Host-parasite co-evolution
- Evolution and medicine: the long reach of "Dr. Darwin"

Lying at the heart of modern evolutionary theory, as it impinges directly on medicine, is the concept of host-parasite co-evolution. Indeed, the study of human responses to infectious, parasitic agents such as bacteria and viruses is one of the few places where evolutionary theory has had a major impact on medical theory and practice. As we will see, however, it has not been "plain sailing" and basic misunderstandings of evolution's implications for these matters are still prevalent.

Paul Ewald has done much to clarify matters in this regard by critically analyzing the views common, albeit erroneous, in the medical community, including (a) that evolution works for the benefit of the species; and (b) that parasitism and the resulting diseases are steps on the road to a state of happy co-existence [2]. According to this author [2], Rene Dubos claimed in 1965, "Given enough time a state of peaceful coexistence eventually becomes established between any host and parasite." In 1972 Lewis Thomas observed that, "Disease usually represents the inconclusive negotiations for symbiosis. . . a biological misrepresentation of borders." [2]. And as late as 1989 Paul Hoeprich could claim, "The ideal of parasitism is actually commensualism" [2].

The claim that evolution works for the benefit of the species, though still common outside of evolutionary circles, has been substantially abandoned by professionals in the field of evolutionary biology in favor of a thoroughly genocentric view of evolution. As we saw earlier, evolution occurs because different individuals leave behind different numbers of offspring – offspring carrying a proportion of alleles identical by descent to those found in the parents. In the case of diploid organisms, the offspring receive (on average) 50% of their alleles from each parent. In asexual, clonal species (the proportion will be 100%, barring horizontal genetic transfers (a non-trivial assumption for bacterial species). One way or another, it is alleles that travel down the generations.

Evolution has no eye for the future – it does not operate with a view to the attainment of teleological ends or typological goals. In particular, neither evolution nor the presence of particular characteristics can properly be characterized as a steady march of progress toward traits beneficial (in our minds) to the species as a whole. As Ewald has observed:

Scientist's errors can often be traced to the belief that natural selection will favor what is best for the long-term stability and survival of the species. In fact natural selection is powerless to favor such long-term survival when it runs counter to short-term competitive gains. By the time the long-term benefits would be accrued, the individuals that could provide them would have vanished from the species by competition. This misunderstanding owes much to the catchiness of the phrase "survival of the species," which emphasizes the species rather than the competitors within the species" [[11]:xiv].

Such misconceptions are intimately linked to the mistaken view that evolution in the context of host-parasite relationships is a steady march to a state of "benign coexistence," and hence to mistaken expectations about the evolution of virulent pathogens and parasites. Again, as Ewald pointed out:

Natural selection favors characteristics that increase the passing on of the genes that code for the characteristics. If more rapid replication of a virus inside of a person leads to a greater passing on of the genes that code for that rapid replication, then replication rate will increase even if the more rapid growth of the virus population within a person causes the person to be severely ill, or leads to an overall decrease in the numbers of the virus among people, or hastens the eventual extinction of the virus [[2]:4].

This phenomenon can be explored in the context of within-host selection. Diseases differ with respect to virulence. For most of us the common cold is a nuisance. The rhinovirus works its evolutionary mischief by keeping its host mobile – and hence typically in contact with other susceptible persons who in turn help with the reproduction and dispersal of the virus. By contrast, highly virulent strains of malaria (e.g., that caused by Plasmodium falciparum), rapidly immobilize the host and kill millions of human each year.

Since malaria is propagated by biting mosquitoes, the parasite pays no penalty for an immobilized host – especially one too weak to swat the insect vector. Moreover, simultaneous infection with different strains of P. falciparum with varying degrees of virulence creates a competitive environment. In such a situation, those strains that attain highest concentrations in the host's blood in the least amount of time (thereby wreaking havoc on the host) are those most likely to be sucked up by biting mosquitoes, who then spread the progeny of these virulent strains to other susceptible hosts [2]. Another example concerning the illogic of obligate evolution to a state of benign co-existence, is provided by Nesse and Williams:

What good would it do a liver fluke to restrain itself so as not to harm the host if that host is about to die of shigellosis? The fluke and the shigella are competing for the same pool of resources within the host, and the one that most ruthlessly exploits that pool will be the winner. Likewise, if there is more than one shigella strain, the one that most effectively converts the host's resources to its own use will disperse the most progeny before the host dies [[12]:57].

That millions of parasitic progeny die with the host does not matter. What matters is differential reproductive success on the part of individual parasites. These are population level phenomena that occur within a single host, but still result in the passing on of characteristics that aid effective dispersal of offspring into fresh hosts. A typological goal of benign coexistence simply does not exist in these instances.

No discussion of host-parasite co-evolution would be complete without at least a nod in the direction of the evolution of drug resistance by bacteria and viruses. Antibiotics are differential poisons – in this case they are more toxic to bacteria than they are to us. But bacterial populations show variation with respect to susceptibility to a given antibiotic. A given clinical dose of antibiotics should so damage the bacterial population that the few survivors should be dealt with by the host's own immune system. But if the full course of treatment is not followed (or the patient resorts to unsupervised self-treatment), the antibiotic becomes an agent of selection favoring bacteria whose genetic constitution can tolerate the antibiotic in question. The result? Offspring of resistant bacteria will inherit alleles coding for these characteristics and these populations will increase. Continued treatment with such an antibiotic will require higher doses – a process that cannot continue indefinitely, since patient toxicity will eventually become an issue. The remedy is to move on to a new antibiotic, and the whole process may repeat itself, sometimes with a similar outcome. Unfortunately, the situation with resistant bacteria is even worse, since individual bacteria also can transfer alleles conferring drug resistance horizontally to other members of their own population, as well as to members of other bacterial species that may be present in the host.

The situation described here has been observed in viral populations, with Human Immunodeficiency Virus (HIV) being a case in point. HIV is an RNA retrovirus that exhibits poor replicative fidelity. In effect, the virus replicates itself with the aid of the host's own cells, but does so with such lack of precision that a viral particle may produce many variants. These variant "offspring" may differ with respect to susceptibility to the hosts' immune surveillance or to anti-viral drugs, creating populations of "new" viral particles with different properties. Nesse and Williams observe:

A single infection, after years of replication, mutation and selection, can result in a diverse mixture of competing strains of the virus within a single host. The predominant strains will be those best able to compete with whatever difficulties must be overcome (e.g., AZT or other drugs). They will be the ones that most rapidly divert host resources to their own use – in other words, the most virulent [[12]:57].

HIV is not the only panic-generating virus in the news. Much worry is being devoted to avian flu and the possibility of another flu pandemic on the scale of the Spanish flu of 1918. Some words of evolutionary caution are called for even here.

The influenza virus particle displays molecules on its surface that can be recognized by the immune system. Different strains of influenza can be identified by their possession of variants of these molecules. Of particular interest are H-type molecules (versions of hemagglutinin) and N-type molecules (versions of neuraminidase). The Spanish flu of 1918 was caused by an H1N1 virus, in contrast to the avian flu currently in the news, which is an H5N1 virus. In 1976, a strain of flu with the H1N1 marker reappeared – causing much panic among flu experts. Was the panic justified? Arguably not, for as Ewald has observed:

The H1N1 marker had been present on dangerous viruses, but there was no reason to think that it made the viruses dangerous – with its high mutation rate, the influenza virus can generate tremendous variation within a matter of weeks while still retaining the H1N1 marker [[11]:23].

While an obsession with such "marker" molecules can be highly misleading, the evolutionary questions run to a deeper level of analysis. We have just seen that parasites and pathogens differ with respect to strategies for reproduction and dispersal – some keep their hosts mobile, some succeed by immobilizing their hosts. An evolutionary analysis considers the virus in ecological context. The conditions that led to the differential reproductive success of the highly virulent Spanish flu of 1918 were somewhat unique – in particular, consideration has to be given to the crowded, unsanitary conditions that existed in the trenches at the Western front during WW1, along with the confinement of flu victims to crowded barracks, and subsequently to over-crowded hospitals. The mere existence of a dangerous virus does not amount to much – unless conditions exist that favor its differential replicative success and subsequent dispersal. Commenting critically of approaches adopted by influenza experts, Ewald points out:

. . . they still confuse the sources of variation – the mutation and recombination of genes – with the process of evolution by natural selection. And they still confuse similarity of hemagglutinin and neuraminidase molecules among different virus strains with similarities in the virulence of these strains. . . By failing to investigate the selective processes that favor increased or decreased virulence of virus strains, experts still run the risk of spending too much time and too many resources in attempts to block a 1918-type pandemic, and too little time on how to deal with the more immediate threats [[11]:25].

The long reach of evolutionary biology into the field of medicine does not stop here, for evolutionary principles can be observed with respect to populations of specialized cells that are found normally in multi-cellular organisms such as ourselves.

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