Published online 27 August 1998 | Nature | doi:10.1038/news980827-8

News

The curse of the pharaoh

On 17th February, 1923, Howard Carter and his patron, Lord Carnarvon, finally broke into the burial chamber of the boy pharaoh, Tutankhamun, after a three-month dig. Lady Carter died from an insect bite in 1929: Lord Carnarvon followed her to the grave four years later, succumbing to a fever following a mosquito bite. More than twenty other people involved in the excavation met untimely deaths from a range of causes, ranging from heart failure to madness. Thus arose the story about the Curse of the Pharaoh.

Could some of the victims have perished from a virulent infection that had lain dormant in the Pharaoh’s sealed tomb for thousands of years? Biologists have been pondering the connections between a parasite’s capacity to lie dormant - for years, in some cases - and its virulence, once it infects a new host.

In short, do parasites and diseases that can lie dormant for longer tend to be more virulent when they meet a new host? Is there a basis to the Curse of the Pharaoh? The answer, according to Sylvain Gandon of the Universitè Pierre et Marie Curie, Paris, France, writing in Proceedings of the Royal Society, is a qualified ‘yes’.

The consequences could be important for public health. Wiping out reservoirs of dormant yet viable parasites would not only reduce the risk of infection for individuals, but decrease the virulence of the disease generally, and save lives.

In 1996, researchers formalized the central idea of the Curse - that a capacity for dormancy means high virulence - as a mathematical model. They found that virulence increased with dormancy only if the parasite run a high risk of dying while dormant. Dormancy is risky, and must be repaid by high virulence and capacity to spread once active.

Gandon now extends this theoretical work by imagining a situation in which a host might receive multiple infections of the parasite. This introduces an additional complication - that of genetic relatedness between parasites. Parasites with different genetic backgrounds infecting the same host will engage in a kind of warfare for supremacy within the hapless host: the consequence will be increased virulence - heightened disease symptoms, and the increased risk that the host will die, taking its load of parasites with it.

Gandon shows that, in general, parasites capable of lying dormant for a long time tend to be more virulent once active, but this conclusion is tempered by relatedness, and how virulence relates to the capacity of the disease to spread.

This is important: a highly virulent disease will kill all its hosts (and therefore itself) without spreading. The trick for a successful disease is to cause moderate or mild symptoms - or, if severe, to delay them - so that it can spread to new hosts before killing off the present ones.

In parasites whose virulence is not related to their capacity to spread, dormancy always increases the virulence, if several parasites infect the same host, and if dormancy carries a risk to the parasite of death before it has had a chance to infect a new host. In other words, riskier passage between hosts tends to make a parasite or disease more virulent. However, virulent diseases that kill a lot of hosts can still spread widely, if they have the ability to lie dormant for a long time, which offers a kind of safety net.

The work shows, that - with several caveats - a parasite that can lie dormant for a long time is likely to claim many lives once a suitable host comes along. Having done its evil work, it will not need to spread any further - provided that it can go back into hiding for another long interval of time. The Curse of the Pharaoh has some basis in fact.

But we can turn the Curse back on the parasites that are its avatars. By improving sanitation and hygiene, we can make it harder for parasites to remain dormant. The consequence will an evolutionary response from the parasite to become less virulent, should an epidemic break out.