Unleashing the Ferrets of Fear

The second of two controversial papers on H5N1 “bird flu” came out yesterday, and if you didn’t hear about it, it wasn’t for lack of publicity. Not only did journalists get the usual embargoed access to the paper at the beginning of the week, we also got a whole package of related commentary and an invitation to a high-powered press conference with the lead researchers, the journal’s editor, and other luminaries. Even before this week, people were leaking information about the new results like Julian Assange on a bender.

I considered working up a whole post on this research and scheduling it to come out when the embargo expired, but besides being snowed under with paying work, I knew that such a post would probably disappear in the noise. Instead, I just waited for my friend and TWiV co-host Vincent Racaniello to put up his summary and analysis, which I expected would be excellent. It is, so go read it now if you haven’t already. I’ll wait.

Unfortunately, the bad reporting on this topic also appeared right on schedule. Here, for example, is The Telegraph’s take on the work:

Headline: Bird flu pandemic just “three mutations” away, scientists show

A bird flu pandemic may be close to being a real threat after scientists discovered the virus is already just “three mutations” away from evolving into a strain which would be able to pass from human to human. Avian H5N1 influenza can currently only be transmitted to humans from birds, meaning it cannot spread quickly through the air between large groups of people. But a recent study at Cambridge University shows that there are strains already existing which are just “three mutations” away from being passable form one human to another.

You know what the problem is here? Rhetorical vomit. There’s a lot of it in the world, from political bumper stickers to fear-mongering headlines. Just like real vomit, it takes only seconds to splatter out into the world, and anyone who sees it can’t help but notice and be affected. It’s also contagious; when we see vomit, we want to. We can’t help it. It grabs us at a visceral level, and leaves our conscious minds struggling to catch up with a more reasoned response. When that finally happens, the cleanup takes far longer than the hurl, and it’s very difficult to erase the original impression.

But there it is, pooling on the floor, sticking to the couch, and stinking up the room. And now that reporters like The Telegraph’s Richard Alleyne and Nick Collins have spoiled lunch with that mess, someone has to get out the mop and clean it up. Fine.

Let’s begin by understanding the requirements for a new flu pandemic, starting from an influenza strain that infects birds. First, the virus needs to adapt to a point where it can transmit efficiently from one human to another. Humans are very different from birds, so that’s going to take some mutating and selecting. Second, it has to retain enough virulence that we actually need to worry about it. A virus can be highly transmissible without being a major concern. Cytomegalovirus infects half of the world’s adults, but odds are you’ll never know you have it. Finally, a pandemic flu virus needs to encounter an immunologically naive human population. That’s a serious hurdle that keeps getting higher. For example, if you had the 2009 H1N1 “swine flu” or got the vaccine against it, there’s a good chance you’re now also immune to the dreaded 1918 flu. If a lot of people are similarly cross-immune to some newly mutated H5N1 strain, the pandemic will fizzle.

In the new studies, researchers found that H5N1 flu has to undergo at least five separate mutations from its ordinary bird form in order to be transmissible through the air from one ferret to another. Ferrets aren’t people, but they’re a bit closer to us evolutionarily than birds are. Looking at isolates of H5N1 that have appeared so far, we see that two of those five mutations have already occurred in nature. The Telegraph’s story appears to be discussing an extension of those findings, in which some of the same scientists used mathematical modeling to gauge the potential for wild H5N1 strains to pick up the remaining three mutations, based on our current understanding of influenza biology. Like all mathematical modeling studies, that work is useful for telling us what our assumptions mean. It does not tell us what will actually happen.

So are we three mutations away from a pandemic? There’s no way to tell. We appear to be three mutations away from obtaining a strain of H5N1 that could be aerosol-transmissible between ferrets, but not lethal to them. We don’t know whether the same mutations would enable the virus to transmit between humans. We don’t know whether it would be virulent. We don’t know how much of the population would be susceptible to it.

We don’t even know how likely it is that the remaining three mutations found in these studies could ever occur in nature. Any of the numerous selective pressures on viruses in the wild could prevent them from making those changes. So far, despite infecting at least several hundred (and probably many more) humans, H5N1 flu hasn’t managed to make the jump. Have we just been extremely lucky, or does this streak of failures point to an underlying biological barrier that keeps bird flu in birds? Nobody knows.

The new H5N1 flu papers do tell us a lot, and they represent vitally important work. We now know some of the types of changes that can make a bird influenza virus aerosol-transmissible in a mammalian host. We also know that H5N1 has the potential to contribute genes to a future pandemic virus, and might even have the ability to spark a pandemic on its own. We should keep an eye on that, try to take reasonable precautions against it, and keep studying H5N1 and other flu viruses to get a better idea of what they’re capable – and not capable – of doing. In the meantime, I encourage my fellow editors and journalists to keep a bucket handy.