Evolution of Virulence

Once upon a time, I thought a lot about evolution and pathogens.  I still do, on occasion.

It used to be the case [and still is] that many biologists thought that natural selection would inevitably tend towards a situation in which pathogens did infinitesimal harm to their host.  This despite the epidemics all around them. I remember reading a book on parasitology in which the gormless author mentioned a certain species of parasitic copepod that routinely blinded the fish they attached to.  He said that many a naive grad student would think that that these parasitic copepods were bad for the fish, but sophisticated evolutionists like himself knew (and would explain to the newbies) that of course the fish didn’t suffer any reduction in fitness by going blind – theory said so !  Clearly, that man had a Ph.D.

If a pathogen can gain increased reproduction by tapping host resources, or by doing any damn thing that helps itself and hurts the host,  that tactic may pay, and be selected for. It depends on the balance between the advantages and costs – almost entirely those to the pathogen, since the pathogen evolves much more rapidly than the host.  In some cases, as much as a million times faster – because of  generations that may be 20 minutes long rather than 20 years, because  pathogens often have very large populations, which favors Fisherian acceleration, and in many cases, a relatively high mutation rate.  Pathogen evolution is, at least some cases, so rapid that you see significant evolutionary change within a single host.  Along the same lines, we have seen very significant evolutionary changes in antibiotic resistance among pathogenic bacteria over the past few decades,    but I’m pretty sure that there hasn’t been much evolutionary change in mankind since I was a kid.

So when analyzing  virulence, people mostly consider evolutionary pressures on the pathogens,  rather than the host.  Something like the Born-Oppenheimer approximation.

There are some patterns we have a pretty good understanding of.  Often, a pathogen gains from leaving the host mobile, which generally entails leaving the host alive, except for the well-known zombiefication germ.  Pathogens spread by vectors – mosquito-born diseases such as  malaria and sleeping sickness, or  water-borne diseases such as cholera – tend to do more harm, because host mobility is not so important for them. Thus, a pathogen that is  originally virulent, like myxomatosis,  may evolve towards lower virulence if it’s killing its hosts too rapidly.

Vertical transmission –  usually transmission from a mother to her children –  pushes a pathogen towards being harmless or even beneficial.   If all transmission is vertical, and the organism reduced fitness, it is easy to see that carriers (and pathogen) would go extinct. So pure vertical transmission selects for  beneficial effects – in females.   There are maternally transmitted organisms that cause parthenogenensis and eliminate all males.  Along the same line, there is evidence that male-harming mutations accumulate in mitochondria, an idea called Mother’s Curse. I don’t think this is what is happening with human male homosexuality, but it has been suggested.

Steve Frank ( who is sharp!) suggests another pattern. Consider a parasite cloaking device, something interferes with or avoids host immunity. This reduces the clearance of the parasite.  Second, the cloaking device causes an increase in virulence at later times, by which we mean a greater chance of host death at that later time.  The fitness sensitivity of changes in survival is always weaker at later ages, because the probability of being alive is always smaller at later ages.  So Frank predicts that a parasite always gains by reducing clearance at earlier times even if that causes an equivalent risk to the parasite at a later time by increasing the host death rate.  If the damage to the host appears farther in the future, after the infection is cleared, then of course  such an action is favored by selection.  This seems to often happen in diseases triggered by molecular mimicry (a way of avoiding clearance) , such as  Type-I diabetes or rheumatic fever. With rheumatic fever, the molecular similarity between the strep germs and heart valves causes cross reactions that leave the patient with long-term heart problems.  This also happens with Chagas disease.

If a pathogen action reduced host fitness, but without killing the host or reducing mobility, there would be no cost to the pathogen at all.  Thus you shouldn’t be too surprised to see pathogens cause sterility in their host.  Even the slightest advantage  (such as a slightly increased chance of avoiding early clearance) would be enough to favor this.  For that matter, if happened by accident – if pathogens drifted into a situation did harm to the host but that would not lead to further transmission – it wouldn’t be disfavored by selection.

Most of the infections that cause sterility or reduced fertility are STDs,  and I would guess that those effects happen, to a large extent, because the pathogens are in the right neighborhood. It’s a lot easier to interfere with the reproductive system if you’re already there.  On the other hand, other pathogens also cause sterility:  tuberculosis is one of the most common causes of infertility in backward countries.

There is another principle that particularly limits the virulence of pathogens attacking humans.  We know of pathogens that can wipe out species, or come close:  you don’t see many American elms or American chestnuts anymore.  Almost all koalas have a retrovirus that is responsible for > 80% of deaths and threatens to wipe out the species.  Tasmanian Devils are being attacked by an infectious host cell line that threatens to put all of them in the cold, cold ground. The chytrid fungus has wiped out many frog species. What’s our secret?

If we had been hit by something that serious, we probably wouldn’t be here at all, and I wouldn’t be writing this.  The anthropic principle rides again!