Presidential address. The role of variation in host-parasite interactions: linking genetic demes and life history schemes.

This paper is dedicated to the memory of our friend and colleague, Chic Richards, whose work significantly advanced our understanding of snail-trematode interactions. It's a variable life. The remarkable diversity of biological systems is the hallmark of life on earth. Variation served as the basic foundation of Darwin's (1859) view of nature. In the Or igin of Species he states, "Among organic beings in a state of nature there is some individual variability; indeed I am not aware that this has ever been disputed." This incredible diver sity attracted many of us to biology. Yet the inherent genotypic and phenotypic variability of biological systems limits our abil ity to predict the behavior of living systems which, in turn, constrains our search for 'unifying processes.' Host-parasite systems are both complex and, not surprisingly, variable. However, at times this fact is not overtly evident. In Darwin's discussion of the variety of adaptations, he states, "We see these beautiful co-adaptations most plainly in the woodpecker and mistletoe; and only a little less plainly in the humblest parasite which clings to the hairs of a quadruped or feathers of a bird. . . " (Darwin, 1859). Early in my career it seemed plain to me that we had not uncovered all of the vari ation present in host-parasite systems, and it was this simplistic view that led me to explore host life histories and parasite ge netics in greater detail. Over the past 20 years or so, work in our laboratory has shown the diversity of these systems to be substantially underestimated and its relevance vastly underap preciated. It is now clear that the level and distribution of ge netic and phenotypic variation in both hosts and parasites have significant effects on the outcome of their interaction. Epidemiology is the study of the determinants of disease in populations, and we have tried to incorporate ideas from evo lutionary ecology and population genetics into our epidemio logical studies of host-parasite systems. We have used a holistic approach to study host-parasite systems in the hopes of gaining a better understanding of the relationships among the environ ment, host genetics, and parasite genetics. Parasite genetic var iability contributes to infection dynamics and parasite exposure outcomes. We believe that a determination of the genetic struc ture of the parasite population will yield evolutionary insights into the epidemiological process, help us identify the genetic consequences of control strategies, and improve our under standing of broader theoretical questions relating to host-para site coevolution. The extent and distribution of genetic variability among par asite populations is shaped by interplay among evolutionary forces, some of which lead to high levels of genetic differen tiation and others that lead to homogeneous populations. The paradigm of parasite population genetic structure as constructed by Peter Price (1980) envisioned many small isolated parasite populations with little gene flow among them, but some studies of parasites have detected panmictic populations (Blouin et al., 1995). Not surprisingly, interactions at the population level are com plicated. Diverse microevolutionary forces may influence the genetic composition of parasite populations. Parasites' life cy cles and transmission subject them to inbreeding pressures and genetic drift. Typically, they also have little opportunity for dis persal to new areas other than that provided by the movement of their hosts, but the environment within the host (and even the possibility of pharmaceutical intervention) provides a sub stantial selective pressure against which parasites must contin ually struggle. Attempts to integrate these evolutionary forces into our understanding of natural parasite populations require us to determine the genetic structure of the parasite population and thus track the dynamic patterns of parasite genotypes within and among populations over time and multiple spatial ranges. For more than a decade, genetic work in our laboratory has involved the trematode parasite Schistosoma mansoni, the eti ologic agent of human schistosomiasis in South America, the Caribbean, Africa, and the Middle East. Although the drug Praziquantel is effective in killing adult parasites that infect human patients, a vaccine that would provide a lasting cure remains elusive. This creates a situation in which patients in endemic areas quickly become reinfected after drug therapy, which results in chronic disease and hepatosplenomegaly. Schistosomes are dioecious worms that reproduce sexually within the blood stream of their mammalian hosts. Female worms lay eggs that pass in the feces and then hatch when exposed to water, releasing miracidia. Miracidia then seek out and invade freshwater snails (Biomphalaria spp.). The parasites reproduce asexually within the snail, leading to the release of thousands of cercariae after a latent period of several weeks. The life cycle is completed when these cercariae infect the mammalian host, migrating and maturing into adult worms in the hepatic portal vasculature of the host. This life cycle includes several points at which schistosome genotypes might become clustered: (1) snail hosts may be si multaneously infected by, and release, larval stages represent ing multiple genotypes, (2) paired worms in the human host may have arisen from cercariae that coinfected the host, and (3) miracidia hatching from eggs in the host's feces might rep resent matings between multiple worm pairs. In addition, interactions with an unpredictable environment and constant adaptation to host defense mechanisms both drive changes in parasite genetic variation. In fact, efforts to control schistosomiasis in human populations may be providing an ad ditional selective force that shapes the range of genetic variation persisting in a parasite population. Current evidence seems to imply that natural schistosome strains exhibit varying resistance to treatment with Praziquantel. Given that each of these differ