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This Transgenic Mouse Is a Flu Pandemic Canary

An early-warning system for the biological 'big one.'

It's a disquieting thought: What lies between us and a civilization-shaking flu pandemic is something like luck. Flu strains evolve and change, becoming more or less lethal yearly. The swine flu pandemic of 2009 is one recent example. That outbreak killed at least 18,000—far less in total than claimed by common seasonal flu strains, but with a far shorter reach. Swine flu was particularly anxiety-inducing for its talent for killing the young and healthy. 

The 2009 swine flu was a new strain related to the flu behind the 1918 flu pandemic, which killed 50 to 100 million people. Its newness meant that it could evade existing flu vaccines. That flu evolves is what makes it frightening. The virus that for most of us means a few days of Netflix and ginger ale could mean far more dire things. And the appearance of a new flu strain, particularly one gaining the ability to jump from animals to humans, is unpredictable. A roll of the genetic dice. 

Researchers in Germany have developed a transgenic mouse with the potential to serve as an early-warning system for new flu virus strains with the potential for causing global pandemics. Basically, the mouse is "hacked" to express a human immune protein called MxA, which normally protects against avian flu viruses but not against viruses that have acquired the ability to infect humans—that has become "zoonotic," in other words. The group's work is described this week in the Journal of Experimental Medicine

"Zoonotic transmission of influenza A viruses can give rise to devastating pandemics, but currently it is impossible to predict the pandemic potential of circulating avian influenza viruses," the paper notes. We know that these viruses have to overcome MxA to spread to and among humans, but translating that observation into something predictive apparently takes a mouse with a human immune system. 

It makes sense. We can't very well go around shooting up human subjects with potentially deadly flu viruses, so we make mice that are just human enough. If a new flu strain needs to be evaluated for its pandemic potential, we can just see if it makes the transgenic mouse sick. If it does, well, that's bad. But it's not as bad is it would have been if we'd waiting for the strain to emerge in IRL human populations, where it would have already been too late. 

"Our MxA-transgenic mouse can readily distinguish between MxA-sensitive influenza virus strains and virus strains that can evade MxA restriction and, consequently, possess a high pandemic potential in humans," study co-author Peter Staeheli offered in a statement. "Such analyses could complement current risk assessment strategies of emerging influenza viruses, including viral genome sequencing and screening for alterations in known viral virulence genes."

Sucks to be the mouse, of course, but preventing another 1918 is a pretty noble sacrifice.