infect humans. Many birds carry the flu without getting sick. Rather than infecting their airways, flu
viruses typically infect the guts of birds; the viruses are then shed in bird droppings. Healthy birds
become infected by ingesting virus-laden water.
Sometimes strains of bird flu jump the species barrier and become human viruses. But for every
successful transition, there are probably many failed crossings. Bird flu viruses are well adapted to
infecting their avian hosts and reproducing quickly inside them. Those adaptations make them ill-
suited to spreading among humans. Starting in 2005, for example, a strain of flu from birds called
H5N1 began to sicken hundreds of people in Southeast Asia. It is much deadlier than ordinary strains
of seasonal flu, and so public health workers have been tracking it closely and taking measures to halt
its spread. For now, at least, H5N1 can only move from a bird to a human; it cannot move from one
human to another.
Unfortunately, a poorly adapted flu virus can evolve into a well-adapted one. Flu viruses are
particularly sloppy at replicating their genes, so many new viruses acquire mutations. These
mutations are like random changes to the letters in the flu’s recipe. Some of the mutations have no
effect on viruses. Some leave them unable to reproduce. But a few mutations give flu viruses a
reproductive advantage. Natural selection favors these beneficial mutations, and flu strains can
become better at infecting humans as mutation after mutation accumulates. Some mutations help the
virus by altering the shape of the proteins that stud the virus shell, allowing them to grab human cells
more effectively. Other mutations help the flu virus cope with human body temperature, which is a
few degrees cooler than that of birds.
Human influenza viruses have also adapted to a new route from host to host. In birds, the viruses
travel from guts to water to guts. In people, the virus moves from airways to droplets to airways. This
new route also causes the flu rise and fall with the seasons. In places like the United States, most flu
cases occur during the winter. According to one hypothesis, this is because the air is dry enough in
those months to allow virus-laden droplets to float in the air for hours, increasing their chances of
encountering a new host. In other times of the year, the humidity causes the droplets to swell and fall
to the ground.
When a flu virus hitches a ride aboard a droplet and infects a new host, it sometimes invades a cell
that’s already harboring another flu virus. And when two different flu viruses reproduce inside the
same cell, things can get messy. The genes of a flu virus are stored on eight separate segments, and
when a host cell starts manufacturing the segments from two different viruses at once, they sometimes
get mixed together. The new offspring end up carrying genetic material from both viruses. This
mixing, known as reassortment, is a viral version of sex. When humans have children, the parents’
genes are mixed together, creating new combinations of the same two sets of DNA. Reassortment
allows flu viruses to mix genes together into new combinations, as well.
As scientists get a closer look at the genes of flu viruses, they’re discovering that reassortment has
played a major role in the natural history of the flu. A quarter of all birds with the flu have two or
more virus strains inside them at once. The viruses swap genes through reassortment, and as a result
they can move easily between bird species. And sometimes, on very rare occasions, an avian
influenza virus can pick up human influenza virus genes through reassortment. That can be a recipe for
disaster, because the new strain that results can easily spread from person to person. And because it