Evolution of Virulence: Malaria, a Case Study

Published on October 1, 2007   34 min

Other Talks in the Series: Evolution and Medicine

0:00
The problem of the evolution of virulence is essentially the question, why do infectious agents harm us? If their survival depends on our survival, why have they not evolved to be harmless? What I'm going to do is illustrate one way evolutionary biologists attempt to answer this question, and I'm going to do so using malaria as an example. I hope to persuade you that it is both intellectually interesting and important to know why malaria parasites-- and by analogy other parasites-- harm us. I have prepared these slides, and the opinions expressed are mine. However, my presentation draws heavily on work of members of my research group and other collaborators. In particular, my view of malaria evolution has been heavily shaped by long and very fruitful collaboration with Margaret Mackinnon.
0:42
Evolutionary biologists often try to understand how natural selection acts. Here I will ask how natural selection acts on malaria virulence. But before discussing the natural selection, I need to define virulence. The word is used to mean a variety of different things by different people. I use it to mean the harm done to us following infection. In other words, the things physicians worry about, morbidity and mortality. Other things, like a parasite's ability to infect or replicate or transmit, are related and very important, but they are not part of my definition of virulence. I'm going to ask how natural selection shapes the virulence of malaria parasites in two steps. First, I'm going to ask, why are they so virulent? What evolutionary advantages are there for parasites which harm their hosts? Why is malaria nasty? It turns out that that is relatively easy to answer. In fact, it's so easy to answer that it begs the next question, which is, why aren't malaria parasites more virulent? Why aren't they nastier? And I'm going to spend most of the lecture on those two questions. I then want to spend a few minutes discussing the implications of evolutionary analysis for medicine. I want to persuade you that we cannot ignore parasite evolution in public health planning. This is obvious in the context of drug resistance. I hope to persuade you that it is very likely to be important for virulence as well, and we are currently overlooking this, possibly to our peril. And then I will end by very briefly discussing two other diseases to illustrate a precautionary plea.
2:06
Malaria is a disease caused by an infectious protozoan, a single-celled animal, which, for most of its life in a human, proliferates in our red cells. It is, of course, transmitted between humans by mosquitoes. Over a million people a year die of malaria, but this is actually only a small minority of people who get infected with the parasites. What determines whether an infected person lives or dies has been the subject of a huge amount of biomedical research over the last century. And we now know that many things are important. Your genes matter. People with sickle cell anemia are less likely to die. It matters whether your immune system has seen the parasites before. It matters how poor you are, the type of house you have, how close you live to mosquito breeding grounds. It probably matters how many parasites you get. And it certainly matters what type of parasites infect you. Did you get a nice or a nasty parasite strain? The evolutionary biology framework I'm going to discuss in this lecture focuses on these parasite genetic factors, virulence determinants encoded by parasite genes, and ask why natural selection favors some genetic variants but not others. Why does it favor nicer or nastier strains? Asking that sort of question is not normal in conventional biomedicine.
3:16
Let me contrast conventional biomedical explanations of disease with the type of explanation evolutionary biologists give. This is easiest with a concrete example. Some people with malaria parasites get cerebral malaria, and they can die from it. Cerebral malaria probably happens when some parasites stick in the brain, where they block brain blood vessels. Conventional modern biomedicine tries to identify the parasite molecules involved. This is a hugely useful thing to do because we might be able to build drugs or vaccines to block the stickiness. But an evolutionary biologist will ask, what is the evolutionary advantage to the parasite in having the molecules that make the parasite stick in the brain? If there was no advantage, natural selection should have got rid of those molecules. If they are good for something, why don't parasites have even more of them? One might hypothesize that the stickiness molecules are good for stopping parasites being swept into the spleen, where they could be killed. So sticky parasites would have an evolutionary advantage, but then they run the risk of causing cerebral malaria and perhaps killing their hosts and therefore themselves. Identifying the evolutionary advantages and disadvantages of the stickiness phenotype allows us to explain the evolution of virulence and perhaps-- and it is a big perhaps-- explain how parasite virulence might evolve in the future if, for instance, we start throwing drugs and vaccines at them. Evolutionary explanations are not in any sense better or worse than those offered by conventional biomedicine. The two types of answers are simply different. Both the mechanistic explanation-- what molecules-- and the evolutionary explanation-- how is selection acting-- together give a complete explanation of things. One on its own is incomplete.
4:50
Let me illustrate the evolutionary argument in more depth. We envisage that all of the parasite strains in a population-- and indeed all of the strains that they could actually ever be-- can be arranged on a spectrum from very benign, where they have no effect on the host whatsoever, to very nasty, where they are effectively instantly lethal. Then we can ask, how does natural selection act on the strain variation? Which part of the spectrum will it start to remove? What we envisage is that there will be selective factors which increase the average level of virulence in a population by removing the very benign strains. Other selective factors will oppose these, removing very lethal strains. And these opposing forces will balance somewhere in the virulence space, and that will be the average level of virulence favored by natural selection in that particular population. We often speak of these opposing forces in terms of costs and benefits of virulence. The evolutionarily benefits of virulence make selection drive up virulence-- the red arrow. Whereas the evolutionary costs draw it down-- the blue arrow. These costs and benefits will vary enormously among different diseases, depending on their biology and ecology, so we can expect the balance point to vary widely among diseases so that some will be nice and some will be nasty.
Hide

Evolution of Virulence: Malaria, a Case Study

Embed in course/own notes