The co-evolution of people, plants, and parasites: biological and cultural adaptations to malaria.

The urgency generated by drug-resistant strains of malaria has accelerated anti-malarial drug research over the last two decades. While synthetic pharmaceutical agents continue to dominate research, attention increasingly has been directed to natural products. The present paper explores the larger context in which plant use occurs and considers how the selection of medicinal plants has evolved over millennia as part of the larger human effort to mediate illness. First attention is directed to indigenous medicinal plants whose anti-malarial activity is based on an oxidant mode of action, by which intracellular constituents lose electrons (become more electropositive). Next, parallels are drawn between these plant substances and a suite of malaria-protective genetic traits: glucose-6-phosphate dehydrogenase deficiency; haemoglobins S, C and E; alpha- and beta-thalassemias. These erythrocyte anomalies are classic examples of Darwinian evolution, occurring in high frequency in populations who have experienced considerable selective pressure from malaria. Characterized by discrete loci and pathophysiologies, they are united through the phenomenon of increased erythrocyte oxidation. In this model, then, oxidant anti-malarial plants are culturally constructed analogues, and molecular mimics, of these genetic adaptations. To further reinforce the scheme, it is noted that the anti-malarial action of pharmaceutical agents such as chloroquine and mefloquine duplicates both the genetic anomalies and the folk therapeutic models based in oxidant plants. This discussion coheres around a theoretical foundation that relates plant secondary metabolites (oxidants) to plasmodial biochemistry and human biological and cultural adaptations to malaria. Co-evolution provides a theoretical link that illuminates how medical cultures manage the relationships among humans, plants, herbivores and their respective pathogens.