The recent spillover of the H7N9 strain from chickens in China has stoked fears of a new flu pandemic. As influenzas go, this strain is pretty deadly. According to Xinhua, the Chinese state news agency, 14 of the 71 people confirmed infected as of April 16 have died, a shockingly high mortality rate. Other infectious disease specialists are concerned that this strain could be the one to go off the rails, jumping from human to human and becoming an epidemic that causes widespread death and disruption.
But Paul Ewald isn’t worried. In fact, he’s relatively calm about the whole situation, though you’d never guess that by talking with him. The energetic evolutionary biologist from the University of Louisville talks a mile a minute—so quickly that my normally deft fingers are having trouble keeping my notes in sync with our phone conversation—and every so often he rocks back and forth in his metal office chair, its groaning springs punctuating his arguments even though they need no embellishment. His formula for determining whether or not we should worry about any influenza outbreak is quite simple, really.
“For influenza, is it transmissible yet, or at all, from person to person?” Ewald asks. “If it is transmissible, is it only under very extreme circumstances?” If the answer is “no” to the first question or “yes” to the second, then there’s little reason to panic, he reasons. Fortunately with H7N9, that seems to be the case; there’s no evidence of sustained human-to-human transmission. Hence, no reason to worry yet.
At present, H7N9 is transmitted directly from birds to humans. Influenza strains nearly always trace their origin from birds if you go back far enough. The virus is common within bird populations. Kept there, the virus doesn’t pose much of a problem. It’s when it jumps from birds to humans, as H7N9 has done—or finds its way to people through an intermediate host like pigs—that we start paying closer attention. When that happens, scientists don’t panic, but they do start getting sweaty palms. If H7N9 does evolve to jump from human to human, the budding anxiety could blossom into a full-blown alarm.
“When it first gets into humans, all bets are off in terms of whether it will be mild or lethal,” Ewald says. But even then, the strain may not make it very far. According to one theory, the trade-off hypothesis, independently developed by Ewald and the team of Roy Anderson and Robert May, incredibly lethal diseases immobilize and kill their victims too quickly to be passed on effectively. Bedridden—or dead—victims don’t give the virus many opportunities to find new hosts.
That’s because evolution ultimately favors pathogens that neatly optimize transmissibility and lethality. An overly lethal virus, Ewald says, is an evolutionary dead end. For a virus strain to succeed, in evolutionary terms, it must pass on it’s genes to new generations. For viruses like the flu that don’t last long in the body—they’re either killed off when attacked by the immune system or die when the host dies—they have to maximize their chances of transmission. This selects for more moderate strains, which allows the host to live longer, giving the virus more opportunities to infect different people. “If you don’t get transmitted, you’re the loser,” Ewald says. “If you get transmitted well, you’re the winner.”
That’s not to say highly deadly viruses can’t spread—it’s just that they’re not very good at doing it on their own. In the case of the flu, that trade-off may also be built into its genome. “There’s a cost benefit that the virus takes on by having mutations that confer extra virulence. Sometimes those same mutations confer less replicative activity,” says Cameron Wofle, an infectious disease specialist at Duke Medicine. Fewer replications would reduce the number of virus particles able jump to a new host.
Looking Back to 1918
What scientists and public health officials fear most is an outbreak similar to the 1918 flu pandemic, which killed tens of millions. Ewald, though, is skeptical that we’ll see another flu outbreak of the same severity because of the unique circumstances at the time. At the end of World War I, a nasty flu strain swept through the stressed, soaked, and malnourished soldiers in trenches on the Western Front. The sickest were whisked from the front in tightly packed train cars to numerous overcrowded triage tents and field hospitals, one after the other, within the span of a few days. In the process, more people were exposed to the lethal virus than under more normal circumstances, where the sick are confined to bed, or perhaps one hospital, and only come into contact with a handful of individuals. Things settled down, according to Ewald’s theory, when the virus made its way through the civilian population. There, people weren’t living packed in sordid trenches and they weren’t being moved from one hospital to another, so the virus evolved to a milder state in a few months.
Unless we reproduce the elaborate transportation system that shuttled deathly ill soldiers from one overcrowded hospital to another, Ewald says it’s unlikely we’ll ever see a flu pandemic on that same scale, where mortality rates exceeded 1%. That’s considered to be among the worst on record. Generally, the flu causes one death in 1,000 if it’s particularly pernicious, or more normally one in 10,000. “The flu virus is unlikely to ever cause profound mortality rates,” Wolfe points out. “But you only need to have 20 percent of your population affected, and you can imagine on a societal level what that would do.” Which is exactly what happened in 1918.
Fortunately, Ewald thinks that what we’re already doing to prevent the spread of the flu is probably enough to prevent a pandemic on the same scale. “I think the standard approaches that have been used are appropriate: Alerting people that there’s an influenza outbreak; if the virus looks like it’s a little nastier, alerting them that it might be a nastier virus; and that people should take precautions to not be in crowds and, if the virus is something we already have a vaccine against, get flu shots.”