By removing themselves from the group, sick mice limit disease spread. (UZH)

In 1665, a bundle of cloth from London arrived at the door of the tailor for the village of Eyam, a tiny community in the midlands of England. Within a week, the tailor's assistant was dead.

The cloth contained fleas that carried the bubonic plague, and it didn't take long for the disease to spread throughout the village. But the destructiveness of the disease is less impressive than the valor of its victims: The villagers voluntarily quarantined themselves to prevent the plague from spreading into the surrounding countryside. In little over a year, all but 83 of Eyam's 350 or so residents were dead. But the infection had been contained.

The Eyam case has been heralded as a rare example of astonishing self-sacrifice. But some scientists believe that each of us does something similar, however unintentionally, when we are ill. According to the "Eyam hypothesis," sickness behaviors — the set of coordinated behavioral changes, such as depression, lethargy and loss of appetite, that help the body cope with illness and injury — might have evolved in part because they make us more reclusive, thereby preventing us from spreading our disease. By refusing food, sleeping all the time and avoiding others, we could be saving our friends and family from our fate.

This hypothesis hasn't been proven experimentally. But it just got a boost thanks to some rather selfless mice.

In a study published Monday in the journal Scientific Reports, biologist Patricia Lopes describes how wild mice living in an abandoned barn in Switzerland began to avoid their social groups when they felt ill. When she and her colleagues modeled the effects of this behavior change, they found that it dramatically slowed down the spread of disease.

"We don't know why the mice are doing this," Lopes said, "But as a consequence of the sick mouse changing its behavior and moving away from the nest, its relatives would have a better chance of not getting the disease and surviving, and they would pass on genes that are common to the sick mouse. ... That could make the behavior evolutionarily advantageous."

The individual advantages of sickness behavior are well known. Lack of hunger means that animals don't need to waste energy and expose themselves to attack by foraging for food. A lower threshold for pain ensures that they are extra gentle with the injured body part. Overall lethargy means the body's energy can be directed entirely toward maintaining a fever — the most metabolically taxing part of the immune response.

But the benefits of some aspects of response are less clear. Why, for example, do animals become anxious and depressed when sick? Why do they stop grooming, which makes their fur and feathers better insulators? Keren and Guy Shakhar, the immunologists who named the "Eyam hypothesis," point out that anorexia deprives sick animals of calories needed to fuel a fever. They also argue that the presence of sickness behavior even in illnesses that aren't accompanied by fever indicates that there might be another reason for the adaptation: altruism.  

"If gains to direct fitness cannot fully explain [sickness behavior], perhaps inclusive fitness could come into play," they wrote in the journal PLOS Biology. "We propose that reduced transmission of infectious disease among related individuals contributed to the evolution of [sickness behavior]."

Mice, which live in close-knit social groups, offer a good test for this theory. Lopes, a researcher at the University of Zurich, looked at 257 wild mice living in about a dozen groups in a huge abandoned barn. Each mouse was outfitted with a radio identification tag, and their nests bore antennae that pinged whenever a mouse entered. This allowed Lopes and her colleagues to monitor where the mice were and who they were with.

To test for sickness behavior in her mice, Lopes injected a few hosts with a bit of bacterial cell wall — which, much like a vaccine, elicited an immune response from the mice without actually making them sick. Immediately, she noticed that the "host" mice were spending much less time with the rest of their social groups. This wasn't because their peers were avoiding them; the healthy rodents were no less likely to enter a nest containing a sick mouse than a healthy one. But the sick mice spent less time visiting other animals and were more likely to linger inside nests that were uninhabited. Overall, the hosts interacted far less with their social groups than they normally would. And 40 percent of the mice avoided any social contact at all.

There's no obvious individual advantage to this. Though it's common for animals to hide when sick to avoid predation, the mice would have been just as well protected in a nest full of their buddies as in one where they were alone. In addition, the study was conducted during winter, when mice usually huddle together for warmth. Voluntarily quarantining themselves would have made the sick mice more vulnerable, not less.

But Lopes's models suggest another possibility. The social isolation she observed in her mice would lead to a drastic reduction in disease spread, according to computer models. In her simulation, when 40 percent of sick mice quarantined themselves from their social groups, only about a quarter of the group got sick. Without quarantine, it was likely that the entire social group would be infected. This suggests that behavioral changes like depression, lethargy and a lack of interest in grooming could promote inclusive fitness — the likelihood that an animal's genes will be passed to the next generation via the organism itself or its close kin, who share many of the same genes.

It's important to note that the mice aren't quarantining themselves consciously as the people in Eyam did. And the idea that an evolutionary mechanism might be behind this behavior still needs to be proven experimentally. Lopes and her colleagues have plans for a follow-up study that would examine whether isolation decreases when the mice in a social group are less closely related.

"We'd expect that groups with less-related animals might do this less," Lopes said.

Perhaps that's not so noble as the self-sacrifice of Eyam. But it's still pretty good for a mouse.

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