One Hoss Shay, Oliver Wendell Holmes Sr. described a carriage so artfully constructed as to have no weakest link. The carriage ran smoothly for exactly a hundred years, and then one day

it went to pieces all at once, –
All at once, and nothing first, –
Just as bubbles do when they burst,

leaving its driver sitting atop a pile of rubble and dust.

Continue Reading »

C. Athena Aktipis 1, 2   Carlo C. Maley 3     Steven L. Neuberg 4

Despite the explanatory power of evolutionary theory in understanding disease and dysfunction, it has not yet become a common framework for thinking about medical problems in the laboratory or clinic.  This unfortunate delay is attributable to a variety of barriers.  Some are institutional and educational, such as the lack of evolutionary training in medical school.  Such barriers may be overcome by providing a clear set of training goals to foster a deep understanding of evolution in medical education, as suggested by Nesse et al (2010).  A second class of barriers are psychological and are likely critical to the integration of evolutionary thinking in medicine.  We suggest that several of these—the tendencies for doctors and patients to “essentialize” disease, to be risk averse, to possess a powerful disgust-elimination reaction, and to cognitively frame disease as an enemy to be vigorously and completely eradicated—limit the integration of evolutionary thinking into medical training and practice.   Continue Reading »

In a couple of previous posts I wrote about investigators who harnessed concepts derived from the study of evolution to generate therapeutic agents, in one case for a viral infection (2009a) and in another case for cancer (2009b). Below, I discuss a study from 2009 that illustrates how evolution of cellular populations can undermine treatment for acute myeloid leukemia or myelodysplastic syndrome, serious conditions affecting the hematopoietic system.

Continue Reading »

Tags: acute myeloid leukemia, donor T-cell infusion, haploidentical hematopoietic cell transplantation, HLA class I and class II antigens, immunoselection, myelodysplastic syndrome, partial uniparental disomy

A constructively critical appraisal of the hygiene hypothesis in evolutionary perspective

Book Review: The Hygiene Hypothesis and Darwinian Medicine
Graham A.W. Rook, Editor,Progres  s in Inflammation Research, Michael J. Parnham, Series Editor
Birkhäuser Verlag AG, Basel, Boston, Bern       ISBN 978-3-7643-8902-4

The hygiene hypothesis (David Strachan, Brit Med J 299:1259-1260, 1989) has done much to literally bring immunology into household conversations, in a meaningful and practical way. How should we balance the risk of acutely dangerous infections in our babies and toddlers with a supposedly healthy exposure to environmental microbes and non-infectious agents to limit the lifetime risk of asthma and autoimmune disease? Continue Reading »

Tags: Mismatch