Albrecht Durer: A Young Hare“Typically, viruses that rapidly kill their host have a very short history, as they rapidly run out of places to reproduce.”

I’m quoting John Timmer from Ars Technica’s Nobel Intent, from a couple of weeks ago. I feel kind of bad about this because I’m only quoting to disagree with him, and I always like Nobel Intent and find it interesting — but this is my most recent sighting of what I think is a very widespread misunderstanding. I commented on it briefly in the thread there (“This is one of those widely-believed rules that’s not nearly as universal as people think. … “), but here’s a chance to expand a bit. 1

The concept is intuitively satisfying: A pathogen that rapidly and inevitably kills its hosts runs out of new hosts; if the host remains alive longer, then there’s a continuing supply of new hosts; therefore rapidly-lethal pathogens hastily evolve toward reduced virulence. It seems to make all kinds of sense, and there are some famous examples that fit this theory beautifully.

Myxomavirus is the type specimen. It also fits with the observation that some of the most virulent virus infections we see are recent introductions into humans — HIV, obviously; also SARS, Ebola, and so on — that may not yet have had time to evolve toward avirulence.

Unfortunately, there are also lots of counterexamples to the theory, starting with rabies (a beautifully-adapted virus that is invariably lethal), and aside from myxomavirus there aren’t all that many good examples pro. The reality is probably that evolution toward reduced virulence is a special case rather than a general rule. What’s more, the lay understanding of the theory — viral evolution toward avirulence — has little if any support, and may not occur at all.

Everyone2 knows about myxomavirus in Australia. Myxomavirus was introduced there in the early 1950s as a biological control agent for the rabbit plague. At first, the virus killed virtually every rabbit it infected (99.8% lethality), reducing the rabbit population by 85%, to a mere 100,000,000; but after some years of adaptation, most rabbits survived infection, and the rabbit population rebounded. While on the one hand the rabbits were obviously selected for resistance to myxomavirus,3 the virus also did in fact evolve to reduced virulence. This was shown in a classic study by Fenner and Marshall in 1957.4

In this unusual situation, they still had samples both of the original virus, and of a non-evolved rabbit population in Europe, so they could do direct comparisons. The new strains of the virus circulating in Australia were less lethal. What’s more, those rabbits that did die, took much longer to do so, surviving for several weeks instead of 5 days or so as with the original highly lethal strain.Fenner 1965

But Fenner’s work also showed why this isn’t a general law, and showed one of the problems with extrapolating this to the extreme of avirulence — because in fact the virus did not evolve to avirulence, it evolved to moderate virulence and then stayed there, killing about 50% of the rabbits it infected. Fenner & Marshall said: “The overall trend towards moderate virulence (grade III) … can be explained by the selective advantage for mosquito transmission of strains which cause extensive and long-persisting infectious skin lesions in rabbits.”

In other words:5

The less-virulent virus took 3 to 4 weeks to kill a rabbit instead of 6 to 10 days, so that sick rabbits could be bitten by mosquitoes and fleas for 3 to 5 times as long as a rabbit suffering from the highly virulent strain. The milder strain was therefore more successful in infecting rabbits, and it spread rapidly. Through this selection the virus evolved to a less-virulent form.

(The map at right is from a later paper by Fenner,6 showing a similar phenomenon in British myxomavirus. Note that most of the strains isolated here, a decade or so into enzootic myxomavirus, are Grade III, “moderate”, killing “just” 70-90% of infected rabbits, rather than the relatively avirulent grade V or the brutally lethal grade I that was the original infection.)

This highlights a key for this sort of evolution to work. There needs to be a direct link between increased transmission of the disease, and reduced virulence. The issue of a new supply of hosts, which is what most people seem to think is the critical factor, seems to be relatively minor. Conversely, if there’s a link between increased transmission and increased virulence, then the balance will not favour the pathogen becoming benign. If, for example, you are a virus that spreads by causing your host’s blood to explode out of its body, or if you destroy your host’s brain and force it to run about furiously biting anything in sight, or if you are spread through insect vectors that find your host an easier target when it’s moribund — then becoming less lethal is unlikely to help you.

This has been proposed in detail, and to some extent experimentally tested, most prominently by Paul Ewald.7 I don’t know enough about the evolutionary and epidemiological sides to comment intelligently,8 so I’ll stop here, but with this quote from Ewald that explains why this sort of theoretical work can be important:9

Insights into the evolution of virulence may aid efforts to control or even prevent emerging diseases. Specifically, dangerous pathogens can be distinguished from those that pose relatively little threat by identifying characteristics that favor intense exploitation of hosts by pathogens, hence causing high virulence. Studies to date have implicated several such characteristics, including transmission by vectors, attendants, water, and durable propagules.


  1. Also, as is usually the source for whatever I’m blathering about here, it’s something I ran across in my reading anyway, and this is one way I help solidify things in my mind.[]
  2. Everyone who is anyone, at least[]
  3. A major complication in interpreting this sort of phenomenon — if you don’t have an original population of the hosts, how can you tell if it was the pathogen or the host that evolved?[]
  4. A comparison of the virulence for European rabbits (Oryctolagus cuniculus) of strains of myxoma virus recovered in the field in Australia, Europe and America. Fenner F, Marshall ID. J Hyg (Lond). 1957 Jun;55(2):149-91. []
  5. From a commentary on rabbit calicivirus at the Australian Academy of Sciences’ Nova page[]
  6. Evolutionary Changes In Myxoma Virus In Britain. An Examination Of 222 Naturally Occurring Strains Obtained From 80 Counties During The Period October-November 1962. Fenner F, Chapple PJ. J Hyg (Lond). 1965 Jun;63:175-85. []
  7. For example, Pathogen survival in the external environment and the evolution of virulence. Walther BA, Ewald PW.. Biol Rev Camb Philos Soc. 2004 Nov;79(4):849-69.) []
  8. Not that that usually stops me[]
  9. The evolution of virulence and emerging diseases. Ewald PW. J Urban Health. 1998 Sep;75(3):480-91.[]